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Sample records for borderline ovarian tumor

  1. Mucinous borderline ovarian tumor with ascites.

    PubMed

    Batool, Tahira; Ullah, Nasreen Rehmat

    2014-11-01

    Borderline mucinous tumors are epithelial ovarian tumors with low rate of growth and low potential to invade or metastasize and associated with significantly better prognosis and excellent disease-free survival after surgical removal than other epithelial ovarian cancers. The accepted initial treatment is surgical removal of the tumor. Fertility-sparing surgery may suffice in young patients with tumors confined to the ovary. Radical surgery is recommended in patients with advanced disease and advanced age. Long-term surveillance is recommended to document and treat late recurrences. We report a case of a 59 years old postmenopausal patient with complex ovarian mucinous tumor and gross ascites; she had received three lines of chemotherapeutic agents pre-operatively, without any favorable outcome. Then, she went for staging laparotomy and histopathology showed borderline ovarian mucinous tumor required no further treatment and is fine till date. PMID:25518783

  2. Sonographic findings of an ovarian serous surface papillary borderline tumor.

    PubMed

    Kwon, Yohan; Park, Sung Bin; Lee, Jong Beum; Park, Hyun Jeong

    2013-01-01

    Sonographic findings of a serous surface papillary borderline tumor of the ovary have rarely been reported in the English literature. Here, we describe a case of serous surface papillary borderline tumor, which was depicted on gray-scale and Doppler ultrasonography as smoothly lobulated and polypoid heterogeneous echoic bilateral adnexal masses encased or surrounded by what was presumed to be normal-appearing ovarian follicles with increased vascular flow. PMID:23938140

  3. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

    PubMed Central

    Zikan, Michal; Dundr, Pavel; Cibula, David

    2012-01-01

    Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155

  4. 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

  5. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  6. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes.

    PubMed

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David G; Hird, Vicky; Brown, Robert; Flanagan, James; Gabra, Hani; Mills, Gordon B; Agarwal, Roshan; El-Bahrawy, Mona

    2013-04-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  7. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes

    PubMed Central

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David Gonzalez; Hird, Vicky; Brown, Robert; Flanagan, James; Hani Gabra, H; Mills, Gordon B.; Agarwal, R; El-Bahrawy, Mona

    2013-01-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study we conducted an extensive analysis of mutations and single nucleotide polymorphisms in borderline ovarian tumors. Using the Sequenom MassARRAY platform we investigated 160 mutations/polymorphisms in 33 genes involved in cell signalling, apoptosis, angiogenesis, cell cycle regulation, and cellular senescence. Of 52 tumors analysed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in 8 tumors (6 serous and 2 mucinous), BRAF V600E mutations in 2 serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in VEGF, ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at 4 loci. PHLPP2 polymorphisms were more frequent in mucinous as compared to serous tumors (p=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional single nucleotide polymorphisms in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbour somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  8. Granulosa cell tumor presenting with ovarian torsion and de novo borderline mucinous ovarian tumor in the contralateral ovary.

    PubMed

    Ates, S; Sevket, O; Sudolmus, S; Sonmez, F C; Dansuk, R

    2015-01-01

    The authors report a case of 25-year-old women with a rare acute presentation of granulosa cell tumor (GCT) as an ovarian torsion. Right salpingoo-ooferectomy was performed. The pathological diagnosis was GCT One month after the surgery there was a three-cm ovarian cyst in the contralateral ovary and the tumor size increased to six cm in diameter in the following month. Serum inhibin-B levels progressively increased. Cystectomy was performed to contralateral ovary as frozen-section examination indicated mucinous tumor. Final histopathological examination revealed borderline mucinous tumor. Regarding her request, the patient was reoperated again and unilateral oophorectomy and hysterectomy were performed. Clinicians must be aware of the possibility of an underlying malignancy associated with adnexal torsion even in young patients. Frozen section will be helpful in order to avoid incomplete surgeries. Cyst rapidly growing in the ovary in young women should raise the suspicion of a de novo malignancy. PMID:26189271

  9. A case-control study of borderline ovarian tumors: the influence of perineal exposure to talc.

    PubMed

    Harlow, B L; Weiss, N S

    1989-08-01

    The authors interviewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineal application of baby powder nor the perineal application of cornstarch was associated with an appreciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or in combination with other talc-containing powders had 2.8 times the risk (95% confidence interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertaining the specific type(s) of powder used. PMID:2750733

  10. 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

  11. Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature.

    PubMed

    Ludovisi, Manuela; Foo, Xulin; Mainenti, Sara; Testa, Antonia Carla; Arora, Rupali; Jurkovic, Davor

    2015-01-01

    Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition. PMID:25706035

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

    PubMed

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

    2016-04-10

    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

  13. 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

  14. 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

  15. 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

  16. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  17. Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

    PubMed

    Mhawech-Fauceglia, Paulette; Ramzan, Amin; Walia, Saloni; Pham, Huyen Q; Yessaian, Annie

    2016-07-01

    A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal. PMID:26598983

  18. Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome.

    PubMed

    McKenney, Jesse K; Gilks, C Blake; Kalloger, Steve; Longacre, Teri A

    2016-09-01

    The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers (κ=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further

  19. Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor

    PubMed Central

    Chen, Longwen; Butler, Kristina A.; Bell, Debra A.

    2016-01-01

    Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42-year-old female had a history of bilateral SBT and postbilateral salpingo-oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis.

  20. KRAS (but not BRAF) mutations in ovarian serous borderline tumor are associated with recurrent low-grade serous carcinoma

    PubMed Central

    Tsang, Yvonne T.; Deavers, Michael T.; Sun, Charlotte C.; Kwan, Suet-Yan; Kuo, Eric; Malpica, Anais; Mok, Samuel C.; Gershenson, David M.; Wong, Kwong-Kwok

    2014-01-01

    BRAF and KRAS mutations in ovarian serous borderline tumors (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumor samples from 23 recurrent LGSC patients with known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for 5 patients, and either OSBT or LGSC were available for another 18 patients. Tumor cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumors that appeared to have wild-type KRAS by conventional PCR–Sanger sequencing were further analyzed by full COLD (coamplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in 10 patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in 7 OSBT samples and 6 LGSC samples. To our surprise, patients with the KRAS G12V mutation appeared to have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumor cells with or without detectable KRAS mutations. PMID:24549645

  1. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  2. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  3. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10-15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  4. 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. PMID:27003157

  5. A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

    PubMed Central

    Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

    2015-01-01

    Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

  6. Ovarian tumors secreting insulin.

    PubMed

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  7. 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. PMID:27587627

  8. A case report of a young girl with mucinous borderline tumor of the ovary

    PubMed Central

    Lee, Hyun-Mi; So, Kyeong A; Kim, Mi Kyung; Lee, Yoo Kyung; Lee, In-Ho; Kim, Tae-Jin

    2016-01-01

    Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient's life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor. PMID:27462604

  9. A case report of a young girl with mucinous borderline tumor of the ovary.

    PubMed

    Lee, Hyun-Mi; So, Kyeong A; Kim, Mi Kyung; Lee, Yoo Kyung; Lee, In-Ho; Kim, Tae-Jin; Lee, Ki Heon

    2016-07-01

    Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient's life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor. PMID:27462604

  10. 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

  11. Detection of Human Papillomavirus-16 E6-Oncoprotein in Epithelial Ovarian Tumors Samples of Iraqi Patients

    PubMed Central

    Mahmood, Fahem Mohsin; Kadhim, Haider Sabah; Mousa Al Khuzaee, Liqaa Riadh

    2014-01-01

    Background: Human papillomavirus (HPV) is the causal factor for cervical cancer. However, the role of HPV infection in ovarian cancer is unclear. Objectives: This study aimed to determine the presence of human papillomavirus-16 (HPV-16) in ovarian tumor tissues. Patients and Methods: This was a retrospective study, which included 61 Archived human ovarian tumor tissues embedded in paraffin blocks. The ovarian tumor tissues were divided into four groups. The first group was the malignant ovarian epithelial tumor group; it included 31 cases with invasive surface epithelial ovarian tumors. The second group was the borderline epithelial ovarian tumor group: it included four cases with borderline intermediate malignancy. The third group was the benign epithelial ovarian tumors group: it included 18 cases with benign epithelial ovarian tumors. The fourth group had functional ovarian cystic lesions: it included eight cases with non-neoplastic functional ovarian cysts. Sections were made from each of the paraffin embedded blocks and examined using immunohistochemistry to detect HPV 16-E6-oncoprotein in ovarian tumor tissues. Results: Out of the eight cases with functional cysts only one case (12.5%) expressed HPV. No HPV expression was seen in cases with benign and borderline tumors. Out of the 31 cases with one malignant surface epithelial ovarian tumor only three (9.67%) cases expressed HPV. There was no significant statistical difference in HPV expression among neoplastic and non-neoplastic ovarian tumors included in the present study (P= 0.476). Conclusions: HPV type 16 was detected in only 9.67% of malignant epithelial tumors. It appears that HPV infection plays a relatively minor role in the pathogenesis of ovarian carcinomas. PMID:25485061

  12. Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer.

    PubMed

    Gram, Inger T; Braaten, Tonje; Adami, Hans-Olov; Lund, Eiliv; Weiderpass, Elisabete

    2008-02-01

    Studies regarding the association between smoking and risk of epithelial ovarian cancer (EOC) are inconsistent. The purpose of this study was to examine the association between smoking and EOC, overall and according to invasiveness and histological subtype in a cohort of women with a high proportion of smokers at enrollment. We followed 103,081 women, aged 30-50 years in 1991/1992, from the Norwegian-Swedish Women's Lifestyle and Health cohort. The women completed a questionnaire on personal characteristics and exposures at enrollment and were subsequently followed with linkages to national registers through December 31, 2004. We used Cox proportional hazard regression models to estimate hazard ratio (RR) of EOC with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 343 [241 (70%) invasive and 102(30%) borderline] incident EOC cases were identified. Former [HR = 2.2(95% CI 1.0-4.7)] and current [HR = 2.7(95% CI 1.2-5.7)] smokers had a more than doubling in risk for borderline tumors compared to never smokers. Women who had smoked for more than 20 years had 3 times [HR = 3.1(95% CI 1.5-6.7)] the risk of borderline tumors compared to never smokers. A test for trend according to smoking status was almost significant for mucinous tumors (p-trend = 0.05). A significant dose response relationship was found according to smoking intensity [pack-years; (0-9, 0-14, >or= 15)] and duration [number of years; (0-10, 11-20, >or= 20)] for borderline and serous tumors (p-trends < 0.05). In conclusion, smoking may increase the risk of borderline EOC. PMID:17918152

  13. Borderline Ovarian Tumors and Diagnostic Dilemma of Intraoperative Diagnosis: Could Preoperative He4 Assay and ROMA Score Assessment Increase the Frozen Section Accuracy? A Multicenter Case-Control Study

    PubMed Central

    Gizzo, Salvatore; Berretta, Roberto; Di Gangi, Stefania; Guido, Maria; Zanni, Giuliano Carlo; Franceschetti, Ilaria; Quaranta, Michela; Plebani, Mario; Nardelli, Giovanni Battista; Patrelli, Tito Silvio

    2014-01-01

    The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P < 0.05), and overdiagnosis in 11.6% versus 0% (P < 0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events. PMID:25431767

  14. Borderline phylloides tumor in an 11-year-old girl.

    PubMed

    Selamzade, M; Gidener, C; Koyuncuoglu, M; Mevsim, A

    1999-07-01

    Phylloides tumor is an uncommon breast tumor in children. Only a few cases have been reported in the literature. A case of borderline phylloides tumor in an 11-year-old girl is described. PMID:10415310

  15. Expression of REG4 in ovarian mucinous tumors.

    PubMed

    Huang, Qiong; Chen, Xiaoduan; Lu, Weiguo; Lai, Maode; Lu, Bingjian

    2014-04-01

    Regenerating islet-deprived gene family, number 4 (REG4), is a novel marker for intestinal differentiation. We performed immunohistochemical studies on REG4, cytokeratin (CK)7, CK20, and caudal type homeobox 2 (CDX2) in 291 ovarian mucinous tumors. There were 226 primary tumors and 65 metastatic tumors. The primary tumors comprised 69/226 mucinous cystadenomas, 79/226 mucinous borderline tumors (64/79 intestinal-type and 15/79 endocervical-like tumors), and 78/226 mucinous carcinomas. We found that REG4 expression was significantly higher in mucinous borderline tumors (30/79, 38.0%) and primary mucinous carcinomas (26/78, 33.3%) than in mucinous cystadenomas (4/69, 5.8%; P<0.05). However, REG4 expression was more commonly associated with intestinal-type, borderline, mucinous tumors rather than the endocervical-like type (30/64 vs. 0/15, P<0.001). There was a significant correlation between the REG4 and CDX2 expression profiles in primary ovarian mucinous tumors (r=0.772, P<0.001). REG4, CDX2, and diffuse CK20 had higher expression frequencies in metastatic lower gastrointestinal adenocarcinoma than in primary mucinous tumors (P<0.01). The CK7/REG4 coordinate expression profile was comparable in diagnostic value to CK7/CK20 or CK7/CDX2 profile. We conclude that REG4 expression is common in mucinous borderline tumors of the intestinal type as it is absent in the endocervical-like form in this series. Expression of CK7/REG4 may contribute to the differential diagnosis between primary and metastatic ovarian mucinous tumors. PMID:23958547

  16. SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type.

    PubMed

    Moh, Michelle; Krings, Gregor; Ates, Deniz; Aysal, Anil; Kim, Grace E; Rabban, Joseph T

    2016-03-01

    The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric

  17. Ovarian tumors of the hen.

    PubMed Central

    Fredrickson, T N

    1987-01-01

    Present available information regarding ovarian tumors in hens is incomplete in most aspects, and this lack of knowledge hampers use of hens as models for study of ovarian cancer. A study of 466 hens ranging from 2 to 7 years of age and covering a period of more than 3 years has provided much needed information relative to reproductive tract neoplasia. On the basis of this study, it is apparent that hens have a high rate of ovarian tumors, but that such tumors are uncommon in hens less than 2 years of age. Adenocarcinomas with a high degree of morphologic variability are the most common ovarian tumors in hens. Hormonal imbalance does not appear to be a factor in the development of these adenocarcinomas. Steroidogenic and morphologically distinctive granulosa cell tumors originating from follicles in atrophic ovaries represent another common ovarian tumor type. Unique to the hen are oviductal adenocarcinomas. These tumors arise from the albumin-secreting glands of the oviduct, occur with relatively high frequency, and must be differentiated from ovarian adenocarcinomas. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PLATE 24. PLATE 25. PMID:3665870

  18. 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

  19. 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

  20. Jejunal Metastasis Colliding With a Borderline Tumor in the Ovary: A Hitherto Unreported Eventuality.

    PubMed

    Piana, Simonetta; Giunta, Alessandro; Valli, Riccardo

    2015-10-01

    Metastatic adenocarcinomas to the ovary can show morphologically innocuous areas simulating primary benign lesions or borderline tumors. Ruling out a metastasis can be a difficult issue for pathologists, especially when facing with cystic tumors. Because of the important clinical implications of differentiating metastatic adenocarcinomas from primary ovarian tumors, the integration of clinical, pathological, and immunohistochemical features is warranted, primarily in case of mucinous adenocarcinomas. Vice versa, the synchronous presence of a metastasis and a primary in the same ovary is virtually excluded as a very unlikely eventuality. Here, we describe a case of metastatic adenocarcinoma from the jejunum colliding with a seromucinous borderline tumor in the same ovary, an unreported eventuality so far. PMID:25911566

  1. Expression profile of mucins in ovarian mucinous tumors: distinguishing primary ovarian from metastatic tumors.

    PubMed

    Wang, Jayson; El-Bahrawy, Mona A

    2014-03-01

    Ovarian mucinous tumors (OMTs) of the intestinal type share morphologic features with primary tumors of other sites, and it can often be difficult to distinguish primary ovarian from metastatic mucinous tumors. MUC1, MUC2, MUC5AC, and MUC6 expressions were studied by immunohistochemistry in 36 OMTs of intestinal type (17 malignant, 19 borderline), 18 pancreatic, 12 biliary, 15 esophageal, 9 gastric, and 7 colorectal/appendiceal adenocarcinomas. All samples were from primary sites, except for colorectal tumors which were from ovarian metastases. Borderline and malignant OMTs show similar mucin immunoprofile, being strongly and uniformly positive for MUC5AC (97.2% of cases), whereas only focally positive for MUC1 (19.4%), MUC2 (38.9%), and MUC6 (22.2%). The positive frequencies of pancreatic adenocarcinomas for MUC1, MUC2, MUC5AC, and MUC6, respectively, were 100%, 16.7%, 94.4%, and 61.1%; for biliary (cholangiocarcinomas) were 91.7%, 0%, 16.7%, and 8.3%; for esophageal carcinomas were 73.3%, 33.3%, 53.3%, and 26.7%; for gastric carcinomas were 44.4%, 44.4%, 44.4%, and 0% and for lower gastrointestinal tract cancers were 28.6%, 85.7%, 42.9%, and 0%. Our study shows that OMTs are usually MUC5AC+/MUC1-, which is different from pancreatic, biliary, esophageal, gastric, and colorectal/appendiceal carcinomas. We recommend that these mucin stains be added to the panel of immunostains to differentiate metastatic tumors to the ovary from primary OMTs. PMID:24487472

  2. S100P is a useful marker for differentiation of ovarian mucinous tumors.

    PubMed

    Umezaki, Y; Ito, M; Nakashima, M; Mihara, Y; Naruke, Y; Kurohama, H; Yatsunami, N; Yasuhi, I

    2015-01-01

    The S100P protein stimulates cell proliferation and survival, thereby contributing to tumor progression. The purpose of this study was to evaluate S100P expression in the three subtypes of mucinous cystic tumors, cystadenomas, borderline tumors, and adenocarcinomas. The authors examined nuclear S100P expression in 60 mucinous ovarian tumor specimens, including 24 specimens of mucinous cystadenoma, 15 of borderline tumors, and 21 of adenocarcinomas. Immunohistochemistry revealed S100P expression followed one of three patterns: (1) Expressed in most nuclei of mucinous epithelial cells, (2) sporadic (spotted or patchy) expression, or (3) absent or rarely expressed in the nuclei of mucinous epithelial cells. Most adenomas showed the first expression pattern, and borderline tumors often showed a patchy expression pattern. Adenocarcinomas generally demonstrated absence of S100P expression. These data suggest that S100P is a useful histological marker to differentiate between benign, borderline, and malignant mucinous tumors of the ovary. PMID:26050349

  3. The diagnostic value of frozen section for borderline ovarian tumours.

    PubMed

    Bozdag, Halenur; Guzin, Kadir; Gocmen, Ahmet; Kabaca, Sedef; Usta, Akın; Akdeniz Duran, Esra

    2016-07-01

    Borderline ovarian tumours (BOTs) are characterised histologically by a low degree of cellular proliferation and nuclear atypia in the absence of infiltrative growth or stromal invasion. Surgical treatment has been a crucial component of BOT therapy. Surgical decisions are established intraoperatively via the frozen section. We evaluated the accuracy of frozen section diagnosis. The rate of correct diagnosis, underdiagnosis and overdiagnosis of BOTs with frozen sections was 78%, 17% and 5%, respectively. The sensitivity and positive predictive values for the diagnosis of BOTs with frozen sections were 82.3% and 93.3%, respectively. The positive likelihood ratio was 0.82 (95% CI: 0.85-0.96). The histological classification of BOTs had a significant effect on the accuracy of diagnosis (p = 0.001). Frozen section diagnosis is not suitable to be considered as the gold standard for a definitive diagnosis. Clinicians should be aware that using frozen sections is insufficient for the accurate staging of BOTs. PMID:26790979

  4. Retropancreatic Ovarian Tumor.

    PubMed

    Acharya, Soumyo Ranjan; Dasgupta, Prosenjit; Das, Subhobroto; Halder, Sandip; Panda, Nilanjan

    2016-06-01

    Retroperitoneal mucinous cystadenomas are rare lesions (less than 50 reported) characterized by presence of ovary like stroma of unknown origin. However, germinal component of ovary has never been found in them. The pancreas occasionally gives rise to mucinous cystadenomas, but they are always intrapancreatic. We report a unique case of a rare retroperitoneal mucinous cystadenomas with presence of ovarian follicles in a 45-year-old lady who presented with an abdominal mass. This was successfully excised. Though retroperitoneal mucinous cystadenomas are rare, presence of ovarian follicle (germ cell) in them has never been reported before. PMID:27358520

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

    PubMed Central

    Wang, Min; Ma, Haifen

    2016-01-01

    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. PMID:27446571

  6. 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

  7. Expression of c-myc and mutation of the KRAS gene in patients with ovarian mucinous tumors.

    PubMed

    Li, X S; Sun, J; He, X L

    2015-01-01

    We examined the expression of c-myc and mutations in the KRAS gene in ovarian mucinous tumors to explore the pathogenesis of these tumors and the feasibility of targeted gene therapy. Expression of c-myc protein and mutations in the KRAS gene in 24 cases of ovarian mucinous cystadenoma, 46 cases of ovarian borderline mucinous cystadenoma, and 46 cases of ovarian mucinous cystadenocarcinoma were detected using the immunohistochemistry PV-9000 2-step method and polymerase chain reaction-restriction fragment length polymorphism. The positive expression rates of c-myc in ovarian mucinous cystadenoma, borderline mucinous cystadenoma, and cystadenocarcinoma were 0, 39.1, and 65.2%, respectively (P < 0.01), while the mutation rates in KRAS were 0, 39.1 and 13.0%, respectively. The mutation rate of the borderline group was significantly higher, while rates in the other 2 groups were similar (P > 0.05). c-myc was not correlated with clinical stage, pathological grade, or age of patients with ovarian mucinous cystadenocarcinoma or borderline mucinous cystadenoma (P > 0.05), but was correlated with tumor size (P < 0.05). Mutations in KRAS were not correlated with clinical stage or tumor size in patients with borderline mucinous cystadenoma (P > 0.05), whereas it was correlated with age (P < 0.05). In borderline mucinous cystadenoma, c-myc expression and KRAS mutations were not correlated (P > 0.05). c-myc is involved in the formation of ovarian borderline mucinous cystadenoma and mucinous cystadenocarcinoma, and the KRAS gene may contribute to the formation of borderline mucinous cystadenoma. PMID:26400304

  8. [Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors].

    PubMed

    Kolstad, P

    1987-10-01

    About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2824278

  9. Early inflammatory response in epithelial ovarian tumor cyst fluids.

    PubMed

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-10-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors. PMID:24947406

  10. Recurrence of Brenner ovary borderline tumor in the abdominal wall postoperative scar--a case report and research of the literature.

    PubMed

    Klasa, Lukasz; Wydra, Dariusz; Biernat, Wojciech

    2014-11-01

    We report a case of a 74-year-old female, who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy due to a solid-cystic tumor of the right ovary. The histopathological diagnosis revealed a borderline Brenner tumor (BBT). After 25 disease-free months the patient was admitted to a hospital because of a tumor in the postoperative scar of the abdominal wall, later diagnosed as infiltrating Brenner tumor consistent with ovarian borderline lesion. The tumor in the postoperative scar was therefore diagnosed as BBT. The article presents results of literature search on BBT in order to find characteristic features of this very rare ovarian tumor. To the best of our knowledge, this is the first report of subcutaneous recurrence of Brenner ovary tumor of low malignant potential. PMID:25675807

  11. Expression of serum amyloid a in human ovarian epithelial tumors: implication for a role in ovarian tumorigenesis.

    PubMed

    Urieli-Shoval, Simcha; Finci-Yeheskel, Zvezdana; Dishon, Shira; Galinsky, Daliah; Linke, Reinhold P; Ariel, Ilana; Levin, Mark; Ben-Shachar, Inbar; Prus, Diana

    2010-11-01

    Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application. PMID:20713982

  12. 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. PMID:26316459

  13. General Information about Ovarian Germ Cell Tumors

    MedlinePlus

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Germ Cell Tumors Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. [Presumed benign ovarian tumors during pregnancy].

    PubMed

    Tariel, O; Huissoud, C; Rudigoz, R C; Dubernard, G

    2013-12-01

    The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4% (LE2). The most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed incidentally during the first trimester ultrasound (LE2) and spontaneous regression is often observed. Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors diagnosed during pregnancy (LE2). The main complication of presumed benign ovarian tumor (PBOT) during pregnancy is adnexal torsion and is estimated at around 8% (LE2), especially at the end of the first trimester and during the second trimester (LE4). Tumor markers are not reliable during pregnancy to assess the risk of malignancy of ovarian tumor (LE2). Ultrasound remains the gold standard for characterizing an ovarian tumor during pregnancy (LE3), but with a lower specificity for the diagnosis of malignancy. Pelvic MRI is accurate in the diagnosis of ovarian tumors during pregnancy and brings additional information to ultrasound (LE4). Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade C). Expectation is recommended in cases of PBOT during pregnancy, which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in patients with symptoms suggesting an adnexal torsion (grade C). Laparoscopy is possible during the first and second trimester of pregnancy for the management of symptomatic PBOT (LE3). The risk of miscarriage following surgery (laparoscopy and laparotomy) for ovarian tumor during pregnancy is estimated at 2.8% (LE3). The route of delivery should not be modified by the ovarian tumour, except in case of praevia cyst requiring a cesarean section, a complication or suspicion of malignancy (grade C). Surgical treatment of PBOT may be performed during a cesarean section indicated for another reason. The risk of torsion is increased during the postpartum period (LE4). PMID:24210242

  15. [Ovarian germ cell tumors in girls].

    PubMed

    Nechushkina, I V; Karseladze, A I

    2015-01-01

    Morphological structure of tumor influences on the clinical course of the disease in children with germ cell tumors. Patients with ovarian dysgerminoma at the time of diagnosis are significantly older than patients with immature teratoma and yolk sac tumor. Immature teratoma and mixed germ cell tumors are significantly larger compared to other germ cell tumors. Yolk sac tumor and embryonal carcinoma are the most common cause of emergency surgical interventions and are accompanied by rupture of tumor capsule. PMID:26087605

  16. Sox10 expression in ovarian epithelial tumors is associated with poor overall survival.

    PubMed

    Kwon, Ah-Young; Heo, Ilyeong; Lee, Hye Jin; Kim, Gwangil; Kang, Haeyoun; Heo, Jin-Hyung; Kim, Tae Hoen; An, Hee Jung

    2016-05-01

    Sox10 is a transcription factor regulating the development of several cell lineages and is involved in tumor development. However, the clinicopathological relevance of Sox10 expression in ovarian cancer has not been examined. We assessed expression of Sox10 in ovarian epithelial tumors by immunohistochemistry and assessed its prognostic value by analyzing the correlation between its expression and clinicopathological factors. We used tissue microarrays including 244 ovarian epithelial tumors. Sox10 staining was found in the cytoplasm or nucleus of tumor cells. Malignant serous, mucinous, and endometrioid tumors were significantly more likely to express Sox10 than benign and borderline tumors. Expression patterns in adenocarcinomas were different for histologic subtypes: nuclear Sox10 staining was common in clear-cell adenocarcinomas and serous adenocarcinomas, whereas all cases of mucinous and endometrioid tumors were negative for nuclear staining. Nuclear Sox10 staining was also associated with chemoresistance and shorter overall survival in ovarian adenocarcinomas, notably in high-grade serous adenocarcinoma. Sox10 is expressed in many ovarian carcinomas, suggesting that it might be involved in oncogenesis of ovarian carcinoma. Expression pattern of Sox10 differs between histological subtypes. Nuclear Sox10 expression is an independent indicator of poor prognosis in ovarian adenocarcinomas, notably in high-grade serous adenocarcinomas. PMID:26951260

  17. Primary uterine müllerian mucinous borderline tumor (MMBT) associated with adenomyosis: a case report.

    PubMed

    Kawamura, Keiko; Kaneki, Eisuke; Ogawa, Shinji; Imamura, Hiroko; Ohishi, Yoshihiro; Kobayashi, Hiroaki; Kato, Kiyoko

    2014-03-01

    Müllerian mucinous borderline tumors (MMBTs) usually arise from the ovary. The present report is the first case of primary uterine MMBTs associated with adenomyosis. A 51-year-old woman was referred to our hospital for a complex cystic and solid 4×3 cm right adnexal mass. She had a history of a left ovarian endometriotic cyst and had undergone a left oophorectomy 2 yr prior. A laparotomy was performed, and the tumor was found to be originating in the posterior wall of the uterus. She underwent a total abdominal hysterectomy, right salpingo-oophorectomy, and left salpingectomy. Microscopically, the solid portion of the tumor contained papillary proliferations of glands, which were covered by a mucinous epithelium with mild to moderate nuclear atypia, accompanied by stromal infiltration of inflammatory cells. Islands of adenomyosis were also observed around the cyst. These pathologic findings were similar to the features of ovarian MMBT. We diagnosed this tumor as a uterine MMBT, probably arising from adenomyosis. PMID:24487469

  18. Ovarian serous cystadenofibromas associated with a low-grade serous carcinoma of the peritoneum.

    PubMed

    Hinson, Stacy A; Silva, Elvio G; Pinto, K

    2013-06-01

    Ovarian serous cystadenofibromas are benign neoplasms that sometimes have focal areas of borderline serous tumor and rarely have been associated with epithelial proliferations in the peritoneum, resembling implants. We are reporting 2 cases of ovarian serous cystadenofibromas with serous peritoneal lesions of higher grade than the ovarian tumor: 1 case had a serous carcinoma and another 1 a serous borderline tumor. PMID:22921726

  19. 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.

  20. Tumor infiltrating lymphocytes in ovarian cancer

    PubMed Central

    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. PMID:25894333

  1. Fertility drug use and risk of ovarian tumors: a debated clinical challenge.

    PubMed

    Gadducci, Angiolo; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

    2013-01-01

    Infertility itself increases the incidence of ovarian carcinoma, while the potential additional risk associated with the use of fertility drugs is still debated. In 1992, the cumulative analysis of 12 US case-control studies revealed that women who received ovulation-inducing drugs had approximately three-fold higher incidence of invasive ovarian carcinoma. Other investigations reported a lower increase of the risk of invasive carcinoma or borderline tumor of the ovary in women treated with these agents. Conversely, several other case-control or cohort studies failed to detect a significant correlation between fertility drug use and ovarian tumor risk in either parous or nulliparous women compared with untreated infertile women. Moreover neither the number of treatment cycles nor the type of drug used was associated with an increased risk in most studies. Incessant ovulation and excessive gonadotropin secretion have been long considered to play a major role in the development of ovarian carcinoma, and therefore fertility drugs, which raise the serum levels of gonadotropins and increase the chances of multiple ovulations, have been retained as a risk factor for this malignancy, However, the large majority of literature data as well as the new hypotheses on ovarian carcinogenesis appear to exclude a relevant impact of fertility drug use on the risk of ovarian tumors, and especially of high-grade invasive epithelial ovarian cancers. PMID:22946709

  2. [Morphology of secondary ovarian tumors and metastases].

    PubMed

    Horn, L-C; Einenkel, J; Handzel, R; Höhn, A K

    2014-07-01

    The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately  85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches. PMID:24859239

  3. Mucinous ovarian tumors associated with mucinous adenocarcinomas of the cervix. A clinicopathological analysis of 16 cases.

    PubMed

    Young, R H; Scully, R E

    1988-01-01

    Sixteen cases of mucinous adenocarcinoma of the cervix that were associated with a mucinous tumor of one or both ovaries are reported. The patients ranged from 25 to 70 (average, 44) years of age; two of them had the Peutz-Jeghers syndrome. Eight patients complained of abdominal swelling; most of the remainder had symptoms of uterine origin. Twelve patients had bilateral and four had unilateral ovarian tumors, which were typically large and cystic. Microscopic examination of most of the ovarian tumors revealed various combinations of benign-appearing, borderline, and carcinomatous mucinous epithelium within the same specimen. Most of the cervical tumors were deeply invasive; 10 of them were of the adenoma malignum type. Although there were varying degrees of uncertainty in individual cases, consideration of several features including the extent and distribution of disease in the abdomen, the comparative histology of the tumors, and the pattern of ovarian involvement suggested that 10 of the ovarian tumors were independent primary tumors, three were metastatic from the cervix, and in three cases the ovaries contained both primary and metastatic tumors. PMID:2840404

  4. [Diagnosis of presumed benign ovarian tumors].

    PubMed

    Laculle-Massin, C; Collinet, P; Faye, N

    2013-12-01

    Symptoms of presumed benign ovarian tumors (PBOT) are not specific (LE4). Personal or family history of gynecological cancers can guide the diagnostic strategy. Clinical examination is ineffective for positive, topographic and etiologic diagnosis of PBOT (LE4). Signs of hormonal impregnation may refer to certain types of tumors (LE4). For any patient presenting with a pelvic mass, pelvic ultrasound is in the first-line exam (grade A); it can classify most ovarian tumors. In case of pure liquid unilocular mass smaller than 7 cm, ultrasound is sufficient to characterize the mass (grade A). In case of indeterminate or complex ovarian mass on ultrasound, MRI is useful to characterize the mass (LE2). Beyond 7 cm, the diagnostic performance of ultrasound decreases (LE2). When a non-unilocular liquid ovarian formation is characterized using ultrasound as determinate mass, ultrasound scan is the only exam recommended (grade B). MRI is indicated as a second-line scan for indeterminate masses or greater than 7 cm (grade B). Cyst puncture for diagnostic purposes has no place in the diagnostic strategy of ovarian cysts (grade C). In case of PBOT in pre-pubertal period, dosing biomarkers is useful but should not delay care. In adult women with PBOT, the measurement of CA125 is not recommended for first-line diagnosis (grade C). Current literature data are not sufficient to specify the diagnostic strategy for an ovarian tumor discovered incidentally during laparoscopy. In case of discovery of a high CA125 value, pelvic ultrasound is the first-line examination. The literature data are still limited to define a CA125 threshold value requiring further exploration or special monitoring, in case of normal pelvic ultrasound. PMID:24210239

  5. Expression of LATS family proteins in ovarian tumors and its significance.

    PubMed

    Xu, Bing; Sun, Duoxiang; Wang, Zhihua; Weng, Haiyan; Wu, Dabao; Zhang, Xuefen; Zhou, Ying; Hu, Weiping

    2015-06-01

    Epithelial ovarian cancer is composed of a diverse group of tumors that can be derived from the fallopian tube, endometrium, or ovary. In this study, we explored the expression levels of LATS family members in ovarian tumors using normal ovaries, fallopian tubes, and endometrium as controls. Immunohistochemistry studies of LATS1, LATS2, Pax8, and calretinin were performed on normal ovary, fallopian tube, normal endometrium, and ovarian tumor sections. Statistical analyses were conducted using the χ(2) test, Fisher exact test, or Kruskal-Wallis H test. Patient survival was analyzed using the Kaplan-Meier method. LATS1 was expressed in normal ovarian epithelia, endometrium, and fallopian tubes, whereas LATS2 expression was observed in the normal fallopian tubes and endometrium. High expressions of LATS1 and LATS2 in serous cystadenomas gradually decreased in borderline cystadenomas and carcinomas, respectively. However, an opposite expression pattern was observed in mucinous tumors. Low expressions of LATS1 and LATS2 were also detected in clear cell carcinoma. Both LATS1 and LATS2 expression levels significantly correlated with recurrence and stage; LATS1 levels were also related with tumor grades in serous carcinoma. However, univariate and multivariate Cox regression analyses revealed that high expression of LATS1 was associated with better prognosis in patients with serous carcinoma. Both LATS1 and LATS2 were not related with the clinical variables in mucinous and clear cell carcinoma. LATS1 expression levels might be a valuable survival indicator in ovarian serous carcinoma. PMID:25841306

  6. Image-guided fine-needle aspiration cytology of ovarian tumors: An assessment of diagnostic efficacy

    PubMed Central

    Mehdi, Ghazala; Maheshwari, Veena; Afzal, Sheerin; Ansari, Hena A; Ansari, Maryem

    2010-01-01

    Background: Image-guided fine-needle aspiration cytology (FNAC) of ovarian lumps is being increasingly used for the successful diagnosis of ovarian tumors, although borderline cases may be difficult to diagnose by this method. Aim: To demonstrate the efficacy of image-guided FNAC in diagnosing ovarian tumors (benign and malignant) and to evaluate the usefulness of cytology as a mode of easy and rapid diagnosis of ovarian lumps. Materials and Methods: The study was conducted on 42 female patients. Clinical evaluation and relevant investigations were carried out. Diagnosis was established by FNAC performed under image guidance (ultrasonography/computed tomography). The cytological diagnosis was confirmed by histopathological examination. Results: Cytological diagnosis was rendered on all the 42 ovarian lesions, with a correct diagnosis in 34 cases, resulting in a diagnostic accuracy of 80.9%. Most of the cases with discordant diagnoses were surface epithelial tumors of low malignant potential and required histopathological examination for a final diagnosis. Conclusions: Image-guided FNAC is an inexpensive, rapid and fairly accurate procedure for the diagnosis of ovarian lesions. It provides a safe alternative to the more expensive, time consuming and cumbersome surgical route to diagnosis. PMID:21187883

  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. PMID:26090781

  8. [Methods and conditions of fertility preservation in early-stage ovarian tumors].

    PubMed

    Szatmári, Erzsébet; Máté, Szabolcs; Sipos, Norbert; Szánthó, András; Silhavy, Mihály; Rigó, János

    2013-04-01

    The aim of this study is to review the literature of fertility-sparing techniques and their safety in early-stage malignant ovarian tumors, especially in epithelial ovarian cancer. Fertility preservation is widely accepted in early-stage borderline, germ cell and sex cord-stromal tumors. Based on data from retrospective studies, fertility-sparing surgery in epithelial ovarian cancer can be recommended in stage IA, grade 1-2 and favorable hystologic type ovarian cancer. Above stage IA, or in grade 3, or in clear-cell tumors decision making process about fertility-sparing surgery should be individual. Correct surgical staging is mandatory and oncologic safety should be of primary importance. In the group of carefully selected patients oncological outcomes are identical to those of radical surgery. Spontaneous pregnancy rates vary, but they are generally high. Adequate counseling with patients, detailed documentation and careful follow-up is of outstanding importance. In order to improve the quality of fertility preservation techniques, establishment of treatment centers is recommended. PMID:23545230

  9. 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

  10. Diagnostic accuracy of intraoperative consultation (frozen section) in borderline ovarian tumours and factors associated with misdiagnosis.

    PubMed

    Basaran, D; Salman, M C; Calis, P; Ozek, A; Ozgul, N; Usubütün, A; Yuce, K

    2014-07-01

    The objective of our study was to evaluate the accuracy of frozen section (FS) in borderline ovarian tumours (BOT) and to define the factors associated with misdiagnosis during FS evaluation. We performed a retrospective review of patients who underwent exploratory laparotomy for an adnexal mass, from January 2007 to July 2012, at a tertiary oncology centre in Turkey. Patients with a diagnosis of BOT either in FS or in permanent pathology were identified. Agreement between FS diagnosis and permanent histology was observed in 37/59 patients (62.7%), which gave a sensitivity and a positive predictive value of 71.2% and 84.1%, respectively. In patients with a diagnosis of BOT by frozen section only (n = 44), the diagnosis was consistent with permanent histopathology in 37/44 patients (84.1%). Frozen section interpreted a malignant tumour as BOT (under-diagnosis) in 6/44 (13.6%) of cases and interpreted a benign lesion as BOT (over-diagnosis) in 1/44 (2.3%) of cases. Slide review of discrepant cases revealed that major pathological causes of under-diagnosis were misinterpretation and sampling errors. Univariate analysis showed that presence of bilateral tumour and positive peritoneal cytology were associated with under-diagnosis. We concluded that, despite significant risk of under-diagnosis, FS analysis is an accurate method for intraoperative diagnosis of BOTs. PMID:24734941

  11. Ovarian hormones and borderline personality disorder features: Preliminary evidence for interactive effects of estradiol and progesterone.

    PubMed

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

    2015-07-01

    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 four 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

  12. General Information about Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... Malignant Potential Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Low Malignant Potential Tumors Go to ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  13. 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

  14. 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. PMID:26595060

  15. NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype

    PubMed Central

    Galic, Vijaya; Shawber, Carrie J.; Reeves, Claire; Shah, Monjri; Murtomaki, Aino; Wright, Jason; Herzog, Thomas; Tong, Guo Xia; Kitajewski, Jan

    2014-01-01

    Background: Notch family members function as both oncogenes and tumor suppressors. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of NOTCH2 in ovarian cancer is unknown. Methods: An immunohistochemical analysis using a polyclonal antibody to the NOTCH2 intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or high NOTCH2 expression. The score distributions for the subtypes were analyzed with the chi square test. Results: Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lower NOTCH2 expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level of NOTCH2 expression and consistently demonstrated intense polarized staining (P<.001). The apical expression of NOTCH2 protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous. Conclusion: Decreased NOTCH2 expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role of NOTCH2 in ovarian cancer and its effect on prognosis. PMID:24707357

  16. Sarcoma-like mural nodule in a borderline mucinous tumor of the ovary: A rare entity.

    PubMed

    Ghosh, Prithwijit; Saha, Kaushik; Bhowmik, Sourav

    2014-10-01

    Sarcoma-like mural nodule (SLMN) is a very uncommon and misleading benign entity which may be associated with benign, borderline or malignant mucinous neoplasm of the ovary. It should be distinguished from other malignant mural nodules with sarcoma, carcinosarcoma or anaplastic carcinoma for proper management. We report a rare case of SLMN in a borderline mucinous tumor of the ovary in a 30-year-old lady. In spite of having confusing histopathological features the final diagnosis was made depending on the younger age of the patient, well circumscription of the nodule, absence of vascular invasion and immunohistochemical profile. PMID:25540570

  17. Tumor microenvironment: The culprit for ovarian cancer metastasis?

    PubMed

    Luo, Zhongyue; Wang, Qiu; Lau, Wayne Bond; Lau, Bonnie; Xu, Lian; Zhao, Linjie; Yang, Huiliang; Feng, Min; Xuan, Yu; Yang, Yanfei; Lei, Lingzi; Wang, Chenlu; Yi, Tao; Zhao, Xia; Wei, Yuquan; Zhou, Shengtao

    2016-07-28

    Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently, with poor prognosis. However, the molecular mechanisms underlying ovarian cancer metastasis still remain unelucidated. The tumor microenvironment, consisting of stromal cells (including fibroblasts, macrophages, regulatory T cells, myeloid-derived suppressor cells, endothelial cells, pericytes and platelets), the extracellular matrix component (EMC) (including inflammatory cytokines, chemokines, matrix metalloproteinases, integrins, and other secreted molecules) and exosomes (small extracellular vesicles loaded with molecules), establishes an autocrine-paracrine communication circuit that reinforces invasion and cancer cell metastasis via reciprocal signaling. Recent evidences have unraveled the significant contribution of tumor microenvironment to ovarian cancer metastasis. In this review, we provide a comprehensive landscape of the reciprocity between tumor stroma and ovarian cancer cells upon metastasis, aiming to offer novel clues on the development of novel diagnostic biomarkers and therapeutic targets for ovarian cancer in future clinical practice. PMID:27131957

  18. Significance of apoptosis related proteins on malignant transformation of ovarian tumors: A comparison between Bcl-2/Bax ratio and p53 immunoreactivity.

    PubMed

    Zeren, Tamer; Inan, Sevinc; Vatansever, H Seda; Sayhan, Sevil

    2014-10-01

    In this study, we compared the immunoreactivities of Bcl-2, Bax and p53 proteins in ovarian tumors and related the immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumors and serous-mucinous adenocarcinoma of the ovary (n=10 each) were stained with hematoxylin-eosin (H&E). After histopathological examination, serial sections were stained immunohistochemically with primary antibodies to Bcl-2, Bax and p53 using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare the immunohistochemical staining intensities. The nuclear DNA fragmentation of apoptosis was determined using TUNEL method. As a result of immunohistochemical staining, increased immunoreactivity of Bcl-2 was observed in adenocarcinomas when compared to borderline tumors (P<0.001). Strong immunoreactivity of Bcl-2 and mild immunoreactivities of Bax and p53 were detected in ovarian adenocarcinomas. There were no significant statistical differences in the immunoreactivity of Bax among the histological type of ovarian tumors. Whereas a balance was observed between the immunoreactivities of Bcl-2 and Bax in the borderline cases, and this balance was strongly changed toward the anti-apoptotic Bcl-2 protein in patients with adenocarcinoma. TUNEL staining of sections indicated apoptotic cells in the serous borderline tumors were about 8-fold higher than in the serous adenocarcinoma. The results of this study on apoptosis-related factors might help to develop novel protective and therapeutic approaches, such as isoflavonoids and isothiocyanates, which were associated with decreased Bcl-2/Bax ratio, against the malignant epithelial ovarian tumors. PMID:25108507

  19. Ovarian tumors in postmenopausal breast cancer patients treated with tamoxifen.

    PubMed

    Cohen, I; Beyth, Y; Tepper, R; Shapira, J; Zalel, Y; Figer, A; Cordoba, M; Yigael, D; Altaras, M M

    1996-01-01

    From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors' institutions. During this period. 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screening with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them. PMID:8557228

  20. 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

    2016-06-29

    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

  1. 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

  2. Recurrent intestinal mucinous borderline tumors of the ovary: a report of 5 cases causing problems in diagnosis, including distinction from mucinous carcinoma.

    PubMed

    Irving, Julie A; Clement, Philip B

    2014-03-01

    Intestinal mucinous borderline tumors (IMBTs) of the ovary are generally associated with a highly favorable outcome and rarely recur. We describe 5 cases of IMBT initially treated by cystectomy or by salpingo-oophorectomy that was likely incomplete, with subsequent recurrences. Three cases were received in consultation, and in each of these, the clinical and intraoperative findings were worrisome for mucinous carcinoma, and diagnostic difficulty was encountered by the referring pathologist. The patient age ranged from 28 to 69 (median 53) yrs. All tumors were clinically Stage I at presentation; in at least 3 cases, extensive adhesiolysis was required during their removal. A pathologic diagnosis of IMBT was made in 4 cases; the remaining tumor was inadequately sampled (3 blocks from a 7.5-cm tumor showed predominantly benign to focally borderline mucinous epithelium). A total of 8 recurrences, all as IMBT, developed at mean follow-up of 26 (range, 6-102) mo; 6 of these occurred within ≤2 yr. In 4 cases, removal of recurrent tumor required an extensive operation because of bowel and/or vaginal involvement. Residual ovarian stroma was identified in all recurrences. There was no evidence of invasive mucinous carcinoma, pseudomyxoma peritonei, or a primary tumor elsewhere (including appendix) in any of the cases. Our findings indicate that patients with IMBTs who undergo cystectomy or oophorectomy requiring adhesiolysis are at increased risk of recurrence, which may occur early, be multiple, and potentially require extensive resection if sites such as bowel or vagina are involved. Recurrences of IMBT that develop in this setting likely represent regrowth of incompletely resected IMBT, or arise within residual ovarian tissue. This is the first detailed clinicopathologic study of such cases. PMID:24487471

  3. Ovarian signet-ring stromal tumor: a potential diagnostic pitfall.

    PubMed

    Shaco-Levy, Ruthy; Kachko, Leonid; Mazor, Moshe; Piura, Benjamin

    2008-04-01

    Signet-ring stromal tumor is a rare ovarian neoplasm with only 10 reported cases in the literature. We report an unusual case of ovarian signet-ring stromal tumor in a 69-year-old woman who presented with right adnexal mass and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The diagnosis was based on histological, histochemical, immunohistochemical, and electron microscopy characteristics. The main significance is to differentiate this benign tumor from the highly malignant Krukenberg tumor, and this differential diagnosis is discussed. PMID:18417676

  4. Bilateral ovarian mixed epithelial adenocarcinoma in a postmenopausal woman with unilateral ovarian yolk sac tumor component.

    PubMed

    Chen, Qin; Chen, Xiaoduan

    2014-01-01

    Ovarian yolk sac tumors (YSTs) usually occur in the young women and have been rarely documented in perimenopausal and postmenopausal women. The different age distribution supposes their complex nomenclature and histogenesis. We report a case of bilateral ovarian epithelial carcinoma with right ovarian YST component in a postmenopausal woman. The patient was treated by surgery and adjuvant combination chemotherapy of taxol and carboplatin for 6 courses and has been clinically free of tumor for 6 months. The correlation between the YST and the epithelial components always confuse us. Ovarian yolk sac tumors are not a discrete entity and represent a multifaceted group of neoplasms. The conjunction of multi antibodies help in differential diagnoses. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed. PMID:25550883

  5. 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

  6. Identification of Epithelial Ovarian Tumor-Specific Aptamers

    PubMed Central

    Benedetto, Gregory; Hamp, Timothy J.; Wesselman, Peter J.

    2015-01-01

    Ovarian cancer is often diagnosed in late stages with few treatment options and poor long-term prognosis. New clinical tools for early detection of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. The objective of this work was to identify ovarian tumor-specific single-stranded DNA aptamers that bind to malignant ovarian tumor cells and internalize with high affinity and specificity. Aptamers can identify unique tumor biomarkers, can aid in early detection and diagnosis of neoplastic disorders, and can be functionalized by conjugation to small molecules. To identify aptamers from random single-stranded DNA pools (60 bases long), we used whole Cell-SELEX (systematic evolution of ligands by exponential enrichment) to enrich and isolate tumor-specific aptamers that bind to tumor-specific receptors in their native state on the cell surface. Next-Generation sequencing identified seven novel aptamers and detailed analyses of three are described. Aptamers bound to, and were internalized by, target Caov-3 cell populations, but not nontarget nonmalignant ovarian epithelial HOSE 6-3 cells or multiple other epithelial tumor cell lines. Furthermore, aptamers showed unique binding affinities with apparent dissociation constants (Kd) measuring in the submicromolar range supporting their physiological relevance and potential use in clinical applications. PMID:25894736

  7. Ovarian mucinous tumor with malignant mural nodules: dedifferentiation or collision?

    PubMed

    Desouki, Mohamed M; Khabele, Dineo; Crispens, Marta A; Fadare, Oluwole

    2015-01-01

    Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumors. The mural nodules are divergent neoplasms that may be benign or malignant. The latter may be in the form of a sarcoma, carcinosarcoma, anaplastic carcinoma, or a variety of other recognized histotypes of carcinoma, which raises the question of whether malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors or whether they represent collision tumors. We recently reported the K-RAS gene mutation status in a case of ovarian mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous and sarcomatous components revealed a mutation in codon 12 of the K-RAS gene of a different nucleotide substitution, indicating that these 2 tumor components were different clones of the same tumor. Herein, we are reporting another case of a 20-yr-old woman who presented with 22 cm pelvic mass, omental caking, and ascites. A diagnosis of invasive mucinous carcinoma with mural nodules of anaplastic carcinoma was rendered. K-RAS gene mutation studies revealed p.G12V, c.35G>T mutation in the 2 components of the tumor, which is the most common mutation reported in mucinous tumors of the ovary. The fact that sarcomatous or anaplastic carcinomatous mural nodules in ovarian mucinous tumors display the same K-RAS mutations as their underlying mucinous neoplasms provides supportive evidence that at least some malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors, rather than a collision of 2 divergent tumor types. PMID:25473748

  8. Robotic surgery for rectosigmoid junction tumor with ovarian metastases

    PubMed Central

    Bedirli, Abdulkadir; Salman, Bulent

    2015-01-01

    Isolated ovarian metastases from colorectal cancer (CRC) are rare disease presenting in approximately 3% of all patients undergoing colorectal resection. Most reports describe an open approach to the disease, but we report a case isolated ovarian metastases from CRC managed completely by robotic technique. A 54-year-old female, with a family history of CRC, was admitted for rectosigmoid junction cancer. Computed tomography scan demonstrated in rectosigmoid tumor and pelvic mass, presumed as teratoma. Robotic surgery discovered a 10-cm encapsulated tumor, attached to the left ovary, with no macroscopic peritoneal involvement. The pathologic diagnosis of the resected pelvic mass, ovarian metastases from CRC. Robotic anterior resection was performed. Operative time was lasted 165 min, considering 25 min for robotic system set up. This is the first report to describe robot-assisted anterior resection and oophorectomy in patient with isolated ovarian metastases from rectosigmoid junction cancer. PMID:25598608

  9. Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast.

    PubMed

    Moutte, Amandine; Chopin, Nicolas; Faure, Christelle; Beurrier, Frédéric; Ho Quoc, Christophe; Guinaudeau, Florence; Treilleux, Isabelle; Carrabin, Nicolas

    2016-09-01

    Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential. PMID:27265474

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

    PubMed

    Yuan, Lei; Liu, Xishi

    2015-04-01

    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

  11. Molecular Genetic Analysis of Ovarian Brenner Tumors and Associated Mucinous Epithelial Neoplasms: High Variant Concordance and Identification of Mutually Exclusive RAS Driver Mutations and MYC Amplification.

    PubMed

    Tafe, Laura J; Muller, Kristen E; Ananda, Guruprasad; Mitchell, Talia; Spotlow, Vanessa; Patterson, Sara E; Tsongalis, Gregory J; Mockus, Susan M

    2016-03-01

    Benign ovarian Brenner tumors often are associated with mucinous cystic neoplasms, which are hypothesized to share a histogenic origin and progression, however, supporting molecular characterization is limited. Our goal was to identify molecular mechanisms linking these tumors. DNA from six Brenner tumors with paired mucinous tumors, two Brenner tumors not associated with a mucinous neoplasm, and two atypical proliferative (borderline) Brenner tumors was extracted from formalin-fixed, paraffin-embedded tumor samples and sequenced using a 358-gene next-generation sequencing assay. Variant calls were compared within tumor groups to assess somatic mutation profiles. There was high concordance of the variants between paired samples (40% to 75%; P < 0.0001). Four of the six tumor pairs showed KRAS hotspot driver mutations specifically in the mucinous tumor. In the two paired samples that lacked KRAS mutations, MYC amplification was detected in both of the mucinous and the Brenner components; MYC amplification also was detected in a third Brenner tumor. Five of the Brenner tumors had no reportable potential driver alterations. The two atypical proliferative (borderline) Brenner tumors both had RAS mutations. The high degree of coordinate variants between paired Brenner and mucinous tumors supports a shared origin or progression. Differences observed in affected genes and pathways, particularly involving RAS and MYC, may point to molecular drivers of a divergent phenotype and progression of these tumors. PMID:26797085

  12. Ovarian-type epithelial tumours of the testis: immunohistochemical and molecular analysis of two serous borderline tumours of the testis.

    PubMed

    Bürger, Tobias; Schildhaus, Hans-Ulrich; Inniger, Reinhard; Hansen, Joachim; Mayer, Peter; Schweyer, Stefan; Radzun, Heinz Joachim; Ströbel, Philipp; Bremmer, Felix

    2015-01-01

    Tumours of ovarian-epithelial type of the testis, including serous borderline tumours, represent very rare entities. They are identical to the surface epithelial tumours of the ovary and have been reported in patients from 14 to 68 years of age. We describe two cases of a 46- and a 39-year old man with incidental findings of intratesticular masses of the left respectively right testis. Under the assumption of a malignant testicular tumour the patients were subjected to inguinal orchiectomy. Histologically, the tumours were identical to their ovarian counterparts: They showed a cystic configuration with a fibrous wall and irregular papillary structures lined by partially multistratified columnar cells and areas of hobnail cells. Furthermore, there was mild cytological atypia with a proliferative activity of below 5% as proved by Ki67 staining; mitoses could not be detected. Immunohistochemically, the tumour cells displayed expression of pan-cytokeratin AE3, progesterone receptor, Wilms' tumour protein (WT1), and PAX8 (Paired box gene 8). Estrogen receptor was expressed in one case. Octamer-binding transcription factor-4 (OCT4), calretinin, thrombomodulin, and D2-40 were not expressed. Mutation testing of BRAF revealed a BRAF V600E mutation in one case, while testing for KRAS mutations proved to be negative in both. The BRAF mutated tumour showed strong cytosolic and membranous positivity for B-Raf also on immunohistochemical analysis. Comparative genomic hybridization of one case could not reveal any chromosomal aberrations. PMID:26197800

  13. Large malignant ovarian tumors during pregnancy: two cases

    PubMed Central

    Xu, Dong; Liang, Cheng; He, Jing

    2014-01-01

    The present study reports two cases of large ovarian malignancy during pregnancy, which is very rare. The two patients were received between Nov 2012 and Feb 2013 at Gynecological and Obstetrical Department, Women’s Hospital, School of Medicine, Zhejiang University (People’s Republic of China). Both cases present tumor sized more than 20 cm, with one case of 40 cm. Both patients underwent timely cesarean section, with survival of the Child, and successful removal of the tumor. All patients showed good outcome in the follow-up period. Therefore the large ovarian malignancy during pregnancy could be well treated after careful clinical evaluation. PMID:25484595

  14. 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.

  15. Autoantibodies to tumor-associated antigens in epithelial ovarian carcinoma.

    PubMed

    Piura, Benjamin; Piura, Ettie

    2009-01-01

    This review will focus on recent knowledge related to circulating autoantibodies (AAbs) to tumor-associated antigens (TAAs) in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7), heat shock proteins (HSP-27, HSP-90), cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1), MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma. PMID:20145720

  16. Ovarian yolk sac tumors in older women arising from epithelial ovarian tumors or with no detectable epithelial component.

    PubMed

    Roth, Lawrence M; Talerman, Aleksander; Levy, Tally; Sukmanov, Oleg; Czernobilsky, Bernard

    2011-09-01

    Yolk sac tumor (YST) occurs rarely in older women, either in association with a variety of ovarian epithelial tumors or, considerably less often, without an identifiable epithelial precursor. The patients often have elevated serum levels of α-fetoprotein that roughly correlate with the amount of the YST component. In postmenopausal women with an ovarian mass and elevated serum levels of α-fetoprotein, a tumor of this type should be suspected. Endometrioid carcinoma is the most common putative precursor, and the tumor is often associated with an endometriotic cyst; however, malignant Müllerian mixed tumor and mucinous neoplasms have also been reported as precursors. We report 4 cases of YST in postmenopausal women. Of the 3 cases with an identified epithelial component, 1 was serous carcinoma, another was clear cell adenocarcinoma, and the third was an admixture of endometrioid and clear cell adenocarcinoma arising from an endometriotic cyst. Although a precursor epithelial ovarian neoplasm, typically a malignancy (somatic carcinoma), is usually identified, no precursor neoplasm was observed in 1 of our cases and in 5 cases from the literature. We believe that YSTs in older women, whether or not an epithelial component is detected histologically, constitute a single entity that is distinct from YSTs in younger patients and should be treated aggressively. Neoplasms with a YST component in older women are less responsive to the chemotherapy currently used for ovarian germ cell tumors; therefore, adjuvant therapy should include platinum-based chemotherapy designed to treat both epithelial ovarian cancer and germ cell tumors. Of the 24 reported cases, including our own, 17 died of neoplasms within 25 months and another was living with disease at 2 months. However, 2 more recent patients treated aggressively with platinum-based chemotherapy designed to treat both epithelial and germ cell tumor components with stage 1 disease are living and have been disease free >1

  17. Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer

    PubMed Central

    Reusser, Nicole M; Dalton, Heather J; Pradeep, Sunila; Gonzalez-Villasana, Vianey; Jennings, Nicholas B; Vasquez, Hernan G; Wen, Yunfei; Rupaimoole, Rajesh; Nagaraja, Archana S; Gharpure, Kshipra; Miyake, Takahito; Huang, Jie; Hu, Wei; Lopez-Berestein, Gabriel; Sood, Anil K

    2014-01-01

    Purpose Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations. Experimental Design Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis. Results Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density. Conclusions Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer. PMID:24841852

  18. Clinicopathologic features of ovarian Sertoli-Leydig cell tumors

    PubMed Central

    Zhang, Hai-Yan; Zhu, Jia-Er; Huang, Wen; Zhu, Jin

    2014-01-01

    Background: Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up. Methods: A total of sixteen patients with ovarian Sertoli-Leydig cell tumor treated at the Obstetrics and Gynecology Hospital, Shanghai, China, between Jan 2001 and Dec 2011 were reviewed. The clinical data, treatment and prognosis were obtained from medical records. Results: The median age of the patients with ovarian Sertoli-Leydig cell tumor was about 27.5 years old in non-menopausal women, while the median age of menopausal women was about 63 years old. The most common complaint was with hormonal-related symptoms in the form of secondary amenorrhea and infinity, features of virilization, abdominal mass or irregular vaginal bleeding. All of sixteen patients underwent surgical staging and all were found to have stage I disease at the time of diagnosis. Eleven patients with intermediate and two patients with poorly differentiated tumors received adjuvant chemotherapy. There were differences found in operative time, blood loss and postoperative recovery time between laparotomy and laparoscopy. There were no disease-related deaths and all patients were under complete remission at the last follow-up. Conclusions: Ovarian Sertoli-Leydig cell tumors could happen in any period age of women. However, the tumors typically occur in the single side while still at the early stage, a favorable outcome could be achieved by surgery and adjuvant chemotherapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages. PMID:25400781

  19. Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth.

    PubMed

    Huang, Jie; Hu, Wei; Hu, Limin; Previs, Rebecca A; Dalton, Heather J; Yang, Xiao-Yun; Sun, Yunjie; McGuire, Michael; Rupaimoole, Rajesha; Nagaraja, Archana S; Kang, Yu; Liu, Tao; Nick, Alpa M; Jennings, Nicholas B; Coleman, Robert L; Jaffe, Robert B; Sood, Anil K

    2016-06-01

    Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344-52. ©2016 AACR. PMID:27009216

  20. TUMOR PENETRATING MICROPARTICLES FOR INTRAPERITONEAL THERAPY OF OVARIAN CANCER

    PubMed Central

    Lu, Ze; Tsai, Max; Lu, Dan; Wang, Jie; Wientjes, M. Guillaume; Au, Jessie L.-S.

    2009-01-01

    Intraperitoneal (IP) chemotherapy prolongs survival of ovarian cancer patients, but its utility is limited by treatment-related complications and inadequate drug penetration in larger tumors. Previous IP therapy used the paclitaxel/Cremophor formulation designed for intravenous use. The present report describes the development of paclitaxel-loaded microparticles designed for IP treatment (referred to as tumor penetrating microparticles or TPM). Evaluation of TPM was performed using IP metastatic, human ovarian SKOV3 xenograft tumor models in mice. TPM were retained in the peritoneal cavity and adhered to tumor surface. TPM consisted of two biocompatible and biodegradable polymeric components with different drug release rates; one component released the drug load rapidly to induce tumor priming while the second component provided sustained drug release. Tumor priming, by expanding interstitial space, promoted transport and penetration of particulates in tumors. These combined features resulted in the following advantages over paclitaxel/Cremophor: greater tumor targeting (16-times higher and more sustained concentration in omental tumors), lower toxicity to intestinal crypts and less body weight loss, greater therapeutic efficacy (longer survival and higher cure rate), and greater convenience (less frequent dosing). TPM may overcome the toxicities and compliance-related problems that have limited the utility of IP therapy. PMID:18780831

  1. Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor

    PubMed Central

    Hale, Demir; Senem, Demiroz Ahu; Ovgu, Aydin; Hakan, Erenel; Sennur, Ilvan; Zerrin, Calay; Fuat, Demirkiran

    2015-01-01

    Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported. PMID:26713165

  2. 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

  3. Review of ovarian tumors in children and adolescents: radiologic-pathologic correlation.

    PubMed

    Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Seo In; Lim, Hyo Soon; Choi, Yoo Duk; Lee, Kyoung Hwa; Kang, Woo Dae; Jeong, Yong Yeon; Kang, Heoung Keun

    2014-01-01

    The incidence, histologic distribution, and clinical manifestations of ovarian tumors in the pediatric population are distinct from those in adults. Although ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be considered in young girls with abdominal pain and a palpable mass. Differential diagnosis in children and adolescents with ovarian tumors should be conducted on the basis of unique clinical manifestations, elevated serum tumor marker levels, and distinctive imaging findings. Although the clinical manifestations are nonspecific and may overlap, they may assist in diagnosis of some types of ovarian tumors. Children who present with a palpable mass or symptoms of precocious puberty have a high likelihood of malignancy. Many ovarian tumors are associated with abnormal hormonal activity and/or abnormal sexual development. Elevated levels of serum tumor markers, including α-fetoprotein, the beta subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian malignancies. However, negative tumor markers do not exclude the possibility of malignancy. Identification of imaging features at ultrasonography, computed tomography, and magnetic resonance imaging can help differentiate benign from malignant ovarian tumors and, in turn, plays a crucial role in determining treatment options. At imaging, malignant ovarian tumors usually appear predominantly solid or heterogeneous and are larger than benign tumors. Because surgery is the primary treatment for ovarian tumors, ovarian salvage with fertility preservation and use of a minimally invasive surgical technique are important in children and adolescents. PMID:25384300

  4. Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

    PubMed

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P; Veras, Emanuela; Park, Kay J; Soslow, Robert A

    2016-03-01

    Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology

  5. In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells

    PubMed Central

    House, Carrie D.; Hernandez, Lidia; Annunziata, Christina M.

    2015-01-01

    Evidence suggests that small subpopulations of tumor cells maintain a unique self-renewing and differentiation capacity and may be responsible for tumor initiation and/or relapse. Clarifying the mechanisms by which these tumor-initiating cells (TICs) support tumor formation and progression could lead to the development of clinically favorable therapies. Ovarian cancer is a heterogeneous and highly recurrent disease. Recent studies suggest TICs may play an important role in disease biology. We have identified culture conditions that enrich for TICs from ovarian cancer cell lines. Growing either adherent cells or non-adherent ‘floater’ cells in a low attachment plate with serum free media in the presence of growth factors supports the propagation of ovarian cancer TICs with stem cell markers (CD133 and ALDH activity) and increased tumorigenicity without the need to physically separate the TICs from other cell types within the culture. Although the presence of floater cells is not common for all cell lines, this population of cells with innate low adherence may have high tumorigenic potential.Compared to adherent cells grown in the presence of serum, TICs readily form spheres, are significantly more tumorigenic in mice, and express putative stem cell markers. The conditions are easy to establish in a timely manner and can be used to study signaling pathways important for maintaining stem characteristics, and to identify drugs or combinations of drugs targeting TICs. The culture conditions described herein are applicable for a variety of ovarian cancer cells of epithelial origin and will be critical in providing new information about the role of TICs in tumor initiation, progression, and relapse. PMID:25742116

  6. Updates in the management of ovarian germ cell tumors.

    PubMed

    Matei, Daniela; Brown, Jubilee; Frazier, Lindsay

    2013-01-01

    Ovarian germ cell tumors are rare events at all ages-in pediatrics, adolescence, and during young adulthood. Combining the knowledge and experience of pediatric and gynecologic oncologists can lead to better outcomes for all. In this review, we intend to present the latest consensus on management of women and children with this disease and highlight the opportunities for collaboration and clinical research going forward. PMID:23714505

  7. An evaluation of the morphologic features of low-grade mucinous neoplasms of the appendix metastatic in the ovary, and comparison with primary ovarian mucinous tumors.

    PubMed

    Stewart, Colin J R; Ardakani, Nima M; Doherty, Dorota A; Young, Robert H

    2014-01-01

    It may be difficult to distinguish ovarian involvement by a low-grade appendiceal mucinous neoplasm (LAMN) from a primary gastrointestinal-type primary borderline (proliferative) ovarian tumor (IBMT) or an ovarian mucinous tumor arising within a teratoma, particularly when the latter is associated with mucinous ascites/pseudomyxoma peritonei. We noted that LAMNs involving the ovaries show 2 distinctive histologic features, "scalloped" glands and subepthelial stromal clefts, whereas IBMTs more often are associated with reactive cellular stroma and histiocyte aggregates (mucin granulomas). The frequency of these features was investigated in 18 LAMNs (16 with pseudomyxoma peritonei), 18 primary IBMTs, and 6 teratoma-associated mucinous tumors (selected on the basis of associated pseudomyxoma peritonei). Scalloped glands and subepithelial clefts were identified in 17 and 16 LAMNs, respectively, and in 3 and 7 IBMTs, respectively. Conversely, reactive stroma and histiocyte aggregates were present in 2 and 0 LAMNs, respectively, and in 11 and 10 IBMTs, respectively. LAMNs were often bilateral (12/18 cases) and they more frequently showed mucin dissection of the ovarian stroma and tall mucin-rich (hypermucinous) epithelial cells compared with IBMTs. Our findings suggest that scalloped glands, subepithelial clefts, cellular stroma, and histiocyte aggregates may be useful additional morphologic parameters to help distinguish these tumor types. However, teratoma-associated mucinous neoplasms can show identical histologic features to those of LAMNs involving the ovary, and therefore accurate diagnosis of such cases requires careful macroscopic and microscopic examinations of the ovaries together with complete histologic assessment of the appendix. PMID:24300528

  8. A new tumor marker: CA125 for ovarian carcinomas

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Nakashima, T.; Koizumi, M.; Ohta, H.; Torizuka, K.; Konishi, I.; Fujii, S.; Mori, T.

    1985-05-01

    To evaluate CA125 as a tumor marker for ovarian carcinomas, CA125 concentrations were measured by the simultaneous immunoradiometric assay. The binding of I-125 labeled monoclonal antibody to the bead-bound antigen was greatly influenced by many factors, such as the incubation time, pH, IgG concentrations of samples, the sequence of addition of the tracer and samples and so on. By applying the forward two-step assay, diminished binding was observed than in the simultaneous assay, probably due to the relatively low affinity of the antibody. This simultaneous immunoradiometric assay resulted in the ''prozone'' or ''hook'' effect at high CA125 samples and proper dilution was necessary to determine the accurate CA125 values. All 72 normal control subjects had low concentrations of under 35 U/ml. Elevated serum CA125 was observed in 43% (9/21) cases with malignant ovarian tumors, depending on the stage and the histopathological findings. All 4 serous cystadenocarcinomas and 2 of 3 endometrioid carcinomas were positive and the measurement of serum CA125 was useful in the sequential monitoring of these cases. In contrast, 51 benign gynecological diseases, none had elevated serum CA125 except one with follicular cyst. Among 75 cases with non-gynecological benign and malignant diseases, only 1 of 12 gastric carcinomas and 2 of 13 pancreatic carcinomas had elevated CA125 levels. In summary, CA125 is a promising and relatively specific marker for ovarian carcinomas.

  9. Young women diagnosed with early-stage ovarian cancer or borderline malignancy of the ovary: a focus on fertility and sexual function.

    PubMed

    Campos, Susana M; Berlin, Suzanne; Matulonis, Ursula A; Muto, Michael G; Pereira, Lauren; Mosquera, Merily M; Horowitz, Neil

    2012-01-01

    Malignant ovarian neoplasms represent the leading cause of death in gynecological malignancies. Although the majority of ovarian neoplasms occur in women of advanced years, ovarian neoplasms can occur in women of the reproductive age group. Preservation of fertility balanced with treatment of disease is the goal of young patients diagnosed with ovarian neoplasms. A new discipline termed "oncofertility" has emerged; however, several informational gaps exist. Concern has centered on the safety of conservative treatment, the uncertain efficacy of fertility options, the detrimental effects of chemotherapy to remaining reproductive organs, and the timing and execution of fertility workup relative to disease requiring treatment. This study involved an evaluation of young premenopausal women who underwent fertility-sparing surgery for an ovarian neoplasm. Given the rarity of this disease in premenopausal women the objective was to assess the feasibility of this study as defined by the completion rate of the survey. The aim was to broaden our knowledge of patient needs to partner with our survivorship clinic thereby ensuring that patients may facilitate their options. Patients were asked to complete a questionnaire titled Ovarian Cancer or Borderline Malignancy of the Ovary: Fertility Sparing Survey and a previously published instrument termed The Sexual Activity Questionnaire, a 21-item scale that assessed the impact of treatment on sexual functioning. All participants completed the survey illustrating the feasibility of the study. The study revealed that the majority of patients (91%) discussed fertility options with their clinicians, yet only 16% engaged in measures to preserve fertility. Patient's sexual interest and activity was maintained in this cohort of patients. This underscores the importance of continued studies in this unique population to ensure optimal fertility counseling and to better delineate the sexual well-being of young women diagnosed with ovarian

  10. New ways to successfully target tumor vasculature in ovarian cancer

    PubMed Central

    Yang, Xiaoyun; Shen, Fangrong; Hu, Wei; Coleman, Robert L.; Sood, Anil K.

    2015-01-01

    Purpose of review The aim of this paper was to review the recent literature on potential therapeutic strategies for overcoming resistance to anti-VEGF drugs in ovarian cancer. Recent findings Although clinical benefits of anti-VEGF therapy were observed in ovarian cancer treatment trials, this use yielded only modest improvement in progression-free survival, and with the exception of cediranib no effect on overall survival. Adaptive resistance and escape from anti-angiogenesis therapy is likely a multifactorial process, including induction of hypoxia, vascular modulators and the immune response. New drugs targeting the tumor vasculature or other components of the surrounding microenvironment have shown promising results. Summary When to start and end antiangiogenesis therapy and the choice of optimal treatment combinations remain controversial. Further evaluation of personalized novel angiogenesis-based therapy is warranted. Defining the critical interaction of these agents and pathways and the appropriate predictive markers will become an increasingly important objective for effective treatment. PMID:25502429

  11. MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    PubMed Central

    2010-01-01

    Background The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52), which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Methods Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. Results MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p < 0.001; n = 124) and was an independent predictor of survival in the overall carcinoma cohort (hazard ratio (HR), 0.498; 95% confidence interval (CI), 0.34-0.728; p < 0.001; n = 221), and in serous carcinomas (HR, 0.440; 95% CI, 0.294-0.658; p < 0.001; n = 182). Conclusions MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients. PMID:20846453

  12. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo

    PubMed Central

    Koneru, Mythili; Purdon, Terence J.; Spriggs, David; Koneru, Susmith; Brentjens, Renier J.

    2015-01-01

    A novel approach for the treatment of ovarian cancer includes immunotherapy with genetically engineered T cells targeted to ovarian cancer cell antigens. Using retroviral transduction, T cells can be created that express an artificial T cell receptor (TCR) termed a chimeric antigen receptor (CAR). We have generated a CAR, 4H11-28z, specific to MUC-16ecto antigen, which is the over-expressed on a majority of ovarian tumor cells and is the retained portion of MUC-16 after cleavage of CA-125. We previously demonstrated that T cells modified to express the 4H11-28z CAR eradicate orthotopic human ovarian cancer xenografts in SCID-Beige mice. However, despite the ability of CAR T cells to localize to tumors, their activation in the clinical setting can be inhibited by the tumor microenvironment, as is commonly seen for endogenous antitumor immune response. To potentially overcome this limitation, we have recently developed a construct that co-expresses both MUC16ecto CAR and IL-12 (4H11-28z/IL-12). In vitro, 4H11-28z/IL-12 CAR T cells show enhanced proliferation and robust IFNγ secretion compared to 4H11-28z CAR T cells. In SCID-Beige mice with human ovarian cancer xenografts, IL-12 secreting CAR T cells exhibit enhanced antitumor efficacy as determined by increased survival, prolonged persistence of T cells, and higher systemic IFNγ. Furthermore, in anticipation of translating these results into a phase I clinical trial which will be the first to study IL-12 secreting CAR T cells in ovarian cancer, an elimination gene has been included to allow for deletion of CAR T cells in the context of unforeseen or off-tumor on-target toxicity. PMID:25949921

  13. Sequence and structure of the Drosophila melanogaster ovarian tumor gene and generation of an antibody specific for the ovarian tumor protein.

    PubMed Central

    Steinhauer, W R; Walsh, R C; Kalfayan, L J

    1989-01-01

    Sequencing cDNA and genomic DNA from the ovarian tumor gene revealed a gene with seven introns spanning 4.5 kilobases. The proline-rich, hydrophilic otu protein is novel. An antibody prepared to a beta-gal-otu fusion protein recognized a 110-kilodalton ovarian protein which was altered in the ovaries of otu gene mutants. Images PMID:2511440

  14. Uterine tumors resembling ovarian sex cord tumors: A case report and literature review

    PubMed Central

    CETINKAYA, NILUFER; BAS, SEVDA; CUYLAN, ZELIHA FIRAT; ERDEM, OZLEM; ERKAYA, SALIM; GUNGOR, TAYFUN

    2016-01-01

    Uterine tumors with ovarian sex cord-like elements are a rarely observed type of uterine body tumor with unknown etiology, and are divided into two groups: Endometrial stromal tumors with sex cord-like elements (ESTSCLEs) and uterine tumors resembling ovarian sex cord tumors (UTROSCTs). While ESTSCLEs are commonly associated with metastasis and recurrence, there is limited data in the relevant literature concerning the behavior of UTROSCTs. However, UTROSCTs are typically benign in nature. Although case numbers are limited, extra-uterine or lymph node metastasis has been reported. Surgical approaches may be altered according to the patient's age and desire for future fertility. Hysterectomies with bilateral salpingo-oopherectomy or hysteroscopic tumor resection are reported to be safe surgical treatment options. However, in the current report, a case of UTROSCT initially misdiagnosed as adenosarcoma following hysteroscopic tumor resection is presented. Staging surgery revealed the precise diagnosis of the tumor using appropriate immunohistochemical evaluations, and led to the discovery of a secondary tumor focus in the myometrium, adjacent to the location of the previously excised tumor. Thus, hysteroscopic resection is questionable as a definitive surgical treatment in patients exhibiting UTROSCT. If hysteroscopic resection is the selected treatment, close follow-up with diagnostic imaging is recommended. PMID:26893767

  15. 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.

  16. 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

  17. 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

  18. Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

    PubMed Central

    WU, DI; ZHANG, HAIPENG; GUO, LIANG; YAN, XU; FAN, ZHIMIN

    2016-01-01

    Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor. PMID:27073506

  19. Changes in expression of differentiation markers between normal ovarian cells and derived tumors.

    PubMed Central

    Van Niekerk, C. C.; Ramaekers, F. C.; Hanselaar, A. G.; Aldeweireldt, J.; Poels, L. G.

    1993-01-01

    The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7678716

  20. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    PubMed

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  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. 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.

    2015-01-01

    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, and 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.

  3. Different staining patterns of ovarian Brenner tumor and the associated mucinous tumor.

    PubMed

    Roma, Andres A; Masand, Ramya P

    2015-02-01

    The association of ovarian Brenner tumors and adjacent mucinous tumors is well known but not completely understood. In this study, we analyzed immunohistochemical markers on Brenner tumors and their associated mucinous tumor to explore Mullerian as well as Wolffian and germ cell derivation and determine if the mucinous component is independent or related to the Brenner tumor. Of 32 consecutive cases of Brenner tumors, 8 were identified with significant mucinous component, and 7 additional cases included foci of mucinous epithelium within the Brenner transitional nests. All Brenner tumors were diffusely positive for GATA3 and negative for Paired box gene 8, PAX2, and Sal-like protein 4. Interestingly, the areas of mucinous epithelium as well as mucinous tumors, intermixed and adjacent to the Brenner tumor, were negative for all 4 markers; however, occasional basal-like cells retained expression of GATA3. The immunoprofile of mucinous tumors associated with Brenner tumors shares the lack of Mullerian markers PAX2 and Paired box gene 8 with the Brenner tumor but differs in the expression of GATA3 only in the Brenner tumor component. PMID:25596159

  4. Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer☆

    PubMed Central

    Makowski, Liza; Zhou, Chunxiao; Zhong, Yan; Kuan, Pei Fen; Fan, Cheng; Sampey, Brante P.; Difurio, Megan; Bae-Jump, Victoria L.

    2014-01-01

    Objectives Obesity is associated with increased risk and worse outcomes for ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer progression in a genetically engineered mouse model of serous ovarian cancer. Methods We utilized a unique serous ovarian cancer mouse model that specifically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60% calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6 months after AdCre injection and evaluated histologically. Untargeted metabolomic and gene expression profiling was performed to assess differences in the ovarian tumors from obese versus non-obese KpB mice. Results At sacrifice, mice on the HFD (obese) were twice the weight of mice on the LFD (non-obese) (51 g versus 31 g, p = 0.0003). Ovarian tumors were significantly larger in the obese versus non-obese mice (3.7 cm2 versus 1.2 cm2, p = 0.0065). Gene expression and metabolomic profiling indicated statistically significant differences between the ovarian tumors from the obese versus non-obese mice, including metabolically relevant pathways. PMID:24680597

  5. Harnessing Pandemonium: The Clinical Implications of Tumor Heterogeneity in Ovarian Cancer

    PubMed Central

    Blagden, Sarah P.

    2015-01-01

    Heterogeneity has emerged as a key feature of ovarian cancer between different ovarian cancer subtypes; within single ovarian cancer subtypes; and within individual patient tumors. At the genomic level, with the advent of ultra-deep sequencing technologies alongside RNA-Seq, epigenomics, and proteomics, the complexity surrounding heterogeneity has deepened. Here, we summarize the emerging understanding of heterogeneity in cancer as a whole and the key discoveries in this area relating to ovarian cancer. We explore the therapeutic limitations and possibilities posed by heterogeneity and how these will influence the future of ovarian cancer treatment and research. PMID:26175968

  6. Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

    PubMed Central

    Kwon, Mi Jeong; Shin, Young Kee

    2013-01-01

    Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

  7. 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. PMID:21389861

  8. Risk factors for deep-vein thrombosis and pulmonary thromboembolism in benign ovarian tumor.

    PubMed

    Shiota, Mitsuru; Kotani, Yasushi; Umemoto, Masahiko; Tobiume, Takako; Tsuritani, Mitsuhiro; Shimaoka, Masao; Hoshiai, Hiroshi

    2011-01-01

    Pulmonary thromboembolism (PE) is a serious postoperative complication. Reported rates of PE following gynecologic surgery are between 0.3% and 0.8%, with deep-vein thrombosis (DVT) as the major cause (via seeding of the lungs). Benign ovarian tumors are treated principally by surgery. Possible risk factors for DVT and PE in patients with benign ovarian tumors include tumor size, patient age, and obesity. To date, however, there has been no report addressing the association of these risk factors in patients with benign ovarian tumors. This study offers a retrospective analysis of the incident of preoperative DVT by age, tumor size, and BMI in patients undergoing surgery for benign ovarian tumors. A total of 843 Japanese patients with a preoperative diagnosis of benign ovarian tumor who underwent tumorectomy or adnexectomy at our institution between July 2003 and December 2010 were enrolled. The incidence of preoperative DVT was monitored and statistically stratified by age (< 50 years and ≥ 50 years), largest tumor diameter (< 10 cm and ≥ 10 cm), and BMI (< 25 and ≥ 25). The result indicates that tumor diameter of ≥ 10 cm is not a risk factor for preoperative DVT in patients with benign ovarian tumor. On the other hand, age ≥ 50 years and BMI > 25 are independent risk factors for preoperative DVT in Japan. The patients with each risk factor should be treated with preoperative, intraoperative, and postoperative precautions against development of PE. PMID:21817850

  9. Detection of the BRAF V600E mutation in serous ovarian tumors: a comparative analysis of immunohistochemistry with a mutation-specific monoclonal antibody and allele-specific PCR.

    PubMed

    Bösmüller, Hans; Fischer, Anna; Pham, Deborah L; Fehm, Tanja; Capper, David; von Deimling, Andreas; Bonzheim, Irina; Staebler, Annette; Fend, Falko

    2013-03-01

    Mutations of components of the mitogen-activated protein kinase pathway, mainly BRAF, are common in serous ovarian borderline tumors, whereas high-grade serous ovarian carcinomas rarely show this feature. With the advent of specific kinase inhibitors active against BRAF-mutated cancers, rapid and sensitive detection of the BRAF V600E, by far the most common mutation of this gene, is of great practical relevance. Currently, BRAF mutations are detected by DNA-based techniques. Recently, a monoclonal antibody (VE1) specific for the BRAF V600E protein suitable for archival tissues has been described. In this study, we compared detection of the V600E mutation in serous ovarian tumors by VE1 immunostaining and by allele-specific polymerase chain reaction. All 141 cases of high-grade serous ovarian cancer showed negative or rarely weak, diffuse background VE1 immunostaining, and BRAF wild type was confirmed by molecular analysis in all tested cases. In contrast, 1 (14%) of 7 low-grade serous carcinomas and 22 (71%) of 31 serous borderline tumors revealed moderate to strong VE1 positivity. Immunostaining was clearly evaluable in all cases with sufficient tumor cells, and only rare cases with narrow cytoplasm were difficult to interpret. The V600E mutation was confirmed by allele-specific polymerase chain reaction and sequencing in all VE1-positive cases. Two VE1-positive cases with low epithelial cell content required repeat microdissection to confirm the presence of the mutation. Immunohistochemistry with the VE1 antibody is a specific and sensitive tool for detection of the BRAF V600E mutation in serous ovarian tumors and may provide a practical screening test, especially in tumor samples with low epithelial content. PMID:23089489

  10. Atypical proliferative endometrioid tumor of ovary: Report of a rare case

    PubMed Central

    Jetley, S; Khetrapal, S; Ahmad, A; Jairajpuri, ZS

    2016-01-01

    Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms that typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. Atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness, microscopic examination is mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma. We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence. PMID:26497398

  11. Treatment of ovarian endodermal sinus tumor to preserve fertility.

    PubMed

    Chang, Yi-Wen; Chao, Kuan-Chong; Sung, Pi-Lin; Li, Wai Hou; Wang, Peng-Hui

    2013-02-01

    Endodermal sinus tumor, also known as yolk sac tumor (YST), is a malignant germ cell tumor that most frequently occurs in the testis, the ovary, and sacrococcygeal areas in children. YSTs are highly aggressive and because of the early metastatic or invasive pattern, their prognosis has been poor. Treatment methods for YSTs are usually intensive, including multiagent chemotherapy, and have shown to improve patient survival significantly; therefore, it is important to consider the reproductive function of these patients with long-term survival. Herein, we present the case of a 31-year-old female, who was diagnosed with unilateral ovarian YST at the age of 13. The patient was treated with fertility-sparing surgery and postoperative adjuvant chemotherapy. During the subsequent long-term follow-up, she was not only free of disease, but also had a successful, naturally conceived pregnancy at 31 years of age. We, therefore, conclude that YST is a curable disease, and that fertility-preservation surgery and subsequent immediate combination chemotherapy is the treatment of choice. PMID:23351423

  12. 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

  13. 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.

  14. Multilocular peritoneal inclusion cyst mimicking an ovarian tumor: A case report

    PubMed Central

    Singh, Anju; Sehgal, Alka; Mohan, Harsh

    2015-01-01

    Peritoneal inclusion cysts are uncommon abdominopelvic cysts seen in perimenopausal women. It is often misdiagnosed clinically as an ovarian tumor due to similar presentation and mimicking findings on radiology. We describe a perimenopausal woman presenting with pelvic mass. Her clinical finding on radiology suggested an ovarian tumor; however, biopsy revealed it as peritoneal inclusion cysts. We discuss the possible ways to avoid such mistakes. PMID:25861208

  15. Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth.

    PubMed

    Becker, Marc A; Farzan, Thahir; Harrington, Sean C; Krempski, James W; Weroha, S John; Hou, Xiaonan; Kalli, Kimberly R; Wong, Tai W; Haluska, Paul

    2013-12-01

    Ovarian cancer mortality ranks highest among all gynecologic cancers with growth factor pathways playing an integral role in tumorigenesis, metastatic dissemination, and therapeutic resistance. The HER and VEGF receptor (VEGFR) are both overexpressed and/or aberrantly activated in subsets of ovarian tumors. While agents targeting either the HER or VEGF pathways alone have been investigated, the impact of these agents have not led to overall survival benefit in ovarian cancer. We tested the hypothesis that cotargeting HER and VEGFR would maximize antitumor efficacy at tolerable doses. To this end, ovarian cancer xenografts grown intraperitoneally in athymic nude mice were tested in response to AC480 (pan-HER inhibitor, "HERi"), cediranib (pan-VEGFR inhibitor "VEGFRi"), or BMS-690514 (combined HER/VEGFR inhibitor "EVRi"). EVRi was superior to both HERi and VEGFRi in terms of tumor growth, final tumor weight, and progression-free survival. Correlative tumor studies employing phosphoproteomic antibody arrays revealed distinct agent-specific alterations, with EVRi inducing the greatest overall effect on growth factor signaling. These data suggest that simultaneous inhibition of HER and VEGFR may benefit select subsets of ovarian cancer tumors. To this end, we derived a novel HER/VEGF signature that correlated with poor overall survival in high-grade, late stage, serous ovarian cancer patient tumors. PMID:24130056

  16. Expression of AQP6 and AQP8 in epithelial ovarian tumor.

    PubMed

    Ma, Jiong; Zhou, Chunxia; Yang, Jianhua; Ding, Xiaoyan; Zhu, Yunshan; Chen, Xuejun

    2016-04-01

    Aquaporins (AQPs), the rapid transition pores for water molecules, play an important role in maintenance of intracellular water balance. Studies showed that AQPs were also involved in occurrence, development, invasion and metastasis of tumors. In this study, we aimed to explore the distribution and expression differences of aquaporin 6 (AQP6) and aquaporin 8 (AQP8) in epithelial ovarian tumors. The expression of AQP6 and AQP8 in 47 cases of epithelial ovarian tumors were measured by immunochemical technique and Western blotting. AQP6 was strongly expressed in benign ovarian tumors, but weak signal was shown in malignant tumors. The difference was not statistically significant (P > 0.05). Compared with serous adenoma and normal tissues, AQP6 expression in serous carcinoma was obviously decreased (P < 0.05). AQP8 expressions were both identified in benign and malignant tumors, but there was no significantly statistical difference (P > 0.05). For patients with large volume of malignant ascites (>1000 ml), AQP8 expression was increased (P < 0.05). AQP8 expression in malignant tumors was not related to different clinical stages, presence of lymphatic metastasis, and differentiation degrees (P > 0.05). These data showed that AQP6 and AQP8 had different expression degrees in epithelial ovarian tissues, which suggests that AQP6 and AQP8 may play certain roles in epithelial ovarian tumors. PMID:26779650

  17. 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

  18. Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature

    PubMed Central

    Lee, Jessica; John, Veena S.; Liang, Sharon X.; D'Agostino, Catherine A.; Menzin, Andrew W.

    2016-01-01

    We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID:27375912

  19. CT imaging of ovarian yolk sac tumor with emphasis on differential diagnosis.

    PubMed

    Li, Yang-Kang; Zheng, Yu; Lin, Jian-Bang; Xu, Gui-Xiao; Cai, Ai-Qun; Zhou, Xiu-Guo; Zhang, Guo-Jun

    2015-01-01

    Ovarian yolk sac tumors (YSTs) are rare neoplasms. No radiological study has been done to compare the imaging findings between this type of tumor and other ovarian tumors. Here we analyzed the CT findings of 11 pathologically proven ovarian YSTs and compared their imaging findings with 18 other types of ovarian tumors in the same age range. Patient age, tumor size, tumor shape, ascites and metastasis of two groups did not differ significantly (P > 0.05). A mixed solid-cystic nature, intratumoral hemorrhage, marked enhancement and dilated intratumoral vessel of two groups differed significantly (P < 0.05). The area under the ROC curve of four significant CT features was 0.679, 0.707, 0.705, and 1.000, respectively. Multivariate logistic regression analysis identified two independent signs of YST: intratumoral hemorrhage and marked enhancement. Our results show that certain suggestive CT signs that may be valuable for improving the accuracy of imaging diagnosis of YST and may be helpful in distinguishing YST from other ovarian tumors. PMID:26074455

  20. Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression

    PubMed Central

    2014-01-01

    Background Hyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study’s objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management. Methods We assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts. Results We showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier. Conclusions For the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks. PMID:24739440

  1. Molecular characterization of circulating tumor cells in ovarian cancer

    PubMed Central

    Kolostova, Katarina; Pinkas, Michael; Jakabova, Anna; Pospisilova, Eliska; Svobodova, Pavla; Spicka, Jan; Cegan, Martin; Matkowski, Rafal; Bobek, Vladimir

    2016-01-01

    The main focus of the study was to detect circulating tumor cells (CTCs) in ovarian cancer (OC) patients using a new methodological approach (MetaCellTM) which is based on size-dependent separation of CTCs and subsequent cytomorphological evaluation. Cytomorphological evaluation using vital fluorescence microscopy approach enables to use the captured cells for further RNA/DNA analysis. The cytomorphological analysis is then completed by gene expression analysis (GEA). GEA showed that relative expression of EPCAM is elevated in CTC-enriched fractions in comparison to the whole peripheral blood sample and that the expression grows with in vitro cultivation time. Comparison of the relative gene expression level in the group of peripheral blood samples and CTC-fraction samples confirmed a statistically significant difference for the following genes (p < 0.02): KRT7, WT1, EPCAM, MUC16, MUC1, KRT18 and KRT19. Thus, we suggest that the combination of the above listed genes could confirm CTCs presence in OC patients with higher specificity than when GEA tests are performed for one marker only. The GEA revealed two separate clusters identifying patients with or without CTCs. PMID:27293992

  2. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report.

    PubMed

    Orsi, Nicolas M; Menon, Mini

    2016-08-01

    Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10-12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area. PMID:27508272

  3. Evaluation and Management of Ultrasonographically Detected Ovarian Tumors in Asymptomatic Women.

    PubMed

    van Nagell, John Rensselaer; Miller, Rachel Ware

    2016-05-01

    Data from screening trials indicate that a significant percent of asymptomatic women older than 50 years of age will develop ovarian abnormalities that are detectable by ultrasonography. Most of these abnormalities are benign, and many will resolve spontaneously. However, the risk of ovarian cancer, particularly in postmenopausal women, is of concern. The goal is to use a diagnostic and treatment algorithm that will reliably detect ovarian cancer at the earliest possible stage while limiting the number of women undergoing surgery for benign disease. The combination of morphology indexing and serum biomarker analysis can accurately predict the risk of malignancy in most ovarian tumors. Ovarian tumors with cystic or septate morphology are at minimal risk of malignancy and can be followed with serial ultrasonography evaluations, thereby avoiding the morbidity and cost of surgery. Complex or solid ovarian tumors with a high morphology index score, or those with increasing biomarker production, are at a high risk of malignancy, and patients with these tumors should be referred to a gynecologic oncologist for further evaluation and treatment. PMID:27054927

  4. Napsin A is a specific marker for ovarian clear cell adenocarcinoma.

    PubMed

    Yamashita, Yoriko; Nagasaka, Tetsuro; Naiki-Ito, Aya; Sato, Shinya; Suzuki, Shugo; Toyokuni, Shinya; Ito, Masafumi; Takahashi, Satoru

    2015-01-01

    Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors. PMID:24721826

  5. The effect of Escherichia coli lipopolysaccharide and Tumor Necrosis Factor alpha on ovarian function

    PubMed Central

    Williams, Erin J.; Sibley, Kelly; Miller, Aleisha N.; Lane, Elizabeth A.; Fishwick, John; Nash, Deborah M.; Herath, Shan; England, Gary CW; Dobson, Hilary; Sheldon, I. Martin

    2009-01-01

    Problem Pelvic inflammatory disease and metritis are important causes of infertility in humans and domestic animals. Uterine infection with Escherichia coli in cattle is associated with reduced ovarian follicle growth and decreased estradiol secretion. We hypothesized that this effect could be mediated by the bacterial lipopolysaccharide (LPS) or cytokines such as tumor necrosis factor alpha (TNFα). Method of study In vitro, bovine ovarian theca and granulosa cells were treated with LPS or TNFα and steroid secretion measured. In vivo, the effect of LPS or TNFα intrauterine infusion was determined by ovarian ultrasonography and measurement of hormones in cattle. Results LPS reduced granulosa cell estradiol secretion, whilst TNFα decreased theca and granulosa cell androstenedione and estradiol production, respectively. In vivo, fewer animals ovulated following intrauterine infusion with LPS or TNFα. Conclusion LPS and TNFα suppress ovarian cell function, supporting the concept that pelvic inflammatory disease and metritis are detrimental for bovine ovarian health. PMID:19238751

  6. A novel biomarker ARMc8 promotes the malignant progression of ovarian cancer.

    PubMed

    Jiang, Guiyang; Yang, Dalei; Wang, Liang; Zhang, Xiupeng; Xu, Hongtao; Miao, Yuan; Wang, Enhua; Zhang, Yong

    2015-10-01

    Ovarian cancer is the most lethal gynecologic malignancy worldwide, and the survival rates have remained low in spite of medical advancements. More research is dedicated to the identification of novel biomarkers for this deadly disease. The association between ARMc8 and ovarian cancer remained unraveled. In this study, immunohistochemical staining was used to examine ARMc8 expression in 247 cases of ovarian cancer, 19 cases of borderline ovarian tumors, 41 cases of benign ovarian tumors, and 9 cases of normal ovarian tissues. It was shown that ARMc8 was predominantly located in the cytoplasm of tumor cells, and its expression was up-regulated in the ovarian cancer (61.9%) and the borderline ovarian tumor tissues (57.9%), in comparison with the benign ovarian tumors (12.2%; P < .05) and the normal ovarian tissues (11.1%; P < .05). In ovarian cancer, ARMc8 expression was closely related to International Federation of Gynecology and Obstetrics stages (P = .002), histology grade (P < .001), lymph node metastasis (P = .008), and poor prognosis (P < .001). Univariate and multivariate Cox analyses revealed that ARMc8 expression was an independent prognostic factor for ovarian cancer (P = .039 and P = .005). In addition, ARMc8 could promote the invasion and migration of ovarian cancer cells. Overexpressing ARMc8 enhanced the invasion and metastasis capacity of ARMc8-low Cavo-3 cells (P < .001), whereas interfering ARMc8 significantly reduced cell invasion and metastasis in ARMc8-high SK-OV-3 cells (P < .001). Furthermore, ARMc8 could up-regulate matrix metalloproteinase-7 and snail and down-regulate α-catenin, p120ctn, and E-cadherin. Collectively, ARMc8 may enhance the invasion and metastasis of ovarian cancer cells and likely to become a potential therapeutic target for ovarian cancer. PMID:26232863

  7. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features.

    PubMed

    Shaaban, Akram M; Rezvani, Maryam; Elsayes, Khaled M; Baskin, Henry; Mourad, Amr; Foster, Bryan R; Jarboe, Elke A; Menias, Christine O

    2014-01-01

    Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient's age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care. PMID:24819795

  8. Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure

    PubMed Central

    Colombo, Pierre-Emmanuel; du Manoir, Stanislas; Orsetti, Béatrice; Bras-Gonçalves, Rui; Lambros, Mario B.; MacKay, Alan; Nguyen, Tien-Tuan; Boissiére, Florence; Pourquier, Didier; Bibeau, Frédéric; Reis-Filho, Jorge S.; Theillet, Charles

    2015-01-01

    Advanced Epithelial Ovarian Cancer (EOC) patients frequently relapse by 24 months and develop resistant disease. Research on EOC therapies relies on cancer cell lines established decades ago making Patient Derived Xenografts (PDX) attractive models, because they are faithful representations of the original tumor. We established 35 ovarian cancer PDXs resulting from the original graft of 77 EOC samples onto immuno-compromised mice. PDXs covered the diversity of EOC histotypes and graft take was correlated with early patient death. Fourteen PDXs were characterized at the genetic and histological levels. PDXs reproduced phenotypic features of the ovarian tumors of origin and conserved the principal characteristics of the original copy number change (CNC) profiles over several passages. However, CNC fluctuations in specific subregions comparing the original tumor and the PDXs indicated the oligoclonal nature of the original tumors. Detailed analysis by CGH, FISH and exome sequencing of one case, for which several tumor nodules were sampled and grafted, revealed that PDXs globally maintained an oligoclonal structure. No overgrowth of a particular subclone present in the original tumor was observed in the PDXs. This suggested that xenotransplantation of ovarian tumors and growth as PDX preserved at least in part the clonal diversity of the original tumor. We believe our data reinforce the potential of PDX as exquisite tools in pre-clinical assays. PMID:26334103

  9. A Giant Ovarian Tumor Causing Anasarca and Dyspnea Successfully Managed after Preoperative Drainage.

    PubMed

    Yamaguchi, Munekage; Tashiro, Hironori; Takaishi, Kiyomi; Honda, Ritsuo; Katabuchi, Hidetaka

    2015-01-01

    Serious complications are likely to accompany the treatment of giant ovarian tumors, and resection with or without preoperative drainage has been previously reported. Here, we report the case of a 27-year-old Japanese woman with a significant weight gain of 50 kg, who was referred to the Kumamoto University Hospital because of gait impairment and dyspnea. Imaging tests revealed an ovarian tumor, 37 cm in diameter, with two solid components. The patient's condition improved after the removal of 31.5 l tumor fluid by using a suprapubic urinary catheter for 3 days. The tumor was subsequently resected without complications, and was diagnosed as a left mucinous ovarian tumor with malignant components, weighing 37 kg (81.5 lb). The patient was discharged after her anasarca improved, and her body weight decreased from 100 to 50 kg with accompanying considerable urination within two weeks. She was in good condition with no evidence of recurrence at 15 months after surgery. Tumor resection after preoperative drainage was effective in the management of a patient with dyspnea induced by a giant ovarian tumor. We suggest the use of a suprapubic urinary catheter for preoperative drainage because of its ease of use in preventing fluid leakage from the possibly malignant tumor. PMID:25661539

  10. 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

  11. Ovarian Yolk Sac Tumor With High-Grade Serous Carcinoma in a 62-Year-Old Woman.

    PubMed

    McCarthy, Whitney A; Masand, Ramya P

    2016-06-01

    Ovarian yolk sac tumors are germ cell tumors that usually present in children and young women. Rarely, these tumors can arise in older women, usually in conjunction with surface epithelial tumors, suggesting divergent differentiation from the latter. The combination of mixed ovarian yolk sac tumor and high-grade serous carcinoma is rare, with only one case documented in the literature. We present a case of mixed ovarian yolk sac tumor and high-grade serous carcinoma in a postmenopausal woman, including a brief discussion of the immunohistochemical findings and differential diagnosis. Despite the rarity of mixed ovarian yolk sac tumor and surface epithelial tumors, it is important to recognize the biphasic nature of the tumor, which should prompt a thorough immunohistochemical evaluation. The therapeutic and prognostic implications of proper diagnosis cannot be overemphasized. PMID:26782153

  12. Inhibition of Ovarian Tumor Growth by Targeting the HU177 Cryptic Collagen Epitope.

    PubMed

    Caron, Jennifer M; Ames, Jacquelyn J; Contois, Liangru; Liebes, Leonard; Friesel, Robert; Muggia, Franco; Vary, Calvin P H; Oxburgh, Leif; Brooks, Peter C

    2016-06-01

    Evidence suggests that stromal cells play critical roles in tumor growth. Uncovering new mechanisms that control stromal cell behavior and their accumulation within tumors may lead to development of more effective treatments. We provide evidence that the HU177 cryptic collagen epitope is selectively generated within human ovarian carcinomas and this collagen epitope plays a role in SKOV-3 ovarian tumor growth in vivo. The ability of the HU177 epitope to regulate SKOV-3 tumor growth depends in part on its ability to modulate stromal cell behavior because targeting this epitope inhibited angiogenesis and, surprisingly, the accumulation of α-smooth muscle actin-expressing stromal cells. Integrin α10β1 can serve as a receptor for the HU177 epitope in α-smooth muscle actin-expressing stromal cells and subsequently regulates Erk-dependent migration. These findings are consistent with a mechanism by which the generation of the HU177 collagen epitope provides a previously unrecognized α10β1 ligand that selectively governs angiogenesis and the accumulation of stromal cells, which in turn secrete protumorigenic factors that contribute to ovarian tumor growth. Our findings provide a new mechanistic understanding into the roles by which the HU177 epitope regulates ovarian tumor growth and provide new insight into the clinical results from a phase 1 human clinical study of the monoclonal antibody D93/TRC093 in patients with advanced malignant tumors. PMID:27216148

  13. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

    PubMed Central

    Cannon, Martin J.; Ghosh, Debopam; Gujja, Swetha

    2015-01-01

    The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines. PMID:26343197

  14. Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors.

    PubMed

    Leung, Dilys T H; Fuller, Peter J; Chu, Simon

    2016-03-01

    Granulosa cell tumors (GCT) are unique sex-cord stromal tumors which account for ∼8% of all ovarian malignancies. They exhibit morphological, biochemical and hormonal features similar to proliferating granulosa cells of the preovulatory follicle, including estrogen and inhibin synthesis. A somatic missense mutation in the forkhead box L2 (FOXL2) gene (C134W) is unique to adult GCT, and absent in other ovarian cancers. FOXL2 is a transcription factor that plays a critical role in ovarian function, in particular, proliferation and differentiation of granulosa cells. The molecular mechanisms underlying the pathogenicity of the mutant FOXL2 remain unresolved. Here we review the molecular alterations known to be associated with mutant FOXL2 and the potential signaling implications. Several studies suggest that dysregulated FOXL2 function may alter cell cycle progression and apoptosis. Further insights into the molecular mechanism of GCT pathophysiology may identify therapeutic targets for the treatment of these tumors. PMID:26791928

  15. Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status and outcome

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Sukhbaatar, Nyamdelger; Reiner, Agnes Teresa; Grimm, Christoph; Horvat, Reinhard; Zeillinger, Robert; Pils, Dietmar

    2015-01-01

    In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14–12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome.. EMT, peritoneal inflammation status, and therapeutic options are discussed. Significance More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use. PMID:25991672

  16. 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. PMID:23967565

  17. Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

    PubMed

    Croce, Sabrina; de Kock, Leanne; Boshari, Talia; Hostein, Isabelle; Velasco, Valerie; Foulkes, William D; McCluggage, W Glenn

    2016-07-01

    Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT. PMID:26598979

  18. 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.

  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. PMID:26339910

  20. Ribosomal S6 kinase 4 (RSK4) expression in ovarian tumors and its regulation by antineoplastic drugs in ovarian cancer cell lines.

    PubMed

    Arechavaleta-Velasco, Fabian; Zeferino-Toquero, Moises; Estrada-Moscoso, Isaias; Imani-Razavi, Fazlollah Shahram; Olivares, Aleida; Perez-Juarez, Carlos Eduardo; Diaz-Cueto, Laura

    2016-02-01

    Survival rate in ovarian cancer depends on the stage of the disease. RSK4, which has been considered as a tumor suppressor factor, controls cells invasion due to its antiinvasive and antimetastatic properties. Modulation of RSK4 expression could be an important event to increase the survival rate in ovarian cancer patients. Thus, the goal of the present study was to establish the differences in RSK4 expression among normal, benign and malignant ovarian tissues and to determine whether antineoplastic drugs regulate its expression in SKOV3 and TOV-112D cells. RSK4 levels in 30 malignant ovarian tumors, 64 benign tumors and 36 normal ovary tissues were determined by reverse transcription polymerase chain reaction and Western blot. Modulation of RSK4 expression by two antineoplastic drugs (cisplatin and vorinostat) was also studied in the SKOV3 and TOV-112D ovarian cancer cell lines using the same techniques. RSK4 mRNA and protein levels were decreased in malignant ovarian tumors as compared to benign tumors and normal tissue. These low-RSK4 levels were significantly associated with advanced stages of ovarian cancer. RSK4 expression was increased after incubation of SKOV3 and TOV-112D cell lines with cisplatin and vorinostat for 24 h. The combination of these antineoplastic drugs did not produce a synergistic or additive effect. These results suggest that RSK4 is expressed at low levels in malignant ovarian tumors, which correlates with advanced stages of the disease. Additionally, RSK4 expression is regulated by cisplatin and vorinostat in two ovarian cancer cell lines. PMID:26732474

  1. [A serous cystadenoma of the ovary of borderline malignancy with a fifteen-year history. A case report].

    PubMed

    Nagata, O; Aramaki, S; Iino, H; Ishikawa, S; Yoshida, H; Azekami, M; Yamaguchi, Y; Iwasa, T; Matsukuma, K; Iwata, Y

    1990-04-01

    A case of a serous cystadenoma of a ovary of borderline malignancy is reported. Sixteen years earlier, the patient had undergone an exploratory laparotomy because of ovarian tumor, and the histologic diagnosis had been a serous cystadenocarcinoma. Postoperative chemotherapy was not effective and drainage of the tumor fluid had been performed for 15 years, with the estimated drainage volume estimated to have reached, 1,000 1. Gradual malnutrition and marked tumor growth then become apparent. A reevaluation of the initial histologic slides and her clinical course strongly suggested a serous cystadenoma of borderline malignancy. Thus a tumor resection, a bilateral salpingo-oophorectomy, and a hysterectomy was performed. A histologic diagnosis of a resected specimen confirmed a serous cystadenoma of borderline malignancy and the histologic features were quite similar to those of the initial biopsy specimens. The patient is living well postoperatively for 8 months without postoperative chemotherapy. PMID:2325270

  2. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    PubMed

    Chowanadisai, Winyoo; Messerli, Shanta M; Miller, Daniel H; Medina, Jamie E; Hamilton, Joshua W; Messerli, Mark A; Brodsky, Alexander S

    2016-01-01

    The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition. PMID:26986722

  3. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors

    PubMed Central

    Miller, Daniel H.; Medina, Jamie E.; Hamilton, Joshua W.; Messerli, Mark A.; Brodsky, Alexander S.

    2016-01-01

    The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition. PMID:26986722

  4. Silencing of p130Cas in Ovarian Carcinoma: A Novel Mechanism for Tumor Cell Death

    PubMed Central

    Nick, Alpa M.; Stone, Rebecca L.; Armaiz-Pena, Guillermo; Ozpolat, Bulent; Tekedereli, Ibrahim; Graybill, Whitney S.; Landen, Charles N.; Villares, Gabriel; Vivas-Mejia, Pablo; Bottsford-Miller, Justin; Kim, Hye Sun; Lee, Ju-Seog; Kim, Soo Mi; Baggerly, Keith A.; Ram, Prahlad T.; Deavers, Michael T.; Coleman, Robert L.; Lopez-Berestein, Gabriel

    2011-01-01

    Background We investigated the clinical and biological significance of p130cas, an important cell signaling molecule, in ovarian carcinoma. Methods Expression of p130cas in ovarian tumors, as assessed by immunohistochemistry, was associated with tumor characteristics and patient survival. The effects of p130cas gene silencing with small interfering RNAs incorporated into neutral nanoliposomes (siRNA-DOPC), alone and in combination with docetaxel, on in vivo tumor growth and on tumor cell proliferation (proliferating cell nuclear antigen) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were examined in mice bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) or taxane-resistant (HeyA8-MDR) ovarian tumors (n = 10 per group). To determine the specific mechanisms by which p130cas gene silencing abrogates tumor growth, we measured cell viability (MTT assay), apoptosis (fluorescence-activated cell sorting), autophagy (immunoblotting, fluorescence, and transmission electron microscopy), and cell signaling (immunoblotting) in vitro. All statistical tests were two-sided. Results Of 91 ovarian cancer specimens, 70 (76%) had high p130cas expression; and 21 (24%) had low p130cas expression. High p130cas expression was associated with advanced tumor stage (P < .001) and higher residual disease (>1 cm) following primary cytoreduction surgery (P = .007) and inversely associated with overall survival and progression-free survival (median overall survival: high p130cas expression vs low expression, 2.14 vs 9.1 years, difference = 6.96 years, 95% confidence interval = 1.69 to 9.48 years, P < .001; median progression-free survival: high p130cas expression vs low expression, 1.04 vs 2.13 years, difference = 1.09 years, 95% confidence interval = 0.47 to 2.60 years, P = .01). In mice bearing orthotopically implanted HeyA8 or SKOV3ip1 ovarian tumors, treatment with p130cas siRNA-DOPC in combination with docetaxel chemotherapy resulted in the greatest

  5. 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. PMID:26548627

  6. Virilizing Ovarian Steroid Cell Tumor: A Rare Case

    PubMed Central

    Rangaiah, Nagarathnamma; Prasad, Nagendra; Channaveeregowda, Savitha

    2015-01-01

    Ovarian steroid cell tumours are fewer than 5 percent of sex-cord stromal tumours and 0.1% of all ovarian tumours. The average age at diagnosis is the mid-20s, but patients can present at virtually any age. We present a case of 38-year-old multipara with history of secondary amenorrhea, clinical signs & symptoms of virilization developed over the past 5 years. With elevated (115ng/dL) serum testosterone level and radiological findings of a left adnexal solid mass; the patient was suspected to have a virilizing tumour of left ovary. Laparoscopic left salpingo-oophorectomy was performed. Histopathology revealed tumour cells in small nests with vacuolated to eosinophilic cytoplasm with nuclear atypia completely replacing the ovarian tissue suggestive of steroid cell tumour (NOS) of ovary. The patient was discharged and advised for follow up with serum testosterone levels after 3 weeks. PMID:26500963

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

    ClinicalTrials.gov

    2016-07-08

    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

  8. 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.

  9. 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

  10. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    PubMed

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P < 0.0001). We further built a least absolute shrinkage and selection operator (LASSO)-Cox proportional hazards model that stratified patients into early relapse and late relapse groups (P = 0.00013). The top proteomic features indicative of platinum response were involved in ATP synthesis pathways and Ran GTPase binding. Overall, we demonstrated that proteomic profiles of ovarian serous carcinoma patients predicted platinum drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  11. Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

    PubMed

    Morgan, Robert J; Armstrong, Deborah K; Alvarez, Ronald D; Bakkum-Gamez, Jamie N; Behbakht, Kian; Chen, Lee-May; Copeland, Larry; Crispens, Marta Ann; DeRosa, Maria; Dorigo, Oliver; Gershenson, David M; Gray, Heidi J; Hakam, Ardeshir; Havrilesky, Laura J; Johnston, Carolyn; Lele, Shashikant; Martin, Lainie; Matulonis, Ursula A; O'Malley, David M; Penson, Richard T; Percac-Lima, Sanja; Pineda, Mario; Plaxe, Steven C; Powell, Matthew A; Ratner, Elena; Remmenga, Steven W; Rose, Peter G; Sabbatini, Paul; Santoso, Joseph T; Werner, Theresa L; Burns, Jennifer; Hughes, Miranda

    2016-09-01

    This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors. PMID:27587625

  12. New construction of an animal model for the orthotopic transplantation of an ovarian tumor.

    PubMed

    Zhang, Hui; Gao, Xinping; Yang, Yongan; Wang, Weiming; Liu, Jin; Liang, Yijuan; Wu, Hongli; Qin, Jinjin; Pan, Kun; Wang, Yifeng; Shi, Junrong; Ma, Youju

    2014-01-01

    A new technique has successfully established the non-obese diabetic/severely combined immunodeficiency (NOD/SCID) mouse model of ovarian cancer. Under 4% chloral hydrate (0.1 mL/g dose) anesthesia, female mice were inoculated with tumor-cell suspension. The expression rate of OVCAR3 to CA125 was assessed using flow cytometry. The inoculated site was hand palpated and the signs and symptoms related to tumor growth were observed with the naked eye. The allophycocyanin (APC) indirectly labeled mouse-antihuman CA125 and fluorescein isothiocyanate (FITC)-labeled anti-mouse MHC Class I molecule (H-2K(d)/H-2D(d)) were observed using a confocal laser scanning microscope. The animal model of ovarian cancer constructed using this method can more directly reflect the characteristics of cancer cells. It provides reliable experimental results and presents a technical platform for the research of ovarian cancer stem cells. PMID:24955132

  13. New construction of an animal model for the orthotopic transplantation of an ovarian tumor

    PubMed Central

    2014-01-01

    A new technique has successfully established the non-obese diabetic/severely combined immunodeficiency (NOD/SCID) mouse model of ovarian cancer. Under 4% chloral hydrate (0.1 mL/g dose) anesthesia, female mice were inoculated with tumor-cell suspension. The expression rate of OVCAR3 to CA125 was assessed using flow cytometry. The inoculated site was hand palpated and the signs and symptoms related to tumor growth were observed with the naked eye. The allophycocyanin (APC) indirectly labeled mouse-antihuman CA125 and fluorescein isothiocyanate (FITC)-labeled anti-mouse MHC Class I molecule (H-2Kd/H-2Dd) were observed using a confocal laser scanning microscope. The animal model of ovarian cancer constructed using this method can more directly reflect the characteristics of cancer cells. It provides reliable experimental results and presents a technical platform for the research of ovarian cancer stem cells. PMID:24955132

  14. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex

    PubMed Central

    He, Zhi-Yao; Deng, Feng; Wei, Xia-Wei; Ma, Cui-Cui; Luo, Min; Zhang, Ping; Sang, Ya-Xiong; Liang, Xiao; Liu, Li; Qin, Han-Xiao; Shen, Ya-Li; Liu, Ting; Liu, Yan-Tong; Wang, Wei; Wen, Yan-Jun; Zhao, Xia; Zhang, Xiao-Ning; Qian, Zhi-Yong; Wei, Yu-Quan

    2016-01-01

    Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer. PMID:27026065

  15. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex.

    PubMed

    He, Zhi-Yao; Deng, Feng; Wei, Xia-Wei; Ma, Cui-Cui; Luo, Min; Zhang, Ping; Sang, Ya-Xiong; Liang, Xiao; Liu, Li; Qin, Han-Xiao; Shen, Ya-Li; Liu, Ting; Liu, Yan-Tong; Wang, Wei; Wen, Yan-Jun; Zhao, Xia; Zhang, Xiao-Ning; Qian, Zhi-Yong; Wei, Yu-Quan

    2016-01-01

    Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer. PMID:27026065

  16. Characterization of Ascites-Derived Ovarian Tumor Cells from Spontaneously Occurring Ovarian Tumors of the Chicken: Evidence for E-Cadherin Upregulation

    PubMed Central

    Tiwari, Anupama; Hadley, Jill A.; Hendricks, Gilbert L.; Elkin, Robert G.; Cooper, Timothy; Ramachandran, Ramesh

    2013-01-01

    Ovarian cancer, a highly metastatic disease, is the fifth leading cause of cancer-related deaths in women. Chickens are widely used as a model for human ovarian cancer as they spontaneously develop epithelial ovarian tumors similar to humans. The cellular and molecular biology of chicken ovarian cancer (COVCAR) cells, however, have not been studied. Our objectives were to culture COVCAR cells and to characterize their invasiveness and expression of genes and proteins associated with ovarian cancer. COVCAR cell lines (n = 13) were successfully maintained in culture for up to19 passages, cryopreserved and found to be viable upon thawing and replating. E-cadherin, cytokeratin and α-smooth muscle actin were localized in COVCAR cells by immunostaining. COVCAR cells were found to be invasive in extracellular matrix and exhibited anchorage-independent growth forming colonies, acini and tube-like structures in soft agar. Using RT-PCR, COVCAR cells were found to express E-cadherin, N-cadherin, cytokeratin, vimentin, mesothelin, EpCAM, steroidogenic enzymes/proteins, inhibin subunits-α, βA, βB, anti-müllerian hormone, estrogen receptor [ER]-α, ER-β, progesterone receptor, androgen receptor, and activin receptors. Quantitative PCR analysis revealed greater N-cadherin, vimentin, and VEGF mRNA levels and lesser cytokeratin mRNA levels in COVCAR cells as compared with normal ovarian surface epithelial (NOSE) cells, which was suggestive of epithelial-mesenchymal transformation. Western blotting analyses revealed significantly greater E-cadherin levels in COVCAR cell lines compared with NOSE cells. Furthermore, cancerous ovaries and COVCAR cell lines expressed higher levels of an E-cadherin cleavage product when compared to normal ovaries and NOSE cells, respectively. Cancerous ovaries were found to express significantly higher ovalbumin levels whereas COVCAR cell lines did not express ovalbumin thus suggesting that the latter did not originate from oviduct. Taken

  17. Characterization of ascites-derived ovarian tumor cells from spontaneously occurring ovarian tumors of the chicken: evidence for E-cadherin upregulation.

    PubMed

    Tiwari, Anupama; Hadley, Jill A; Hendricks, Gilbert L; Elkin, Robert G; Cooper, Timothy; Ramachandran, Ramesh

    2013-01-01

    Ovarian cancer, a highly metastatic disease, is the fifth leading cause of cancer-related deaths in women. Chickens are widely used as a model for human ovarian cancer as they spontaneously develop epithelial ovarian tumors similar to humans. The cellular and molecular biology of chicken ovarian cancer (COVCAR) cells, however, have not been studied. Our objectives were to culture COVCAR cells and to characterize their invasiveness and expression of genes and proteins associated with ovarian cancer. COVCAR cell lines (n = 13) were successfully maintained in culture for up to19 passages, cryopreserved and found to be viable upon thawing and replating. E-cadherin, cytokeratin and α-smooth muscle actin were localized in COVCAR cells by immunostaining. COVCAR cells were found to be invasive in extracellular matrix and exhibited anchorage-independent growth forming colonies, acini and tube-like structures in soft agar. Using RT-PCR, COVCAR cells were found to express E-cadherin, N-cadherin, cytokeratin, vimentin, mesothelin, EpCAM, steroidogenic enzymes/proteins, inhibin subunits-α, βA, βB, anti-müllerian hormone, estrogen receptor [ER]-α, ER-β, progesterone receptor, androgen receptor, and activin receptors. Quantitative PCR analysis revealed greater N-cadherin, vimentin, and VEGF mRNA levels and lesser cytokeratin mRNA levels in COVCAR cells as compared with normal ovarian surface epithelial (NOSE) cells, which was suggestive of epithelial-mesenchymal transformation. Western blotting analyses revealed significantly greater E-cadherin levels in COVCAR cell lines compared with NOSE cells. Furthermore, cancerous ovaries and COVCAR cell lines expressed higher levels of an E-cadherin cleavage product when compared to normal ovaries and NOSE cells, respectively. Cancerous ovaries were found to express significantly higher ovalbumin levels whereas COVCAR cell lines did not express ovalbumin thus suggesting that the latter did not originate from oviduct. Taken

  18. Ovarian Tumors in Children and Adolescents: A 10-Yr Histopathologic Review in Korle-Bu Teaching Hospital, Ghana.

    PubMed

    Akakpo, Patrick K; Derkyi-Kwarteng, Leonard; Quayson, Solomon E; Gyasi, Richard K; Anim, Jehoram T

    2016-07-01

    To determine the histopathologic types, frequency of occurrence, age distribution, presenting signs, and symptoms of ovarian tumors in children and adolescents diagnosed at the Korle-Bu Teaching Hospital all histopathology slides and request cards of ovarian tumors diagnosed in subjects aged, 0 to 19 yr over a 10-yr period (2001-2010) were reviewed. Biographical and clinical data of the patients were collected. The results were entered into Epi-info to determine the frequency of various ovarian tumors in different age groups and their association with presenting signs and symptoms. A total of 67 (9.5%) ovarian tumors were diagnosed in patients aged 0 to 19 yr of a total of 706 diagnosed in all age groups during the period. The majority [44 (65.7%)] were germ cell tumors, the commonest being mature cystic teratoma. Burkitt lymphoma was the single most common malignant tumor, comprising 6(9%) of all the tumors, although as a group malignant germ cell tumors were still the most common malignant ovarian tumors in children and adolescents. Although germ cell tumors were the most common tumors in this age group (both benign and malignant), Burkitt lymphoma, a peculiar malignant tumor in this subregion, was the single most common malignant tumor of the ovary. PMID:26630227

  19. 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

  20. 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.

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

    PubMed

    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

  2. [Anesthetic Induction in a Patient with Giant Ovarian Tumor Who Developed Severe Hemodynamic Instability].

    PubMed

    Aoi, Ryota; Ishihara, Mariko; Soh, Mirei; Kohno, Michihiko; Soga, Mayumi; Kohata, Hisakazu; Takahashi, Kan

    2015-08-01

    A 45 year-old woman underwent a laparotomy for a giant ovarian tumor under general anesthesia. Preoperative CT scan revealed a 30 cm-diameter tumor compressing IVC. She had slight respiratory discomfort on supine position, but respiratory function test showed no abnormalities. In the operating room, after oxygenation for 3 minutes, general anesthesia was induced with fentanyl 100 μg, propofol 90 mg and rocuronium 40 mg on supine position. Immediately after the induction, her systolic blood pressure and heart rate fell to 45 mmHg and 40 beats per minute, respectively. We considered that her hemodynamic instability was supine hypotensive syndrome due to giant ovarian tumor. Therefore we placed her 30 degree right side up and pushed her tumor to the left so as not to compress the IVC. We rapidly injected acetated Ringer's solution 500 ml, ephedrine 12 mg and phenylephrine 0.1 mg, and her hemodynamic status soon recovered to normal ranges. The anesthetic induction of a patient with a giant ovarian tumor is challenging. Some reports recommend strategies such as induction on lateral position or suctioning tumor contents before induction. Careful induction of general anesthesia is required for these patients. PMID:26442415

  3. Human Ovarian Cancer Stroma Contains Luteinized Theca Cells Harboring Tumor Suppressor Gene GT198 Mutations*

    PubMed Central

    Peng, Min; Zhang, Hao; Jaafar, Lahcen; Risinger, John I.; Huang, Shuang; Mivechi, Nahid F.; Ko, Lan

    2013-01-01

    Ovarian cancer is a highly lethal gynecological cancer, and its causes remain to be understood. Using a recently identified tumor suppressor gene, GT198 (PSMC3IP), as a unique marker, we searched for the identity of GT198 mutant cells in ovarian cancer. GT198 has germ line mutations in familial and early onset breast and ovarian cancers and recurrent somatic mutations in sporadic fallopian tube cancers. GT198 protein has been shown as a steroid hormone receptor coregulator and also as a crucial factor in DNA repair. In this study, using GT198 as a marker for microdissection, we find that ovarian tumor stromal cells harboring GT198 mutations are present in various types of ovarian cancer including high and low grade serous, endometrioid, mucinous, clear cell, and granulosa cell carcinomas and in precursor lesions such as inclusion cysts. The mutant stromal cells consist of a luteinized theca cell lineage at various differentiation stages including CD133+, CD44+, and CD34+ cells, although the vast majority of them are differentiated overexpressing steroidogenic enzyme CYP17, a theca cell-specific marker. In addition, wild type GT198 suppresses whereas mutant GT198 protein stimulates CYP17 expression. The chromatin-bound GT198 on the human CYP17 promoter is decreased by overexpressing mutant GT198 protein, implicating the loss of wild type suppression in mutant cells. Together, our results suggest that GT198 mutant luteinized theca cells overexpressing CYP17 are common in ovarian cancer stroma. Because first hit cancer gene mutations would specifically mark cancer-inducing cells, the identification of mutant luteinized theca cells may add crucial evidence in understanding the cause of human ovarian cancer. PMID:24097974

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

    ClinicalTrials.gov

    2016-07-12

    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

  5. 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

  6. 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

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

    PubMed

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

    2016-06-28

    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

  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. A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat

    PubMed Central

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A.; Tsubura, Airo

    2015-01-01

    Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies. PMID:26989303

  11. 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

  12. 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

  13. Mucinous tumors of the ovary: current thoughts on diagnosis and management.

    PubMed

    Brown, Jubilee; Frumovitz, Michael

    2014-06-01

    Mucinous tumors of the ovary represent a spectrum of neoplastic disorders, including benign mucinous cystadenoma, pseudomyxoma peritonei, mucinous tumors of low malignant potential (borderline), and invasive mucinous ovarian carcinoma. These tumors are related closely to each other and are distinct from other histologic subtypes of epithelial ovarian neoplasms from a clinical, histologic, and molecular standpoint. A continuum appears to be present from benign to borderline to malignant, which is different from other types of epithelial ovarian cancer. Mutational profiles are also distinct, as KRAS mutations are common, but p53 and BRCA mutations are infrequent. These characteristics lead to specific biologic behavior and guide both clinical management and research efforts in patients with mucinous ovarian tumors. PMID:24777667

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

    PubMed

    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

  15. 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

  16. Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy

    PubMed Central

    PASTOREK, MICHAL; SIMKO, VERONIKA; TAKACOVA, MARTINA; BARATHOVA, MONIKA; BARTOSOVA, MARIA; HUNAKOVA, LUBA; SEDLAKOVA, OLGA; HUDECOVA, SONA; KRIZANOVA, OLGA; DEQUIEDT, FRANCK; PASTOREKOVA, SILVIA; SEDLAK, JAN

    2015-01-01

    One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules. PMID:25955133

  17. Ovarian Tumor Attachment, Invasion, and Vascularization Reflect Unique Microenvironments in the Peritoneum: Insights from Xenograft and Mathematical Models

    PubMed Central

    Steinkamp, Mara P.; Winner, Kimberly Kanigel; Davies, Suzy; Muller, Carolyn; Zhang, Yong; Hoffman, Robert M.; Shirinifard, Abbas; Moses, Melanie; Jiang, Yi; Wilson, Bridget S.

    2013-01-01

    Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian cancer cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-red fluorescent protein (RFP) cell populations injected into the peritoneum demonstrated that cancer cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM) that examines ovarian cancer cell attachment, chemotaxis, growth, and vascularization. OvTM simulations provide insight into the relative influence of cancer cell–cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum, or spleen readily invade the “open” architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer

  18. Tubo-ovarian abscess presenting as an ovarian tumor in a virginal adolescent: a case report.

    PubMed

    Sakar, M N; Gul, T; Atay, A E

    2012-01-01

    Tubo-ovarian abscess (TOA), a serious complication of pelvic inflammatory disease, unites the fallopian tube and ovary and, is rarely observed in sexually inactive adolescent girls. A pelvic mass, supposedly originating from the ovary, was detected in a 13-year-old sexually inactive girl suffering from abdominal pain and menstrual disorder. Pelvic ultrasonography pointed out a semisolid, hyperechogenic mass of 57x73 mm in the left adnexal area. Laparotomy revealed an unilateral TOA adhering to the bowel and omentum. Abscess drainage and adhesiolysis were performed and postoperative antibiotherapy was administered. TOA should be considered in the differential diagnosis of females with abdominal pain and adnexal mass whether sexual activity is present or not. PMID:23157053

  19. 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. PMID:26974995

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

    PubMed

    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

  1. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman

    PubMed Central

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  2. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    PubMed

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  3. Personalized ovarian cancer disease surveillance and detection of candidate therapeutic drug target in circulating tumor DNA.

    PubMed

    Martignetti, John A; Camacho-Vanegas, Olga; Priedigkeit, Nolan; Camacho, Catalina; Pereira, Elena; Lin, Li; Garnar-Wortzel, Leopold; Miller, Dagny; Losic, Bojan; Shah, Hardik; Liao, Jun; Ma, Jian; Lahiri, Pratik; Chee, Mark; Schadt, Eric; Dottino, Peter

    2014-01-01

    Retrospective studies have demonstrated that nearly 50% of patients with ovarian cancer with normal cancer antigen 125 (CA125) levels have persistent disease; however, prospectively distinguishing between patients is currently impossible. Here, we demonstrate that for one patient, with the first reported fibroblast growth factor receptor 2 (FGFR2) fusion transcript in ovarian cancer, circulating tumor DNA (ctDNA) is a more sensitive and specific biomarker than CA125, and it can also inform on a candidate therapeutic. For a 4-year period, during which the patient underwent primary debulking surgery and chemotherapy, tumor recurrences, and multiple chemotherapeutic regimens, blood samples were longitudinally collected and stored. Whereas postsurgical CA125 levels were elevated only three times for 28 measurements, the FGFR2 fusion ctDNA biomarker was readily detectable by quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all of these same blood samples and in the tumor recurrences. Given the persistence of the FGFR2 fusion, we treated tumor cells derived from this patient and others with the FGFR2 inhibitor BGJ398. Only tumor cells derived from this patient were sensitive to FGFR2 inhibitor treatment. Using the same methodologic approach, we demonstrate in a second patient with a different fusion that PCR and agarose gel electrophoresis can also be used to identify tumor-specific DNA in the circulation. Taken together, we demonstrate that a relatively inexpensive, PCR-based ctDNA surveillance assay can outperform CA125 in identifying occult disease. PMID:24563622

  4. 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

  5. [Malignant ovarian tumors in childhood and adolescence in Novi Sad (1946-1989)].

    PubMed

    Berić, B; Gebauer, E; Dordević, M; Konstantinidis, N; Stojić, S

    1991-01-01

    In the period from 1946-1989, at the Department of Gynecology and Obstetrics University of Novi Sad, 79 ovarian tumors in children and adolescents were registered. There were 10 (12.6%) malignant tumours. The most common were dysgerminoma and carcinoma (total 6-7.6%). The treatment depended on the extent of the disease at the time of diagnosis (surgery, irradiation, chemotherapy or combination). PMID:1749284

  6. An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors.

    PubMed

    Carvalho, S; Lindzen, M; Lauriola, M; Shirazi, N; Sinha, S; Abdul-Hai, A; Levanon, K; Korach, J; Barshack, I; Cohen, Y; Onn, A; Mills, G; Yarden, Y

    2016-01-28

    Growth factors of the epidermal growth factor (EGF)/neuregulin family are involved in tumor progression and, accordingly, antibodies that intercept a cognate receptor, epidermal growth factor receptor (EGFR)/ERBB1, or a co-receptor, HER2, have been approved for cancer therapy. Although they might improve safety and delay onset of chemoresistance, no anti-ligand antibodies have been clinically approved. To identify suitable ligands, we surveyed fluids from ovarian and lung cancer patients and found that amphiregulin (AREG) is the most abundant and generalized ligand secreted by advanced tumors. AREG is a low affinity EGFR ligand, which is upregulated following treatment with chemotherapeutic drugs. Because AREG depletion retarded growth of xenografted ovarian tumors in mice, we generated a neutralizing monoclonal anti-AREG antibody. The antibody inhibited growth of ovarian cancer xenografts and strongly enhanced chemotherapy efficacy. Taken together, these results raise the possibility that AREG and other low- or high-affinity binders of EGFR might serve as potential targets for cancer therapy. PMID:25915843

  7. 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

  8. 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

  9. 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. PMID:26436697

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

    PubMed Central

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

    2015-01-01

    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. PMID:26436697

  11. 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

  12. 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

  13. Prolonged Survival of a Patient With Pelvic Recurrence of Ovarian Malignant Mixed Mullerian Tumor After Chemoradiotherapy

    PubMed Central

    Homaei Shandiz, Fatemeh; Kadkhodayan, Sima; Hsanzade Mofrad, Malihe; Yousefi Roodsari, Zohre; Sharifi Sistani, Noorieh; Nabizadeh Marvast, Majid; Sadeghei, Mahbobe

    2014-01-01

    Introduction: Malignant Mixed Mullerian Tumor (MMMT) is a very rare tumor, accounting for less than 1% of all ovarian cancers. Case Presentation: We present a 64-year-old woman with stage III MMMT of ovary that was treated with platinum-based chemotherapy after optimal cytoreductive surgery. After 25 months of being disease free, she had a pelvic recurrence and a good response to chemoradiotherapy. Conclusions: Optimal cytoreductive surgery and chemotherapy may be the best treatment in MMMT but more discussion and experiences are needed regarding the effectiveness of radiotherapy. PMID:25593719

  14. 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

  15. Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer.

    PubMed

    He, X; Arslan, A D; Pool, M D; Ho, T-T; Darcy, K M; Coon, J S; Beck, W T

    2011-01-20

    Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were upregulated in epithelial ovarian cancer (EOC) and knockdown of PTB expression inhibited ovarian tumor cell growth and transformation properties. In this report, we show that knockdown of SRp20 expression in ovarian cancer cells also causes substantial inhibition of tumor cell growth and colony formation in soft agar and the extent of such inhibition appeared to correlate with the extent of suppression of SRp20. Massive knockdown of SRp20 expression triggered remarkable apoptosis in these cells. These results suggest that overexpression of SRp20 is required for ovarian tumor cell growth and survival. Immunohistochemical staining for PTB and SRp20 of two specialized tissue microarrays, one containing benign ovarian tumors, borderline/low malignant potential (LMP) ovarian tumors as well as invasive EOC and the other containing invasive EOC ranging from stage I to stage IV disease, reveals that PTB and SRp20 are both expressed differentially between benign tumors and invasive EOC, and between borderline/LMP tumors and invasive EOC. There were more all-negative or mixed staining cases (at least two evaluable section cores per case) in benign tumors than in invasive EOC, whereas there were more all-positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the majority of cases were stained all positive for both PTB and SRp20, and there were no significant differences in average staining or frequency of positive cancer cells between any of the tumor stages. Therefore, the expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive EOC. PMID:20856201

  16. Knockdown of splicing factor SRp20 causes apoptosis in ovarian cancer cells and its expression is associated with malignancy of epithelial ovarian cancer

    PubMed Central

    He, Xiaolong; Arslan, Ahmet Dirim; Pool, Mark D.; Ho, Tsui-Ting; Darcy, Kathleen M.; Coon, John S.; Beck, William T.

    2010-01-01

    Our previous study revealed that two splicing factors, polypyrimidine tract-binding protein (PTB) and SRp20, were up-regulated in epithelial ovarian cancer (EOC) and knockdown of PTB expression inhibited ovarian tumor cell growth and transformation properties. In this report, we show that knockdown of SRp20 expression in ovarian cancer cells also causes substantial inhibition of tumor cell growth and colony formation in soft agar and the extent of such inhibition appeared to correlate with the extent of suppression of SRp20. Massive knockdown of SRp20 expression triggered remarkable apoptosis in these cells. These results suggest that overexpression of SRp20 is required for ovarian tumor cell growth and survival. Immunohistochemical staining for PTB and SRp20 of two specialized tissue microarrays (TMAs), one containing benign ovarian tumors, borderline/low malignant potential (LMP) ovarian tumors as well as invasive EOC and the other containing invasive EOC ranging from stage I to stage IV disease, reveals that PTB and SRp20 are both expressed differentially between benign tumors and invasive EOC, and between borderline/LMP tumors and invasive EOC. There were more all-negative or mixed staining cases (at least two evaluable section cores per case) in benign tumors than in invasive EOC while there were more all positive staining cases in invasive EOC than in the other two disease classifications. Among invasive EOC, the great majority of cases were stained all-positive for both PTB and SRp20 and there were no significant differences in average staining or frequency of positive cancer cells between any of the tumor stages. Therefore, the expression of PTB and SRp20 is associated with malignancy of ovarian tumors but not with stage of invasive EOC. PMID:20856201

  17. Ovarian mixed germ cell tumor with yolk sac and teratomatous components in a dog.

    PubMed

    Robinson, Nicholas A; Manivel, J Carlos; Olson, Erik J

    2013-05-01

    Mixed germ cell tumors of the ovary have rarely been reported in veterinary species. A 3-year-old intact female Labrador Retriever dog was presented for lethargy, abdominal distention, and a midabdominal mass. An exploratory laparotomy revealed a large (23 cm in diameter) left ovarian tumor and multiple small (2-3 cm in diameter) pale tan masses on the peritoneum and abdominal surface of the diaphragm. Histological examination of the left ovary revealed a mixed germ cell tumor with a yolk sac component with rare Schiller-Duval bodies and a teratomatous component comprised primarily of neural differentiation. The abdominal metastases were solely comprised of the yolk sac component. The yolk sac component was diffusely immunopositive for cytokeratin with scattered cells reactive for α-fetoprotein and placental alkaline phosphatase. Within the teratomatous component, the neuropil was diffusely immunopositive for S100, neuron-specific enolase, and neurofilaments with a few glial fibrillary acidic protein immunopositive cells. Ovarian germ cell tumors may be pure and consist of only 1 germ cell element or may be mixed and include more than 1 germ cell element, such as teratoma and yolk sac tumor. PMID:23604259

  18. Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India

    PubMed Central

    Mallick, Supriya; Joshi, Nikhil P.; Roy, Soumyajit; Gandhi, Ajeet Kumar; Pandit, Subhash; Sharma, Dayanand; Julka, Pramod Kumar; Rath, Goura Kishore

    2016-01-01

    Background: Phyllodes tumor (PT) of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful. Materials and Methods: We have analyzed details of all patients of PT (n = 33) treated with adjuvant multi-modality approach in our institute since 1994–2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented. Results: All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank). The disease free survival (DFS) favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank). The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015). The mode of surgery did not have any impact on survival. Conclusion: Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure. PMID:27169106

  19. Ovarian large cell neuroendocrine carcinoma in the youngest woman.

    PubMed

    Kwon, Y S; Im, K S; Choi, D I

    2016-01-01

    Large cell neuroendocrine carcinoma (LCNC) of the ovary is a rare tumor in gynecologic oncologic field. An 18-year-old woman presented with abdominal distention and a pelvic mass measuring ten cm in diameter, who previously underwent laparoscopic ovarian cystectomy due to large borderline mucinous ovarian neoplasm 18 months prior. A debulking operation was optimally performed, which included total abdominal hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic lymph node dissection, bilateral paraaortic lymph node dissection, omentectomy, optimal debulking of gastrohepatic mass and subdiaphragmatic mass, and pelvic peritonectomy. Despite adjuvant chemotherapy with paclitaxel and carboplatin, the patient died of progressive disease seven months after surgery. The authors report the youngest case of LCNC of the ovary, that failed chemotherapy and had the previous history of the conservative surgical treatment due to mucinous borderline tumor. PMID:27172753

  20. Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma.

    PubMed

    Bergman, S; Medeiros, L J; Radr, T; Mangham, D C; Lewandrowski, K B

    1995-08-01

    We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The findings of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor. PMID:7594774

  1. NDN is an imprinted tumor suppressor gene that is downregulated in ovarian cancers through genetic and epigenetic mechanisms

    PubMed Central

    Yu, Yinhua; Mao, Weiqun; Wang, Yan; Baggerly, Keith; Wang, Ying; Marquez, Rebecca T.; Bedi, Anuja; Liu, Jinsong; Fishman, David; Lu, Zhen; Bast, Robert C.

    2016-01-01

    NDN is a maternally imprinted gene consistently expressed in normal ovarian epithelium, is dramatically downregulated in the majority of ovarian cancers. Little or no NDN expression could be detected in 73% of 351 epithelial ovarian cancers. NDN was also downregulated in 10 ovarian cancer cell lines with total loss in 6 of 10. Re-expression of NDN decreased Bcl-2 levels and induced apoptosis, which significantly inhibited ovarian cancer cell growth in cell culture and in xenografts. In addition, re-expression of NDN inhibited cell migration by decreasing actin stress fiber and focal adhesion complex formation through deactivation of Src, FAK and RhoA. Loss of NDN expression in ovarian cancers could be attributed to LOH in 28% of 18 informative cases and to hypermethylation of CpG sites 1 and 2 of NDN promoter in 23% and 30% of 43 ovarian cancers, respectively. Promoter hypermethylation was also found in 5 of 10 ovarian cancer cell lines. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored NDN expression in 4 of 7 cell lines with enhanced promoter methylation levels. These observations support the conclusion that NDN is an imprinted tumor suppressor gene which affects cancer cell motility, invasion and growth and that its loss of function in ovarian cancer can be caused by both genetic and epigenetic mechanisms. PMID:26689988

  2. Imprint cytology of high-grade immature ovarian teratoma: a case report, literature review, and distinction from other ovarian small round cell tumors.

    PubMed

    Ramalingam, Preetha; Teague, Daniel; Reid-Nicholson, Michelle

    2008-08-01

    Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm characterized by immature neural tissue. The cytomorphologic features have only rarely been described. We herein describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with imprint cytology. A 35-year-old woman presented with a pelvic mass which was resected and sent for frozen section evaluation. Imprint smears and frozen section of the mass were diagnostic of IOT. IOT has diagnostic cytologic features which show complete concordance with histology. Differential diagnoses include other small round cell neoplasms such as ovarian neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and Non-Hodgkin lymphoma. Distinguishing IOT from these tumors can be challenging however if diligent morphologic study and/or ancillary studies are performed accurate diagnosis is possible. PMID:18618728

  3. 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.

  4. 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

  5. Mature Ovarian Teratoma with Carcinoid Tumor in a 28-Year-Old Patient

    PubMed Central

    Petousis, Stamatios; Kalogiannidis, Ioannis; Margioula-Siarkou, Chrysoula; Traianos, Alexandros; Miliaras, Dimosthenis; Kamparoudis, Apostolos; Mamopoulos, Apostolos; Rousso, David

    2013-01-01

    Introduction. Coexistence of carcinoid tumor inside a mature cystic teratoma is an extremely rare phenomenon, especially in young women. We present the case of a 28-year-old woman diagnosed with a right ovarian carcinoid and treated uneventfully with conservative surgical approach. Case Report. A 28-year-old woman, gravid 0, parity 0, presented to our department for her annual gynecological examination and Pap smear test. During her examination, a mobile cystic mass was detected in the right lower abdomen. Ultrasound indicated a right ovarian mass 10.5 × 6.3 cm, confirmed by CT scan. Further investigation revealed AFP levels (1539 ng/mL). The ovarian mass was excised by laparoscopy, leaving intact the remaining right ovary. Frozen sections showed a mature cystic teratoma. However, paraffin sections revealed the presence of a small carcinoid within the teratoma's gastric-type mucosa. The patient was set to a close followup. Nine months postoperatively, ultrasound pelvis imaging and CT scan of the abdomen as well as serum tumor markers have shown no evidence of recurrence disease. Conclusion. Despite the weak evidence, fertility spare surgical approach for women wanting to preserve their genital tract might be a reasonable option. PMID:23984130

  6. Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay

    PubMed Central

    ZHANG, JIN; LI, HONGXIA

    2015-01-01

    Ovarian cancer has a poor prognosis, primarily due to the heterogeneity in chemosensitivity among patients. In the present study, this heterogeneity was evaluated in ovarian epithelial cancer (OEC) using an in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA). Specimens were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for sensitivity to paclitaxel (PTX), carboplatin (CBP), topotecan (TPT), gemcitabine (GEM), docetaxel (TXT), etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The sensitivity, specificity, positive predictive value and negative predictive value for the clinical chemotherapy sensitivity of OEC were 88.6, 77.8, 83 and 84.8%, respectively. PTX demonstrated the highest sensitivity of all agents tested (82.5% in all specimens, 85.7% in recurrent specimens), followed by CBP (58.8 and 60.7%, respectively). The sensitivities to PTX and docetaxel (P<0.001) were correlated, in addition to those of CBP, TPT and GEM (P<0.001). Early-stage (I/II) and high- to mildly-differentiated OEC specimens revealed a lower chemosensitivity than advanced-stage (III) or low-differentiated specimens, respectively. The present study indicated that ATP-TCA is an effective method for guiding the choice of chemotherapy drugs. Notable heterogeneity of chemosensitivity was observed in the OEC specimens. PMID:26137074

  7. 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

  8. High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

    PubMed Central

    Wang, Ke; Li, Dan; Sun, Lu

    2016-01-01

    Purpose The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. Methods Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. Results EGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. Conclusion High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID:26855586

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

    PubMed

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

    2016-08-01

    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

  11. Virilizing ovarian stromal tumor in a young woman with Carney complex.

    PubMed

    Carney, J Aidan; Stratakis, Constantine A

    2011-10-01

    A woman with Carney complex presented at the age of 22 years with abdominal pain and hirsutism. As a baby, she had undergone excision of a right eyelid lesion, and at age 14 years she had undergone 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, she experienced relief from abdominal pain, the serum level of testosterone normalized, and the hirsutism 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 likely that is occurrence was related to Carney complex. PMID:21934476

  12. A Quick Responsive Fluorogenic pH Probe for Ovarian Tumor Imaging

    PubMed Central

    Tung, Ching-Hsuan; Qi, Jianjun; Hu, Lingchuan; Han, Myung Shin; Kim, Young

    2015-01-01

    A novel cell-permeable compound, CypH-1, that is non-fluorescent at neutral pH, but fluoresces under mildly acidic conditions with a near infrared maximum emission wavelength was designed for the detection of tumors in the clinical setting. The potential of CypH-1 in ovarian cancer imaging was demonstrated using a murine model. The intraperitoneally administered CypH-1 results in a robust fluorescence signal of discrete neoplastic lesions with millimeter range resolution within few hours. Moreover, fluorescence signal is strikingly enhanced at peripheral regions of tumors at the microscopic level suggesting a sharp physiological difference at the tumor/normal tissue interface. This robust acid-activated imaging agent is expected to have significant impact in broad surgical and diagnostic applications. PMID:26284146

  13. An Ovarian Carcinoid Tumor With Peptide YY-Positive Insular Component: A Case Report and Review of the Literature.

    PubMed

    Erdenebaatar, Chimeddulam; Yamaguchi, Munekage; Saito, Fumitaka; Motooka, Chisato; Tashiro, Hironori; Katabuchi, Hidetaka

    2016-07-01

    Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries. PMID:26630222

  14. Prognostic impact of KI67, p53, human epithelial growth factor receptor 2, topoisomerase IIalpha, epidermal growth factor receptor, and nm23 expression of ovarian carcinomas and disseminated tumor cells in the bone marrow.

    PubMed

    Schindlbeck, C; Hantschmann, P; Zerzer, M; Jahns, B; Rjosk, D; Janni, W; Rack, B; Sommer, H; Friese, K

    2007-01-01

    Examination of tumor biological factors for prognostic and predictive indicators is not part of routine testing in ovarian cancer. As in other tumors, the detection of hematogenous tumor spread could help to estimate the risk of metastatic disease. We examined the expression of p53, KI67, topoisomerase IIalpha (Top IIa), epidermal growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2) and nm23 in tumor tissues from 90 patients with ovarian cancer. All underwent bone marrow (BM) aspiration and screening for disseminated tumor cells in the bone marrow (DTC-BM) at primary diagnosis. BM aspiration, cytospin preparation, and immunocytochemical staining with the anticytokeratin antibody (A45-B/B3) were done following a standardized protocol. The expression of p53, KI67, Top IIa, EGFR, HER2, and nm23 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells or immunoreactive score (IRS). The prognostic impact of the individual factors together with standard histologic parameters was calculated by univariate and multivariate analyses. Expression rates for HER2 (2+/3+: 34.5%), KI67 (median 30%), p53 (median IRS 5), and Top IIa (median IRS 4) were relatively high, whereas nm23 (median IRS 2) and EGFR (IRS 0: 61%) showed weak staining. In 21/90 patients (23.3%), DTC-BM (>/=1/2 x 10(6) cells) could be detected. The presence of DTC-BM was inversely related to nodal status (P = .015) but not to the other factors examined. Tumor stage (P = .02), lymph node involvement (P = .003), grade (P = .046), postoperative tumor residue (P < .001), peritoneal seeding (P = .02), and KI67 (P = .046) significantly correlated with overall survival (OS) after a median observation time of 28 months (2-105). The finding of ascites was borderline significant (P = .050). The presence of DTC-BM (P = .04) and KI67 positivity (P = .02) predicted reduced distant disease-free survival. By multivariate analysis

  15. Carcinoembryonic antigen-related cell adhesion molecule 1 is expressed and as a function histotype in ovarian tumors.

    PubMed

    Li, Ning; Yang, Jing-Yan; Wang, Xiao-Ying; Wang, Hai-Tao; Guan, Bing-Xin; Zhou, Cheng-Jun

    2016-02-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell-cell adhesion receptor and is implicated in several cellular functions. It is rarely reported in ovarian tumors. The aim of this study is to determine the expression of CEACAM1 in ovarian tumors, trying to see whether CEACAM1 has different expression patterns as a function of histotype. Antigen expression was examined by immunohistochemistry with mouse anti-human antibody for CEACAM1. Immunohistochemistry was performed using avidin-biotin-diaminobenzide staining. The results were expressed as average score ± SD (0, negative; 8, highest) for each histotype. In ovarian tumors, the benign serous and mucinous cystadenoma negatively or weakly expressed CEACAM1, the malignant epithelial tumors strongly expressed CEACAM1, and there was significant difference between benign epithelial tumor and adenocarcinoma (P < .05). The well-differentiated serous adenocarcinoma expressed CEACAM1 mainly with membrane pattern, and the intermediately and poorly differentiated serous adenocarcinomas expressed CEACAM1 mainly with cytoplasmic pattern (P < .05). In addition, CEACAM1 expression is elevated in solid tumors of ovary but variable as a function of histotype. Compared with membranous expression, the cytoplasmic expression was observed almost in metastatic carcinoma that might decrease the adhesive interactions of the carcinoma cells with the surrounding cells, especially with tumor cells, and this could facilitate the tumor cells to metastasize to distant regions. So, we thought that cytoplasmic CEACAM1 might play an important role in tumor progression, especially in tumor metastasis. PMID:26653024

  16. Ovarian Malignant Mixed Germ Cell Tumor: A Case of Unusual Presentation as Molar Pregnancy

    PubMed Central

    Aminimoghaddam, Soheila; Mohseni, Iman; Afzalzadeh, Azadeh; Esmaeeli, Shooka

    2016-01-01

    Background: This research was conducted to introduce a patient with rare ovarian mixed germ cell tumor, presented as molar pregnancy. Case Presentation: The patient was a 16 year old woman admitted with diagnosis of molar pregnancy. Abdominal enlargement was the only complaint. She had a large pelvic mass in physical examination. The first diagnosis was molar pregnancy due to previous ultrasonic reports and positive βeta HCG. Urine pregnancy test was positive. As suction curettage was performed for her, surprisingly, the size of uterus was normal and no molar tissue was found in pathologic examination. At intraoperative ultrasound exam, an extra-uterine heterogeneous mass was found. Extra-uterine mass was confirmed by CT and MRI done after suction curettage. Mixed germ cell tumor was confirmed by histological examination after laparatomy and removing tumoral mass. Finally, she received Bleomycin, Etoposide and Cisplatin (BEP) regimen in four courses and Vincristine, Actinomycin D (Dactinomycin) and Cyclophosphamide (VAC) regimen in two courses and Diphereline for saving the other ovary. Conclusion: Some young patients misinterpret the early symptoms of an ovarian neoplasm as those of pregnancy which can lead to a delay in the diagnosis. PMID:27141469

  17. 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

  18. Fluorescence-lifetime molecular imaging can detect invisible peritoneal ovarian tumors in bloody ascites

    PubMed Central

    Nakajima, Takahito; Sano, Kohei; Sato, Kazuhide; Watanabe, Rira; Harada, Toshiko; Hanaoka, Hirofumi; Choyke, Peter L; Kobayashi, Hisataka

    2014-01-01

    Blood contamination, such as bloody ascites or hemorrhages during surgery, is a potential hazard for clinical application of fluorescence imaging. In order to overcome this problem, we investigate if fluorescence-lifetime imaging helps to overcome this problem. Samples were prepared at concentrations ranging 0.3–2.4 μm and mixed with 0–10% of blood. Fluorescence intensities and lifetimes of samples were measured using a time-domain fluorescence imager. Ovarian cancer SHIN3 cells overexpressing the D-galactose receptor were injected into the peritoneal cavity 2.5 weeks before the experiments. Galactosyl serum albumin-rhodamine green (GSA-RhodG), which bound to the D-galactose receptor and was internalized thereafter, was administered intraperitoneally to peritoneal ovarian cancer-bearing mice with various degrees of bloody ascites. In vitro study showed a linear correlation between fluorescence intensity and probe concentration (r2 > 0.99), whereas the fluorescence lifetime was consistent (range, 3.33 ± 0.15–3.75 ± 0.04 ns). By adding 10% of blood to samples, fluorescence intensities decreased to <1%, while fluorescence lifetimes were consistent. In vivo fluorescence lifetime of GSA-RhodG stained tumors was longer than the autofluorescence lifetime (threshold, 2.87 ns). Tumor lesions under hemorrhagic peritonitis were not depicted using fluorescence intensity imaging; however, fluorescence-lifetime imaging clearly detected tumor lesions by prolonged lifetimes. In conclusion, fluorescence-lifetime imaging with GSA-RhodG depicted ovarian cancer lesions, which were invisible in intensity images, in hemorrhagic ascites. PMID:24479901

  19. A Primary Retroperitoneal Mucinous Tumor

    PubMed Central

    Heelan Gladden, Alicia A.; Wohlauer, Max; McManus, Martine C.; Gajdos, Csaba

    2015-01-01

    A twenty-five-year-old female presented with a large retroperitoneal mass. Workup included history and physical exam, imaging, biopsy, colonoscopy, and gynecologic exam. After surgical resection, the mass was determined to be a primary retroperitoneal mucinous tumor (PRMT). Clinically and histologically, these tumors are similar pancreatic and ovarian mucinous neoplasms. PRMTs are rare and few case reports have been published. PRMTs are divided into mucinous cystadenomas, mucinous borderline tumors of low malignant potential, and mucinous carcinoma. These tumors have malignant potential so resection is indicated and in some cases adjuvant chemotherapy and/or surveillance imaging. PMID:25874152

  20. Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin.

    PubMed

    Fujii, Kaho; Yamashita, Yoriko; Yamamoto, Toshimichi; Takahashi, Koji; Hashimoto, Katsunori; Miyata, Tomoko; Kawai, Kumi; Kikkawa, Fumitaka; Toyokuni, Shinya; Nagasaka, Tetsuro

    2014-04-01

    Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. PMID:24485845

  1. α-Fetoprotein-producing ovarian tumor in a postmenopausal woman with germ cell differentiation.

    PubMed

    Meguro, Shiori; Yasuda, Masanori

    2013-02-01

    α-Fetoprotein (AFP)-producing ovarian tumors (APOTs) are rarely encountered in postmenopausal women, irrespective of whether they are of the germ cell or non-germ cell type. The APOTs that do occur in postmenopausal women are characterized by variable histologies such as hepatoid carcinoma, yolk sac tumor, and epithelial malignancies, most of which are combined. We herein present a case with APOT, which arose in a 58-year-old, gravida 2, para 2, postmenopausal woman. Preoperatively, the tumor, which was in the right ovary, was found to produce AFP (102768.0 ng/mL). The tumor was evenly composed of glands mimicking secretory endometrial gland or fetal gut accompanied by abundant stroma. Immunohistochemically, these glands were positive for SALL4, glypican-3, and hepatocyte nuclear factor 1β. We considered the present case as an AFP-producing adenocarcinoma with adenofibroma showing germ cell differentiation, but it seemed controversial that this tumor should be designated as a yolk sac tumor of the glandular type. The expression profiles of SALL4, OCT4, glypican-3, and hepatocyte nuclear factor 1β were thought to provide interesting implications to characterize the present case. PMID:22056036

  2. Downregulation of SASH1 correlates with tumor progression and poor prognosis in ovarian carcinoma

    PubMed Central

    REN, XIAOYAN; LIU, YIFEI; TAO, YUMEI; ZHU, GUOXIANG; PEI, MEILAN; ZHANG, JIANGUO; LIU, JIAN

    2016-01-01

    SAM- and SH3-domain containing 1 (SASH1) is a recently identified tumor suppressor gene that is required in the tumorigenesis of breast and other solid carcinomas. The SASH1 protein contains SH3 and SAM domains, indicating that it may serve an important role in intracellular signal transduction. The purpose of the present study was to investigate the expression of SASH1 in ovarian carcinoma and the correlation between its expression with clinical pathological features and clinical significance, and the effect of SASH1 on cell proliferation, apoptosis and migration of ovarian SKOV3 cells. The human ovarian carcinoma tissues and adjacent normal tissues were collected following surgery. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression levels of SASH1 mRNA and protein, respectively. The expression levels of SASH1 mRNA and protein in ovarian carcinoma tissues were significantly lower than that observed in adjacent normal tissues (P<0.05). The expression levels of SASH1 in samples from patients without lymph nodes metastasis and patients with early FIGO stage was lower than those with lymph nodes metastasis and patients with advanced FIGO stage (P<0.05). Flow cytometry analysis and Transwell invasion chamber experiments were used to investigate the effect of SASH1 on the cell proliferation, apoptosis and migration of SKOV3 cells. The recombinant plasmid pcDNA3.1-SASH1 was constructed and transfected into SKOV3 cells. In addition, the SKOV3 cells in the pcDNA3.1-SASH1 group exhibited significantly reduced cell growth, proliferation, and migration ability compared to the empty vector group and normal group (P<0.01). There were a greater number of apoptotic cells in the pcDNA3.1-SASH1 group compared to the empty vector group and normal group (P<0.01). Taken together, these results indicated that SASH1 may be a tumor suppressor gene in ovarian carcinoma, and SASH1 expression inhibited growth

  3. 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

  4. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    PubMed Central

    Ohman, Anders W.; Hasan, Noor; Dinulescu, Daniela M.

    2014-01-01

    The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early-stages and improving the disease prognosis. PMID:25478323

  5. Effect of preemptive analgesia with intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor

    PubMed Central

    Wang, Na; Wang, Yuantao; Pang, Lei; Wang, Jinguo

    2015-01-01

    Objective: To evaluate the efficacy of preemptive intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor. Methods: Sixty ASA I or II patients undergoing elective laparoscopic resection of ovarian tumor were randomly allocated to one of two groups: Group O (n=30) received intravenous oxycodone (0.1 mg·kg-1) 10 minutes before surgery over 2 minutes, and Group N (n=30) received an equivalent volume of normal saline. All patients received a standardized general anesthesia. MBP and HR at the time of arrival of the operating room (T1), 5 min before pneumoperitoneum (T2), 5 minutes (T3), 10 minutes (T4), and 15 minutes after pneumoperitoneum (T5), and VAS scores at postoperative 2, 4, 8, 12 and 24 hour were recorded. The tramadol consumption and side effects in 24 h after surgery were recorded. Results: VAS pain scores at 2, 4, 8 and 12 hour after operation were significantly lower in Group O (P<0.05). MBP and HR increased significantly due to pneumoperitoneum at T3, T4 and T5, compared with T1 and T2 within Group N, and were higher at T3, T4 and T5 in Group N than at the same time points in Group O. Tramadol consumption was statistically lower in Group O (P=0.0003). Conclusions: Preemptive intravenous oxycodone was an efficient and safe method to reduce intraoperative haemodynamic effect and postoperative pain. PMID:26101479

  6. 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

  7. 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

  8. Feto-maternal outcomes of pregnancy complicated by ovarian sex-cord stromal tumor: a systematic review of literature.

    PubMed

    Blake, Erin A; Carter, Charelle M; Kashani, Banafsheh N; Kodama, Michiko; Mabuchi, Seiji; Yoshino, Kiyoshi; Matsuo, Koji

    2014-04-01

    Sex-cord stromal tumors (SCSTs) are rare ovarian cancers and their behavior during pregnancy is not well understood. To evaluate the maternal and fetal outcomes of pregnancy complicated by ovarian SCST, a systematic literature search was conducted in PubMed/MEDLINE using entry key words "pregnancy" and each type of ovarian SCST ("sex cord stromal tumor," "granulosa cell tumor," "thecoma," "Sertoli-Leydig cell tumor," or "gynandroblastoma") between 1955 and 2012 that identified 46 cases eligible for the analysis. Clinical characteristics, pregnancy outcome, tumor characteristics, and survival outcomes were evaluated. Serious adverse events were defined as complications related to the SCST that resulted in severe morbidity or mortality for mother, fetus, or both. The most common histology was granulosa cell tumor (22.0%), followed by thecoma (18.6%) and Sertoli-Leydig cell tumor (8.5%). Abdomino-pelvic pain (45.7%), palpable mass (30.4%), and virilization (26.1%) were the three most common symptoms. The majority were stage I (76.1%), tumor size <15cm (64.9%), and underwent unilateral adnexectomy (80.4%). Fetal conservation surgery was seen in 54.3%. Most cases had live births (78.3%) at full term (60.9%). Among cases proceeded expectant delay of delivery (45.7%), most cases resulted in live birth (95.2%) with median expectant interval of 20.7 weeks. Maternal and/or fetal serious adverse events (SAEs) were observed in 41.3% with maternal shock/hemoperitoneum being the most common complication (13.0%). Logistic regression test identified younger age (<30 versus ≥30, 73.3% versus 26.7%, odds ratio [OR] 11.7, 95%CI 1.35-101, p=0.026), large tumor (size ≥15cm versus <15cm, 64.9% versus 35.1%, OR 10.0, 95%CI 1.29-26.2, p=0.004), and advanced-stage (stages II-IV versus I, 76.1% versus 23.9%, OR 5.82, 95%CI 2.05-48.9, p=0.022) as risk factors of increased SAE. Overall survival of patients diagnosed with ovarian SCST during pregnancy was comparable to ovarian SCST not

  9. Mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma.

    PubMed

    Wang, Ying; Zhou, Feng; Qian, Zhida; Qing, Jiale; Zhao, Mengdam; Huang, Lili

    2014-11-01

    We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors. PMID:25518772

  10. Unusual Sertoli Cell Tumor Associated With Sex Cord Tumor With Annular Tubules in Peutz-Jeghers Syndrome: Report of a Case and Review of the Literature on Ovarian Tumors in Peutz-Jeghers Syndrome.

    PubMed

    Ravishankar, Sanjita; Mangray, Shamlal; Kurkchubasche, Arlet; Yakirevich, Evgeny; Young, Robert H

    2016-05-01

    We report the case of an 11-year-old girl with Peutz-Jeghers syndrome and a unilateral ovarian tumor most consistent with Sertoli cell tumor associated with sex cord tumor with annular tubules. The ovary was replaced by a lobular, solid, yellow tumor. Microscopic examination showed 2 components that focally merged. The first was composed of uniform, cytologically bland cells arranged mostly in diffuse sheets and focally in tubules. The second showed typical sex cord tumor with annular tubules with extensive calcification. The predominant component of the tumor clearly fell in the sex cord category and most closely resembled Sertoli cell tumor. This case adds to the limited information on ovarian sex cord tumors, other than typical sex cord tumor with annular tubules, arising in association with Peutz-Jeghers syndrome, a topic reviewed herein. PMID:26621753

  11. 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

  12. 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.

  13. Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis

    PubMed Central

    Abbott, Karen L.; Lim, Jae-Min; Wells, Lance; Benigno, Benedict B.; McDonald, John F.; Pierce, Michael

    2016-01-01

    Epithelial ovarian cancer is diagnosed less than 25% of the time when the cancer is confined to the ovary, leading to 5-year survival rates of less than 30%. Therefore, there is an urgent need for early diagnostics for ovarian cancer. Our study using glycotranscriptome comparative analysis of endometrioid ovarian cancer tissue and normal ovarian tissue led to the identification of distinct differences in the transcripts of a restricted set of glycosyltransferases involved in N-linked glycosylation. Utilizing lectins that bind to glycan structures predicted to show changes, we observed differences in lectin-bound glycoproteins consistent with some of the transcript differences. In this study, we have extended our observations by the use of selected lectins to perform a targeted glycoproteomic analysis of ovarian cancer and normal ovarian tissues. Our results have identified several glycoproteins that display tumor-specific glycosylation changes. We have verified these glycosylation changes on glycoproteins from tissue using immunoprecipitation followed by lectin blot detection. The glycoproteins that were verified were then analyzed further using existing microarray data obtained from benign ovarian adenomas, borderline ovarian adenocarcinomas, and malignant ovarian adenocarcinomas. The verified glycoproteins found to be expressed above control levels in the microarray data sets were then screened for tumor-specific glycan modifications in serum from ovarian cancer patients. Results obtained from two of these glycoprotein markers, periostin and thrombospondin, have confirmed that tumor-specific glycan changes can be used to distinguish ovarian cancer patient serum from normal serum. PMID:19953551

  14. In vitro production of cyclic AMP and steroids from an ovarian Sertoli-Leydig cell tumor. Notes on clinical management.

    PubMed

    Abrahamsson, G; Dahlgren, E; Hahlin, M; Knutson, F; Norström, A; Janson, P O

    1995-04-01

    A 27 year old nulliparous woman with a history of chronic anovulation and signs of virilization with a markedly elevated serum level of testosterone, underwent a laparotomy with peroperative bilateral ovarian vein catheterization and bilateral bisection of both ovaries. A solid, 1.5 cm, well delimited tumor located centrally in the right ovary, was excised. Testosterone levels in ovarian venous blood from the tumor bearing side, were 88.4 nmol/l and from the contralateral ovary 3.9 nmol/l. Histopathological examination showed a Sertoli-Leydig cell tumor which was radically extirpated. Postoperatively, the serum levels of androgen normalized, the woman had regular cycles, became pregnant and delivered a normal female baby. Pieces of tumor tissue were incubated for 2 h, with and without addition of gonadotropins and adrenocorticotropic hormone (ACTH). Human chorionic gonadotropin (CG), follicle stimulating hormone (FSH) and adrenocorticotropic hormone (ACTH) caused significant increases in cyclic monophosphate (cAMP) production in tumor tissue in vitro, as compared to controls. Furthermore, ACTH also significantly stimulated 17 beta-estradiol production. In tumor cells cultured for 48 h, FSH slightly, but not significantly, increased the production of progesterone. In the cell culture, [3H]-thymidine incorporation into deoxyribonucleic acid (DNA) was stimulated by IGF1 alpha but not by hCG and FSH. It is concluded that Sertoli-Leydig cell tumors may be sensitive to gonadotropins and ACTH and that their small size, solid shape and intra-ovarian localization can cause diagnostic difficulties. PMID:7732806

  15. Inhibition of focal adhesion kinase (FAK) activity prevents anchorage-independent ovarian carcinoma cell growth and tumor progression

    PubMed Central

    Ward, Kristy K.; Tancioni, Isabelle; Lawson, Christine; Miller, Nichol L.G.; Jean, Christine; Chen, Xiao Lei; Uryu, Sean; Kim, Josephine; Tarin, David; Stupack, Dwayne G.; Plaxe, Steven C.; Schlaepfer, David D.

    2013-01-01

    Recurrence and spread of ovarian cancer is the 5th leading cause of death for women in the United States. Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase located on chromosome 8q24.3 (gene is Ptk2), a site commonly amplified in serous ovarian cancer. Elevated FAK mRNA levels in serous ovarian carcinoma are associated with decreased (logrank P = 0.0007, hazard ratio 1.43) patient overall survival, but how FAK functions in tumor progression remains undefined. We have isolated aggressive ovarian carcinoma cells termed ID8-IP after intraperitoneal (IP) growth of murine ID8 cells in C57Bl6 mice. Upon orthotopic implantation within the periovarian bursa space, ID8-IP cells exhibit greater tumor growth, local and distant metastasis, and elevated numbers of ascites-associated cells compared to parental ID8 cells. ID8-IP cells exhibit enhanced growth under non-adherent conditions with elevated FAK and c-Src tyrosine kinase activation compared to parental ID8 cells. In vitro, the small molecule FAK inhibitor (Pfizer, PF562,271, PF-271) at 0.1 uM selectively prevented anchorage-independent ID8-IP cell growth with the inhibition of FAK tyrosine (Y)397 but not c-Src Y416 phosphorylation. Oral PF-271 administration (30 mg/kg, twice daily) blocked FAK but not c-Src tyrosine phosphorylation in ID8-IP tumors. This was associated with decreased tumor size, prevention of peritoneal metastasis, reduced tumor-associated endothelial cell number, and increased tumor cell-associated apoptosis. FAK knockdown and re-expression assays showed that FAK activity selectively promoted anchorage-independent ID8-IP cell survival. These results support the continued evaluation of FAK inhibitors as a promising clinical treatment for ovarian cancer. PMID:23275034

  16. A novel truncated form of HMGA2 in tumors of the ovaries

    PubMed Central

    Agostini, Antonio; Panagopoulos, Ioannis; Davidson, Ben; Trope, Claes Goran; Heim, Sverre; Micci, Francesca

    2016-01-01

    Neoplasms of the ovary are the second most common tumor of the female reproductive system, and the most lethal of the gynecological malignancies. Ovarian tumors are divided into a copious number of different groups reflecting their different features. The present study analyzed 187 ovarian tumors (39 sex-cord stromal tumors, 22 borderline tumors and 126 carcinomas) for the expression of the high-mobility group AT-hook 2 (HMGA2) gene, for mutations in the isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1), isocitrate dehydrogenase (NADP(+)) 2, mitochondrial (IDH2) and telomerase reverse transcriptase (TERT) genes, and for methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter. Reverse transcription-polymerase chain reaction analysis showed that HMGA2 was expressed in 74.5% of the samples (120/161). A truncated transcript of HMGA2 was identified in 11 cases. A novel truncated form of HMGA2 was found in 4 serous high-grade carcinomas. Only 4 tumors (4/185) showed the TERT C228T mutation. No IDH1 or IDH2 mutations were found. Methylation of the promoter of MGMT was found in 2 borderline tumors (2/185). HMGA2 was expressed, in its truncated and native form, in different ovarian tumors, even the less aggressive types, underscoring the general importance of this gene in ovarian tumorigenesis. Mutations involving TERT, as well as MGMT promoter methylation, are rare events in ovarian tumors. PMID:27446471

  17. Ovarian tumor (OTU)-domain containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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, a...

  18. 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...

  19. Borderline personality disorder

    MedlinePlus

    Personality disorder - borderline ... Cause of borderline personality disorder (BPD) is unknown. Genetic, family, and social factors are thought to play roles. Risk factors for BPD include: Abandonment ...

  20. Association between ambient ultraviolet radiation and risk of epithelial ovarian cancer.

    PubMed

    Tran, Bich; Jordan, Susan J; Lucas, Robyn; Webb, Penelope M; Neale, Rachel

    2012-11-01

    Evidence is accumulating to suggest that higher exposure to solar ultraviolet radiation (UVR) is associated with decreased risk of internal cancers, but data for ovarian cancer are unclear. We aimed to examine the association between lifetime ambient UVR and ovarian cancer in a population-based-case-control study. The study included women aged 18 to 79 years with a new diagnosis of invasive (n = 1,215) or borderline (n = 285) epithelial ovarian cancer identified through a network of clinics and state cancer registries throughout Australia. Controls (n = 1,459), frequency matched to cases by age (5-year groups) and state of residence, were randomly selected from the National Electoral Roll. We asked participants to report where they had lived at different periods of their life and assigned an estimate of UVR using data from NASA's Total Ozone Mapping Spectrometer database (1997-2003). We estimated the association between ambient UVR and risk of ovarian cancer using conditional logistic regression adjusted for potential confounders. Women in the highest third of average daily ambient UVR over their lifetime were at significantly lower risk of all epithelial ovarian cancers than those in the lowest third [OR, 0.70; 95% confidence interval (CI), 0.56-0.88]. The inverse association was stronger for borderline tumors (0.47, 0.31-0.71) than invasive tumors (0.78, 0.61-1.00). The effect sizes for overall and borderline tumors were unchanged after adjusting for confounders, whereas the inverse association for invasive tumors was attenuated. These data suggest that exposure to ambient UVR may reduce the risk of ovarian cancer. PMID:23034146

  1. OVARIAN CANCER

    PubMed Central

    Cho, Kathleen R.; Shih, Ie-Ming

    2009-01-01

    Ovarian carcinomas are a heterogeneous group of neoplasms traditionally sub-classified based on type and degree of differentiation. Although current clinical management of ovarian carcinoma largely fails to take this heterogeneity into account, it is becoming evident that each major histological type has characteristic genetic defects that deregulate specific signaling pathways in the tumor cells. Moreover, within the most common histological types, the molecular pathogenesis of low-grade versus high-grade tumors appears to be largely distinct. Mouse models of ovarian carcinoma have been developed that recapitulate many of the morphological features, biological behavior, and gene expression patterns of selected subtypes of ovarian cancer. Such models will likely prove useful for studying ovarian cancer biology and for pre-clinical testing of molecularly targeted therapeutics, which may ultimately lead to better clinical outcomes for women with ovarian cancer. PMID:18842102

  2. Anti-KDEL-coated nanoparticles: a promising tumor targeting approach for ovarian cancer?

    PubMed

    Delie, Florence; Ribaux, Pascale; Petignat, Patrick; Cohen, Marie

    2012-11-01

    The purpose of this study was to target ovarian cancer cells by coupling paclitaxel (Tx)-loaded nanoparticles (NPs-Tx) to antibodies against KDEL sequence, able to recognize GRP94 and GRP78 that are located at cell surface in cancer cells whereas they are in the endoplasmic reticulum in healthy cells. Tx-loaded poly (DL-lactic acid) nanoparticles coated with anti-KDEL antibodies (NPs-Tx-KDEL) were successfully prepared and characterized. Interaction between tumor cells and NPs-Tx or NPs-Tx-KDEL was observed by microscopy with fluorescently labeled NPs and the efficacy of the different formulations was compared by a viability assay. Particles functionalized with monoclonal antibodies (mAb) showed a higher binding to the cells even though the internalization rate appeared limited. The effect of NPs-Tx-KDEL on cell viability (proliferation) was compared to Tx, NPs, NPs-Tx, anti-KDEL mAb or anti-KDEL mAb in combination with NPs-Tx in Bg-1 ovarian cell line. Our data indicate that NPs-Tx-KDEL significantly increase sensitivity of Bg-1 cells to Tx compared to other treatments. This study confirms the interest of anti-cancer therapy by targeting cell surface GRP78 and GRP94 on cancer cells, and demonstrates the efficiency of coupling KDEL antibodies to NPs. PMID:22713763

  3. Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors.

    PubMed Central

    Risma, K A; Clay, C M; Nett, T M; Wagner, T; Yun, J; Nilson, J H

    1995-01-01

    Hypersecretion of luteinizing hormone (LH) is implicated in infertility and miscarriages in women. A lack of animal models has limited progress in determining the mechanisms of LH toxicity. We have recently generated transgenic mice expressing a chimeric LH beta subunit (LH beta) in gonadotropes. The LH beta chimera contains the C-terminal peptide of the human chorionic gonadotropin beta subunit. Addition of this peptide to bovine LH beta resulted in a hormone with a longer half-life. Furthermore, targeted expression of the LH beta chimera led to elevated LH levels and infertility in female transgenics. These mice ovulated infrequently, maintained a prolonged luteal phase, and developed pathologic ovarian changes such as cyst formation, marked enlargement of ovaries, and granulosa cell tumors. Testosterone and estradiol levels were increased compared to nontransgenic littermates. An unusual extragonadal phenotype was also observed: transgenic females developed hydronephropathy and pyelonephritis. The pathology observed demonstrates a direct association between abnormal secretion of LH and infertility and underscores the utility of the transgenic model for studying how excess LH leads to cyst formation, ovarian tumorigenesis, and infertility. Images Fig. 2 Fig. 3 Fig. 5 PMID:7877975

  4. Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2016-06-14

    Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  5. 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

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed 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 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

  6. Toward an integrative analysis of the tumor microenvironment in ovarian epithelial carcinoma.

    PubMed

    Serio, Ryan N

    2012-08-01

    Ovarian epithelial carcinomas are heterogeneous malignancies exhibiting great diversity in histological phenotypes as well as genetic and epigenetic aberrations. A general early event in tumorigenesis is regional dissemination into the peritoneal cavity. Initial spread to the peritoneum is made possible by cooperative signaling between a wide array of molecules constituting the tissue microenvironment in the coelomic epithelium. Changes in the activity of key microenvironmental components not constitutively expressed in normal tissue, including several disclosed adhesion molecules, growth factors, proteases, and G-protein coupled receptors (GPCRs), coordinate the transition. Remodeling of the extracellular matrix (ECM) and subsequent cell surface interactions enable transformation by promoting chromosomal instability (CIN) and stimulating several common signal transduction cascades to prepare the tissue for harboring and facilitating growth, angiogenesis and metastasis of the developing tumor. PMID:22109660

  7. 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. PMID:19234121

  8. 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

  9. 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.

  10. Solitary fibrous tumor of the greater omentum mimicking an ovarian tumor in a young woman.

    PubMed

    Rodriguez Tarrega, Elisabet; Hidalgo Mora, Juan Jose; Paya Amate, Vicente; Vega Oomen, Olivia

    2016-08-01

    We report a case of solitary fibrous tumor (SFT) of greater omentum in a young woman. SFT arising from the greater omentum can mimic a gynecologic neoplasm. SFTs are generally benign but some of them are malignant and have uncertain prognosis. An adequate follow-up is essential in these patients. PMID:27354994

  11. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

    PubMed Central

    2012-01-01

    Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R) agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and for TPO-R protein expression by immunohistochemistry (IHC). Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43%) and malignant (3-17%) breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and megakaryocyte precursors. PMID

  12. Recent concepts of ovarian carcinogenesis: type I and type II.

    PubMed

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2014-01-01

    Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC) arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT). With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs) of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the "tubal peritoneal junction" (TPJ), undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells. PMID:24868556

  13. F3-targeted cisplatin-hydrogel nanoparticles as an effective therapeutic that targets both murine and human ovarian tumor endothelial cells in vivo

    PubMed Central

    Winer, I.; Wang, S.; Lee, Y-E K.; Fan, W.; Gong, Y.; Burgos-Ojeda, D.; Spahlinger, G.; Kopelman, R.; Buckanovich, Ronald J.

    2010-01-01

    Recent studies indicate that ovarian cancer may be highly responsive to anti-vascular therapeutics. We have developed an anti-vascular tumor therapeutic using the F3 peptide to target cisplatin loaded nanoparticles (F3-Cis-Np) to tumor vessels. We demonstrate that while F3-Cis-Np bind with high specificity to both human ovarian tumor cells and tumor endothelial cells in vitro, they only demonstrate cytotoxic activity against the tumor endothelial cells. In vivo these nanoparticles bind primarily to tumor endothelial cells. Therapeutic studies in both flank and orthotopic intraperitoneal murine ovarian tumor models, as well as human tumor xenograft models, demonstrate rapid tumor regression with treatment. Treatment was associated with significant vascular necrosis consistent with an anti-vascular effect. Furthermore treatment was active in both platinum sensitive and platinum resistant cell lines. Importantly we demonstrate that F3-Cis-Np bind to human tumor endothelial cells in vitro and to human tumor vessels in vivo. Therapy targeting human vasculature in vivo with F3-Cis-Np led to near complete loss of all human tumor vessels in a murine model of human tumor vasculature. Our studies indicate that F3-targeted vascular therapeutics may be an effective treatment modality in human ovarian cancer. PMID:20959470

  14. 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

  15. Identification of salt-inducible kinase 3 as a novel tumor antigen associated with tumorigenesis of ovarian cancer.

    PubMed

    Charoenfuprasert, S; Yang, Y-Y; Lee, Y-C; Chao, K-C; Chu, P-Y; Lai, C-R; Hsu, K-F; Chang, K-C; Chen, Y-C; Chen, L-T; Chang, J-Y; Leu, S-J; Shih, N-Y

    2011-08-18

    Existence of humoral immunity has been previously demonstrated in malignant ascitic fluids. However, only a limited number of immunogenic tumor-associated antigens (TAAs) were identified, and few of which are associated with ovarian cancer. Here, we identified salt-inducible kinase 3 (SIK3) as a TAA through screening of a random peptide library in the phage display system. Overexpression of SIK3 markedly promoted cell proliferation, attenuated p21(Waf/Cip1) and p27(Kip) expressions in low-grade OVCAR3 cells, and permitted the cells to grow in mice. Decrease in SIK3 expression in high-grade SK-OV3 cells consistently demonstrated its tumorigenic potency by modulating the protein levels of cell cycle regulators. When the expressions of SIK3 and CA125 were compared in cancer tissues, immunohistochemical (IHC) studies indicated that cytoplasm-localized SIK3 was highly expressed in 55% of the ovarian cancer samples. In contrast, it was rarely detected in adenomyosis, leiomyoma and normal ovary tissues, showing its higher specificity (97%) to CA125 (65%) in ovarian cancer. Moreover, experiments using pharmacological inhibitors to block SIK3-induced p21(Waf/Cip1) expression revealed that activation of c-Src and phosphoinositide-3-kinase were critically required for its biological activity, suggesting that they are the downstream signaling mediators of SIK3. These data were further supported by IHC studies, showing coexpression of c-Src with SIK3 in 85% of the ovarian tumor samples stained positive for SIK3. Collectively, our findings indicate that SIK3 is a novel ovarian TAA. Overexpression of SIK3 promotes G1/S cell cycle progression, bestows survival advantages to cancer cells for growth and correlates the clinicopathological conditions of patients with ovarian cancer. PMID:21399663

  16. Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis

    PubMed Central

    Kawana, Kei; Adachi, Katsuyuki; Kawata, Akira; Ogishima, Juri; Nakamura, Hiroe; Fujimoto, Asaha; Sato, Masakazu; Inoue, Tomoko; Nishida, Haruka; Furuya, Hitomi; Tomio, Kensuke; Arimoto, Takahide; Koga, Kaori; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Kiyono, Tohru; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    The most common properties of oncogenes are cell proliferation and the prevention of apoptosis in malignant cells, which, as a consequence, induce tumor formation and dissemination. However, the effects of oncogenes on the tumor microenvironment (TME) have not yet been examined in detail. The accumulation of ascites accompanied by chronic inflammation and elevated concentrations of VEGF is a hallmark of the progression of ovarian cancer. We herein demonstrated the mechanisms by which oncogenes contribute to modulating the ovarian cancer microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the peritoneal cavities of C57/BL6 mice and the production of ascites was assessed. ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in vivo, whereas no significant differences were observed in proliferative activity in vitro. ID8-KRAS in particular induced the production of ascites, which accumulated between approximately two to three weeks after the injection, more rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and seven weeks, respectively). VEGF concentrations in ascites significantly increased in c-MYC-induced ovarian cancer, whereas the concentrations of inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian cancer and were accompanied by an increased number of neutrophils in ascites. A cytokine array revealed that KRAS markedly induced the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest that oncogenes promote cancer progression by modulating the TME in favor of cancer progression. PMID:27483433

  17. Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis.

    PubMed

    Yoshida, Mitsuyo; Taguchi, Ayumi; Kawana, Kei; Adachi, Katsuyuki; Kawata, Akira; Ogishima, Juri; Nakamura, Hiroe; Fujimoto, Asaha; Sato, Masakazu; Inoue, Tomoko; Nishida, Haruka; Furuya, Hitomi; Tomio, Kensuke; Arimoto, Takahide; Koga, Kaori; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Kiyono, Tohru; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    The most common properties of oncogenes are cell proliferation and the prevention of apoptosis in malignant cells, which, as a consequence, induce tumor formation and dissemination. However, the effects of oncogenes on the tumor microenvironment (TME) have not yet been examined in detail. The accumulation of ascites accompanied by chronic inflammation and elevated concentrations of VEGF is a hallmark of the progression of ovarian cancer. We herein demonstrated the mechanisms by which oncogenes contribute to modulating the ovarian cancer microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the peritoneal cavities of C57/BL6 mice and the production of ascites was assessed. ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in vivo, whereas no significant differences were observed in proliferative activity in vitro. ID8-KRAS in particular induced the production of ascites, which accumulated between approximately two to three weeks after the injection, more rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and seven weeks, respectively). VEGF concentrations in ascites significantly increased in c-MYC-induced ovarian cancer, whereas the concentrations of inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian cancer and were accompanied by an increased number of neutrophils in ascites. A cytokine array revealed that KRAS markedly induced the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest that oncogenes promote cancer progression by modulating the TME in favor of cancer progression. PMID:27483433

  18. miR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1R.

    PubMed

    Li, Na; Zhao, Xiaosu; Wang, Lufei; Zhang, Shi; Cui, Manhua; He, Jin

    2016-06-01

    A growing body of evidence suggests that microRNA-494 (miR-494) could act as tumor-suppressive or oncogenic microRNAs (miRNAs) in different types of tumors. However, the biological roles and underlying mechanisms of miR-494 remain unknown in human epithelial ovarian carcinoma (EOC). Therefore, the aims of this study were to investigate the miR-494 expression and the significance of its clinical diagnosis in patients suffering EOC and to analyze its role and underlying molecular mechanism on the carcinogenesis of EOC. Here, we found that miR-494 was significantly decreased in EOC cell lines and tissues and its expression was negatively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high pathological grade, and lymph node metastasis (all P < 0.01). Functional studies showed that overexpression of miR-494 in EOC cells could remarkably inhibit proliferation, colony formation, migration, and invasion and induce cell apoptosis, G0/G1 phase arrest. An in vivo analysis revealed that the overexpression of miR-494 suppressed tumor growth in a nude mouse xenograft model system. Bioinformatic assay and dual-luciferase assay confirmed that insulin-like growth factor 1 receptor (IGF1R) was as a direct target of miR-494 in EOC cells. Western blot assay showed that overexpression of miR-494 inhibited IGF1R expression and its downstream signal protein expression. In addition, downregulation of IGF1R has similar effects with miR-494 overexpression on EOC cells and overexpression of IGF1R effectively rescued the inhibition of overexpressed miR-494 in EOC cells. These data suggested that miR-494 functions as a tumor suppressor in EOC by targeting IGF1R. PMID:26695144

  19. FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development.

    PubMed

    Liu, Zhilin; Ren, Yi A; Pangas, Stephanie A; Adams, Jaye; Zhou, Wei; Castrillon, Diego H; Wilhelm, Dagmar; Richards, JoAnne S

    2015-07-01

    The forkhead box (FOX), FOXO1 and FOXO3, transcription factors regulate multiple functions in mammalian cells. Selective inactivation of the Foxo1 and Foxo3 genes in murine ovarian granulosa cells severely impairs follicular development and apoptosis causing infertility, and as shown here, granulosa cell tumor (GCT) formation. Coordinate depletion of the tumor suppressor Pten gene in the Foxo1/3 strain enhanced the penetrance and onset of GCT formation. Immunostaining and Western blot analyses confirmed FOXO1 and phosphatase and tensin homolog (PTEN) depletion, maintenance of globin transcription factor (GATA) 4 and nuclear localization of FOXL2 and phosphorylated small mothers against decapentaplegic (SMAD) 2/3 in the tumor cells, recapitulating results we observed in human adult GCTs. Microarray and quantitative PCR analyses of mouse GCTs further confirmed expression of specific genes (Foxl2, Gata4, and Wnt4) controlling granulosa cell fate specification and proliferation, whereas others (Emx2, Nr0b1, Rspo1, and Wt1) were suppressed. Key genes (Amh, Bmp2, and Fshr) controlling follicle growth, apoptosis, and differentiation were also suppressed. Inhbb and Grem1 were selectively elevated, whereas reduction of Inha provided additional evidence that activin signaling and small mothers against decapentaplegic (SMAD) 2/3 phosphorylation impact GCT formation. Unexpectedly, markers of Sertoli/epithelial cells (SRY [sex determining region Y]-box 9/keratin 8) and alternatively activated macrophages (chitinase 3-like 3) were elevated in discrete subpopulations within the mouse GCTs, indicating that Foxo1/3/Pten depletion not only leads to GCTs but also to altered granulosa cell fate decisions and immune responses. Thus, analyses of the Foxo1/3/Pten mouse GCTs and human adult GCTs provide strong evidence that impaired functions of the FOXO1/3/PTEN pathways lead to dramatic changes in the molecular program within granulosa cells, chronic activin signaling in the presence of

  20. Active targeting using HER-2-affibody-conjugated nanoparticles enabled sensitive and specific imaging of orthotopic HER-2 positive ovarian tumors.

    PubMed

    Satpathy, Minati; Wang, Liya; Zielinski, Rafal; Qian, Weiping; Lipowska, Malgorzata; Capala, Jacek; Lee, Gee Young; Xu, Hong; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2014-02-12

    Despite advances in cancer diagnosis and treatment, ovarian cancer remains one of the most fatal cancer types. The development of targeted nanoparticle imaging probes and therapeutics offers promising approaches for early detection and effective treatment of ovarian cancer. In this study, HER-2 targeted magnetic iron oxide nanoparticles (IONPs) are developed by conjugating a high affinity and small size HER-2 affibody that is labeled with a unique near infrared dye (NIR-830) to the nanoparticles. Using a clinically relevant orthotopic human ovarian tumor xenograft model, it is shown that HER-2 targeted IONPs are selectively delivered into both primary and disseminated ovarian tumors, enabling non-invasive optical and MR imaging of the tumors as small as 1 mm in the peritoneal cavity. It is determined that HER-2 targeted delivery of the IONPs is essential for specific and sensitive imaging of the HER-2 positive tumor since we are unable to detect the imaging signal in the tumors following systemic delivery of non-targeted IONPs into the mice bearing HER-2 positive SKOV3 tumors. Furthermore, imaging signals and the IONPs are not detected in HER-2 low expressing OVCAR3 tumors after systemic delivery of HER-2 targeted-IONPs. Since HER-2 is expressed in a high percentage of ovarian cancers, the HER-2 targeted dual imaging modality IONPs have potential for the development of novel targeted imaging and therapeutic nanoparticles for ovarian cancer detection, targeted drug delivery, and image-guided therapy and surgery. PMID:24038985

  1. Use of fertility drugs and risk of ovarian cancer

    PubMed Central

    Diergaarde, Brenda; Kurta, Michelle L.

    2014-01-01

    Purpose of review To highlight recent research and insights into the relationship between fertility drug use and ovarian cancer risk. Recent findings Results from two large case-control studies provided further evidence that fertility drug use does not significantly contribute to risk of ovarian cancer among the majority of women when adjusting for known confounding factors. However, questions regarding the effect on certain subgroups, including long-term fertility drug users, women who remain nulligravid after fertility treatment, women with BRCA1 or BRCA2 mutations, and borderline ovarian tumors, still remain. In addition, it may currently just be too early to determine whether there is an association between fertility drug use and ovarian cancer risk given that many of the exposed women are only now beginning to reach the ovarian cancer age range. Summary Whether use of fertility drugs increases the risk of ovarian cancer is an important question that requires further investigation, in particular given the large number of women utilizing fertility treatments. Fortunately, results from recent studies have been mainly reassuring. Large well-designed studies with sufficient follow-up time are needed to further evaluate the effects of fertility treatments within subgroups defined by patient and tumor characteristics. PMID:24752005

  2. Mixed angiosarcoma, clear cell adenocarcinoma and mature teratoma elements in an ovarian tumor: a case report and literature review.

    PubMed

    Takahashi, Hiroyuki; Chaopotong, Pattama; Kajita, Sabine; Hashimura, Miki; Yamazaki, Hitoshi; Saegusa, Makoto

    2012-08-01

    Malignant transformation of a mature teratoma in the ovary is a rare event, with an approximate rate of only 1-2%. Here, we report an ovarian tumor with a unique combination of epithelial and non-epithelial malignant components, including mature teratoma elements. A 59 year-old postmenopusal woman underwent total hysterectomy and bilateral salpingo-oophorectomy to remove a huge solid mass of the right ovary. The ovarian tumor was 16 × 12 × 4.5 cm in dimensions, composed of red-brown and greyish-white tissue with several cystic areas. Microscopically, atypical cells immunopositive for both CD31 and CD34 formed irregular ectatic vascular patterns with a high MIB-1 labeling index in red-brown areas. In contrast, tubule-cystic and papillary structures were lined by HNF-1β-immunopositive atypical cuboidal and hobnail cells with clear cytoplasm in greyish-white areas. In addition, normal-looking epithelial and stromal components, including mature squamous, cuboidal and ciliated epithelial cells, and adipose tissues, were observed in red-brown areas, suggesting an ovarian tumor combining angiosarcoma, clear cell adenocarcinoma, and mature teratoma features. We could demonstrate identical X-chromosome inactivation patterns among all three components by human androgen receptor gene (HUMARA) assays, pointing to complex inter-relationships regarding their pathogenesis. These observations suggest that a malignant tumor composed of two characteristic phenotypes arose in mature teratoma. PMID:22827762

  3. High-throughput sequencing of T cell receptors reveals a homogeneous repertoire of tumor-infiltrating lymphocytes in ovarian cancer

    PubMed Central

    Rieder, Mark J.; Guenthoer, Jamie; Williamson, David W.; Carlson, Christopher S.; Drescher, Charles W.; Tewari, Muneesh; Bielas, Jason H.; Robins, Harlan S.

    2014-01-01

    The cellular adaptive immune system mounts a response to many solid tumors mediated by tumor infiltrating T lymphocytes (TILs). Basic measurements of these TILs, including total count, show promise as prognostic markers for a variety of cancers, including ovarian and colorectal. In addition, recent therapeutic advances are thought to exploit this immune response to effectively fight melanoma with promising studies showing efficacy in additional cancers. However, many of the basic properties of TILs are poorly understood including specificity, clonality, and spatial heterogeneity of the T cell response. We utilize deep sequencing of rearranged T-cell receptor beta (TCRB) genes to characterize the basic properties of TILs in ovarian carcinoma. Due to somatic rearrangement during T cell development, the TCR beta chain sequence serves as a molecular tag for each T cell clone. Using these sequence tags, we assess similarities and differences between infiltrating T cells in discretely sampled sections of large tumors and compare to T cells from peripheral blood. Within the limits of sensitivity of our assay, the TIL repertoires show strong similarity throughout each tumor and are distinct from the circulating T cell repertoire. We conclude that the cellular adaptive immune response within ovarian carcinomas is spatially homogeneous and distinct from the T cell compartment of peripheral blood. PMID:24027095

  4. Borderline Personality

    PubMed Central

    Sansone, Randy A.; Sansone, Lori A.

    2004-01-01

    BORDERLINE PERSONALITY DISORDER (BPD) IS A COMPLEX AXIS II Phenomenon that is typically described in a psychological or psychiatric context. In this article, we translate the various aspects of BPD to the primary care setting. Previous work in this area has explored specific relationships between BPD and individual medical disorders or between BPD and general somatic symptoms, but the synthesis of these findings and their augmentation with cogent psychological theory is new to the field. Specifically, we highlight the prevalence rate of BPD in the primary care setting, the effects on healthcare utilization, the themes of somatic preoccupation and somatization disorder, several medical syndromes that illustrate the dynamics of the disorder in the medical setting, and the relationship of BPD to disability. We believe that the BPD concept needs to extend beyond its traditional psychological/psychiatric borders to include the subset of BPD patients with somatic symptoms who are seen in primary care settings. PMID:21197375

  5. Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model

    PubMed Central

    Singh, Sheela P.; Lu, Chunhua; Han, Lin; Hobbs, Brian P.; Pradeep, Sunila; Choi, Hyun J.; Bankson, James A.

    2015-01-01

    Purpose To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T1 maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed. Results Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T1 relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis. Conclusions Findings suggest that increased tumor T1 relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response. PMID:26098849

  6. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma

    PubMed Central

    Sung, Pi-Lin; Jan, Yi-Hua; Lin, Shih-Chieh; Huang, Chao-Cheng; Lin, Hao; Wen, Kuo-Chang; Chao, Kuan-Chong; Lai, Chiung-Ru; Wang, Peng-Hui; Chuang, Chi-Mu; Wu, Hua-Hsi; Twu, Nae-Fang; Yen, Ming-Shyen; Hsiao, Michael; Huang, Chi-Ying F.

    2016-01-01

    The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics. PMID:26716408

  7. 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. PMID:26546024

  8. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma.

    PubMed

    Sung, Pi-Lin; Jan, Yi-Hua; Lin, Shih-Chieh; Huang, Chao-Cheng; Lin, Hao; Wen, Kuo-Chang; Chao, Kuan-Chong; Lai, Chiung-Ru; Wang, Peng-Hui; Chuang, Chi-Mu; Wu, Hua-Hsi; Twu, Nae-Fang; Yen, Ming-Shyen; Hsiao, Michael; Huang, Chi-Ying F

    2016-01-26

    The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics. PMID:26716408

  9. Distinct and Competitive Regulatory Patterns of Tumor Suppressor Genes and Oncogenes in Ovarian Cancer

    PubMed Central

    Zhao, Min; Sun, Jingchun; Zhao, Zhongming

    2012-01-01

    Background So far, investigators have found numerous tumor suppressor genes (TSGs) and oncogenes (OCGs) that control cell proliferation and apoptosis during cancer development. Furthermore, TSGs and OCGs may act as modulators of transcription factors (TFs) to influence gene regulation. A comprehensive investigation of TSGs, OCGs, TFs, and their joint target genes at the network level may provide a deeper understanding of the post-translational modulation of TSGs and OCGs to TF gene regulation. Methodology/Principal Findings In this study, we developed a novel computational framework for identifying target genes of TSGs and OCGs using TFs as bridges through the integration of protein-protein interactions and gene expression data. We applied this pipeline to ovarian cancer and constructed a three-layer regulatory network. In the network, the top layer was comprised of modulators (TSGs and OCGs), the middle layer included TFs, and the bottom layer contained target genes. Based on regulatory relationships in the network, we compiled TSG and OCG profiles and performed clustering analyses. Interestingly, we found TSGs and OCGs formed two distinct branches. The genes in the TSG branch were significantly enriched in DNA damage and repair, regulating macromolecule metabolism, cell cycle and apoptosis, while the genes in the OCG branch were significantly enriched in the ErbB signaling pathway. Remarkably, their specific targets showed a reversed functional enrichment in terms of apoptosis and the ErbB signaling pathway: the target genes regulated by OCGs only were enriched in anti-apoptosis and the target genes regulated by TSGs only were enriched in the ErbB signaling pathway. Conclusions/Significance This study provides the first comprehensive investigation of the interplay of TSGs and OCGs in a regulatory network modulated by TFs. Our application in ovarian cancer revealed distinct regulatory patterns of TSGs and OCGs, suggesting a competitive regulatory mechanism acting

  10. 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

  11. Human ovarian tumor cell interactions with extracellular matrix: development of a model to study tumor cell invasion

    SciTech Connect

    Niedbala, M.J.

    1986-01-01

    In order to investigate the mechanisms involved in ovarian carcinoma cell implantation and the associated tumor cell-host interactions, a model system was developed employing a mesothelial cell line grown on bovine corneal endothelial cell extracellular matrix (ECM), in an attempt to reconstruct the mesothelium in vitro. Morphologic alterations of the reconstructed mesothelium induced by OCC were observed using immunohistochemical staining, light and electron microscopy. A relationship was observed between extracellular ..beta..-N-acetylhexosaminidase activity and (1) the ability of OCC to morphologically degrade ECM; (2) the capacity of OCC to degrade (/sup 3/H)-glucosamine radiolabelled ECM. The rate of accumulation of extracellular hexosaminidase in cell free-conditioned medium was progressive and closely paralleled the rate of OCC mediated release of (/sup 3/H)-glucosamine from ECM. Purified hexosaminidase (placental and/or OCC) was observed to directly hydrolzye (/sup 3/H)-glucosamine radiolabelled structurally intact ECM (up to 70% radiolabel) and resulted in the cumulative release of free (/sup 3/H)-N-acetylglucosamine.

  12. 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. PMID:25818671

  13. Disseminated cervical adenoma malignum and bilateral ovarian sex cord tumors with annular tubules associated with Peutz-Jeghers syndrome.

    PubMed

    Srivatsa, P J; Keeney, G L; Podratz, K C

    1994-05-01

    Adenoma malignum is a highly differentiated mucinous adenocarcinoma of the cervix with a deceptively innocent histologic appearance but a highly aggressive behavior. We describe a patient who had adenoma malignum associated with Peutz-Jeghers syndrome (PJS) and bilateral ovarian sex cord tumor with annular tubules (SCTAT). The relatively frequent occurrence of cervical adenoma malignum in women with PJS warrants close surveillance by gynecologists for early detection and treatment of this cancer. We report the 16th known case of PJS with adenoma malignum and only the 8th known case of PJS with adenoma malignum and bilateral SCTAT. The highly aggressive nature of cervical adenoma malignum is exemplified, and the difficulties associated with early diagnosis are discussed. The clinical significance of cervical and ovarian tumors associated with PJS is reviewed. PMID:8188091

  14. The second annual conference of International ovarian cancer consortium and the symposium on tumor microenvironment and therapeutic resistance

    PubMed Central

    Isidoro, Ciro; Song, Yong Sang; Surh, Young-Joon; Dhanasekaran, Danny N.

    2016-01-01

    The second Annual Meeting of the International Ovarian Cancer Consortium (IOCC) was held in conjunction with the Symposium on Tumor Microenvironment and Therapeutic Resistance at the Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, and USA. A brief welcoming event along with the banquet on Aug 16th was followed by the eight thematic scientific sessions from August 16 to 18, 2015. Forty-three lectures, organized in eight sessions, were discussed in front of an audience of more than hundred attendees. Emphasis was put on oncogene signaling in cancer genesis and progression, new approaches in Precision Medicine and therapy of ovarian cancer, the role of tumor microenvironment in carcinogenesis, and preventive/curative potential of natural products. In this meeting-report, we highlight the findings and the perspectives in cancer biology and therapeutic strategies that emerged during the conference.

  15. 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

  16. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis.

    PubMed

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini; Skotheim, Rolf I; Abeler, Vera M; Rajpert-De Meyts, Ewa; Lothe, Ragnhild A

    2013-06-01

    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

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

    PubMed Central

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

    2016-01-01

    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. PMID:26797759

  18. 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

  19. PSP94 contributes to chemoresistance and its peptide derivative PCK3145 represses tumor growth in ovarian cancer.

    PubMed

    Yan, B-X; Ma, J-X; Zhang, J; Guo, Y; Riedel, H; Mueller, M D; Remick, S C; Yu, J J

    2014-11-01

    Tumor drug resistance remains a major challenge in the treatment of cancer. Here, we show that Prostatic secretory protein 94 (PSP94) levels are reduced in ovarian cancer patients with high levels of excision repair cross-complementing 1 (ERCC1), a marker for chemoresistance. We find that PSP94 is decreased in an ovarian cancer drug-resistant cell line, and plays an important role in the development of drug resistance in vitro. Our studies indicate that PSP94 can partially reverse drug resistance in mouse tumor models in vivo and that a PSP94 peptide derivative PCK3145 suppresses chemoresistant cancer cell and tumor growth in vitro and in vivo. Our investigation of the involved molecular mechanisms suggests that PSP94 may confer drug resistance by modulating the Lin28b/Let-7 signaling pathway. We introduce PSP94 and its peptide derivative PCK3145 as potential target to reverse chemoresistance in ovarian cancer and have begun to identify their relevant molecular targets in specific signaling pathways. PMID:24186202

  20. Endometriosis and Ovarian Cancer: A Review of Clinical, Pathologic, and Molecular Aspects

    PubMed Central

    Wei, Jian-Jun; William, Josette; Bulun, Serdar

    2014-01-01

    Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592

  1. Expression of the Homeobox Gene HOXA9 in Ovarian Cancer Induces Peritoneal Macrophages to Acquire an M2 Tumor-Promoting Phenotype

    PubMed Central

    Ko, Song Yi; Ladanyi, Andras; Lengyel, Ernst; Naora, Honami

    2015-01-01

    Tumor-associated macrophages (TAMs) exhibit an M2 macrophage phenotype that suppresses anti-tumor immune responses and often correlates with poor outcomes in patients with cancer. Patients with ovarian cancer frequently present with peritoneal carcinomatosis, but the mechanisms that induce naïve peritoneal macrophages into TAMs are poorly understood. In this study, we found an increased abundance of TAMs in mouse i.p. xenograft models of ovarian cancer that expressed HOXA9, a homeobox gene that is associated with poor prognosis in patients with ovarian cancer. HOXA9 expression in ovarian cancer cells stimulated chemotaxis of peritoneal macrophages and induced macrophages to acquire TAM-like features. These features included induction of the M2 markers, CD163 and CD206, and the immunosuppressive cytokines, IL-10 and chemokine ligand 17, and down-regulation of the immunostimulatory cytokine, IL-12. HOXA9-mediated induction of TAMs was primarily due to the combinatorial effects of HOXA9-induced, tumor-derived transforming growth factor-β2 and chemokine ligand 2 levels. High HOXA9 expression in clinical specimens of ovarian cancer was strongly associated with increased abundance of TAMs and intratumoral T-regulatory cells and decreased abundance of CD8+ tumor-infiltrating lymphocytes. Levels of immunosuppressive cytokines were also elevated in ascites fluid of patients with tumors that highly expressed HOXA9. HOXA9 may, therefore, stimulate ovarian cancer progression by promoting an immunosuppressive microenvironment via paracrine effects on peritoneal macrophages. PMID:24332016

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

    ClinicalTrials.gov

    2015-05-01

    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

  3. Structural Basis for Ubiquitin Recognition by the Otu1 Ovarian Tumor Domain Protein

    SciTech Connect

    T Messick; N Russel; A Iwata; K Sarachan; R Shiekhattar; I Shanks; F Reyes-Turcu; K Wilkinson; R Marmorstein

    2011-12-31

    Ubiquitination of proteins modifies protein function by either altering their activities, promoting their degradation, or altering their subcellular localization. Deubiquitinating enzymes are proteases that reverse this ubiquitination. Previous studies demonstrate that proteins that contain an ovarian tumor (OTU) domain possess deubiquitinating activity. This domain of {approx}130 amino acids is weakly similar to the papain family of proteases and is highly conserved from yeast to mammals. Here we report structural and functional studies on the OTU domain-containing protein from yeast, Otu1. We show that Otu1 binds polyubiquitin chain analogs more tightly than monoubiquitin and preferentially hydrolyzes longer polyubiquitin chains with Lys{sup 48} linkages, having little or no activity on Lys{sup 63}- and Lys{sup 29}-linked chains. We also show that Otu1 interacts with Cdc48, a regulator of the ER-associated degradation pathway. We also report the x-ray crystal structure of the OTU domain of Otu1 covalently complexed with ubiquitin and carry out structure-guided mutagenesis revealing a novel mode of ubiquitin recognition and a variation on the papain protease catalytic site configuration that appears to be conserved within the OTU family of ubiquitin hydrolases. Together, these studies provide new insights into ubiquitin binding and hydrolysis by yeast Otu1 and other OTU domain-containing proteins.

  4. TLR4 activates NFkB in human ovarian granulosa tumor cells

    PubMed Central

    Woods, Dori C.; White, Yvonne A. R.; Dau, Caroline; Johnson, A.L.

    2011-01-01

    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-κB) 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 IκB degradation and activation of NF-κB. NF-κB activation was confirmed by nuclear localization of NF-κB p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-κB signaling attenuated LPS-induced TNFαplus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-κB 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-κB does not sensitize GCTs to TRAIL or cisplatin. PMID:21616060

  5. 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

  6. Borderline resectable pancreatic cancer.

    PubMed

    Hackert, Thilo; Ulrich, Alexis; Büchler, Markus W

    2016-06-01

    Surgery followed by adjuvant chemotherapy remains the only treatment option for pancreatic ductal adenocarcinoma (PDAC) with the chance of long-term survival. If a radical tumor resection is possible, 5-year survival rates of 20-25% can be achieved. Pancreatic surgery has significantly changed during the past years and resection approaches have been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), which has recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), has become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. Preoperative diagnostic accuracy to define resectability of PDAC is a keypoint in this context as well as the surgical and interdisciplinary expertise to perform advanced pancreatic surgery and manage complications. The present mini-review summarizes the current state of definition, management and outcome of BR-PDAC. Furthermore, the topic of ongoing and future studies on neoadjuvant treatment which is closely related to borderline resectability in PDAC is discussed. PMID:26970276

  7. Upregulation of centrosomal protein 55 is associated with unfavorable prognosis and tumor invasion in epithelial ovarian carcinoma.

    PubMed

    Zhang, Weijing; Niu, Chunhao; He, Weiling; Hou, Teng; Sun, Xiaoying; Xu, Liqun; Zhang, Yanna

    2016-05-01

    Centrosomal protein 55 (CEP55) is a cell cycle regulator implicated in development of certain cancers. However, characteristics of CEP55 expression and its clinical/prognostic significance are unclear in human epithelial ovarian carcinoma (EOC). Therefore, we investigated the expression and clinicopathological significance of CEP55 in patients with EOC and its role in regulating invasion and metastasis of ovarian cell lines. CEP55 mRNA and protein expression levels were detected by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Potential associations of CEP55 expression scores with clinical parameters and patient survival were evaluated. CEP55 function was investigated further using RNA interference, wound healing assay, transwell assay, immunofluorescence analysis, qRT-PCR, and Western blotting. CEP55 was significantly upregulated in ovarian cancer cell lines and lesions compared with normal cells and adjacent noncancerous ovarian tissues. In the 213 EOC samples, CEP55 protein levels were positively correlated with clinical stage (P < 0.001), lymph node metastasis (P < 0.001), intraperitoneal metastasis (P < 0.001), tumor recurrence (P < 0.001), differentiation grade (P < 0.001), residual tumor size (P < 0.001), ascites see tumor cells (P = 0.020), and serum CA153 level (P < 0.001). Moreover, patients with aberrant CEP55 protein expression showed tendencies to receive neoadjuvant chemotherapy (P < 0.001) and cytoreductive surgery (P = 0.020). By contrast, no significant correlation was detected between the protein levels and patient age, histological type, or serum CA125, CA199, CA724, NSE, CEA, and β-HCG levels. Patients with high CEP55 protein expression had shorter overall survival and disease-free survival compared with those with low CEP55 expression. Multivariate analysis implicated CEP55 as an independent prognostic indicator for EOC patients. Additionally, downregulation of

  8. 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

  9. 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. PMID:27033454

  10. Enhanced Stimulation of Anti-Ovarian Cancer CD8+ T Cells by Dendritic Cells Loaded with Nanoparticle Encapsulated Tumor Antigen

    PubMed Central

    Hanlon, Douglas J; Aldo, Paulomi B.; Devine, Lesley; Alvero, Ayesha B.; Engberg, Anna K.; Edelson, Richard; Mor, Gil

    2011-01-01

    Problem Dendritic cell (DC)-based cancer therapies are favored approaches to stimulate anti-tumor T cells responses. Unfortunately, tolerance to tumor antigens is difficult to overcome. Biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) are effective reagents in the delivery of drugs and tumor-associated antigens (TAA). In this study, we assessed the capacity of a PLGA NP-based delivery system to augment CD8 T cell responses to ovarian cancer TAA. Method of Study Human DC were generated from blood monocytes by conventional in vitro differentiation and loaded with either soluble tumor lysate or NP/lysate conjugates (NPL). These antigen-loaded DC were then used to stimulate autologous CD8+ T cells. Cytokine production and activation markers were evaluated in the CD8+T cells. Results DC loading with NPL increased cytokine production by stimulated CD8 T cells and induced T cell expression of cell surface co-stimulatory molecules, typical of anti-tumor immune responses. In contrast, delivery of naked tumor lysate antigens preferentially induced a T cell profile characteristic of tolerization/exhaustion. Conclusion These findings indicate that delivery of TAA in NP enables DC to efficiently activate anti-tumor CD8+ T cells. PLGA NP encapsulation of tumor-derived lysate protein antigens is an encouraging new preparative methodology for DC-based vaccination meriting clinical testing. PMID:21241402

  11. Tumor suppressor effect of follistatin-like 1 in ovarian and endometrial carcinogenesis: a differential expression and functional analysis.

    PubMed

    Chan, Queeny K Y; Ngan, Hextan Y S; Ip, Philip P C; Liu, Vincent W S; Xue, W C; Cheung, Annie N Y

    2009-01-01

    Endometrial and ovarian cancers are the most common and the most lethal gynecologic malignancies worldwide, respectively. By performing differential expression analysis using annealing control primer-based reverse transcription (RT)-polymerase chain reaction (PCR) on pooled complementary DNA (cDNA) from 45 endometrial and 36 ovarian cancers and their non-tumor samples, reduced expression of the follistatin-like 1 (FSTL1) was identified. Downregulation of FSTL1 was further confirmed on individual samples and cell lines by quantitative real-time RT-PCR and western blotting. For in vitro functional study, full-length cDNA of FSTL1 was cloned and transiently transfected into the ovarian cancer cell line Ovca420 and endometrial cancer cell line AN3CA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count demonstrated significantly slower proliferation rate. By terminal uridine deoxynucleotidyl transferase dUTP nick end labeling and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G(1) cell population were observed in transfected cells, suggesting that FSTL1 induced apoptosis in cancer cells. Subsequent messenger RNA and protein expression analysis on downstream apoptotic molecules revealed upregulation and/or activation of FAS, FASLG, TRADD, Caspase-3, Caspase-7 and PARP by FSTL1 transfection, suggesting that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor-ligand binding. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2. Our findings suggested that a tumor suppressor role of FSTL1 may be important in ovarian and endometrial carcinogenesis. PMID:18796737

  12. 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

  13. Diversity of Ubiquitin and ISG15 Specificity among Nairoviruses' Viral Ovarian Tumor Domain Proteases

    PubMed Central

    Capodagli, Glenn C.; Deaton, Michelle K.; Baker, Erica A.; Lumpkin, Ryan J.

    2013-01-01

    Nairoviruses are responsible for numerous diseases that affect both humans and animal. Recent work has implicated the viral ovarian tumor domain (vOTU) as a possible nairovirus virulence factor due to its ability to edit ubiquitin (Ub) bound to cellular proteins and, at least in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), to cleave the Ub-like protein interferon-stimulated gene 15 (ISG15), a protein involved in the regulation of host immunity. The prospective roles of vOTUs in immune evasion have generated several questions concerning whether vOTUs act through a preserved specificity for Ub- and ISG15-conjugated proteins and where that specificity may originate. To gain insight into the substrate specificity of vOTUs, enzymological studies were conducted on vOTUs from Dugbe, CCHFV, and Erve nairoviruses. These studies revealed that vOTUs originating from different nairoviruses display a significant divergence in their preference toward Ub and ISG15. In addition, a recently identified vOTU from turnip yellow mosaic tymovirus was evaluated to elucidate any possible similarities between vOTUs originating from different viral families. Although possessing a similar preference for certain polymeric Ub moieties, its activity toward Ub in general was significantly less then those of nairoviruses. Lastly, the X-ray crystallographic structure of the vOTU from the Dugbe nairovirus was obtained in complex with Ub to reveal structural commonalities of vOTUs originating from nairoviruses. The structure suggests that divergences between nairovirus vOTUs specificity originate at the primary structural level. Comparison of this structure to that originating from CCHFV identified key residues that infer the substrate specificity of vOTUs. PMID:23345508

  14. Immune checkpoint blockade reveals the stimulatory capacity of tumor-associated CD103(+) dendritic cells in late-stage ovarian cancer.

    PubMed

    Flies, Dallas B; Higuchi, Tomoe; Harris, Jaryse C; Jha, Vibha; Gimotty, Phyllis A; Adams, Sarah F

    2016-08-01

    Although immune infiltrates in ovarian cancer are associated with improved survival, the ovarian tumor environment has been characterized as immunosuppressive, due in part to functional shifts among dendritic cells with disease progression. We hypothesized that flux in dendritic cell subpopulations with cancer progression were responsible for observed differences in antitumor immune responses in early and late-stage disease. Here we identify three dendritic cell subsets with disparate functions in the ovarian tumor environment. CD11c+CD11b(-)CD103(+) dendritic cells are absent in the peritoneal cavity of healthy mice but comprise up to 40% of dendritic cells in tumor-bearing mice and retain T cell stimulatory capacity in advanced disease. Among CD11c+CD11b+ cells, Lair-1 expression distinguishes stimulatory and immunoregulatory DC subsets, which are also enriched in the tumor environment. Notably, PD-L1 is expressed by Lair-1(hi) immunoregulatory dendritic cells, and may contribute to local tumor antigen-specific T cell dysfunction. Using an adoptive transfer model, we find that PD-1 blockade enables tumor-associated CD103(+) dendritic cells to promote disease clearance. These data demonstrate that antitumor immune capacity is maintained among local dendritic cell subpopulations in the tumor environment with cancer progression. Similar dendritic cell subsets are present in malignant ascites from women with ovarian cancer, supporting the translational relevance of these results. PMID:27622059

  15. Delivery of Therapeutics Targeting the mRNA-Binding Protein HuR Using 3DNA Nanocarriers Suppresses Ovarian Tumor Growth.

    PubMed

    Huang, Yu-Hung; Peng, Weidan; Furuuchi, Narumi; Gerhart, Jacquelyn; Rhodes, Kelly; Mukherjee, Neelanjan; Jimbo, Masaya; Gonye, Gregory E; Brody, Jonathan R; Getts, Robert C; Sawicki, Janet A

    2016-03-15

    Growing evidence shows that cancer cells use mRNA-binding proteins and miRNAs to posttranscriptionally regulate signaling pathways to adapt to harsh tumor microenvironments. In ovarian cancer, cytoplasmic accumulation of mRNA-binding protein HuR (ELAVL1) is associated with poor prognosis. In this study, we observed high HuR expression in ovarian cancer cells compared with ovarian primary cells, providing a rationale for targeting HuR. RNAi-mediated silencing of HuR in ovarian cancer cells significantly decreased cell proliferation and anchorage-independent growth, and impaired migration and invasion. In addition, HuR-depleted human ovarian xenografts were smaller than control tumors. A biodistribution study showed effective tumor-targeting by a novel Cy3-labeled folic acid (FA)-derivatized DNA dendrimer nanocarrier (3DNA). We combined siRNAs against HuR with FA-3DNA and found that systemic administration of the resultant FA-3DNA-siHuR conjugates to ovarian tumor-bearing mice suppressed tumor growth and ascites development, significantly prolonging lifespan. NanoString gene expression analysis identified multiple HuR-regulated genes that function in many essential cellular and molecular pathways, an attractive feature of candidate therapeutic targets. Taken together, these results are the first to demonstrate the versatility of the 3DNA nanocarrier for in vivo-targeted delivery of a cancer therapeutic and support further preclinical investigation of this system adapted to siHuR-targeted therapy for ovarian cancer. PMID:26921342

  16. Microcystic stromal tumor of the ovary: report of 16 cases of a hitherto uncharacterized distinctive ovarian neoplasm.

    PubMed

    Irving, Julie A; Young, Robert H

    2009-03-01

    We have encountered 16 ovarian neoplasms of probable stromal origin whose most distinctive feature is microcystic change, which is usually conspicuous. On the basis of our extensive experience with ovarian tumors, the neoplasm is unique and warrants separate categorization; we have elected to designate it "microcystic stromal tumor" because of its most striking feature. The patients ranged from 26 to 63 (mean 45) years of age and typically presented with a pelvic mass. Hormonal manifestations were possibly present in only 2. All tumors were unilateral with a mean size of 8.7 (range: 2 to 27) cm and none had evidence of extraovarian spread. The tumors were solid-cystic (11 cases), solid (3 cases), or predominantly cystic (2 cases). The solid component was usually firm and tan or white-tan, but in 1 case was yellowish; soft foci were present in 3 cases and small foci of hemorrhage, necrosis, or both, in 3. On microscopic examination the appearance of the tumors varied according to the relative prominence of their 3 fundamental components: microcysts, solid cellular regions, and fibrous stroma. Microcysts dominated in 9 cases, were roughly equal to noncystic morphology in 5 cases and were minor in 2. The microcystic pattern was characterized by small rounded to oval cystic spaces, in areas coalescing to larger irregular channels; intracytoplasmic vacuoles were also frequently present. The solid cellular areas were usually focally intersected by fibrous bands and hyaline plaques reminiscent of thecoma. The cells contained moderately conspicuous finely granular, lightly eosinophilic cytoplasm, with generally bland, round to oval or spindle-shaped nuclei with fine chromatin and small indistinct nucleoli. Foci of bizarre nuclei were, however, present in 10 cases. Mitotic rate was low in all cases, ranging from 0 to 2 mitoses/10 high-power fields. Immunohistochemical results were as follows: CD10, 16/16 cases positive; vimentin, 16/16 cases positive; inhibin, 1/16 cases

  17. Tumor suppressor role of miR-217 in human epithelial ovarian cancer by targeting IGF1R.

    PubMed

    Li, Jieyan; Li, Dongmei; Zhang, Weiyuan

    2016-03-01

    Accumulating evidence shows that microRNA-217 (miR-217) is frequently dysregulated in various cancers, and plays crucial roles in tumorigenesis and metastasis; however, the role and underlying molecular mechanism of miR-217 in human epithelial ovarian cancer (EOC) remains unclear. Here, we report that miR-217 expression was downregulated in EOC tissue and inversely correlated with advanced FIGO stage, high histological grading and lymph node metastasis (P<0.01). Function analysis revealed that the ectopic expression of miR-217 in EOC cells inhibited cell proliferation, migration and invasion in vitro, as well as suppressed tumor growth in vivo. Bioinformatics analysis and dual luciferase assays identified insulin-like growth factor 1 receptor (IGF1R) as a direct target of miR-217 in EOC cells. Western blot assay showed that overexpression of miR-217 in EOC cells inhibited IGF1R expression. In addition, downregulation of IGF1R mimicked the tumor-suppressive effects of miR-217 in EOC cells, whereas the reintroduction of IGF1R partially abrogated the suppression effect induced by miR-217 on EOC cells. Collectively, these results demonstrated that miR-217 plays a tumor suppressor role in human epithelial ovarian cancer by directly targeting IGF1R gene, suggesting a new potential therapeutic target in EOC. PMID:26708715

  18. 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. PMID:26797858

  19. Solanum Incanum Extract Downregulates Aldehyde Dehydrogenase 1-Mediated Stemness and Inhibits Tumor Formation in Ovarian Cancer Cells

    PubMed Central

    Wu, Yi-Hui; Chiu, Wen-Tai; Young, Ming-Jer; Chang, Tzu-Hao; Huang, Yu-Fang; Chou, Cheng-Yang

    2015-01-01

    Solanum incanum extract (SR-T100), containing the active ingredient solamargine, can induce apoptosis via upregulation of tumor necrosis factor receptor expression and activation of the mitochondrial apoptosis pathway, and has therapeutic effects in patients with actinic keratosis. Here, we evaluate the novel molecular mechanisms underlying SR-T100-regulated stemness and chemoresistance. The concentration of SR-T100 that inhibited 50% cell viability (IC50) was lower in ovarian cancer cells than in nonmalignant cells. Furthermore, the SR-T100 IC50 in chemoresistant cells was similar to the IC50 in chemosensitive cells. Additionally, SR-T100 increased cisplatin and paclitaxel sensitivity in chemoresistant cells. SR-T100 downregulated the expression of stem cell markers, including aldehyde dehydrogenase 1 (ALDH1), Notch1, and FoxM1, and reduced sphere formation in ovarian cancer cells. Using microarray analyses, immunoblotting, luciferase activity, and chromatin immunoprecipitation (ChIP) assays, we showed that SR-T100 suppressed the expression of c/EBPβ and COL11A1, and its promoter activity, in resistant cells, but not sensitive cells. SR-T100, paclitaxel, and cisplatin inhibited the growth of A2780CP70 cells in mouse xenografts, as compared to the vehicle control, and the combination of cisplatin and SR-T100 was more effective than either treatment alone. SR-T100 may represent a potential therapeutic adjunct to chemotherapy for ovarian cancer treatment. PMID:26366215

  20. What Are the Key Statistics about Ovarian Cancer?

    MedlinePlus

    ... factors for 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.) ...

  1. GSTP1-1 in ovarian cyst fluid and disease outcome of patients with ovarian cancer.

    PubMed

    Kolwijck, Eva; Zusterzeel, Petra L M; Roelofs, Hennie M J; Hendriks, Jan C; Peters, Wilbert H M; Massuger, Leon F A G

    2009-08-01

    Detoxification enzymes, especially glutathione S-transferase P1-1 (GSTP1-1), have been implicated in resistance to platinum-based chemotherapy. We studied GSTP1-1 levels in ovarian cyst fluid (oCF), obtained during surgery before chemotherapy, of patients with epithelial ovarian cancer and clinical outcomes were correlated. GSTP1-1 was determined by ELISA in oCF of 56 patients with epithelial ovarian cancer and 109 noncancer controls (21 borderline and 88 benign ovarian tumors). Differences in median GSTP1-1 between clinicopathologic subgroups were studied using Mann-Whitney U and Kruskal Wallis tests. Differences in disease-free (DFS) and overall survival (OS) between groups were analyzed by applying Kaplan-Meyer estimates and log-rank tests. Univariate and multivariate analysis were done using Cox proportional hazard model. Significantly higher levels of GSTP1-1 were found in the oCF of malignant (median, 383; range, 10-32,695 ng/mL) compared with benign (median, 20; range, 0-1,128 ng/mL) ovarian tumors (P < 0.01). Significantly higher GSTP1-1 levels were found in patients with advanced International Federation of Gynaecologists and Obstetricians stage (P = 0.01), high-grade tumors (P = 0.44), and/or high levels of preoperative CA 125 (P = 0.01). Of patients who received chemotherapy (stage, >or=Ic; n = 30), high GSTP1-1 levels were significantly associated with a poor DFS and OS (log-rank P = 0.047 and P = 0.033, respectively). International Federation of Gynaecologists and Obstetricians stage was the only independent predictor for DFS. GSTP1-1 was the only independent predictor for OS. PMID:19661073

  2. Temsirolimus, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-06-18

    Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  3. 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.

  4. Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

    PubMed Central

    2014-01-01

    Background Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. Methods The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Results Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated

  5. 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

  6. The added value of circulating tumor cells examination in ovarian cancer staging.

    PubMed

    Kolostova, Katarina; Matkowski, Rafał; Jędryka, Marcin; Soter, Katarzyna; Cegan, Martin; Pinkas, Michael; Jakabova, Anna; Pavlasek, Jiri; Spicka, Jan; Bobek, Vladimir

    2015-01-01

    Delayed diagnosis of ovarian cancer (OC) is usually a cause of its high mortality. OC counts for one of the most aggressive gynecological malignancies. Noninvasive biomarkers may be used to help with diagnostic and treatment decisions in OC management. The incidence and clinical significance of occult OC cells (circulating tumor cells-CTCs) in the peripheral blood of patients with newly diagnosed or nondiagnosed OC at the time of surgical intervention were examined in our study. The objective of the study was to isolate and cultivate CTCs in OC patients (mainly stage IIIB-C) by a recently introduced size-based separation method (MetaCell(®)). CTCs were successfully isolated in patients with OC capturing cells with proliferation potential. The cells were enriched in good fitness, which enabled the short term in vitro culture of the CTCs. The CTCs may be used for further downstream applications (e.g. gene expression analysis) even if in the majority of the in vitro CTC cultures no confluence was reached. The CTCs were detected in 77 out of 118 patients (65.2%). CTC positivity was given to the relationship with different disease stage parameters with special focus on CA125 marker levels. The results show that the information on CTC presence may provide new and independent prognosis staging information to the patient description. Several interesting relationships of CA125, age and ascites presence are reported. As shown in our patient sample, patients with ascites tend to have higher CA125 levels, even if the CTCs were not found in the peripheral blood. It suggests that hematogenous dissemination is fully represented by the CTCs while lymphogenic dissemination is represented by elevated CA125. In this context, easy access to CTCs provided by the method applied in our study, both at the time of diagnosis and relapse, may become an increasingly valuable tool in future. This methodology may provide an opportunity for more personalized medicine where treatment for OC may

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

    PubMed Central

    KREIMANN, ERICA LORENA; RATAJSKA, MAGDALENA; KUZNIACKA, ALINA; DEMACOPULO, BRENDA; STUKAN, MACIEJ; LIMON, JANUSZ

    2015-01-01

    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. PMID:26788197

  8. 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.

  9. Borderline personality disorder

    MedlinePlus

    ... Names Personality disorder - borderline References American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. ...

  10. 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.

  11. 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

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

    PubMed

    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

  13. Colonic adenocarcinoma and bilateral malignant ovarian sex cord tumor with annular tubules in Peutz-Jeghers syndrome.

    PubMed

    Ayadi-Kaddour, A; Bouraoui, S; Bellil, K; Bellil, S; Kchir, N; Zitouna, M M; Haouet, S

    2004-06-01

    Peutz-Jeghers syndrome is characterized by multiple polyps throughout the gastrointestinal tract in association with mucocutaneous pigmentation. Although Peutz-Jeghers syndrome polyps are hamartomas, frequent association of this syndrome with both gastrointestinal and non-gastrointestinal tumours had led to reassessment of the cancer risk in this hereditary disorder. The most common gynaecological tumors in this syndrome are adenoma malignum of the uterine cervix and ovarian sex cord tumor, particularly sex cord tumor with annular tubules. The question of malignant change in a polyp or of the association of gastro intestinal carcinomas still discuss. The authors report a case of Peutz-Jeghers syndrome in a young patient who developed a colonic adenocarcinoma in a hamartomatous polyp together with an incidentally discovered bilateral malignant sex cord tumours. We discuss its association with certain benign and malignant tumors and the risk of rare complications of these hamartomatous polyps. Although malignant tumors are increasingly reported in association with the Peutz-Jeghers syndrome, to our knowledge, there have been no previous reports of such an association in the literature. PMID:15524052

  14. The co-occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome.

    PubMed

    Durieux, Emeline; Descotes, Françoise; Mauduit, Claire; Decaussin, Myriam; Guyetant, Serge; Devouassoux-Shisheboran, Mojgan

    2016-05-01

    The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Pleuropulmonary blastoma is the most frequent lesion seen in this syndrome. Thyroid abnormalities are also a common finding, essentially concerning multinodular goiter. However, differentiated thyroid carcinoma is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 RNase IIIb catalytic domain in several tumor types, including ovarian Sertoli-Leydig cell tumors. We report two cases of differentiated thyroid carcinoma associated with ovarian Sertoli-Leydig cell tumor and with a heterozygous DICER1 gene mutation, occurring in two unrelated young girls without pleuropulmonary blastoma. Both thyroid carcinomas showed an E1813 mutation in exon 25 while the ovarian tumors harboured a somatic mutation in E1705 in exon 24 and a D1709 mutation in exon 25. Our observations confirm that the occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome. We contend that the possibility of a relationship between sporadic thyroid carcinoma in young patients and somatic DICER1 gene mutation needs further investigation. PMID:26983701

  15. Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer.

    PubMed

    Peng, Jin; Hamanishi, Junzo; Matsumura, Noriomi; Abiko, Kaoru; Murat, Kumuruz; Baba, Tsukasa; Yamaguchi, Ken; Horikawa, Naoki; Hosoe, Yuko; Murphy, Susan K; Konishi, Ikuo; Mandai, Masaki

    2015-12-01

    Emerging evidence has highlighted the host immune system in modulating the patient response to chemotherapy, but the mechanism of this modulation remains unclear. The aim of this study was to analyze the effect of chemotherapy on antitumor immunity in the tumor microenvironment of ovarian cancer. Treatment of ovarian cancer cell lines with various chemotherapeutic agents resulted in upregulated expression of MHC class I and programmed cell death 1 ligand 1 (PD-L1) in a NF-κB-dependent manner and suppression of antigen-specific T-cell function in vitro. In a mouse model of ovarian cancer, treatment with paclitaxel increased CD8(+) T-cell infiltration into the tumor site, upregulated PD-L1 expression, and activated NF-κB signaling. In particular, tumor-bearing mice treated with a combination of paclitaxel and a PD-L1/PD-1 signal blockade survived longer than mice treated with paclitaxel alone. In summary, we found that chemotherapy induces local immune suppression in ovarian cancer through NF-κB-mediated PD-L1 upregulation. Thus, a combination of chemotherapy and immunotherapy targeting the PD-L1/PD-1 signaling axis may improve the antitumor response and offers a promising new treatment modality against ovarian cancer. PMID:26573793

  16. Overexpression of Rab27B is correlated with distant metastasis and poor prognosis in ovarian cancer

    PubMed Central

    Ren, Ping; Yang, Xiao-Qing; Zhai, Xiao-Lu; Zhang, Yu-Quan; Huang, Jian-Fei

    2016-01-01

    The secretory small guanosine-5′-triphosphate-binding enzyme, Rab27B, has been identified to be an oncogene that is involved in the progression of certain tumors. The current study was designed to evaluate the expression pattern of Rab27B in ovarian cancer (OC), borderline tumors and benign ovarian adenoid tumors, as well as its association with survival prognosis and clinical parameters. The expression of Rab27B protein was examined by immunohistochemistry in 204 patients who had undergone ovarian resection without preoperative systemic chemotherapy at the Surgical Department of the Affiliated Hospital of Nantong University (Nantong, China), including 57 benign ovarian adenoid tumors, 44 borderline tumors and 103 malignant tumors. Rab27B expression and clinicopathological features were analyzed with the χ2 test. Patient survival rate was analyzed with the Kaplan-Meier method. Univariate and multivariate analysis of the prognostic factors was performed using the Cox regression model. Increased expression of Rab27B was positively correlated with histological type (P=0.012), level of differentiation (P=0.015), lymph node metastasis (P=0.024), distant metastasis (P<0.001) and International Federation of Gynecology and Obstetrics stage (P=0.001). Survival analysis revealed an association between Rab27B-positivity and poor overall survival rate. Multivariate analysis indicated that Rab27B (P<0.031) and distant metastases (P=0.031) were independent prognostic factors for OC patients' survival. The results of the present study supported the hypothesis that Rab27B may be a valuable prognostic indicator in patients with OC. PMID:27446467

  17. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas.

    PubMed

    Karanian-Philippe, Marie; Velasco, Valérie; Longy, Michel; Floquet, Anne; Arnould, Laurent; Coindre, Jean-Michel; Le Naoures-Méar, Cécile; Averous, Gerlinde; Guyon, Frédéric; MacGrogan, Gaëtan; Croce, Sabrina

    2015-09-01

    Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are characterized by inactivation of the SMARCA4 gene (encoding the BRG1 protein) resulting in a loss of BRG1 protein expression in IHC. We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas. Forty-four adult granulosa cell tumors were interpretable by IHC. All 12 SCCOHTs were devoid of BRG1 expression and expressed INI1. All other interpretable 119 tumors showed BRG1 nuclear positivity, with variable staining proportions, ranging from 10% to 100% of positive cells (mean: 77%, median: 80%), variable intensities (weak: 5%, moderate: 37%, strong: 58%), and distributions: diffuse in 82 cases (70%) and heterogenous in 36 cases (30%). BRG1 positivity was heterogenous in desmoplastic round cell tumors and adult granulosa cell tumors. Overall, BRG1 is a useful diagnostic marker in SCCOHT, showing the absence of expression in SCCOHT. Nevertheless, the possible heterogeneity and the variable intensity of this staining warrant caution in the interpretation of BRG1 staining in biopsy specimens. PMID:26135561

  18. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors

    PubMed Central

    Gubbels, Jennifer AA; Belisle, Jennifer; Onda, Masanori; Rancourt, Claudine; Migneault, Martine; Ho, Mitchell; Bera, Tapan K; Connor, Joseph; Sathyanarayana, Bangalore K; Lee, Byungkook; Pastan, Ira; Patankar, Manish S

    2006-01-01

    Background The mucin MUC16 and the glycosylphosphatidylinositol anchored glycoprotein mesothelin likely facilitate the peritoneal metastasis of ovarian tumors. The biochemical basis and the kinetics of the binding between these two glycoproteins are not clearly understood. Here we have addressed this deficit and provide further evidence supporting the role of the MUC16-mesothelin interaction in facilitating cell-cell binding under conditions that mimic the peritoneal environment. Results In this study we utilize recombinant-Fc tagged human mesothelin to measure the binding kinetics of this glycoprotein to MUC16 expressed on the ovarian tumor cell line OVCAR-3. OVCAR-3 derived sublines that did not express MUC16 showed no affinity for mesothelin. In a flow cytometry-based assay mesothelin binds with very high affinity to the MUC16 on the OVCAR-3 cells with an apparent Kd of 5–10 nM. Maximum interaction occurs within 5 mins of incubation of the recombinant mesothelin with the OVCAR-3 cells and significant binding is observed even after 10 sec. A five-fold molar excess of soluble MUC16 was unable to completely inhibit the binding of mesothelin to the OVCAR-3 cells. Oxidation of the MUC16 glycans, removal of its N-linked oligosaccharides, and treatment of the mucin with wheat germ agglutinin and erythroagglutinating phytohemagglutinin abrogates its binding to mesothelin. These observations suggest that at least a subset of the MUC16-asscociated N-glycans is required for binding to mesothelin. We also demonstrate that MUC16 positive ovarian tumor cells exhibit increased adherence to A431 cells transfected with mesothelin (A431-Meso+). Only minimal adhesion is observed between MUC16 knockdown cells and A431-Meso+ cells. The binding between the MUC16 expressing ovarian tumor cells and the A431-Meso+ cells occurs even in the presence of ascites from patients with ovarian cancer. Conclusion The strong binding kinetics of the mesothelin-MUC16 interaction and the cell

  19. A Giant Hydronephrosis Mistakenly Diagnosed as Ovarian Tumor in a Pregnant Woman

    PubMed Central

    Nerli, Rajendra B.; Mungarwadi, Amit; Mudegowdar, Abhijith S.; Patil, Amey; Hiremath, Murigendra B.; Ghagane, Shridhar

    2015-01-01

    We report a case of giant hydronephrosis that was wrongly diagnosed as an ovarian cyst and explored in a pregnant woman. Giant hydronephrosis are uncommon and need to be kept in mind as a differential diagnosis while making a clinical diagnosis. PMID:26793569

  20. 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…

  1. Ovarian endometrioid adenocarcinoma: incidence and clinical significance of the morphologic and immunohistochemical markers of mismatch repair protein defects and tumor microsatellite instability.

    PubMed

    Aysal, Anil; Karnezis, Anthony; Medhi, Irum; Grenert, James P; Zaloudek, Charles J; Rabban, Joseph T

    2012-02-01

    A subset of women with uterine cancer exhibiting defective mismatch repair (MMR) proteins and microsatellite instability (MSI) may have Lynch syndrome, which also confers a risk for colorectal cancer and other cancers in the patient and in her family. Screening algorithms based on clinical and pathologic criteria are effective in determining which patients with uterine cancer are most likely to benefit from definitive genetic testing for Lynch syndrome. Ovarian cancer, particularly endometrioid adenocarcinoma, is also associated with Lynch syndrome, although the risk is much smaller than for uterine cancer. This study evaluated whether the morphologic criteria [tumor-infiltrating lymphocytes (TILs), peritumoral lymphocytes (PTLs), dedifferentiated morphology)] currently used to screen uterine cancer for further Lynch syndrome testing can be applied to ovarian cancer. Among 71 patients with pure ovarian endometrioid adenocarcinoma treated at a single institution, 13% had a tumor with TILs, 3% had PTLs, and none had dedifferentiated morphology. Overall, 10% of tumors had abnormal MMR protein status, defined as complete immunohistochemical loss of expression of MLH1, MSH2, MSH6, and/or PMS2. Each of these tumors with abnormal MMR status demonstrated MSI using a polymerase chain reaction-based assay evaluating 5 mononucleotide repeat markers. No relationship was found between patient age, TILs, PTLs, or a spectrum of other morphologic variables and MMR protein status/MSI. Only 1/7 tumors with abnormal MMR/MSI had TILs/PTLs. Among 14 patients who died, 12 (86%) had normal MMR status. Among 7 patients with tumors with abnormal MMR/MSI, 5 (71%) were alive without disease. Concurrent uterine tumor was present in 5/7 patients whose ovarian tumor had abnormal MMR/MSI. This study suggests that the morphologic criteria used to screen patients with uterine cancer for further Lynch syndrome testing are not applicable in patients with ovarian cancer. Although abnormal MMR/MSI did

  2. A New Method for Isolation of Interstitial Fluid from Human Solid Tumors Applied to Proteomic Analysis of Ovarian Carcinoma Tissue

    PubMed Central

    Haslene-Hox, Hanne; Oveland, Eystein; Berg, Kaja C.; Kolmannskog, Odd; Woie, Kathrine; Salvesen, Helga B.

    2011-01-01

    Major efforts have been invested in the identification of cancer biomarkers in plasma, but the extraordinary dynamic range in protein composition, and the dilution of disease specific proteins make discovery in plasma challenging. Focus is shifting towards using proximal fluids for biomarker discovery, but methods to verify the isolated sample's origin are missing. We therefore aimed to develop a technique to search for potential candidate proteins in the proximal proteome, i.e. in the tumor interstitial fluid, since the biomarkers are likely to be excreted or derive from the tumor microenvironment. Since tumor interstitial fluid is not readily accessible, we applied a centrifugation method developed in experimental animals and asked whether interstitial fluid from human tissue could be isolated, using ovarian carcinoma as a model. Exposure of extirpated tissue to 106 g enabled tumor fluid isolation. The fluid was verified as interstitial by an isolated fluid:plasma ratio not significantly different from 1.0 for both creatinine and Na+, two substances predominantly present in interstitial fluid. The isolated fluid had a colloid osmotic pressure 79% of that in plasma, suggesting that there was some sieving of proteins at the capillary wall. Using a proteomic approach we detected 769 proteins in the isolated interstitial fluid, sixfold higher than in patient plasma. We conclude that the isolated fluid represents undiluted interstitial fluid and thus a subproteome with high concentration of locally secreted proteins that may be detected in plasma for diagnostic, therapeutic and prognostic monitoring by targeted methods. PMID:21541282

  3. 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. PMID:25356755

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

    PubMed Central

    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.

    2014-01-01

    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. PMID:25356755

  5. Borderline Personality and Criminality

    PubMed Central

    Sansone, Lori A.

    2009-01-01

    Borderline personality disorder is characteristically associated with a broad variety of psychiatric symptoms and aberrant behaviors. In this edition of The Interface, we discuss the infrequently examined association between borderline personality disorder and criminality. According to our review of the literature, in comparison with the rates of borderline personality disorder encountered in the general population, borderline personality disorder is over-represented in most studies of inmates. At the same time, there is considerable variation in the reported rates of this Axis II disorder in prison populations, which may be attributed to the methodologies of and populations in the various studies. Overall, female criminals appear to exhibit higher rates of borderline personality disorder, and it is oftentimes associated with a history of childhood sexual abuse, perpetration of impulsive and violent crimes, comorbid antisocial traits, and incarceration for domestic violence. PMID:20011575

  6. Selective inhibition of tumor cell associated Vacuolar-ATPase 'a2' isoform overcomes cisplatin resistance in ovarian cancer cells.

    PubMed

    Kulshrestha, Arpita; Katara, Gajendra K; Ginter, Jordyn; Pamarthy, Sahithi; Ibrahim, Safaa A; Jaiswal, Mukesh K; Sandulescu, Corina; Periakaruppan, Ramayee; Dolan, James; Gilman-Sachs, Alice; Beaman, Kenneth D

    2016-06-01

    Development of resistance to platinum compounds significantly hinders successful ovarian cancer (OVCA) treatment. In tumor cells, dysregulated pH gradient across cell membranes is a key physiological mechanism of metastasis/chemo-resistance. These pH alterations are mediated by aberrant activation of key multi-subunit proton pumps, Vacuolar-ATPases (V-ATPases). In tumor cells, its 'a2' isoform (V-ATPase-V0a2) is a component of functional plasma-membrane complex and promotes tumor invasion through tumor-acidification and immuno-modulation. Its involvement in chemo-resistance has not been studied. Here, we show that V-ATPase-V0a2 is over-expressed in acquired-cisplatin resistant OVCA cells (cis-A2780/cis-TOV112D). Of all the 'a' subunit isoforms, V-ATPase-V0a2 exhibited an elevated expression on plasma membrane of cisplatin-resistant cells compared to sensitive counterparts. Immuno-histochemistry revealed V-ATPase-V0a2 expression in both low grade (highly drug-resistant) and high grade (highly recurrent) human OVCA tissues indicating its role in a centralized mechanism of tumor resistance. In cisplatin resistant cells, shRNA mediated inhibition of V-ATPase-V0a2 enhanced sensitivity towards both cisplatin and carboplatin. This improved cytotoxicity was mediated by enhanced cisplatin-DNA-adduct formation and suppressed DNA-repair pathway, leading to enhanced apoptosis. Suppression of V0a2 activity strongly reduced cytosolic pH in resistant tumor cells, which is known to enhance platinum-associated DNA-damage. As an indicator of reduced metastasis and chemo-resistance, in contrast to plasma membrane localization, a diffused cytoplasmic localization of acidic vacuoles was observed in V0a2-knockdown resistant cells. Interestingly, pre-treatment with monoclonal V0a2-inhibitory antibody enhanced cisplatin cytotoxicity in resistant cells. Taken together, our findings suggest that the isoform specific inhibition of V-ATPase-V0a2 could serve as a therapeutic strategy for chemo

  7. A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCA1

    PubMed Central

    Godwin, Andrew K.; Vanderveer, Lisa; Schultz, David C.; Lynch, Henry T.; Altomare, Deborah A.; Buetow, Kenneth H.; Daly, Mary; Getts, Lori A.; Masny, Agnes; Rosenblum, Norman; Hogan, Michael; Ozols, Robert F.; Hamilton, Thomas C.

    1994-01-01

    Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17pl3.1 and 17pl3.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17ql2-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans −25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene. ImagesFigure 1Figure 3 PMID:7942844

  8. Synthesis of a monofunctional platinum compound and its activity alone and in combination with phytochemicals in ovarian tumor models.

    PubMed

    Arzuman, Laila; Beale, Philip; Yu, Jun Qing; Proschogo, Nick; Huq, Fazlul

    2014-12-01

    Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. In this study, a new monofunctional planaramineplatinum(II) complex, namely tris(8-hydroxyquinoline)monochloroplatinum(II) chloride (coded as LH3), was synthesised and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistant A2780 (A2780(ZD0473R)) cancer cell lines, alone and in combination with the phytochemicals curcumin, genistein and resveratrol. Cellular levels of glutathione in A2780 and A2780(cisR) cell lines before and after treatment with LH3 and its combinations with genistein and curcumin were also determined. Interaction of the compounds with salmon sperm DNA, pBR322 plasmid DNA and damage to DNA in A2780 and A2780(cisR) cells due to interaction with LH3-alone and in combination with phytochemicals were also investigated. LH3 was found to be much more active than cisplatin against the resistant tumor models and greatest synergism in activity was observed when combinations of LH3 with genistein and curcumin were administered as a bolus. For combinations of LH3 with the phytochemicals, platinum accumulation and the level of Pt-DNA binding were found to be greater in the resistant A2780(cisR) cell line than in the parental A2780 cell line. Greater activity of LH3 than cisplatin against the resistant ovarian cell lines indicates that it may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy. PMID:25503135

  9. 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

  10. Body size and risk of epithelial ovarian and related cancers: a population-based case-control study.

    PubMed

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C; Purdie, David M; Green, Adèle C; Webb, Penelope M

    2008-07-15

    Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer. PMID:18449887

  11. Broad Ligament Fibroid Mimicking as Ovarian Tumor on Ultrasonography and Computed Tomography Scan

    PubMed Central

    Rajanna, Dayananda Kumar; Pandey, Vaibhav; Janardhan, Sujit; Datti, Sujatha N

    2013-01-01

    Giant fibroids are known to arise from the uterus, and very rarely from the broad ligament. Large fibroids often undergo hyaline, cystic, and at times, red degeneration. In the present case, cystic degeneration with intervening septations in an adnexal mass raised the suspicion of ovarian neoplasm as the ovaries were not seen as separate from the lesion. The ultrasonographic and contrast-enhanced computed tomographic findings of this case were characteristic of ovarian neoplasm. The differential diagnosis included rare possibility of giant fibroid with cystic degeneration. The diagnosis was confirmed on histopathological examination. The patient underwent excision of the broad ligament fibroid, hysterectomy, and bilateral salpingo-oophorectomy. Magnetic resonance imaging has a role in the diagnosis of such lesions. PMID:23607077

  12. Small Cell Ovarian Carcinomas – Characterisation of Two Rare Tumor Entities

    PubMed Central

    Münstedt, K.; Estel, R.; Dreyer, T.; Kurata, A.; Benz, A.

    2013-01-01

    Objective: Small cell ovarian carcinomas (SCOC) are differentiated into two types: hypercalcaemic (SCOCHT) and pulmonary (SCOCPT). Unfortunately, little is known about pulmonary-type small cell ovarian carcinoma. Study Design: We carried out a systematic analysis of all available reports in the literature on individual cases of SCOCHT and SCOCPT. Results: We found that patients with SCOCPT were significantly older than those with SCOCHT. Vimentin and chromogranin detection by immunohistochemistry allow good differentiation between the two types. Interestingly, SCOCPT but not SCOCHT was found to be associated with other benign and malignant ovarian tumours in about 44 % of cases. Although the percentage of R0/R1 resections was high (~ 74 %), survival was poor; even in patients with disease limited to the ovaries (stage Ia and Ib) the recurrence rate was 40 %. Chemotherapy with etoposide or anthracyclines could be useful. Conclusion: Taking the limitations of our study such as its retrospective nature into account and based on the results from studies of small cell carcinomas originating from other tumour sites, we conclude that treatment of SCOCPT should be based on the therapies used to treat other small cell carcinomas. Surgery is appropriate, especially in very early stages of disease, but chemotherapy should not be omitted. Newer concepts such as treatment with somatostatin analogues could help to control symptoms and stabilise some slow-growing tumours. PMID:24771926

  13. Cystic tumor of the liver without ovarian-like stroma or bile duct communication: two case reports and a review of the literature.

    PubMed

    Kishida, Norihiro; Shinoda, Masahiro; Masugi, Yohei; Itano, Osamu; Fujii-Nishimura, Yoko; Ueno, Akihisa; Kitago, Minoru; Hibi, Taizo; Abe, Yuta; Yagi, Hiroshi; Tanimoto, Akihiro; Tanabe, Minoru; Sakamaoto, Michiie; Kitagawa, Yuko

    2014-01-01

    We report two cases of cystic neoplasm of the liver with mucinous epithelium in which both ovarian-like stroma and bile duct communication were absent. The first case was a 41-year-old woman. She underwent right trisegmentectomy due to a multilocular cystic lesion, 15 cm in diameter, with papillary nodular components in the medial segment and right lobe. Histologically, arborizing papillae were seen in the papillary lesion. The constituent neoplastic cells had sufficient cytoarchitectural atypia to be classified as high-grade dysplasia. The second case was a 60-year-old woman. She underwent left lobectomy due to a unilocular cystic lesion, 17 cm in diameter, in the left lobe. Histologically, the cyst wall was lined by low columnar epithelia with slight cellular atypia. In both cases, neither ovarian-like stroma nor bile duct communications were found throughout the resected specimen. According to the most recent World Health Organization (WHO) classification in 2010, cystic tumors of the liver with mucinous epithelium are classified as mucinous cystic neoplasms when ovarian-like stromata are found, and as intraductal papillary neoplasm of bile duct when bile duct communication exists. Therefore, we diagnosed the cystic tumors as 'biliary cystadenoma' according to the past WHO classification scheme from 2000. We believe that the combined absence of both ovarian-like stroma and bile duct communication is possible in mucinous cystic tumors of the liver. Herein, we have described the clinicopathologic features of the two cases and reviewed past cases in the literature. PMID:25047921

  14. Lonidamine Induces Intracellular Tumor Acidification and ATP Depletion in Breast, Prostate and Ovarian Cancer Xenografts and Potentiates Response to Doxorubicin

    PubMed Central

    Nath, Kavindra; Nelson, David S.; Heitjan, Daniel F.; Leeper, Dennis B.; Zhou, Rong; Glickson, Jerry D.

    2015-01-01

    We demonstrate that the effects of lonidamine (LND, 100 mg/kg, i.p.) are similar for a number of xenograft models of human cancer including DB-1 melanoma and HCC1806 breast, BT-474 breast, LNCaP prostate and A2870 ovarian carcinomas. Following treatment with LND, each of these tumors exhibits a rapid decrease in intracellular pH, a small decrease in extracellular pH, a concomitant monotonic decrease in nucleoside triphosphate and increase in inorganic phosphate over a 2–3 hr period. We previously demonstrated that selective intracellular tumor acidification potentiates response of this melanoma model to melphalan (7.5 mg/kg, i.v.), producing an estimated 89% cell kill based on tumor growth delay analysis. We now show that in both DB-1 melanoma and HCC1806 breast carcinoma, LND potentiates response to doxorubicin producing 95% cell kill in DB-1 melanoma at 7.5 mg/kg, i.v. doxorubicin and 98% cell kill at 10.0 mg/kg doxorubicin, and in HCC1806 breast carcinoma producing a 95% cell kill at 12.0 mg/kg doxorubicin. Potentiation of doxorubicin can result from cation trapping of the weakly basic anthracycline. Recent experience with the clinical treatment of melanoma and other forms of human cancer suggests that these diseases will probably not be cured by a single therapeutic procedure other than surgery. A multimodality therapeutic approach will be required. As a potent modulator of tumor response to N-mustards and anthracyclines as well as tumor thermo- and radiosensitivity, LND promises to play an important clinical role in the management and possible complete local control of a number of prevalent forms of human cancer. PMID:25504852

  15. Ovarian Cysts

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ075 GYNECOLOGIC PROBLEMS Ovarian Cysts • What is an ovarian cyst? • What are the symptoms of ovarian cysts? • How are ovarian cysts diagnosed? • How are ovarian ...

  16. 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

  17. Parametric mapping of contrasted ovarian transvaginal sonography.

    PubMed

    Korhonen, Katrina; Moore, Ryan; Lyshchik, Andrej; Fleischer, Arthur C

    2015-06-01

    The purpose of this study was to assess the accuracy of parametric analysis of transvaginal contrast-enhanced ultrasound (TV-CEUS) for distinguishing benign versus malignant ovarian masses. A total of 48 ovarian masses (37 benign and 11 borderline/malignant) were examined with TV-CEUS (Definity; Lantheus, North Billerica, MA; Philips iU22; Philips Medical Systems, Bothell, WA). Parametric images were created offline with a quantification software (Bracco Suisse SA, Geneva, Switzerland) with map color scales adjusted such that abnormal hemodynamics were represented by the color red and the presence of any red color could be used to differentiate benign and malignant tumors. Using these map color scales, low values of the perfusion parameter were coded in blue, and intermediate values of the perfusion parameter were coded in yellow. Additionally, for each individual color (red, blue, or yellow), a darker shade of that color indicated a higher intensity value. Our study found that the parametric mapping method was considerably more sensitive than standard region of interest (ROI) analysis for the detection of malignant tumors but was also less specific than standard ROI analysis. Parametric mapping allows for stricter cutoff criteria, as hemodynamics are visualized on a finer scale than ROI analyses, and as such, parametric maps are a useful addition to TV-CEUS analysis by allowing ROIs to be limited to areas of the highest malignant potential. PMID:26002525

  18. Polyinosinic-Polycytidylic Acid Perturbs Ovarian Functions Through Toll-Like Receptor 3-Mediated Tumor Necrosis Factor A Production in Female Mice.

    PubMed

    Yan, Keqin; Cheng, Lijing; Liu, Peng; Liu, Zhenghui; Zhao, Shutao; Zhu, Weiwei; Wang, Qing; Wu, Han; Han, Daishu

    2015-07-01

    Viral infections may perturb ovarian functions and female fertility. Mechanisms underlying viral perturbation of ovarian functions are incompletely understood. This study found that intraperitoneal injection of polyinosinic-polycytidylic acid [poly (I:C)] in female mice inhibits estradiol synthesis and induces ovarian granulosa cell apoptosis. Poly (I:C) is a synthetic viral double-stranded RNA analog, which induces innate antiviral responses mimicking a viral infection through activation of pattern recognition receptors, including toll-like receptor 3 (TLR3), retinoic acid-inducible gene I, and melanoma differentiation-associated gene 5. Injection of poly (I:C) significantly induced granulosa cell apoptosis in antral follicles and reduced antral follicle numbers. These effects were significantly diminished in Tlr3 knockout or tumor necrosis factor-alpha (Tnfa) knockout mice. We demonstrated that poly (I:C) induced TNFA production at a relatively high level in wild-type mice compared with that in Tlr3 knockout mice. Notably, TNFA neutralizing antibody significantly reduced poly (I:C)-induced ovarian dysfunction. In vitro assays confirmed that TNFA inhibits estradiol synthesis and induces granulosa cell apoptosis. Results provide novel insights into the mechanisms by which a mimicked viral infection perturbs ovarian functions in mice. PMID:26040668

  19. Gene expression profiling of single circulating tumor cells in ovarian cancer - Establishment of a multi-marker gene panel.

    PubMed

    Blassl, Christina; Kuhlmann, Jan Dominik; Webers, Alessandra; Wimberger, Pauline; Fehm, Tanja; Neubauer, Hans

    2016-08-01

    The presence of circulating tumor cells (CTCs) in the blood of ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs with epithelial-mesenchymal-transition (EMT) or stem-like traits are supposed to be involved in metastatic progression and recurrence. Thus, investigating the transcriptional profiles of CTCs might help to identify therapy resistant tumor cells and to overcome treatment failure. For this purpose, we established a multi-marker panel for the molecular characterization of single CTCs, detecting epithelial (EpCAM, Muc-1, CK5/7), EMT (N-cadherin, Vimentin, Snai1/2, CD117, CD146, CD49f) and stem cell (CD44, ALDH1A1, Nanog, SOX2, Notch1/4, Oct4, Lin28) associated transcripts. First primer specificity and PCR-performance of the multiplex-RT-PCRs were successfully validated on genomic DNA and cDNA isolated from OvCar3 cells. The assay sensitivity of the epithelial panel was evaluated by adding defined numbers of tumor cells into the blood of healthy donors and performing a subsequent immunomagnetic tumor cell enrichment (AdnaTest OvarianCancerSelect), resulting in a 100% concordance for the epithelial markers EpCAM and Muc-1 to the AdnaTest OvarianCancerDetect. Additionally, by processing blood from ovarian cancer patients, high assay sensitivity could be verified. In blood of healthy donors no signals for epithelial markers were detected, for EMT and stem cell markers, however, signals were obtained mainly originating from leukocytes which calls for single cell analysis. To that aim by using the ovarian cancer cell line OvCar3, we successfully established a workflow enabling the characterization of single CTCs. It consists of a density gradient-dependent enrichment for nucleated cells, a depletion of CD45-positive cells of hematopoietic origin followed by immunofluorescent labeling of CTCs by EpCAM and Muc-1. Single CTCs are then isolated by micromanipulation and processed for panel gene expression profiling. Finally

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

    PubMed Central

    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

  1. Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Ose, Jennifer; Fortner, Renée T; Rinaldi, Sabina; Schock, Helena; Overvad, Kim; Tjonneland, Anne; Hansen, Louise; Dossus, Laure; Fournier, Agnes; Baglietto, Laura; Romieu, Isabelle; Kuhn, Elisabetta; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Ramon Quiros, Jose; Obón-Santacana, Mireia; Larrañaga, Nerea; Chirlaque, María-Dolores; Sánchez, María-José; Barricarte, Aurelio; Peeters, Petra H; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Weiderpass, Elisabete; Gram, Inger T; Lund, Eiliv; Kaw, Kay-Tee; Travis, Ruth C; Merritt, Melissa A; Gunther, Marc J; Riboli, Elio; Kaaks, Rudolf

    2015-01-15

    The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. PMID:24890047

  2. Perivascular Epithelioid Cell Tumor of the Uterus with Ovarian Involvement: A Case Report and Review of the Literature

    PubMed Central

    Fitzpatrick, Megan; Pulver, Tanya; Klein, Molly; Murugan, Paari; Khalifa, Mahmoud; Amin, Khalid

    2016-01-01

    Patient: Female, 61 Final Diagnosis: Uterine PEComa with ovarian involvement Symptoms: Palpable abdominal mass Medication: — Clinical Procedure: Hysterectomy and bilateral salpingo-oophorectomy Specialty: Obstetrics and Gynecology Objective: Rare disease Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of neoplasms composed of epithelioid cells that express both melanocytic and myoid markers. When considering PEComas of the female genital tract, the uterus is the most common location. Involvement of the ovary in the context of a primary uterine PEComa, in the absence of systemic disease associated with tuberous sclerosis, however, has only been reported in 1 previous case. Case Report: We report a case of a PEComa of the uterus with metastasis to the left ovary in a 61-year-old Caucasian woman. Gross examination of the uterus revealed a 10.7×10.5×10.2 cm tan-brown, mostly solid, partially cystic mass. Microscopic examination showed epithelioid cells with clear to eosinophilic cytoplasm, arranged in fascicles. Intranuclear pseudoinclusions were also noted. The tumor cells were smooth muscle actin, caldesmon, and desmin positive (diffuse); HMB-45 positive (focal); and Melan-A, AE1/AE3, CD10, and S100 negative by immunohistochemistry. Conclusions: Distinguishing among mesenchymal neoplasms, including PEComas, endometrial stromal sarcomas, and leiomyosarcomas, can be difficult. Careful analysis of morphologic and immunohistochemical features is of the utmost importance. Differential diagnosis, including morphologic features and immunohistochemical patterns, is also discussed. PMID:27150246

  3. Nanoscale Coordination Polymers Codeliver Chemotherapeutics and siRNAs to Eradicate Tumors of Cisplatin-Resistant Ovarian Cancer.

    PubMed

    He, Chunbai; Poon, Christopher; Chan, Christina; Yamada, S Diane; Lin, Wenbin

    2016-05-11

    Drug resistance impedes the successful treatment of many types of cancers, especially ovarian cancer (OCa). To counter this problem, we developed novel long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles that efficiently deliver multiple therapeutics with different mechanisms of action to enhance synergistic therapeutic effects. These NCP particles contain high payloads of chemotherapeutics cisplatin or cisplatin plus gemcitabine in the core and pooled siRNAs that target multidrug resistant (MDR) genes in the shell. The NCP particles possess efficient endosomal escape via a novel carbon dioxide release mechanism without compromising the neutral surface charge required for long blood circulation and effectively downregulate MDR gene expression in vivo to enhance chemotherapeutic efficacy by several orders of magnitude. Even at low doses, intraperitoneal injections of nanoparticles led to effective and long-lasting tumor regression/eradication in subcutaneous and intraperitoneal xenograft mouse models of cisplatin-resistant OCa. By silencing MDR genes in tumors, self-assembled core-shell nanoparticles promise a more effective chemotherapeutic treatment for many challenging cancers. PMID:27088560

  4. 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

  5. Anti-Tumor Effect of Pinus massoniana Bark Proanthocyanidins on Ovarian Cancer through Induction of Cell Apoptosis and Inhibition of Cell Migration

    PubMed Central

    Liu, Jia; Bai, Jing; Jiang, Guoqiang; Li, Xinli; Wang, Jing; Wu, Dachang; Owusu, Lawrence; Zhang, Ershao; Li, Weiling

    2015-01-01

    Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties. Here, we investigated the anti-tumor effect of PMBPs on ovarian cancer. The results indicated that PMBPs significantly reduced the growth of ovarian cancer cells and induced dose-dependent apoptosis. The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway. In addition, wound healing and transwell chamber assays revealed that PMBPs could suppress migration and invasion of ovarian cancer cells. PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK. Our findings suggest that PMBPs has the potential to be developed as an anti-tumor drug for ovarian cancer treatment and/ or disease management. PMID:26539720

  6. Intraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-06-21

    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

  7. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    ClinicalTrials.gov

    2016-04-07

    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

  8. Advanced stage ovarian juvenile granuloza cell tumor causing acute abdomen: a case report.

    PubMed

    Bedir, Recep; Mürtezaoğlu, Afşin Rahman; Calapoğlu, Ahmet Salih; Şehitoğlu, İbrahim; Yurdakul, Cüneyt

    2014-09-01

    Ovary juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors that are most commonly encountered in prepubertal girls. These tumors can be of the adult type (95%) and juvenile type (5%). The main causes of complaint are abdominal distention and abdominal pain. Definitive diagnosis is confirmed by histopathologal and immunohistochemical examinations. A 10-year old girl presented with massive abdominal distention, acute abdomen findings and ascites. Abdominopelvic magnetic resonance imaging showed masses with multiple cysts and solid components in the left ovary. Tumor markers were normal, but serum estradiol level was elevated. The patient underwent mass resection with left salpingo-oophorectomy and total omentectomy. Final histopathological diagnosis was JGCT. We herein reporte an extremely rare case of advanced stage JGCT causing massive ascites and acute abdomen. PMID:25204485

  9. 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.

  10. A Novel Subset of Human Tumors That Simultaneously Overexpress Multiple E2F-responsive Genes Found in Breast, Ovarian, and Prostate Cancers

    PubMed Central

    Shackney, Stanley E; Chowdhury, Salim Akhter; Schwartz, Russell

    2014-01-01

    Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer. In breast cancer, a group of tumors was identified, each of which simultaneously overexpressed multiple E2F-responsive genes. Seventy percent of these genes were concerned with cell cycle progression, DNA repair, or mitosis. These E2F-responsive gene overexpressing (ERGO) tumors frequently exhibited additional evidence of Rb/E2F axis dysfunction, were mostly triple negative, and preferentially overexpressed multiple basal cytokeratins, suggesting that they overlapped substantially with the basal-like tumor subset. ERGO tumors were also identified in serous ovarian cancer and prostate cancer. In these cancer types, there was no evidence for a tumor subset comparable to the breast cancer basal-like subset. A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types. Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes. PMID:25392696

  11. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

    PubMed Central

    Corvigno, Sara; Wisman, G. Bea A.; Mezheyeuski, Artur; van der Zee, Ate G.J.; Nijman, Hans W.; Åvall-Lundqvist, Elisabeth; Östman, Arne; Dahlstrand, Hanna

    2016-01-01

    Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features. Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer. PMID:26918345

  12. Peutz-Jeghers Syndrome with Multiple Genital Tract Tumors and Breast Cancer: A Case Report with a Review of Literatures

    PubMed Central

    Song, Seung-Hun; Lee, Jae-Kwan; Saw, Ho-Suk; Choi, Sang-Yong; Koo, Bum-Hwan; Kim, Aeree; Yeom, Bum-Woo

    2006-01-01

    We report here on the multiple genital tract neoplasms in a 41-yr-old Korean woman with Peutz-Jeghers Syndrome (PJS). The patient presented with lower abdominal pain. Her previous medical history was PJS and breast cancer. Pelvic ultrasound showed a multilocular cyst at the right adnexal region, diagnosed as bilateral ovarian mucinous borderline tumors. An ovarian sex cord tumor with annular tubules was incidentally diagnosed together with a minimal deviation adenocarcinoma of the uterine cervix and mucinous metaplasia of both the Fallopian tubal mucosa and the endometrium. Although the cases of multiple genital tract tumors with PJS has rarely been reported, the present case appears to be the first in Korea in which the PJS syndrome was complicated by multiple genital tract tumors and infiltrating carcinoma of the breast. The clinical significance of the multiple genital tract tumors and breast cancer associated with PJS is reviewed. PMID:16891826

  13. Peutz-Jeghers Syndrome with multiple genital tract tumors and breast cancer: a case report with a review of literatures.

    PubMed

    Song, Seung-Hun; Lee, Jae-Kwan; Saw, Ho-Suk; Choi, Sang-Yong; Koo, Bum-Hwan; Kim, Aeree; Yeom, Bum-Woo; Kim, Insun

    2006-08-01

    We report here on the multiple genital tract neoplasms in a 41-yr-old Korean woman with Peutz-Jeghers Syndrome (PJS). The patient presented with lower abdominal pain. Her previous medical history was PJS and breast cancer. Pelvic ultrasound showed a multilocular cyst at the right adnexal region, diagnosed as bilateral ovarian mucinous borderline tumors. An ovarian sex cord tumor with annular tubules was incidentally diagnosed together with a minimal deviation adenocarcinoma of the uterine cervix and mucinous metaplasia of both the Fallopian tubal mucosa and the endometrium. Although the cases of multiple genital tract tumors with PJS has rarely been reported, the present case appears to be the first in Korea in which the PJS syndrome was complicated by multiple genital tract tumors and infiltrating carcinoma of the breast. The clinical significance of the multiple genital tract tumors and breast cancer associated with PJS is reviewed. PMID:16891826

  14. 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

  15. Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment

    PubMed Central

    Finkernagel, Florian; Lieber, Sonja; Schnitzer, Evelyn; Legrand, Nathalie; Schober, Yvonne; Nockher, W. Andreas; Toth, Philipp M.; Diederich, Wibke E.; Nist, Andrea; Stiewe, Thorsten; Wagner, Uwe; Reinartz, Silke; Müller-Brüsselbach, Sabine; Müller, Rolf

    2015-01-01

    The nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor associated with macrophage polarization. However, its function in tumor-associated macrophages (TAMs) has not been investigated to date. Here, we report the PPARβ/δ-regulated transcriptome and cistrome for TAMs from ovarian carcinoma patients. Comparison with monocyte-derived macrophages shows that the vast majority of direct PPARβ/δ target genes are upregulated in TAMs and largely refractory to synthetic agonists, but repressible by inverse agonists. Besides genes with metabolic functions, these include cell type-selective genes associated with immune regulation and tumor progression, e.g., LRP5, CD300A, MAP3K8 and ANGPTL4. This deregulation is not due to increased expression of PPARβ/δ or its enhanced recruitment to target genes. Instead, lipidomic analysis of malignancy-associated ascites revealed high concentrations of polyunsaturated fatty acids, in particular linoleic acid, acting as potent PPARβ/δ agonists in macrophages. These fatty acid ligands accumulate in lipid droplets in TAMs, thereby providing a reservoir of PPARβ/δ ligands. These observations suggest that the deregulation of PPARβ/δ target genes by ligands of the tumor microenvironment contributes to the pro-tumorigenic polarization of ovarian carcinoma TAMs. This conclusion is supported by the association of high ANGPTL4 expression with a shorter relapse-free survival in serous ovarian carcinoma. PMID:25968567

  16. Tumor Sensitive Matching Flow: A Variational Method to Detecting and Segmenting Perihepatic and Perisplenic Ovarian Cancer Metastases on Contrast-Enhanced Abdominal CT

    PubMed Central

    Liu, Jianfei; Wang, Shijun; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M.

    2015-01-01

    Accurate automated segmentation and detection of ovarian cancer metastases may improve the diagnosis and prognosis of women with ovarian cancer. In this paper, we focus on an important subset of ovarian cancer metastases that spread to the surface of the liver and spleen. Automated ovarian cancer metastasis detection and segmentation are very challenging problems to solve. These metastases have a wide variety of shapes and intensity values similar to that of the liver, spleen and adjacent soft tissues. To address these challenges, this paper presents a variational approach, called tumor sensitive matching flow (TSMF), to detect and segment perihepatic and perisplenic ovarian cancer metastases. TSMF is an image motion field that only highlights metastasis-caused deformation on the surface of liver and spleen while dampening all other image motion between the patient image and the atlas image. It provides several benefits: 1) juxtaposing the roles of image matching and metastasis classification within a variational framework; 2) only requiring a small set of features from a few patient images to train a metastasis-likelihood function for classification; and 3) dynamically creating shape priors for geodesic active contour (GAC) to prevent inaccurate metastasis segmentation. We compared the TSMF to an organ surface partition (OSP) baseline approach. At a false positive rate of 2 per patient, the sensitivities of TSMF and OSP were 87% and 17% (p < 0.001), respectively. In a comparison of the segmentations conducted using TSMF-constrained GAC and conventional GAC, the volume overlap rates were 73±9% and 46±26% (p < 0.001) and average surface distances were 2.4±1.2mm and 7.0±6.0mm (p < 0.001), respectively. These encouraging results demonstrate that TSMF could accurately detect and segment ovarian cancer metastases. PMID:24835180

  17. The tumor suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways

    PubMed Central

    Badgwell, Donna B.; Lu, Zhen; Le, Kim; Gao, Fengqin; Yang, Maojie; Suh, Grace K.; Bao, Jia-Ju; Das, Partha; Andreeff, Michael; Chen, Wenting; Yu, Yinhua; Ahmed, Ahmed Ashour; Liao, Warren S.-L.; Bast, Robert C.

    2011-01-01

    Ovarian cancers migrate and metastasize over the surface of the peritoneal cavity. Consequently, dysregulation of mechanisms that limit cell migration may be particularly important in the pathogenesis of the disease. ARHI is an imprinted tumor suppressor gene that is down regulated in >60% of ovarian cancers and its loss is associated with decreased progression-free survival. ARHI encodes a 26 kDa GTPase with homology to Ras. In contrast to Ras, ARHI inhibits cell growth, but whether it also regulates cell motility has not been previously studied Here we report that re-expression of ARHI decreases motility of IL-6- and EGF-stimulated SKOv3 and Hey ovarian cancer cells, inhibiting both chemotaxis and haptotaxis. ARHI binds and sequesters Stat3 in the cytoplasm, preventing its translocation to the nucleus and localization in focal adhesion complexes. Stat3 siRNA or the JAK2 inhibitor AG490 produced similar inhibition of motility. However, the combination of ARHI expression with Stat3 knockdown or inhibition produced greatest inhibition in ovarian cancer cell migration, consistent with Stat3-dependent and Stat3-independent mechanisms. Consistent with two distinct signaling pathways, knockdown of Stat3 selectively inhibited IL-6-stimulated migration, whereas knockdown of FAK preferentially inhibited EGF-stimulated migration. In EGF-stimulated ovarian cancer cells, re-expression of ARHI inhibited FAKY397 and SrcY416 phosphorylation, disrupted focal adhesions, and blocked FAK-mediated RhoA signaling, resulting in decreased levels of GTP-RhoA. Re-expression of ARHI also disrupted formation of actin stress fibers in a FAK- and RhoA-dependent manner. Thus, ARHI plays a critical and previously uncharacterized role in regulation of ovarian cancer cell migration, exerting inhibitory effects on two distinct signaling pathways. PMID:21643014

  18. 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

  19. Prognostic value of serum α-fetoprotein in ovarian yolk sac tumors: A systematic review and meta-analysis.

    PubMed

    Guo, Yang-Long; Zhang, Ying-Li; Zhu, Jian-Qing

    2015-01-01

    This study was conducted to determine the prognostic value of serum α-fetoprotein (AFP) levels in patients with ovarian yolk sac tumor (OYST). We performed a systematic review and meta-analysis to assess the associations between serum AFP level and prognosis in OYST. A total of 12 quantitative studies met the inclusion criteria. Preoperative AFP was not found to be associated with overall survival (OS) [odds ratio (OR)=0.84, 95% confidence interval (CI): 0.43-1.62] in OYST. However, a high postoperative AFP level was associated with worse OS (OR=0.16, 95% CI: 0.05-0.48) and relapse-free survival (RFS) (OR=0.18, 95% CI: 0.08-0.43) compared to a low postoperative AFP level in patients with OYST. In addition, a postoperative AFP level of >1,000 ng/ml was associated with a decrease in OS (OR=0.16, 95% CI: 0.05-0.50) and RFS (OR=0.21, 95% CI: 0.08-0.57). In conclusion, the postoperative, but not the preoperative, AFP level was found to be a prognostic factor in patients with OYST. In particular, a postoperative AFP level of >1,000 ng/ml was an indicator of poor prognosis in patients with OYST. PMID:25469282

  20. [An analysis of 117 cases of patients who died from tumor recurrence or from the progression of ovarian malignancies].

    PubMed

    Kano, T; Sakakibara, K; Kamiya, N; Mizuno, K; Miyazaki, T; Ohta, M; Tomoda, Y

    1987-10-01

    Out of 403 patients with ovarian with malignancies during 1978 to, 1985, 117 (29.0%) died from the progression of a non-curative cancer (56 cases, 47.9%) or from a cancer recurrence (61 cases, 52.1%). The mean survival rate 117 cases was 13.4 months, of which 103 (88.0%) cases concerned patients who died within 2 years and 114 (97.4%) who died within 3 years. A histological analysis revealed that patients with a serous or an endometrial cancer had a longer survival rate than others. Among 61 recurrent cases, 59 (96.7%) fell into recurrence within 2 years. Regarding the relationship between a recurrent of cancer and its prognosis, patients with a recurrence of an ascitic or a metastatic disease had a poorer prognosis than patients with a pelvic or an abdominal mass. An aggressive operation, such as a resection of a recurrent tumor, even if small in volume, led to a better prognostic result than no therapy. PMID:3694804

  1. Emblica officinalis Extract Induces Autophagy and Inhibits Human Ovarian Cancer Cell Proliferation, Angiogenesis, Growth of Mouse Xenograft Tumors

    PubMed Central

    De, Alok; De, Archana; Papasian, Chris; Hentges, Shane; Banerjee, Snigdha; Haque, Inamul; Banerjee, Sushanta K.

    2013-01-01

    Patients with ovarian cancer (OC) may be treated with surgery, chemotherapy and/or radiation therapy, although none of these strategies are very effective. Several plant-based natural products/dietary supplements, including extracts from Emblicaofficinalis (Amla), have demonstrated potent anti-neoplastic properties. In this study we determined that Amla extract (AE) has anti-proliferative effects on OC cells under both in vitro and in vivo conditions. We also determined the anti-proliferative effects one of the components of AE, quercetin, on OC cells under in vitro conditions. AE did not induce apoptotic cell death, but did significantly increase the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. Quercetin also increased the expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also significantly reduced the expression of several angiogenic genes, including hypoxia-inducible factor 1α (HIF-1α) in OVCAR3 cells. AE acted synergistically with cisplatin to reduce cell proliferation and increase expression of the autophagic proteins beclin1 and LC3B-II under in vitro conditions. AE also had anti-proliferative effects and induced the expression of the autophagic proteins beclin1 and LC3B-II in mouse xenograft tumors. Additionally, AE reduced endothelial cell antigen – CD31 positive blood vessels and HIF-1α expression in mouse xenograft tumors. Together, these studies indicate that AE inhibits OC cell growth both in vitro and in vivo possibly via inhibition of angiogenesis and activation of autophagy in OC. Thus AE may prove useful as an alternative or adjunct therapeutic approach in helping to fight OC. PMID:24133573

  2. 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

  3. 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

  4. 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

  5. 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

    2016-09-12

    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

  6. Peutz-Jeghers syndrome with ovarian sex cord tumor with annular tubules and cervical adenoma malignum.

    PubMed

    Podczaski, E; Kaminski, P F; Pees, R C; Singapuri, K; Sorosky, J I

    1991-07-01

    A patient with Peutz-Jeghers syndrome, a sex cord tumor with annular tubules, and an initially unrecognized adenoma malignum of the cervix is described. The patient presented with a mucinous adenocarcinoma in the vaginal apex. Review of the hysterectomy slides demonstrated an adenoma malignum of the cervix. In addition to a microscopic sex cord tumor with annular tubules of the right ovary, the left ovary contained mucinous cystadenomas. Adenoma malignum remains a difficult diagnosis and is frequently made only after hysterectomy for a presumed benign indication; pathology frequently demonstrates a deeply invasive, unusually well-differentiated adenocarcinoma of the cervix. Patients with Peutz-Jeghers syndrome need careful clinical and cytologic follow-up to exclude such lesions. PMID:1916514

  7. Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.

    PubMed

    Kim, Sang Kyum; Song, Si Young; Kim, Sunghoon; Cho, Nam Hoon; Yim, Ga Won; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji

    2014-01-01

    Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor. PMID:25197383

  8. Gastrointestinal stromal tumors as an incidental finding in patients with a presumptive diagnosis of ovarian cancer

    PubMed Central

    Muñoz, Mario; Ramirez, Pedro T.; Echeverri, Carolina; Álvarez, Luis Guillermo; Palomino, Maria Alejandra

    2012-01-01

    Objective To report the clinical presentation and oncologic outcomes of a series of patients who presented with an abdominal or pelvic mass and were diagnosed with a gastrointestinal stromal tumor (GIST). Methods Data were obtained on all patients who presented with an abdominal or pelvic mass between September 2007 and June 2010 and who were ultimately diagnosed with a GIST. The patients' medical records were reviewed. A literature review was also conducted. Results Six patients were identified who met the inclusion criteria. All six patients had a tumor in the intestinal tract arising from the small bowel. The mean tumor size was 12 cm (range, 6 to 22 cm). A complete resection was achieved in five of the six patients. There were no intraoperative complications; one patient had a postoperative complication. Two patients were treated with imatinib after surgery. The mean follow-up time was 32 months (range, 0.3 to 40 months). At the last follow-up, five of the six patients were without any evidence of disease. One patient died of an unrelated hepatic encephalopathy. The incidence in our institution is 3%. Conclusion GISTs are uncommon; however, they should be considered in the differential diagnosis of patients presenting with an abdominal or pelvic mass. PMID:22355467

  9. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-05-18

    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

  10. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma

    PubMed Central

    Kir, Gozde; Gurbuz, Ayse; Karateke, Ates; Kir, Mustafa

    2010-01-01

    Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the differential diagnosis of metastatic colorectal tumors to the ovary and primary ovarian tumors are detailed. PMID:21160859

  11. [Mucinous ovarian neoplasms. Prognostically mostly excellent, infrequently a wolf in sheep's clothing].

    PubMed

    Lax, S; Staebler, A

    2014-07-01

    Mucinous ovarian neoplasms represent the second largest group of epithelial ovarian tumors after serous neoplasms, of which benign cystadenomas constitute more than 80 %. Mucinous cystadenomas and carcinomas cannot be distinguished by the clinical features or the mean age of onset of the disease. They typically occur unilaterally, are confined to the adnexae (FIGO stage I) and clinically present with non-specific abdominal symptoms or are diagnosed by chance. The mean age of disease onset is around 50 years old. The prognosis is excellent. Implants, peritoneal metastases and bilateral occurrence of ovarian mucinous neoplasms should lead to the suspicion of metastasis particularly from a gastrointestinal tumor. Neither microinvasion defined as a maximum extent of invasion of 5 mm, nor intraepithelial carcinoma characterized by high grade atypia without invasion, affect the prognosis of mucinous borderline tumors. Mucinous carcinomas typically show confluent glandular, expansile growth that leads to a labyrinth-like pattern. A destructive infiltrative or nodular growth pattern, however, should lead to the consideration of metastasis. Mural nodules that may reveal a spindle cell sarcomatous or anaplastic carcinomatous pattern occur infrequently in mucinous and do not affect the prognosis. Pax8 positivity is indicative of a primary ovarian neoplasm. In this case, however, mucinous tumors associated with teratomas may show the colonic immunoreaction pattern (CK7-/CK20+/CDX2+). The rare mucinous tumors with endocervical differentiation are now designated as seromucinous tumors and consist of two or more distinct cell types, are frequently associated with endometriosis and seem to show a molecular genetic relationship to endometrioid neoplasms. PMID:24962632

  12. Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

    PubMed Central

    Meier, Julia C; Haendler, Bernard; Seidel, Henrik; Groth, Philip; Adams, Robert; Ziegelbauer, Karl; Kreft, Bertolt; Beckmann, Georg; Sommer, Anette; Kopitz, Charlotte

    2015-01-01

    Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer. PMID:25490861

  13. Polymorphisms of MUC16 (CA125) and MUC1 (CA15.3) in Relation to Ovarian Cancer Risk and Survival

    PubMed Central

    Williams, Kristina A.; Terry, Kathryn L.; Tworoger, Shelley S.; Vitonis, Allison F.; Titus, Linda J.; Cramer, Daniel W.

    2014-01-01

    Objective To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival. Methods We genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models. Results Cases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset. Conclusion This targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted. PMID:24551091

  14. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2016-04-12

    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

  15. Arterivirus and Nairovirus Ovarian Tumor Domain-Containing Deubiquitinases Target Activated RIG-I To Control Innate Immune Signaling

    PubMed Central

    van Kasteren, Puck B.; Beugeling, Corrine; Ninaber, Dennis K.; Frias-Staheli, Natalia; van Boheemen, Sander; García-Sastre, Adolfo; Snijder, Eric J.

    2012-01-01

    The innate immune response constitutes the first line of defense against viral infection and is extensively regulated through ubiquitination. The removal of ubiquitin from innate immunity signaling factors by deubiquitinating enzymes (DUBs) therefore provides a potential opportunity for viruses to evade this host defense system. It was previously found that specific proteases encoded by the unrelated arteri- and nairoviruses resemble the ovarian tumor domain-containing (OTU) family of DUBs. In arteriviruses, this domain has been characterized before as a papain-like protease (PLP2) that is also involved in replicase polyprotein processing. In nairoviruses, the DUB resides in the polymerase protein but is not essential for RNA replication. Using both in vitro and cell-based assays, we now show that PLP2 DUB activity is conserved in all members of the arterivirus family and that both arteri- and nairovirus DUBs inhibit RIG-I-mediated innate immune signaling when overexpressed. The potential relevance of RIG-I-like receptor (RLR) signaling for the innate immune response against arterivirus infection is supported by our finding that in mouse embryonic fibroblasts, the production of beta interferon primarily depends on the recognition of arterivirus RNA by the pattern-recognition receptor MDA5. Interestingly, we also found that both arteri- and nairovirus DUBs inhibit RIG-I ubiquitination upon overexpression, suggesting that both MDA5 and RIG-I have a role in countering infection by arteriviruses. Taken together, our results support the hypothesis that arteri- and nairoviruses employ their deubiquitinating potential to inactivate cellular proteins involved in RLR-mediated innate immune signaling, as exemplified by the deubiquitination of RIG-I. PMID:22072774

  16. Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation: Case Report and Review of The Literature.

    PubMed

    Liang, Li; Menzin, Andrew; Lovecchio, John Louis; Navarro, Maria D

    2015-01-01

    Sertoli-Leydig cell tumor is a rare ovarian neoplasm and belongs to the group of sex cord stromal tumors. We present a case of a 15-year old girl diagnosed with Sertoli-Leydig cell tumor with heterologous elements consisting predominantly of mucinous epithelium and a sparse Sertoli-Leydig cell component, mimicking mucinous neoplasm. Furthermore, foci of hepatocytic differentiation were also identified. Immunohistochemical stains showed the component of Sertoli cell differentiation was positive for cytokeratin 18 and inhibin. The component of Leydig cell differentiation was strongly positive for inhibin. The component of hepatocytic differentiation was positive for low molecular weight keratin, HepPar1, alpha-fetoprotein and weakly positive for inhibin. Thus, this was a very rare case which created a challenge for pathologists, especially on frozen sections. PMID:26116602

  17. Real-Time Imaging of Resident T Cells in Human Lung and Ovarian Carcinomas Reveals How Different Tumor Microenvironments Control T Lymphocyte Migration

    PubMed Central

    Bougherara, Houcine; Mansuet-Lupo, Audrey; Alifano, Marco; Ngô, Charlotte; Damotte, Diane; Le Frère-Belda, Marie-Aude; Donnadieu, Emmanuel; Peranzoni, Elisa

    2015-01-01

    T cells play a key role in the battle against cancer. To perform their antitumor activities, T cells need to adequately respond to tumor antigens by establishing contacts with either malignant cells or antigen-presenting cells. These latter functions rely on a series of migratory steps that go from entry of T cells into the tumor followed by their locomotion in the tumor stroma. Our knowledge of how T cells migrate within tumors mainly comes from experiments performed in mouse models. Whereas such systems have greatly advanced our understanding, they do not always faithfully recapitulate the disease observed in cancer patients. We previously described a technique based on tissue slices that enables to track with real-time imaging microscopy the motile behavior of fluorescent T cells plated onto fresh sections of human lung tumors. We have now refined this approach to monitor the locomotion of resident tumor-infiltrating CD8 T cells labeled with fluorescently coupled antibodies. Using this approach, our findings reveal that CD8 T cells accumulate in the stroma of ovarian and lung carcinomas but move slowly in this compartment. Conversely, even though less populated, tumors islets were found to be zones of faster migration for resident CD8 T cells. We also confirm the key role played by collagen fibers, which, by their orientation, spacing and density, control the distribution and migration of resident CD8 T cells within the tumor stroma. We have subsequently demonstrated that, under some physical tissue constraints, CD8 T cells exhibited a mode of migration characterized by alternate forward and backward movements. In sum, using an ex vivo assay to track CD8 T cells in fresh human tumor tissues, we have identified the extracellular matrix as a major stromal component in influencing T cell migration, thereby impacting the control of tumor growth. This approach will aid in the development and testing of novel immunotherapy strategies to promote T cell migration in

  18. Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer.

    PubMed

    Ganapathi, Mahrukh K; Jones, Wendell D; Sehouli, Jalid; Michener, Chad M; Braicu, Ioana E; Norris, Eric J; Biscotti, Charles V; Vaziri, Susan A J; Ganapathi, Ram N

    2016-02-01

    Tumor recurrence, following initial response to adjuvant chemotherapy, is a major problem in women with high-grade serous ovarian cancer (HGSOC). Microarray analysis of primary tumors has identified genes that may be useful in risk stratification/overall survival, but are of limited value in predicting the >70% rate for tumor recurrence. In this study, we performed RNA-Seq analysis of primary and recurrent HGSOC to first identify unique differentially expressed genes. From this dataset, we selected 21 archetypical coding genes and one noncoding RNA, based on statistically significant differences in their expression profile between tumors, for validation by qPCR in a larger cohort of 110 ovarian tumors (71 primary and 39 recurrent) and for testing association of specific genes with time-to-recurrence (TTR). Kaplan-Meier tests revealed that high expression of collagen type II, alpha 1 (COL2A1) was associated with delayed TTR (HR = 0.47, 95% CI: 0.27-0.82, p = 0.008), whereas low expression of the pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with longer TTR (HR = 0.53, 95% CI: 0.30-0.93, p = 0.027). Notably, TTR was significantly delayed for tumors that simultaneously highly expressed COL2A1 and lowly expressed SLC6A10P (HR = 0.21, 95% CI: 0.082-0.54, p = 0.0011), an estimated median of 95 months as compared to an estimated median of 16 months for subjects expressing other levels of COL2A1 and SLC6A10P. Thus, evaluating expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial for clinically managing recurrence of HGSOC. PMID:26311224

  19. Inhibition of hexokinase-2 with targeted liposomal 3-bromopyruvate in an ovarian tumor spheroid model of aerobic glycolysis

    PubMed Central

    Gandham, Srujan Kumar; Talekar, Meghna; Singh, Amit; Amiji, Mansoor M

    2015-01-01

    Background The objective of this study was to evaluate the expression levels of glycolytic markers, especially hexokinase-2 (HK2), using a three-dimensional multicellular spheroid model of human ovarian adenocarcinoma (SKOV-3) cells and to develop an epidermal growth factor receptor-targeted liposomal formulation for improving inhibition of HK2 and the cytotoxicity of 3-bromopyruvate (3-BPA). Methods Multicellular SKOV-3 tumor spheroids were developed using the hanging drop method and expression levels of glycolytic markers were examined. Non-targeted and epidermal growth factor receptor-targeted liposomal formulations of 3-BPA were formulated and characterized. Permeability and cellular uptake of the liposomal formulations in three-dimensional SKOV-3 spheroids was evaluated using confocal microscopy. The cytotoxicity and HK2 inhibition potential of solution form of 3-BPA was compared to the corresponding liposomal formulation by using cell proliferation and HK2 enzymatic assays. Results SKOV-3 spheroids were reproducibly developed using the 96-well hanging drop method, with an average size of 900 µm by day 5. HK2 enzyme activity levels under hypoxic conditions were found to be higher than under normoxic conditions (P<0.0001, Student’s t-test, unpaired and two-tailed). Liposomal formulations (both non-targeted and targeted) of 3-BPA showed a more potent inhibitory effect (P<0.001, Student’s t-test, unpaired and two-tailed) at a dose of 50 µM than the aqueous solution form at 3, 6, and 24 hours post administration. Similarly, the cytotoxic activity 3-BPA at various concentrations (10 µM–100 µM) showed that the liposomal formulations had an enhanced cytotoxic effect of 2–5-fold (P<0.0001, Student’s t-test, unpaired and two-tailed) when compared to the aqueous solution form for both 10 µM and 25 µM concentrations. Conclusion SKOV-3 spheroids developed by the hanging drop method can be used as a tumor aerobic glycolysis model for evaluation of therapies

  20. Quinacrine promotes autophagic cell death and chemosensitivity in ovarian cancer and attenuates tumor growth

    PubMed Central

    Mondal, Susmita; Wen, Xuyang; He, Xiaoping; Dowdy, Sean; Shridhar, Viji

    2015-01-01

    A promising new strategy for cancer therapy is to target the autophagic pathway. In the current study, we demonstrate that the antimalarial drug Quinacrine (QC) reduces cell viability and promotes chemotherapy-induced cell death in an autophagy-dependent manner more extensively in chemoresistant cells compared to their isogenic chemosensitive control cells as quantified by the Chou-Talalay methodology. Our preliminary data, in vitro and in vivo, indicate that QC induces autophagy by downregulating p62/SQSTM1 to sensitize chemoresistant cells to autophagic- and caspase-mediated cell death in a p53-independent manner. QC promotes autophagosome accumulation and enhances autophagic flux by clearance of p62 in chemoresistant ovarain cancer (OvCa) cell lines to a greater extent compared to their chemosensitive controls. Notably, p62 levels were elevated in chemoresistant OvCa cell lines and knockdown of p62 in these cells resulted in a greater response to QC treatment. Bafilomycin A, an autophagy inhibitor, restored p62 levels and reversed QC-mediated cell death and thus chemosensitization. Importantly, our in vivo data shows that QC alone and in combination with carboplatin suppresses tumor growth and ascites in the highly chemoresistant HeyA8MDR OvCa model compared to carboplatin treatment alone. Collectively, our preclinical data suggest that QC in combination with carboplatin can be an effective treatment for patients with chemoresistant OvCa. PMID:26497553

  1. RNA Interference-Mediated Inhibition of Erythropoietin Receptor Expression Suppresses Tumor Growth and Invasiveness in A2780 Human Ovarian Carcinoma Cells

    PubMed Central

    Paragh, Gyorgy; Kumar, Suresh M.; Rakosy, Zsuzsa; Choi, Soek-Choel; Xu, Xiaowei; Acs, Geza

    2009-01-01

    Although recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia, recent clinical trials suggested that rHuEpo use may be associated with decreased survival in cancer patients. Although the expression of erythropoietin (Epo) receptor (EpoR) has been demonstrated in various human cancers, the effect of exogenous Epo on the growth and therapy resistance of EpoR-bearing tumor cells is unclear at present. In the current study, we examined the hypothesis that EpoR may contribute to tumor growth independent of Epo in A2780 human ovarian carcinoma cells. A2780 human ovarian carcinoma cells showed high levels of EpoR expression, but lacked expression of Epo mRNA and biologically active Epo protein under both normoxic and hypoxic conditions. Exogenous Epo did not stimulate EpoR-mediated signaling, proliferation, invasiveness, or resistance to cytotoxic drugs in A2780 cells. In contrast, specific inhibition of EpoR expression using a short hairpin RNA (shRNA) expression plasmid resulted in markedly reduced proliferation and invasiveness in vitro. In addition, inhibition of EpoR expression led to abrogated in vivo ovarian cancer cell growth in a tumor xenograft system and resulted in decreased EpoR signaling. Our findings suggest that EpoR may be constitutively active in some cancer cells in the absence of Epo and provide the first evidence for a potential role of an Epo-independent, EpoR-mediated pathway in the growth of some human cancers. PMID:19264915

  2. Extracting a low-dimensional description of multiple gene expression datasets reveals a potential driver for tumor-associated stroma in ovarian cancer.

    PubMed

    Celik, Safiye; Logsdon, Benjamin A; Battle, Stephanie; Drescher, Charles W; Rendi, Mara; Hawkins, R David; Lee, Su-In

    2016-01-01

    Patterns in expression data conserved across multiple independent disease studies are likely to represent important molecular events underlying the disease. We present the INSPIRE method to infer modules of co-expressed genes and the dependencies among the modules from multiple expression datasets that may contain different sets of genes. We show that INSPIRE infers more accurate models than existing methods to extract low-dimensional representation of expression data. We demonstrate that applying INSPIRE to nine ovarian cancer datasets leads to a new marker and potential driver of tumor-associated stroma, HOPX, followed by experimental validation. The implementation of INSPIRE is available at http://inspire.cs.washington.edu . PMID:27287041

  3. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment

    PubMed Central

    Garibay-Cerdenares, OL; Hernández-Ramírez, VI; Osorio-Trujillo, JC; Gallardo-Rincón, D; Talamás-Rohana, P

    2015-01-01

    Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype. PMID:26211665

  4. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: exploring a new role of haptoglobin in the tumoral microenvironment.

    PubMed

    Garibay-Cerdenares, O L; Hernández-Ramírez, V I; Osorio-Trujillo, J C; Gallardo-Rincón, D; Talamás-Rohana, P

    2015-01-01

    Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly "preparing" these cells for the potential induction of the metastatic phenotype. PMID:26211665

  5. Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model

    PubMed Central

    Yang, Ming; Yu, Tao; Wood, Joseph; Wang, Ying-Ying; Tang, Benjamin C.; Zeng, Qi; Simons, Brian W.; Fu, Jie; Chuang, Chi-Mu; Lai, Samuel K.; Wu, T.-C.; Hung, Chien-Fu; Hanes, Justin

    2014-01-01

    Intraperitoneal (IP) chemotherapy is more effective than systemic chemotherapy for treating advanced ovarian cancer, but is typically associated with severe complications due to high dose, frequent administration schedule, and use of non-biocompatible excipients/delivery vehicles. Here, we developed paclitaxel (PTX)-loaded microspheres composed of di-block copolymers of poly(ethylene glycol) and poly(sebacic acid) (PEG-PSA) for safe and sustained IP chemotherapy. PEG-PSA microspheres provided efficient loading (~ 13% w/w) and prolonged release (~ 13 days) of PTX. In a murine ovarian cancer model, a single dose of IP PTX/PEG-PSA particles effectively suppressed tumor growth for more than 40 days and extended the median survival time to 75 days compared to treatments with Taxol® (47 days) or IP placebo particles (34 days). IP PTX/PEG-PSA was well tolerated, with only minimal to mild inflammation. Our findings support PTX/PEG–PSA microspheres as a promising drug delivery platform for IP therapy of ovarian cancer, and potentially other metastatic peritoneal cancers. PMID:24816829

  6. 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

    2016-07-05

    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

  7. Ovarian sex cord tumor with annular tubules: review of 74 cases including 27 with Peutz-Jeghers syndrome and four with adenoma malignum of the cervix.

    PubMed

    Young, R H; Welch, W R; Dickersin, G R; Scully, R E

    1982-10-01

    The sex cord tumor with annular tubules (SCTAT) is a distinctive ovarian neoplasm the predominant component of which has morphologic features intermediate between those of the granulosa cell tumor and those of the Sertoli cell tumor; focal differentiation into either granulosa cell or Sertoli cell tumor may occur. Of the 74 cases that form the basis of this investigation 27 were associated with the Peutz-Jeghers syndrome; these tumors were all benign and were typically multifocal, bilateral, very small or even microscopical in size and calcified. Twelve of the 27 patients had symptoms suggestive of hyperestrinism attributable to the SCTAT; menstrual irregularity had occurred in eleven cases and postmenopausal bleeding in one. Four of the 27 patients had "adenoma malignum" of the cervix and two of them died of it. The 47 tumors from patients without evidence of the Peutz-Jeghers syndrome were unilateral and usually large. Twenty-five of them were accompanied by symptoms suggestive of hyperestrinism, such as menstrual irregularity, postmenopausal bleeding or sexual precocity; seven were malignant and four of these were fatal. PMID:7104978

  8. Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis

    PubMed Central

    Andersson, Emilia; Poschke, Isabel; Villabona, Lisa; Carlson, Joseph W; Lundqvist, Andreas; Kiessling, Rolf; Seliger, Barbara; Masucci, Giuseppe V

    2016-01-01

    In our previous studies, we have shown that patients with serous ovarian carcinoma in advanced surgical stage disease have a particularly poor prognosis if they carry the HLA-A*02 genotype. This represent a stronger prognostic factor than loss or downregulation of the MHC class I heavy chain (HC) on tumor cells. In this study, we investigated the expression of the non-classical, immune tolerogenic HLA -G and -E on the tumor cells along with the infiltration of immune cells in the tumor microenvironment. FFPE primary tumors from 72 patients with advanced stages of serous adenocarcinoma and metastatic cells present in ascites fluid from 8 additional patients were included in this study. Both expression of HLA-G and aberrant expression of HLA-E were correlated to a significant worse prognosis in patients with HLA-A*02, but not with different HLA genotypes. Focal cell expression of HLA-G correlated to a site-specific downregulation of classical MHC class I HC products and aberrant HLA-E expression, showing a poor survival. HLA-G was more frequently expressed in metastatic cells than in primary tumor lesions and the expression of HLA-G inversely correlated with the frequency of tumor infiltrating immune cells. All these parameters can contribute together to identify and discriminate subpopulations of patients with extremely poor prognosis and can give them the opportunity to receive, and benefit of individually tailored treatments. PMID:26942060

  9. 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

  10. Childhood ovarian malignancy.

    PubMed

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-04-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients. PMID:24757335

  11. 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 ...

  12. Ovarian Cancer

    MedlinePlus

    Ovarian Cancer There are five main types of cancer that affect a woman’s reproductive organs: cervical, ovarian, uterine, ... rare fallopian tube cancer.) This fact sheet about ovarian cancer is part of the Centers for Disease Control ...

  13. Ovarian cysts

    MedlinePlus

    Physiologic ovarian cysts; Functional ovarian cysts; Corpus luteum cysts; Follicular cysts ... cyst often contains a small amount of blood. Ovarian cysts are more common in the childbearing years between ...

  14. Ultrasonography for early detection of ovarian carcinoma.

    PubMed

    Andolf, E; Svalenius, E; Astedt, B

    1986-12-01

    Ultrasound scan for detection of ovarian enlargements was performed in a target group of out-patients attending the clinic for various reasons in the 40-70 years range. Overall 805 women were examined, in 99% of whom the ovaries and/or their vessels could be identified. Pathological findings were suspected in 83 patients at the first scan, and were confirmed in 50 after a repeat scan, 39 of whom subsequently underwent surgery. Various ovarian lesions were found in 35 women, including five mucinous and serous cystadenomas, one carcinoma, two borderline tumours, and a cancer of the caecum. None of the borderline or malignant ovarian lesions were found by manual pelvic examination. Ultrasound screening appears to be a useful diagnostic aid, though its usefulness might be further improved if other risk factors such as heredity and period of ovulatory activity are taken into consideration. PMID:3542015

  15. 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

  16. The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription.

    PubMed

    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

  17. Label-Free LC-MSe in Tissue and Serum Reveals Protein Networks Underlying Differences between Benign and Malignant Serous Ovarian Tumors

    PubMed Central

    Wegdam, Wouter; Argmann, Carmen A.; Kramer, Gertjan; Vissers, Johannes P.; Buist, Marrije R.; Kenter, Gemma G.; Aerts, Johannes M. F. G.; Meijer, Danielle; Moerland, Perry D.

    2014-01-01

    Purpose To identify proteins and (molecular/biological) pathways associated with differences between benign and malignant epithelial ovarian tumors. Experimental Procedures Serum of six patients with a serous adenocarcinoma of the ovary was collected before treatment, with a control group consisting of six matched patients with a serous cystadenoma. In addition to the serum, homogeneous regions of cells exhibiting uniform histology were isolated from benign and cancerous tissue by laser microdissection. We subsequently employed label-free liquid chromatography tandem mass spectrometry (LC-MSe) to identify proteins in these serum and tissues samples. Analyses of differential expression between samples were performed using Bioconductor packages and in-house scripts in the statistical software package R. Hierarchical clustering and pathway enrichment analyses were performed, as well as network enrichment and interactome analysis using MetaCore. Results In total, we identified 20 and 71 proteins that were significantly differentially expressed between benign and malignant serum and tissue samples, respectively. The differentially expressed protein sets in serum and tissue largely differed with only 2 proteins in common. MetaCore network analysis, however inferred GCR-alpha and Sp1 as common transcriptional regulators. Interactome analysis highlighted 14-3-3 zeta/delta, 14-3-3 beta/alpha, Alpha-actinin 4, HSP60, and PCBP1 as critical proteins in the tumor proteome signature based on their relative overconnectivity. The data have been deposited to the ProteomeXchange with identifier PXD001084. Discussion Our analysis identified proteins with both novel and previously known associations to ovarian cancer biology. Despite the small overlap between differentially expressed protein sets in serum and tissue, APOA1 and Serotransferrin were significantly lower expressed in both serum and cancer tissue samples, suggesting a tissue-derived effect in serum. Pathway and subsequent

  18. LOH at 6q and 10q in fractionated circulating DNA of ovarian cancer patients is predictive for tumor cell spread and overall survival

    PubMed Central

    2012-01-01

    Background We recently showed that LOH proximal to M6P/IGF2R locus (D6S1581) in primary ovarian tumors is predictive for the presence of disseminated tumor cells (DTC) in the bone marrow (BM). For therapy-monitoring, it would be highly desirable to establish a blood-based biomarker. Therefore, we quantified circulating DNA (cirDNA) in sera of 63 ovarian cancer patients before surgery and after chemotherapy, measured incidence of LOH at four cancer-relevant chromosomal loci, correlated LOH with tumor cell spread to the BM and evaluated prognostic significance of LOH. Methods cirDNA was fractionated into high- and low molecular-weight fraction (HMWF, LMWF) for LOH-profiling, utilizing PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Results cirDNA levels in the HMWF before surgery were predictive for residual tumor load (p = 0.017). After chemotherapy, we observed a significant decline of cirDNA in the LMWF (p = 0.0001) but not in the HMWF. LOH was prevalently detected in the LMWF with an overall frequency of 67%, only moderately ablating after chemotherapy (45%). Before surgery, LOH in the LMWF at marker D10S1765 and D13S218 significantly correlated with tumor grading and FIGO stage (p = 0.033, p = 0.004, respectively). In both combined fractions, LOH at D6S1581 additionally associated with overall survival (OS) (p = 0.030). Moreover, solely LOH at D10S1765 in LMWF after therapy correlated with DTC in BM after therapy (p = 0.017). Conclusion We demonstrate the applicability and necessity of DNA-fractionation prior to analyzing circulating LOH and identify LOH at D10S1765 and D6S1581 as novel blood-based biomarkers for ovarian cancer, being relevant for therapy-monitoring. PMID:22849543

  19. 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.

  20. 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

  1. The Use of Lattice Radiation Therapy (LRT) in the Treatment of Bulky Tumors: A Case Report of a Large Metastatic Mixed Mullerian Ovarian Tumor

    PubMed Central

    Amendola, Beatriz E; Perez, Naipy; Amendola, Marco; Wu, Xiaodong

    2015-01-01

    The objective of this teaching case is to report the excellent results of using lattice radiation therapy (LTR) for the treatment of a large metastasis from ovarian carcinosarcoma. This new technical concept extrapolates the traditional spatially fractionated radiation therapy (GRID) technique to advanced three-dimensional (3D) high-dose radiation therapy using modern instrumentation in radiation oncology. We report a case of a 61-year-old female with a large metastatic mass from ovarian carcinosarcoma treated by this procedure with excellent clinical and image-based follow-up results for more than four years. PMID:26719832

  2. Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers.

    PubMed

    Felix, Ashley S; Sherman, Mark E; Hewitt, Stephen M; Gunja, Munira Z; Yang, Hannah P; Cora, Renata L; Boudreau, Vicky; Ylaya, Kris; Lissowska, Jolanta; Brinton, Louise A; Wentzensen, Nicolas

    2015-01-01

    Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case-control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, and p27) and ki67 was examined with immunohistochemical staining of tissue microarrays. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarkers, risk factors, and tumor characteristics. Survival outcomes were only available for ovarian cancer patients and examined using Kaplan-Meier plots and Cox proportional hazards regression. Among ovarian cancer patients (n = 175), positive p21 expression was associated with endometrioid tumors (OR = 12.22, 95% CI = 1.45-102.78) and higher overall survival (log-rank p = 0.002). In Cox models adjusted for stage, grade, and histology, the association between p21 expression and overall survival was borderline significant (hazard ratio = 0.65, 95% CI = 0.42-1.05). Among endometrial cancer patients (n = 289), positive p21 expression was inversely associated with age (OR ≥ 65 years of age = 0.25, 95% CI = 0.07-0.84) and current smoking status (OR: 0.33, 95% CI 0.15, 0.72) compared to negative expression. Our study showed heterogeneity in expression of cell-cycle proteins associated with risk factors and tumor characteristics of gynecologic cancers. Future studies to assess these markers of etiological classification and behavior may be warranted. PMID:25709969

  3. Downregulation of microRNA‑146a inhibits ovarian granulosa cell apoptosis by simultaneously targeting interleukin‑1 receptor‑associated kinase and tumor necrosis factor receptor‑associated factor 6.

    PubMed

    Chen, Xi; Xie, Mingxuan; Liu, Da; Shi, Ke

    2015-10-01

    Premature ovarian failure (POF), an ovarian disorder of multifactorial origin, is defined as the occurrence of amenorrhea, hypergonadotropism and hypoestrogenism in females <40 years old. Apoptosis of ovarian granulosa cells is important in POF and understanding the regulatory mechanism underlying ovarian granulosa cell apoptosis may be beneficial for the management of POF. Increasing evidence suggests that microRNAs (miRs) have a regulatory function in oocyte maturation and ovarian follicular development. In the present study, the expression of miR‑146a in plasma and ovarian granulosa cells obtained from patients with POF, its effect on the apoptosis of ovarian granulosa cells and the possible underlying mechanisms were examined. The present study demonstrated that compared with the control groups, the expression of miR‑146a in the plasma and in ovarian granulosa cells of patients with POF was significantly upregulated. Furthermore, it was found that miR‑146a simultaneously targeted interleukin‑1 receptor‑associated kinase (IRAK1) and tumor necrosis factor receptor‑associated factor 6 (TRAF6), which regulated the activity of nuclear factor‑κB and IκBα. In addition, the results demonstrated that inhibition of the caspase cascade by caspase inhibitors attenuated the effects of miR‑146a on ovarian granulosa cell apoptosis. Taken together, these results suggest that miR‑146a has an important promoting effect on the apoptosis of granulosa cells by targeting IRAK1 and TRAF6 via the caspase cascade pathway. These results may be useful for the management of POF. PMID:26151128

  4. Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-09-12

    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

  5. Clinically occult tubal and ovarian high-grade serous carcinomas presenting in uterine samples: diagnostic pitfalls and clues to improve recognition of tumor origin.

    PubMed

    Bagby, Christina; Ronnett, Brigitte M; Yemelyanova, Anna; Maleki, Zahra; Kuhn, Elisabetta; Vang, Russell

    2013-09-01

    We report the clinicopathologic and immunohistochemical features in 8 patients with tubal or ovarian high-grade serous carcinoma that was present in uterine samples, in which there was the potential for clinical and morphologic misinterpretation as a primary uterine lesion before hysterectomy/bilateral salpingo-oophorectomy. Patients ranged in age from 45 to 70 yr (mean, 57 yr). The initial presentation was variable, ranging from incidental findings on routine Pap smears to pleural effusion. During the preoperative clinical investigation, 7 of 8 patients did not have evidence of an adnexal tumor based on physical examination and radiologic imaging, and serum CA-125 levels were normal to low in 4 of 5 patients. Six patients required multiple rounds of uterine samples, and the preoperative uterine specimens that contained lesional tissue and were available for rereview in all 8 patients included endometrial biopsies/curettages (n=6), endocervical curettages (n=3), Pap smears (n=2), and a hysteroscopic myomectomy specimen (n=1). The amount of carcinoma in these specimens was typically scanty. The lesions in most cases were characterized by detached and minute epithelial clusters, small papillae, and/or individual cells. The constituent glandular cells exhibited notable atypia. Psammoma bodies were identified in only 2 cases. Immunostains for WT-1 were positive in 3 of 4 preoperative specimens. All patients ultimately underwent a hysterectomy/bilateral salpingo-oophorectomy, which revealed an invasive high-grade serous carcinoma of tubal (n=6) or ovarian (n=2) origin. The mean/median tumor size was 3.2/1.7 cm. Transtubal spread was considered the most likely mechanism resulting in tubal/ovarian carcinoma being found in the preoperative uterine samples. These findings highlight the deceptive clinical features of some tubal/ovarian high-grade serous carcinomas, and demonstrate that small and clinically undetectable adnexal high-grade serous carcinomas can initially

  6. 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

    2016-06-21

    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

  7. [Massive ovarian edema in a 13-year-old girl].

    PubMed

    Sailer, V; Huss, S; Wardelmann, E; Müller, A M

    2013-11-01

    Massive ovarian edema is a rare tumor-like condition found in young women resulting from accumulation of fluid mostly due to partial or intermittent torsion of the ovary or secondary, to a preexisting ovarian lesion. We report a case of a 13-year-old girl presenting with an ovarian mass measuring 16 cm. CA-12-5 levels were slightly elevated. Concerns regarding underlying malignancy led to salpingo-oophorectomy. Pathological evaluation revealed a massive ovarian edema and multiple thromboses of ovarian veins. Differentiating massive ovarian edema from malignant ovarian tumor is crucial to prevent patients from undergoing unnecessary surgery. PMID:23649810

  8. 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

  9. 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

  10. Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-08-24

    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

  11. Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.

    PubMed

    He, Y; Wu, A C; Harrington, B S; Davies, C M; Wallace, S J; Adams, M N; Palmer, J S; Roche, D K; Hollier, B G; Westbrook, T F; Hamidi, H; Konecny, G E; Winterhoff, B; Chetty, N P; Crandon, A J; Oliveira, N B; Shannon, C M; Tinker, A V; Gilks, C B; Coward, J I; Lumley, J W; Perrin, L C; Armes, J E; Hooper, J D

    2016-01-28

    Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC

  12. 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

  13. Deregulated miR-296/S100A4 axis promotes tumor invasion by inducing epithelial-mesenchymal transition in human ovarian cancer

    PubMed Central

    Yan, Wang; Chen, Jiaqi; Chen, Zhaoying; Chen, Huimin

    2016-01-01

    S100A4 represents an important member of the S100 family of small calcium-binding proteins. Increased expression of S100A4 has been observed in chronic inflammatory and autoimmune diseases, such as idiopathic inflammatory myopathies. The majority of studies of S100A4 are focused on cancer research; however, the oncogenic roles of S100A4 in epithelial ovarian cancer (EOC) remain largely unexplored. In this study, S100A4 expression is significantly up-regulated in ovarian cancer and associated with the clinical stage of EOC patients. Attenuation of S100A4 expression results in decreased cell mobility and metastatic capacity, whereas overexpression of S100A4 enhanced the invasive ability of EOC cells. Then by an integrated informatics analysis and luciferase reporter assay, we identify that miR-296 is a critical upstream regulator of S100A4. In addition, deregulated miR-296/S100A4 axis facilitates epithelial-mesenchymal transition (EMT) process as demonstrated by altered expression of EMT-related markers. In conclusion, our study reveals that deregulated miR-296/S100A4 promotes tumor progression in EOC, and provides evidence that miR-296/S100A4 axis-related signaling may represent a potential target for EOC therapy. PMID:27186401

  14. Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice.

    PubMed

    Sakurai, Noritaka; Suzuki, Kazuyuki; Nagaoka, Tetsuya; Saito, Teruyoshi; Yoshimura, Hisashi; Yano, Tomohiro; Sadzuka, Yasuyuki; Asano, Ryuji

    2008-01-01

    The present study was designed to confirm whether the Bowman-Birk inhibitor (BBI) induces an increase in p27 accumulation without S phase kinase-associated protein 2 (skp2) degradation by means of the expression of connexin (Cx) 43 as a gap junctional intercellular communication (GJIC)-dependent pathway in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x105 cells/animal) were subcutaneously transplanted onto the backs of BDF1 mice receiving 10, 20 or 40 mg/kg of purified BBI intraperitoneally. Relative tumor weight (p<0.01, r=0.503) was negatively correlated with the dose of BBI. In contrast, the relative density of Cx43 mRNA (p<0.01, r=0.570) and Cx43 (p<0.01, r=0.718) was positively correlated with the dose of BBI, as were p21 (p<0.01, r=0.633), p27 (p<0.01, r=0.561) and skp2 (p<0.01, r=0.733). We therefore suggest that the anti-carcinogenic effects of BBI induce negative growth control by means of an increase in p27 accumulation caused by the expression of Cx43 as a GJIC pathway. PMID:21479471

  15. Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer

    PubMed Central

    Wei, Na; Liu, Stephanie S; Leung, Thomas HY; Tam, Kar F; Liao, Xiao Y; Cheung, Annie NY; Chan, Karen KL; Ngan, Hextan YS

    2009-01-01

    Background Programmed cell death 4 (Pdcd4) is a novel tumour suppressor and originally identified as a neoplastic transformation inhibitor. The aim of this study was to investigate the expression, prognostic significance and potential function of Pdcd4 in ovarian cancer. Results The expression of Pdcd4 was examined in 30 normal ovarian tissues, 16 borderline and 93 malignant ovarian tissues. A continuous down regulation of Pdcd4 expression in the sequence of normal, borderline and malignant tissues was observed. The expressions of Pdcd4 in both ovarian borderline tissues and carcinomas were significantly lower than the expression in normal ovarian tissues (p < 0.001). Furthermore, patients with lower Pdcd4 expressions were found to have shorter disease-free survival (p = 0.037). The expression of Pdcd4 was also assessed by immunohistochemical analysis in 13 ovarian normal tissues and 44 carcinomas. Different subcellular localization of Pdcd4 was observed in normal compared to malignant cells. Predominant nuclear localization of Pdcd4 was found in normal ovarian tissues while ovarian carcinomas showed mainly cytoplasmic localization of Pdcd4. Conclusion Our study demonstrated that the loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients. PMID:19728867

  16. High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time.

    PubMed

    He, Yi-feng; Zhang, Mei-ying; Wu, Xin; Sun, Xiang-jun; Xu, Ting; He, Qi-zhi; Di, Wen

    2013-01-01

    Mucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells. Previous in vitro studies have indicated that MUC2 promotes cancer growth and metastasis through a tumor-associated macrophage (TAM)-dependent mechanism. However, this mechanism has never been linked to clinical oncology, and its prognostic significance needed to be clarified. Here, we collected 102 consecutive ovarian cancer specimens and used the multiple immuno-histo-chemical/-fluorescent technique to determine the correlations between the MUC2 expression status, the ratio of M1/M2 TAMs and the densities of cyclooxygenase-2 (COX-2)(+) TAMs and COX-2(+) cancer cells. The Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to evaluate the prognostic influences of these parameters. As a result, we found that the MUC2 overexpression (immunostaining ++/+++) was significantly correlated with a reduced ratio of M1/M2 TAMs (p<0.001), an increased density of COX-2(+) TAMs (p<0.001) and an increased density of COX-2(+) cancer cells (p=0.017). Moreover, most of the M2 TAMs (93%-100%) and COX-2(+) TAMs (63%-89%) overlapped; and the COX-2(+) cancer cells were frequently observed near the COX-2(+) TAMs. In the Cox regression analysis, MUC2 overexpression was found to be an independent prognostic factor for ovarian cancer patients, of which the hazard ratio (HR) was 2.354 (95% confidence interval (CI): 1.031-10.707, p=0.005). Also, the reduced ratio of M1/M2 TAMs and the increased densities of COX-2(+) TAMs and COX-2(+) cancer cells were demonstrated to be the predictors of poor prognosis, among which the reduced M1/M2 ratio possessed the highest HR (1.767, 95% CI: 1.061-6.957, p=0.019). All these findings revealed that MUC2 can concurrently exert M2-polarizing and COX-2-inducing effects on TAMs, by which it causes an imbalanced TAM M1-/M2-polarization pattern and induces local PGE2 synthesis (in both TAMs and cancer cells). The positive feedback between local PGE2

  17. Ovarian involvement of a desmoplastic small round cell tumor of unknown primary origin with lymph node and lung metastases: A case report

    PubMed Central

    XIE, YU-PING; SHEN, YANG-MEI

    2016-01-01

    Desmoplastic small round cell tumors (DSRCTs) were initially characterized as exhibiting divergent differentiation and were extremely aggressive, belonging to the family of ‘small round blue cell tumors’. Due to a male predominance, to date, only 15 cases in women have been reported in the English literature. The present study describes a case of DSRCT in a young woman who initially presented with ovarian masses accompanied with lymph node and lung metastases. A correct diagnosis was reached by combining the hematoxylin and eosin, and immunohistochemical staining results. Following surgery, the patient underwent the chemotherapy and, 3 months later, is in a good condition. The study also provides an overview of this uncommon disease. PMID:26893704

  18. High preoperative blood levels of HE4 predicts poor prognosis in patients with ovarian cancer

    PubMed Central

    2012-01-01

    Abstract The aim of this study was to assess the clinical value of preoperative blood levels of HE4 as a predictor of overall survival in patients with ovarian cancer and to validate previous data of HE4 and the ROMA algorithm including HE4 and CA125 in discriminating benign and malignant ovarian tumors. Experimental design The preoperative plasma levels of HE4 and CA125 were analyzed with ELISA in 312 patients with adnexal lesions. Tumors were classified as benign (n= 206), borderline (i.e. low malignant potential tumors) (n= 25), and well (n= 14), moderately (n= 15), and poorly (n= 51) differentiated malignant. Results In univariate Cox regression analyses high levels (dichotomized at the median) of HE4, CA125, increased age (continuous variable), advanced-stage of disease 2–4, histological grade 3 and non-optimal tumor debulking at primary surgery were all significantly associated with shorter overall survival. A multivariate Cox regression model including pre-operative available covariates HE4 and CA125 both dichotomized at median in addition to age as continuous variable showed that high levels of HE4 was an independent prognostic marker for worse prognosis HR 2.02 (95% CI 1.1-3.8). In postmenopausal women the ROMA algorithm gave the highest AUC of 0.94 (95% CI, 0.90-0.97) which was higher than the separate markers HE4 AUC 0.91 (95% CI 0.86-0.95) and CA125 AUC 0.91(95% CI 0.87-0.96). Conclusions High concentration of plasma HE4 is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The algorithm ROMA discriminates in postmenopausal women between malignant and benign tumors with an AUC of 0.94. PMID:22909379

  19. GATA-4 and FOG-2 Expression in Pediatric Ovarian Sex Cord-Stromal Tumors Replicates Embryonal Gonadal Phenotype: Results from the TREP Project

    PubMed Central

    Virgone, Calogero; Cecchetto, Giovanni; Ferrari, Andrea; Bisogno, Gianni; Donofrio, Vittoria; Boldrini, Renata; Collini, Paola; Dall’Igna, Patrizia; Alaggio, Rita

    2012-01-01

    Aim GATA proteins are a family of zinc finger transcription factors regulating gene expression, differentiation and proliferation in various tissues. The expression of GATA-4 and FOG-2, one of its modulators, was studied in pediatric Sex Cord-Stromal tumors of the ovary, in order to evaluate their potential role as diagnostic markers and prognostic factors. Materials and Methods Clinical and histological data of 15 patients, enrolled into the TREP Project since 2000 were evaluated. When available, immunostaines for FOG-2, GATA-4, α-Inhibin, Vimentin and Pancytokeratin were also analyzed. Results In our series there were 6 Juvenile Granulosa Cell Tumors (JGCT), 6 Sertoli-Leydig Cell Tumors (SLCT), 1 Cellular Fibroma, 1 Theca Cell Tumor and 1 Stromal Sclerosing Tumor (SST). Thirteen patients obtained a complete remission (CR), 1 reached a second CR after the removal of a metachronous tumor and 1 died of disease. Inhibin was detectable in 11/15, Vimentin in 13/15, Pancytokeratin in 6/15, GATA-4 in 5/13 and FOG-2 in 11/15. FOG-2 was highly expressed in 5/6 JGCT, while GATA-4 was weakly detectable only in 1 of the cases. SLCT expressed diffusely FOG-2 (4/6) and GATA-4 (3/5). GATA-4 and FOG-2 were detected in fibroma and thecoma but not in the SST. Conclusions Pediatric granulosa tumors appear to express a FOG-2/GATA-4 phenotype in keeping with primordial ovarian follicles. High expression of GATA-4 does not correlate with aggressive behaviour as seen in adults, but it is probably involved in cell proliferation its absence can be associated with the better outcome of JGCT. SLCTs replicate the phenotype of Sertoli cells during embryogenesis in normal testis. In this group, the lack of expression of FOG-2 in tumors in advanced stages might reveal a hypothetical role in inhibiting GATA-4 cell proliferation pathway. In fibroma/thecoma group GATA-4 and FOG-2 point out the abnormal activation of GATA pathway and might be involved in the onset of these tumors. PMID:23029311

  20. 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

  1. The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27.

    PubMed

    d'Almeida, Sènan M; Kauffenstein, Gilles; Roy, Charlotte; Basset, Laetitia; Papargyris, Loukas; Henrion, Daniel; Catros, Véronique; Ifrah, Norbert; Descamps, Philippe; Croue, Anne; Jeannin, Pascale; Grégoire, Marc; Delneste, Yves; Tabiasco, Julie

    2016-07-01

    Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages. PMID:27622030

  2. Ovarian cavernous hemangioma.

    PubMed

    Alvarez, M; Cerezo, L

    1986-01-01

    Vascular tumors of the female genital tract are rare, especially those of the ovary. Most cases are small lesions that are discovered incidentally. We describe a 68-year-old woman with a benign hemangioma that presented clinically as a very large ovarian mass. PMID:3753575

  3. Ovarian Cysts

    MedlinePlus

    ... new cysts. A health problem that may involve ovarian cysts is polycystic ovary syndrome (PCOS). Women with ... male hormones, irregular or no periods and small ovarian cysts. Dept. of Health and Human Services Office ...

  4. Ovarian cancer

    MedlinePlus

    Cancer - ovaries ... Ovarian cancer is the fifth most common cancer among women. It causes more deaths than any other type of female reproductive organ cancer. The cause of ovarian cancer is unknown. Risk ...

  5. Ovarian cancer

    MedlinePlus

    ... of ovarian cancer Already been diagnosed with ovarian cancer to determine how well treatment is working Other tests that may be done include: Complete blood count and blood chemistry Pregnancy test (serum HCG) CT or MRI of ...

  6. 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

  7. Ovulation and extra-ovarian origin of ovarian cancer.

    PubMed

    Yang-Hartwich, Yang; Gurrea-Soteras, Marta; Sumi, Natalia; Joo, Won Duk; Holmberg, Jennie C; Craveiro, Vinicius; Alvero, Ayesha B; Mor, Gil

    2014-01-01

    The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies. PMID:25135607

  8. 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 ...

  9. 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

  10. 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.

  11. A calicheamicin conjugate with a fully humanized anti-MUC1 antibody shows potent antitumor effects in breast and ovarian tumor xenografts.

    PubMed

    Hamann, Philip R; Hinman, Lois M; Beyer, Carl F; Lindh, Delores; Upeslacis, Janis; Shochat, Dan; Mountain, Andrew

    2005-01-01

    Murine CTM01 is an internalizing murine IgG(1) monoclonal antibody that recognizes the MUC1 antigen expressed on many solid tumors of epithelial origin. Calicheamicin conjugates of this antibody have previously been shown to be potent, selective antitumor agents in preclinical models. A conjugate has now been made with a genetically engineered human version of this antibody, hCTM01. The hCTM01 is an IgG(4) isotype, has an immunoaffinity approximately 30% higher than mCTM01 by competitive RIA, and is efficiently internalized into target cells. The hCTM01-NAc-gamma calicheamicin DM amide conjugate, referred to as CMB-401, shows targeted killing of MUC1-expressing cells in vitro and produces pronounced dose-related antitumor effects over an 8-fold dose range against a MUC1-expressing, ovarian xenograft tumor, OvCar-3. The specificity of CMB-401 was confirmed by comparing its antitumor effects with those of an isotype-matched nonspecific conjugate against the MX-1 breast carcinoma. CMB-401, given either ip or iv, was highly active in these models in single and multiple dose regimens and gave complete regressions at the highest doses examined with good overall therapeutic ratios. CMB-401 also gave good antitumor effects at similar doses with a cisplatin-resistant MUC1-expressing cell line. PMID:15769089

  12. Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers

    PubMed Central

    De Vlieghere, Elly; Carlier, Charlotte; Ceelen, Wim; Bracke, Marc; De Wever, Olivier

    2016-01-01

    This data paper contains information about the in vivo model for peritoneal implants used in the paper “Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells” (De Vlieghere et al., 2015) [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included. PMID:26904717

  13. Data on in vivo selection of SK-OV-3 Luc ovarian cancer cells and intraperitoneal tumor formation with low inoculation numbers.

    PubMed

    De Vlieghere, Elly; Carlier, Charlotte; Ceelen, Wim; Bracke, Marc; De Wever, Olivier

    2016-03-01

    This data paper contains information about the in vivo model for peritoneal implants used in the paper "Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells" (De Vlieghere et al., 2015) [1]. A double in vivo selection of SK-OV-3 Luc human ovarian cancer cell line was used to create SK-OV-3 Luc IP1 and SK-OV-3 Luc IP2 cell lines. This data paper shows functional activities of the three cell lines in vitro and in vivo. Phase-contrast images show the morphology of these cells, metabolic and luciferase activity has been determined. Survival data of mice peritoneally injected with SK-OV-3 Luc or SK-OV-3 Luc IP2 is available with H&E histology of the peritoneal implants. Tumor growth curves and bioluminescent images of mice inoculated with a different number of SK-OV-3 Luc IP2 cells are also included. PMID:26904717

  14. Treatment histories of borderline inpatients.

    PubMed

    Zanarini, M C; Frankenburg, F R; Khera, G S; Bleichmar, J

    2001-01-01

    In this study, we describe the types and amounts of psychiatric treatment received by a well-defined sample of borderline personality disorder (BPD) inpatients, and compare these parameters with those of a group of carefully diagnosed personality-disordered controls. Finally, we assess the risk factors associated with a history of intensive, high-cost treatment, which we defined as having had two or more prior psychiatric hospitalizations. The treatment histories of 290 borderline inpatients and 72 axis II controls were assessed using a reliable semistructured interview. All nine forms of treatment studied except electroconvulsive therapy (ECT) were common among borderline patients (36% to 96%). In addition, a significantly higher percentage of borderline patients than axis II controls reported a history of individual and group therapy, day and residential treatment, psychiatric hospitalization, participating in self-help groups, and taking standing medications. They were also significantly younger when they first entered individual therapy and began to take standing medications. In addition, borderline patients spent more time than axis II controls in individual therapy and psychiatric hospitals, and were on standing medications for a significantly longer period of time. They also reported a significantly higher number of psychiatric hospitalizations, lifetime number of standing medications, and number of psychotropic medications taken at the same time. In addition, we found a highly significant multivariate predictive model for multiple prior hospitalizations. The six significant predictors were age 26 or older, a history of quasi psychotic thought, lifetime number of self-mutilative efforts and suicide attempts, a childhood history of reported sexual abuse, and an adult history of being physically and/or sexually assaulted. Taken together, these results confirm clinical impressions concerning the high rates of mental health services used by borderline patients

  15. Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-08-03

    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

  16. Ovarian tissue characterization in ultrasound: a review.

    PubMed

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

    2015-06-01

    Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given. PMID:25230716

  17. 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

  18. 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 Central

    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.

    2013-01-01

    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. PMID:24005572

  19. 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. PMID:24005572

  20. 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.

  1. Surveillance After Initial Surgery for Pediatric and Adolescent Girls With Stage I Ovarian Germ Cell Tumors: Report From the Children's Oncology Group

    PubMed Central

    Billmire, Deborah F.; Cullen, John W.; Rescorla, Frederick J.; Davis, Mary; Schlatter, Marc G.; Olson, Thomas A.; Malogolowkin, Marcio H.; Pashankar, Farzana; Villaluna, Doojduen; Krailo, Mark; Egler, Rachel A.; Rodriguez-Galindo, Carlos; Frazier, A. Lindsay

    2014-01-01

    Purpose To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. Patients and Methods Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m2 on days 1 to 3, etoposide 167 mg/m2 on days 1 to 3, bleomycin 15 U/m2 on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. Results Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). Conclusion Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults. PMID:24395845

  2. CXCL12 expression by healthy and malignant ovarian epithelial cells

    PubMed Central

    2011-01-01

    Background CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value. Methods Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves. Results Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribut