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Sample records for malignant potential ovarian

  1. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  2. A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA, and risk malignancy index (RMI for the classification of ovarian masses

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    Cristina Anton

    2012-01-01

    Full Text Available OBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4 as well as the risk ovarian malignancy algorithm (ROMA and risk malignancy index (RMI values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128 were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal, and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.

  3. Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.

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    Liying Gu

    Full Text Available The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF-like weak inducer of apoptosis (TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14 in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC, we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%. Similarly, 35 out of 41 (85.37% malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α, whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1 production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.

  4. MR imaging of malignant ovarian tumors

    International Nuclear Information System (INIS)

    Kim, Jun Ho; Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Choi, Ho Sun

    1994-01-01

    To evaluate MRI findings of malignant ovarian tumors. MRI findings were retrospectively reviewed in 25 patients with surgically confirmed 30 malignant ovarian tumors(common epithelial tumor; 23, sex cord stromal tumor; 2, endo dermal sinus tumor; 1, metastatic tumor; 4). The findings evaluated were the lesion size, solid and/or cystic component, wall thickness, septal thickness, necrosis, invasion of adjacent organ, ascites, and adenopathy. MRI findings of the malignant ovarian tumors were as follow: Size of lesion was 5-35cm(mean 14cm); solid component was present in 80%(24/30); wall thickness was more than 3mm in 90%(27/30); septal thickness was more than 3mm in 70%(21/30); tumor necrosis was present in 40%(12/30%); invasion of adjacent organ was present in 76%(19/25); ascites was present in 56%(14/25); lymphadenopathy was present in 24% (6/25). MRI findings of absence of solid component(6/6), even wall and septal thickness(7/7, 19/19) were found only in epithelial tumors. Uneven septal thickness more than 3mm(7/11) was a predominant MRI findings of non-epithelial tumors. Well-defined cystic lesion within solid component was seen in Krukenberg tumors. Evaluation of the lesion size, internal architecture, invasion of adjacent organ, ascites, and lymphadenopathy in MRI would enable diagnosis of malignant ovarian tumors and could lead to possible differential diagnosis of epithelial tumors from non-epithelial tumors

  5. [Modern kind of treatment for ovarian tumors with low malignant potential/summarized our and foreign experience].

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    Ivanov, S

    2011-01-01

    Our aim was to assess the ovarian tumors with low malignant potential. We tried to summarize our and foreign experience for 10 years period (2000-2011) in this field. The method of choice is the surgical treatment with total cytoreduction if possible. Appendectomy is performed for the serous pathological types of ovarian tumors. In the early stages we try to spare the reproductive functions of the patients. In the advanced stages hysterectomy with BSO, omentecromy and appendectomy is performed. Systematic pelvic and paraaortal lymph node dissection is not recommended. Resection only of the suspected lymph nodes is performed. The chemotherapy has no prognostic significance.

  6. Lack of HPV in Benign and Malignant Epithelial Ovarian Tumors in Iran

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    Farzaneh, Farah; Nadji, Seyed Alireza; Khosravi, Donya; Hosseini, Maryam Sadat; Hashemi Bahremani, Mohammad; Chehrazi, Mohammad; Bagheri, Ghazal; Sigaroodi, Afsaneh; Haghighatian, Zahra

    2017-05-01

    Background: Ovarian epithelial tumors one of the most common gynecological neoplasms; we here evaluated the presence of HPV in benign and malignant examples. Methods: In this cross-sectional study the records of 105 patients with epithelial ovarian tumors (benign and malignant) referred to Imam Hossein University Hospital from 2012 to 2015 were evaluated along with assessment of the presence of the HPV infection using PCR. Results: Among 105 patients, comprising 26 (24.8%) with malignant and 79 (75.2%) with benign lesions, the factors found to impact on malignancy were age at diagnosis, age at first pregnancy, number of pregnancies and hormonal status. However, malignancies was not related to abortion, late menopause, and early menarche. In none of the ovarian tissues (benign and malignant) was HPV DNA found. Conclusion: In this study HPV DNA could not be found in any epithelial ovarian tumors (benign and malignant) removed from 105 women; more studies with larger sample size are needed for a definite conclusion. Creative Commons Attribution License

  7. Risk of malignancy index in the preoperative evaluation of patients with ovarian masses

    International Nuclear Information System (INIS)

    Jabeen, R.; Khan, S.A.; Naveed, S.

    2015-01-01

    Objective: To evaluate the ability of RMI in preoperative discrimination of benign from malignant ovarian mass among women presenting at Nishtar Hospital Multan Pakistan. Methodology: It was a prospective study conducted at department of obstetrics/gynae Nishtar Hospital Multan between September 2008 to August 2009. 60 patients of more than 30 years of age admitted in gynaecology department for surgical exploration of ovarian mass were included. All the women in whom ovarian malignancy had already been diagnosed and admitted for second laparotomy were excluded. Results: The median age at presentation of ovarian malignancy is 56 years. The sensitivity of RMI in our group was 82.3%,the specificity was 88.3%, positive predictive value was 73.7% and the negative predictive value was 92.6%. Receiver operating curves reveal that RMI was a better diagnostic marker than CA-125 or ultrasound score alone for the prediction of malignancy in ovarian masses. Conclusion: The risk of malignancy index has high specificity and sensitivity. It yielded a better diagnostic performance as compared to CA-125 or ultrasound score alone in differentiating benign from malignant ovarian lesions. (author)

  8. Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours.

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    Garg, Sugandha; Kaur, Amarjit; Mohi, Jaswinder Kaur; Sibia, Preet Kanwal; Kaur, Navkiran

    2017-08-01

    IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use.

  9. The value of contrast-enhanced 64-row CT in differentiating benign from malignant serous ovarian neoplasms

    International Nuclear Information System (INIS)

    Dong Tianfa; Wu Meixian; Zhang Jiayun; Song Ting

    2009-01-01

    Objective: To assess the diagnostic value of contrast-enhanced 64-row CT scanning in deciding benign or malignant serous ovarian tumors. Methods: Fifty-eight cases of serous ovarian tumors proved pathologically were reviewed, including 25 malignant tumors, 25 benign, 8 borderline tumors. All patients underwent 64-row CT scanning, including plain scanning and contrast-enhance scanning. The tumors' shape, density, blood supply and enhancement features were evaluated. Results: Twenty-five cases of benign serous cystic adenoma were mostly unicameral, and showed a moderate mural enhancement only in 4 cases (16%) due to chronic pelvic infection and the others (21/25, 84%) had no of slight enhancement. Malignant tumors were cystic-solid mass with unclear margin, irregular shape and septa. Twenty-two cases of serous cystadenocarcinoma out of 25 cases (88%) appeared obvious enhancement and other 3 cases no enhancement. And 7 cases out of 8 (87.5%) borderlined serous cystadenomas showed different enhancement patterns. Conclusion: Benign ovarian serous neoplasms were mostly unicameral and no strong mural enhancement, suggesting a lack of blood supply. While, there were obvious enhancement in the ovarian serous cystadenocarcinoma and borderline serous cystadenoma with malignant potential. The 64-row CT is helpful for differentiating the nature of the serous ovarian neoplasm. (authors)

  10. Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours

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    Kaur, Amarjit; Mohi, Jaswinder Kaur; Sibia, Preet Kanwal; Kaur, Navkiran

    2017-01-01

    Introduction IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. Aim To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. Materials and Methods A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. Results Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. Conclusion IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use. PMID:28969237

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

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    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

  12. Circulating Microparticles in Patients with Benign and Malignant Ovarian Tumors

    NARCIS (Netherlands)

    Rank, A.; Liebhardt, S.; Zwirner, J.; Burges, A.; Nieuwland, R.; Toth, B.

    2012-01-01

    Background: Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Patients and Methods: Microparticles from platelets/megakaryocytes, activated platelets and endothelial

  13. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques

    2013-01-01

    Ovarian tissue cryopreservation and transplantation is a real option to preserve and restore fertility in young cancer patients. However, there is a concern regarding the possible presence of malignant cells in the ovarian tissue, which could lead to recurrence of the primary disease after reimpl...

  14. Value of 18F-FDG PET/CT in the detection of ovarian malignancy

    International Nuclear Information System (INIS)

    Park, Tae Gyu; Lee, Si Nae; Park, So Yeon

    2015-01-01

    Ovarian cancer is a leading cause of gynecologic malignancy. As symptoms of ovarian cancer are nonspecific, only 20 % of ovarian cancers are diagnosed while they are still limited to the ovaries. Thus, early and accurate detection of disease is important for an improved prognosis. For the accurate and effective diagnosis of ovarian malignancy on 18 F-fluorodeoxyglucose ( 18 F--FDG) positron emission tomography/computed tomography (PET/CT), we analyzed several parameters, including visual assessment. A total of 51 peritoneal lesions in 19 patients who showed ovarian masses with diffuse peritoneal infiltration were enrolled. Twelve patients were confirmed to have ovarian malignancy and seven patients with benign disease by pathologic examination. All patients were examined by 18 F--FDG PET/CT, and an additional 2-h delayed 18 F--FDG PET/CT was also performed for 15 patients with 42 peritoneal lesions. We measured semiquantitative parameters including maximum and mean standardized uptake values (SUV max , SUV mean ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on a 1-h initial 18 F--FDG PET/CT image (Parameter1) and on a 2-h delayed image (Parameter2). Additionally, retention indices of each parameter were calculated, and each parameter among the malignant and benign lesions was compared by Mann-Whitney U test. We also assessed the visual characteristics of each peritoneal lesion, including metabolic extent, intensity, shape, heterogeneity, and total visual score. Associations between visual grades and malignancy were analyzed using linear by linear association methods. Moreover, a receiver operating characteristic (ROC) curve was analyzed to compare the effectiveness of significant parameters. In a comparison between the malignant and benign groups in the analysis of 51 total peritoneal lesions, SUV max1 , SUV mean1 , and TLG1 showed significant differences. Also, in the analysis of 42 peritoneal lesions that underwent an additional 2-h 18 F

  15. Reliability of IOTA score and ADNEX model in the screening of ovarian malignancy in postmenopausal women.

    Science.gov (United States)

    Nohuz, Erdogan; De Simone, Luisa; Chêne, Gautier

    2018-04-28

    The IOTA (International Ovarian Tumor Analysis) group has developed the ADNEX (Assessment of Different NEoplasias in the adneXa) model to predict the risk that an ovarian mass is benign, borderline or malignant. This study aimed to test reliability of these risks prediction models to improve the performance of pelvic ultrasound and discriminate between benign and malignant cysts. Postmenopausal women with an adnexal mass (including ovarian, para-ovarian and tubal) and who underwent a standardized ultrasound examination before surgery were included. Prospectively and retrospectively collected data and ultrasound appearances of the tumors were described using the terms and definitions of the IOTA group and tested in accordance with the ADNEX model and were compared to the final histological diagnosis. Of the 107 menopausal patients recruited between 2011 and 2016, 14 were excluded (incomplete inclusion criteria). Thus, 93 patients constituted a cohort in whom 89 had benign cysts (83 ovarian and 6 tubal or para-ovarian cysts), 1 had border line tumor and 3 had invasive ovarian cancers (1 at first stage, 1 at advanced stage and 1 metastatic tumor in the ovary). The overall prevalence of malignancy was 4.3%. Every benign ovarian cyst was classified as probably benign by IOTA score which showed also a high specificity with the totality of probably malignant lesion proved malignant by histological exam. The limit of this score was the important rate of not classified or undetermined cysts. However, the malignancy risks calculated by ADNEX model allowed identifying the totality of malignancy. Thus, the combination of the two methods of analysis showed a sensitivity and specificity rates of respectively 100% and 98%. Evaluation of malignancy risks by these 2 tests highlighted a negative predictive value of 100% (there was no case of false negative) and a positive predictive value of 80%. On the basis of our findings, the IOTA classification and the ADNEX multimodal

  16. Diagnosis and surgical management of malignant ovarian teratoma in a green iguana (Iguana iguana).

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    Bel, Lucia; Tecilla, Marco; Borza, Gabriel; Pestean, Cosmin; Purdoiu, Robert; Ober, Ciprian; Oana, Liviu; Taulescu, Marian

    2016-07-19

    Ovarian tumors in reptiles are uncommonly reported in the literature and for green iguanas previously reported cases include teratomas, one adenocarcinoma and one papillary cystadenocarcinoma. The present report is the first of a malignant ovarian teratoma in a green iguana. Complete and detailed pathological features, differential diagnosis and surgical management of malignant ovarian teratoma are discussed in this paper. A 9-year-old intact female green iguana (Iguana iguana) with a clinical history of persistent anorexia and progressive abdominal distension was referred to the surgery department. On physical examination, a presumptive diagnosis of follicular stasis was established. Radiographic evaluation showed a large radioopaque mass within the abdomen, which was visible both in latero-lateral and ventro-dorsal exposures. Abdominal ultrasonography showed a large intra-abdominal mass, with numerous cyst-like structures filled with liquid and a heterogeneous aspect with hypoechoic areas. Exploratory laparatomy was thus suggested and the mass was removed surgically. The histologic findings of the neoplasm were consistent with those of ovarian malignant teratoma. Surgical excision of the mass in our case was considered curative and after a follow-up period of 6 months the animal has recovered completely. A malignant ovarian teratoma has not been previously reported in green iguana and should be included in the list of differential diagnosis of ovarian tumors in this species. This report will contribute to a better understanding of the pathology of this rare tumor in green iguanas.

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Radiologic findings of malignant tumors arising from ovarian endometriosis

    International Nuclear Information System (INIS)

    Lee, Eun Ju; Joo, Hee Jae; Kim, Bo Hyun

    1999-01-01

    To determine the radiologic characteristics of malignant tumors arising from ovarian endometriosis. The radiologic findings of eleven patients with pelvic masses histologically confirmed as malignant ovarian tumors arising from endometriosis were retrospectively reviewed. All patients underwent MR, and six underwent ultrasonography. The findings were evaluated with regard to tumor size and shape, locularity, thickness and enhancement of the wall and septa, the presence of papillary nodule or solid portion, signal intensity of the locule, the presence of mass in contralateral ovary, ascites, local invasion, distant metastases, and the Pathologic diagnosis included clear cell carcinoma in six cases, endometrioid carcinoma in three, and mucinous cystadenocarcinoma of borderline malignancy and endometrial stromal sarcoma in one case each. Tumor size ranged from 8 to 20 (mean, 12.7)cm. The tumors were mixed in four cases, entirely cystic in three, predominantly cystic in three, and predominantly solid in one. Six cases were unilocular and five were multilocular. The wall and septa varied in thickness and regularity and were well enhanced in all but one case. In all cases papillary nodules or solid portions with similar enhancement to uterine myometrium were seen. On T1WI, the signal intensity of fluid was seen to be high in eight cases, low or intermediate in two, and of differing intensity in one. Ten cases showed high signal intensity on T2WI, whereas in one case in which high signal intensity was seen on T1WI, there was low signal intensity(shading). In three cases the contralateral ovary contained an endometrioma. Other features included ascites in seven cases and peritoneal seeding in one. Malignant ovarian tumors arising from endometriosis showed radiologic features of malignancy:they were larger than 10cm, there was enhancement of the wall and septa, and a papillary nodule or solid portion was present. However, the presence of hyperintense fluid, as seen on T1WI

  19. Radiologic findings of malignant tumors arising from ovarian endometriosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Joo, Hee Jae [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Kim, Bo Hyun [SungkyunKwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-11-01

    To determine the radiologic characteristics of malignant tumors arising from ovarian endometriosis. The radiologic findings of eleven patients with pelvic masses histologically confirmed as malignant ovarian tumors arising from endometriosis were retrospectively reviewed. All patients underwent MR, and six underwent ultrasonography. The findings were evaluated with regard to tumor size and shape, locularity, thickness and enhancement of the wall and septa, the presence of papillary nodule or solid portion, signal intensity of the locule, the presence of mass in contralateral ovary, ascites, local invasion, distant metastases, and the Pathologic diagnosis included clear cell carcinoma in six cases, endometrioid carcinoma in three, and mucinous cystadenocarcinoma of borderline malignancy and endometrial stromal sarcoma in one case each. Tumor size ranged from 8 to 20 (mean, 12.7)cm. The tumors were mixed in four cases, entirely cystic in three, predominantly cystic in three, and predominantly solid in one. Six cases were unilocular and five were multilocular. The wall and septa varied in thickness and regularity and were well enhanced in all but one case. In all cases papillary nodules or solid portions with similar enhancement to uterine myometrium were seen. On T1WI, the signal intensity of fluid was seen to be high in eight cases, low or intermediate in two, and of differing intensity in one. Ten cases showed high signal intensity on T2WI, whereas in one case in which high signal intensity was seen on T1WI, there was low signal intensity(shading). In three cases the contralateral ovary contained an endometrioma. Other features included ascites in seven cases and peritoneal seeding in one. Malignant ovarian tumors arising from endometriosis showed radiologic features of malignancy:they were larger than 10cm, there was enhancement of the wall and septa, and a papillary nodule or solid portion was present. However, the presence of hyperintense fluid, as seen on T1WI

  20. Comparison of the Usefulness of four Risk-of-Malignancy Indices using Ultrasonography in Ovarian masses

    International Nuclear Information System (INIS)

    Jo, Moo Sung; Moon, Su Hyun; Joo, Jong Kil; Suh, Dong Soo; Kim, Ki Hyung; Yoon, Man Soo

    2010-01-01

    The aim of this study was to evaluate the usefulness of four Risk-of- Malignancy Indices (RMI) in women with ovarian masses. Between January 2007 and December 2008, 344 women who visited our hospital for surgical exploration due to an ovarian mass were enrolled in this study. Each RMI was based on the combination of menopausal status, ultrasound findings of ovarian masses, and absolute level of serum CA-125. A cutoff level of 200 was chosen as the threshold for determining between malignant and benign ovarian masses in RMI 1, RMI 2, and RMI 3. A cutoff level of 450 was chosen as the threshold in RMI 4. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. The combination of four malignancy indices is more accurate than menopausal status, ultrasound findings, and serum CA-125 alone, respectively for determining whether a mass is benign or malignant. RMI 1 and RMI 4 were found to be better than RMI 2 and RMI 3. RMI 4 was the most reliable test among them. The relationship between RMI 1 and RMI 4 was not statistically significant. With the cutoff level for RMI 4 at 450, the corresponding, sensitivity, specificity, positive predictive value, and negative predictive value were 72.1%, 88.0%, 56.4%, 93.9%, respectively. All four RMI were reliable tests for determining whether ovarian masses are malignant or benign, and RMI 4 was the most reliable index among them

  1. Value of {sup 18}F-FDG PET/CT in the detection of ovarian malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Gyu; Lee, Si Nae; Park, So Yeon [Dept. of Nuclear Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of); and others

    2015-03-15

    Ovarian cancer is a leading cause of gynecologic malignancy. As symptoms of ovarian cancer are nonspecific, only 20 % of ovarian cancers are diagnosed while they are still limited to the ovaries. Thus, early and accurate detection of disease is important for an improved prognosis. For the accurate and effective diagnosis of ovarian malignancy on {sup 18}F-fluorodeoxyglucose ({sup 18}F--FDG) positron emission tomography/computed tomography (PET/CT), we analyzed several parameters, including visual assessment. A total of 51 peritoneal lesions in 19 patients who showed ovarian masses with diffuse peritoneal infiltration were enrolled. Twelve patients were confirmed to have ovarian malignancy and seven patients with benign disease by pathologic examination. All patients were examined by {sup 18}F--FDG PET/CT, and an additional 2-h delayed {sup 18}F--FDG PET/CT was also performed for 15 patients with 42 peritoneal lesions. We measured semiquantitative parameters including maximum and mean standardized uptake values (SUV{sub max}, SUV{sub mean}), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on a 1-h initial {sup 18}F--FDG PET/CT image (Parameter1) and on a 2-h delayed image (Parameter2). Additionally, retention indices of each parameter were calculated, and each parameter among the malignant and benign lesions was compared by Mann-Whitney U test. We also assessed the visual characteristics of each peritoneal lesion, including metabolic extent, intensity, shape, heterogeneity, and total visual score. Associations between visual grades and malignancy were analyzed using linear by linear association methods. Moreover, a receiver operating characteristic (ROC) curve was analyzed to compare the effectiveness of significant parameters. In a comparison between the malignant and benign groups in the analysis of 51 total peritoneal lesions, SUV{sub max1}, SUV{sub mean1}, and TLG1 showed significant differences. Also, in the analysis of 42 peritoneal lesions

  2. [Methylation of selected tumor-supressor genes in benign and malignant ovarian tumors].

    Science.gov (United States)

    Cul'bová, M; Lasabová, Z; Stanclová, A; Tilandyová, P; Zúbor, P; Fiolka, R; Danko, J; Visnovský, J

    2011-09-01

    To evaluate the usefullness of examination of methylation status of selected tumor-supressor genes in early diagnosis of ovarian cancer. Prospective clinical study. Department of Gynecology and Obstetrics, Department of Molecular Biology, Jessenius Medical Faculty, Commenius University, Martin, Slovak Republic. In this study we analyzed hypermethylation of 5 genes RASSF1A, GSTP, E-cadherin, p16 and APC in ovarian tumor samples from 34 patients - 13 patients with epithelial ovarian cancer, 2 patients with border-line ovarian tumors, 12 patients with benign lesions of ovaries and 7 patients with healthy ovarian tissue. The methylation status of promoter region of tumor-supressor genes was determined by Methylation Specific Polymerase Chain Reaction (MSP) using a nested two-step approach with bisulfite modified DNA template and specific primers. Gene methylation analysis revealed hypermethylation of gene RASSF1A (46%) and GSTP (8%) only in malignant ovarian tissue samples. Ecad, p16 and APC genes were methylated both in maignant and benign tissue samples. Methylation positivity in observed genes was present independently to all clinical stages of ovarian cancer and to tumor grades. However, there was observed a trend of increased number and selective involvement of methylated genes with increasing disease stages. Furthermore, there was no association between positive methylation status and histological subtypes of ovarian carcinomas. RASSF1A and GSTP promoter methylation positivity is associated with ovarian cancer. The revealed gene-selective methylation positivity and the increased number of methylated genes with advancing disease stages could be considered as a useful molecular marker for early detection of ovarian cancer. However, there is need to find diagnostic approach of specifically and frequently methylated genes to determining a methylation phenotype for early detection of ovarian malignancies.

  3. Spectropolarimetry in the differential diagnosis of benign and malignant ovarian tumors

    Science.gov (United States)

    Peresunko, O. P.; Yermolenko, S. B.; Gruia, I.

    2018-01-01

    The aim of this study was to use the spectrophotometry method to develop a diagnostic algorithm for blood studies and the content of douglas deepening in women with ovarian tumors. A comparative analysis of the blood of healthy women and patients with ovarian cancer revealed significantly greater optical anisotropy of the latter. Qualitative studies of polarization microscopic blood images revealed a very developed microcrystalline structure. Based on the study of blood and puncture and douglas deepening of healthy women and patients with benign and malignant tumors of the ovaries, using the method of laser polarimetry, experimentally developed and clinically tested photometric and polarization criteria indicating the presence of malignancy of the tumor.

  4. Symptoms, CA125 and HE4 for the preoperative prediction of ovarian malignancy in Brazilian women with ovarian masses

    International Nuclear Information System (INIS)

    Pitta, Denise da Rocha; Sarian, Luis Otávio; Barreta, Amilcar; Campos, Elisabete Aparecida; Andrade, Liliana Lucci de Angelo; Fachini, Ana Maria Dias; Campbell, Leonardo Martins; Derchain, Sophie

    2013-01-01

    This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound. This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae. Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI. Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in

  5. Mutant epidermal growth factor receptor in benign, borderline, and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Olsen, Dorte Aalund

    2008-01-01

    . RESULTS: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level. CONCLUSIONS: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should...

  6. IOTA simple rules in differentiating between benign and malignant ovarian tumors.

    Science.gov (United States)

    Tantipalakorn, Charuwan; Wanapirak, Chanane; Khunamornpong, Surapan; Sukpan, Kornkanok; Tongsong, Theera

    2014-01-01

    To evaluate the diagnostic performance of IOTA simple rules in differentiating between benign and malignant ovarian tumors. A study of diagnostic performance was conducted on women scheduled for elective surgery due to ovarian masses between March 2007 and March 2012. All patients underwent ultrasound examination for IOTA simple rules within 24 hours of surgery. All examinations were performed by the authors, who had no any clinical information of the patients, to differentiate between benign and malignant adnexal masses using IOTA simple rules. Gold standard diagnosis was based on pathological or operative findings. A total of 398 adnexal masses, in 376 women, were available for analysis. Of them, the IOTA simple rules could be applied in 319 (80.1%) including 212 (66.5%) benign tumors and 107 (33.6%) malignant tumors. The simple rules yielded inconclusive results in 79 (19.9%) masses. In the 319 masses for which the IOTA simple rules could be applied, sensitivity was 82.9% and specificity 95.3%. The IOTA simple rules have high diagnostic performance in differentiating between benign and malignant adnexal masses. Nevertheless, inconclusive results are relatively common.

  7. A novel serum microRNA panel to discriminate benign from malignant ovarian disease.

    LENUS (Irish Health Repository)

    Langhe, Ream

    2015-01-28

    Ovarian cancer is the seventh most common cancer in women and the most frequent cause of gynaecological malignancy-related mortality in women. Currently, no standardized reliable screening test exists. MicroRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumours. The aim of this study was to determine if a microRNA signature could distinguish between malignant and benign ovarian disease. A training set of 5 serous ovarian carcinomas and 5 benign serous cystadenomas were selected for the initial experiments. The validation set included 20 serous ovarian carcinomas and 20 benign serous cystadenomas. The serum\\/plasma focus microRNA Exiqon panel was used for the training set. For the validation set a pick and mix Exiqon panel, which focuses on microRNAs of interest was used. A panel of 4 microRNAs (let-7i-5p, miR-122, miR-152-5p and miR-25-3p) was significantly down regulated in cancer patients. These microRNAs target WNT signalling, AKT\\/mTOR and TLR-4\\/MyD88, which have previously been found to play a role in ovarian carcinogenesis and chemoresistance. let-7i-5p, miR-122, miR-152-5p and miR-25-3p could act as diagnostic biomarkers in ovarian cancer.

  8. MR Imaging Findings of Ovarian Cystadenofibroma: Clues for Making the Differential Diagnosis from Ovarian Malignancy

    International Nuclear Information System (INIS)

    Byun, Jae Young

    2006-01-01

    Ovarian cystadenofibromas are uncommon epithelial ovarian tumors in which fibrous stroma is the dominant component of the neoplasm, in addition to the epithelial lining of the cystic tumor. These tumors are classified, according to the epithelial cell types, into the serous, endometrioid, mucinous, clear cell and mixed categories. Outwater et al. have reported that ovarian cystadenofibromas were multilocular cystic masses with a solid component and they had a specific MR signal intensity for the solid portion, which consisted of fibrous tissue that had very low signal intensity on the T2-weighted sequences. Takeuchi et al. reported that small or tiny cystic locules within the solid component are the characteristic findings of cystadenofibroma, corresponding to a black sponge-like appearance on T2-weignted image. Cho et al. found that about half of ovarian cystadenofibromas are purely cystic and the other half are complex cystic masses with one or more solid components on CT or MR imaging. The imaging findings of purely cystic ovarian cystadenofibromas were identical to those of ovarian cystadenomas on CT or MR imaging. Upon reviewing of the pathology of these tumors, they had small foci of fibrous stromas that were detected only on microscopic examination. The cystadenofibromas with a complex cystic nature demonstrated variable amounts of solid components in the cystic tumor on the CT or MR imaging. Familiarity with the above mentioned MR imaging features of ovarian cystadenofibromas may allow a specific diagnosis and help distinguish this benign tumor from malignant tumors, and this can be a big help during surgical planning to avoid inappropriate management or excessive surgical intervention

  9. Comparison of Effectiveness in Differentiating Benign from Malignant Ovarian Masses between IOTA Simple Rules and Subjective Sonographic Assessment.

    Science.gov (United States)

    Tongsong, Theera; Tinnangwattana, Dangcheewan; Vichak-Ururote, Linlada; Tontivuthikul, Paponrad; Charoenratana, Cholaros; Lerthiranwong, Thitikarn

    2016-01-01

    To compare diagnostic performance in differentiating benign from malignant ovarian masses between IOTA (the International Ovarian Tumor Analysis) simple rules and subjective sonographic assessment. Women scheduled for elective surgery because of ovarian masses were recruited into the study and underwent ultrasound examination within 24 hours of surgery to apply the IOTA simple rules by general gynecologists and to record video clips for subjective assessment by an experienced sonographer. The diagnostic performance of the IOTA rules and subjective assessment for differentiation between benign and malignant masses was compared. The gold standard diagnosis was pathological or operative findings. A total of 150 ovarian masses were covered, comprising 105 (70%) benign and 45 (30%) malignant. Of them, the IOTA simple rules could be applied in 119 (79.3%) and were inconclusive in 31 (20.7%) whereas subjective assessment could be applied in all cases (100%). The sensitivity and the specificity of the IOTA simple rules and subjective assessment were not significantly different, 82.9% vs 86.7% and 94.0% vs 94.3% respectively. The agreement of the two methods in prediction was high with a Kappa index of 0.835. Both techniques had a high diagnostic performance in differentiation between benign and malignant ovarian masses but the IOTA rules had a relatively high rate of inconclusive results. The IOTA rules can be used as an effective screening technique by general gynecologists but when the results are inconclusive they should consult experienced sonographers.

  10. Appendectomy in primary and secondary staging operations for ovarian malignancy.

    Science.gov (United States)

    Rose, P G; Reale, F R; Fisher, A; Hunter, R E

    1991-01-01

    Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures.

  11. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    Science.gov (United States)

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. The utility of multi-detector computed tomography in the diagnosis of malignant pleural effusion in the patients with ovarian cancer

    International Nuclear Information System (INIS)

    Kim, Kyung Won; Choi, Hyuck Jae; Kang, Sokbom; Park, Sang-Yoon; Jung, Dae Chul; Cho, Jeong Yeon; Cho, Kyung-Sik; Kim, Seung Hyup

    2010-01-01

    Purpose: The purpose of this study was to retrospectively assess possible clinical predictors of malignant pleural effusion in patients with ovarian cancer. Materials and methods: This review was performed on 38 ovarian cancer patients that showed pleural effusion in a CT scan and who underwent thoracocentesis before treatment. CT scans were obtained using a 4-channel multi-detector CT scanner. Fisher's exact test was used to determine the probability of malignant pleural effusion as a function of; amount of ascites, lymph node enlargement, amount of pleural effusion, pleural nodules, and pleural thickening. Results: Sixteen (42.1%) of the 38 patients had malignant pleural effusion and malignant pleural effusion amounts were greater than those with nonmalignant effusion. Pleural nodules were more frequently found in the malignant pleural effusion group (eight [50%] patients) than in the nonmalignant group (zero [0%] patient) (p < 0.001). Supradiaphragmatic lymph node enlargement (with short axis diameter 1 cm or more) was more frequent in malignant group (12 [75%] patients) than in the nonmalignant group (two [9.1%] patients) (p < 0.001). Conclusion: The probability of malignant pleural effusion in patients with ovarian cancer was found to be correlated with the amount of pleural effusion, the presence of pleural nodules, and supradiaphragmatic lymph node enlargement.

  13. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

    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 pr...

  14. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    Directory of Open Access Journals (Sweden)

    Laura Lehtinen

    Full Text Available Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

  15. Degenerated uterine leiomyomas mimicking malignant bilateral ovarian surface epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yi Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Chung, Soo Ho [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2017-07-15

    Uterine leiomyomas are the most common benign uterine neoplasms. Undegenerated uterine leiomyomas are easily recognizable by the typical imaging findings on radiologic studies. However, degenerated fibroids can have unusual and variable appearances. The atypical appearances due to degenerative changes may cause confusion in diagnosis of leiomyomas. In this article, we report a case of a patient with extensive cystic and myxoid degeneration of uterine leiomyoma, mimicking malignant bilateral ovarian surface epithelial tumors.

  16. Angioleiomyoma of uterus masquerading as malignant ovarian tumor

    Directory of Open Access Journals (Sweden)

    Sweta Singh

    2017-01-01

    Full Text Available Uterine angioleiomyoma is rare. A 40-year-old nulliparous woman presented with heavy menstrual bleeding (HMB for the past 2 years and mass per abdomen with severe dysmenorrhea for three cycles. She had received 8 units of packed cell transfusion outside. Clinical examination revealed a huge 32-week-sized abdominopelvic mass with irregular margins. Ultrasonography (USG of the abdomen and pelvis showed a large solid cystic mass on the right side of the abdomen with a well-defined hypoechoeic rounded lesion of size 5.7 cm × 5.0 cm, in the right lobe of the liver, with ovaries not being imaged separately. On color Doppler USG, there was moderate vascularity throughout. A provisional diagnosis of malignant ovarian tumor with hepatic metastasis was made. Her hemoglobin was 5.7 g/dl, and she had repeated episodes of HMB upon admission. She was transfused with 5 units of packed cells. Computed tomography (CT showed a large fundal subserosal uterine fibroid on the right side, with a solid ovarian tumor measuring 5.0 cm × 4.5 cm on the left side, with ascitis, right-sided hydronephrosis, and a well-defined hypoechoeic lesion in the right lobe of the liver, suggestive of hepatic hemangioma. Tumor markers were within normal limits. In view of discrepancy in clinical findings, ultrasound, and CT report, CT-guided biopsy of the huge mass was done which revealed leiomyoma, with no evidence of mitosis, pleomorphism, or malignancy. Laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy was done. Histopathology revealed an angioleiomyoma uterus. At 1-year follow-up, she was asymptomatic, and the liver mass was stable.

  17. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is

  18. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  19. Multicystic peritoneal mesothelioma after fertility-sparing surgery for an ovarian tumor of borderline malignancy: A case report

    Directory of Open Access Journals (Sweden)

    Hidetaka Nomura

    2015-02-01

    Full Text Available We report a case of a 19-year-old woman with multicystic peritoneal mesothelioma (MCPM who had previously undergone left adnexectomy due to an ovarian tumor of borderline malignancy at the age of 17 years. Follow-up imaging studies after adnexectomy revealed multiple cystic lesions of increasing size and number, suggesting recurrence of the tumor. Diagnostic laparoscopic surgery was performed, and the cystic lesion was pathologically determined to be MCPM. To our knowledge, this is the first report of MCPM diagnosed and successfully treated by laparoscopic surgery during the course of follow-up for an ovarian tumor. It is important to recognize that MCPM can occur in patients who have previously undergone abdominal surgery, and laparoscopic surgery is recommended for patients of reproductive age, because of the potential risk of infertility associated with extensive pelvic surgery.

  20. Bilateral Tubo Ovarian Abscess Mimics Ovarian Cancer on MRI and {sup 18F} FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Rakheja, Rajan; Hickeson, Marc [Royal Victoria Hospital, McGill Univ. Health Centre, Montreal (Canada); Makis, William [Brandon Regional Health Centre, Brandon (Canada)

    2011-09-15

    A 20 year old woman, who presented with a several week history of abdominal pain, was referred for magnetic resonance imaging (MRI) and {sup 18F} fluorodeoxy glucose (FDG) positron emission tomography (PET)/computed tomography (CT) after an ultrasound showed complex cystic masses arising from both ovaries. The MRI and {sup 18F} FDG PET/CT imaging characteristics of the ovarian masses were strongly suspicious for malignancy, and the masses were surgically removed. Histopathological evaluation revealed a bilateral tuboovarian abscess, with no evidence of malignancy. This case highlights a potentially serious pitfall in the evaluation of suspicious pelvic masses by {sup 18F} FDG PET/CT, Whereby a complex bilateral tuboovarian abscess may mimic the PET/CT imaging characteristics of an ovarian or pelvic malignancy.

  1. Ovarian metastasis of malignant melanoma: The first pediatric case

    Directory of Open Access Journals (Sweden)

    Yuko Araki

    2014-10-01

    Full Text Available We report a case of an 8-year-old girl with metastasis of malignant melanoma (MM to the ovary. She was initially diagnosed with cutaneous MM on the left buttock for which she underwent wide local excision, left inguinal/pelvic lymph node dissection, and subcutaneous injection of interferon beta. In spite of the treatment, she developed dissemination of MM to the liver, the bone, and the right ovary. All the lesions responded well to systemic chemotherapy (intravenous dacarbazine, except for the right ovarian tumor. She underwent an elective right salpingo-oophorectomy to avoid torsion or rupture of the tumor. However, she developed metastases to the contralateral ovary with peritoneal dissemination in 4 months. She received home palliative care and died at home 14 months after the last surgery. Ovarian metastasis of MM is a rare form of dissemination, and only 15 adult cases have ever been reported. Our patient is the first pediatric case. Since there is no standard of surgical indication for metastatic MM to the ovary, palliative resection can be an option for improving quality of life of a patient with this rare condition.

  2. Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Fredslund Andersen, Rikke

    2008-01-01

    , but this is not elucidated in detail in ovarian tissue. High tumor-to-normal-tissue concentration ratios would be favorable for molecular targeted anti-cancer treatment. The primary aim of the study was to analyze the potential differential protein content and gene expression of the four receptors in benign and malignant...

  3. Management of ovarian cysts

    DEFF Research Database (Denmark)

    Knudsen, Ulla Breth; Tabor, Ann; Mosgaard, Berit Jul

    2004-01-01

    BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts....... METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed....... The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal...

  4. Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

    NARCIS (Netherlands)

    Vermeij, R.; Daemen, T.; de Bock, G.H.; de Graeff, P.; Leffers, N.; Lambeck, A.; Ten Hoor, K.A.; Hollema, H.; van der Zee, A.G.J.; Nijman, H.W.

    2010-01-01

    The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a "universal" vaccine strategy. We determined the expression

  5. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

    International Nuclear Information System (INIS)

    Pal, Manish K.; Jaiswar, Shyam P.; Dwivedi, Vinaya N.; Tripathi, Amit K.; Dwivedi, Ashish; Sankhwar, Pushplata

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish miRNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers

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

    Science.gov (United States)

    2018-04-27

    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

  7. Preoperative serum levels of epidermal growth factor receptor, HER2, and vascular endothelial growth factor in malignant and benign ovarian tumors

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla

    2008-01-01

    , and malignant ovarian tumors. Patients and Methods: Serum from 233 patients (75 serous ovarian/tubal/peritoneal cancers, 24 borderline tumors, 110 benign ovarian tumors, and 24 with normal ovaries) were analyzed for EGFR, HER2, and VEGF using commercially available enzyme-linked immunosorbent assays (ELISA......). Results: The median EGFR serum level in patients with ovarian cancer was 51 ng/mL, and this was significantly lower than the median serum levels in borderline tumors (P =.0054) and benign ovarian tumors (P ovaries (P =.00028). The HER2 median serum level...... as in patients with normal ovaries (P =.00024). Conclusion: Significantly lower serum EGFR levels and higher VEGF levels were noted in patients with ovarian cancer compared with the levels in benign tumors and normal ovaries. Vascular endothelial growth factor and EGFR could have clinical importance as serum...

  8. Exosomes are fingerprints of originating cells: potential biomarkers for ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kobayashi M

    2015-03-01

    Full Text Available Miharu Kobayashi, Gregory E Rice, Jorge Tapia, Murray D Mitchell, Carlos Salomon Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Abstract: The past decade has seen an extraordinary explosion of research in the field of extracellular vesicles, especially in a specific type of extracellular vesicles originating from endosomal compartments, called exosomes. Exosomes are a specific subtype of secreted vesicles that are defined as small (~30–120 nm but very stable membrane vesicles that are released from a wide range of cells, including normal and cancer cells. As the content of exosomes is cell type specific, it is believed that they are a "fingerprint" of the releasing cell and its metabolic status. We hypothesized that the exosomes and their specific exosomal content (eg, microribonucleic acid represent a precious biomedical tool and may be used as biomarkers for the diagnosis and prognosis of malignant tumors. In addition, exosomes may modify the phenotype of the parent and/or target cell by transferring pro-oncogenic molecules to induce cancerous phenotype of recipient cells and contribute to the formation of the premetastatic niche. The mechanism involved in these phenomena remains unclear; however, inclusion of signaling mediators into exosomes or exosome release may reduce their intracellular bioavailability in the parent cell, thereby altering cell phenotype and their metastatic potential. The aim of this review therefore is to analyze the biogenesis and role of exosomes from tumor cells, focusing primarily on ovarian cancer. Ovarian cancer is the most lethal gynecologic cancer, and an effective early diagnosis has the potential to improve patient survival. Ovarian cancer currently lacks a reliable method for early detection, however, exosomes have received great attention as potential biomarkers and mediators

  9. Protein expression levels of carcinoembryonic antigen (CEA) in Danish ovarian cancer patients: from the Danish 'MALOVA'ovarian cancer study

    DEFF Research Database (Denmark)

    Hogdall, E.V.; Christensen, L.; Blaakaer, J.

    2008-01-01

    from 189 women diagnosed with low malignant potential ovarian tumours (LMP, borderline ovarian tumours) and 571 women diagnosed with ovarian cancer (OC). RESULTS: Using 30% as the cut-off level for CEA over-expression, 18% of LMPs and 4% of OCs were positive. A higher proportion of mucinous tumours...... (I to IV), the highest CEA expression compared with no expression was found to be a prognostic factor (level 3 versus negative: HR = 2.12, 95%CI 1.11-4.05). FIGO stage, residual tumour after primary surgery, age at diagnosis, other histological types versus serous adenocarcinoma and low versus high...

  10. Role of Chemokine Network in the Development and Progression of Ovarian Cancer: A Potential Novel Pharmacological Target

    Directory of Open Access Journals (Sweden)

    Federica Barbieri

    2010-01-01

    Full Text Available Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development.

  11. Laparoscopic Removal of a Large Ovarian Mass Utilizing Planned Trocar Puncture

    OpenAIRE

    Stitely, Michael L.

    2012-01-01

    Background: Large cystic ovarian masses pose technical challenges to the laparoscopic surgeon. Removing large, potentially malignant specimens must be done with care to avoid the leakage of cyst fluid into the abdominal cavity. Case: We present the case of a large ovarian cystic mass treated laparoscopically with intentional trocar puncture of the mass to drain and remove the mass. Discussion: Large cystic ovarian masses can be removed laparoscopically with intentional trocar puncture of the ...

  12. Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Simonsen, Anja Hviid; Yip, Tai-Tung

    2008-01-01

    samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations...... of chromatographic techniques and tandem mass spectrometry. RESULTS: Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p...OBJECTIVE: To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. METHODS...

  13. Appendectomy in the surgical staging of ovarian carcinoma.

    Science.gov (United States)

    Beşe, T; Kösebay, D; Kaleli, S; Oz, A U; Demirkiran, F; Gezer, A

    1996-06-01

    Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.

  14. Imaging malignant and apparent malignant transformation of benign gynaecological disease

    Energy Technology Data Exchange (ETDEWEB)

    Lee, A.Y.; Poder, L.; Qayyum, A.; Wang, Z.J.; Yeh, B.M. [Department of Radiology, University of California San Francisco, San Francisco, CA (United States); Coakley, F.V., E-mail: Fergus.Coakley@radiology.ucsf.ed [Department of Radiology, University of California San Francisco, San Francisco, CA (United States)

    2010-12-15

    Common benign gynaecological diseases, such as leiomyoma, adenomyosis, endometriosis, and mature teratoma, rarely undergo malignant transformation. Benign transformations that may mimic malignancy include benign metastasizing leiomyoma, massive ovarian oedema, decidualization of endometrioma, and rupture of mature teratoma. The aim of this review is to provide a contemporary overview of imaging findings in malignant and apparent malignant transformation of benign gynaecological disease.

  15. Characterization of exosomes derived from ovarian cancer cells and normal ovarian epithelial cells by nanoparticle tracking analysis.

    Science.gov (United States)

    Zhang, Wei; Peng, Peng; Kuang, Yun; Yang, Jiaxin; Cao, Dongyan; You, Yan; Shen, Keng

    2016-03-01

    Cellular exosomes are involved in many disease processes and have the potential to be used for diagnosis and treatment. In this study, we compared the characteristics of exosomes derived from human ovarian epithelial cells (HOSEPiC) and three epithelial ovarian cancer cell lines (OVCAR3, IGROV1, and ES-2) to investigate the differences between exosomes originating from normal and malignant cells. Two established colloid-chemical methodologies, electron microscopy (EM) and dynamic light scattering (DLS), and a relatively new method, nanoparticle tracking analysis (NTA), were used to measure the size and size distribution of exosomes. The concentration and epithelial cellular adhesion molecule (EpCAM) expression of exosomes were measured by NTA. Quantum dots were conjugated with anti-EpCAM to label exosomes, and the labeled exosomes were detected by NTA in fluorescent mode. The normal-cell-derived exosomes were significantly larger than those derived from malignant cells, and exosomes were successfully labeled using anti-EpCAM-conjugated quantum dots. Exosomes from different cell lines may vary in size, and exosomes might be considered as potential diagnosis biomarkers. NTA can be considered a useful, efficient, and objective method for the study of different exosomes and their unique properties in ovarian cancer.

  16. Accuracy of frozen section in borderline ovarian tumor

    Directory of Open Access Journals (Sweden)

    Maryam Dadzan

    2015-01-01

    Full Text Available Borderline ovarian tumor or low malignant ovarian tumor presents in 10-15% of all ovarian cancers, which usually affects younger women and have favorable prognosis even with conservative surgery, in which fertility can be preserved. Lack of reliable diagnostic tool to indicate the type of malignancy before or at the time of surgery makes the borderline ovarian tumor one of the most controversial topics in gynecology. This might lead to many overtreatment cases with radical surgery or undertreatment with conservative surgery with the higher rate of overtreatment compared to under treatment.In this review article, we extensively searched for all reported data regarding the accuracy of frozen section in borderline ovarian tumor. Reviewing the results of six studies, which specifically considered the accuracy of frozen section in borderline ovarian tumors, revealed an accuracy of 60% with an agreement between final pathology and frozen section results. Overall, 24.5% of under-diagnosed malignant cases interpreted to be benign and 4.9% overdiagnosed cases with benign tumor considered as a malignant. Frozen section is a reliable tool to exclude benign tumor from borderline and malignant but underdiagnosed percentage is higher. There are limitations in this review including the small number of enrolled cases, different time of diagnosis and different investigated countries and the discrepancies between the studied articles in this review.

  17. Initial evaluation and referral guidelines for management of pelvic/ovarian masses.

    Science.gov (United States)

    Le, Tien; Giede, Christopher; Salem, Shia; Lefebvre, Guylaine; Rosen, Barry; Bentley, James; Kupets, Rachel; Power, Patti; Renaud, Marie-Claude; Bryson, Peter; Davis, Donald B; Lau, Susie; Lotocki, Robert; Senikas, Vyta; Morin, Lucie; Bly, Stephen; Butt, Kimberly; Cargill, Yvonne M; Denis, Nanette; Gagnon, Robert; Hietala-Coyle, Marja Anne; Lim, Kenneth Ian; Ouellet, Annie; Raciot, Maria-Hélène

    2009-07-01

    To optimize the management of adnexal masses and to assist primary care physicians and gynaecologists determine which patients presenting with an ovarian mass with a significant risk of malignancy should be considered for gynaecologic oncology referral and management. Laparoscopic evaluation, comprehensive surgical staging for early ovarian cancer, or tumour debulking for advanced stage ovarian cancer. To optimize conservative versus operative management of women with possible ovarian malignancy and to optimize the involvement of gynaecologic oncologists in planning and delivery of treatment. Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and the Cochrane Library, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified by searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. 1. Primary care physicians and gynaecologists should always consider the possibility of an underlying ovarian cancer in patients in any age group who present with an adnexal or ovarian mass. (II-2B) 2. Appropriate workup of a perimenopausal or postmenopausal woman presenting with an adnexal mass should include evaluation of symptoms and signs suggestive of malignancy, such as persistent pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, and difficulty eating. In addition, CA125 measurement should be considered. (II-2B) 3. Transvaginal or transabdominal ultrasound examination is recommended as part of the initial workup of a complex adnexal/ovarian mass. (II-2B) 4. Ultrasound reports should be standardized to include size and unilateral/bilateral location of the adnexal mass and

  18. Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors

    NARCIS (Netherlands)

    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

    To identify proteins and (molecular/biological) pathways associated with differences between benign and malignant epithelial ovarian tumors. 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

  19. Report of the survey on current opinions and practice of German Society for Gynecologic Endoscopy (AGE) members regarding the laparoscopic treatment of ovarian malignancies.

    Science.gov (United States)

    Radosa, Julia Caroline; Radosa, Marc Philipp; Schweitzer, Pascal Albert; Juhasz-Boess, Ingolf; Rimbach, Stefan; Solomayer, Erich-Franz

    2018-05-01

    The purpose of this survey was to assess the opinions of members of the German Society of Gynecologic Endoscopy (AGE) regarding the laparoscopic treatment of ovarian malignancies and current practice at their institutions. Between February and October 2015, the AGE sent an anonymous online survey via mail to its members. The questionnaire solicited participants' opinions about the laparoscopic treatment of ovarian cancers according to T stage and borderline tumors, and information about current practice at their institutions. Participants were also asked their opinions on currently available data on this issue. Of 228 AGE members who completed the survey, 132 (58%) were fellows or attending physicians and 156 (68%) worked at university hospitals or tertiary referral centers. Most [212 (93%)] respondents stated that < 10% of all ovarian cancer cases were currently treated laparoscopically at their institutions. Most participants indicated that T1 (a, b, c) tumors [145 (64%)] and ovarian borderline tumors [206 (90%)], but not T2 [48 (21%)] or T3/4 [9 (4%) ovarian tumors] should or could be treated laparoscopically. One hundred seventy-two (75%) participants considered currently available data on this topic to be insufficient and 152 (66%) stated that they would take part in a clinical trial assessing a laparoscopic approach to T1/2 ovarian cancer. According to this survey, to the opinion of the majority of AGE members, laparoscopy might be a considerable option for the treatment of early ovarian malignancies and borderline tumors and should be evaluated further in future studies.

  20. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  1. The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer.

    Science.gov (United States)

    Li, Xiaoduan; Wang, Xipeng

    2017-05-15

    Ovarian cancer (OC) is one of the three types of malignant tumors in the female reproductive system, and epithelial ovarian cancer (EOC) is its most typical form. Due to the asymptomatic nature of the early stages and resistance to chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current treatments for OC are very limited, and the 5-years survival rate is approximately 30%. Exosomes, which are microvesicles ranging from approximately 30-100 nm in size that are secreted by living cells, can be produced from different cell types and detected in various body fluids. Cancer cells can secrete more exosomes than healthy cells, and more importantly, the content of cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells are considered to be involved in tumor progression and metastasis. As such, exosomes are expected to be potential tools for tumor diagnosis and treatment. In this review, we briefly present the emerging roles of exosomes in OC and summarize related articles about their roles as diagnostic or prognostic biomarkers and in the treatment and drug resistance of OC.

  2. A hybrid positron and OCT intraoperative probe for ovarian cancer detection and characterization

    Science.gov (United States)

    Yang, Yi; Biswal, Nrusingh C.; Wang, Tianheng; Kumavor, Patrick; Karimeddini, Mozafareddin; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2011-03-01

    Ovarian cancer has the lowest survival rate of the gynecologic cancers with a 5-year survival of about 50% in the United States. With current screening and diagnostic abilities for ovarian cancers, most of the diagnosed patients are already with advanced stages and the majority of them will die of this deadly disease. In this paper, we report a multimodal imaging approach which combines optical coherence tomography (OCT) and positron detection for early ovarian cancer detection. The dual modality system has the capability of providing both functional and morphological images simultaneously. While the positron detection provides the metabolism activity of the ovary due to the uptake of radiotracer, the OCT provides the high resolution (25μm X 25μm X 12μm - longitudinal X lateral X axial in air) structural imaging at 20k A-lines per second. Total 18 ovaries obtained from 10 patients classified as normal, abnormal and malignant ovarian tissues were characterized ex vivo. Positron counts of 1.2-fold higher was found between abnormal and normal ovaries and 3~30-fold higher was found between malignant and normal ovaries. OCT imaging of malignant and abnormal ovaries revealed many detailed morphologic features that could be potentially valuable for detecting early malignant changes in the ovary.

  3. Fas and Fas ligand in cyst fluids, serum and tumors of patients with benign and (borderline) malignant ovarian tumors

    NARCIS (Netherlands)

    Arts, HJG; De Jong, S; Hollema, H; Ten Hoor, KA; De Vries, EGE; Van Der Zee, AGJ

    Drug resistance in ovarian cancer treatment urges the exploration of new targets for drugs against this malignancy. Fas is a cell membrane receptor which, after engagement with Fas ligand (FasL), triggers apoptotic death. In this study Fas and FasL levels in cyst fluids and sera of patients with

  4. Laparoscopic Removal of a Large Ovarian Mass Utilizing Planned Trocar Puncture

    Science.gov (United States)

    2012-01-01

    Background: Large cystic ovarian masses pose technical challenges to the laparoscopic surgeon. Removing large, potentially malignant specimens must be done with care to avoid the leakage of cyst fluid into the abdominal cavity. Case: We present the case of a large ovarian cystic mass treated laparoscopically with intentional trocar puncture of the mass to drain and remove the mass. Discussion: Large cystic ovarian masses can be removed laparoscopically with intentional trocar puncture of the mass to facilitate removal without leakage of cyst fluid. PMID:22906344

  5. Ovarian granulosa cell tumors : histopathology, immunopathology and prognosis

    NARCIS (Netherlands)

    S. Chadha-Ajwani (Savi)

    1987-01-01

    textabstractGranulosa cell tumors (GCT) of the ovary account for 2% of all ovarian tumors. As the name indicates, they are composed of granulosa cells but may also contain an admixture of theca cells. They are potentially malignant but, except for extraovarian spread, which is generally agreed

  6. Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors

    Directory of Open Access Journals (Sweden)

    Matyunina Lilya V

    2008-05-01

    Full Text Available Abstract Background Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in an ovarian cancer cell line treated with 5-aza-deoxycytidine (5-aza-dC and in malignant and benign ovarian tumor samples and ovarian surface epithelial cells (OSE isolated from patients with normal ovaries. Results A region containing an intact hypoxia response element (HRE remained completely methylated in the cell line after treatment with 5-aza-dC and was completely methylated in all of the ovarian tumor (malignant and benign samples examined, but only variably methylated in normal OSE samples. HLA-G expression was significantly increased in the 5-aza-dC treated cell line but no significant difference was detected between the tumor and OSE samples examined. Conclusion Since HRE is the binding site of a known repressor of HLA-G expression (HIF-1, we hypothesize that methylation of the region surrounding the HRE may help maintain the potential for expression of HLA-G in ovarian tumors. The fact that no correlation exists between methylation and HLA-G gene expression between ovarian tumor samples and OSE, suggests that changes in methylation may be necessary but not sufficient for HLA-G expression in ovarian cancer.

  7. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    Science.gov (United States)

    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

  8. Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

    Directory of Open Access Journals (Sweden)

    Shiro Koizume

    2015-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

  9. Gynecologic Malignancies Post-LeFort Colpocleisis

    Directory of Open Access Journals (Sweden)

    Rayan Elkattah

    2014-01-01

    Full Text Available Introduction. LeFort colpocleisis (LFC is a safe and effective obliterative surgical option for older women with advanced pelvic organ prolapse who no longer desire coital activity. A major disadvantage is the limited ability to evaluate for post-LFC gynecologic malignancies. Methods. We present the first case of endometrioid ovarian cancer diagnosed after LFC and review all reported gynecologic malignancies post-LFC in the English medical literature. Results. This is the second reported ovarian cancer post-LFC and the first of the endometrioid subtype. A total of nine other gynecologic malignancies post-LFC have been reported in the English medical literature. Conclusions. Gynecologic malignancies post-LFC are rare. We propose a simple 3-step strategy in evaluating post-LFC malignancies.

  10. Ovarian mass mimicking malignancy: a case report

    International Nuclear Information System (INIS)

    Kim, Yong Il; Kim, Seok Ki; Lee, Jeong Won; Lee, Sang Mi; Kim, Tae Sung

    2010-01-01

    A 32-year-old female who suffered from abdominal pain underwent 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the diagnostic workup of pelvic mass lesions. Cystic mass lesions in the bilateral ovaries showed wall thickening and intense hypermetabolism along the rim. In addition, multifocal intense hypermetabolic lymphadenopathies were seen in the left paraaortic lymph node (LN), aortocaval LN, and both common iliac LNs. We interpreted these findings as bilateral ovarian cancer with retroperitoneal metastatic lymphadenopathies rather than endometriosis with reactive lymphadenopathies rather than endometriosis with reactive lymphadenopathies. However, Histopathological examination confirmed the ovarian mass lesions as tubo-ovarian abscesses. We report a case that even if simultaneous hypermetabolic retroperitoneal LNs are seen, intense hypermetabolic lesions in both ovaries can be in consequence of inflammatory change

  11. Ovarian mass mimicking malignancy: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Il; Kim, Seok Ki; Lee, Jeong Won; Lee, Sang Mi; Kim, Tae Sung [National Cancer Center, Goyang (Korea, Republic of)

    2010-12-15

    A 32-year-old female who suffered from abdominal pain underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the diagnostic workup of pelvic mass lesions. Cystic mass lesions in the bilateral ovaries showed wall thickening and intense hypermetabolism along the rim. In addition, multifocal intense hypermetabolic lymphadenopathies were seen in the left paraaortic lymph node (LN), aortocaval LN, and both common iliac LNs. We interpreted these findings as bilateral ovarian cancer with retroperitoneal metastatic lymphadenopathies rather than endometriosis with reactive lymphadenopathies rather than endometriosis with reactive lymphadenopathies. However, Histopathological examination confirmed the ovarian mass lesions as tubo-ovarian abscesses. We report a case that even if simultaneous hypermetabolic retroperitoneal LNs are seen, intense hypermetabolic lesions in both ovaries can be in consequence of inflammatory change

  12. The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Shunfei Yan

    2017-01-01

    Full Text Available Overall survival for patients with ovarian cancer (OC has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC. HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose polymerase (PARP inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC.

  13. Serum peptide/protein profiling by mass spectrometry provides diagnostic information independently of CA125 in women with an ovarian tumor

    DEFF Research Database (Denmark)

    Callesen, Anne; Madsen, Jonna S; Iachina, Maria

    2010-01-01

    In the present study, the use of a robust and sensitive mass spectrometry based protein profiling analysis was tested as diagnostic tools for women with an ovarian tumor. The potential additional diagnostic value of serum protein profiles independent of the information provided by CA125 were also...... investigated. Protein profiles of 113 serum samples from women with an ovarian tumor (54 malign and 59 benign) were generated using MALDI-TOF MS. A total of 98 peaks with a significant difference (pwomen with benign tumors/cysts and malignant ovarian tumors were identified. After...... average linkage clustering, a profile of 46 statistical significant mass peaks was identified to distinguish malignant tumors and benign tumors/cysts. In the subgroup of women with normal CA125 values (

  14. Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE Based Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    Diana P. English

    2013-05-01

    Full Text Available Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE, a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.

  15. Diagnosis of ovarian tumors by ultrasonography and x-ray CT

    International Nuclear Information System (INIS)

    Watanabe, Hiromu

    1986-01-01

    A drawback in ultrasonography, an indispensable technique in imaging ovarian malignancies, is that it sometimes shows false positive for benign tumors including dermoid cyst and ovarian endometriosis. To overcome this, the concurrent use of X-Ray CT seems warrantable and this led us to carry out the study summarized below. CT was carried out on 268 of 322 ovarian disease cases which had undergone ultrasonography. The results obtained were as follows. Sensitivity of ultrasonography and CT in ovarian malignancies were 82 % and 88 % respectively. Of the cases subjected to both techniques, those who were deemed false positive were 39 in ultrasonography and 12 in CT. Ultrasonographic imagings of dermoid cyst and ovarian endometriosis were classified on the basis of their patterns. The results obtained revealed that those in which it was difficult to discriminate the image from ovarian malignancy were types V and VI in dermoid cyst and type III-C in ovarian endometriosis. In both dermoid cyst and ovarian endometriosis, nearly a 100 % accuracy rate was obtainable with CT for diagnosis of benign tumors. This strongly suggested that concurrent use of CT was required, in diagnosing ovarian diseases with the V or VI and III-C patterns referred to above. (author)

  16. Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression

    International Nuclear Information System (INIS)

    Tuhkanen, Hanna; Soini, Ylermi; Kosma, Veli-Matti; Anttila, Maarit; Sironen, Reijo; Hämäläinen, Kirsi; Kukkonen, Laura; Virtanen, Ismo; Mannermaa, Arto

    2009-01-01

    Transcription factor Snail1 has a central role in induction of epithelial-mesenchymal transition (EMT). The aim of the present study was to elucidate the expression of Snail1 protein during epithelial ovarian tumourigenesis and to study the association of Snail1 expression with clinicopathological factors and prognosis. Epithelial and stromal fibroblast-like fusiform cells of 14 normal ovarian samples, 21 benign, 24 borderline and 74 malignant epithelial ovarian tumours were studied for Snail1 protein using immunohistochemistry. Nuclei of surface peritoneal cells of normal ovaries (n = 14) were regarded as negative for Snail1. Nuclear expression of Snail1 protein in epithelial ovarian tumours was increased during tumour progression from precursor lesions into carcinomas both in epithelial (p = 0.006) and stromal cells (p = 0.007). Nuclei of benign tumours (n = 21) were negative for Snail1. In borderline tumours (n = 24) occasional positive epithelial cells were found in 2 (8%) samples and in 3 (13%) samples stromal cells were focally positive for Snail1. In carcinomas (n = 74) focal Snail1 staining in epithelial cells was present in 17 (23%) tumours, and in stromal cells in 18 (24%) tumours. Nuclear expression of Snail1 in epithelial or stromal cells was not associated with clinicopathological factors or prognosis. Nuclear Snail1 expression seems to be related to tumour progression, and expression in borderline tumours indicates a role for Snail1 in early epithelial ovarian tumour development. Snail1 also appears to function more generally in tissue remodelling as positive staining was demonstrated in stromal cells

  17. Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer

    International Nuclear Information System (INIS)

    Merritt, Melissa A; Parsons, Peter G; Newton, Tanya R; Martyn, Adam C; Webb, Penelope M; Green, Adèle C; Papadimos, David J; Boyle, Glen M

    2009-01-01

    The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression. Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes. We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity. These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis

  18. Serum level of tumor marker CA-125 in ovarian pathology

    International Nuclear Information System (INIS)

    Bagni, B.; Feggi, L.M.; Prandini, N.; Pasini, S.; Mollica, G.

    1987-01-01

    The tumor marker CA-125 is an embrional glycoprotein detectable in tissues derived from celomatic epitelium. Serum Ca-125 was determined by RIA in 66 patients with various ovarian pathologies (16 malignant at stage III-IV and 50 benign). Six patients with ovarian carcinoma were monitored during the first week after surgery and chemiotherapy for a total of 150 days of treatment. It has been observed that CA-125 serum level is consistently above the normal range (>35 U/ml) in all malignant diseases. In benign pathology, levels above the normal were found to be represented almost exclusively by ovarian endometriosis. Furthermore, the results demonstrate that chemiotherapy alone is capable of lowering CA-125 serum levels. This tumor marker may be of great advantage in diagnosis and follow-up of ovarian malignancy

  19. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

    2014-01-01

    expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

  20. Ovarian yolk sac tumour in a girl - case report.

    Science.gov (United States)

    Sharma, Charu; Shah, Hemanshi; Sisodiya Shenoy, Neha; Makhija, Deepa; Waghmare, Mukta

    2017-01-01

    Yolk sac tumours are rare ovarian malignancies accounting for less than 1% of malignant ovarian germ cell tumours. They are mostly seen in adolescents and young women and are usually unilateral making fertility preservation imperative. Raised alpha-feto protein level is the hallmark of this tumour. We describe stage III yolk sac tumour in a girl child.

  1. Malign mural nodules associated with serous ovarian tumor of borderline malignancy: a case report and literature review.

    Science.gov (United States)

    Gungor, Tayfun; Altinkaya, S Ozlem; Akbay, Serap; Bilge, Umit; Mollamahmutoglu, Leyla

    2010-03-01

    Cystic tumors of ovary, whether benign, borderline, or malignant may be associated with mural nodule of various types, including sarcomas, sarcoma-like mural nodules (SLMN), and foci of anaplastic carcinoma. Cases of serous borderline ovarian tumor with mural nodules of mixed type are very rare. A 54-year-old woman referred with abdominal swelling. Imaging studies revealed a huge mass localized in pelvis and lower abdomen and grade 1-2 left renal hydronephrosis. Preoperative Ca-125 was 798 U/ml. In exploratory laparotomy there was a 16 cm mass adherent to lateral abdominal wall and intestines. Adhesiolysis and de-bulking surgery were performed including bilateral pelvic, para-aortic lymphadenectomy, appendectomy and omentectomy. Left ureter was found to be dilated because of the infiltration of distal part by the tumor, so distal ureteral resection and neoureterocystostomy were performed. Final pathology revealed borderline serous ovarian tumor with mural nodules which were consisted of SLMNs, multiple and sharply demarcated from the adjacent tumor, and sarcomatous nodules showing infiltrative appearance in metastatic regions. Mural nodules showed a positive reaction for vimentin and SMA but were negative for cytokeratin and also necrosis, hemorrhage, and 10-15 mitoses in 10 high power fields were noted. She had postoperative chemotherapy and follow-up is going on without metastases in her first year. The existence of sarcomatous nodules combined with the SLMN necessitates a careful histologic analysis for treatment and the determination of prognosis. However, too few cases of mixed type mural nodules have been published to warrant a conclusion regarding their prognosis.

  2. Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

  3. Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients.

    Science.gov (United States)

    Cheng, Yu; Li, Li; Zhu, Bangjie; Liu, Feng; Wang, Yan; Gu, Xue; Yan, Chao

    2016-01-01

    We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Female genital tract tuberculosis presenting as ovarian cancer

    Directory of Open Access Journals (Sweden)

    Malihe Hasanzadeh

    2014-01-01

    Full Text Available Background: Tuberculosis (TB is still a major worldwide concern. There is no pathognomonic clinical feature or imaging findings for definite diagnosis of extra pulmonary TB. Therefore, TB involvement of Gastrointestinal or Genitourinary tract can be easily confused with peritoneal carcinomatosis and advanced ovarian carcinoma. Our aim is to emphasize the importance of considering the disease based upon the epidemiologic clues of the patients, while interpreting the positive results for a suspicious ovarian malignancy. Cases: This paper illustrates 8 cases of ovarian or peritoneal tuberculosis, whose initial diagnoses were malignant processes of the GU tract. Conclusion: Tuberculosis ( TB should be always being considered in the differential diagnosis of advanced ovarian cancer, especially in the regions that are endemic for the disease.

  5. Ovarian failure in long-term survivors of childhood malignancy

    International Nuclear Information System (INIS)

    Stillman, R.J.; Schinfeld, J.S.; Schiff, I.; Gelber, R.D.; Greenberger, J.; Larson, M.; Jaffe, N.; Li, F.P.

    1981-01-01

    The frequency and causes of ovarian failure among 182 long-term survivors of childhood cancer were examined. Twenty-two patients (12%) had ovarian failure. Ovarian failure was found in 17 of 25 patients (68%) who had both ovaries within abdominal radiotherapy fields, in five of 35 patients (14%) whose ovaries were at the edge of the treatment field, and in none of 122 patients with one or both ovaries outside of an abdominal treatment field. Covariate and multivariate analyses of tumor type, age at diagnosis, duration of follow-up, abdominal tumor surgery, abdominal radiotherapy, number of chemotherapeutic agents administered, and cumulative doses of several drugs revealed that the location of the ovaries relative to radiation treatment fields was the only risk factor for subsequent ovarian failure

  6. Prevention of ovarian cancer.

    Science.gov (United States)

    Hanna, Louise; Adams, Malcolm

    2006-04-01

    Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.

  7. The role of preoperative serum cancer antigen 125 in malignant ovarian germ cell tumors

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Kim

    2018-04-01

    Full Text Available Objective: To determine the role of preoperative serum cancer antigen 125 (CA 125 in malignant ovarian germ cell tumors (MOGCTs. Materials and methods: Using information from medical databases of Asan Medical Center (Seoul, Korea, we investigated 161 patients with histologically diagnosed MOGCTs and whose preoperative serum CA 125 had been checked. We determined the optimal cutoff value of CA 125 as > 249.5 U/mL in MOGCTs using a receiver operating characteristic curve. Results: The median patient age was 24 years (range, 6–52 years. The most common histologic type was immature teratoma. Most patients had stage I disease. Thirty-two patients (19.9% had elevated preoperative serum CA 125 levels over 249.5 U/mL. On univariate analysis, tumor size, advanced stage, the presence of ascites, ovarian surface involvement, and tumor rupture were significantly associated with elevated preoperative CA 125 levels (>249.5 U/mL. In the median follow-up time of 87 months (range, 9–271 months, 14 patients had a recurrence, and 5 died of the disease. Patients with an elevated serum preoperative CA 125 level (>249.5 U/mL had poorer disease-free survival, but this was not statistically significant. However, elevated preoperative CA 125 (>249.5 U/mL was significantly associated with poorer overall survival. Conclusions: Elevated preoperative serum CA 125 may have prognostic value in patients with MOGCTs. Keywords: CA-125 antigen, Ovarian germ cell cancer, Prognosis

  8. Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma

    International Nuclear Information System (INIS)

    Milas, Luka; Saito, Yoshihiro; Hunter, Nancy; Milross, Christopher G.; Mason, Kathryn A.

    1996-01-01

    Background. Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G 2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Methods. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD 50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Results. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD 50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Conclusions. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain

  9. Initial experience with TPA as a tumour marker in ovarian malignancy

    International Nuclear Information System (INIS)

    Dalen, A. van; Favier, J.; Eastham, W.N.

    1984-01-01

    The Tissue Polypeptide Antigen (TPA) and Carcinoembryonic Antigen (CEA) content of serum were estimated in samples taken from 21 patients with malignant ovarian tumours. The patients were followed for variable period ranging from 6 to 22 months and the TPA and CEA levels were estimated after debulking operations and courses of CHAP-5 therapy. The relative success of the operation and/or treatment was reflected in an appropriate alteration of the serum TPA level. CEA levels remained more or less stationary. The serum TPA levels of 13 of the 21 patients, irrespective of the tumour type, differentiation or stage of tumour growth, exhibited a good concordance with the clinical observations at second look operations. The one patient with a disseminated form of adenoacanthoma failed to show an elevation of the TPA levels and 7 patients continue to have a constantly elevated TPA levels but as yet no clinical evidence of recurrent or metastatic disease. (orig.) [de

  10. [The molecular biology of epithelial ovarian cancer].

    Science.gov (United States)

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

  11. New knowledge and insights about the malignant transformation of endometriosis.

    Science.gov (United States)

    Taniguchi, Fuminori

    2017-07-01

    Endometriosis may be a definitive risk factor for ovarian cancer, the most fatal gynecological cancer. The ability of endometriosis to transform into malignancy, first described by Dr. Sampson in 1925, is considered a rare occurrence, affecting approximately 1% of ovarian endometriomas. Recently we conducted a retrospective study regarding the malignant transformation of endometriosis in Japanese women. Many studies have reported a consistent correlation between endometriosis and ovarian cancer according to histological subtypes. However, the existing epidemiological evidence linking this association is insufficient to define the role of endometriosis as a cause of ovarian cancer and to influence changes to current clinical practice. Prospective cohort studies are therefore needed to clarify this issue. Additionally, the results of many molecular studies are conflicting, and earlier studies showing the molecular aberrations involved in genomic instability and mutation that enable malignant transformation have not been replicated in later studies. Careful long-term observation of a patient with endometrioma is required to detect possible subsequent incidence of malignant transformation. More importantly, a precise strategy should be set up for better prevention, early detection, specific diagnosis and treatment targeting molecular pathogenesis to understand the mechanisms of endometriosis-associated ovarian cancer. Clinicians need to be aware of the increased ovarian cancer risk in women with endometriosis. © 2017 Japan Society of Obstetrics and Gynecology.

  12. Research Perspective: Potential Role of Nitazoxanide in Ovarian Cancer Treatment. Old Drug, New Purpose?

    Directory of Open Access Journals (Sweden)

    Jessie Ehrisman

    2013-09-01

    Full Text Available Among gynecological malignancies epithelial ovarian cancer (EOC is the leading cause of death. Despite improvements in conventional chemotherapy combinations, the overall cure rate has remained mostly stable over the years, and only 10%–15% of patients maintain a complete response following first-line therapy. To improve the efficacy of ovarian cancer chemotherapy it is essential to develop drugs with new mechanisms of action. Compared to normal tissues, protein disulfide isomerase (PDI is overexpressed in ovarian tumors. PDI is a cellular enzyme in the lumen of the endoplasmic reticulum (ER of eukaryotes or the periplasmic region of prokaryotes. This protein catalyzes the formation and breakage of disulphide bonds between cysteine residues in proteins, which affects protein folding. Selective inhibition of PDI activity has been exhibited both in vitro and in vivo anticancer activity in human ovarian cancer models. PDI inhibition caused accumulation of unfolded or misfolded proteins, which led to ER stress and the unfolded protein response (UPR, and in turn resulted in cell death. Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolylbenzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths. In this article, we propose that NTZ, acting as PDI inhibitor, may be a new and potent addition to the chemotherapeutic strategy against ovarian cancer.

  13. Research Perspective: Potential Role of Nitazoxanide in Ovarian Cancer Treatment. Old Drug, New Purpose?

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail: nico.disanto@duke.edu; Ehrisman, Jessie [Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2013-09-10

    Among gynecological malignancies epithelial ovarian cancer (EOC) is the leading cause of death. Despite improvements in conventional chemotherapy combinations, the overall cure rate has remained mostly stable over the years, and only 10%–15% of patients maintain a complete response following first-line therapy. To improve the efficacy of ovarian cancer chemotherapy it is essential to develop drugs with new mechanisms of action. Compared to normal tissues, protein disulfide isomerase (PDI) is overexpressed in ovarian tumors. PDI is a cellular enzyme in the lumen of the endoplasmic reticulum (ER) of eukaryotes or the periplasmic region of prokaryotes. This protein catalyzes the formation and breakage of disulphide bonds between cysteine residues in proteins, which affects protein folding. Selective inhibition of PDI activity has been exhibited both in vitro and in vivo anticancer activity in human ovarian cancer models. PDI inhibition caused accumulation of unfolded or misfolded proteins, which led to ER stress and the unfolded protein response (UPR), and in turn resulted in cell death. Nitazoxanide [NTZ: 2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide] is a thiazolide antiparasitic agent with excellent activity against a wide variety of protozoa and helminths. In this article, we propose that NTZ, acting as PDI inhibitor, may be a new and potent addition to the chemotherapeutic strategy against ovarian cancer.

  14. Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

    Science.gov (United States)

    Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

    2014-12-01

    Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tsz-Lun Yeung

    2016-01-01

    Full Text Available Ovarian cancer is a histologically, clinically, and molecularly diverse disease with a five-year survival rate of less than 30%. It has been estimated that approximately 21,980 new cases of epithelial ovarian cancer will be diagnosed and 14,270 deaths will occur in the United States in 2015, making it the most lethal gynecologic malignancy. Ovarian tumor tissue is composed of cancer cells and a collection of different stromal cells. There is increasing evidence that demonstrates that stromal involvement is important in ovarian cancer pathogenesis. Therefore, stroma-specific signaling pathways, stroma-derived factors, and genetic changes in the tumor stroma present unique opportunities for improving the diagnosis and treatment of ovarian cancer. Cancer-associated fibroblasts (CAFs are one of the major components of the tumor stroma that have demonstrated supportive roles in tumor progression. In this review, we highlight various types of signaling crosstalk between ovarian cancer cells and stromal cells, particularly with CAFs. In addition to evaluating the importance of signaling crosstalk in ovarian cancer progression, we discuss approaches that can be used to target tumor-promoting signaling crosstalk and how these approaches can be translated into potential ovarian cancer treatment.

  16. MULTIPLE PRIMARY MALIGNANCIES IN PATIENTS.cdr

    African Journals Online (AJOL)

    RICHY

    the youngest was 36 years old. Four of our patients were females. Two patients had cancers of the colon followed by ovarian malignancy in one and a rectal malignancy in the other. Of the other patients, one had cancer of the cervix and later she developed None Hodgkin's lymphoma. Two had bilateral breast malignancies.

  17. Mathematical Models of Breast and Ovarian Cancers

    Science.gov (United States)

    Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

    2016-01-01

    Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, since answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible, in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. PMID:27259061

  18. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort

    NARCIS (Netherlands)

    F.E. van Leeuwen; H. Klip; T.M. Mooij (Thea); A.M.G. van de Swaluw; C.B. Lambalk (Cornelius); M. Kortman; J.S.E. Laven (Joop); C.A.M. Jansen; F.M. Helmerhorst; B.J. Cohlen; W.N.P. Willemsen (Wim); J.M.J. Smeenk; A.H.M. Simons; F. van der Veen; J.L.H. Evers (Johannes); P.A. van Dop; N.S. Macklon (Nick); C.W. Burger (Curt)

    2011-01-01

    textabstractBackground: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown.Methods: We identified a nationwide historic cohort of 19 146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile

  19. A comparative study of 99Tcm (V)-DMSA imaging with histopathological examination in ovarian neoplasms

    International Nuclear Information System (INIS)

    Zhao Xinming; Wang Jianfang; Xu Fang; Yin Jie; Wei Lanxiu; Sun Li

    1999-01-01

    Objective: To assess the clinical value of 99 Tc m (V)-Dmsa imaging in detecting the ovarian and the pelvic cavity neoplasms. Methods: 99 Tc m (V)-DMSA imaging was performed on 24 patients with diagnosed ovarian neoplasms which were pathologically confirmed after operation. Results: 14 of the 15 patients with malignant ovarian tumors had positive 99 Tc m (V)-DMSA scintigraphy. However, 7 of 9 cases with benign ovarian tumors had negative 99 Tc m (V)-DMSA scintigraphy. The sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate, and accuracy of 99 Tc m (V)-DMSA imaging for detecting malignant ovarian tumors were 93.33%, 77.78%, 87.50%, 87.50%, 14.29%, 6.67% and 87.50%, respectively. Conclusions: 99 Tc m (V)-DMSA imaging is of important value in detecting malignant and benign ovarian and pelvic tumors

  20. Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of diagnostic test performance.

    Science.gov (United States)

    Pi, Shan; Cao, Rong; Qiang, Jin Wei; Guo, Yan Hui

    2018-01-01

    Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion coefficient (ADC) values are widely used in the differential diagnosis of ovarian tumors. Purpose To assess the diagnostic performance of quantitative ADC values in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and local databases were searched for studies assessing ovarian tumors using quantitative ADC values. We quantitatively analyzed the diagnostic performances for two clinical problems: benign vs. malignant tumors and borderline vs. malignant tumors. We evaluated diagnostic performances by the pooled sensitivity and specificity values and by summary receiver operating characteristic (SROC) curves. Subgroup analyses were used to analyze study heterogeneity. Results From the 742 studies identified in the search results, 16 studies met our inclusion criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors and six studies assessed malignant vs. borderline ovarian tumors. Regarding the diagnostic accuracy of quantitative ADC values for distinguishing between malignant and benign ovarian tumors, the pooled sensitivity and specificity values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was 0.96. For differentiating borderline from malignant tumors, the pooled sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The methodological quality of the included studies was moderate. Conclusion Quantitative ADC values could serve as useful preoperative markers for predicting the nature of ovarian tumors. Nevertheless, prospective trials focused on standardized imaging parameters are needed to evaluate the clinical value of quantitative ADC values in ovarian tumors.

  1. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

    International Nuclear Information System (INIS)

    Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

    2005-01-01

    The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer

  2. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer.

    Science.gov (United States)

    Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

    2005-04-29

    The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

  3. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

    Directory of Open Access Journals (Sweden)

    Campbell Ian G

    2005-04-01

    Full Text Available Abstract The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

  4. Vedolizumab as a Potential Culprit in the Development of Ovarian Teratoma?

    Directory of Open Access Journals (Sweden)

    Judy A. Trieu

    2017-12-01

    Full Text Available Vedolizumab is a new humanized monoclonal antibody that has been reserved for those with moderate-to-severe Crohn’s disease and ulcerative colitis who have failed immunomodulator and TNF-α antagonist therapy, and for those who have an increased risk for developing progressive multifocal leukoencephalopathy. Because it targets gastrointestinal tract-specific lymphocytes, meta-analyses and integrated studies have shown that vedolizumab causes fewer extraintestinal adverse effects, such as opportunistic infections and malignancies, compared with anti-TNF therapies. We present the case of a patient who developed an ovarian teratoma after initiation of vedolizumab therapy.

  5. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort

    NARCIS (Netherlands)

    van Leeuwen, F. E.; Klip, H.; Mooij, T. M.; de Swaluw, A. M. G. van; Lambalk, C. B.; Kortman, M.; Laven, J. S. E.; Jansen, C. A. M.; Helmerhorst, F. M.; Cohlen, B. J.; Willemsen, W. N. P.; Smeenk, J. M. J.; Simons, A. H. M.; van der Veen, F.; Evers, J. L. H.; van Dop, P. A.; Macklon, N. S.; Burger, C. W.

    2011-01-01

    BACKGROUND: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown. METHODS: We identified a nationwide historic cohort of 19 146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not

  6. Fertility preservation and refreezing of transplanted ovarian tissue-a potential new way of managing patients with low risk of malignant cell recurrence

    DEFF Research Database (Denmark)

    Kristensen, Stine Gry; Giorgione, Veronica; Humaidan, Peter

    2017-01-01

    OBJECTIVE: To report the first successful refreezing of ovarian tissue recovered more than 3 years after transplantation in a woman previously treated for early-stage ovarian cancer. DESIGN: Evaluation of cryopreserved and grafted ovarian tissue. SETTING: University hospital. PATIENT(S): A 23-yea...

  7. Role of Gd-DTPA enhanced fat-suppression MR imaging on ovarian tumors

    International Nuclear Information System (INIS)

    Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Park, Jin Gyoon; Choi, Ho Sun

    1995-01-01

    To determine the value of Gd-DTPA enhanced fat-suppression (GEFS) MR imaging in the characterization and differentiation of benign from malignant ovarian tumors. MRI findings of thirty-seven patients with surgically proved 44 ovarian tumors (30 benign, 14 malignant) were studied retrospectively. MR imaging with conventional spin echo (CSE; T1-weighted image TR/TE 450/20, T2-weighted image TR/TE 3500/30, 90) and GEFS were performed with a 1.5T GE signa. MRI findings of tumors including cystic or solid, wall and septal thickness, necrosis, invasion to adjacent organ, ascites and lymphadenopathy were assessed separately by using CSE and GEFS images, and then tumors were characterized as benign or malignant. Compared with CSE image, GEFS MR image showed better visualization of solid component in 5 malignant lesions, wall thickness in 5 malignant and 1 benign lesions, septal thickness in 3 malignant and 1 benign lesions, necrosis in 1 malignant lesion, and adjacent soft tissue invasion in 5 malignant lesions. Correct characterization of malignant tumors was increased from 71% on CSE image to 93% on GEFS image. However, correct characterization of benign tumors was 93% on both images. GEFS MR imaging could be useful for characterization of ovarian tumors, especially in malignant cases, and employed for differentiation of benign from malignant tumors

  8. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  9. Tubo-ovarian abscess of tuberculous origin in the pediatric patient: a case report

    International Nuclear Information System (INIS)

    Rodriguez, Luz Stella; Moreno, Luz Angela; Henao, Liliana; Jaramillo, Lina; Montoya, Ruben Danilo

    2007-01-01

    We report a case of bilateral tuberculous tubo-ovarian abscess in a 13 year old girl which is noteworthy, because pelvic tuberculosis is an uncommon presentation of the disease in children, the diagnosis may be difficult. tuberculous tubo-ovarian abscess frequently mimic ovarian malignancies radiologically and clinically and their association with increased serum level of serum ea 125 in the absence of malignancy. Risks factors, CT and MRI appearances are essentials for their differentiation. The possibility of tubo-ovarian abscess must be considered in all women who presents with abdominal pain and adnexal mass regardless of their sexual activity

  10. Intraperitoneal chemotherapy in the management of ovarian cancer: focus on carboplatin

    Directory of Open Access Journals (Sweden)

    Maurie Markman

    2009-02-01

    Full Text Available Maurie MarkmanUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: Both pre-clinical studies and phase 1–2 clinical trials have provided strong support for the potential role of regional drug delivery in the management of epithelial ovarian cancer, a disease process whose major manifestations remain largely localized to the peritoneal cavity in the majority of individuals with this malignancy. The results of 3 phase 3 randomized trials have revealed the favorable impact of primary cisplatin-based intraperitoneal chemotherapy in women who initiate drug treatment with small-volume residual ovarian cancer following an attempt at optimal surgical cytoreduction. Concerns have been raised regarding the toxicity of regional treatment, particularly the side-effect profile associated with cisplatin. One rational approach to improving the tolerability of intraperitoneal chemotherapy is to substitute carboplatin for cisplatin. This review discusses the rationale for and data supporting regional treatment of epithelial ovarian cancer, and highlights the potential role for intraperitoneal carboplatin in this clinical setting.Keywords: ovarian cancer, intraperitoneal chemotherapy, cisplatin, carboplatin

  11. Vascular endothelial growth factor polymorphisms and a synchronized examination of plasma and tissue expression in epithelial ovarian cancers.

    Science.gov (United States)

    Bhaskari, J; Premalata, C S; Shilpa, V; Rahul, B; Pallavi, V R; Ramesh, G; Krishnamoorthy, Lakshmi

    2016-01-01

    In this study, we have analyzed six genetic polymorphisms of the VEGF-A gene and correlated the genetic data with plasma and tissue expression of VEGF-A in epithelial ovarian carcinomas. A total of 130 cases including 95 malignant carcinomas, 17 low malignant potential and 18 benign tumours were studied. rs699947, rs833061, rs1570360, rs2010963, rs1413711 and rs3025039 were studied by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma levels of VEGF-A were estimated by enzyme-linked immunosorbent assay (ELISA) and tissue expression of VEGF-A by immunohistochemistry (IHC). Four polymorphisms of the above excluding rs699947 and rs3025039 showed significant association with malignancy, and we observed the presence of positive correlation between haplotype CCGGCC and increased expression of VEGF-A in both plasma and tissues which also correlated with poor prognosis and recurrence suggesting a probable increase in resistance to treatment in such carriers. Highly upregulated tissue expression of VEGF-A was seen in all epithelial ovarian carcinomas with intensity of expression increasing from benign to malignant cases. ELISA data from our study showed an increase in circulating levels of VEGF-A in malignancies. VEGF-A plasma levels can be employed as a biomarker for high-grade malignancy in epithelial ovarian cancers alongside tissue expression and CA-125 levels. This study is unique due to the fact that a simultaneous analysis of plasma and tissue expression has been demonstrated and is a first such study in epithelial ovarian cancers and representing the Indian population (South-east Asian) synchronized with genetic polymorphism data as well.

  12. Spectrum of fluorodeoxyglucose-positron emission tomography/computed tomography and magnetic resonance imaging findings of ovarian tumors.

    Science.gov (United States)

    Kitajima, Kazuhiro; Ueno, Yoshiko; Maeda, Tetsuo; Murakami, Koji; Kaji, Yasushi; Kita, Masato; Suzuki, Kayo; Sugimura, Kazuro

    2011-11-01

    The purpose of this article is to review fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) findings in a variety of benign, malignant, and borderline malignant ovarian tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT findings of this entity. Benign ovarian tumors generally have faint uptake, whereas endometriomas, fibromas, and teratomas show mild to moderate uptake. Malignant ovarian tumors generally have intense uptake, whereas tumors with a small solid component often show minimal uptake.

  13. Epigenetic Characterization of Ovarian Cancer

    National Research Council Canada - National Science Library

    Murphy, Susan K

    2005-01-01

    .... The approach is to use normal ovarian surface epithelium (NOSE) and malignant cells obtained directly from surgically removed specimens in order to most closely approximate the methylation status in vivo...

  14. [Early detection of ovarian cancer: tomorrow? A review].

    Science.gov (United States)

    Chene, G; Penault-Llorca, F; Robin, N; Cayre, A; Provencher, D M; Dauplat, J

    2013-02-01

    Ovarian cancer is the most lethal of the gynaecological malignancies because this «silent killer» is almost always diagnosed at an advanced stage. Precursor lesions have at least been discovered. This review will describe in details specific features of tubal and ovarian preinvasive lesions and the old and novel techniques that could be used for early detection of ovarian cancer. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  16. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  17. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  18. Prognostic significance of cytosolic pS2 content in ovarian tumors

    International Nuclear Information System (INIS)

    Raigoso, P.; Allende, T.; Zeidan, N.; Llana, B.; Bernardo, L.; Roiz, C.; Tejuca, S.; Vazquez, J.; Lamelas, M.L.

    2002-01-01

    Aim: pS2 is an estrogen regulated peptide which has been associated with a good prognosis an with a more favorable response to treatment in breast cancer patients. In ovarian tumors, the expression of pS2 was demonstrated at both mRNA and protein levels. In addition, it has been showed significant association of pS2 with mucinous differentiation or well differentiation grade of the tumors. However, it is little know about the prognostic significance of the pS2 content in ovarian carcinomas. The aims of the present work were to analyze the cytosolic pS2 content in benign and malignant ovarian tumors, its relationship with clinico-pathologic parameters, steroid receptor status, and prognostic significance. Material and Methods: We analysed the cytosolic concentrations of pS2 in 91 specimen ovarian tissues by an immunoradiometric assay (ELSA-pS2, CIS, France). The tissues were 8 normal ovaries, 43 benign tumors and 40 malignant ovarian tumors. The same ovarian tissues processed to pS2 were analyzed to Estrogen (ER) and Progesterone (PgR) Receptor status. These steroid receptors were quantified biochemically following commercial ELISA method (ABBOTT Diagnostics, Germany). The relationship between cytosolic content and clinico-pathologic factors was examined by the Mann-Whitney or Kruskall-Wallis test. Correlation between steroid receptors and pS2 content was calculated with the Spearman test. Survival curves were calculated using the Kaplan-Meier method and compared by the log-rank test. Differences were considered significant at 5% probability level. Results: pS2 could be detected in 30 cases (32.9%) with values ranged from 0.04 to 89 ng/mg prt. Only one normal ovary showed detectable levels of pS2 and there were not differences in cytosolic content between benign and malignant ovarian tumors. The pS2 levels were only associated to mucinous differentiation in both benign and malignant ovarian tumors (p=0.029 and p=0.015, respectively). Significantly higher

  19. Targeting HOX and PBX transcription factors in ovarian cancer

    International Nuclear Information System (INIS)

    Morgan, Richard; Plowright, Lynn; Harrington, Kevin J; Michael, Agnieszka; Pandha, Hardev S

    2010-01-01

    Ovarian cancer still has a relatively poor prognosis due to the frequent occurrence of drug resistance, making the identification of new therapeutic targets an important goal. We have studied the role of HOX genes in the survival and proliferation of ovarian cancer cells. These are a family of homeodomain-containing transcription factors that determine cell and tissue identity in the early embryo, and have an anti-apoptotic role in a number of malignancies including lung and renal cancer. We used QPCR to determine HOX gene expression in normal ovary and in the ovarian cancer cell lines SK-OV3 and OV-90. We used a short peptide, HXR9, to disrupt the formation of HOX/PBX dimers and alter transcriptional regulation by HOX proteins. In this study we show that the ovarian cancer derived line SK-OV3, but not OV-90, exhibits highly dysregulated expression of members of the HOX gene family. Disrupting the interaction between HOX proteins and their co-factor PBX induces apoptosis in SK-OV3 cells and retards tumour growth in vivo. HOX/PBX binding is a potential target in ovarian cancer

  20. Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis

    Directory of Open Access Journals (Sweden)

    Shu-Wing Ng

    2013-03-01

    Full Text Available Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC. Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.

  1. Transplantation of frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Gellert, S E; Pors, S E; Kristensen, Stine Gry

    2018-01-01

    . CONCLUSION: This study found no indications of sufficient numbers of malignant cells present in the ovarian tissue to cause recurrence of cancer after OTT. Further, it is unlikely that OTC affects the well-being of children born. OTC is now an established method of fertility preservation in Denmark......PURPOSE: The purpose of the study is to review all peer-reviewed published reports of women receiving ovarian tissue transplantation (OTT) with frozen/thawed tissue (OTC) with respect to age, diagnosis, transplantation site, fertility outcome, and potential side effects, including data from all...... women in the Danish program. METHODS: A systematic review of the literature was performed in PubMed combined with results from all patients who had received OTT in Denmark up to December 2017. RESULTS: OTT has been reported from 21 different countries comprising a total of 360 OTT procedures in 318...

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

    Directory of Open Access Journals (Sweden)

    Erickson-Miller Connie L

    2012-09-01

    Full Text Available Abstract 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

  3. Benefits of nanoencapsulation for the hypercin-mediated photodetection of ovarian micrometastases.

    Science.gov (United States)

    Zeisser-Labouèbe, Magali; Delie, Florence; Gurny, Robert; Lange, Norbert

    2009-02-01

    The high recurrence and lethality of ovarian cancer at advanced stages is problematic, especially due to the development of numerous micrometastases scattered throughout the abdominal cavity. Fluorescence photodetection (PD) used in combination with surgical resection of malignant tissues has been suggested to improve recovery. Based on promising in vivo results for the detection of bladder cancer, hypericin (Hy), a natural photosensitizer (PS), stands as a good candidate for the photodetection of ovarian cancer. However, due to its hydrophobicity, systemic administration of Hy is problematic. Polymeric nanoparticles (NPs) help to overcome these delivery and stability problems and enable intravenous administration of Hy. In this study, Hy-loaded NPs of polylactic acid were produced with the following properties: (i) mean size of 268 nm, (ii) negative zeta potential, (iii) low residual surfactant and (iv) drug loading of 3.7 % (w/w). The potential of hypericin-loaded nanoparticles for the fluorescence photodetection of ovarian metastases in Fischer 344 rats bearing ovarian tumours was compared to free drug. The selectivity of Hy administered with both formulations was assessed first by fluorescence endoscopy, and then quantified after tissue extraction. The results showed an improved selective accumulation of Hy in ovarian micrometastases when NPs were used.

  4. Ovarian mucinous cystadenocarcinoma in 17-year-old girl : a case report

    International Nuclear Information System (INIS)

    Lee, Jong Koo; Ko, Jae Kook; Moon, Hee Jung; Kim, Mi Young; Yu, Hyun; Shin, Hyun Ja; Seo, Kung Yong; Kim, Jeong Rye

    1997-01-01

    Malignant epithelial neoplasm usually occurs in postmenopausal women, with less than 10% of cases occurring in women under the age of 20. In patients below this age, the majority of ovarian tumors are of germ cell origin and malignant ovarian epithelial tumors are uncommon. We report US and CT imaging in a case of mucinous cystadenocarcinoma in a 17-year-old nullipara who complained of amenorrhea for 45 days and a palpable mass

  5. Ovarian mucinous cystadenocarcinoma in 17-year-old girl : a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Koo; Ko, Jae Kook; Moon, Hee Jung; Kim, Mi Young; Yu, Hyun; Shin, Hyun Ja; Seo, Kung Yong; Kim, Jeong Rye [Korea Veterans' Hospital, Seoul (Korea, Republic of)

    1997-08-01

    Malignant epithelial neoplasm usually occurs in postmenopausal women, with less than 10% of cases occurring in women under the age of 20. In patients below this age, the majority of ovarian tumors are of germ cell origin and malignant ovarian epithelial tumors are uncommon. We report US and CT imaging in a case of mucinous cystadenocarcinoma in a 17-year-old nullipara who complained of amenorrhea for 45 days and a palpable mass.

  6. Utility of 18F-fluorodeoxyglucose-positron emission tomography in the differential diagnosis of benign and malignant gynaecological tumours.

    Science.gov (United States)

    Takagi, Hiroaki; Sakamoto, Jinichi; Osaka, Yasuhiro; Shibata, Takeo; Fujita, Satoko; Sasagawa, Toshiyuki

    2018-02-05

    Positron emission tomography/computed tomography (PET/CT) involving 18F-fluorodeoxyglucose (FDG) is widely used for systemic cancer and recurrence diagnosis. However, the differential diagnosis of benign and malignant gynaecological tumours according to FDG accumulation is unclear. This study aimed to investigate the intensity of FDG uptake/metabolic activity for the differential diagnosis of benign and malignant gynaecological tumours. This study included seven patients with physiological phenomena, 34 with benign tumours, 13 with borderline malignant tumours and 119 with malignant tumours who underwent 18F-FDG PET/CT. We assessed the maximum standardized uptake value (SUVmax) and determined its utility in the diagnosis of benign and malignant tumours using a receiver operating characteristic (ROC) curve analysis. Among the 63 patients with ovarian tumours, the mean SUVmax of 22 patients with benign ovarian tumours was 2.48 and the mean SUVmax of 41 patients with malignant ovarian tumours was 10.98 (P benign and malignant ovarian tumours, as well as uterine myomas and uterine sarcomas. © 2018 The Royal Australian and New Zealand College of Radiologists.

  7. Effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Wei-Dong Chen

    2017-05-01

    Full Text Available Objective: To study the effect of continuous recombinant human endostatin pumping combined with TP chemotherapy on serum malignant molecules and angiogenesis molecules in patients with advanced ovarian cancer. Methods: 78 patients with advanced ovarian cancer who were treated in our hospital between July 2011 and December 2015 were selected and divided into observation group and control group (n=39 according to the single-blind randomized control method. Before treatment and after 4 cycles of treatment, electrochemical luminescence immunity analyzer was used to detect serum tumor marker levels; RIA method was used to determine serum apoptosis molecule levels; enzyme-linked immunosorbent assay (ELISA was used to detect the serum angiogenesis molecule levels. Results: Before treatment, differences in serum levels of tumor markers, apoptosis molecules and angiogenesis molecules were not statistically significant between two groups of patients (P>0.05. After 4 cycles of treatment, serum carbohydrate antigen 125 (CA125, carbohydrate antigen 153 (CA153, human epididymis protein 4 (HE4, carcinoembryonic antigen (CEA, human chorionic gonadotropin (β-HCG, Bcl-2, Survivin, Bag-1, angiogenin-2 (Ang-2, vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF levels of observation group were significantly lower than those of control group (P<0.05 while Bax level was significantly higher than that of control group (P<0.05. Conclusions: Continuous recombinant human endostatin pumping combined with TP chemotherapy can decrease the malignant degree of advanced ovarian cancer and inhibit angiogenesis.

  8. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    International Nuclear Information System (INIS)

    Zheng, Hong; Liu, Jia-Yu; Song, Feng-Ju; Chen, Ke-Xin

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70% of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30% because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer

  9. Primary ovarian leiomyosarcoma in an adolescent following radiation for medulloblastoma

    International Nuclear Information System (INIS)

    O'Sullivan, S.G.; Das Narla, L.; Ferraro, E.

    1998-01-01

    Primary ovarian leiomyosarcomas are rare neoplasms of the ovary, particularly in the pediatric population. Their occurrence following radiation therapy for previous malignancy has important implications. We present a case of primary ovarian leiomyosarcoma in an adolescent following therapy for medulloblastoma. (orig.)

  10. Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Yusuf Gunay

    2012-01-01

    Full Text Available Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas. Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients. Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

  11. Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions.

    Science.gov (United States)

    Saigal, Sonal; Bhargava, Ankur; Mehra, S K; Dakwala, Falguni

    2011-07-01

    The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia.

  12. Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions

    Directory of Open Access Journals (Sweden)

    Sonal Saigal

    2011-01-01

    Full Text Available Background and Objective: The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. Materials and Methods: Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud′s dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. Results: In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. Conclusion: The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia.

  13. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer—Health Professional Version

    Science.gov (United States)

    Ovarian epithelial, fallopian tube, and peritoneal cancers are diseases in which malignant cells form in the tissue covering the ovary, lining the fallopian tube, or peritoneum. Find evidence-based information on ovarian cancer treatment, causes and prevention, screening, research, genetics and statistics.

  14. Large twisted ovarian fibroma in menopausal women: a case report ...

    African Journals Online (AJOL)

    Ovarian fibroma is the most common benign solid tumors of the ovary, commonly misdiagnosed as uterine fibromaor as malignant ovarian tumors. It occurs generally in older perimenopausal and postmenopausal women. Occasionally large fibromas may undergo torsion causing acute abdominal pain. Doppler ...

  15. Characterization of sonographically indeterminate ovarian tumors with MR imaging. A logistic regression analysis

    International Nuclear Information System (INIS)

    Yamashita, Y.; Hatanaka, Y.; Torashima, M.; Takahashi, M.; Miyazaki, K.; Okamura, H.

    1997-01-01

    Purpose: The goal of this study was to maximize the discrimination between benign and malignant masses in patients with sonographically indeterminate ovarian lesions by means of unenhanced and contrast-enhanced MR imaging, and to develop a computer-assisted diagnosis system. Material and Methods: Findings in precontrast and Gd-DTPA contrast-enhanced MR images of 104 patients with 115 sonographically indeterminate ovarian masses were analyzed, and the results were correlated with histopathological findings. Of 115 lesions, 65 were benign (23 cystadenomas, 13 complex cysts, 11 teratomas, 6 fibrothecomas, 12 others) and 50 were malignant (32 ovarian carcinomas, 7 metastatic tumors of the ovary, 4 carcinomas of the fallopian tubes, 7 others). A logistic regression analysis was performed to discriminate between benign and malignant lesions, and a model of a computer-assisted diagnosis was developed. This model was prospectively tested in 75 cases of ovarian tumors found at other institutions. Results: From the univariate analysis, the following parameters were selected as significant for predicting malignancy (p≤0.05): A solid or cystic mass with a large solid component or wall thickness greater than 3 mm; complex internal architecture; ascites; and bilaterality. Based on these parameters, a model of a computer-assisted diagnosis system was developed with the logistic regression analysis. To distinguish benign from malignant lesions, the maximum cut-off point was obtained between 0.47 and 0.51. In a prospective application of this model, 87% of the lesions were accurately identified as benign or malignant. (orig.)

  16. Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and ca125 in predicting epithelial ovarian cancer: A meta-analysis

    International Nuclear Information System (INIS)

    Li, Fake; Tie, Ruxiu; Chang, Kai; Wang, Feng; Deng, Shaoli; Lu, Weiping; Yu, Lili; Chen, Ming

    2012-01-01

    Risk for Ovarian Malignancy Algorithm (ROMA) and Human epididymis protein 4 (HE4) appear to be promising predictors for epithelial ovarian cancer (EOC), however, conflicting results exist in the diagnostic performance comparison among ROMA, HE4 and CA125. Remote databases (MEDLINE/PUBMED, EMBASE, Web of Science, Google Scholar, the Cochrane Library and ClinicalTrials.gov) and full texts bibliography were searched for relevant abstracts. All studies included were closely assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). EOC predictive value of ROMA was systematically evaluated, and comparison among the predictive performances of ROMA, HE4 and CA125 were conducted within the same population. Sensitivity, specificity, DOR (diagnostic odds ratio), LR ± (positive and negative likelihood ratio) and AUC (area under receiver operating characteristic-curve) were summarized with a bivariate model. Subgroup analysis and sensitivity analysis were used to explore the heterogeneity. Data of 7792 tests were retrieved from 11 studies. The overall estimates of ROMA for EOC predicting were: sensitivity (0.89, 95% CI 0.84-0.93), specificity (0.83, 95% CI 0.77-0.88), and AUC (0.93, 95% CI 0.90-0.95). Comparison of EOC predictive value between HE4 and CA125 found, specificity: HE4 (0.93, 95% CI 0.87-0.96) > CA125 (0.84, 95% CI 0.76-0.90); AUC: CA125 (0.88, 95% CI 0.85-0.91) > HE4 (0.82, 95% CI 0.78-0.85). Comparison of OC predictive value between HE4 and CA125 found, AUC: CA125 (0.89, 95% CI 0.85-0.91) > HE4 (0.79, 95% CI 0.76-0.83). Comparison among the three tests for EOC prediction found, sensitivity: ROMA (0.86, 95%CI 0.81-0.91) > HE4 (0.80, 95% CI 0.73-0.85); specificity: HE4 (0.94, 95% CI 0.90-0.96) > ROMA (0.84, 95% CI 0.79-0.88) > CA125 (0.78, 95%CI 0.73-0.83). ROMA is helpful for distinguishing epithelial ovarian cancer from benign pelvic mass. HE4 is not better than CA125 either for EOC or OC prediction. ROMA is promising predictors of

  17. Spectrum of Childhood and Adolescent Ovarian Tumors in India: 25 Years Experience at a Single Institution

    Directory of Open Access Journals (Sweden)

    Ruchi Rathore

    2016-09-01

    Full Text Available BACKGROUND: Ovarian tumour in children and adolescent girls form an uncommon but important part of gynaecological malignancies. They account for 1% of all the childhood malignancies and 8% of all abdominal tumours in children. Since the ovarian cysts are thought to arise from mature follicles, these tumours were considered to be infrequent in the paediatric population. AIM: The rarity of this condition prompted us to conduct this study and share our experience on the incidence and clinicopathological features of different ovarian tumours in girls up to 20 years of age observed in last 25 years at a single tertiary care hospital. MATERIAL AND METHODS: This was a retrospective study conducted in the Department of Pathology at a tertiary hospital, Delhi. All ovarian tumours up to the age of 20 years in the past 25 years (1990-2014 were included for the purpose of studying the clinicopathological aspects of ovarian tumours in this age group. Descriptive statistics for prevalence and age-wise prevalence was done. Chi-square test, to find an association between the age, laterality and size with malignancy was performed. RESULTS: We received a total of 1102 cases of ovarian tumours over the period of 25 years  (1990 to 2014, of which 112 (10% cases were seen in girls up to 20 years of age. The mean age of the patients was 15.3 ± 4 years. The most common presenting complaint was pain abdomen (46.4 % There was a statistically significant correlation found between size and malignancy status of tumours in our study (p = 0.00. Of 112 cases of ovarian tumours, 39/112 (34.8% were malignant and 73/112 (65.2% were benign. Mature  cystic teratoma (27.6% was the most common type of benign tumour in this age group and immature teratomas were the most common type of malignant ovarian neoplasms. CONCLUSION: Premenarchal girls with ovarian masses may have varied presentations. Abdominal pain is the most common presenting complaint of young adolescent girls with

  18. Validation of the Performance of International Ovarian Tumor Analysis (IOTA) Methods in the Diagnosis of Early Stage Ovarian Cancer in a Non-Screening Population.

    Science.gov (United States)

    Froyman, Wouter; Wynants, Laure; Landolfo, Chiara; Bourne, Tom; Valentin, Lil; Testa, Antonia; Sladkevicius, Povilas; Franchi, Dorella; Fischerova, Daniela; Savelli, Luca; Van Calster, Ben; Timmerman, Dirk

    2017-06-02

    The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery. 230 (13.9%) patients proved to have stage I-II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%). This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease.

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

    Science.gov (United States)

    Lazennec, Gwendal

    2006-01-01

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

  20. Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

    International Nuclear Information System (INIS)

    Yavelsky, Victoria; Chan, Gerald; Kalantarov, Gavreel; Trakht, Ilya; Lobel, Leslie; Rohkin, Sarit; Shaco-Levy, Ruthy; Tzikinovsky, Alina; Amir, Tamar; Kohn, Hila; Delgado, Berta; Rabinovich, Alex; Piura, Benjamin

    2008-01-01

    We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue. The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples. By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors. The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that

  1. CA125 in ovarian cancer

    DEFF Research Database (Denmark)

    Duffy, M J; Bonfrer, J M; Kulpa, J

    2005-01-01

    women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease...

  2. Intestinal Obstruction due to Bilateral Ovarian Cystic Teratoma in a ...

    African Journals Online (AJOL)

    Teratoma is the most common ovarian tumour associated with pregnancy. The complications in pregnancy include torsion, rupture and malignant transformation mimicking ovarian carcinoma. Its association with intestinal obstruction is uncommon. Case: A 35 year old gravida 5 para 4 woman with 18 week gestation was ...

  3. MRI appearances of borderline ovarian tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

    2009-04-15

    This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

  4. High impact of FDG-PET/CT in diagnostic strategies for ovarian cancer

    International Nuclear Information System (INIS)

    Zytoon, Ashraf Anas; Murakami, Koji; Eid, Hazem; El-Gammal, Mahmoud

    2013-01-01

    Background: Ovarian cancer has the highest mortality of all gynecologic malignancies. FDG-PET/CT was proven to be accurate for identification of primary ovarian tumors, regional lymph nodes, and distant metastases. Purpose: To evaluate ovarian masses at FDG-PET/CT in correlation with histopathologic findings. Material and Methods: Ninety-eight patients underwent whole body FDG-PET/CT examination. Eighty-six patients with primary ovarian cancer and 12 patients with metastatic disease to the ovaries were included. Results: PET/CT imaging was true-positive in 87/94 patients with malignant tumors. In 4/4 patients with benign tumors, PET/CT results were true-negative, with sensitivity of 92.6%, specificity 100%, total test accuracy 92.9%. Fifty-seven patients were diagnosed as stage IV ovarian cancer with distant metastasis. Conclusion: The anatomical/functional examination by FDG-PET/CT was proven to be valuable in increasing the diagnostic accuracy that can help improve patient management

  5. Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.

    Directory of Open Access Journals (Sweden)

    Wouter Wegdam

    Full Text Available 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

  6. Quantification of photoacoustic microscopy images for ovarian cancer detection

    Science.gov (United States)

    Wang, Tianheng; Yang, Yi; Alqasemi, Umar; Kumavor, Patrick D.; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2014-03-01

    In this paper, human ovarian tissues with malignant and benign features were imaged ex vivo by using an opticalresolution photoacoustic microscopy (OR-PAM) system. Several features were quantitatively extracted from PAM images to describe photoacoustic signal distributions and fluctuations. 106 PAM images from 18 human ovaries were classified by applying those extracted features to a logistic prediction model. 57 images from 9 ovaries were used as a training set to train the logistic model, and 49 images from another 9 ovaries were used to test our prediction model. We assumed that if one image from one malignant ovary was classified as malignant, it is sufficient to classify this ovary as malignant. For the training set, we achieved 100% sensitivity and 83.3% specificity; for testing set, we achieved 100% sensitivity and 66.7% specificity. These preliminary results demonstrate that PAM could be extremely valuable in assisting and guiding surgeons for in vivo evaluation of ovarian tissue.

  7. Transforming Growth Factor-β and Nitrates in Epithelial Ovarian Cancer

    Science.gov (United States)

    Khalifa, Ali; Kassim, Samar K.; Ahmed, Maha I.; Fayed, Salah T.

    1999-01-01

    The role of transforming growth factor-β (TGF-β) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-β by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-β, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-â, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-β (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-β had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-β above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-β and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-β could be of prognostic significance. PMID:10689548

  8. Transforming Growth Factor-β and Nitrates in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ali Khalifa

    1999-01-01

    Full Text Available The role of transforming growth factor-β (TGF-β and nitric oxide (NO in ovarian neoplasia is still not clear. We studied the expression of TGF-β by enzyme immunoassay, and nitrates (as a stable end product of NO in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant. Ploidy status and synthetic phase fraction (SPF were also assessed by flow cytometry. Mean ranks of TGF-β, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively. Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000. A significant correlation was shown between TGF-â, and nitrate levels in all tissues (r = 0.24, P = 0.01, as well as in malignant tissues (r = 0.3, P = 0.026. Cutoff values were determined for both TGF-β (290 pg/mg protein, and nitrates (310 nmole/mg non protein nitrogenous substances. At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-β had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-β above the cut-off had worse prognosis (X2 = 12.69, P = 0.004. The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-β and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-β could be of prognostic significance.

  9. Transforming growth factor-beta and nitrates in epithelial ovarian cancer.

    Science.gov (United States)

    Khalifa, A; Kassim, S K; Ahmed, M I; Fayed, S T

    1999-12-01

    The role of transforming growth factor-beta (TGF-beta) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-beta by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-beta, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 = 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2 = 17.6, P = 0.000). A significant correlation was shown between TGF-beta, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-beta (290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-beta had 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-beta above the cut-off had worse prognosis (X2 = 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-beta and NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-beta could be of prognostic significance.

  10. The Role of the Immune System in Ovarian Cancer and Implications on Therapy.

    Science.gov (United States)

    Menderes, Gulden; Schwab, Carlton L; Black, Jonathan; Santin, Alessandro D

    2016-06-01

    Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States. While the treatment options have improved with conventional cytotoxic chemotherapy and advanced surgical techniques, disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the role of immune system in disease pathogenesis and different immunotherapies available for the treatment of ovarian cancer as well as current ongoing studies and potential future directions.

  11. Current status on microRNAs as biomarkers for ovarian cancer

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Novotny, Guy Wayne; Høgdall, Claus

    2016-01-01

    Ovarian cancer (OC) is the most lethal gynecological malignancy in the Western world, and has a very poor prognosis, often due to late diagnosis and emergence of chemotherapy resistance. Therefore, there is an essential need for new diagnostic and prognostic markers that can improve and initiate ......RNAs in different types of OC. In this review we summarize the current knowledge of microRNAs as potential biomarkers for OC, with focus on their clinical relevance....

  12. Diagnostic accuracy of diffusion-weighted imaging with conventional MR imaging for differentiating complex solid and cystic ovarian tumors at 1.5T

    Directory of Open Access Journals (Sweden)

    Zhang Ping

    2012-11-01

    Full Text Available Abstract Background Preoperative characterization of complex solid and cystic adnexal masses is crucial for informing patients about possible surgical strategies. Our study aims to determine the usefulness of apparent diffusion coefficients (ADC for characterizing complex solid and cystic adnexal masses. Methods One-hundred and 91 patients underwent diffusion-weighted (DW magnetic resonance (MR imaging of 202 ovarian masses. The mean ADC value of the solid components was measured and assessed for each ovarian mass. Differences in ADC between ovarian masses were tested using the Student’s t-test. The receiver operating characteristic (ROC was used to assess the ability of ADC to differentiate between benign and malignant complex adnexal masses. Results Eighty-five patients were premenopausal, and 106 were postmenopausal. Seventy-four of the 202 ovarian masses were benign and 128 were malignant. There was a significant difference between the mean ADC values of benign and malignant ovarian masses (p -3 mm2/s may be the optimal one for differentiating between benign and malignant tumors. Conclusions A high signal intensity within the solid component on T2WI was less frequently in benign than in malignant adnexal masses. The combination of DW imaging with ADC value measurements and T2-weighted signal characteristics of solid components is useful for differentiating between benign and malignant ovarian masses.

  13. Immunohistochemical localization of HE4 in benign, borderline, and malignant lesions of the ovary.

    Science.gov (United States)

    Georgakopoulos, Penelope; Mehmood, Saira; Akalin, Ali; Shroyer, Kenneth R

    2012-11-01

    Despite advances in the development of novel methods to improve treatment, ovarian carcinoma is still the leading cause of gynecologic cancer death in the United States and other industrialized nations. Improvements in the clinical outcome of ovarian cancer will be achieved if methods can be developed to enable the detection of these tumors at the earliest possible stage. Thus, it is critically important to identify and validate new biomarkers of ovarian cancer. HE4 expression was defined by immunohistochemical analysis of a wide range of benign, borderline, and malignant ovarian lesions, including serous, endometrioid, mucinous, and clear cell lesions of the ovary and in primary tubal carcinomas and the normal fallopian tube. At the cellular level, HE4 was highly expressed in malignant ovarian tumors and in a wide range of benign and borderline ovarian lesions. In addition, HE4 was highly expressed in primary fallopian tube carcinomas and benign fallopian tubal epithelial cells. These results support the conclusion that HE4 is widely expressed in most benign, borderline, and malignant lesions of the ovary and the fallopian tube. The detection of HE4 expression at high levels in some benign lesions and normal tissues suggests that HE4 could have limited specificity as a marker of ovarian or tubal carcinoma. Furthermore, the relatively weak expression that was observed in many ovarian carcinomas indicates that HE4 could fail to detect some cases of primary or recurrent disease.

  14. Krukenberg Tumor: A Rare Cause of Ovarian Torsion

    Directory of Open Access Journals (Sweden)

    Sameer Sandhu

    2012-01-01

    Full Text Available Ovarian torsion is the fifth most common gynecological surgical emergency. Ovarian torsion is usually associated with a cyst or a tumor, which is typically benign. The most common is mature cystic teratoma. We report the case of a 43-year-old woman who came to the Emergency Department with rare acute presentation of bilateral Krukenberg tumors, due to unilateral ovarian torsion. In this case report, we highlight the specific computed tomography (CT features of ovarian torsion and demonstrate the unique radiological findings on CT imaging. Metastasis to the ovary is not rare and 5 to 10% of all ovarian malignancies are metastatic. The stomach is the common primary site in most Krukenberg tumors (70%; an acute presentation of metastatic Krukenberg tumors with ovarian torsion is rare and not previously reported in radiology literature.

  15. Cryobanking of human ovarian tissue

    DEFF Research Database (Denmark)

    Ernst, Erik; Andersen, Anders Nyboe; Andersen, Claus Yding

    2014-01-01

    Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond...... an initial 5-year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate...... women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family....

  16. Asiatic acid attenuates malignancy of human metastatic ovarian ...

    African Journals Online (AJOL)

    vimetin, N-cad and. ZEB1/2) were suppressed, indicating the EMT process was significantly suppressed by AA treatment at the concentration of 10 μM. DISCUSSION. As a highly metastatic disease, patients with a stage III/IV ovarian cancer ...

  17. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  18. Case report of ovarian torsion mimicking ovarian cancer as an uncommon late complication of laparoscopic supracervical hysterectomy

    Directory of Open Access Journals (Sweden)

    Michał Ciebiera

    2017-02-01

    Full Text Available Laparoscopic supracervical hysterectomy (LSH is an example of a partial hysterectomy, performed due to benign gynaecological complaints. Better endoscopic instruments and operational techniques have led to a great reduction in the number of abdominal hysterectomies. It is believed that LSH is a safe and minimally invasive hysterectomy technique. The Cochrane Database meta-analysis proves the benefits of minimally invasive surgery compared with abdominal gynaecological surgery, including decreased pain, surgical-site infections and hospital stay, quicker return to activity, and fewer postoperative adhesions. According to recent publications, the overall complication rate of all hysterectomy methods is about 1-4.5%. Adnexal torsion is a correlated complication. About 3-5% of patients undergoing emergency surgery due to pelvic pain are diagnosed with this condition. It may be the cause of acute abdomen and correlated symptoms such as vomiting, nausea, or severe pain. To the best of our knowledge a case of asymptomatic, delayed ovarian torsion mimicking ovarian tumour has not been reported so far. In the presented case, torsion successfully imitated neoplastic process as both ROMA score and IOTA ‘simple rules’ indicated a malignancy with high degree of probability. This case demonstrates that, if ovarian tumour is detected in the postoperative period, a torsion of ovarian pedicle should be taken into consideration as it may mimic malignant neoplasm.

  19. Diagnosis and management of simple ovarian cysts: an audit

    International Nuclear Information System (INIS)

    Simcock, B.

    2005-01-01

    Simple ovarian cysts are common. The aim of clinical management is to optimize the treatment of malignant and premalignant cysts while minimizing intervention for cysts likely to resolve spontaneously. In this retrospective study, ovarian cysts over 30 mm in diameter were detected in 90 women. Of this population, 75 were premenopausal, 13 postmenopausal, and two had undergone a hysterectomy. Thirteen women presented acutely. Family history of breast, ovary or colon cancer was not ascertained in any of the women. None had CA125 levels performed. In 22 cases, the cyst was aspirated; only 10 of these had follow-up ultrasound. Laparotomy was performed in 25 premenopausal women, the two perimenopausal women and eight postmenopausal women. Average cyst size was 71 mm (range 40-80 mm) in the laparoscopy group, and 72 mm (range 36-180 mm) in the laparotomy group. After initial diagnosis at ultrasound, a follow-up scan was performed 4-16 weeks later. The final diagnosis was ovarian neoplasm in 13 and hydrosalpinx in two. None had a malignancy. Documentation at ultrasound was often inadequate, and management of the women with an ovarian cyst was haphazard. Guidelines on management of simple ovarian cysts are likely to improve clinical practice. Copyright (2005) Blackwell Science Pty Ltd

  20. The safety of transplanting cryopreserved ovarian tissue in cancer patients

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Greve, Tine; Andersen, Claus Yding

    2013-01-01

    Transplantation of frozen/thawed ovarian tissue from patients with a malignant condition is associated with a risk of re-introduction of the disease as the tissue usually is removed before anti-cancer therapy and may thus contain malignant cells. We review studies investigating the presence...

  1. Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer.

    Science.gov (United States)

    Korsunsky, Ilya; Parameswaran, Janaki; Shapira, Iuliana; Lovecchio, John; Menzin, Andrew; Whyte, Jill; Dos Santos, Lisa; Liang, Sharon; Bhuiya, Tawfiqul; Keogh, Mary; Khalili, Houman; Pond, Cassandra; Liew, Anthony; Shih, Andrew; Gregersen, Peter K; Lee, Annette T

    2017-10-01

    MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Histones and their modifications in ovarian cancer - drivers of disease and therapeutic targets.

    Science.gov (United States)

    Marsh, Deborah J; Shah, Jaynish S; Cole, Alexander J

    2014-01-01

    Epithelial ovarian cancer has the highest mortality of the gynecological malignancies. High grade serous epithelial ovarian cancer (SEOC) is the most common subtype, with the majority of women presenting with advanced disease where 5-year survival is around 25%. Platinum-based chemotherapy in combination with paclitaxel remains the most effective treatment despite platinum therapies being introduced almost 40 years ago. Advances in molecular medicine are underpinning new strategies for the treatment of cancer. Major advances have been made by international initiatives to sequence cancer genomes. For SEOC, with the exception of TP53 that is mutated in virtually 100% of these tumors, there is no other gene mutated at high frequency. There is extensive copy number variation, as well as changes in methylation patterns that will influence gene expression. To date, the role of histones and their post-translational modifications in ovarian cancer is a relatively understudied field. Post-translational histone modifications play major roles in gene expression as they direct the configuration of chromatin and so access by transcription factors. Histone modifications include methylation, acetylation, and monoubiquitination, with involvement of enzymes including histone methyltransferases, histone acetyltransferases/deacetylases, and ubiquitin ligases/deubiquitinases, respectively. Complexes such as the Polycomb repressive complex also play roles in the control of histone modifications and more recently roles for long non-coding RNA and microRNAs are emerging. Epigenomic-based therapies targeting histone modifications are being developed and offer new approaches for the treatment of ovarian cancer. Here, we discuss histone modifications and their aberrant regulation in malignancy and specifically in ovarian cancer. We review current and upcoming histone-based therapies that have the potential to inform and improve treatment strategies for women with ovarian cancer.

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

    Science.gov (United States)

    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

  4. The role of computed tomography in diagnosis of ovarian tumors

    International Nuclear Information System (INIS)

    Yasuda, Yukihiko; Kohchiyama, Masahiko; Tsuru, Hiroshi; Shirai, Shigeo; Kikuchi, Shigeru; Koganemaru, Michihiko; Ohtake, Hisashi

    1985-01-01

    CT is useful in the diagnosis of pelvic tumors. CT can differenciate solid from cystic, and benign from malignant tumors and further provide important diagnostic informations for differential diagnosis. Twenty cases of ovarian tumors have been studied at Kurume University Hospital. This included 3 cystadenomas, 7 cystadenocarcinomas, 5 cystic teratomas, 2 endometriosis cysts and 3 metastatic ovarian cancers. CT was very valuable in differenciation of benign from malignant lesions on the basis of contrast enhancement, presence of ascites and adheison as well as irregularity of the cyst walls. It was difficult to differenciate ovarian tumors on the basis of the density of the tumor or calcification in the wall of the tumor. Cystic teratomas were diagnosed quite accurately in all cases because of its specific CT findings. Differenciation of endometriosis cysts of the ovary was difficult from degenerated uterine myoma. (author)

  5. Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

    International Nuclear Information System (INIS)

    Ye, Shuangmei; Chen, Yin; You, Lanying; Zhang, Yiqun; Xu, Gang; Zhou, Jianfeng; Ma, Ding; Wang, Shixuan; Hao, Xing; Zhou, Ting; Wu, Mingfu; Wei, Juncheng; Wang, Yongjun; Zhou, Li; Jiang, Xuefeng; Ji, Li

    2010-01-01

    Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro. Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKT Ser473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining. Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not

  6. Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors

    Directory of Open Access Journals (Sweden)

    Chen F

    2018-05-01

    Full Text Available Fawen Chen,1,2 Jing Shen,3 Jianwei Wang,1 Pengwei Cai,1 Yi Huang3 1Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, 2Department of Blood Transfusion, 3Department of Clinical Laboratory, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China Purpose: To investigate the diagnostic values of human epididymis protein 4 (HE4, carbohydrate antigen 125 (CA125, carbohydrate antigen 19-9 (CA19-9, and carcinoembryonic antigen (CEA for ovarian tumors. Methods: The participants were divided into three groups: 386 healthy women (control group, 262 patients with benign ovarian tumors (the benign group, and 196 patients with malignant pelvic tumors (the malignant group. The serum levels of HE4, CA125, CA19-9, and CEA were analyzed by electrochemiluminescent immunoassay. Results: It showed that serum levels of HE4, CA125, CA19-9, and CEA of patients with ­malignant ovarian tumors were significantly higher than those in the control group and benign group (P<0.01. HE4 had a high specificity (96.56% in malignant ovarian tumors. The tumor markers HE4, CA125, CA19-9, and CEA had a sensitivity of 63.78%, 62.75%, 35.71%, and 38.78%, respectively. The combined use of two or more tumor markers (parallel test had a higher diagnostic sensitivity but lower specificity than a single tumor marker. The combined efficiency of HE4 and CA125 was the highest, with a sensitivity and specificity of 80.10% and 69.08%, respectively. HE4 and CA125 combined with the Risk of Ovarian Malignancy Algorithm provided an efficient means of screening and diagnosis of ovarian malignancies. The diagnostic sensitivity increased to 88.52% when three or four tumor markers were used but showed no significant difference compared with the combination of HE4 and CA125 (P>0.05. Conclusion: The combination of three or four tumor markers did not improve the diagnostic efficacy when compared with the combination

  7. 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

    Science.gov (United States)

    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

  8. Safety considerations for transplanting cryopreserved ovarian tissue to restore fertility in female patients who have recovered from Ewing's sarcoma

    DEFF Research Database (Denmark)

    Sørensen, Stine D; Greve, Tine; Wielenga, Vera Timmermans

    2014-01-01

    ovarian tissue, potentially causing recrudescence of the original cancer after transplantation. The risk of EWS metastasizing to the ovary is probably low but has not been studied in great detail. This review describes the available evidence on the risk of malignant cell contamination in the ovaries...

  9. Histopathological Pattern and Age Distribution, of Malignant Ovarian Tumor among Sudanese Ladies

    Directory of Open Access Journals (Sweden)

    Sumeya A. Khieri

    2018-02-01

    CONCLUSION: The incidence of different types of ovarian cancers in the present study is similar to worldwide incidence. The surface epithelial tumour is the commonest ovarian cancer, of which serous adenocarcinoma is the commonest and most of our patients present in late stages.

  10. Spontaneous rupture of ovarian cystadenocarcinoma: pre- and post-rupture computed tomography evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Salvadori, Priscila Silveira; Atzingen, Augusto Castelli von; D' Ippolito, Giuseppe [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina; Bomfim, Lucas Novais [Universidade Tiradentes (UNIT), Maceio, AL, (Brazil)

    2015-09-15

    Epithelial ovarian tumors are the most common malignant ovarian neoplasms and, in most cases, eventual rupture of such tumors is associated with a surgical procedure. The authors report the case of a 54-year-old woman who presented with spontaneous rupture of ovarian cystadenocarcinoma documented by computed tomography, both before and after the event. In such cases, a post-rupture staging tends to be less favorable, compromising the prognosis. (author)

  11. Ovarian tumours in children : A review of 18 cases

    Directory of Open Access Journals (Sweden)

    Abdelouhab Ammor

    2012-01-01

    Full Text Available Background : To review the experience of Children′s Hospital of Rabat in managing ovarian tumours in children. Materials and Methods: There were 18 patients between 2 and 15 years of age who presented with an ovarian tumour at Children′s Hospital of Rabat between January 2000 and December 2008. Data collected from the hospital medical records included age at diagnosis, patient′s history, presenting complaints, radiological examination, tumour markers, management, operative procedure, histopathological examination and outcome of the patients. Results : The most common presenting complaint was abdominal pain in 10 (55% patient. 77% of ovarian tumours were germ cell tumours; 71% of these were teratomas which were benign in 66% of cases. Unilateral salpingo-oophorectomy was the most common surgical procedure performed in 15 patients (83% through laparotomy. Laparoscopic ovarian cystectomy was carried out in 2 (11% patients with benign cystic teratoma. Of the 7 (39% patients with malignant tumours, three received postoperative chemotherapy. Outcome was good in most cases. There were no cases of resistance to treatment, or death. Conclusion : Early diagnosis of ovarian tumours in children and adolescents is important. Since most of these tumours are benign, surgical treatment should be conservative to minimise the risk of subsequent infertility, while the treatment of malignant tumours should include complete staging, resection of the tumour, postoperative chemotherapy when indicated, to give the patient a chance for future childbearing.

  12. CT and MRI diagnosis of tubo-ovarian masses

    International Nuclear Information System (INIS)

    Xiong Minghui; Zhang Wanshi; Wang Dong

    2000-01-01

    Objective: To evaluate the diagnostic value of CT and MRI in tubo-ovarian masses. Methods: CT scan was performed in 67 patients with tubo-ovarian masses confirmed by pathology. 19 of them underwent MRI. Results: (1) 20 primary malignant ovarian tumors showed cystic,solid or cystic-solid masses; papillary projections on cystic wall; pelvic organs and pelvic wall invasion. Chocolate cysts with malignant degeneration exhibited small nodules on thickened cystic wall on CT and MRI. T 1 WI was better for revealing the lesions. (2) Of 11 cases of metastasis to tubo-ovary, 4 showed peritoneal linear enhancement. (3) There were 9 cystadenomas and 2 adenofibromas, one of the cystadenomas contained fat, two adenofibromas were similar to uterus in density on CT while showing lower signal intensity on MRI (both T 1 WI and T 2 WI). (4) Three cases of thecoma exhibited cystic or solid masses, solid thecomas revealed granular enhancement. (5) Teratomas were most specific, one of them was associated with thecoma. (6) Tubo-ovarian abscesses and tuberculosis depicted cystic or cystic-solid masses. (7) Two cases of tubal pregnancy showed inhomogeneous soft tissue masses, the lower density areas in the centers were clot and organized tissues confirmed by pathology. Conclusion: (1) CT and MRI had higher sensitivity but lower specificity for tubo-ovarian masses, the diagnosis should be combined with clinical history and patients' age. (2) Tumors of two different types may coexist and sometimes fat may be present in tumors other than teratoma

  13. Profound nephrotic syndrome in a patient with ovarian teratoma

    Directory of Open Access Journals (Sweden)

    Abdallah Jeroudi

    2013-01-01

    Full Text Available The nephrotic syndrome (NS has been associated with a variety of malignancies in a number of reports in the literature, but has been reported in only nine cases associated with ovarian neoplasms. Membranous nephropathy is the most common glomerular pathology causing the NS in patients with solid tumors. There has been only one report of an ovarian neoplasm associated with minimal change disease (MCD. We describe the case of a 36-year-old woman who presented with the NS secondary to biopsy-proven MCD, likely secondary to mature ovarian teratoma. Treatment by tumor removal and prednisone led to remission of the NS. To the best of our knowledge, this is the first report of an ovarian teratoma and the second report of an ovarian neoplasm associated with MCD.

  14. The Diagnostic Value of Transvaginal Sonograph (TVS), Color Doppler, and Serum Tumor Marker CA125, CEA, and AFP in Ovarian Cancer.

    Science.gov (United States)

    Zhang, Fang; Zhang, Zhou-Long

    2015-06-01

    The purpose of this study is to investigate the diagnostic value of transvaginal sonograph (TVS), color Doppler, and serum tumor marker CA125, CEA, and AFP in ovarian cancer. From June, 2011 to May, 2013, 102 cases with adnexal mass were recruited in this study (32 cases of malignant ovarian cancer and 70 cases of benign ovarian tumor according to pathological diagnosis). TVS, color Doppler, and serum tumor markers were used for tumor diagnosis. The sensitivity, specifity, positive prediction, negative prediction, and Youden's index were analyzed. Of the 102 patients, 32 were diagnosed with malignant ovarian cancer and 70 were diagnosed with benign ovarian tumor according to pathological diagnosis. Based on TVS results, 37 cases were malignant while 65 cases were benign. Based on color Doppler results, 34 cases were malignant while 68 cases were benign. Based on TVS and color Doppler results, 35 cases were malignant while 65 were benign. Based on CA125 test results, 34 cases were malignant while 68 cases were benign. Based on CEA test results, 8 cases were malignant and 94 cases were benign. Bases on AFP test results, 9 cases were malignant while 93 cases were benign. Based on the results of combination tumor marker test, 38 cases were malignant while 64 cases were benign. The combination of TVS, color Doppler, and tumor marker test showed optimal diagnostic value with a sensitivity of 90.63 %, specificity of 97.14 %, positive prediction of 93.94 %, negative prediction of 98.55 %, and Youden's index of 94.02 %. The combination of TVS, color Doppler, and tumor marker test is of great diagnostic value, which should be widely used in clinical practice.

  15. Radioimmunoassay of the normal serum glycoprotein (CX1) in monitoring ovarian malignancy

    International Nuclear Information System (INIS)

    Wass, M.; Searle, F.; Bagshawe, K.D.

    1981-01-01

    A glycoprotein designated CX 1, of molecular weight 80,000, has been extracted from adenocarcinomas of the ovary and its measurement by radioimmunoassay established. CX 1 is present in the normal ovary and in normal serum. It is present in various non-ovarian carcinomas but in much greater amount in ovarian adenocarcinoma and in ascitic fluid associated with this cancer. Increased concentrations are found in the serum of patients with various cancers. In about 60% of patients with Stage III and IV ovarian adenocarcinoma, serum values are elevated and they correlate with the course of the disease, providing information which probably has clinical value. (author)

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

    Directory of Open Access Journals (Sweden)

    Varvara Vitiazeva

    Full Text Available 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.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.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.Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from

  17. The Serum CA-125 Concentration Data Assists in Evaluating CT Imaging Information When Used to Differentiate Borderline Ovarian Tumor from Malignant Epithelial Ovarian Tumors

    International Nuclear Information System (INIS)

    Shin, Ji Eun; Choi, Hyuck Jae; Kim, Mi Hyun; Cho, Kyoung Sik

    2011-01-01

    We wanted to evaluate the diagnostic value of serum CA-125 concentration, when used in combination with the preoperative contrast-enhanced CT results, to differentiate borderline ovarian tumors (BOTs) from stage I malignant epithelial ovarian tumors (MEOTs). Ninety-eight masses (46 BOTs and 52 stage I MEOTs) from 87 consecutive patients (49 with BOTs and 38 with stage I MEOTs) who had undergone preoperative contrast-enhanced computed tomography (CT) and surgical staging were evaluated retrospectively and independently by two radiologists. The preoperative serum CA-125 concentration was measured in all patients. The utility of analyzing serum CA-125 concentration in combination with the CT results was evaluated by receiver operating characteristic (ROC) curve analysis. An irregular tumor surface and lymphadenopathy were predictive of a MEOT. ROC analysis showed that the combination of CT data and the serum CA-125 level resulted in a higher diagnostic performance than did using the CT alone for differentiating BOTs from MEOTs. The areas under the curves (AUCs) without and with the use of the serum CA-125 level data were 0.67 (95% confidence interval [CI]: 0.57-0.77) and 0.78 (95% CI: 0.68-0.85), respectively, for reader 1 (p = 0.029) and 0.71 (95% CI: 0.61-0.80) and 0.81 (95% CI: 0.72-0.89), respectively, for reader 2 (p = 0.009). The serum CA-125 concentration is of additional diagnostic value when used in conjunction with the CT imaging results for differentiating BOTs from MEOTs.

  18. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    International Nuclear Information System (INIS)

    Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

    2010-01-01

    Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes

  19. Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion.

    LENUS (Irish Health Repository)

    Cooke, Niamh M

    2015-09-09

    Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level.

  20. Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Carine Bossard

    Full Text Available Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb, phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.

  1. Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

    Science.gov (United States)

    Gaudin, Françoise; Machelon, Véronique; Brigitte, Madly; Jacquard, Carine; Pillon, Arnaud; Balaguer, Patrick; Balabanian, Karl; Lazennec, Gwendal

    2012-01-01

    Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients. PMID:22970307

  2. Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer--a nationwide case-control study.

    Science.gov (United States)

    Baandrup, Louise

    2015-07-01

    Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in

  3. SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma

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    Yuen Yee Cheng

    2017-01-01

    Full Text Available Malignant pleural mesothelioma (MPM is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56% and SFRP5 (70% in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.

  4. Ovarian Fibroma with Meigs Syndrome associated with Elevated CA125 - A Rare Case

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    Prasad. K. Shetty

    2010-07-01

    Full Text Available Postmenopausal women with solid adnexal masses, ascites and pleural effusion with elevated CA 125 are highly suggestive for malignant ovarian tumor. However in literature 28 cases Meigs syndrome (Benign ovarian tumor, ascites and right pleural effusion with raised CA 125 have been reported. We report a case of Meigs syndrome caused by right ovarian fibroma with elevated serum CA125 level in a postmenopausal woman

  5. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan; Bajic, Vladimir B.; Brendan, Pang NK; Huak, Chan Y; Keow, Peh B; Razvi, Khalil; Salto-Tellez, Manuel; Choolani, Mahesh

    2010-01-01

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We

  6. Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium

    DEFF Research Database (Denmark)

    Henriksen, Rudi; Sørensen, Flemming Brandt; Orntoft, Torben Falck

    2011-01-01

    to be followed by a strongly increased risk of ovarian cysts. We performed the present study to reveal how FKBP65 is expressed in the ovary and in ovarian tumors and to see if this expression might be related to ovarian tumor development, a relationship we have found in colorectal cancer. Biopsies from...... prospectively collected samples from ovaries and benign, borderline, and invasive ovarian tumors were analyzed for expression of FKBP65 by immunohistochemistry. The expression was compared to survival and several clinicopathological parameters. FKBP65 is strongly expressed in ovarian epithelium and in benign...... ovarian tumor cells. In the ovary, a positive staining was also found in endothelial cells of blood vessels. In non-invasive and in invasive malignant tumor cells, a decreased staining was observed, which was not correlated to stage, histology, or survival. A significant inversed correlation to expression...

  7. The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer

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    Md Zahidul Islam Pranjol

    2015-11-01

    Full Text Available Epithelial ovarian cancer (EOC is the leading cause of death from gynecologic malignancies and has a poor prognosis due to relatively unspecific early symptoms, and thus often advanced stage, metastasized cancer at presentation. Metastasis of EOC occurs primarily through the transcoelomic route whereby exfoliated tumor cells disseminate within the abdominal cavity, particularly to the omentum. Primary and metastatic tumor growth requires a pool of proangiogenic factors in the microenvironment which propagate new vasculature in the growing cancer. Recent evidence suggests that proangiogenic factors other than the widely known, potent angiogenic factor vascular endothelial growth factor may mediate growth and metastasis of ovarian cancer. In this review we examine the role of some of these alternative factors, specifically cathepsin D and cathepsin L.

  8. The Potential Role of the Proteases Cathepsin D and Cathepsin L in the Progression and Metastasis of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Pranjol, Md Zahidul Islam; Gutowski, Nicholas; Hannemann, Michael; Whatmore, Jacqueline

    2015-11-20

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and has a poor prognosis due to relatively unspecific early symptoms, and thus often advanced stage, metastasized cancer at presentation. Metastasis of EOC occurs primarily through the transcoelomic route whereby exfoliated tumor cells disseminate within the abdominal cavity, particularly to the omentum. Primary and metastatic tumor growth requires a pool of proangiogenic factors in the microenvironment which propagate new vasculature in the growing cancer. Recent evidence suggests that proangiogenic factors other than the widely known, potent angiogenic factor vascular endothelial growth factor may mediate growth and metastasis of ovarian cancer. In this review we examine the role of some of these alternative factors, specifically cathepsin D and cathepsin L.

  9. Computed tomographic findings of ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Kwi Ryeon; Lee, Ki Man; Woo, Seong Ku; Suh, Soo Jhi [Keimyung University School of Medicine, Seoul (Korea, Republic of); Kang, Duk Sik [Kyungpook National University College of Medicine, Taegu (Korea, Republic of)

    1986-08-15

    The diagnosis of ovarian tumor has been mainly dependent on manual pelvic examination and ultrasonography. But in case of malignant ovarian tumor, CT has more advantages over ultrasonography in assessing anatomic details, relationships to bowel loops, precise extents of tumors and follow-up examinations after surgery. Authors analyzed CT features of 46 cases of pathologically proven ovarian tumors for recent 4 years at Keimyung University Dongsan Hospital. The results were as follows: 1. The most common tumor was serous cyst adenocarcinoma (9 cases: 20%), followed by metastases (8 cases: 17%), mucinous cyst adenocarcinoma (7 cases: 15%), mucinous cyst adenocarcinoma (5 cases: 11%), teratoma (5 cases: 11%), lymphoma (3 cases: 7%) and dysgerminoma (2 cases: 4%). 2. The ovarian tumors were variable in size from 2.5 cm to 33 cm in diameter. Most of the solid tumors were smaller than 10 cm in diameter and most of the cystic tumors were larger than 10 cm in diameter. Usually mucinous tumors were much larger than serous tumors. Mucinous cyst adenomas were the largest tumors. 3. Unilateral tumors (left 19, right 13 cases) were more common than bilateral tumors (12 cases). Bilateral tumors were seen in serous and mucinous cyst adenocarcinoma, metastases and lymphoma. 4. CT features of mucinous cyst adenomas were smooth margins and thin wall of the tumor masses and multifaceted cysts with internal septa in all 7 cases. 5. In contrast, CT demonstration of bilaterally, irregular margin, thick wall, enhancing solid lesion, septal irregularity, adhesion to adjacent structures, peritoneal/omental implantation, ascites and hydronephrosis were signs suggesting malignancy. CT features of the serous cyst adenocarcinoma were mostly solid to mixed nature (83%), irregular margin (75%), enhancing solid lesion (67%), papillary growth (75%), internal septa (58%), multilocularity (58%) and calcification (25%) in descending order of frequency. 6. On CT, mucinous cystadenocarcinoma were

  10. A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer - An international multicenter study in women with an ovarian mass

    DEFF Research Database (Denmark)

    Karlsen, Mona Aarenstrup; Høgdall, Estrid V S; Christensen, Ib J

    2015-01-01

    masses and 550 patients with ovarian cancer. RESULTS: Overall, 2665 patients were included. CPH-I was highly significant in discriminating benign from malignant ovarian disease. At the defined cut-off of 0.070 for CPH-I the sensitivity and specificity were 95.0% and 78.4% respectively in the training...

  11. A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value.

    Science.gov (United States)

    Lu, Karen H; Skates, Steven; Hernandez, Mary A; Bedi, Deepak; Bevers, Therese; Leeds, Leroy; Moore, Richard; Granai, Cornelius; Harris, Steven; Newland, William; Adeyinka, Olasunkanmi; Geffen, Jeremy; Deavers, Michael T; Sun, Charlotte C; Horick, Nora; Fritsche, Herbert; Bast, Robert C

    2013-10-01

    A 2-stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high-risk scores were referred for transvaginal ultrasound (TVS). A single-arm, prospective study of postmenopausal women was conducted. Participants underwent an annual CA125 blood test. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to next annual CA125 test (low risk), repeat CA125 test in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. ROCA followed by TVS demonstrated excellent specificity and positive predictive value in a population of US women at average risk for ovarian cancer. Copyright © 2013 American Cancer Society.

  12. Persistent ovarian masses and pregnancy outcomes.

    Science.gov (United States)

    Goh, William A; Rincon, Monica; Bohrer, Justin; Tolosa, Jorge E; Sohaey, Roya; Riaño, Rene; Davis, James; Zalud, Ivica

    2013-07-01

    To determine if persistent ovarian masses in pregnancy are associated with increased adverse outcomes. This is a retrospective cohort of 126 pregnant women with a persistent ovarian mass measuring 5 cm or greater who delivered at two university hospitals between 2001 and 2009. Maternal outcomes included gestational age (GA) at diagnosis, delivery and surgery as well as miscarriage, preterm birth (PTB), ovarian torsion and hospital admission for pain. Neonatal outcomes included birth weight, respiratory distress syndrome (RDS), intra-ventricular hemorrhage (IVH), death and sepsis. A total of 1225 ovarian masses were identified (4.9%) in 24,868 patients. A persistent ovarian mass was found in 0.7%. Average GA at diagnosis was 17.8 weeks. Miscarriage rate was 3.3%. Average GA at delivery was 37.9 weeks. Of the patients, 8.5% had ovarian torsion, 10.3% had admission for pain and 9.3% had PTBs. The mean cesarean delivery rate was 46.3%. The average neonatal weight was 3273 g. There was one neonatal death in this cohort. The rate of RDS was 2.8%, IVH 0.9% and neonatal sepsis 1.9%. The most common surgical pathologic diagnosis was dermoids (37.6%). No overt malignancies were seen. A persistent ovarian mass in pregnancy does not confer an increased risk of adverse pregnancy outcomes.

  13. ACTIVITY OF NATURAL KILLER CELLS IN BIOLOGICAL FLUIDS FROM PATIENTS WITH COLORECTAL AND OVARIAN CANCERS

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    N. V. Yunusova

    2017-01-01

    Full Text Available Objective. To compare the functional activity of natural killer cells in peripheral blood and ascites from patients with different stages of colorectal and ovarian cancers and benign ovarian tumors. Material and methods. The study included 10 patients with stage IIIC ovarian cancer (FIGO, 2009, 5 patients with benign ovarian tumors (BOTs, and 15 patients with colorectal cancer (T2–4N0–2M0 . The control group consisted of 5 healthy donors. To evaluate the number and functional activity of NK-cells in peripheral blood and ascites, the FACS Canto II Flow Cytometer was used. Results. In peripheral blood of patients with ovarian and colorectal cancers, the relative number of activated NK-cells capable of secreting granzyme B (GB (CD56 + CD107a + GB + PF- was significantly lower and the proportion of degranulated NK-cells (CD56 + CD107a + GB- PF- was higher than those of healthy donors. Low total NK-cell counts in peripheral blood were a distinctive feature of ovarian cancer patients (p<0.05. The proportion of activated peripheral blood NK-cells, containing granules of cytolytic enzymes GB and perforin (PF increased with tumor growth. However, lymph node metastasis in patients with colorectal cancer did not affect the level and activation of NK-cells. The comparative analysis of NK-populations in patients with benign and malignant ovarian tumors revealed that the level of CD56 + cells was significantly higher in tumor ascites compared to peripheral blood. In patients with BTs, the levels of CD56 + CD107a + and activated CD56 + CD107a + GB-PF-degranulated cells was higher in ascites than in blood. In patients with ovarian cancer, the level of degranulated cells was higher in peripheral blood than in malignant ascites. Conclusion. The tumor cells and tumor microenvironment were found to affect the number and the functional activity of NK-cells. The accumulation of free fluid within the peritoneal cavity in patients with both benign and malignant

  14. Histone Deacetylase Inhibitor Therapy in Epithelial Ovarian Cancer

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    Noriyuki Takai

    2010-01-01

    Full Text Available Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials.

  15. Review of theories on development of ovarian cancer. Leptin as a potential agent engaged in carcinogenesis

    International Nuclear Information System (INIS)

    Markowska, A.

    2007-01-01

    Many different hypotheses and theories have been formulated regarding the development of sporadic ovarian cancer. The augmented risk is associated with nulliparity or low fecundity. Apart from changes in the genital system, leptin can be linked in several ways to infertility or low fecundity, from poor alimentation (severe dieting) and its effects on the hypothalamushypophysis-ovary axis to improper blastocyst implantation in the endometrium. Ovulation used to be regarded as representing one of the factors which promote the development of ovarian cancer due to the associated lesions of the ovarian epithelium and the development of inclusion cysts. The risk is reduced by the long-term use of contraceptive pills. However, it has been demonstrated, that hormonal contraception is linked to the stabilization of plasma leptin levels and that it, possibly, has less pronounced effects on target tissues. In view of the suggestions on leptin involvement, the hypothesis regarding the effects of HRT on ovarian cancer development remains unsupported since leptin levels during a course of HRT manifest no increases or decreases- they remain stable. The inflammatory theory of ovarian cancer development might also be linked to the potential involvement of leptin in the pathogenesis of endometriosis, promoting endometrioid and clarocellular ovarian cancers. Leptin has been shown to be linked to the development of endometriosis, particularly due to its mitogenic and angiogenic effects. Bilateral ovariectomy, aimed at preventing the development of ovarian cancer, induces a decrease in serum leptin levels, in contrast to the reversible effects of pharmacological gonadectomy. Ovarian cancer develops more frequently in women who have high living standards, which is significantly associated with increased BMI and augmented serum leptin levels. The described theory concerning the two pathways of ovarian cancer development, including one typical for more aggressive serous cancers, may

  16. Ovarian cancer: the clinical role of US, CT, and MRI

    International Nuclear Information System (INIS)

    Togashi, K.

    2003-01-01

    This article presents an overview of ovarian cancer, which addresses the clinical roles of imaging studies, including US, CT, and MR imaging in the course of diagnosis and treatment of this important disease. US is the modality of choice in the evaluation of patients with suspected adnexal masses. Although its accuracy is not sufficient to avert surgery, morphological analysis of adnexal masses with US helps narrow the differential diagnosis, determining the degree of suspicion for malignancy, usually in concert with a serum CA-125 level. Combined morphological and vascular imaging obtained by US appear to further improve the preoperative assessment of adnexal masses. For uncertain or problematic cases, MR imaging helps to distinguish benign from malignant, with an overall accuracy for the diagnosis of malignancy of 93%. The accuracy of MR imaging in the confident diagnosis of mature cystic teratoma, endometrial cysts, and leiomayomas is very high. CT is not indicated for differential diagnosis of adnexal masses because of poor soft tissue discrimination, except for fatty tissue and for calcification, and the disadvantages of irradiation. In the staging of ovarian cancer, CT, US, and MR imaging all have a similarly high accuracy. Although it is difficult to suggest a simple algorithm for evaluating the state of women with adnexal masses, the correct preoperative diagnosis and staging of ovarian cancer with the use of any of these imaging studies will lead to an appropriate referral to a specialist in gynecologic oncology and offer a significant survival advantage for patients with ovarian cancer. (orig.)

  17. Failure of Elevating Calcium Induces Oxidative Stress Tolerance and Imparts Cisplatin Resistance in Ovarian Cancer Cells

    OpenAIRE

    Ma, Liwei; Wang, Hongjun; Wang, Chunyan; Su, Jing; Xie, Qi; Xu, Lu; Yu, Yang; Liu, Shibing; Li, Songyan; Xu, Ye; Li, Zhixin

    2016-01-01

    Cisplatin is a commonly used chemotherapeutic drug, used for the treatment of malignant ovarian cancer, but acquired resistance limits its application. There is therefore an overwhelming need to understand the mechanism of cisplatin resistance in ovarian cancer, that is, ovarian cancer cells are insensitive to cisplatin treatment. Here, we show that failure of elevating calcium and oxidative stress tolerance play key roles in cisplatin resistance in ovarian cancer cell lines. Cisplatin induce...

  18. Focal Endometrial Adenocarcinoma in Atypical Polypoid Adenomyoma of Low Malignant Potential

    Directory of Open Access Journals (Sweden)

    Coskun Salman

    2009-12-01

    This report describes a perimenopausal woman with atypical polypoid adenomyoma of low malignant potential with focal adenocarcinoma on endometrial biopsy who subsequently underwent hysterectomy in which no residual malignant lesion was found.

  19. Estrogen, Progesterone and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ho Shuk-Mei

    2003-10-01

    Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

  20. Silencing of BAG3 promotes the sensitivity of ovarian cancer cells to cisplatin via inhibition of autophagy.

    Science.gov (United States)

    Qiu, Shuang; Sun, Liang; Jin, Ye; An, Qi; Weng, Changjiang; Zheng, Jianhua

    2017-07-01

    Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin‑based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy. In the present study, as a novel autophagy regulator, BCL2‑associated athanogene 3 (BAG3) was investigated to study its role in cisplatin sensitivity in epithelial ovarian cancer. However, whether BAG3 participates in cisplatin sensitivity by inducing autophagy and the underlying mechanism in ovarian cancer cells remain to be clarified. Through the use of quantitative real-time PCR, western blot analysis, CCK-8 and immunofluorescence assays our data revealed that cisplatin-induced autophagy protected ovarian cancer cells from the toxicity of the drug and that this process was regulated by BAG3. Silencing of BAG3 increased cisplatin-induced apoptosis. The results also revealed BAG3 as a potential therapeutic target which enhanced the efficacy of cisplatin in ovarian cancer.

  1. Histones and their modifications in ovarian cancer – drivers of disease and therapeutic targets

    Directory of Open Access Journals (Sweden)

    Deborah Joy Marsh

    2014-06-01

    Full Text Available Epithelial ovarian cancer has the highest mortality of the gynecological malignancies. High grade serous epithelial ovarian cancer (SEOC is the most common subtype, with the majority of women presenting with advanced disease where 5 year survival is around 25%. Platinum-based chemotherapy in combination with paclitaxel remains the most effective treatment despite platinum therapies being introduced almost 40 years ago. Advances in molecular medicine are underpinning new strategies for the treatment of cancer. Major advances have been made by international initiatives to sequence cancer genomes. For SEOC, with the exception of TP53 that is mutated in virtually 100% of these tumors, there is no other gene mutated at high frequency. There is extensive copy number variation, as well as changes in methylation patterns that will influence gene expression. To date, the role of histones and their post-translational modifications in ovarian cancer is a relatively understudied field. Post-translational histone modifications play major roles in gene expression as they direct the configuration of chromatin and so access by transcription factors. Histone modifications include methylation, acetylation and monoubiquitination, with involvement of enzymes including histone methyl transferases (HMTases, histone acetyltransferases/deacetylases and ubiquitin ligases/deubiquitinases respectively. Complexes such as the Polycomb Repressive Complex also play roles in the control of histone modifications and more recently roles for long non-coding (lnc RNA and microRNAs (miRNAs are emerging. Epigenomic-based therapies targeting histone modifications are being developed and offer new approaches for the treatment of ovarian cancer. Here we discuss histone modifications and their aberrant regulation in malignancy and specifically in ovarian cancer. We review current and upcoming histone-based therapies that have the potential to inform and improve treatment strategies for

  2. Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Timmermans Wielenga, Vera; Nedergaard, Lotte

    2011-01-01

    Cryopreserved ovarian cortical biopsies from 51 patients with breast cancer were examined by histologic and immunohistochemical analysis and showed no sign of metastases. Autotransplantation of ovarian cortex to patients with low-stage breast cancer disease appears safe, but confirmatory studies ...

  3. A THREE YEAR RETROSPECTIVE STUDY OF OVARIAN NEOPLASMS WITH SPECIAL EMPHASIS ON SURFACE EPITHELIAL TUMOURS

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    Krishna Bharathi Yarlagadda

    2016-07-01

    Full Text Available BACKGROUND Ovarian tumours being second most common gynaecological cancer in India account for 30% of all cancers of female genital tract. Study conducted to determine relative frequencies of various histological types based on WHO classification and their age distribution with particular emphasis on surface epithelial tumours. This study is undertaken to find out the frequency of incidence of different histopathological subtypes with particular emphasis on surface epithelial tumours and age distribution of ovarian tumours in our institute located in coastal Andhra Pradesh. METHODS This is a retrospective study of 100 cases of ovarian neoplasms collected during a period of 3 years from June 2013 to May 2016 from the Department of Pathology, Katuri Medical College and Hospital, Chinakondrupadu, Guntur, A. P, India. The patients attending our hospital are mostly from rural areas around. Paraffin blocks of all 100 ovarian neoplasms retrieved. Complete clinical and radiological findings analysed from our records. RESULTS The tumours are grouped according to the nature of tumour whether benign or borderline or malignant according to cell of origin, histological subtyping, and age group. Surface epithelial tumours are the most common. Benign tumours outnumber the malignant tumours. Benign ovarian tumours showed a peak in 21-40 Yrs. age group and malignant in the age group of 41- 60 Yrs. Results of our study compared with other studies. CONCLUSION Because of the geographic location, poverty, and illiteracy, patients seek medical advice late. So, awareness among public by health education, passive surveillance, and community screening facility will be helpful in early detection of ovarian neoplasms.

  4. Are ovarian cancer stem cells the target for innovative immunotherapy?

    Directory of Open Access Journals (Sweden)

    Wang L

    2018-05-01

    Full Text Available Liang Wang, Tianmin Xu, Manhua Cui Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Abstract: Cancer stem cells (CSCs, a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy, immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR- T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. Keywords: cancer stem cells, ovarian cancer, epigenetics, tumor cell surface marker, immunotherapy, CAR

  5. Dysregulation of mitotic machinery genes precedes genome instability during spontaneous pre-malignant transformation of mouse ovarian surface epithelial cells

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    Ulises Urzúa

    2016-10-01

    Full Text Available Abstract Background Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE. Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. Results At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05 comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1, Birc5 (Survivin, Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Conclusion Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes

  6. Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11.

    Science.gov (United States)

    van der Steen, Sophieke C H A; van Tilborg, Angela A G; Vallen, Myrtille J E; Bulten, Johan; van Kuppevelt, Toin H; Massuger, Leon F A G

    2016-03-01

    The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology. The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status. The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status. Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Salivary micro RNA as a potential biomarker in oral potentially malignant disorders: A systematic review

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    T N Uma Maheswari

    2018-01-01

    Full Text Available Oral potentially malignant disorders (OPMD are oral mucosal disorders which have a high potential to turn into malignancy. A recent report suggests that 16%–62% of epithelial dysplasia cases of OPMD undergo malignant transformation, showing the need for early detection of malignancy in these disorders. Micro RNA (miRNA plays an important role in cellular growth, differentiation, apoptosis, and immune response, and hence, deregulation of miRNA is considered a signature of oral carcinogenesis. A search was done using MeSH terms in the PubMed, ScienceDirect databases, hand search, and finally, six studies were included in this systematic review. A total of 167 patients with oral cancer, 78 with OPMDs, 147 healthy controls, and 20 disease controls were analyzed for the expression of salivary miRNAs. Quality assessment based on the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to obtain a risk of bias chart using Revman 5.3 software and it was proved that the study done by Zahran et al. in 2015 had a low risk of bias. The results of this study revealed upregulated miRNA 184 with an area under the curve (AUC of 0.86 and miRNA 21 with an AUC of 0.73 and downregulated miRNA 145 with an AUC of 0.68, which proved that these miRNAs are significant in detecting early malignancy in OPMD and should be further analyzed in various populations. This systematic review explored the potential of expression of salivary miRNA in OPMD for future studies. This could pave the way to utilize saliva as a surrogate marker in diagnosing early malignant changes in OPMD.

  8. Advanced Ovarian Dysgerminoma Infiltrating Both Ovaries and Uterus in a 7-Year-Old Girl

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    Nexhmi Hyseni

    2014-01-01

    Full Text Available Introduction. Ovarian dysgerminoma is a rare malignant ovarian germ cell tumor with its peak incidence in young women. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. Depending on the FIGO stage at presentation the prognosis of dysgerminomas after surgical treatment, adjuvant chemotherapy, and radiotherapy is promising. Case Presentation. A 7-year-old girl was presented at our clinic with abdominal pain in all abdominal quadrants. Later the pain localized in the region of her right ovary. CT scan revealed a massive formation which was connected to her right ovary. Conclusion. Although malignant ovarian germ cell tumours are rare in children, physicians must always consider the possibility of MOGT-occurrences. The clinical symptoms might not be specific: abdominal pain, abdominal distention, nausea, and vomiting. In order to make a correct diagnosis the patients should undergo a complete clinical examination including radiological scans. Initial management is frequently surgery, followed by adjuvant chemotherapy and radiotherapy. Although disgerminoma is malignant tumor, the prognosis is promising.

  9. Potential role of miR-9 and miR-223 in recurrent ovarian cancer

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    McGuinness Eamonn

    2008-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease. Results Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6 in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18 and FFPE serous ovarian tumours (n = 22. Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry. Conclusion We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.

  10. My Personal Journey With Ovarian Cancer Treatment: Caring and Chemotherapy Tips.

    Science.gov (United States)

    Decker, Kim A

    2016-12-01

    Six years ago, I was diagnosed with stage IIIA ovarian low malignant cell potential cancer. It was the most shocking situation I have ever experienced. I didn't realize I had any symptoms, except occasional back pain, which I attributed to starting a new workout program. I had scheduled an abdominal computerized tomography (CT) scan for recurrent microscopic hematuria, which my internist wanted to check. I was told I would hear the results in two days. Two hours after my CT scan, while I was eating ice cream and watching television, an on-call genitourinary doctor (who I did not personally know) called to tell me the good news-that I had kidney stones, thus the microscopic hematuria. However, the bad news was that I had ovarian cancer that had spread to my omentum. He said he would call my gynecologist right away.

  11. Infrequent Expression of the Cancer-Testis Antigen, PASD1, in Ovarian Cancer

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    Ghazala Khan

    2015-01-01

    Full Text Available Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I, there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs, such as Per ARNT SIM (PAS domain containing 1 (PASD1, are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I ( n = 164 and stage II ( n = 14 disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue.

  12. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

    Science.gov (United States)

    Teinturier, C; Hartmann, O; Valteau-Couanet, D; Benhamou, E; Bougneres, P F

    1998-11-01

    We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.

  13. [Microcytomorphometric video-image detection of nuclear chromatin in ovarian cancer].

    Science.gov (United States)

    Grzonka, Dariusz; Kamiński, Kazimierz; Kaźmierczak, Wojciech

    2003-09-01

    Technology of detection of tissue preparates precisious evaluates contents of nuclear chromatine, largeness and shape of cellular nucleus, indicators of mitosis, DNA index, ploidy, phase-S fraction and other parameters. Methods of detection of picture are: microcytomorphometry video-image (MCMM-VI), flow, double flow and activated by fluorescence. Diagnostic methods of malignant neoplasm of ovary are still nonspecific and not precise, that is a reason of unsatisfied results of treatment. Evaluation of microcytomorphometric measurements of nuclear chromatine histopathologic tissue preparates (HP) of ovarian cancer and comparison to normal ovarian tissue. Estimated 10 paraffin embedded tissue preparates of serous ovarian cancer, 4 preparates mucinous cancer and 2 cases of tumor Kruckenberg patients operated in Clinic of Perinatology and Gynaecology Silesian Medical Academy in Zabrze in period 2001-2002, MCMM-VI estimation based on computer aided analysis system: microscope Axioscop 20, camera tv JVCTK-C 1380, CarlZeiss KS Vision 400 rel.3.0 software. Following MCMM-VI parameters assessed: count of pathologic nucleus, diameter of nucleus, area, min/max diameter ratio, equivalent circle diameter (Dcircle), mean of brightness (mean D), integrated optical density (IOD = area x mean D), DNA index and 2.5 c exceeding rate percentage (2.5 c ER%). MCMM-VI performed on the 160 areas of 16 preparates of cancer and 100 areas of normal ovarian tissue. Statistical analysis was performed by used t-Student test. We obtained stastistically significant higher values parameters of nuclear chromatine, DI, 2.5 c ER of mucinous cancer and tumor Kruckenberg comparison to serous cancer. MCMM-VI parameters of chromatine malignant ovarian neoplasm were statistically significantly higher than normal ovarian tissue. Cytometric and karyometric parametres of nuclear chromatine estimated MCMM-VI are useful in the diagnostics and prognosis of ovarian cancer.

  14. New perspectives on targeted therapy in ovarian cancer

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    Coward JIG

    2015-02-01

    Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

  15. Potential Mechanisms for Racial and Ethnic Differences in Antimüllerian Hormone and Ovarian Reserve

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    Reshef Tal

    2013-01-01

    Full Text Available Accumulating evidence suggests that reproductive potential and function may be different across racial and ethnic groups. Racial differences have been demonstrated in pubertal timing, infertility, outcomes after assisted reproductive technology (ART treatment, and reproductive aging. Recently, racial differences have also been described in serum antimüllerian hormone (AMH, a sensitive biomarker of ovarian reserve, supporting the notion that ovarian reserve differs between racial/ethnic groups. The existence of such racial/ethnic differences in ovarian reserve, as reflected by AMH, may have important clinical implications for reproductive endocrinologists. However, the mechanisms which may underlie such racial differences in ovarian reserve are unclear. Various genetic factors and environmental factors such as obesity, smoking, and vitamin D deficiency which have been shown to correlate with serum AMH levels and also display significant racial/ethnic variations are discussed in this review. Improving our understanding of racial differences in ovarian reserve and their underlying causes may be essential for infertility treatment in minority women and lead to better reproductive planning, improved treatment outcomes, and timely interventions which may prolong reproductive lifespan in these women.

  16. New advances in ovarian autotransplantation to restore fertility in cancer patients.

    Science.gov (United States)

    Salama, Mahmoud; Woodruff, Teresa K

    2015-12-01

    Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results.

  17. THE ABERRANT PROMOTER HYPERMETHYLATION PATTERN OF THE ANTI - ANGIOGENIC TSP1 GENE IN EPITHELIAL OVARIAN CARCINOMA: AN INDIAN STUDY

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    Ramesh

    2015-06-01

    Full Text Available PURPOSE: The promoter hypermethylation patterns of Thrombospodin - 1 gene in 50 EOC patients were studied and the methylation pattern was correlated with various clinic pathological parameters. METHODS: The promoter hypermethylation pattern of the TSP - 1 gene was assessed using nested PCR and Methylation specific PCR. STATISTICAL ANALYSIS: All the available data was statistically analyzed using the Chi square test or Fisher Exact Test on the SPSS software version 22.0 and a value <0.0 5 was considered statistically significant. RESULTS: Forty of the fifty ovarian carcinoma samples reported positive for methylation corresponding to a methylation frequency of 80%. A methylation frequency of 89.2%, 83.3% and 42.8% was observed in malignant , Low malignant potential (borderline and benign sample cohorts. CONCLUSION: From the results drawn from this study, it clearly shows that the anti angiogenic protein TSP - 1 is extensively hypermethylated in ovarian carcinoma and that it accumulates over t he progression of the disease from benign to malignant. As previous reports suggest that there is no evidence of mutation of this gene, promoter hypermethylation may be a crucial factor for the down regulation of the gene. Further by clubbing together the promoter hypermethylation pattern of TSP - 1 gene with hypermethylation patterns of other TSG may provide a better insight into the application of using methylation profiles of TSG as a biomarker in the detection of ovarian carcinoma.

  18. Benign ovarian and endometrial uptake on FDG PET-CT. Patterns and pitfalls

    International Nuclear Information System (INIS)

    Liu, Y.

    2009-01-01

    Increased ovarian or endometrial uptake may cause a dilemma in the interpretation of whole body F18-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging or even misdiagnosis of malignant disease. Knowledge of benign FDG uptake of the ovaries and uterus is important for daily practice of nuclear medicine radiologists. Increased uptake in the ovaries or uterus indicates a pathologic or neoplastic process in postmenopausal patients. In premenopausal women, increased ovarian or endometrial uptake can be functional or malignant. Benign functional uptake of premenopausal ovaries or uterus is related to the menstrual cycle; therefore, information about the patient's menstrual status is crucial for interpretation. In addition, correlation with computed tomography (CT), especially diagnostic CT acquired at the same time of PET/CT is very useful in clarifying the location of the uptake and the existence or disappearance of the discrete lesion. Increased ovarian uptake may also be identified in histologically different benign tumor entities. Nonmenstrual-related endometrial uptake may be present in many benign diseases as well. (author)

  19. Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

    International Nuclear Information System (INIS)

    Ricciardelli, Carmela; Ween, Miranda P; Lokman, Noor A; Tan, Izza A; Pyragius, Carmen E; Oehler, Martin K

    2013-01-01

    Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance. We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance. HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin. Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC

  20. Characteristic odour in the blood reveals ovarian carcinoma

    International Nuclear Information System (INIS)

    Horvath, György; Andersson, Håkan; Paulsson, Gunnar

    2010-01-01

    Ovarian carcinoma represents about 4% of all cancers diagnosed in women worldwide. Mortality rate is high, over 50%, mainly due to late diagnosis. Currently there are no acceptable screening techniques available, although ovarian cancer belongs to the group of malignancies for which mortality could be dramatically reduced by early diagnosis. In a recently published study, we clearly demonstrated that human ovarian carcinoma tissues can be characterized by a specific odour, detectable by a trained dog. Another recent study confirmed these results using an electronic nose. In the present work, we examined whether the cancer-specific odour can also be found in the blood. Two specially trained dogs were used. Both ovarian cancer tissues and blood from patients with ovarian carcinoma were tested. The tissue tests showed sensitivity of 100% and specificity of 95%, while the blood tests showed sensitivity of 100% and specificity of 98%. The present study strongly suggests that the characteristic odour emitted by ovarian cancer samples is also present in blood (plasma) taken from patients with the disease. This finding opens possibilities for future screening of healthy populations for early diagnosis of ovarian carcinoma. A future challenge is to develop a sensitive electronic nose for screening of ovarian carcinoma by testing the blood/plasma to detect the disease at a stage early enough for treatment to be effective

  1. Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck

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    Asotra Kamlesh

    2010-02-01

    Full Text Available Abstract Matrix metalloproteinases (MMPs are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G, MMP-2 (-1306 C/T, MMP-3 (-1171 5A/6A, MMP-9 (-1562 C/T and TIMP-2 (-418 G/C or C/C. Tissue inhibitors of metalloproteinases (TIMPs are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities.

  2. p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer.

    Science.gov (United States)

    Ito, Tomohiro; Hamasaki, Makoto; Matsumoto, Shinji; Hiroshima, Kenzo; Tsujimura, Tohru; Kawai, Toshiaki; Shimao, Yoshiya; Marutsuka, Kousuke; Moriguchi, Sayaka; Maruyama, Riruke; Miyamoto, Shingo; Nabeshima, Kazuki

    2015-06-01

    It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC. p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion. According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%. Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected. Copyright© by the American Society for Clinical Pathology.

  3. Meta-analysis of the predictive value of DNA aneuploidy in malignant transformation of oral potentially malignant disorders.

    Science.gov (United States)

    Alaizari, Nader A; Sperandio, Marcelo; Odell, Edward W; Peruzzo, Daiane; Al-Maweri, Sadeq A

    2018-02-01

    DNA aneuploidy is an imbalance of chromosomal DNA content that has been highlighted as a predictor of biological behavior and risk of malignant transformation. To date, DNA aneuploidy in oral potentially malignant diseases (OPMD) has been shown to correlate strongly with severe dysplasia and high-risk lesions that appeared non-dysplastic can be identified by ploidy analysis. Nevertheless, the prognostic value of DNA aneuploidy in predicting malignant transformation of OPMD remains to be validated. The aim of this meta-analysis was to assess the role of DNA aneuploidy in predicting malignant transformation in OPMD. The questions addressed were (i) Is DNA aneuploidy a useful marker to predict malignant transformation in OPMD? (ii) Is DNA diploidy a useful negative marker of malignant transformation in OPMD? These questions were addressed using the PECO method. Five studies assessing aneuploidy as a risk marker of malignant change were pooled into the meta-analysis. Aneuploidy was found to be associated with a 3.12-fold increased risk to progress into cancer (RR=3.12, 95% CI 1.86-5.24). Based on the five studies meta-analyzed, "no malignant progression" was more likely to occur in DNA diploid OPMD by 82% when compared to aneuploidy (RR=0.18, 95% CI 0.08-0.41). In conclusion, aneuploidy is a useful marker of malignant transformation in OPMD, although a diploid result should be interpreted with caution. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Malignant and benign ovarian neoplasms among atomic bomb survivors, Hiroshima and Nagasaki, 1950 - 80

    International Nuclear Information System (INIS)

    Tokuoka, Shoji; Kawai, Kioko; Shimizu, Yukiko; Inai, Kouki; Ohe, Kazuhiko; Fujikura, Toshio; Kato, Hiroo.

    1988-09-01

    For 1950 - 80, 194 ovarian cancer cases were ascertained among the 70,030 females of the RERF Life Span Study (LSS-E85) sample, and 106 autopsied cases with benign ovarian neoplasms were ascertained among all 3,046 autopsies performed in the same sample. On the basis of microscopic review, 66 % of the cancer and 84 % of the benign tumor cases were classified by histological type. The age-adjusted ovarian cancer incidence rates showed a statistically significant increase with increased exposure dose, both in the entire exposed group (P 0.10). The distribution of histological types of both cancer and benign tumor of the ovary did not vary significantly with radiation dose. The data are consistent with the hypothesis that radiation injury of ovaries with secondary excess of gonadotrophic hormones are important causative factors in the development of ovarian neoplasms. (author)

  5. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    International Nuclear Information System (INIS)

    Li, Fang-qiu; Han, Yan-ling; Liu, Qun; Wu, Bo; Huang, Wen-bin; Zeng, Su-yun

    2009-01-01

    Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. We found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy

  6. [Ovarian tissue cryopreservation in cancer patients--six years of clinical experience].

    Science.gov (United States)

    Huser, M; Záková, J; Crha, I; Smardová, L; Král, Z; Revel, A; Ventruba, P

    2012-04-01

    Presentation of clinical results and experience with this technique during past six years. Original paper. Gynekologicko-porodnická klinika LF MU a FN Brno, Interní hemato-onkologická klinika LF MU a FN Brno, Department of Obstetrics and Gynecology. Hadassah University Hospital Ein-Karem, Jerusalem, Izrael. Ovarian tissue cryopreservation (OTC) and its future auto-transplantation becomes an alternative for patients to prevent serious damage of ovarian function by oncology treatment. Patient is indicated to OTC in case of high risk of ovarian failure due to planned chemotherapy and impossibility to use other oncofertility techniques. Ovarian tissue harvesting is done by laparoscopy in short-term general anesthesia. After tissue processing the samples are cryopreserved in programmable automatic freezer or by vitrification. The auto-transplantation of ovarian tissue is planned after the complete cure of patient's malignancy. Our workplace doesn't have own experience with tissue transplantation - until now cryopreserved tissue has not yet been utilized by the patients. Clinical experience with this technique gained by our team during academic stay in abroad Israeli clinic is presented. During the years of 2005-2011 the OTC was performed in 19 cancer patients before chemotherapy. In majority of cases, patients suffered from blood or lymph node systemic malignancy (84%). Average age of women was 26 years. The patient set consisted of mostly nulliparous women (88%). Patient's average body mass index was 23,9 kg/m2. The length of systemic chemotherapy averaged 7.1 months. Time from fertility preservation counseling to chemotherapy was not exceeding one week (7.2 days on average). Ovarian tissue harvesting was conducted by laparoscopic surgery in all cases. The length of surgery did not exceed 60 minutes and no surgical complications were observed. The case of ovarian tissue transplantation performed on abroad university settings is discussed. In the consensus of with

  7. Ovarian neoplasms in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tokuoka, Shoji

    1986-01-01

    A recent pathological and epidemiological study on females with ovarian neoplasms among the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) Extended Sample ascertained 194 malignant and 106 benign ovarian tumor cases which had occurred during the period 1950 - 80. Of the 194 cases of ovarian cancer, 128 (66 %) were reviewed microscopically and the age-adjusted incidence of ovarian cancer revealed a statistically significant linear increase with increasing exposure dose, both in microscopically reviewed and in all cases. The radiation-related excess of ovarian cancer appeared to be highest in women less than 20 years of age when exposed, with these women having the longest latent period for tumor development, compared to the older age groups. The histological distribution of cancer types among exposed individuals appeared not very different from that seen in the general population. The analysis of 106 autopsy subjects with benign ovarian tumors, of which 89 were reviewed microscopically, depicted a trend of increasing radiation-related tumor excess with increasing exposure dose among exposed cases, though the trend is not statistically significant when observation was limited to microscopically reviewed subjects. The histological distribution of benign tumor types among exposed cases appeared not very different from that seen in the general population. The findings are consistent with a hypothesis that radiation-injured ovaries in association with secondary excess of gonadotrophic hormones are important causative factors in the development of ovarian tumors, which has been suggested by experimental findings concerning the induction of ovarian tumors by ionizing radiation and by a recent analysis of breast carcinogenesis in exposed females of Hiroshima and Nagasaki. (author)

  8. Targeting Insulin and Insulin-Like Growth Factor Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Marie-Claude Beauchamp

    2010-01-01

    Full Text Available Ovarian cancer is the most lethal of all gynecological malignancies, due in part to the diagnosis at an advanced stage caused by the lack of specific signs and symptoms and the absence of reliable tests for screening and early detection. Most patients will respond initially to treatment but about 70% of them will suffer a recurrence. Therefore, new therapeutic modalities are urgently needed to overcome chemoresistance observed in ovarian cancer patients. Evidence accumulates suggesting that the insulin/insulin growth factor (IGF pathways could act as a good therapeutic target in several cancers, including ovarian cancer. In this paper, we will focus on the role of insulin/IGF in ovarian cancer tumorigenesis and treatment.

  9. Ovarian maldescent

    Energy Technology Data Exchange (ETDEWEB)

    Trinidad, Carmen; Tardaguila, Francisco; Fernandez, Gabriel C.; Martinez, Concepcion; Chavarri, Elena; Rivas, Isabel [Departments of Radiology and Gynecology, Povisa Medical Center, Salamanca St. 5, 36211, Vigo (Pontevedra) (Spain)

    2004-05-01

    Undescended ovary is a rare disorder that can be associated with muellerian malformations. There is an unclear association with infertility and malignant disease. When an ovary is not in its normal location, it is sought in other locations above the pelvic brim. This is important in cases of undetermined cyclical abdominal pain, follicle aspiration and surgical castration. MRI has proven to be the best imaging method for finding an ovary in an anomalous position and for disregarding associated malformations. We report two patients with unilateral ovarian maldescent, one of them with Rokitansky-Kuester-Hauser syndrome. A review of the literature is included. (orig.)

  10. Synchronous occult metastasising duodenal carcinoid and ovarian mucinous cystadenocarcinoma- Multiple primary malignancies in the same patient

    Directory of Open Access Journals (Sweden)

    Devadass Clement W, Sridhar Honnappa, Aarathi R Rau, Sharat Chandra

    2014-01-01

    Full Text Available Gastrointestinal carcinoid tumors are uncommon neuroendocrine tumours that may be associated with synchronous or metachronous primary tumours of other histological type, most frequently colorectal adenocarcinomas. Primary ovarian mucinous adenocarcinomas have been reported to coincide with few other ovarian tumours and minority of these tumours may occur in association with Lynch syndrome. However association of duodenal carcinoid with ovarian mucinous adenocarcinoma is distinctly unusual and, to our knowledge, has not been previously described. We report a case of occult metastasising duodenal atypical carcinoid that was incidentally detected during surgical intervention performed for left ovarian mucinous cystadenocarcinoma in a middle aged female. The carcinoid tumour was Stage IIIB with regional nodal metastasis and the ovarian tumour was Stage IA with low grade histology.

  11. The Molecular Fingerprint of High Grade Serous Ovarian Cancer Reflects Its Fallopian Tube Origin

    Directory of Open Access Journals (Sweden)

    Thomas Meyer

    2013-03-01

    Full Text Available High grade serous ovarian cancer (HGSC, the most lethal and frequent type of epithelial ovarian cancer (EOC, has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and the capacity to develop resistance to available therapeutic drugs. Furthermore, there has been considerable controversy concerning the etiology of this malignancy. New studies, both clinical and molecular, strongly suggest that HGSC originates not from the surface of the ovary, but from the epithelial layer of the neighboring fallopian tube fimbriae. In this paper we summarize data supporting the central role of fallopian tube epithelium in the development of HGSC. Specifically, we address cellular pathways and regulatory mechanisms which are modulated in the process of transformation, but also genetic changes which accumulate during disease progression. Similarities between fallopian tube mucosa and the malignant tissue of HGSC warrant a closer analysis of homeostatic mechanisms in healthy epithelium in order to elucidate key steps in disease development. Finally, we highlight the importance of the cancer stem cell (CSC identification and understanding of its niche regulation for improvement of therapeutic strategies.

  12. Synchronous papillary carcinoma thyroid with malignant struma ovarii: A management dilemma

    International Nuclear Information System (INIS)

    Krishnamurthy, Arvind; Ramshankar, Vijayalakshmi; Vaidyalingam, Venkatesh; Majhi, Urmila

    2013-01-01

    Struma ovarii (SO) is a rare form of ovarian tumor, which is defined by the presence of thyroid tissue comprising more than 50% of the overall tumor volume. The vast majority of the variants of SO are benign; however, malignant tumors have been reported in a small percentage of cases. An aggressive multimodality approach using ovarian cancer staging laparotomy, total thyroidectomy along with radioactive iodine-131 ablation, and thyroxin suppression therapy has been shown to safely treat malignant SO both its initial presentation as well as in the event of any subsequent recurrence with excellent efficacy and possibly better oncological outcomes. The rarity of the disease and the lack of evidence surrounding its management and prognosis continue to remain a challenge to the treating clinician. We present a unique case of malignant SO with an incidental synchronous association of follicular variant of papillary carcinoma of the cervical thyroid gland, this is possibly the second case reported in the English language literature

  13. Myofibrillogenesis regulator 1 (MR-1 is a novel biomarker and potential therapeutic target for human ovarian cancer

    Directory of Open Access Journals (Sweden)

    Feng Jingjing

    2011-06-01

    Full Text Available Abstract Background Myofibrillogenesis regulator 1 (MR-1 is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, the significance of MR-1 in human ovarian cancer has not yet been explored. The aim of this study was to examine whether MR-1 is a predictor of ovarian cancer and its value as a therapeutic target in ovarian cancer patients. Methods Reverse-transcription polymerase chain reaction (PCR and quantitative real-time PCR were used to detect MR-1 mRNA levels in tissue samples from 26 ovarian cancer patients and 25 controls with benign ovarian disease. Anti-MR-1 polyclonal antibodies were prepared, tested by ELISA and western blotting, and then used for immunohistochemical analysis of the tissue samples. Adhesion and invasion of 292T cells was also examined after transfection of a pMX-MR-1 plasmid. Knockdown of MR-1 expression was achieved after stable transfection of SKOV3 cells with a short hairpin DNA pGPU6/GFP/Neo plasmid against the MR-1 gene. In addition, SKOV3 cells were treated with paclitaxel and carboplatin, and a potential role for MR-1 as a therapeutic target was evaluated. Results MR-1 was overexpressed in ovarian cancer tissues and SKOV3 cells. 293T cells overexpressed MR-1, and cellular spread and invasion were enhanced after transfection of the pMX-MR-1 plasmid, suggesting that MR-1 is critical for ovarian cancer cell growth. Knockdown of MR-1 expression inhibited cell adhesion and invasion, and treatment with anti-cancer drugs decreased its expression in cancer cells. Taken together, these results provide the first evidence of the cellular and molecular mechanisms by which MR-1 might serve as a novel biological marker and potential therapeutic target for ovarian cancer. Conclusions MR-1 may be a biomarker for diagnosis of ovarian cancer. It may also be useful for monitoring of the effects of anti-cancer therapies. Further studies are needed to clarify whether MR-1 is an early

  14. Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer.

    Science.gov (United States)

    Yokoyama, Yoshihito; Xin, Bing; Shigeto, Tatsuhiko; Umemoto, Mika; Kasai-Sakamoto, Akiko; Futagami, Masayuki; Tsuchida, Shigeki; Al-Mulla, Fahd; Mizunuma, Hideki

    2007-04-01

    Recent reports have shown that peroxisome proliferator-activated receptor (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE(2) level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.

  15. A correlation between altered O-GlcNAcylation, migration and with changes in E-cadherin levels in ovarian cancer cells

    International Nuclear Information System (INIS)

    Jin, Feng-zhen; Yu, Chao; Zhao, De-zhang; Wu, Ming-jun; Yang, Zhu

    2013-01-01

    O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins. In recent years, the roles of O-GlcNAcylation in several human malignant tumors have been investigated, and O-GlcNAcylation was found to be linked to cellular features relevant to metastasis. In this study, we modeled four diverse ovarian cancer cells and investigated the effects of O-GlcNAcylation on ovarian cancer cell migration. We found that total O-GlcNAcylation level was elevated in HO-8910PM cells compared to OVCAR3 cells. Additionally, through altering the total O-GlcNAcylation level by OGT silencing or OGA inhibition, we found that the migration of OVCAR3 cells was dramatically enhanced by PUGNAc and Thiamet G treatment, and the migration ability of HO-8910PM cells was significantly inhibited by OGT silencing. Furthermore, we also found that the expression of E-cadherin, an O-GlcNAcylated protein in ovarian cancer cells, was reduced by OGA inhibition in OVCAR3 cells and elevated by OGT silencing in HO-8910PM cells. These results indicate that O-GlcNAcylation could enhance ovarian cancer cell migration and decrease the expression of E-cadherin. Our studies also suggest that O-GlcNAcylation might become another potential target for the therapy of ovarian cancer. -- Highlights: • We examine the migration potential of diverse ovarian cancer cells. • We examine the total O-GlcNAcylation level of diverse ovarian cancer cells. • Increasing O-GlcNAcylation level will enhance the migration of ovarian cancer cells. • Reducing O-GlcNAcylation level will inhibit the migration of ovarian cancer cells. • The mechanism explains O-GlcNAcylation enhance ovarian cancer cell migration

  16. MRI appearances of pure epithelial papillary serous borderline ovarian tumours

    International Nuclear Information System (INIS)

    Naqvi, J.; Nagaraju, E.; Ahmad, S.

    2015-01-01

    Borderline epithelial ovarian tumours (BOT) represent 15–20% of all non-benign ovarian epithelial neoplasms. Compared to malignant ovarian tumours, they usually present at a younger age and carry a far superior prognosis. Fertility-conserving surgery is an important treatment option for patients with BOT. Ultrasound and CT are both widely available and play roles in the initial investigation and staging of BOT, respectively. However, lack of soft-tissue contrast limits their ability to characterize BOT. MRI can facilitate recognition of pure epithelial serous BOT (SBOT), including the cystic papillary and surface papillary subtypes. An abundance of hyperintense papillary projections with low signal internal branching and ovarian stroma preservation with a hypointense ovarian capsular margin on T2-weighted imaging are features strongly suggestive of SBOT. In this review we will discuss the general morphological features of SBOT, the benefits and drawbacks of ultrasound and CT in the initial work-up, and the principal MRI features enabling recognition of surface papillary and cystic papillary SBOT

  17. Sonographic diagnosis of the contralateral ovary in patients with ovarian tumor

    International Nuclear Information System (INIS)

    Lee, Eun Ju; Jung, Jin Young; Lee, Chang Ho; Suh; Jung Ho

    1999-01-01

    To assess the usefulness of transvaginal sonography(TVS) in the detection of normal contralateral ovary and disease involvement of contralateral ovary in the patients with ovarian tumor. We compared sonographic findings with histopathologic findings of the contralateral ovary retrospectively in 87 patients, who underwent preoperative ultrasonography and laparotomy for ovarian tumor for recent 4 years. Abnormality of the contralateral ovary was confirmed in 49 (56.3%) of 87 patients. The pathologic diagnoses of contralateral ovarian lesions were bilateral involvement of the same disease in 39 patients, different tumor in four patients and non-tumorous lesion in six patients. Abnormal TVS findings of the contralateral ovary were detected in 34 of 49 patients, which shows diagnostic accuracy of 82.8%. The sensitivity and specificity were 69.4% and 100%, respectively. 15 cases which were not diagnosed by ultrasound were bilateral involvement of the same disease in 10 cases (1 serous cystadenoma, 2 cystadenocarcinoma with low malignant potential, 1 brenner tumor, 1 metastatic endometrioid cancer, 1 metastasis, 4 teratoma) and different lesions in the remaining 5 patients (2 endosalpingiosis, 1 surface inclusion cyst, 2 tuboovarian cyst). Ultrasound of the contralateral ovary in the patients with ovarian tumor shows low to a moderate degree sensitivity and accuracy. So, more intensive and targeted evaluation of contralateral ovary is needed for the more accurate diagnosis and proper treatment.

  18. Transforming Growth Factor-? and Nitrates in Epithelial Ovarian Cancer

    OpenAIRE

    Khalifa, Ali; Kassim, Samar K.; Ahmed, Maha I.; Fayed, Salah T.

    2002-01-01

    The role of transforming growth factor-β (TGF-β) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-β by enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-β, nitrate, and SPF were significant among different groups (X2 = 12.01, P = 0.0025, X2 = 67.42, P = 0.000, X2 =...

  19. Modeling extracellular matrix (ECM) alterations in ovarian cancer by multiphoton excited fabrication of stromal models (Conference Presentation)

    Science.gov (United States)

    Campagnola, Paul J.; Ajeti, Visar; Lara, Jorge; Eliceiri, Kevin W.; Patankar, Mansh

    2016-04-01

    A profound remodeling of the extracellular matrix (ECM) occurs in human ovarian cancer but it unknown how this affects tumor growth, where this understanding could lead to better diagnostics and therapeutic approaches. We investigate the role of these ECM alterations by using multiphoton excited (MPE) polymerization to fabricate biomimetic models to investigate operative cell-matrix interactions in invasion/metastasis. First, we create nano/microstructured gradients mimicking the basal lamina to study adhesion/migration dynamics of ovarian cancer cells of differing metastatic potential. We find a strong haptotactic response that depends on both contact guidance and ECM binding cues. While we found enhanced migration for more invasive cells, the specifics of alignment and directed migration also depend on cell polarity. We further use MPE fabrication to create collagen scaffolds with complex, 3D submicron morphology. The stromal scaffold designs are derived directly from "blueprints" based on SHG images of normal, high risk, and malignant ovarian tissues. The models are seeded with different cancer cell lines and this allows decoupling of the roles of cell characteristics (metastatic potential) and ECM structure and composition (normal vs cancer) on adhesion/migration dynamics. We found the malignant stroma structure promotes enhanced migration and proliferation and also cytoskeletal alignment. Creating synthetic models based on fibers patterns further allows decoupling the topographic roles of the fibers themselves vs their alignment within the tissue. These models cannot be synthesized by other conventional fabrication methods and we suggest the MPE image-based fabrication method will enable a variety of studies in cancer biology.

  20. Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

    Science.gov (United States)

    Li, Li; Xie, Wengming; Li, Hui

    2012-12-01

    The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

  1. Restaging and Survival Analysis of 4036 Ovarian Cancer Patients According to the 2013 FIGO Classification for Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Høgdall, Claus Kim; Mosgaard, Berit Jul

    2016-01-01

    OBJECTIVE: With the 2013 International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian, fallopian tube, and primary peritoneal cancer, the number of substages changed from 10 to 14. Any classification of a malignancy should easily assign patients to prognostic groups, refer....... MATERIALS AND METHODS: Demographic, surgical, histological, and survival data from 4036 ovarian cancer patients were used in the analysis. Five-year survival rates (5YSR) and hazard ratios for the old and revised FIGO staging were calculated using Kaplan-Meier curves and Cox regression. RESULTS: A total...

  2. Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.

    Science.gov (United States)

    Sharrow, Allison C; Perkins, Brandy; Collector, Michael I; Yu, Wayne; Simons, Brian W; Jones, Richard J

    2016-08-01

    The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer. We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3. Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Malignant Struma Ovarii in a Postmenopausal Asymptomatic Woman: A Case Report

    Directory of Open Access Journals (Sweden)

    Behiye Pınar Çilesiz Göksedef

    2011-09-01

    Full Text Available Introduction: Struma ovarii is an ovarian tumor that consists predominantly thyroid tissue and accounts for only 2% of all mature teratomas. It is usually a benign condition - malignant transformation has been reported to occur in about 5% of all struma ovarii cases. Case: A 58-year-old postmenopausal woman attended our outpatient clinic for her annual gynecologic exam, on which a palpable ovary was incidentally found. Ultrasound and magnetic resonance imaging work-up showed two-centimeter solid mass on the right ovary. Laparoscopic salpingo-oophorectomy was performed; the histology report revealed a focus of thyroid papillary carcinoma in a struma ovarii. The patient underwent surgical staging procedure according to the ovarian cancer guideline. The tumor was in stage 1A, thus, no further treatment was indicated apart from follow-up. Conclusion: Malignant struma ovarii is a rare neoplasm of the ovary. Surgical staging should be included in the treatment, like in the other germ cell ovarian tumors. (The Medical Bulletin of Haseki 2011;49: 117-9

  4. Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis

    DEFF Research Database (Denmark)

    Vestergaard, Anna Lindeløv; Thorup, Katrine; Knudsen, Ulla Breth

    2011-01-01

    Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the p......Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute...... to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score (rAFS) stage 1 (N=1), 2 (N=10), 3 (N=11), or 4 (N=1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1, and ESR1) were analyzed for promoter hypermethylation...... in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order...

  5. Anastomoses of the Ovarian and Uterine Arteries: A Potential Pitfall and Cause of Failure of Uterine Embolization

    International Nuclear Information System (INIS)

    Matson, Matthew; Nicholson, Anthony; Belli, Anna-Maria

    2000-01-01

    Four women with symptomatic uterine fibroids were treated by uterine artery embolization (UAE). In all cases both uterine arteries were embolized via a single femoral puncture with polyvinyl alcohol using a selective catheter technique. In three cases, the ovarian artery was not visible on the initial angiogram before embolization, but appeared after the second uterine artery had been treated. In one case of clinical failure following UAE, a repeat angiogram demonstrated filling of the fibroids from the ovarian artery. Anastomoses between uterine and ovarian arteries may cause problems for radiologists performing UAE and are a potential cause of treatment failure

  6. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  7. A preliminary study of radioimmunoimaging of ovarian malignancy with I-131 labelled CEA monoclonal antibody

    International Nuclear Information System (INIS)

    Hu Likuan

    1988-01-01

    Ten cases of ovarian cancers have been detected with I-131 labelled CEA McAb and computer assisted clual radionuclide subtraction technique. The lesions (both primary and secondary) are clearly visualized and proved by surgical and pathohistological findings. 30 of 31 metastatic lesions are localized with a positive rate 97%. It seems to be a sensitive and specific procedure for early diagnosis of ovarian cancer so far. It is also valuable for staging clinical course and making decision on treatment, assessing the prognosis of ovarian cancer as well

  8. Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome Comorbid with Endometriosis.

    Science.gov (United States)

    Khodaverdi, Sepideh; Nazari, Leila; Mehdizadeh-Kashi, Abolfazl; Vahdat, Mansoureh; Rokhgireh, Samaneh; Farbod, Ali; Tajbakhsh, Banafsheh

    2018-04-01

    Ovarian fibromas are the most common benign solid ovarian tumors, which are often difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral cases, may be cases of Gorlin-Goltz syndrome (GGS), a rare autosomal dominant disorder with predisposition to basal cell carcinomas (BCCs) and other various benign and malignant tumors. This case report describes a 25 year-old female with GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016. This patient had facial asymmetry due to recurrent odontogenic keratocysts. In young cases of ovarian fibromas as reported here, conservative surgical management can preserve ovarian function and fertility. These patients must be followed up by a multidisciplinary team and submitted to periodic tests. Copyright© by Royan Institute. All rights reserved.

  9. Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome Comorbid with Endometriosis

    Directory of Open Access Journals (Sweden)

    Sepideh Khodaverdi

    2018-01-01

    Full Text Available Ovarian fibromas are the most common benign solid ovarian tumors, which are often difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral cases, may be cases of Gorlin-Goltz syndrome (GGS, a rare autosomal dominant disorder with predisposition to basal cell carcinomas (BCCs and other various benign and malignant tumors. This case report describes a 25 year-old female with GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016. This patient had facial asymmetry due to recurrent odontogenic keratocysts. In young cases of ovarian fibromas as reported here, conservative surgical management can preserve ovarian function and fertility. These patients must be followed up by a multidisciplinary team and submitted to periodic tests.

  10. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer.

    Science.gov (United States)

    Brunckhorst, Melissa K; Lerner, Dimitry; Wang, Shaomeng; Yu, Qin

    2012-07-01

    Ovarian carcinoma is the most deadly gynecological malignancy. Current chemotherapeutic drugs are only transiently effective and patients with advance disease often develop resistance despite significant initial responses. Mounting evidence suggests that anti-apoptotic proteins, including those of the inhibitor of apoptosis protein (IAP) family, play important roles in the chemoresistance. There has been a recent emergence of compounds that block the IAP functions. Here, we evaluated AT-406, a novel and orally active antagonist of multiple IAP proteins, in ovarian cancer cells as a single agent and in the combination with carboplatin for therapeutic efficacy and mechanism of action. We demonstrate that AT-406 has significant single agent activity in 60% of human ovarian cancer cell lines examined in vitro and inhibits ovarian cancer progression in vivo and that 3 out of 5 carboplatin-resistant cell lines are sensitive to AT-406, highlighting the therapeutic potential of AT-406 for patients with inherent or acquired platinum resistance. Additionally, our in vivo studies show that AT-406 enhances the carboplatin-induced ovarian cancer cell death and increases survival of the experimental mice, suggesting that AT-406 sensitizes the response of these cells to carboplatin. Mechanistically, we demonstrate that AT-406 induced apoptosis is correlated with its ability to down-regulate XIAP whereas AT-406 induces cIAP1 degradation in both AT-406 sensitive and resistance cell lines. Together, these results demonstrate, for the first time, the anti-ovarian cancer efficacy of AT-406 as a single agent and in the combination with carboplatin, suggesting that AT-406 has potential as a novel therapy for ovarian cancer patients, especially for patients exhibiting resistance to the platinum-based therapies.

  11. [Central retinal vein occlusion as the first symptom of ovarian cancer].

    Science.gov (United States)

    Asensio-Sánchez, V M; Hernaez-Ortega, M C; Castresana-Jauregui, I

    2013-12-01

    A healthy 57-year-old woman presented with decreased vision in her right eye. Dilated fundus examination revealed central retinal vein occlusion (CRVO). The laboratory test results for hypercoagulability state showed an abnormal protein S. A few months later she developed an ovarian malignancy. This case illustrates an association between CRVO and ovarian tumour. Coagulation disorders in cancer may be a mechanism for CRVO. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  12. Automated characterisation of ultrasound images of ovarian tumours: the diagnostic accuracy of a support vector machine and image processing with a local binary pattern operator.

    Science.gov (United States)

    Khazendar, S; Sayasneh, A; Al-Assam, H; Du, H; Kaijser, J; Ferrara, L; Timmerman, D; Jassim, S; Bourne, T

    2015-01-01

    Preoperative characterisation of ovarian masses into benign or malignant is of paramount importance to optimise patient management. In this study, we developed and validated a computerised model to characterise ovarian masses as benign or malignant. Transvaginal 2D B mode static ultrasound images of 187 ovarian masses with known histological diagnosis were included. Images were first pre-processed and enhanced, and Local Binary Pattern Histograms were then extracted from 2 × 2 blocks of each image. A Support Vector Machine (SVM) was trained using stratified cross validation with randomised sampling. The process was repeated 15 times and in each round 100 images were randomly selected. The SVM classified the original non-treated static images as benign or malignant masses with an average accuracy of 0.62 (95% CI: 0.59-0.65). This performance significantly improved to an average accuracy of 0.77 (95% CI: 0.75-0.79) when images were pre-processed, enhanced and treated with a Local Binary Pattern operator (mean difference 0.15: 95% 0.11-0.19, p images of ovarian masses into benign and malignant categories. The accuracy improves if texture related LBP features extracted from the images are considered.

  13. Ovarian cancer-related hypophosphatemic osteomalacia--a case report.

    Science.gov (United States)

    Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao; Tsai, Keh-Sung

    2014-12-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. We investigated a 57-year-old woman with progressive low back pain. Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

  14. Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

    Science.gov (United States)

    Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

    2014-01-01

    Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

  15. Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer.

    Science.gov (United States)

    Cao, Ya-Lei; Zhuang, Ting; Xing, Bao-Heng; Li, Na; Li, Qin

    2017-08-01

    Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum-based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V-PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co-incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1-containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients. Copyright © 2017 John Wiley & Sons, Ltd.

  16. microRNA-494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer.

    Science.gov (United States)

    Yang, Aijun; Wang, Xuenan; Yu, Chunna; Jin, Zhenzhen; Wei, Lingxia; Cao, Jinghe; Wang, Qin; Zhang, Min; Zhang, Lin; Zhang, Lei; Hao, Cuifang

    2017-09-01

    Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.

  17. A Hormonally Active Malignant Struma Ovarii

    Directory of Open Access Journals (Sweden)

    Carolina Lara

    2016-01-01

    Full Text Available Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii.

  18. Towards prevention of ovarian cancer.

    Science.gov (United States)

    Ali, Aus Tariq

    2018-01-01

    Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Iron addiction: a novel therapeutic target in ovarian cancer

    International Nuclear Information System (INIS)

    Basuli, D.

    2017-01-01

    Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependence on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Some mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). Here, we show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.

  20. Relationship between promoter methylation & tissue expression of MGMT gene in ovarian cancer

    Directory of Open Access Journals (Sweden)

    V Shilpa

    2014-01-01

    Full Text Available Background & objectives: Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumour suppressor genes. O 6 -methyguanine-DNA methyltransferase (MGMT is a DNA repair gene that removes mutagenic and cytotoxic adducts from the O 6 -position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression has been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human epithelial ovarian carcinoma. Methods: A total of 88 epithelial ovarian cancer (EOC tissue samples, 14 low malignant potential (LMP tumours and 20 benign ovarian tissue samples were analysed for MGMT promoter methylation by nested methylation-specific polymerase chain reaction (MSP after bisulphite modification of DNA. A subset of 64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples were analysed for protein expression by immunohistochemistry. Results: The methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and 20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP, benign tumours and normal ovarian tissue samples. Promoter hypermethylation with loss of protein expression was seen only in one case of EOC. Interpretation & conclusions: Our results suggest that MGMT promoter hypermethylation does not always reflect gene expression.

  1. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    International Nuclear Information System (INIS)

    Furuya, Mitsuko

    2012-01-01

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers

  2. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Mitsuko [Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 (Japan)

    2012-07-18

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.

  3. ULTRASOUND CRITERIA OF EARLY DIAGNOSTICS OF OVARIAN CARCINOMA

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan

    2015-01-01

    Full Text Available Introduction. Ovarian cancer (OC in Russia is ranked the seventh within the structure of general cancer diseases and the third within the gynecological tumors, due to such reasons the problem of early diagnostics is still actual. New technologies, such as color Doppler ultrasonography,3D power Doppler ultrasonography contribute to increasing of opportunities of ultrasound analysis to detect any malignancy signs.Materials and methods. The paper sets out the results of comprehensive ultrasound study of 68 patients with morphologically verified OC at stages IА–В, IIА–В. The control group was made of 100 female patients with morphologically verified ovarian tumors (serosal cystadenomas, thecomas, fibromas. A complex of the following ultrasound methods was used during the study: 2D and 3D ultrasonography in B mode, in color Doppler and power mapping mode, 3D angiography, spectrum Doppler imaging.Results. Maximum size of tumor varied within a range between 37 and 300 mm (108 ± 61.2 mm. It worth noting that no direct dependence between the size of neoplasm and process phase was established. When assessing the echostructure, all ovarian tumors were divided into 3 structure types: cystic type (57.8 % of cases, cystic and solid type (33.3 % of cases, solid type (8.9 % of cases. The conducted analysis of types of small pelvis neoplasm echostructures enabled to evolve the sonographic types of ovarian tumors, more or less associated with the malignant transformation. The most relevanl Doppler ultrasonography exponents characteristic for benignant and malignant processes: resistance index in benignant tumors was 0.56, at OC – 0.32 (р < 0.001; average arterial blood velocity in benignant tumors – 7.8 cm/s, at OC – 20.1 cm/s (р < 0.001; average maximum venous flow velocity in benignant tumors – 3.2 cm/s, at OC – 9.3 cm/s (р < 0.001.Conclusion. Therefore modern ultrasonography can detect and differentiate rather efficiently the localized

  4. The role of hypoxia in oral cancer and potentially malignant disorders: a review.

    Science.gov (United States)

    Kujan, Omar; Shearston, Kate; Farah, Camile S

    2017-04-01

    Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated 'potentially malignant disorders'. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia-induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Bilateral ovarian fibroma associated with Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    Shahnaz Aram

    2009-02-01

    Full Text Available

    • Gorlin syndrome (GS, also known as nevoid basal cell carcinoma syndrome (NBCCS, is a rare inherited multisystem disorder. This paper presents a 22-years-old Iranian woman with this syndrome whose past history was multiple keratocysts of maxillary bone. She was referred to gynecology clinic with the chief complaint of irregular menses and vaginal spotting. On examination, frontal bossing and hypertelorism were detected. Physical examination of genitalia disclosed bilateral adnexal masses. Pelvic ultrasound showed two solid, echogenous and calcified masses measuring 100*50*10 & 60*50*45 mm in the left and right ovaries, respectively. The patient underwent right oophorectomy and ovarian mass resection with preservation of intact ovarian tissue on the left side. On frozen and permanent histological sections, bilateral and calcified ovarian fibromas were diagnosed. Surprisingly, during the last follow-up one year after the surgery, we found that our patient was expecting a baby. It can be concluded that in the presence of bilateral and calcified ovarian fibromas, the possibility of GS should be considered. Accurate diagnosis is only possible with close attention to the familial and past medical history and physical examination. In these patients, careful follow up for detecting malignancies and other complications is highly recommended.
    • KEY WORDS: Gorlin syndrome, ovarian fibroma, multiple keratocysts.

  6. The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis.

    Science.gov (United States)

    Ma, X-M; Sun, X; Yang, G-W; Yu, M-W; Zhang, G-L; Yu, J; Zhang, Y; Wang, X-M

    2017-10-01

    The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a meta-analysis to estimate the prognostic value of the PLR in ovarian cancer. We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference = 63.57, 95% CI 39.47-87.66, p < 0.00001). An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer.

  7. The role of ovarian fossa evaluation in patients with ovarian endometriosis.

    Science.gov (United States)

    De Cicco Nardone, Carlo; Terranova, Corrado; Plotti, Francesco; Ricciardi, Roberto; Capriglione, Stella; Luvero, Daniela; Caserta, Donatella; Moscarini, Massimo; Benedetti Panici, Pierluigi; Angioli, Roberto

    2015-10-01

    The aim of this study is to evaluate prospectively the presence of endometriosis in the peritoneum of the ovarian fossa of patients affected by endometriomas and its correlation with the adhesion between this peritoneum and endometrioma. Patients presenting ovarian endometriomas and candidate to laparoscopy were considered for inclusion in the study. Patients underwent laparoscopic excision of endometriomas. The presence of adherence of the ovarian fossa to endometrioma was investigated. In all patients, the removal of a peritoneum fragment from the ovarian fossa of the affected ovary was carried out. 68 patients were enrolled in the study. 48 patients presented adhesions to the ovarian fossa. Histopathologic examination of the peritoneum of the ovarian fossa revealed the presence of endometriosis in 87 % of patients presenting adhesions of the endometriomas with ovarian fossa; surprisingly it was present only in 15 % of patients not presenting this condition (p endometriosis on the peritoneal surface of the fossa. This condition significantly correlates with pain symptoms and may predict endometrioma recurrence. The removal of this peritoneum in case of adherent endometrioma may potentially reduce the incidence of recurrence.

  8. Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Faber, Mette T; Jensen, Allan

    2013-01-01

    PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

  9. Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture'…?

    Science.gov (United States)

    Thomson, P J; Goodson, M L; Smith, D R

    2017-11-01

    Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO 2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. MCM-2 expression differentiates potentially malignant verrucous lesions from oral carcinomas.

    Science.gov (United States)

    Niranjan, Kochli Channappa; Sarathy, Niharika Abhay; Alrani, Devendra

    2018-03-13

    Mcm-2 is a biomarker belonging to Mcm family of proteins which has rarely been used in oral potentially malignant and malignant lesions of the verrucous type. The objective of this study is to assess the expression of Mcm-2 in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC) and Oral Squamous Cell Carcinoma (OSCC) and compare it with the clinicopathological characteristics. A total of 70 formalin fixed paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by using the SPSS software. There was a significant difference in Mcm-2 expression with quantitative analysis among all the groups (p Mcm-2 may be a sensitive proliferation marker in oral potentially malignant and malignant lesions which may be useful for differentiating between VH with/ without dysplasia, VC and OSCC. Copyright © 2018. Published by Elsevier Inc.

  11. Ovarian cancer mimicking recurrence at colorectal anastomosis: report of a case.

    LENUS (Irish Health Repository)

    Reardon, C M

    2012-02-03

    PURPOSE: The aim of this article is to emphasize the increased risk of developing metachronous ovarian tumors after resection of rectal cancer. METHOD AND RESULTS: We report the case of a postmenopausal female patient who, five years after anterior resection, developed a primary ovarian malignancy that invaded a rectal anastomosis and in so doing mimicked a recurrence of a Dukes A rectal cancer. To our knowledge, such an occurrence has not been described previously in the literature. CONCLUSION: This case illustrates the possible benefits of routine prophylactic oophorectomy at the time of colorectal cancer resection.

  12. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep; MacPherson, Cameron R; Schmeier, Sebastian; Narasimhan, Kothandaraman; Choolani, Mahesh; Bajic, Vladimir B.

    2011-01-01

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  13. In Silico discovery of transcription factors as potential diagnostic biomarkers of ovarian cancer

    KAUST Repository

    Kaur, Mandeep

    2011-09-19

    Background: Our study focuses on identifying potential biomarkers for diagnosis and early detection of ovarian cancer (OC) through the study of transcription regulation of genes affected by estrogen hormone.Results: The results are based on a set of 323 experimentally validated OC-associated genes compiled from several databases, and their subset controlled by estrogen. For these two gene sets we computationally determined transcription factors (TFs) that putatively regulate transcription initiation. We ranked these TFs based on the number of genes they are likely to control. In this way, we selected 17 top-ranked TFs as potential key regulators and thus possible biomarkers for a set of 323 OC-associated genes. For 77 estrogen controlled genes from this set we identified three unique TFs as potential biomarkers.Conclusions: We introduced a new methodology to identify potential diagnostic biomarkers for OC. This report is the first bioinformatics study that explores multiple transcriptional regulators of OC-associated genes as potential diagnostic biomarkers in connection with estrogen responsiveness. We show that 64% of TF biomarkers identified in our study are validated based on real-time data from microarray expression studies. As an illustration, our method could identify CP2 that in combination with CA125 has been reported to be sensitive in diagnosing ovarian tumors. 2011 Kaur et al; licensee BioMed Central Ltd.

  14. Malignant Transformation of Endometriosis in the Ischioanal Fossa

    Directory of Open Access Journals (Sweden)

    Jordan S. Klebanoff

    2018-01-01

    Full Text Available We present the case of a 28-year-old nulliparous female with malignant transformation of an ectopic focus of endometriosis in the right ischioanal fossa. A 28-year-old nulliparous patient with a past medical history of polycystic ovarian syndrome (PCOS was diagnosed with endometrioid adenocarcinoma in her right ischioanal fossa. Initially, patient presented to an emergency department and underwent a CT scan of the appendix to rule out appendicitis. A multiloculated cystic lesion adjacent to the right obturator internus muscle was found. She underwent surgical resection of the mass, which confirmed FIGO grade 2 endometrioid adenocarcinoma, followed by localized radiation therapy. Malignancy arising in endometriosis is rare, and the influence of PCOS on the rate of malignant transformation is not well established.

  15. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    Directory of Open Access Journals (Sweden)

    Mitsuko Furuya

    2012-07-01

    Full Text Available Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.

  16. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...... sampling. We required that cases and controls have no previous cancer and that controls have no previous bilateral oophorectomy. METHODS: Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders. MAIN OUTCOME MEASURES: Epithelial...

  17. First case of transformation for breast fibroadenoma to high-grade malignant cystosarcoma in an in vitro fertilization patient.

    Science.gov (United States)

    Pacchiarotti, Arianna; Frati, Paola; Caserta, Donatella; Pacchiarotti, Alessandro; Frega, Antonio; Moscarini, Massimo

    2011-11-01

    To evaluate the possible malignant transformation of fibroadenoma of the breast in patients undergoing an IVF cycle. Case report. Assisted reproduction center. A 41-year-old female patient undergoing assisted fertilization treatment. The patient underwent fine needle aspiration biopsy that confirmed fibroadenoma before the IVF attempt. She started a short stimulation protocol with triptorelin and recombinant FSH. After the first unsuccessful IVF attempt, she underwent a second short ovarian stimulation protocol with triptorelin and urinary FSH and she become pregnant. At 17 weeks, due to an increase in volume of the fibroadenoma, an excisional biopsy was performed that showed a malignant phyllode tumor. Then she underwent quadrantectomy. Malignant transformation of breast fibroadenoma. Cytologic examination of the first fine needle aspiration biopsy specimen showed a fibroadenoma of the breast; excisional biopsy showed a high-grade malignant cystosarcoma. Fibroadenoma was transformed into high-grade malignant cystosarcoma after ovarian stimulation in an IVF patient. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Regulation of semaphorin 4D expression and cell proliferation of ovarian cancer by ERalpha and ERbeta

    Directory of Open Access Journals (Sweden)

    Y. Liu

    Full Text Available Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2 significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.

  19. An 11-year experience with ovarian surgery during pregnancy

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    Fan-Hlan Koo

    2013-08-01

    Conclusion: In our study cohort, surgical intervention during pregnancy was safe, since neither surgical approach, such as exploratory laparotomy or laparoscopic surgery, nor anesthesia methods, for example general anesthesia or spinal anesthesia showed negative impact on the pregnancy outcomes. Reported cases of malignant ovarian tumor are still rare, thus, the possibility of metastatic tumor should be considered first.

  20. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Trabert, Britton; Ness, Roberta B; Lo-Ciganic, Wei-Hsuan

    2014-01-01

    BACKGROUND: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. METHODS: We analyzed pooled data from 12...... population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression...... and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. RESULTS: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval...

  1. Meta-Analysis of Microarray Data Identifies GAS6 Expression as an Independent Predictor of Poor Survival in Ovarian Cancer

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    Michelle Buehler

    2013-01-01

    Full Text Available Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed that GAS6 was highly expressed in ovarian cancer and therefore was selected as our candidate of choice. GAS6 encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (. In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.

  2. Small ribosomal protein subunit S7 suppresses ovarian tumorigenesis through regulation of the PI3K/AKT and MAPK pathways.

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    Ziliang Wang

    Full Text Available Small ribosomal protein subunit S7 (RPS7 has been reported to be associated with various malignancies, but the role of RPS7 in ovarian cancer remains unclear. In this study, we found that silencing of RPS7 by a specific shRNA promoted ovarian cancer cell proliferation, accelerated cell cycle progression, and slightly reduced cell apoptosis and response to cisplatin treatment. Knockdown of RPS7 resulted in increased expression of P85α, P110α, and AKT2. Although the basal levels of ERK1/2, MEK1/2, and P38 were inconsistently altered in ovarian cancer cells, the phosphorylated forms of MEK1/2 (Ser217/221, ERK1/2 (Thr202/Tyr204, JNK1/2 (Thr183/Tyr185, and P38 (Thr180/Tyr182 were consistently reduced after RPS7 was silenced. Both the in vitro anchorage-independent colony formation and in vivo animal tumor formation capability of cells were enhanced after RPS7 was depleted. We also showed that silencing of RPS7 enhanced ovarian cancer cell migration and invasion. In sum, our results suggest that RPS7 suppresses ovarian tumorigenesis and metastasis through PI3K/AKT and MAPK signal pathways. Thus, RPS7 may be used as a potential marker for diagnosis and treatment of ovarian cancer.

  3. Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

    Science.gov (United States)

    Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

    2014-02-01

    Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

  4. MicroRNA-194 promotes the growth, migration, and invasion of ovarian carcinoma cells by targeting protein tyrosine phosphatase nonreceptor type 12

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    Liang T

    2016-07-01

    Full Text Available Tian Liang, Liru Li, Yan Cheng, Chengcheng Ren, Guangmei Zhang Department of Gynecology and Obstetrics, The first Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Hei Longjiang, People’s Republic of China Abstract: Ovarian carcinoma is the most lethal gynecologic malignancy among women. Ovarian cancer metastasis is the main reason for poor prognosis. MicroRNAs (miRNAs have been shown to play an important role in tumorigenesis and metastasis in various cancers by affecting the expression of their targets. In this study, we explored the role of miR-194 in ovarian cancer. Real-time polymerase chain reaction assays showed that miR-194 was significantly upregulated in ovarian cancer tissues. Overexpression of miR-194 in ovarian cancer cells promotes cell proliferation, migration, and invasion; in contrast, inhibition of the expression of miR-194 has the opposite effects. Meanwhile, bioinformatics tools were used to identify protein tyrosine phosphatase nonreceptor type 12 (PTPN12 as a potential target of miR-194. The luciferase assay showed that miR-194 directly binds to the 3'-untranslated region of PTPN12. Western blot analysis and quantitative real-time polymerase chain reaction assay revealed that PTPN12 expression was negatively associated with miR-194 expression in both ovarian cancer tissues and cells. Thus, we conclude that miR-194 targets PTPN12 and functions as an oncogene in ovarian cancer cells. This novel pathway may provide a new insight to explain ovarian cancer development and metastasis. Keywords: miR-194, ovarian cancer, PTPN12, metastasis

  5. BRCA1 Expression Is Epigenetically Repressed in Sporadic Ovarian Cancer Cells by Overexpression of C-Terminal Binding Protein 2

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    Taymaa May

    2013-06-01

    Full Text Available INTRODUCTION: Ovarian cancer is the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. We have recently demonstrated that the transcriptional co-repressor C-terminal binding protein 2 (CtBP2 is overexpressed in epithelial ovarian carcinoma. MATERIALS AND METHODS: Reverse-transcribed cDNA from CtBP2 wild-type and knockdown ovarian cancer cell lines was hybridized to Affymetrix Gene 1.0 ST microarrays, and differentially expressed genes were studied. Immunohistochemical analysis of CtBP2 and BRCA1 staining of ovarian tissues was performed. Chromatin immunoprecipitation (ChIP and luciferase assays were carried out. The effect of the drugs 4-methylthio-2-oxobutyric acid (MTOB and poly(ADP-ribose polymerase (PARP inhibitor Olaparib on CtBP2 wild-type and knockdown cell lines was examined using methylthiazol tetrazolium assays and an xCELLigence System. RESULTS: Eighty-five genes involved in DNA repair, mitotic checkpoint, nucleosome assembly, and the BRCA1 network were differentially regulated by CtBP2 expression. ChIP and luciferase reporter assays using a BRCA1 promoter-regulated luciferase construct indicated that the CtBP2 complex binds the BRCA1 promoter and represses BRCA1 transcription. Immunohistochemistry illustrated a significant inverse CtBP2 and BRCA1 expression in a panel of malignant ovarian tumor tissues. The CtBP2 inhibitor MTOB suppressed ovarian cancer cell survival in a CtBP2-dependent manner. Ovarian cancer cells with CtBP2 knockdown did not display increased sensitivity to the PARP inhibitor Olaparib. CONCLUSION: CtBP2 is an ovarian cancer oncogene that may play a significant role in epigenetically silencing BRCA1 function in sporadic epithelial ovarian cancer. CtBP2-specific inhibitors, such as MTOB, may be effective adjunct therapies in the management of patients with CtBP2-positive ovarian carcinoma.

  6. Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients.

    Science.gov (United States)

    Pochechueva, Tatiana; Alam, Shahidul; Schötzau, Andreas; Chinarev, Alexander; Bovin, Nicolai V; Hacker, Neville F; Jacob, Francis; Heinzelmann-Schwarz, Viola

    2017-02-10

    Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Here we investigated the levels of naturally occurring anti-glycan antibodies to Globo H in blood plasma obtained from high-grade serous ovarian cancer patients (SOC) and women without gynaecological malignancies (control) using suspension glycan array technology employing chemically synthesized glycans as antibody targets. We found that anti-human Globo H IgG antibodies were able to significantly discriminate SOC from controls (P anti-Globo H antibodies highly correlated (r = 0.992). The incubation of plasma-derived anti-glycan antibodies with chemically synthesized (presented on fluorescence microspheres) and native Globo H (expressed on Globo H-positive cell lines) revealed strong reactivity of naturally occurring human anti-Globo H antibodies towards its antigen expressed on ovarian cancer cells. Our data demonstrate that human plasma-derived antibodies to Globo H as well as the presence of the antigen might be considered as therapeutic option in ovarian cancer.

  7. Radioimmunoimaging of ovarian cancer with 131I labelled CEA monoclonal antibody

    International Nuclear Information System (INIS)

    Hu Likuan; Li Zhen; Huo Zhenguo; Jiang Sen; Jia Shiquan

    2001-01-01

    Objective: To investigate radioimmunoimaging with 131 I labelled CEA McAb and its value in diagnosis and treatment of ovarian cancer. Methods: CEA McAb was labelled with 131 I by standard chloramine T procedure. The radiolabeled McAb was given intravenously to the patients. The scintigraphy was performed at different time. Results: In 105 patients with histopathology proved ovarian cancers, for 96 patients the lesions were well located with RII (true positives), for the remaining 9 patients, the results were false negative. 22/23 cases with RII diagnosed benign ovarian tumors were proved to be true negative by surgical pathology in RII. Of 96 ovarian cancers 87 were stratified into identical stages by surgical pathology all RII. 141/151 metastatic tumors were found in RII and the positive rate was as high as 93.4%. The smallest tumor defected by RII was of 1 cm in diameter. Conclusions: RII is as good as ultrasonography and CT in distinguishing benignancy and malignancy. The location, size and number of the lesions can also be determined with RII. RII of ovarian cancer with 131 I-CEA McAb is valuable and helpful in early detection of ovarian cancer. It is also helpful for clinical staging, treatment programing and prognosticating

  8. Suppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissues.

    Science.gov (United States)

    Chen, Jin-Long; Chen, Fang; Zhang, Ting-Ting; Liu, Nai-Fu

    2016-06-01

    Epithelial ovarian cancer (EOC), the sixth most common cancer in women worldwide, is the most commonly fatal gynecologic malignancy in developed countries. One of the main reasons for this is that relatively little was known about the molecular events responsible for the development of this highly aggressive disease. In the present study, we demonstrated that salt‑inducible kinase 1 (SIK1; which is also known as MSK/SIK/SNF1LK) was downregulated in ovarian cancer tissue samples. Using HEY ovarian cancer cells, we noted that SIK1 overexpression inhibited proliferation as well as cancer stem cell-associated traits. Silencing SIK1 promoted the proliferation of the EG ovarian cancer cell line. We performed an analysis of potential microRNAs (miRNAs or miRs) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-141 targets the 3'UTR of SIK1. Subsequent experiments not only confirmed this prediction, but also showed that miR-141 was associated with the progression of this disease. Finally, we found that miR-141 promoted proliferation of EG cells, whereas silencing miR-141 restored SIK1 expression and inhibited the proliferation of the HEY cells. Elucidating the molecular mechanism of ovarian cancer not only enables us to further understand the pathogenesis and progression of the disease, but also provides new targets for effective therapies.

  9. [The morphological and immunohistochemical characteristics of changes in the fallopian tube mucosa in ovarian epithelial tumors].

    Science.gov (United States)

    Asaturova, A V; Ezhova, L S; Faizullina, N M; Sannikova, M V; Khabas, G N

    2016-01-01

    to study the incidence of fallopian tube lesions (secretory cell proliferations (SCP), p53 signature, serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinomas (STIC) in ovarian epithelial tumors and to propose their pathogenetic association with a certain histotype of the ovarian tumor. The investigation enrolled 136 patients with ovarian epithelial tumors, whose fallopian tubes were morphologically and immunohistochemically (IHC) examined using p53, Ki-67, and PAX2. Statistical analysis was carried out applying the Mann-Whitney test and χ(2) test. Lesions meeting the STIC criteria were found in 14.7% of cases (only in ovarian serous carcinoma (OSC)), those suspecting STICs were in 25.7%, and those without signs of STICs were in 59.6%. IFC examination diagnosed STIC in 10% of cases (only in OSC), STIL in 13.3%, p53 signature in 11.7% (only in serous tumors), and the normal/reactively changed tubal epithelium in 65%. The incidence of STILs correlated with the malignant potential of serous tumors significantly (pSTIC and high-grade OSC and revealed significant differences in the incidence of other fallopian tubal intraepithelial lesions in serous cystadenomas, borderline tumors, and OSC, in different ovarian carcinomas. The findings may suggest that the earliest stage in the pathogenesis of OSC is the development of SCP, followed by the formation of p53 signatures that may further give rise to STIL, and finally STC (due to the acquisition of additional mutations).

  10. [Malignant tumors of the female genital track in the elderly].

    Science.gov (United States)

    Gottwald, Leszek; Akoel, Kindah Mo; Wójcik-Krowiranda, Katarzyna; Bieńkiewicz, Andrzej

    2003-09-01

    In senium the increase in the incidence of most malignant neoplasms, as well as gynecological cancers is found. In this period of life the vast number of women do not apply for the preventive and follow-up examinations, which increases the number of malignant diseases diagnosed at advanced clinical stages. The coexisting another diseases often limits the possibility of the operative treatment in those cases. To assess the profile of malignant tumors of the genital tract and their treatment in women above 70 year old. 61 women aged from 71 yrs. to 88 yrs. treated operatively between 1997-2001 due to gynecological cancers were included into the study. The structure and detectability of the neoplasms, as well as the type of performed surgical procedures were analysed. 30 endometrial cancers (49.2%), 16 ovarian cancers (26.2%), 14 vulvar cancers (22.9%) and 1 cervical cancer were diagnosed and surgically treated. The endometrial cancer stage I was detected in 18 cases, stage II in 4 cases and stage III in 8 cases. In each case the radical operation was done (total hysterectomy, lymphadenectomy and appendectomy). The ovarian cancer stage I was detected in 3 cases, stage II in 2 cases, stage III in 5 cases, and stage IV in 6 cases. Only in 5 cases out of this group the radical surgery was performed (total hysterectomy, omentectomy and appendectomy). The vulvar cancer stage I was detected in 2 cases, stage II in 11 cases, and FIGO stage III in 4 cases. In each of these women the vulva and bilateral inguinal lymph nodes were resected, and in 2 cases additionally at the same time the Miles operation was performed. The cervical cancer clinical stage I was detected, and the Wertheim operation was performed. The most often diagnosed malignant neoplasm in women above 70 yrs. was the endometrial cancer. The worst first-time diagnosis structure was observed in the ovarian cancer, what significantly decreased the ability of surgical treatment in this group.

  11. Ovarian Surface Epithelium in Patients with Severe Ovarian Infertility: A Potential Source of Cells Expressing Markers of Pluripotent/Multipotent Stem Cells

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    Irma Virant-Klun

    2011-01-01

    Full Text Available The aim of this study was to confirm the presence of stem cells in the ovarian surface epithelium of patients with premature ovarian failure and no mature follicles and oocytes. In these patients, small round cells of unknown origin expressing SOX-2 marker of pluripotency were observed among the epithelial cells just after the ovarian surface epithelium scraping. These cells were an integral part of the ovarian surface epithelium. When the scraped cells were cultured in a medium with added follicular fluid to provide some ovarian niche, primitive oocyte-like cells and typical round-shaped cell clusters positively stained on alkaline phosphatase, and markers of pluripotency, such as SOX-2 and SSEA-4, were developed. These markers were expressed early and also later in the culture. Single oocyte-like cells expressed genes OCT4A, SOX-2, NANOG, NANOS, STELLA, CD9, LIN28, KLF4, GDF3, and MYC, characteristic for pluripotent stem cells. The results of this study confirmed the presence of putative stem cells in the ovarian surface epithelium of these patients and provided some basis to create a stem cell line in the future.

  12. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene; Søgaard, Charlotte

    quality of treatment.   Patients/ Methods We developed an interdisciplinary programme including patient data from the records of doctors, nurses, anaesthetists and observations. This programme was applied on a population of 65 women with ovarian malignancies. Subsequently analyses were performed.......   Results This study has had implications concerning organisation, quality of treatment and psychosocial support. The study identified correlations not previously discovered between the different elements of the programme. Correlations e.g. between patient information, pain, nausea and mobilisation were...

  13. Treatment of ovarian cancer ascites by intra-peritoneal injection of diphtheria toxin A chain-H19 vector: a case report

    Directory of Open Access Journals (Sweden)

    Abu-lail Rasha

    2010-07-01

    Full Text Available Abstract Introduction Ovarian cancer ascitic fluid, which contains malignant cells, is usually present in women with an advanced stage disease. There are currently no effective therapies for the treatment of ovarian cancer ascitic fluid. We developed a new therapeutic strategy to target expression of the diphtheria toxin fragment A gene in ovarian tumor cells under the control of H19 regulatory sequences. Case presentation A 64-year-old Caucasian woman was diagnosed with a stage IIIc epithelial ovarian cancer. She suffered from progressive disease, accumulation of malignant ascites that needed to be drained weekly, abdominal pain, vomiting, anorexia and severe weakness. Infusion of the diphtheria toxin A chain-H19 plasmid into the peritoneum of our patient resulted in complete resolution of the ascites with minimum adverse events. Conclusion On the basis of this preliminary experience, we are currently conducting an extensive Phase I study on a larger number of patients in order to assess the safety and preliminary efficacy of this novel patient-oriented treatment approach.

  14. Markers of potential malignancy in chronic hyperplastic candidiasis.

    Science.gov (United States)

    Darling, Mark R; McCord, Christina; Jackson-Boeters, Linda; Copete, Maria

    2012-08-01

    To examine the presence of markers associated with malignancy, including p53, p21 cyclin-dependent kinase inhibitor 1A, murine double minutes-2, and others, in chronic hyperplastic candidiasis. Immunohistochemical methods were used to examine the expression of p53, murine double minutes-2, p21 cyclin-dependent kinase inhibitor 1A, metallothionein, and proliferating cell nuclear antigen in 42 chronic hyperplastic candidiasis lesions and 11 non-infected control tissues. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling was used to examine apoptosis, which was correlated with p53 expression. These markers were measured in lesions of chronic hyperplastic candidiasis that did not show any epithelial dysplasia or histological signs of malignancy. p53 scores were higher in chronic hyperplastic candidiasis than in controls (P = 0.0046). Murine double-minutes 2 levels were not elevated. p21 cyclin-dependent kinase inhibitor 1A was increased in parabasal (P candidiasis lesions showed a similar basal/parabasal metallothionein staining pattern to that seen in normal squamous epithelium. Proliferating cell nuclear antigen was increased (P = 0.0007), as was apoptosis (P = 0.0033). Increased p53 in oral chronic hyperplastic candidiasis suggests an increased potential for malignant change in the epithelium, above that of normal tissues. Further functional investigation is required, as well as clinical follow-up studies. © 2012 Blackwell Publishing Asia Pty Ltd.

  15. Malignant struma ovarii: a rare oncologic entity

    International Nuclear Information System (INIS)

    Barbosa, Frederico Paes; Mendonca, Sandro Bichara; Souza, Thiago Ferreira de

    2004-01-01

    Struma ovarii (SO) malignant is a rare ovarian teratoid tumor, consisting predominantly of thyroid tissue. It has low incidence and a few cases described by the literature. Usually appears in the 4th or 5th decade of life. Generally they are diagnosed after surgery, being the diagnostic reserved for the lesions on the ectopic thyroid tissue based on cellular atypia, mitotic activity, capsular invasion and metastases. Due to its rarity,it does not still have a consensus about the best therapeutical management and protocol of accompaniment for patients with this neoplastic entity. This article reports a case of a patient with malignant S O, reviewing the relevant aspects of the literature. (author)

  16. Study of the potential effect of selenium on gamma-radiation induced ovarian failure

    International Nuclear Information System (INIS)

    Said, R.S.M.

    2012-01-01

    Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma radiation (3.2 Gy, LD 20 ), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles’ maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.

  17. Ependymoma and Carcinoid Tumor Associated with Ovarian Mature Cystic Teratoma in a Patient with Multiple Endocrine Neoplasia I

    Directory of Open Access Journals (Sweden)

    Reed Spaulding

    2014-01-01

    Full Text Available Ovarian teratomas rarely undergo new neoplastic transformation and account for a small percentage of malignant ovarian germ cell neoplasms. Here we report a case of a 51-year-old woman with multiple endocrine neoplasia type I (MEN I who was found to have an ependymoma and neuroendocrine tumor (trabecular carcinoid associated with mature cystic teratoma of her left ovary. The ependymoma component displayed cells with round nuclei and occasional small nucleoli which were focally arranged in perivascular pseudorosettes and true rosettes. Rare mitoses were identified. No necrosis was present. Immunohistochemical staining was positive for S-100 and GFAP. The Ki67 proliferation index was very low (2-3%. In contrast, the endocrine tumor component was composed of small uniform cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin. Immunohistochemical staining was positive for synaptophysin and focally positive for chromogranin. This rare case illustrates that MEN I may have an influence on the pathogenesis of ovarian teratomas as they undergo malignant transformation.

  18. Pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from transverse colon cancer.

    Science.gov (United States)

    Kyo, Kennoki; Maema, Atsushi; Shirakawa, Motoaki; Nakamura, Toshio; Koda, Kenji; Yokoyama, Hidetaro

    2016-05-14

    Pseudo-Meigs' syndrome associated with colorectal cancer is extremely rare. We report here a case of pseudo-Meigs' syndrome secondary to metachronous ovarian metastases from colon cancer. A 65-year-old female with a history of surgery for transverse colon cancer and peritoneal dissemination suffered from metachronous ovarian metastases during treatment with systemic chemotherapy. At first, neither ascites nor pleural effusion was observed, but she later complained of progressive abdominal distention and dyspnea caused by rapidly increasing ascites and pleural effusion and rapidly enlarging ovarian metastases. Abdominocenteses were repeated, and cytological examinations of the fluids were all negative for malignant cells. We suspected pseudo-Meigs' syndrome, and bilateral oophorectomies were performed after thorough informed consent. The patient's postoperative condition improved rapidly after surgery. We conclude that pseudo-Meigs' syndrome should be included in the differential diagnosis of massive or rapidly increasing ascites and pleural effusion associated with large or rapidly enlarging ovarian tumors.

  19. Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

    Science.gov (United States)

    Liu, Changmei; Yang, Fangmei

    2015-09-01

    Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

  20. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

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    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  1. Toward understanding the genetics of regulatory T cells in ovarian cancer.

    Science.gov (United States)

    Derycke, Melissa S; Charbonneau, Bridget; Preston, Claudia C; Kalli, Kimberly R; Knutson, Keith L; Rider, David N; Goode, Ellen L

    2013-06-01

    Tumor-infiltrating regulatory T cells (Tregs) promote immune evasion and are associated with poor disease outcome in patients affected by various malignancies. We have recently demonstrated that several, inherited single nucleotide polymorphisms affecting Treg-related genes influence the survival of ovarian cancer patients, providing novel insights into possible mechanisms of immune escape.

  2. Application of interferon modulators to overcome partial resistance of human ovarian cancers to VSV-GP oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Catherine Dold

    2016-01-01

    Full Text Available Previously, we described an oncolytic vesicular stomatitis virus variant pseudotyped with the nonneurotropic glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, which was highly effective in glioblastoma. Here, we tested its potency for the treatment of ovarian cancer, a leading cause of death from gynecological malignancies. Effective oncolytic activity of VSV-GP could be demonstrated in ovarian cancer cell lines and xenografts in mice; however, remission was temporary in most mice. Analysis of the innate immune response revealed that ovarian cancer cell lines were able to respond to and produce type I interferon, inducing an antiviral state upon virus infection. This is in stark contrast to published data for other cancer cell lines, which were mostly found to be interferon incompetent. We showed that in vitro this antiviral state could be reverted by combining VSV-GP with the JAK1/2-inhibitor ruxolitinib. In addition, for the first time, we report the in vivo enhancement of oncolytic virus treatment by ruxolitinib, both in subcutaneous as well as in orthotopic xenograft mouse models, without causing significant additional toxicity. In conclusion, VSV-GP has the potential to be a potent and safe oncolytic virus to treat ovarian cancer, especially when combined with an inhibitor of the interferon response.

  3. Betel Quid and Oral Potentially Malignant Disorders in a Periurban Township in Myanmar.

    Science.gov (United States)

    Zaw, Ko-Ko; Ohnmar, Mya; Hlaing, Moh-Moh; Oo, Yin-Thet-Nu; Win, Swe-Swe; Htike, Maung-Maung-Than; Aye, Phyu-Phyu; Shwe, Sein; Htwe, Moe-Thida; Thein, Zaw-Moe

    2016-01-01

    This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem.

  4. Minimal invasive biopsy results of 'uncertain malignant potential' in digital mammography screening. High prevalence but also high predictive value for malignancy

    International Nuclear Information System (INIS)

    Weigel, S.; Heindel, W.; Universitaetsklinikum Muenster; Decker, T.; Universitaetsklinikum Muenster; Korsching, E.; Biesheuvel, C.; Woestmann, A.; Boecker, W.; Hungermann, D.; Roterberg, K.; Tio, J.

    2011-01-01

    Purpose: To evaluate the rate, the histological spectrum and the positive predictive value (PPV) for malignancy of minimally invasive biopsies with 'uncertain malignant potential (B3)' in digital mammography screening. Methods and Materials: Consecutive data of 37 178 participants of one digital unit of the German screening program were included. Results: The B 3 rate was 15.1 % (148/979). The frequencies of lesion subtypes were as follows: atypical epithelial proliferation of ductal type (AEPDT) 35.1 % (52/148), radial scar (RS) 28.4 % (42/148), papillary lesions (PAP) 20.3 % (30/148), lobular carcinoma in situ 8.8 % (13/148), flat epithelial atypia 5.4 % (8/148), and mucocele-like lesions 2.0 % (3/148). The PPV for malignancy in surgical excisions was overall 0.28 (25/91); in detail 0.40 (19/47) for AEPDT, 0.20 (5/25) for RS, 0.08 (1/12) for PAP. Conclusion: Despite a higher B 3 rate of minimally invasive biopsies with 'uncertain malignant potential' in digital screening, the benign surgical biopsy rate is not disproportionally increased compared with analog screening programs. Together with defined management protocols, this results in an increased cancer detection rate per screening participant with surgical excision. (orig.)

  5. The role of EMMPRIN expression in ovarian epithelial carcinomas.

    Science.gov (United States)

    Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

    2013-09-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemistry. EMMPRIN siRNA treatment resulted in a lower growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (PEMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (PEMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.

  6. The diagnostic value of determination of serum GOLPH3 associated with CA125, CA19.9 in patients with ovarian cancer.

    Science.gov (United States)

    Fan, H-Y; Duan, D-M; Liu, Y-F

    2017-09-01

    To evaluate the value of three tumor markers serum Golgi phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19.9) in the diagnosis and postoperative evaluation of ovarian cancer by detecting these three markers. A total of 187 patients were studied and included in the ovarian cancer group, benign pelvic mass group, and the normal control group. The levels of serum Golgi phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 199 (CA19.9) were detected, respectively, and their effects on the diagnosis, evaluation, pathology typing and staging of ovarian cancer were measured. The sensitivity of the detection of ovarian cancer by GOLPH3 combined with CA125 and CA19.9 was higher than that by a single marker (pserum GOLPH3 in patients with serous and endometrioid carcinoma was significantly higher than that in patients with mucinous carcinoma, clear-cell carcinoma and germ cell tumor (pserum GOLPH3 level between patients with ovarian malignancies at stage III-IV and those at stage I-II (p>0.05). The levels of serum GOLPH3, CA125 and CA19.9 in patients with ovarian malignancies after surgery were significantly lower than those before surgery (p<0.05). The combined detection by GOLPH3, CA125, and CA19.9 may improve the diagnosis rate of ovarian epithelial cancer. GOLPH3, as a new ovarian cancer tumor marker used in clinical diagnosis, is expected to become an important indicator for the early diagnosis of ovarian cancer and the determination of clinical surgery efficacy.

  7. Primary ovarian insufficiency: an update

    Directory of Open Access Journals (Sweden)

    Cox L

    2014-02-01

    Full Text Available Leticia Cox, James H LiuUH Case Medical Center, MacDonald Women's Hospital, Department of Obstetrics and Gynecology, Case Western Reserve University School of Medicine, Department of Reproductive Biology, Cleveland, OH, USAAbstract: Primary ovarian insufficiency is a condition that represents impaired ovarian function on a continuum with intermittent ovulation. This condition commonly leads to premature menopause, defined as cessation of ovulation prior to the age of 40 years. Because there are potential immediate and long-term consequences of hypoestrogenism, a timely diagnosis is invaluable. This comprehensive review will discuss identifiable causes for primary ovarian insufficiency, including genetic disorders and metabolic abnormalities, as well as review current strategies for diagnosis, evaluation, and management of women with this condition.Keywords: premature ovarian failure, premature menopause, ovarian dysfunction

  8. Use of monoclonal antibody B72.3 in the management of gynecologic malignancies

    International Nuclear Information System (INIS)

    Simpson, J.; Schlom, J.

    1988-01-01

    Monoclonal antibodies are currently used in the diagnosis of gynecologic malignancies by way of immunohistochemical assays, serum assays, and in situ radiolocalization of carcinoma lesions. Among them is MAb B72.3, generated against a human tumor-associated antigen (TAG-72). Using immunohistochemical techniques, MAb B72.3 has shown reactivity with 100 percent of common epithelial ovarian carcinomas and endometrial carcinomas and non-reactivity with normal adult tissues, with the exception of normal secretory endometrium. B72.3 appears to be a valuable immunocytologic adjunct, with greater than 90 percent of effusions and fine-needle aspiration biopsies from gynecologic carcinomas showing reactivity. Using a serum assay developed to detect the presence of the TAG-72 antigen, 48 percent of patients with ovarian carcinoma demonstrated TAG-72-positive sera versus 1 percent of control sera. 131 I-labeled MAb B72.3 IgG and gamma scanning have been used for the in situ detection of metastatic carcinoma. Twelve of 15 patients with ovarian carcinoma showed positive gamma scans, and approximately 80 percent of the lesions demonstrated specific localization of the antibody. These studies indicate the potential utility of MAb B72.3 in the diagnosis of gynecologic carcinoma. 57 references

  9. Metastatic malignant struma ovarii with coexistence of Hashimoto’s thyroiditis

    Directory of Open Access Journals (Sweden)

    Marco Russo

    2016-05-01

    Full Text Available Struma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with 131I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients.

  10. Epigenetic alteration of p16 and retinoic acid receptor beta genes in the development of epithelial ovarian carcinoma.

    Science.gov (United States)

    Bhagat, Rahul; Kumar, Sandeep Sriram; Vaderhobli, Shilpa; Premalata, Chennagiri S; Pallavi, Venkateshaiah Reddihalli; Ramesh, Gawari; Krishnamoorthy, Lakshmi

    2014-09-01

    Silencing of tumor suppressor and tumor-related genes by promoter hypermethylation is one of the major events in ovarian carcinogenesis. In this study, we analyzed aberrant promoter methylation of p16 and RAR-β genes in 134 epithelial ovarian carcinomas (EOCs), 23 low malignant potential (LMP) tumors, 26 benign cystadenomas, and 15 normal ovarian tissues. Methylation was investigated by methylation-specific PCR (MSP), and the results were confirmed by bisulfite DNA sequencing. Relative gene expression of p16 and RAR-β was done using quantitative reverse transcriptase PCR (qRT-PCR) on 51 EOC cases, 9 LMP tumors, and 7 benign cystadenomas with 5 normal ovarian tissues. Aberrant methylation for p16 and RAR-β was present in 43 % (58/134) and 31 % (41/134) in carcinoma cases, 22 % (05/23) and 52 % (12/23) in LMP tumors, and 42 % (11/26) and 69 % (18/26) in benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of p16 and RAR-β was significantly downregulated in EOC and LMP tumors than the corresponding normal tissues whereas the expression level was normal in benign cystadenomas for p16 and slightly reduced for RAR-β. A significant correlation of p16 promoter methylation was observed with reduced gene expression in EOC. For RAR-β, no significant correlation was observed between promoter methylation and gene expression. Our results suggest that epigenetic alterations of p16 and RAR-β have an important role in ovarian carcinogenesis and that mechanism along with methylation plays a significant role in downregulation of RAR-β gene in ovarian cancer.

  11. Noninvasive assessment of cell proliferation in ovarian cancer using [18F] 3'deoxy-3-fluorothymidine positron emission tomography/computed tomography imaging

    International Nuclear Information System (INIS)

    Richard, Scott D.; Bencherif, Badreddine; Edwards, Robert P.; Elishaev, Esther; Krivak, Thomas C.; Mountz, James M.; DeLoia, Julie A.

    2011-01-01

    Introduction: Positron emission tomography (PET)/computed tomography (CT) imaging of suspected new and recurrent ovarian carcinoma was performed to assess the relationship between [ 18 F] 3'deoxy-3'fluorothymidine ( 18 FLT) uptake and histopathological tissue markers of cellular proliferation (Ki67) and thymidine kinase-1 (TK-1) expression. Methods: Six subjects were included in this pilot study. Subjects were injected with 5 mCi of 18 FLT prior to a planned surgery and then scanned on a GE Discovery-ST PET/CT scanner within an hour of injection. Regions of interest in tumor and control tissue were identified on the diagnostic CT scans and marked for later surgical biopsy. Surgery was performed within 2 days after the scan. At the time of surgery, the regions of interest identified on PET/CT were available to guide the surgeon to the tumor biopsy sites. Tissue from normal ovarian tissue control regions was also sampled. 18 FLT uptake in tumor and control tissue regions was calculated by measuring the maximum standardized uptake values (SUV max ). The excised tumor and normal ovarian tissue control tissues were analyzed by immunohistochemical staining for Ki67 and CD34. TK-1 messenger RNA expression was measured by real-time polymerase chain reaction. Results: 18 FLT uptake (SUV max ) was higher in malignant (mean 4.85/range 1.7-8.8) compared to benign (1.65/range 1.4-1.9) and normal ovarian control tissue (1.12/range 0.6-1.5). Mitotic index, as determined by Ki67 staining, was higher in malignant (18.89/range 11.97-27.19) compared to benign (0.59/range 0.23-0.95) and control tissue (0.45/range 0.06-1.20). TK-1 expression was also higher in malignant (35.52/range 5.21-106.62) compared to benign (8.71/range 4.74-12.67) and control tissue (9.79/range 0.85-39.46). An increasing trend between 18 FLT uptake and Ki67 mitotic index is seen in malignant tissue CD 34 staining between malignant, benign and control tissues was not qualitatively different. Conclusion: An

  12. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    C.E. Henry

    2017-06-01

    Full Text Available OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n = 178. Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

  13. Transformation of Epithelial Ovarian Cancer Stemlike Cells into Mesenchymal Lineage via EMT Results in Cellular Heterogeneity and Supports Tumor Engraftment

    Science.gov (United States)

    Jiang, Hua; Lin, Xiaolong; Liu, Yingtao; Gong, Wenjia; Ma, Xiaoling; Yu, Yinhua; Xie, Yi; Sun, Xiaoxi; Feng, Youji; Janzen, Viktor; Chen, Tong

    2012-01-01

    Ovarian cancers are heterogeneous and contain stemlike cells that are able to self-renew and are responsible for sustained tumor growth. Metastasis in the peritoneal cavity occurs more frequently in ovarian cancer than in other malignancies, but the underlying mechanism remains largely unknown. We have identified that ovarian cancer stemlike cells (CSCs), which were defined as side population (SP) cells, were present in patients’ ascitic fluid and mesenchymally transformed cell lines, ES-2 and HO-8910PM. SP cells, which were sorted from both cell lines and implanted into immunocompromised mice, were localized to the xenografted tumor boundary. In addition, SP cells exhibited an epithelial phenotype and showed a distinct gene expression profile with reduced expression of cell adhesion molecules (CAMs), indicating that SP cells exert an important role in ovarian cancer progression on the basis of their delicate interaction with the surrounding microenvironment and anatomical localization in tumors. In contrast, non-SP cells exhibited a more mesenchymal phenotype and showed more increased invasive potential than SP cells. This heterogeneity was observed as an endogenous transformation via the epithelial–mesenchymal transition (EMT) process. Inhibition of the EMT process by Snail1 silencing reduced the SP cell frequency, and affected their invasive capacity and engraftment. These findings illustrate the interplay between epithelial ovarian CSCs and the EMT, and exert a link to explain tumor heterogeneity and its necessity for ovarian cancer maintenance, metastasis and progression. PMID:22801793

  14. Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

    Science.gov (United States)

    Terlikowska, Katarzyna M.; Witkowska, Anna M.; Zujko, Malgorzata E.; Dobrzycka, Bozena; Terlikowski, Slawomir J.

    2014-01-01

    Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies. PMID:25429431

  15. Distinguishing benign from malignant pelvic mass utilizing an algorithm with HE4, menopausal status, and ultrasound findings

    Science.gov (United States)

    Chan, Karen KL; Chen, Chi-An; Nam, Joo-Hyun; Ochiai, Kazunori; Aw, Tar-Choon; Sabaratnam, Subathra; Hebbar, Sudarshan; Sickan, Jaganathan; Schodin, Beth A; Charakorn, Chuenkamon; Sumpaico, Walfrido W

    2015-01-01

    Objective The purpose of this study was to develop a risk prediction score for distinguishing benign ovarian mass from malignant tumors using CA-125, human epididymis protein 4 (HE4), ultrasound findings, and menopausal status. The risk prediction score was compared to the risk of malignancy index and risk of ovarian malignancy algorithm (ROMA). Methods This was a prospective, multicenter (n=6) study with patients from six Asian countries. Patients had a pelvic mass upon imaging and were scheduled to undergo surgery. Serum CA-125 and HE4 were measured on preoperative samples, and ultrasound findings were recorded. Regression analysis was performed and a risk prediction model was developed based on the significant factors. A bootstrap technique was applied to assess the validity of the HE4 model. Results A total of 414 women with a pelvic mass were enrolled in the study, of which 328 had documented ultrasound findings. The risk prediction model that contained HE4, menopausal status, and ultrasound findings exhibited the best performance compared to models with CA-125 alone, or a combination of CA-125 and HE4. This model classified 77.2% of women with ovarian cancer as medium or high risk, and 86% of women with benign disease as very-low, low, or medium-low risk. This model exhibited better sensitivity than ROMA, but ROMA exhibited better specificity. Both models performed better than CA-125 alone. Conclusion Combining ultrasound with HE4 can improve the sensitivity for detecting ovarian cancer compared to other algorithms. PMID:25310857

  16. Percutaneous drainage without sclerotherapy for benign ovarian cysts.

    Science.gov (United States)

    Zerem, Enver; Imamović, Goran; Omerović, Safet

    2009-07-01

    To evaluate percutaneous short-term catheter drainage in the management of benign ovarian cysts in patients at increased surgical risk. Thirty-eight patients with simple ovarian cysts were treated with drainage of fluid content by catheters until output stopped. All patients were poor candidates for surgery. All procedures were performed under ultrasonographic (US) control and local anesthesia. Cytologic examination was performed in all cases. The patients were followed up monthly with color Doppler US for 12 months. Outcome measure was the recurrence of a cyst. During the 12-month follow-up period, 10 of 38 cysts recurred. Seven of the 10 cysts required further intervention, and three were followed up without intervention. Four of the seven patients who required further intervention underwent repeat transabdominal aspiration and three declined repeat aspiration and subsequently underwent surgery. After repeated aspirations, two of four cysts disappeared, one necessitated follow-up only, and one necessitated surgical intervention. Cyst volume (P = .009) and diameter (P = .001) were significantly larger in the cysts that recurred. No evidence of malignancy was reported in the cytologic examination in any patient. No patients developed malignancy during follow-up. No major complications were observed. The hospital stay was 1 day for all patients. The median duration of drainage in the groups with resolved and recurrent cysts was 1 day (interquartile range, 1-1) and 2 days (interquartile range, 1-3), respectively (P = .04). In patients considered poor candidates for open surgery or laparoscopy, percutaneous treatment of ovarian cysts with short-term catheter drainage without sclerotherapy appears to be a safe and effective alternative, with low recurrence rates.

  17. Diffusion-weighted magnetic resonance imaging in the assessment of ovarian masses with suspicious features: Strengths and challen

    Directory of Open Access Journals (Sweden)

    Sahar Mansour

    2015-12-01

    Conclusion: DWI supported by conventional MRI data can confirm or exclude malignancy in suspicious ovarian masses. The combined analysis of quantitative and qualitative criteria and knowledge of the sequence pitfalls are required.

  18. Ascites promotes cell migration through the repression of miR-125b in ovarian cancer.

    Science.gov (United States)

    Yang, Lan; Zhang, Xiaoli; Ma, Yiming; Zhao, Xinhua; Li, Bin; Wang, Hongying

    2017-08-01

    Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. Here, we investigated the molecular mechanisms by which malignant ascites promote the metastasis of ovarian cancer. It was found that ovarian cancer ascites promoted ovarian cancer cell migration which was attenuated by either heat inactivation or antibody blockade of TGF-β. High level (at ng/ml level) of TGF-β was detected in the ascites. In addition, ascites repressed the expression of miRNA-125b in a TGF-β-dependent manner. Mimic of miR-125b blocked ascites-induced cell migration. Furthermore, Gab2 (a target gene of miR-125b) was elevated by ascites in a TGF-β-dependent manner. And forced expression of Gab2 reversed the inhibition of migration induced by miR-125b mimic. Most importantly, the expression of miR-125b and Gab2 mRNA was negatively correlated in ovarian cancer specimens. Taken together, our finding suggested that TGF-β in ascites promoted cancer cell migration through repression of miR-125b in ovarian cancer. This might provide a novel therapeutic target for ovarian cancer in the future.

  19. Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E; Kraggerud, Sigrid M; Abeler, Vera M

    2007-01-01

    BACKGROUND: Ovarian germ cell tumours (OGCTs) typically arise in young females and their pathogenesis remains poorly understood. We investigated the origin of malignant OGCTs and underlying molecular events in the development of the various histological subtypes of this neoplasia. RESULTS: We exa...

  20. TGF-β1 and IL-10 expression in epithelial ovarian cancer cell line ...

    African Journals Online (AJOL)

    Purpose: Ovarian cancer is a leading cause of death among gynaecological malignancies. Transforming growth factor-beta 1 and interleukin-10 (IL-10) are cytokines in the tumour microenvironment and may play critical roles in immune suppression. This study highlights these roles and immunosuppressive functions in ...

  1. Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

    Science.gov (United States)

    REIN, DANIEL T.; VOLKMER, ANNE KATHRIN; VOLKMER, JENS; BEYER, INES M.; JANNI, WOLFGANG; FLEISCH, MARKUS C.; WELTER, ANNE KATHRIN; BAUERSCHLAG, DIRK; SCHÖNDORF, THOMAS; BREIDENBACH, MARTINA

    2012-01-01

    Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment. PMID:22740945

  2. Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.

    Science.gov (United States)

    Patnaik, A K; Greenlee, P G

    1987-11-01

    In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.

  3. Cisplatin-induced caspase activation mediates PTEN cleavage in ovarian cancer cells: a potential mechanism of chemoresistance

    International Nuclear Information System (INIS)

    Singh, Mohan; Chaudhry, Parvesh; Fabi, Francois; Asselin, Eric

    2013-01-01

    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study, we have investigated the regulation of PTEN during cisplatin induced apoptosis in A2780, A270-CP (cisplatin resistant), OVCAR-3 and SKOV3 ovarian cancer cell lines. Cells were treated with 10μM of cisplatin for 24h. Transcript and protein levels were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, respectively. Immunofluorescence microscopy was used to assess the intracellular localization of PTEN. Proteasome inhibitor and various caspases inhibitors were used to find the mechanism of PTEN degradation. PTEN protein levels were found to be decreased significantly in A2780 cells; however, there was no change in PTEN protein levels in A2780-CP, OVCAR-3 and SKOV3 cells with cisplatin treatment. The decrease in PTEN protein was accompanied with an increase in the levels of AKT phosphorylation (pAKT) in A2780 cells and a decrease of BCL-2. Cisplatin treatment induced the activation/cleavage of caspase-3, -6, -7, -8, -9 in all cell lines tested in this study except the resistant variant A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-DEVD-FMK (broad range caspases inhibitor) and not with MG132 (proteasome inhibitor) and by overexpression of BCL-2, suggesting that caspases and BCL-2 are involved in the decrease of PTEN protein levels in A2780 cells. The decrease in pro-apoptotic PTEN protein levels and increase in survival factor pAKT in A2780 ovarian cancer cells suggest that cisplatin treatment could further exacerbate drug resistance in A2780 ovarian cancer cells

  4. Cisplatin-induced caspase activation mediates PTEN cleavage in ovarian cancer cells: a potential mechanism of chemoresistance.

    Science.gov (United States)

    Singh, Mohan; Chaudhry, Parvesh; Fabi, Francois; Asselin, Eric

    2013-05-10

    The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor protein is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study, we have investigated the regulation of PTEN during cisplatin induced apoptosis in A2780, A270-CP (cisplatin resistant), OVCAR-3 and SKOV3 ovarian cancer cell lines. Cells were treated with 10μM of cisplatin for 24h. Transcript and protein levels were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, respectively. Immunofluorescence microscopy was used to assess the intracellular localization of PTEN. Proteasome inhibitor and various caspases inhibitors were used to find the mechanism of PTEN degradation. PTEN protein levels were found to be decreased significantly in A2780 cells; however, there was no change in PTEN protein levels in A2780-CP, OVCAR-3 and SKOV3 cells with cisplatin treatment. The decrease in PTEN protein was accompanied with an increase in the levels of AKT phosphorylation (pAKT) in A2780 cells and a decrease of BCL-2. Cisplatin treatment induced the activation/cleavage of caspase-3, -6, -7, -8, -9 in all cell lines tested in this study except the resistant variant A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-DEVD-FMK (broad range caspases inhibitor) and not with MG132 (proteasome inhibitor) and by overexpression of BCL-2, suggesting that caspases and BCL-2 are involved in the decrease of PTEN protein levels in A2780 cells. The decrease in pro-apoptotic PTEN protein levels and increase in survival factor pAKT in A2780 ovarian cancer cells suggest that cisplatin treatment could further exacerbate drug resistance in A2780 ovarian cancer cells.

  5. Using trainable segmentation and watershed transform for identifying unilocular and multilocular cysts from ultrasound images of ovarian tumour

    Science.gov (United States)

    Ibrahim, Dheyaa Ahmed; Al-Assam, Hisham; Du, Hongbo; Jassim, Sabah

    2017-05-01

    Ovarian masses are categorised into different types of malignant and benign. In order to optimize patient treatment, it is necessary to carry out pre-operational characterisation of the suspect ovarian mass to determine its category. Ultrasound imaging has been widely used in differentiating malignant from benign cases due to its safe and non-intrusive nature, and can be used for determining the number of cysts in the ovary. Presently, the gynaecologist is tasked with manually counting the number of cysts shown on the ultrasound image. This paper proposes, a new approach that automatically segments the ovarian masses and cysts from a static B-mode image. Initially, the method uses a trainable segmentation procedure and a trained neural network classifier to accurately identify the position of the masses and cysts. After that, the borders of the masses can be appraised using watershed transform. The effectiveness of the proposed method has been tested by comparing the number of cysts identified by the method against the manual examination by a gynaecologist. A total of 65 ultrasound images were used for the comparison, and the results showed that the proposed solution is a viable alternative to the manual counting method for accurately determining the number of cysts in a US ovarian image.

  6. Common variants at 19p13 are associated with susceptibility to ovarian cancer

    DEFF Research Database (Denmark)

    Bolton, Kelly L.; Tyrer, Jonathan; Song, Honglin

    2010-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available s...

  7. Features of proteasome functioning in malignant tumors

    Science.gov (United States)

    Kondakova, I. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Slonimskaya, E. M.; Kolomiets, L. A.; Afanas'ev, S. G.; Choinzonov, Y. L.

    2017-09-01

    Proteasome ubiquitin system is the important system of intracellular proteolysis. The activity of the proteasomes may undergo changes during cancer development. We studied the chymotrypsin-like activity of proteasomes, their subunit composition, and their association with tumor stage in breast cancer, head and neck squamous cell carcinoma, endometrial cancer, renal cancer, bladder cancer, stomach cancer, ovarian cancer, and colorectal cancer. The increase in chymotrypsin-like activity of proteasomes and decrease in total proteasome pool compared with adjacent tissues were shown in all malignant tumors excluding kidney cancer. The increase in chymotrypsin-like activity of proteasomes was found in primary tumors with all types of metastasis: lymphogenous of head and neck squamous cell carcinoma, intraperitoneal metastasis of ovarian cancer, hematogenous metastasis colorectal cancer. The exception was kidney cancer, in which there was a decrease in chymotrypsin-like activity with distant metastasis.

  8. Ovarian damage due to cyst removal

    DEFF Research Database (Denmark)

    Perlman, Signe; Kjer, Jens J

    2016-01-01

    INTRODUCTION: Surgical treatment of endometriomas and potential damage to the ovary have been debated. Studies have described the inconsistent risk of unintended removal of ovarian tissue when a cystectomy of an endometrioma is performed. We evaluated the risk of inadvertently removed ovarian tis...

  9. A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

    Directory of Open Access Journals (Sweden)

    Yuji Tada

    2013-01-01

    Full Text Available Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

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

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    Fanayan Susan

    2010-09-01

    Full Text Available Abstract 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 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.

  11. Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer.

    Science.gov (United States)

    Miyata, Kohei; Yotsumoto, Fusanori; Fukagawa, Satoshi; Kiyoshima, Chihiro; Ouk, Nam Sung; Urushiyama, Daichi; Ito, Tomohiro; Katsuda, Takahiro; Kurakazu, Masamitsu; Araki, Ryota; Sanui, Ayako; Miyahara, Daisuke; Murata, Masaharu; Shirota, Kyoko; Yagi, Hiroshi; Takono, Tadao; Kato, Kiyoko; Yaegashi, Nobuo; Akazawa, Kohei; Kuroki, Masahide; Yasunaga, Shin'ichiro; Miyamoto, Shingo

    2017-07-01

    Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Sustaining hope and life courage in patients undergoing ovarian cancer surgery - the impact of care

    DEFF Research Database (Denmark)

    Seibaek, L; Delmar, C; Hounsgaard, L

    2018-01-01

    Ovarian cancer is the leading cause of death from a gynaecological malignancy in the Western World. To explore if experiences of physical comfort influenced hope and life courage during final diagnosis and early treatment, qualitative research interviews were performed with women undergoing surgery...

  13. YY1 modulates taxane response in epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

  14. Effect of curcumin in reducing burning sensation in potentially malignant disorders of oral cavity

    Directory of Open Access Journals (Sweden)

    Nitin Nigam

    2017-01-01

    Full Text Available Introduction: Curcumin, chemically named as diferuloylmethane is a yellow coloured pigment which shows anti inflammatory, antioxidant, pro apoptotic, antibacterial, antiviral and antifungal activities. It suppresses cyclooxygenase, lipooxygenase and other inflammatory mediators and destroys free radicals. Aim: To evaluate the efficacy of curcumin in reducing the burning sensation in potentially malignant disorders of oral cavity. Materials and Methods: 100 subjects diagnosed clinically with potentially malignant disorders of oral cavity were included in this study. The patients were administered commercially available turmeric systemically and topical application of turmeric and honey was advised. Their burning sensation on VAS scale was evaluated after 15 days, and the data was then statistically analysed by Wilcoxon sign rank test. Results: After the treatment there was a significant decrease in VAS scale. The median showed decrease from 7 to 4. The mean value also showed decrease from 6.91 to 3.98. Conclusion: Hence, it is concluded that turmeric and honey showed positive results in reducing burning sensation in potentially malignant disorders of oral cavity.

  15. Environmental and developmental origins of ovarian reserve.

    Science.gov (United States)

    Richardson, M C; Guo, M; Fauser, B C J M; Macklon, N S

    2014-01-01

    BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu, and environmental factors may represent important developmental determinants. Environmental and nutritional factors may also modify the downward trajectory of ovarian reserve in adult life. The combination of these early and later life influences has the potential to lead to diminished ovarian reserve, compromising fertility in later reproductive years and altering age at natural menopause. METHODS Literature searches of the ISI Web of Knowledge database were carried out using the main terms 'ovarian reserve' and 'menopause AND age' in conjunction with a range of other terms encompassing a variety of factors with potential effects on ovarian reserve. The various searches were inspected manually and the relevant papers selected for critical analysis and interpretation. RESULTS Evidence was identified supporting the view that elevated prenatal androgens have an adverse effect on the early establishment of ovarian reserve, although the implications for ovarian reserve in the polycystic ovary syndrome (which may also be programmed through prenatal androgen exposure) remain uncertain. Recent evidence is cited suggesting that effects of maternal nutrient restriction on ovarian reserve may also involve changes in prenatal androgen exposure. A general rationale is developed through examination of evidence which emphasizes the roles of the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve modulation. Because of their similarity to the natural ligands, many environmental compounds have the ability to bind to these receptors (albeit at lower affinities) and thereby have the potential to

  16. Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Mitra, Ramkrishna; Chen, Xi; Greenawalt, Evan J; Maulik, Ujjwal; Jiang, Wei; Zhao, Zhongming; Eischen, Christine M

    2017-11-17

    Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT. Genome-wide mapping shows 73% of MEG3-regulated EMT-linked pathway genes contain MEG3 binding sites. DNM3OS overexpression, but not MEG3 or MIAT, significantly correlates to worse overall patient survival. DNM3OS knockdown results in altered EMT-linked genes/pathways, mesenchymal-to-epithelial transition, and reduced cell migration and invasion. Proteotranscriptomic characterization further supports the DNM3OS and ovarian cancer EMT connection. TWIST1 overexpression and DNM3OS amplification provides an explanation for increased DNM3OS levels. Therefore, our results elucidate lncRNA that regulate EMT and demonstrate DNM3OS specifically contributes to EMT in ovarian cancer.

  17. Clinicopathologic aspects and treatment results in malignant sex cord-stromal tumor of ovary

    Directory of Open Access Journals (Sweden)

    Fatemeh Homaee

    2015-10-01

    Full Text Available Background: Ovarian sex cord-stromal tumors (SCST account for rare ovarian malignancy. These tumors are 5-8% of all ovarian neoplasms. The most common type of sex cord ovarian tumors is granulosa cell tumor (GCT. In this study our purpose was to have a look at some of clinicopathologic aspects and treatment results of these tumors. Methods: In a retrospective study, all documents of patients with SCST was referred to tumor clinics of Ghaem and Omid Hospitals, from 1998 to 2008. The data of patients were collected and analyzed. Results: In 39 (5.9 of the 398 cases, ovarian malignancies was present in SCST. Eight Patients omitted from the study because there were not enough data for them. The commonest pathology was adult granulosa cell tumor in 25 patients (80.6%. Two patients (8.33% had juvenile granulosa cell tumor, they were 25 and 38 years old. At time of diagnosis, 27 cases (87.1% were in early stages (stage I. Mean age of patients was 41 years (range 16-76 years at time of diagnosis of disease. Surgical staging of cancer was performed in 14 patients (46.7%. We did fertility sparing surgery in 12 patients (40%. Two patients were pregnant after surgery. 17 patients (54.80% did not receive chemotherapy. Three patients (9.7% received radiotherapy. Overall survival rates were 95% at both 2 years and 5 years. Longer survival had correlation with early stages of disease (P= 0.002. Age, conservative surgery and chemotherapy had no correlations with survival. Conclusion: The prognosis of SCST is almost good. Most of the patients were diagnosed in early stage of disease. In sex cord ovarian tumor, the only factor that have a full effect on survival, is stage of the disease. If the patients desire to preserve fertility, we can do fertility sparing surgery with minimal effect on survival.

  18. Evaluation of unilateral versus bilateral ovarian drilling in clomiphene citrate resistant cases of polycystic ovarian syndrome.

    Science.gov (United States)

    Roy, K K; Baruah, Jinee; Moda, Nidhi; Kumar, Sunesh

    2009-10-01

    Laparoscopic ovarian drilling (LOD) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS), with tubo-ovarian adhesion formation as the major disadvantage. Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling. This prospective randomized study included 44 patients with anovulatory infertility due to PCOS. Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007. The number of drilling site in each ovary was limited to five. The clinical and biochemical response, ovulation and pregnancy rates over a follow-up period of 1 year were compared. Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy. There was no statistical difference between the two groups in terms of clinical and biochemical response, ovulation rate and pregnancy rate. Postoperatively, tubo-ovarian adhesions could be assessed in 36.3% of the patients and no adhesions were found in a single case in either group. Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy. Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation.

  19. Fluorescence spectroscopy for the detection of potentially malignant disorders of the oral cavity: analysis of 30 cases

    International Nuclear Information System (INIS)

    Francisco, A L N; Correr, W R; Kurachi, C; Azevedo, L H; Galletta, V K; Pinto, C A L; Kowalski, L P

    2014-01-01

    Oral cancer is a major health problem worldwide and although early diagnosis of potentially malignant and malignant diseases is associated with better treatment results, a large number of cancers are initially misdiagnosed, with unfortunate consequences for long-term survival. Fluorescence spectroscopy is a noninvasive modality of diagnostic approach using induced fluorescence emission in tumors that can improve diagnostic accuracy. The objective of this study was to determine the ability to discriminate between normal oral mucosa and potentially malignant disorders by fluorescence spectroscopy. Fluorescence investigation under 408 and 532 nm excitation wavelengths was performed on 60 subjects, 30 with potentially malignant disorders and 30 volunteers with normal mucosa. Data was analyzed to correlate fluorescence patterns with clinical and histopathological diagnostics. Fluorescence spectroscopy used as a point measurement technique resulted in a great variety of spectral information. In a qualitative analysis of the fluorescence spectral characteristics of each type of injury evaluated, it was possible to discriminate between normal and abnormal oral mucosa. The results show the potential use of fluorescence spectroscopy for an improved discrimination of oral disorders. (paper)

  20. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

    Science.gov (United States)

    Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

    2016-01-01

    Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in

  1. Demethoxycurcumin inhibited human epithelia ovarian cancer cells' growth via up-regulating miR-551a.

    Science.gov (United States)

    Du, Zhenhua; Sha, Xianqun

    2017-03-01

    Curcumin is a natural agent that has ability to dampen tumor cells' growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells' malignant progress via up-regulating miR-551a.

  2. Appendiceal pathology at the time of oophorectomy for ovarian neoplasms.

    Science.gov (United States)

    Timofeev, Julia; Galgano, Mary T; Stoler, Mark H; Lachance, Jason A; Modesitt, Susan C; Jazaeri, Amir A

    2010-12-01

    To investigate the prevalence of appendiceal pathology in women undergoing surgery for a suspected ovarian neoplasm and the predictive value of intraoperative findings to determine the need for appendectomy at the time of surgery. Retrospective analysis of patients who underwent oophorectomy and appendectomy during the same surgical procedures at the University of Virginia Health System from 1992 to 2007. Observations were stratified based on the nature (benign, borderline, or malignant) and histology (serous compared with mucinous) of the ovarian neoplasm, frozen compared with final pathological diagnosis, and the gross appearance of the appendix. Among the 191 patients identified, frozen section was consistent with seven mucinous and 35 serous carcinomas, 16 serous and 33 mucinous borderline tumors, 71 mucinous and serous cystadenomas, and 29 cases of suspected metastatic tumor from a gastrointestinal primary. The highest rates of coexisting appendiceal pathology were associated with serous ovarian cancers (94.4% of grossly abnormal and 35.3% of normal appendices) and ovarian tumors suspected to be of primary gastrointestinal origin (83.3% grossly abnormal and 60.0% normal appendices harbored coexisting mucinous neoplasms). Linear regression analysis revealed that appearance of the appendix and frozen section diagnosis of the ovarian pathology were statistically significant predictors of coexisting appendiceal pathology, but the latter was more important. The prevalence of coexisting, clinically significant appendiceal pathology is low with a frozen section diagnosis of serous or mucinous cystadenoma. Appendectomy is recommended when frozen section diagnosis is mucinous or serous ovarian carcinoma, borderline tumor or metastatic carcinoma of suspected gastrointestinal origin.

  3. Isolated peritoneal hydatidosis clinically mimicking ovarian tumor: A rare case report

    Directory of Open Access Journals (Sweden)

    Pradhan M Pagaro

    2014-01-01

    Full Text Available Hydatid cyst disease is rare and it is a parasitic infection where humans accidentally get infected by ingesting larval forms of parasite whereas, the definitive hosts are dog. The common sites of hydatid cyst are liver, lungs, spleen. Unusual sites of the hydatid cyst is reported in subcutaneous tissue of anterior abdominal wall, peritoneum. We report an unusual form of the primary hydatid cyst disease involving peritoneum in a 65-year-old female, presenting as swelling in the abdomen since 3 months. Sonography revealed a cystic mass and diagnosis of ovarian tumor was considered. The Cancer Antigen 125 (CA--125, an ovarian malignant marker was normal. Exploratory laprotomy was carried out. Cytological examination, gross, and the histopathological findings suggested the diagnosis of hydatid cyst disease involving only peritoneum. Primary isolated hydatidosis involving peritoneum is very rare and only few cases have been reported. Moreover, it mimics other tumors of the abdomen like in our case we considered it as an ovarian tumor.

  4. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  5. The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life.

    Science.gov (United States)

    Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo

    2015-01-01

    Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life.

  6. Minimal invasive biopsy results of 'uncertain malignant potential' in digital mammography screening. High prevalence but also high predictive value for malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Weigel, S.; Heindel, W. [Universitaetsklinikum Muenster (Germany). Inst. fuer Klinische Radiologie; Universitaetsklinikum Muenster (Germany). Referenzzentrum Mammographie; Decker, T. [Dietrich Bonhoeffer Klinikum, Neubrandenburg (Germany). Inst. fuer Pathologie; Universitaetsklinikum Muenster (Germany). Referenzzentrum Mammographie; Korsching, E. [Universitaetsklinikum Muenster (Germany). Inst. fuer Bioinformatik; Biesheuvel, C.; Woestmann, A.; Boecker, W. [Universitaetsklinikum Muenster (Germany). Referenzzentrum Mammographie; Hungermann, D. [Universitaetsklinikum Muenster (Germany). Gerhard-Domagk-Inst. fuer Pathologie; Roterberg, K.; Tio, J. [Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe, Bereich Senologie

    2011-08-15

    Purpose: To evaluate the rate, the histological spectrum and the positive predictive value (PPV) for malignancy of minimally invasive biopsies with 'uncertain malignant potential (B3)' in digital mammography screening. Methods and Materials: Consecutive data of 37 178 participants of one digital unit of the German screening program were included. Results: The B 3 rate was 15.1 % (148/979). The frequencies of lesion subtypes were as follows: atypical epithelial proliferation of ductal type (AEPDT) 35.1 % (52/148), radial scar (RS) 28.4 % (42/148), papillary lesions (PAP) 20.3 % (30/148), lobular carcinoma in situ 8.8 % (13/148), flat epithelial atypia 5.4 % (8/148), and mucocele-like lesions 2.0 % (3/148). The PPV for malignancy in surgical excisions was overall 0.28 (25/91); in detail 0.40 (19/47) for AEPDT, 0.20 (5/25) for RS, 0.08 (1/12) for PAP. Conclusion: Despite a higher B 3 rate of minimally invasive biopsies with 'uncertain malignant potential' in digital screening, the benign surgical biopsy rate is not disproportionally increased compared with analog screening programs. Together with defined management protocols, this results in an increased cancer detection rate per screening participant with surgical excision. (orig.)

  7. Ovarian cancer surgery

    DEFF Research Database (Denmark)

    Seibaek, Lene; Blaakaer, Jan; Petersen, Lone Kjeld

    2013-01-01

    PURPOSE: The study objective was to survey general health and coping in women undergoing ovarian cancer surgery, and subsequently to develop and test a supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on the suspicion of ovarian cancer participated in a follow...... standard levels. Concerning mental health, levels were below standard during the entire period, but did improve with time, also in women in whom the potential cancer diagnosis was refuted. The preoperative differences between these groups leveled out postoperatively in terms of physical health. At the end...

  8. Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer

    International Nuclear Information System (INIS)

    Xia, Xi; Weng, Yanjie; Liao, Shujie; Han, Zhiqiang; Liu, Ronghua; Zhu, Tao; Wang, Shixuan; Xu, Gang; Meng, Li; Zhou, Jianfeng; Ma, Ding; Ma, Quanfu; Li, Xiao; Ji, Teng; Chen, Pingbo; Xu, Hongbin; Li, Kezhen; Fang, Yong; Weng, Danhui

    2011-01-01

    P21 (WAF1/Cip1) binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer. RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry. p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment. Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment

  9. Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

    Science.gov (United States)

    Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

    2011-06-01

    Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

  10. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers ...

  11. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Ramus, Susan J.; Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E. J.; van Asperen, Christi J.; van Roozendaal, K. E. P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O.; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; van Le, Linda; Hoffman, James S.; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M.; van Rensburg, Elizabeth J.; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D. P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Ong, Kai-Ren; Hoffman, Jonathan; Donaldson, Alan; James, Margaret; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Barton, David; Porteous, Mary; Drummond, Sarah; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Haque, Eshika; Tobias, Ed; Duncan, Alexis; Izatt, Louise; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Serra-Feliu, Gemma; Ellis, Ian; Houghton, Catherine; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Claber, Oonagh; Jobson, Irene; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anita; Robertson, Lisa; Quarrell, Oliver; Bardsley, Cathryn; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Sinilnikova, Olga; Barjhoux, Laure; Verny-Pierre, Carole; Giraud, Sophie; Léone, Mélanie; Buecher, Bruno; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; Tirapo, Carole; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrede, Véronique; Caron, Olivier; Lenoir, Gilbert; Urhammer, Nancy; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Eisinger, François; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Pujol, Pascal; Peyrat, Jean-Philippe; Fournier, Joëlle; Révilliion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Megalie; Coron, Fanny; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Frénay, Marc; Vénat-Bouvet, Laurence; Delnatte, Capucine; Mortemousque, Isabelle; Lynch, Henry T.; Snyder, Carrie L.; Hogervorst, F. B. L.; Verhoef, S.; Verheus, M.; van't Veer, L. J.; van Leeuwen, F. E.; Collée, M.; van den Ouweland, A. M. W.; Jager, A.; Hooning, M. J.; Tilanus-Linthorst, M. M. A.; Seynaeve, C.; van Asperen, C. J.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Ligtenberg, M. J.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; van Os, T. A.; Gille, J. J. P.; Waisfisz, Q.; Gomez-Garcia, E. B.; van Roozendaal, C. E.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Thorne, Heather; Niedermayr, Eveline; Gill, Mona; Collins, Lucine; Gokgoz, Nalan; Selander, Teresa; Weerasooriya, Nayana; Karlsson, Per; Nordlilng, Margareta; Bergman, Annika; Einbeigi, Zakaria; Liedgren, Sigrun; Borg, Åke; Loman, Niklas; Soller, Maria; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Arver, Brita; von Wachenfeldt, Anna; Barbany-Bustinza, Gisela; Rantala, Johanna; Grönberg, Henrik; Stattin, Eva-Lena; Emanuelsson, Monica; Ehrencrona, Hans; Rosenquist, Richard; Dahl, Niklas

    2012-01-01

    Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of

  12. Menstrual pain and risk of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Babic, Ana; Harris, Holly R; Vitonis, Allison F

    2018-01-01

    to lack of power. We assessed menstrual pain using either direct questions about having experienced menstrual pain, or indirect questions about menstrual pain as indication for use of hormones or medications. We used multivariate logistic regression to calculate the odds ratio (OR) for the association......Menstrual pain, a common gynecological condition, has been associated with increased risk of ovarian cancer in some, but not all studies. Furthermore, potential variations in the association between menstrual pain and ovarian cancer by histologic subtype have not been adequately evaluated due...... between severe menstrual pain and ovarian cancer, adjusting for potential confounders and multinomial logistic regression to calculate ORs for specific histologic subtypes. We observed no association between ovarian cancer and menstrual pain assessed by indirect questions. Among studies using direct...

  13. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis

    Directory of Open Access Journals (Sweden)

    Yang X

    2018-03-01

    Full Text Available Xiao Yang,1 Shaoming Zhu,2 Li Li,3 Li Zhang,1 Shu Xian,1 Yanqing Wang,1 Yanxiang Cheng1 1Department of Obstetrics and Gynecology, 2Department of Urology, Renmin Hospital of Wuhan University, 3Department of Pharmacology, Wuhan University Health Science Center, Wuhan, Hubei, People’s Republic of China Background: The mortality rate associated with ovarian cancer ranks the highest among gynecological malignancies. However, the cause and underlying molecular events of ovarian cancer are not clear. Here, we applied integrated bioinformatics to identify key pathogenic genes involved in ovarian cancer and reveal potential molecular mechanisms. Results: The expression profiles of GDS3592, GSE54388, and GSE66957 were downloaded from the Gene Expression Omnibus (GEO database, which contained 115 samples, including 85 cases of ovarian cancer samples and 30 cases of normal ovarian samples. The three microarray datasets were integrated to obtain differentially expressed genes (DEGs and were deeply analyzed by bioinformatics methods. The gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichments of DEGs were performed by DAVID and KOBAS online analyses, respectively. The protein–protein interaction (PPI networks of the DEGs were constructed from the STRING database. A total of 190 DEGs were identified in the three GEO datasets, of which 99 genes were upregulated and 91 genes were downregulated. GO analysis showed that the biological functions of DEGs focused primarily on regulating cell proliferation, adhesion, and differentiation and intracellular signal cascades. The main cellular components include cell membranes, exosomes, the cytoskeleton, and the extracellular matrix. The molecular functions include growth factor activity, protein kinase regulation, DNA binding, and oxygen transport activity. KEGG pathway analysis showed that these DEGs were mainly involved in the Wnt signaling pathway, amino acid metabolism, and the

  14. Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.

    Directory of Open Access Journals (Sweden)

    Shun Liang

    Full Text Available The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE is largely unclear.Using the Müllerian inhibiting substance type II receptor (MISIIR promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.

  15. Evaluation of Potential Risk Factors that contribute to Malignant Transformation of Oral Lichen Planus: A Literature Review.

    Science.gov (United States)

    Agha-Hosseini, Farzaneh; Sheykhbahaei, Nafiseh; SadrZadeh-Afshar, Maryam-Sadat

    2016-08-01

    Many studies have suggested that a lesion originally diagnosed as oral lichen planus (OLP) has different possibilities of undergoing malignant transformation in time, although these findings remain a controversial issue; for example, some studies reported different values of potential malignancy of OLP. World Health Organization (WHO) classifies OLP as a "potentially malignant disorder" with unspecified malignant transformation risk, and suggests that OLP patients should be closely monitored. Numerous studies have attempted to confirm the malignant transformation potential of OLP. The Cochrane Controlled Trials Register, Medline and EMBASE databases, PubMed, Google Scholar, Ovid, Up To Date, BMJ Clinical Evidence, MD Consult, and Science Direct were searched for papers published between 1997 and 2015. The medical subject heading search terms were "lichen planus," "oral lichen planus," "erosive oral lichen planus," "dysplasia," "oral precancerous condition," "oral premalignant condition," oral cancer, oral squamous cell carcinoma (OSCC), and atrophic lichen planus. A total of 120 English language abstracts were reviewed, and 50 relevant articles identified. Because of the extensive literature on the association between OLP and SCC, we have divided the data into genetic and non-genetic factors for more accurate assessment. In this evidence base, malignant transformation ranges from 0 to 37% with a mean of 4.59%. The highest rate of malignancy was noted in erythematosus and erosive lesions. In this way, follow-up of OLP patients could be carried out more efficiently and appropriately. Oral lichen planus is a premalignant lesion. All types of OLP in any site of oral mucosa must be monitored regularly.

  16. Genital tract malign ancies in postmenopausal women

    International Nuclear Information System (INIS)

    Khursheed, F.; Jatoi, N.; Das, C.M.

    2010-01-01

    Background: The most common malignancy in women is breast carcinoma. The next common cancer is genital tract malignancies which constitute 14% of cancers in women. Objective of this study was to determine the type and frequency of genital tract malignancy in postmenopausal women and to find the age distribution of genital tract malignancies. Methods: This descriptive cross sectional study was conducted in Department of Obstetrics ad Gynaecology Unit-II at Liaquat University of Medical and Health Sciences, Jamshoro. All postmenopausal women, admitted in the unit due to various pathologies (abdominal masses, bleeding P/V etc.) from January 2005 to December 2007 were included in the study. Clinical evaluation and investigations were done on all patients. Those women who had benign diseases were excluded from the study. Malignancy was confirmed from histopathology report of biopsy specimen. These women were divided into 3 age groups: group I 70 years. Results: Out of 265 postmenopausal women admitted in ward during the study period, malignancy was confirmed in 68 cases (25.66%). The type of malignancy was cervical carcinoma (41, 60.28%), ovarian carcinoma (11, 16.17%), endometrial carcinoma (8, 11.76%), vulval carcinoma (5, 7.35%) vaginal carcinoma (2, 2.94%), and leiomyosarcoma of uterus (1, 1.47%). Increased frequency of cervical and endometrial carcinomas were seen in Group-I cases, while vulval carcinoma was seen more commonly in Group-II cases ( p =0.004). Conclusion: A very high frequency of cervical carcinoma was seen in our patients. There is need for more public awareness to integrate routine Gynae-Pap screening. (author)

  17. Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; AbdulMajeed, Ahmad A; Farah, Camile S

    2014-01-01

    Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC

  18. Malignant tumours of the genital tract among Batswana women

    International Nuclear Information System (INIS)

    Tanko, M. N.; Cainelli, F.; Vento, S.; Kayembe, M. A.

    2012-01-01

    To determine the frequency and pattern of malignant tumours of the female genital tract among Batswana women. A four-year retrospective histological study of the pattern of female genital tract malignancy in Botswana. University of Botswana and the National Health Laboratory Gaborone, Botswana. The National Health Laboratory is the only public tertiary referral laboratory that provides diagnostic pathology services in the South-Eastern part of Botswana. It is located just adjacent to Princess Marina Hospital, the major tertiary referral hospital in the country. All histologically confirmed diagnoses of female genital tract malignancies from January 1st 2006 to December 31st 2009 were reviewed by two pathologists and diagnoses re-confirmed by taking fresh tissue sections from paraffin embedded archival tissue blocks. The age of patients ranged from 13-96 years with a mean age of 54.5 ± 6.4 years. Cancer of the cervix constituted 80.6%, followed by uterine cancer (10.0%), carcinomas of the vulva (4.5%) and ovary (3.4%) in that order. Ovarian cancers predominated in the younger age group. There was a steady increase in the frequencies of cervical, uterine and ovarian cancers over the 4-year study period with a decline in uterine cancer in the 4th year. Cervical cancer incidence is high among Batswana women and all female genital tract cancers occurred at a relatively early mean age. Therefore the importance of established and accessible screening programs and awareness campaigns need more emphasis than it is being given currently. (au)

  19. Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

    Science.gov (United States)

    Alborzi, S; Khodaee, R; Parsanejad, M E

    2001-09-01

    To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

  20. [18F]FDG PET/MRI vs. PET/CT for whole-body staging in patients with recurrent malignancies of the female pelvis: initial results

    International Nuclear Information System (INIS)

    Beiderwellen, Karsten; Grueneisen, Johannes; Forsting, Michael; Lauenstein, Thomas C.; Umutlu, Lale; Ruhlmann, Verena; Buderath, Paul; Aktas, Bahriye; Heusch, Philipp; Kraff, Oliver

    2015-01-01

    To evaluate the diagnostic potential of PET/MRI with [ 18 F]FDG in recurrent ovarian and cervical cancer in comparison to PET/CT. A group of 19 patients with suspected recurrence of pelvic malignancies (ovarian cancer, 11 patients; cervical cancer, 8 patients) scheduled for an [ 18 F]FDG PET/CT were subsequently enrolled for a PET/MRI. The scan protocol comprised: (1) a T1-W axial VIBE after contrast agent adminstration, (2) an axial T2-W HASTE, (3) a coronal TIRM, (4) an axial DWI, and dedicated MR sequences of the female pelvis including (5) a T1-W VIBE before contrast agent adminstration, (6) a sagittal T2-W TSE, and (7) a sagittal T1-W dynamic VIBE. The datasets (PET/CT, PET/MRI) were rated separately by two readers regarding lesion count, lesion localization, lesion conspicuity (four-point scale), lesion characterization (benign/malignant/indeterminate) and diagnostic confidence (three-point scale). All available data (histology, prior examinations, PET/CT, PET/MRI, follow-up examinations) served as standard of reference. Median values were compared using the Wilcoxon rank sum test. Metastatic lesions were present in 16 of the 19 patients. A total of 78 lesions (malignant, 58; benign, 20) were described. Both PET/CT and PET/MRI allowed correct identification of all malignant lesions and provided equivalent conspicuity (3.86 ± 0.35 for PET/CT, 3.91 ± 0.28 for PET/MRI; p > 0.05). Diagnostic confidence was significantly higher for PET/MRI in malignant (p < 0.01) and benign lesions (p < 0.05). Both PET/CT and PET/MRI offer an equivalently high diagnostic value for recurrent pelvic malignancies. PET/MRI offers higher diagnostic confidence in the discrimination of benign and malignant lesions. Considering the reduced radiation dose and superior lesion discrimination, PET/MRI may serve as a powerful alternative to PET/CT in the future. (orig.)

  1. The effect of bipolar electrocoagulation during ovarian cystectomy on ovarian reserve: a systematic review.

    Science.gov (United States)

    Pergialiotis, Vasilios; Prodromidou, Anastasia; Frountzas, Maximos; Bitos, Konstantinos; Perrea, Despina; Doumouchtsis, Stergios K

    2015-11-01

    The aim of the present systematic review was to study the effect of bipolar electrocoagulation during ovarian cystectomy on ovarian reserve. We searched Medline (1966-2015), Scopus (2004-2015), ClinicalTrials.gov (2008-2015), and Cochrane Central Register (CENTRAL) databases along with reference lists of electronically retrieved studies. The levels of antimullerian hormone (AMH) and antral follicle count (AFC) at 1, 3, 6, and 12 months following the excision of the benign ovarian cyst were defined as primary outcomes. Eight studies were finally included in our systematic review, which recruited 545 women. A metaanalysis was precluded because of significant heterogeneity in the methodological characteristics of the included studies. Data from the included studies suggest that the use of bipolar coagulation compared with ovarian sutures seems to result in significantly lower AMH and AFC during the first 3 months following the excision of the ovarian cyst. Two studies reported that this effect seems to persist at 6 and 12 months postoperatively. Bipolar electrodiathermy seems to be accompanied by increased damage to ovarian reserve, which is indicated by the lower levels of AMH and AFC. However, definitive results are precluded because of the significant heterogeneity of included studies and the potential bias. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Risk of malignancy index used as a diagnostic tool in a tertiary centre for patients with a pelvic mass

    DEFF Research Database (Denmark)

    Håkansson, Fanny; Høgdall, Estrid V S; Nedergaard, Lotte

    2012-01-01

    Abstract Objective. Risk of malignancy index (RMI), based on a serum cancer antigen 125 level, ultrasound findings and menopausal status, is used to discriminate ovarian cancer from benign pelvic mass. In Denmark, patients with pelvic mass and RMI =200 are referred to tertiary gynecologic oncology...... the use of RMI =200 as a tool for preoperative identification of ovarian cancer at a tertiary center. Design. Prospective observational study. Setting. A tertiary center in Copenhagen, Denmark. Population. One thousand one hundred and fifty-nine women with pelvic mass. Methods. The RMI was calculated...... pelvic mass. Results. There were 778 women diagnosed with benign pelvic mass, while 251 had ovarian cancer and 74 had borderline ovarian tumor. Fifty-six women were diagnosed with other forms of cancer. Sensitivity and specificity for ovarian cancer vs. benign pelvic mass for RMI =200 were 92 and 82...

  3. The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery

    NARCIS (Netherlands)

    Rutten, I.J.; Ubachs, J.; Kruitwagen, R.F.P.M.; Dijk, D.P. van; Beets-Tan, R.G.; Massuger, L.F.A.G.; Oude Damink, S.W.; Gorp, T. Van

    2017-01-01

    BACKGROUND: Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary

  4. Distinguishing benign and malignant pelvic masses : The value of different diagnostic methods in everyday clinical practice

    NARCIS (Netherlands)

    Engelen, Mirjam J. A.; Bongaerts, Alphons H. H.; Sluiter, Wim J.; De Haan, Harm H.; Bogchelman, Dick H.; TenVergert, Els M.; Willemse, Pax H. B.; van der Zee, Ate G. J.

    Objective: To optimize referral to specialized gynaecologists for surgical treatment of ovarian cancer by improving preoperative discrimination between benign and malignant pelvic tumours. Study design: In a prospective multicentre study 143 patients with a pelvic mass were included. At several

  5. Massive ovarian edema, due to adjacent appendicitis.

    Science.gov (United States)

    Callen, Andrew L; Illangasekare, Tushani; Poder, Liina

    2017-04-01

    Massive ovarian edema is a benign clinical entity, the imaging findings of which can mimic an adnexal mass or ovarian torsion. In the setting of acute abdominal pain, identifying massive ovarian edema is a key in avoiding potential fertility-threatening surgery in young women. In addition, it is important to consider other contributing pathology when ovarian edema is secondary to another process. We present a case of a young woman presenting with subacute abdominal pain, whose initial workup revealed marked enlarged right ovary. Further imaging, diagnostic tests, and eventually diagnostic laparoscopy revealed that the ovarian enlargement was secondary to subacute appendicitis, rather than a primary adnexal process. We review the classic ultrasound and MRI imaging findings and pitfalls that relate to this diagnosis.

  6. Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.

    Science.gov (United States)

    Ye, Haifeng; Zheng, Tuochen; Li, Wei; Li, Xiaoyan; Fu, Xinxin; Huang, Yaoqi; Hu, Chuan; Li, Jia; Huang, Jian; Liu, Zhengyv; Zheng, Liping; Zheng, Yuehui

    2017-01-01

    The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility. © 2017 The Author(s). Published by S. Karger AG, Basel.

  7. Characterization of chemically induced ovarian carcinomas in an ethanol-preferring rat model: influence of long-term melatonin treatment.

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo A Chuffa

    Full Text Available Ovarian cancer is the fourth most common cause of cancer deaths among women, and chronic alcoholism may exert co-carcinogenic effects. Because melatonin (mel has oncostatic properties, we aimed to investigate and characterize the chemical induction of ovarian tumors in a model of ethanol-preferring rats and to verify the influence of mel treatment on the overall features of these tumors. After rats were selected to receive ethanol (EtOH, they were surgically injected with 100 µg of 7,12-dimethyl-benz[a]anthracene (DMBA plus sesame oil directly under the left ovarian bursa. At 260 days old, half of the animals received i.p. injections of 200 µg mel/100 g b.w. for 60 days. Four experimental groups were established: Group C, rats bearing ovarian carcinomas (OC; Group C+EtOH, rats voluntarily consuming 10% (v/v EtOH and bearing OC; Group C+M, rats bearing OC and receiving mel; and Group C+EtOH+M, rats with OC consuming EtOH and receiving mel. Estrous cycle and nutritional parameters were evaluated, and anatomopathological analyses of the ovarian tumors were conducted. The incidence of ovarian tumors was higher in EtOH drinking animals 120 days post-DMBA administration, and mel efficiently reduced the prevalence of some aggressive tumors. Although mel promoted high EtOH consumption, it was effective in synchronizing the estrous cycle and reducing ovarian tumor mass by 20%. While rats in the C group displayed cysts containing serous fluid, C+EtOH rats showed solid tumor masses. After mel treatment, the ovaries of these rats presented as soft and mobile tissues. EtOH consumption increased the incidence of serous papillary carcinomas and sarcomas but not clear cell carcinomas. In contrast, mel reduced the incidence of sarcomas, endometrioid carcinomas and cystic teratomas. Combination of DMBA with EtOH intake potentiated the incidence of OC with malignant histologic subtypes. We concluded that mel reduces ovarian masses and the incidence of

  8. Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

    Directory of Open Access Journals (Sweden)

    Feng Su

    2007-01-01

    Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

  9. Distribution volumes of macromolecules in human ovarian and endometrial cancers--effects of extracellular matrix structure.

    Science.gov (United States)

    Haslene-Hox, Hanne; Oveland, Eystein; Woie, Kathrine; Salvesen, Helga B; Tenstad, Olav; Wiig, Helge

    2015-01-01

    Elements of the extracellular matrix (ECM), notably collagen and glucosaminoglycans, will restrict part of the space available for soluble macromolecules simply because the molecules cannot occupy the same space. This phenomenon may influence macromolecular drug uptake. To study the influence of steric and charge effects of the ECM on the distribution volumes of macromolecules in human healthy and malignant gynecologic tissues we used as probes 15 abundant plasma proteins quantified by high-resolution mass spectrometry. The available distribution volume (VA) of albumin was increased in ovarian carcinoma compared with healthy ovarian tissue. Furthermore, VA of plasma proteins between 40 and 190 kDa decreased with size for endometrial carcinoma and healthy ovarian tissue, but was independent of molecular weight for the ovarian carcinomas. An effect of charge on distribution volume was only found in healthy ovaries, which had lower hydration and high collagen content, indicating that a condensed interstitium increases the influence of negative charges. A number of earlier suggested biomarker candidates were detected in increased amounts in malignant tissue, e.g., stathmin and spindlin-1, showing that interstitial fluid, even when unfractionated, can be a valuable source for tissue-specific proteins. We demonstrate that the distribution of abundant plasma proteins in the interstitium can be elucidated by mass spectrometry methods and depends markedly on hydration and ECM structure. Our data can be used in modeling of drug uptake, and give indications on ECM components to be targeted to increase the uptake of macromolecular substances. Copyright © 2015 the American Physiological Society.

  10. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  11. Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Aristotle Bamias

    2013-07-01

    Full Text Available Ovarian Cancer represents the most fatal type of gynecological malignancies. A number of processes are involved in the pathogenesis of ovarian cancer, especially within the tumor microenvironment. Angiogenesis represents a hallmark phenomenon in cancer, and it is responsible for tumor spread and metastasis in ovarian cancer, among other tumor types, as it leads to new blood vessel formation. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Growth factors have been identified to play key roles in driving angiogenesis and, thus, the formation of new blood vessels that assist in “feeding” cancer. Such molecules include the vascular endothelial growth factor (VEGF, the platelet derived growth factor (PDGF, the fibroblast growth factor (FGF, and the angiopoietin/Tie2 receptor complex. These proteins are key players in complex molecular pathways within the tumor cell and they have been in the spotlight of the development of anti-angiogenic molecules that may act as stand-alone therapeutics, or in concert with standard treatment regimes such as chemotherapy. The pathways involved in angiogenesis and molecules that have been developed in order to combat angiogenesis are described in this paper.

  12. [{sup 18}F]FDG PET/MRI vs. PET/CT for whole-body staging in patients with recurrent malignancies of the female pelvis: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, Karsten; Grueneisen, Johannes; Forsting, Michael; Lauenstein, Thomas C.; Umutlu, Lale [University Hospital Essen, University of Duisburg-Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ruhlmann, Verena [University Hospital Essen, University of Duisburg-Essen, Clinic for Nuclear Medicine, Essen (Germany); Buderath, Paul; Aktas, Bahriye [University Hospital Essen, University of Duisburg-Essen, Clinic for Obstetrics and Gynecology, Essen (Germany); Heusch, Philipp [University of Dusseldorf, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Kraff, Oliver [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany)

    2015-01-15

    To evaluate the diagnostic potential of PET/MRI with [{sup 18}F]FDG in recurrent ovarian and cervical cancer in comparison to PET/CT. A group of 19 patients with suspected recurrence of pelvic malignancies (ovarian cancer, 11 patients; cervical cancer, 8 patients) scheduled for an [{sup 18}F]FDG PET/CT were subsequently enrolled for a PET/MRI. The scan protocol comprised: (1) a T1-W axial VIBE after contrast agent adminstration, (2) an axial T2-W HASTE, (3) a coronal TIRM, (4) an axial DWI, and dedicated MR sequences of the female pelvis including (5) a T1-W VIBE before contrast agent adminstration, (6) a sagittal T2-W TSE, and (7) a sagittal T1-W dynamic VIBE. The datasets (PET/CT, PET/MRI) were rated separately by two readers regarding lesion count, lesion localization, lesion conspicuity (four-point scale), lesion characterization (benign/malignant/indeterminate) and diagnostic confidence (three-point scale). All available data (histology, prior examinations, PET/CT, PET/MRI, follow-up examinations) served as standard of reference. Median values were compared using the Wilcoxon rank sum test. Metastatic lesions were present in 16 of the 19 patients. A total of 78 lesions (malignant, 58; benign, 20) were described. Both PET/CT and PET/MRI allowed correct identification of all malignant lesions and provided equivalent conspicuity (3.86 ± 0.35 for PET/CT, 3.91 ± 0.28 for PET/MRI; p > 0.05). Diagnostic confidence was significantly higher for PET/MRI in malignant (p < 0.01) and benign lesions (p < 0.05). Both PET/CT and PET/MRI offer an equivalently high diagnostic value for recurrent pelvic malignancies. PET/MRI offers higher diagnostic confidence in the discrimination of benign and malignant lesions. Considering the reduced radiation dose and superior lesion discrimination, PET/MRI may serve as a powerful alternative to PET/CT in the future. (orig.)

  13. Noninvasive assessment of cell proliferation in ovarian cancer using [{sup 18}F] 3'deoxy-3-fluorothymidine positron emission tomography/computed tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Richard, Scott D. [Department of Obstetrics, Gynecology and Reproductive Services, Division of Gynecologic Oncology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Bencherif, Badreddine, E-mail: bencherifbb@upmc.ed [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Edwards, Robert P. [Department of Obstetrics, Gynecology and Reproductive Services, Division of Gynecologic Oncology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Elishaev, Esther [Department of Obstetrics, Gynecology and Reproductive Services, Division of Gynecologic Oncology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Krivak, Thomas C.; Mountz, James M. [Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213 (United States); DeLoia, Julie A. [Department of Obstetrics, Gynecology and Reproductive Services, Division of Gynecologic Oncology, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2011-05-15

    Introduction: Positron emission tomography (PET)/computed tomography (CT) imaging of suspected new and recurrent ovarian carcinoma was performed to assess the relationship between [{sup 18}F] 3'deoxy-3'fluorothymidine ({sup 18}FLT) uptake and histopathological tissue markers of cellular proliferation (Ki67) and thymidine kinase-1 (TK-1) expression. Methods: Six subjects were included in this pilot study. Subjects were injected with 5 mCi of {sup 18}FLT prior to a planned surgery and then scanned on a GE Discovery-ST PET/CT scanner within an hour of injection. Regions of interest in tumor and control tissue were identified on the diagnostic CT scans and marked for later surgical biopsy. Surgery was performed within 2 days after the scan. At the time of surgery, the regions of interest identified on PET/CT were available to guide the surgeon to the tumor biopsy sites. Tissue from normal ovarian tissue control regions was also sampled. {sup 18}FLT uptake in tumor and control tissue regions was calculated by measuring the maximum standardized uptake values (SUV{sub max}). The excised tumor and normal ovarian tissue control tissues were analyzed by immunohistochemical staining for Ki67 and CD34. TK-1 messenger RNA expression was measured by real-time polymerase chain reaction. Results: {sup 18}FLT uptake (SUV{sub max}) was higher in malignant (mean 4.85/range 1.7-8.8) compared to benign (1.65/range 1.4-1.9) and normal ovarian control tissue (1.12/range 0.6-1.5). Mitotic index, as determined by Ki67 staining, was higher in malignant (18.89/range 11.97-27.19) compared to benign (0.59/range 0.23-0.95) and control tissue (0.45/range 0.06-1.20). TK-1 expression was also higher in malignant (35.52/range 5.21-106.62) compared to benign (8.71/range 4.74-12.67) and control tissue (9.79/range 0.85-39.46). An increasing trend between {sup 18}FLT uptake and Ki67 mitotic index is seen in malignant tissue CD 34 staining between malignant, benign and control tissues was not

  14. Development of A Mouse Model of Menopausal Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Smith

    2014-02-01

    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

  15. Expression of Hyaluronan Synthases (HAS1–3) and Hyaluronidases (HYAL1–2) in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content

    International Nuclear Information System (INIS)

    Nykopp, Timo K; Anttila, Maarit; Rilla, Kirsi; Sironen, Reijo; Tammi, Markku I; Tammi, Raija H; Hämäläinen, Kirsi; Heikkinen, Anna-Mari; Komulainen, Marja; Kosma, Veli-Matti

    2009-01-01

    Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity. Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens. The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025). The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words)

  16. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  17. RNA-based ovarian cancer research from 'a gene to systems biomedicine' perspective.

    Science.gov (United States)

    Gov, Esra; Kori, Medi; Arga, Kazim Yalcin

    2017-08-01

    Ovarian cancer remains the leading cause of death from a gynecologic malignancy, and treatment of this disease is harder than any other type of female reproductive cancer. Improvements in the diagnosis and development of novel and effective treatment strategies for complex pathophysiologies, such as ovarian cancer, require a better understanding of disease emergence and mechanisms of progression through systems medicine approaches. RNA-level analyses generate new information that can help in understanding the mechanisms behind disease pathogenesis, to identify new biomarkers and therapeutic targets and in new drug discovery. Whole RNA sequencing and coding and non-coding RNA expression array datasets have shed light on the mechanisms underlying disease progression and have identified mRNAs, miRNAs, and lncRNAs involved in ovarian cancer progression. In addition, the results from these analyses indicate that various signalling pathways and biological processes are associated with ovarian cancer. Here, we present a comprehensive literature review on RNA-based ovarian cancer research and highlight the benefits of integrative approaches within the systems biomedicine concept for future ovarian cancer research. We invite the ovarian cancer and systems biomedicine research fields to join forces to achieve the interdisciplinary caliber and rigor required to find real-life solutions to common, devastating, and complex diseases such as ovarian cancer. CAF: cancer-associated fibroblasts; COG: Cluster of Orthologous Groups; DEA: disease enrichment analysis; EOC: epithelial ovarian carcinoma; ESCC: oesophageal squamous cell carcinoma; GSI: gamma secretase inhibitor; GO: Gene Ontology; GSEA: gene set enrichment analyzes; HAS: Hungarian Academy of Sciences; lncRNAs: long non-coding RNAs; MAPK/ERK: mitogen-activated protein kinase/extracellular signal-regulated kinases; NGS: next-generation sequencing; ncRNAs: non-coding RNAs; OvC: ovarian cancer; PI3K

  18. Multidetector CT Patterns of Peritoneal Involvement in Patients with Abdominopelvic Malignancies

    International Nuclear Information System (INIS)

    Yawar, B.; Babar, S.; Rehman, I.; Sana, F.; Javed, F.; Chaudhary, M. Y.

    2015-01-01

    Objective: To determine the patterns of peritoneal involvement in patients with abdominopelvic malignancies. Study Design:Retrospective observational study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from May 2004 to May 2012. Methodology: Two hundred and three patients with histopathologically proven abdominopelvic malignancies with peritoneal involvement who underwent contrast-enhanced CT abdomen and pelvis were identified through electronic data base system and were included in this study after ethical committee approval. Peritoneal disease pattern, predominant sites of involvement and associated findings of ascites, lymph nodes and metastasis were assessed. Patients with tuberculosis and lymphoproliferative disorders were excluded. Results: The malignancies showing peritoneal involvement, in decreasing order of frequency, were ovarian cancer (n=118), colorectal cancer (n=45), pancreatic cancer (n=11), gastric cancer (n=7), endometrial cancer (n=6), gallbladder/ challenge-carcinoma and hepatocellular cancer (n=5 each), cervical cancer (n=3), renal cell carcinoma (n=2) and transitional cell urinary bladder cancer (n=1). The most common pattern of peritoneal involvement was mixed in 79 patients (39 percentage), omental caking in 74 patients (37 percentage) and nodular deposits in 50 patients (24 percentage). The most common sites of peritoneal involvement were pelvic peritoneum followed by greater omentum. Conclusion: Peritoneal involvement is the commonest with ovarian and colorectal carcinoma. Mixed pattern of peritoneal disease was most frequently seen in these patients followed by omental caking and nodular peritoneal deposits. (author)

  19. Automatic classification of ovarian cancer types from cytological images using deep convolutional neural networks.

    Science.gov (United States)

    Wu, Miao; Yan, Chuanbo; Liu, Huiqiang; Liu, Qian

    2018-06-29

    Ovarian cancer is one of the most common gynecologic malignancies. Accurate classification of ovarian cancer types (serous carcinoma, mucous carcinoma, endometrioid carcinoma, transparent cell carcinoma) is an essential part in the different diagnosis. Computer-aided diagnosis (CADx) can provide useful advice for pathologists to determine the diagnosis correctly. In our study, we employed a Deep Convolutional Neural Networks (DCNN) based on AlexNet to automatically classify the different types of ovarian cancers from cytological images. The DCNN consists of five convolutional layers, three max pooling layers, and two full reconnect layers. Then we trained the model by two group input data separately, one was original image data and the other one was augmented image data including image enhancement and image rotation. The testing results are obtained by the method of 10-fold cross-validation, showing that the accuracy of classification models has been improved from 72.76 to 78.20% by using augmented images as training data. The developed scheme was useful for classifying ovarian cancers from cytological images. © 2018 The Author(s).

  20. Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

    Science.gov (United States)

    Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

    2017-10-01

    The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Expression of cytokeratin 18 and 19 in oral potentially malignant disorders: A systematic review

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    Sam Prasad Prabakaran

    2014-01-01

    Full Text Available The aim of this review is to evaluate the expression of cytokeratin 18 and 19 in oral potentially malignant disorders (OPMD. Systematic review was performed using Medline and PubMed. Hand searches were taken from the back references. Articles published till 15 July 2014 were included in the search. The search yielded a total of 20 articles, out of which 16 articles were eliminated, as they did not fulfill the inclusion criteria and 4 articles were included for the final analysis. The available literature showed that cytokeratin 18 and 19 were expressed in all OPMDs. The level of expression varied among different oral, potentially malignant disorders and among different studies.

  2. Suppression of Cancer Stemness p21-regulating mRNA and microRNA Signatures in Recurrent Ovarian Cancer Patient Samples

    LENUS (Irish Health Repository)

    Gallagher, Michael F

    2012-01-19

    Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21

  3. Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples

    Directory of Open Access Journals (Sweden)

    Gallagher Michael F

    2012-01-01

    Full Text Available Abstract Background Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs. However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA data to assess the involvement of cancer stemness signatures in recurrent ovarian disease. Methods Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples. Results Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC and embryonic stem (mES cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component. Conclusion We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p

  4. Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target.

    Science.gov (United States)

    Perales-Puchalt, Alfredo; Svoronos, Nikolaos; Rutkowski, Melanie R; Allegrezza, Michael J; Tesone, Amelia J; Payne, Kyle K; Wickramasinghe, Jayamanna; Nguyen, Jenny M; O'Brien, Shane W; Gumireddy, Kiranmai; Huang, Qihong; Cadungog, Mark G; Connolly, Denise C; Tchou, Julia; Curiel, Tyler J; Conejo-Garcia, Jose R

    2017-01-15

    To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells. FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells. FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells. T cells redirected against FSHR + tumor cells with full-length FSH represent a promising therapeutic alternative against a broad range of ovarian malignancies, with negligible toxicity even in the presence of cognate targets in tumor-free ovaries. Clin Cancer Res; 23(2); 441-53. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Expression of zinc finger E-box-binding homeobox factor 1 in epithelial ovarian cancer: A clinicopathological analysis of 238 patients

    OpenAIRE

    LI, XIUFANG; HUANG, RUIXIA; LI, RUTH HOLM; TROPE, CLAES G.; NESLAND, JAHN M.; SUO, ZHENHE

    2015-01-01

    A growing body of evidence indicates that aberrant activation of epithelial-to-mesenchymal transition (EMT) plays a key role in tumor cell invasion and metastasis. Zinc finger E-box-binding homeobox factor 1 (ZEB1), as a crucial mediator of EMT, contributes to the malignant progression of various epithelial tumors. To determine whether ZEB1 is involved in the progression of ovarian cancer, we immunohistochemically evaluated the expression of ZEB1 in 238 cases of epithelial ovarian cancer (EOC...

  6. Tobacco use, Body Mass Index, and Potentially Malignant Disorders Among petrol fillers in Pimpri-Pune (India: A descriptive study

    Directory of Open Access Journals (Sweden)

    Mamatha G. S. Reddy

    2014-01-01

    Full Text Available Background: Since petrol is combustible and smoking is banned at the petrol pumps, it may be predicted that use of smokeless tobacco is more prevalent among the petrol fillers. Also, smokeless tobacco is a major risk factor for developing oral potentially malignant disorders. The present study was conducted to determine the tobacco use, body mass index (BMI, and potentially malignant disorders among a cohort of petrol fillers and also to evaluate the interaction of tobacco use and BMI with the presence of potentially malignant disorders. Settings and Design: The study was conducted at 45 petrol stations located at Pimpri-Pune, India. A descriptive study design was used. Materials and Method: Four hundred and ten petrol fillers aged 17-64 years participated in the study. General information and tobacco history was obtained by interview. Height and weight were recorded to obtain BMI. Oral examination was conducted to identify the potentially malignant disorders. Statistical analysis: Chi-square test, Z test, and logistic regression were used. The level of significance was fixed at 5%. Results and Conclusions: It was found that 242 (59.02% used tobacco in different forms. 77.68% were tobacco chewers, and 8.26% were smokers. Leukoplakia was prevalent among 68.47%, oral submucous fibrosis among 27.45%, and 5.08% had erythroplakia. Age (χ2 = 11.46, P < 0.05, duration (χ2 = 17.46, P < 0.05, and frequency of tobacco chewing (χ2 = 14.16, P < 0.05 were significantly associated with potentially malignant disorders. Tobacco chewing was more prevalent as compared to smoking. It can be concluded that the petrol fillers are at a high risk for developing oral potentially malignant disorders.

  7. A case-control study of risk factors for epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ghaem Maghami Noori F

    2001-09-01

    Full Text Available Ovarian cancer is second prevalent cancer among gynecologic malignancies and the most common type of ovarian cancer is epithelial form (85-90 percent. To detect the risk factors for the epithelial ovarian cancer, a case-control study was conducted in Valieasr hospital in 1988. In this study, 118 cases with epithelial ovarian cancer (according histological records and 240 controls without any gynecological cancer in gynecologic clinic had been interviewed. For data analysis, T-test, Chi2 test and logistic regression have been used at a =0.05 as level of significance. The mean age in cases was 50±13 and in controls was 49.9±12 years, without significant different. The mean number of pregnancies and parity in cases was less than controls, significantly (P<0.03. The mean months of breast feeding in cases was less than controls (54.9±71.2 versus 82.4±62.7 (P<0.001. The cases had a lower mean age of menarch than controls (P=0.03. 58 percent of cases and 21.3 percent of controls hadn't used any contraception methods (P=0.00001. The mean years of contraception was significantly less in cases versus controls (P<0.001. The odds ratio for epithelial ovarian cancer was 0.24 (95 percent CI: 0.13-0.48 in OCP users, 0.47 (95 percent CI: 0.005-0.43 in TL method, and was 0.41 (95 percent CI: 0.22-0.76 in other contraception methods, relative to women who hadn't used any contraception methods. This study reveals that epithelial ovarian cancer risk increases significantly with earlier menarch, decreasing number of pregnancy, deliveries duration of breast feeding and use of contraception methods. Use of contraception pill and tubal ligation method decreases risk of epithelial ovarian cancer.

  8. LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194

    Directory of Open Access Journals (Sweden)

    An J

    2017-11-01

    Full Text Available Jihong An,* Weiling Lv,* Yongzhou Zhang Department of Clinical Pharmacy, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China *These authors contributed equally to this work Background: Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Nuclear paraspeckle assembly transcript 1 (NEAT1 has been reported as an oncogene in most malignancies such as lung cancer, esophageal cancer, and gastric cancer. This study is designed to investigate the function of NEAT1 in paclitaxel (PTX resistance of ovarian cancer and its potential molecular mechanism. Patients and methods: The expressions of NEAT1 and miR-194 in ovarian cancer tissues and cells were estimated by quantitative real-time polymerase chain reaction (qRT-PCR. MTT, flow cytometry, and Western blot assays were used to assess the effect of NEAT1 on PTX resistance in PTX-resistant ovarian cancer cells. Luciferase reporter assay was applied to examine the association between NEAT1, zinc finger E-box-binding homeobox 1 (ZEB1 and miR-194. Xenograft tumor model was established to confirm the biological role of NEAT1 in PTX resistance of ovarian cancer in vivo. Results: NEAT1 was upregulated, and miR-194 was downregulated in PTX-resistant ovarian cancer tissues and cells. Functionally, NEAT1 knockdown enhanced cell sensitivity to PTX via promoting PTX-induced apoptosis in vitro. NEAT1 was identified as a molecular sponge of miR-194 to upregulate ZEB1 expression. Mechanistically, NEAT1-knockdown-induced PTX sensitivity was mediated by miR-194/ZEB1 axis. Moreover, NEAT1 knockdown improved PTX sensitivity of ovarian cancer in vivo. Conclusion: NEAT1 contributed to PTX resistance of ovarian cancer cells at least partly through upregulating ZEB1 expression by sponging miR-194, elucidating a novel regulatory pathway of chemoresistance in PTX-resistant ovarian cancer cells and providing a possible long noncoding RNA (lncRNA-targeted therapy for ovarian cancer

  9. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

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    Masafumi Koshiyama

    2014-01-01

    Full Text Available 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.

  10. NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols

    Directory of Open Access Journals (Sweden)

    Ignarro Louis J

    2008-02-01

    Full Text Available Abstract Background Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. Methods NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP, was studied in cisplatin-sensitive (A2780 WT and cisplatin-resistant (A2780 cDDP cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. Results Cells treated with NCX-4040 (25 μM showed a significant reduction of cell viability (A2780 WT, 34.9 ± 8.7%; A2780 cDDP, 41.7 ± 7.6%; p versus NCX-4040+cisplatin, 26.4 ± 7.6%; p versus NCX-4040+cisplatin, 56.4 ± 7.8%; p Conclusion The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies.

  11. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

    Science.gov (United States)

    Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

    2017-12-01

    Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination.

    Science.gov (United States)

    Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-Ichirou; Kimura, Tadashi

    2017-10-27

    In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer.

  13. [Preneoplasias of ovarian carcinoma: biological and clinical aspects of different pathways of tumorigenesis].

    Science.gov (United States)

    Staebler, A

    2011-11-01

    Ovarian carcinomas consist of a heterogeneous group of malignant epithelial neoplasms with specific pathogenic mechanisms. This review provides a brief introduction to the different pathways of tumor progression and the associated molecular changes. However, the main focus will be on two areas with major paradigm shifting developments in recent years. Mutational analysis of ovarian clear cell carcinomas, endometrioid carcinomas and endometriotic lesions identified mutations in the ARID1A gene as common and early genetic changes in carcinomas with associated endometriosis and in atypical endometriosis itself. Extensive pathological work-up of the fallopian tubes of BRCA1/2 mutation carriers have demonstrated the existence of serous tubal intraepithelial carcinomas (STIC). Further studies showed that this lesion can also be found in 50-60% of patients with serous ovarian carcinomas without BRCA1/2 germline mutations. Pre-precursors which share the p53 mutations with STICs but proliferate very little are called p53-signatures and provide conclusive evidence that STICs develop in the fallopian tubes.

  14. A transplant recipient with a mixed germ-cell ovarian tumor

    Directory of Open Access Journals (Sweden)

    Ketata Hafed

    2008-01-01

    Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

  15. Elevated serum angiotensin converting enzyme levels in metastatic ovarian dysgerminoma.

    LENUS (Irish Health Repository)

    Cotter, T P

    2012-02-03

    A case of a 32-year-old XY genotype female is described, presenting with mediastinal and abdominal lymphadenopathy and associated with an elevated serum angiotensin I converting enzyme (SACE) level. Lymph node histology showed a malignant dysgerminoma of ovarian origin. Combined chemotherapy led to a radiological regression of the lymphadenopathy and coincided with a decrease in SACE concentration. The authors suggest that SACE may be a marker for disseminated germinoma tumours and may be useful for monitoring treatment.

  16. Evaluation of bovine (Bos indicus ovarian potential for in vitro embryo production in the Adamawa plateau (Cameroon

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    J. Kouamo

    2014-12-01

    Full Text Available An abattoir study was conducted to evaluate the ovarian potential of 201 local zebu cattle from Ngaoundere, Adamawa region (Cameroon for in vitro embryo production (IVEP. The ovaries were excised, submerged in normal saline solution (0.9% and transported to the laboratory for a detailed evaluation. Follicles on each ovary were counted, their diameters (Φ measured and were grouped into 3 categories: small (Φ 8 mm. Each ovary was then sliced into a petri dish; the oocytes were recovered in Dulbecco’s phosphate buffered saline, examined under a stereoscope (x10 and graded into four groups based on the morphology of cumulus oophorus cells and cytoplasmic changes of the oocytes. Grade I (GI: oocytes with more than 4 layers of bunch of compact cumulus cells mass with evenly granulated cytoplasm; grade II (GII: oocyte with at least 2-4 layers of compact cumulus cell mass with evenly granulated cytoplasm; grade III (GIII: oocyte with at least one layer of compact cumulus cell mass with evenly granulated cytoplasm; grade IV (GIV: denuded oocyte with no cumulus cells or incomplete layer of cumulus cell or expanded cells and having dark or unevenly granulated cytoplasm. The effects of both ovarian (ovarian localization, corpus luteum, size and weight of ovary and non-ovarian factors (breed, age, body condition score (BCS and pregnancy status of cow on the follicular population and oocyte recovery rate were determined. There were an average of 16.75±0.83 follicles per ovary. The small, medium and large follicles were 8.39±0.60, 8.14±0.43 and 0.21±0.02 respectively. Oocyte recovery was 10.97±0.43 per ovary (65%. Oocytes graded I, II, III and IV were 3.53±0.19 (32.21%, 2.72±0.15 (24.82%, 2.24±0.15 (20.43% and 2.47±0.20 (22.54% respectively. The oocyte quality index was 2.26. Younger non pregnant cows having BCS of 3 and large ovaries presented higher number of follicles and oocyte quality (P < 0.05 compared with other animals. Oocytes with

  17. A study of the use of radioimmunoscintigraphy (RIA) with the monoclonal antibody MAb-170, and fluorine-18 flurodeoxyglucose positron emission tomography (18FDG-PET) for the preoperative imaging of complex ovarian masses and their ability to identify ovarian cancer

    Science.gov (United States)

    Lieberman, Gidon

    The hypothesis for this study is whether the newer diagnostic techniques of radioimmunoscintigraphy (RIS) utilising radiolabelled monoclonal antibodies and 2-[[18]F] fluoro-2-deoxy-D-glucose ([18]FDG) imaging using a double headed gamma camera offer improvements in preoperative selection for referral of patients to Cancer Centres. Monoclonal antibody radioimmunoscintigraphy (RIS) is hindered by several factors including false positive results due to physiological excretion, concern over production of human anti-mouse antibodies (HAMA) that would prevent repeated doses and difficulty in precisely relating areas of accumulation and anatomy. [18]FDG imaging relies on the accumulation of radiolabelled sugars, and subsequent breakdown products within tumour. [18]FDG imaging with dedicated positron emission tomography has real potential, but its use is limited by large capital outlay. Newer techniques involving "dual headed cameras" (DHC) offer PET capability at a lower cost. Chapter two describes the evaluation of a monoclonal antibody (MAb-170) in 27 women who presented with suspicious pelvic masses. The preoperative clinical, radiological and radioimmunoscintigraphy findings are compared to those at surgery and subsequent histology. All 18 patients with malignant or borderline ovarian cancer were correctly identified using RIS. The overall sensitivity and specificity for all sites were 100% and 38%. RIS was particularly useful in the identification of (intra-abdominal) serosal deposits. Enzyme linked immunosorbant assay (ELISA) was used to quantify the HAMA. A strong HAMA production was seen in at least 3 patients, however HAMA response was independent of clinical parameters. Chapter three describes the immunohistochemical staining of paraffin embedded biopsy specimens from the 27 patients who underwent RIS with MAb-170. The original research into the cellular location of the specific epitope to which the antibody interacts was performed on isopentane frozen biopsies

  18. Virus-resembling nano-structures for near infrared fluorescence imaging of ovarian cancer HER2 receptors

    Science.gov (United States)

    Guerrero, Yadir A.; Bahmani, Baharak; Singh, Sheela P.; Vullev, Valentine I.; Kundra, Vikas; Anvari, Bahman

    2015-10-01

    Ovarian cancer remains the dominant cause of death due to malignancies of the female reproductive system. The capability to identify and remove all tumors during intraoperative procedures may ultimately reduce cancer recurrence, and lead to increased patient survival. The objective of this study is to investigate the effectiveness of an optical nano-structured system for targeted near infrared (NIR) imaging of ovarian cancer cells that over-express the human epidermal growth factor receptor 2 (HER2), an important biomarker associated with ovarian cancer. The nano-structured system is comprised of genome-depleted plant-infecting brome mosaic virus doped with NIR chromophore, indocyanine green, and functionalized at the surface by covalent attachment of monoclonal antibodies against the HER2 receptor. We use absorption and fluorescence spectroscopy, and dynamic light scattering to characterize the physical properties of the constructs. Using fluorescence imaging and flow cytometry, we demonstrate the effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors in vitro. These functionalized nano-materials may provide a platform for NIR imaging of ovarian cancer.

  19. Virus-resembling nano-structures for near infrared fluorescence imaging of ovarian cancer HER2 receptors

    International Nuclear Information System (INIS)

    Guerrero, Yadir A; Bahmani, Baharak; Vullev, Valentine I; Anvari, Bahman; Singh, Sheela P; Kundra, Vikas

    2015-01-01

    Ovarian cancer remains the dominant cause of death due to malignancies of the female reproductive system. The capability to identify and remove all tumors during intraoperative procedures may ultimately reduce cancer recurrence, and lead to increased patient survival. The objective of this study is to investigate the effectiveness of an optical nano-structured system for targeted near infrared (NIR) imaging of ovarian cancer cells that over-express the human epidermal growth factor receptor 2 (HER2), an important biomarker associated with ovarian cancer. The nano-structured system is comprised of genome-depleted plant-infecting brome mosaic virus doped with NIR chromophore, indocyanine green, and functionalized at the surface by covalent attachment of monoclonal antibodies against the HER2 receptor. We use absorption and fluorescence spectroscopy, and dynamic light scattering to characterize the physical properties of the constructs. Using fluorescence imaging and flow cytometry, we demonstrate the effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors in vitro. These functionalized nano-materials may provide a platform for NIR imaging of ovarian cancer. (paper)

  20. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.

    Science.gov (United States)

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S L; Chen, Zhihua; Chen, Ann Y; Permuth-Wey, Jennifer; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kelemen, Linda E; Kellar, Mellissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis N; Berchuck, Andrew; Iversen, Edwin S; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-01-01

    Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). These results, generated on a large cohort of women, revealed associations between inherited cellular transport

  1. A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

    Science.gov (United States)

    Wu, Lan; Sun, Yazhou; Wan, Jun; Luan, Ting; Cheng, Qing; Tan, Yong

    2017-07-01

    Ovarian hyperstimulation syndrome (OHSS) is a potentially life‑threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography‑mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

  2. Ovarian tubercular abscess mimicking ovarian carcinoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Abinash Agarwala

    2015-01-01

    Full Text Available Although genito-urinary tuberculosis is common, reports of isolated ovarian tubercular abscess are rare. Ovarian tubercular abscess may mimics that of an ovarian tumor, leading to diagnostic difficulties. We reported a case report of 35 years woman presented with chronic pain abdomen, weight loss, low-grade fever and a right ovarian mass on ultrasound, with a significantly elevated CA-125 level. On clinical and radiological evidence, diagnosis of ovarian carcinoma was made, and laparotomy was performed with resection of the ovary. Postoperative specimen sent for histological examination that revealed classic epithelioid granuloma and acid-fast bacilli were present in Ziehl-Neelsen stain. Patient was put on antitubercular regimen from our Dots center. She is improving clinical after taking antitubercular drug and is on regular follow up at our chest outpatient department. Ovarian tubercular abscess is common in young women living in endemic zones, but case report of isolated tubercular abscess is rarely reported. CA-125 can be raised in both ovarian tubercular abscess and ovarian carcinoma, and only imaging is not always conclusive. Laparotomy followed by tissue diagnosis can be helpful in this situation. As the prognosis and treatment outcome of ovarian tubercular abscess and ovarian carcinoma is different, proper diagnosis by laparotomy should be done. Early diagnosis of ovarian tubercular abscess is vital as untreated disease can lead to infertility.

  3. On the path to translation: Highlights from the 2010 Canadian Conference on Ovarian Cancer Research

    Directory of Open Access Journals (Sweden)

    Thériault Brigitte L

    2011-06-01

    Full Text Available Abstract Ovarian cancer continues to be the most lethal of the gynaecologic malignancies due to the lack of early detection, screening strategies and ineffective therapeutics for late-stage metastatic disease, particularly in the recurrent setting. The gathering of researchers investigating fundamental pathobiology of ovarian cancer and the clinicians who treat patients with this insidious disease is paramount to meeting the challenges we face. Since 2002, the Canadian Conference on Ovarian Cancer Research, held every two years, has served this essential purpose. The objectives of this conference have been to disseminate new information arising from the most recent ovarian cancer research and identify the most pressing challenges we still face as scientists and clinicians. This is best accomplished through direct encounters and exchanges of innovative ideas among colleagues and trainees from the realms of basic science and clinical disciplines. This meeting has and continues to successfully facilitate rapid networking and establish new collaborations from across Canada. This year, more guest speakers and participants from other countries have extended the breadth of the research on ovarian cancer that was discussed at the meeting. This report summarizes the key findings presented at the fifth biennial Canadian Conference on Ovarian Cancer Research held in Toronto, Ontario, and includes the important issues and challenges we still face in the years ahead to make a significant impact on this devastating disease.

  4. Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

    International Nuclear Information System (INIS)

    Nagashima, Kei

    1992-01-01

    There has been increasing interest in the use of heat in the treatment of cancer. Theoretically cells are the most sensitive to ionizing radiation at mitosis, whereas the cycle phase that is the most resistant to ionizing radiation namely late in the DNA. Synthetic phase (late S) is the most sensitive to hyperthermia. Hyperthermia has been reported to enhance the cytocidal effects of several active chemotherapeutic agents. When thermal potentiation of chemotherapeutic agents against malignant cells is contemplated, normal tissues have a relatively high ambient blood flow which increases in response to thermal stress, thereby dissipating heat, compared to tumors. Tumors, with relatively poor blood flow and a responsive neovasculature, are in capable of augmenting flow and acting as a heat reservoir. This is the phenomenon of a heat reservoir which is one factor to enhance the cytocidal effects of several active anticancer agents for enhancing the uptake in tumor. The importance is in the adjuvant chemotherapy treated for post operative, advanced and recurrent ovarian cancer. Heating enhances the effects of radiotherapy and chemotherapy. Thirty patients with ovarian cancer were subjected to the multidisciplinary treatment with combination of hyperthermochemotherapy and radiation. The 30 patients consisted of 18 with endometrioid adenocarcinoma and 7 with serious post operative or recurrent status. Two types of equipments with rediofrequencies of 70 MHz (BSD-1000) or 434 MHZ (TAG MED·HS 434) were used for hyperthermia. Chemotherapeutic agents such as adriamycin, cis DDP, cyclophosphamide and etoposide were injected intravenously. Arterial infusion with reservoir was very effective in advanced stage of ovarian cancer. No severe or fatal side effects were observed. Hyperthermochemotherapy is useful and effective for the postoperative management or the treatment of recurrent cancer of the ovary. (J.P.N.)

  5. Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

    Science.gov (United States)

    Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

    2017-06-01

    Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

  6. Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens.

    Science.gov (United States)

    Sahin, Kazim; Yenice, Engin; Tuzcu, Mehmet; Orhan, Cemal; Mizrak, Cengizhan; Ozercan, Ibrahim H; Sahin, Nurhan; Yilmaz, Bahiddin; Bilir, Birdal; Ozpolat, Bulent; Kucuk, Omer

    2018-03-01

    Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence ( P Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes ( P lycopene-fed hens compared to control birds ( P lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

  7. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

    Science.gov (United States)

    Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

    2008-08-15

    The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

  8. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Conte, Annalea; Guerra, Flora; Felline, Serena [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Rimoli, Maria Grazia [Dipartimento di Farmacia, Università di Napoli Federico II, Napoli (Italy); Mollo, Ernesto [Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (Italy); Zara, Vincenzo [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Terlizzi, Antonio [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Stazione Zoologica Anton Dohrn, Napoli (Italy)

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  9. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    International Nuclear Information System (INIS)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-01-01

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  10. Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity.

    Science.gov (United States)

    Siew, Yin-Yin; Neo, Soek-Ying; Yew, Hui-Chuing; Lim, Shun-Wei; Ng, Yi-Cheng; Lew, Si-Min; Seetoh, Wei-Guang; Seow, See-Voon; Koh, Hwee-Ling

    2015-12-01

    Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, we explored the effects of oxaliplatin, an immunogenic cell death inducer, on the induction of stress ligands and promotion of natural killer (NK) cell-mediated cytotoxicity in human ovarian cancer cells. The results indicated that treatment of tumor cells with oxaliplatin induced the production of type I interferons and chemokines and enhanced the expression of major histocompatibility complex class I-related chains (MIC) A/B, UL16-binding protein (ULBP)-3, CD155 and TNF-related apoptosis-inducing ligand (TRAIL)-R1/R2. Furthermore, oxaliplatin but not cisplatin treatment enhanced susceptibility of ovarian cancer cells to NK cell-mediated cytolysis. In addition, activated NK cells completely abrogated the growth of cancer cells that were pretreated with oxaliplatin. However, cancer cells pretreated with the same concentration of oxaliplatin alone were capable of potentiating regrowth over a period of time. These results suggest an advantage in combining oxaliplatin and NK cell-based therapy in the treatment of ovarian cancer. Further investigation on such potential combination therapy is warranted. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Multivariate Analysis of Reproductive Risk Factors for Ovarian Cancer in Alexandria, Egypt

    International Nuclear Information System (INIS)

    El-Khwsky, F.S.; Maghraby, H.K.; Rostom, Y.A.; Abdel-Rahman, A.H.

    2006-01-01

    Background: Ovarian cancer is the eighth leading cancer in women, as it accounts for 4% of all malignant tumors in females. The incidence of ovarian cancer is up to 10 times higher in western countries than in rural Asian and Africa ones. Different reproductive characteristics, life styles and specific medical conditions are responsible for different pattern and incidence of ovarian cancer worldwide. Material and Methods: A case control study was conducted during the time period from 2000 to 2003 including 172 cases of epithelial ovarian cancer, recently diagnosed and confirmed by histopathology. The patients were accessed at the hospitals currently covered by Alexandria Cancer Registry. In addition, 441 control subjects, comparable by age and address, were randomly selected from patients admitted to the same hospitals for non gynecological, non endocrinal acute diseases. Both cases and controls were subjected to a specific predesigned questionnaire to cover menstrual, reproductive and lifestyle indicators. Univariate and multivariate analysis were conducted and 5% level of significance was adopted. Results: Significantly increased risks were reported with increased number of abortions and increased number of ovarian cycles (OR=1.8, 95% CI (1.7-2.8), and 2.8, 95% CI 2.8 (1.5-5.2), respectively. Similarly, high risks were also reported for increased number of pregnancies, OR= 1.6, 95% CI 1.1-2.4) for I to three pregnancies and 4.2,95% CI 1.2-15.9) for more than four pregnancies On the other hand, decreased risks were reported for those with increased parity compared to nulliparous. Conclusion: Although ovarian cancer is less frequent in our community, yet the significant positive and negative associations between risk factors and ovarian cancer were similar to the results of other studies, apart from the primary prevention program that should be outlined according to prevalence of significant risk factors in the studied local community

  12. Tubal origin of ovarian cancer - the double-edged sword of haemoglobin.

    Science.gov (United States)

    Lin, Shiou-Fu; Gerry, Emily; Shih, Ie-Ming

    2017-05-01

    Ovarian high-grade serous carcinoma (HGSC) is the most malignant neoplasm of the gynaecological tract. While the origins of many human malignant neoplasms are clear, the origin of HGSC remains poorly understood. This lack of knowledge limits our understanding of its pathogenesis and compromises efforts devoted to developing better early detection tools and effective preventative interventions. The paradigm of the tubal origin of HGSC has been advanced since the initial report of dysplastic lesions (now known as serous tubal intraepithelial carcinomas or STICs) that morphologically resemble HGSC in the Fallopian tube. These were observed in a group of patients with a genetic predisposition to ovarian cancer who were undergoing risk-reducing salpingo-oophorectomy. Since then, a series of clinico-pathological and molecular studies have characterized STICs and their concurrent HGSCs, and the results support the new paradigm of a tubal origin of many 'ovarian' HGSCs. Reactive oxygen species-containing ovulatory follicular fluid has been thought to be the major culprit behind DNA damage in tubal epithelial cells, leading to either cell death or, if the cells survive, mutagenesis. A recent report from this journal demonstrates that ferryl haemoglobin (Hb) in peritoneal fluid could prevent cell death from DNA-damaged fimbrial epithelial cells, facilitating ovulation-induced carcinogenesis of tubal epithelium. This timely study provides new insight into the tumour initiation event in HGSC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer

    NARCIS (Netherlands)

    Brouwer, Jan; Kluiver, Joost; de Almeida, Rodrigo C.; Modderman, Rutger; Terpstra, Martijn; Kok, Klaas; Withoff, Sebo; Hollema, Harry; Reitsma, Welmoed; de Bock, Geertruida H.; Mourits, Marian J. E.; van den Berg, Anke

    2016-01-01

    AimsBRCA1 mutation carriers are at increased risk of developing high-grade serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube epithelium. We aimed to identify differentially expressed known and novel miRNAs in BRCA1-associated HGSOC. Methods Small RNA sequencing was

  14. Bilateral Ovarian Fibrothecoma Associated with Ascites, Bilateral Pleural Effusion, and Marked Elevated Serum CA-125

    Directory of Open Access Journals (Sweden)

    Védi André Serges Loué

    2013-01-01

    Full Text Available Background. The risk of ovarian cancer is increased in the association of ovarian tumor, ascites, and hydrothorax with the significant elevated tumor marker CA-125. However, this association can be observed in a rare clinical and benign pathological entity, that is Demons-Meigs’ syndrome. Objective. To describe a rare case of Demons-Meigs' syndrome observed in our department. Methods. A black African woman of 35 years old, seventh gravida and fourth parous, underwent a total abdominal hysterectomy with bilateral salpingoophorectomy for large bilateral ovarian masses associated with significant ascites, bilateral pleural effusion, and particular highly elevated tumor marker CA-125 (1835 UI/mL in a pronounced general alteration condition. Results. The postoperative course was uneventful characterized by a complete remission of hydrothorax and ascites with normal level of CA-125 three months after tumor excision. Histology of both masses revealed a bilateral ovarian fibrothecoma, a benign tumor of the ovary, thus confirming the diagnosis of Demons-Meigs’ syndrome. Conclusion. The Demons-Meigs syndrome, although it strongly mimics the clinical picture of malignant metastatic ovarian cancer, remains a disease with benign prognosis after surgical tumor resection. This is a rare condition that must be known and recognized by practitioners to avoid unnecessary practices.

  15. INCIDENCE OF OVARIAN CYST IN HYPOTHYROIDISM: AN INSTITUTIONAL STUDY

    Directory of Open Access Journals (Sweden)

    Ramesan C

    2016-09-01

    Full Text Available BACKGROUND Primary hypothyroidism is the decrease in production and secretion of thyroid hormones by the thyroid gland. This is characterised by slackening of metabolism and leading to multiple system impairment. The important aetiological factors for primary hypothyroidism are congenital, iodine deficiency, autoimmune thyroiditis and iatrogenic.[1] Ovarian cysts are a common cause for gynaecological surgeries. The aetiology[2] of ovarian cysts can vary greatly including benign or malignant tumours, endometriosis and inflammation, etc. However, some cysts are direct result of endocrine disorders and do not require surgery. Hypothyroidism may cause reproductive and endocrinological disorders as well. The aetiopathogenesis is complex. In 1960 Van Wyk and Grumbach first described the relation between ovarian cyst and hypothyroidism. They proposed that there was a hormonal overlap in the pituitary feedback mechanism. It is due to the fact that TSH, GH, FSH and LH are all glycoproteins with a common alpha chain and may thus cross react. High TSH could produce FSH and LH like activity leading to luteinised ovarian cyst. The TRH may also act on pituitary cells to stimulate gonadotropin release and hence FSH and LH. Other postulated mechanisms are increased ovarian sensitivity to gonadotropins, altered metabolism of oestrogen, hypothalamopituitary dysfunction and altered prolactin metabolism. AIMS To study the percentage of ovarian cyst among the diagnosed cases of primary hypothyroidism and then to find out the association between hypothyroidism and ovarian cyst. To study the relation between level of TSH and size of ovarian cyst. To study the percentage of ovarian cyst among patients with TSH 100 mIU/L separately. SETTINGS Study Design: Descriptive: Cross-sectional study. Duration: One year. Period: March 2013 to February 2014. Sample Size: 100. Study Area: Government Medical College, Calicut. INCLUSION CRITERIA Female patients of age more than 12

  16. Galectin-3 as a Potential Therapeutic Target in Tumors Arising from Malignant Endothelia

    Directory of Open Access Journals (Sweden)

    Kim D. Johnson

    2007-08-01

    Full Text Available Angiosarcoma (ASA in humans, hemangiosarcoma (HSA in dogs are deadly neoplastic diseases characterized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, poor response to chemotherapy. Galectin-3 (Gal-3, a p-galactoside-binding lectin implicated in tumor progression, metastasis, endothelial cell biology, angiogenesis, regulation of apoptosis, neoplastic cell response to cytotoxic drugs, has not been studied before in tumors arising from malignant endothelia. Here, we tested the hypothesis that Gal-3 could be widely expressed in human ASA, canine HSA, could play an important role in malignant endothelial cell biology. Immunohistochemical analysis demonstrated that 100% of the human ASA (10 of 10, canine HSA (17 of 17 samples analyzed expressed Gal-3. Two carbohydrate-based Gal-3 inhibitors, modified citrus pectin (MCP, lactulosyl-l-leucine (LL, caused a dose-dependent reduction of SVR murine ASA cell clonogenic survival through the inhibition of Gal-3 antiapoptotic function. Furthermore, both MCP, LL sensitized SVR cells to the cytotoxic drug doxorubicin to a degree sufficient to reduce the in vitro IC50 of doxorubicin by 10.7-fold, 3.64old, respectively. These results highlight the important role of Gal-3 in the biology of ASA, identify Gal-3 as a potential therapeutic target in tumors arising from malignant endothelial cells.

  17. Role of intraoperative imprint cytology in diagnosis of suspected ovarian neoplasms.

    Science.gov (United States)

    Dey, Soumit; Misra, Vatsala; Singh, P A; Mishra, Sanjay; Sharma, Nishant

    2010-01-01

    The present study was conducted to assess whether cytology can help in rapid diagnosis of ovarian neoplasms and thus facilitate individualised treatment. A prospective investigation was performed on 30 cases of suspected ovarian neoplasms. Imprint smears were made intraperatively from fresh samples from various representative areas, and stained with Leishman Giemsa for air-dried smears, and with hematoxylin and eosin and Papanicolaou for alcohol-fixed smears. A rapid opinion regarding the benign or malignant nature of the lesion and the type of tumour was given. The overall sensitivity was 96.2%, specificity 75%, positive predictive value 96.3%, and diagnostic accuracy of 83.3%. Characteristic cytological patterns were noted in various epithelial and germ cell tumours. Imprint cytology can be used as an adjunct to histopathology for rapid and early diagnosis in the operation theatre, thus helping better management of patients.

  18. The adhesion molecule NCAM promotes ovarian cancer progression via FGFR signalling

    DEFF Research Database (Denmark)

    Zecchini, Silvia; Bombardelli, Lorenzo; Decio, Alessandra

    2011-01-01

    glycoprotein involved in brain development and plasticity, in EOC. NCAM is absent from normal ovarian epithelium but becomes highly expressed in a subset of human EOC, in which NCAM expression is associated with high tumour grade, suggesting a causal role in cancer aggressiveness. We demonstrate that NCAM......Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm, which mainly disseminates to organs of the peritoneal cavity, an event mediated by molecular mechanisms that remain elusive. Here, we investigated the expression and functional role of neural cell adhesion molecule (NCAM), a cell surface...... stimulates EOC cell migration and invasion in vitro and promotes metastatic dissemination in mice. This pro-malignant function of NCAM is mediated by its interaction with fibroblast growth factor receptor (FGFR). Indeed, not only FGFR signalling is required for NCAM-induced EOC cell motility, but targeting...

  19. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... stages. In addition, extreme testosterone excess is not only likely to induce adverse events but has also the potential to be ineffective and even detrimental. Thus, evidence from clinical studies is not enough to either "reopen" or "close" the "androgen chapter" in poor responders, mainly because...

  20. Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

    International Nuclear Information System (INIS)

    Yadav, Budhi S.; Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

    2009-01-01

    Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

  1. Follistatin during pregnancy and its potential role as an ovarian suppressing agent.

    Science.gov (United States)

    Köninger, Angela; Schmidt, Börge; Damaske, Daniela; Birdir, Cahit; Enekwe, Antje; Kimmig, Rainer; Strowitzki, Thomas; Gellhaus, Alexandra

    2017-05-01

    Ovarian quiescence is a common condition during pregnancy. In vitro, follistatin, an antagonist of follicle-stimulating hormone, blocks follicular development at early stages, and its serum levels increase during pregnancy. A possible surrogate biomarker of ovarian arrest during pregnancy is a decrease in anti-mullerian hormone (AMH) levels followed by an increase in these levels on the second day after labor. The purpose of this study was to determine whether follistatin could act as an ovarian-suppressing agent during pregnancy. Follistatin levels and AMH levels were determined at various stages of pregnancy and postpartum. The follistatin and AMH levels of 69 patients were retrospectively determined with the AMH Gen II ELISA and with the Human Follistatin Quantikine ELISA Kit. For 49 patients, samples were available from various trimesters for cross-sectional analysis; for the other 20, samples were available longitudinally from day one before labor and then daily on days 1 through 4 after labor. Statistical significance was determined with linear regression, the Friedman rank sum test and the Wilcoxon-Nemenyi-McDonald-Thompson post hoc test. The behavior of follistatin levels was exactly opposite that of AMH levels: Follistatin levels increased significantly during pregnancy and on the first day after parturition but declined afterwards, whereas AMH levels decreased significantly during pregnancy and increased after labor. Follistatin can induce ovarian arrest during pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Reprogramming T-cells for adoptive immunotherapy of ovarian cancer.

    Science.gov (United States)

    Genta, Sofia; Ghisoni, Eleonora; Giannone, Gaia; Mittica, Gloria; Valabrega, Giorgio

    2018-04-01

    Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies. Despite surgical and pharmacological efforts to improve patients' outcome, persistent and recurrent EOC remains an un-eradicable disease. Chimeric associated antigens (CAR) T cells are T lymphocytes expressing an engineered T cell receptor that activate the immune response after an MHC unrestricted recognition of specific antigens, including tumor associated antigens (TAAs). CART cells have been shown to be effective in the treatment of hematologic tumors even if frequently associated with potentially severe toxicity and high production costs. Areas covered: In this review, we will focus on preclinical and clinical studies evaluating CART activity in EOC in order to identify possible difficulties and advantages of their use in this particular setting. Expert Opinion: The pattern of diffusion within the peritoneal cavity, the tumor microenvironment and the high rate of TAAs make EOC a particularly interesting model for CART cells use. Data from preclinical studies indicate a potential activity of CARTs in EOC, but robust clinical data are still awaited. Further studies are needed to determine the best methods of administration and the most effective CAR type to treat EOC patients.

  3. Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Ramalingam, Preetha

    2016-02-01

    Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical

  4. Lesions of uncertain malignant potential in the breast (B3): what do we know?

    International Nuclear Information System (INIS)

    Purushothaman, H.N.; Lekanidi, K.; Shousha, S.; Wilson, R.

    2016-01-01

    Breast lesions classified as of uncertain malignant potential (B3) on biopsy form a diverse group of abnormalities, which pose a diagnostic and management challenge. In this paper, we discuss the imaging and pathology features as well as the management of the most controversial B3 lesions, consisting of papillary lesions, complex sclerosing lesions/radial scars, lobular intraepithelial neoplasia, and atypical epithelial proliferation of ductal type. As there is an association with malignancy at the time of diagnosis, as well as an increase in the risk of subsequent development of cancer, a multidisciplinary discussion is almost always required to tailor treatment.

  5. Serous papillary adenocarcinoma possibly related to the presence of primitive oocyte-like cells in the adult ovarian surface epithelium: a case report

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    Virant-Klun Irma

    2011-08-01

    Full Text Available Abstract Introduction The presence of oocytes in the ovarian surface epithelium has already been confirmed in the fetal ovaries. We report the presence of SSEA-4, SOX-2, VASA and ZP2-positive primitive oocyte-like cells in the adult ovarian surface epithelium of a patient with serous papillary adenocarcinoma. Case presentation Ovarian tissue was surgically retrieved from a 67-year old patient. Histological analysis revealed serous papillary adenocarcinoma. A proportion of ovarian cortex sections was deparaffinized and immunohistochemically stained for the expression of markers of pluripotency SSEA-4 and SOX-2 and oocyte-specific markers VASA and ZP2. The analysis confirmed the presence of round, SSEA-4, SOX-2, VASA and ZP2-positive primitive oocyte-like cells in the ovarian surface epithelium. These cells were possibly related to the necrotic malignant tissue. Conclusion Primitive oocyte-like cells present in the adult ovarian surface epithelium persisting probably from the fetal period of life or developed from putative stem cells are a pathological condition which is not observed in healthy adult ovaries, and might be related to serous papillary adenocarcinoma manifestation in the adult ovarian surface epithelium. This observation needs attention to be further investigated.

  6. Acute respiratory failure following ovarian hyperstimulation syndrome

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    Antonello Nicolini

    2013-03-01

    Full Text Available Ovarian hyperstimulation syndrome is a serious and potentially life-threatening physiological complication that may be encountered in patients who undergo controlled ovarian hyperstimulation cycles. The syndrome is typically associated with regimes of exogenous gonadotropins, but it can be seen, albeit rarely, when clomiphene is administered during the induction phase. Although this syndrome is widely described in scientific literature and is well known by obstetricians, the knowledge of this pathological and potentially life-threatening condition is generally less than satisfactory among physicians. The dramatic increase in therapeutic strategies to treat infertility has pushed this condition into the realm of acute care therapy. The potential complications of this syndrome, including pulmonary involvement, should be considered and identified so as to allow a more appropriate diagnosis and management. We describe a case of a woman with an extremely severe (Stage 6 ovarian hyperstimulation syndrome who presented ascites, bilateral pleural effusion and severe respiratory failure treated with non-invasive ventilation. The patient was admitted to the intensive care unit because of severe respiratory failure, ascites, and bilateral pleural effusion due to ovarian hyperstimulation syndrome. Treatment included non-invasive ventilation and three thoracentesis procedures, plus the administration of albumin, colloid solutions and high-dose furosemid. Severe form of ovarian hyperstimulation syndrome is observed in 0.5-5% of the women treated, and intensive care may be required for management of thromboembolic complications, renal failure and severe respiratory failure. Pulmonary intensive care may involve thoracentesis, oxygen supplementation and, in more severe cases, assisted ventilation. To our knowledge, there have been only two studies in English language medical literature that describe severe respiratory failure treated with non

  7. ICG-fluorescence imaging for detection of peritoneal metastases and residual tumoral scars in locally advanced ovarian cancer: A pilot study.

    Science.gov (United States)

    Veys, Isabelle; Pop, Florin-Catalin; Vankerckhove, Sophie; Barbieux, Romain; Chintinne, Marie; Moreau, Michel; Nogaret, Jean-Marie; Larsimont, Denis; Donckier, Vincent; Bourgeois, Pierre; Liberale, Gabriel

    2018-02-01

    No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue. Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS. A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%. ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC. © 2017 Wiley Periodicals, Inc.

  8. Expression and significance of cyclooxygenase-2 mRNA in benign and malignant ascites

    Science.gov (United States)

    Lu, Jing; Li, Xiao-Feng; Kong, Li-Xia; Ma, Lin; Liao, Su-Huan; Jiang, Chang-You

    2013-01-01

    AIM: To investigate the mRNA expression of cyclooxygensae-2 (COX-2) in benign and malignant ascites, and to explore the difference in COX-2 mRNA expression among different diseases. METHODS: A total of 36 samples were collected from the Fifth Affiliated Hospital of Sun Yat-Sen University and divided into two experimental groups: benign ascites (n = 21) and malignant ascites (n = 15). Benign ascites included cirrhotic ascites (n = 10) and tuberculous ascites (n = 5). Malignant ascites included oophoroma (n = 7), cancer of colon (n = 5), cancer of the liver (n = 6), gastric cancer (n = 2), and bladder carcinoma (n = 1). The mRNA expression of COX-2 in ascites was examined with reverse transcriptase polymerase chain reaction (RT-PCR) technology, and the positive rate of COX-2 mRNA was compared between different diseases. RESULTS: The positive rate of COX-2 mRNA in malignant ascites was 42.9% (9/21), which was significantly higher than in benign ascites, 6.7% (1/15), difference being significant between these two groups (χ2 = 4.051, P = 0.044). The proportion of the positive rate in the malignant ascites was as follows: ovarian cancers 57.1% (4/7), colon cancer 40.0% (2/5), liver cancer 33.3% (2/6), gastric cancer 50.0% (1/2), and bladder cancer 0.00% (0/1). However, there was no significant difference in COX-2 mRNA expression among various tumors with malignant ascites (χ2 = 1.614, P = 0.806). Among the benign ascites, COX-2 mRNA levels were different between the tuberculous ascites (0/5) and cirrhotic ascites (1/10), but there was no significant difference (P = 1.000). CONCLUSION: COX-2 mRNA, detected by RT-PCR, is useful in the differential diagnosis of benign and malignant ascites, which also has potential value in the clinical diagnosis of tumors. PMID:24187465

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

    International Nuclear Information System (INIS)

    Byrne, Jennifer A; Sutherland, Robert L; Fazio, Anna de; O'Brien, Philippa M; Maleki, Sanaz; Hardy, Jayne R; Gloss, Brian S; Murali, Rajmohan; Scurry, James P; Fanayan, Susan; Emmanuel, Catherine; Hacker, Neville F

    2010-01-01

    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. 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. 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). 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

  10. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

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    Guang Zhang

    2013-01-01

    Full Text Available Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC remains disastrous. Cancer stem cells (CSCs may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2 is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

  11. Molecular epigenetics in the management of ovarian cancer: Are we investigating a rational clinical promise?

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    Ha eNguyen

    2014-04-01

    Full Text Available Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. While liquid tumors are benefitting from epigenetically-related therapies, solid tumors like ovarian cancer are not (yet?. Herein we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Preclinical and clinical research on the role of epigenetic modifications is summarized as well. Sadly, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have preclinical utility in pharmacology and clinical applications for prognosis and diagnosis. Lastly, drugs currently in clinical trials (i.e. histone deacetylase inhibitors are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; what we have now is hope.

  12. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

    International Nuclear Information System (INIS)

    Feng, Xue; Li, Ling; Jiang, Hong; Jiang, Keping; Jin, Ye; Zheng, Jianhua

    2014-01-01

    Highlights: • Phosphorylation of mTOR is abnormal activation in SKOV3/DDP ovarian cancer cells. • Downregulation of mTOR by DHA helps to sensitize the SKOV3/DDP cells to chemotherapy. • DHA has the potential of induce autophagy in cancer cells. - Abstract: Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells

  13. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Xue [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Li, Ling [Department of Brain Cognition Computing Lab, University of Kent, Kent CT2 7NZ (United Kingdom); Jiang, Hong; Jiang, Keping; Jin, Ye [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Zheng, Jianhua, E-mail: zhengjianhua1115@126.com [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China)

    2014-02-14

    Highlights: • Phosphorylation of mTOR is abnormal activation in SKOV3/DDP ovarian cancer cells. • Downregulation of mTOR by DHA helps to sensitize the SKOV3/DDP cells to chemotherapy. • DHA has the potential of induce autophagy in cancer cells. - Abstract: Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells.

  14. Ovarian chocolate cysts

    International Nuclear Information System (INIS)

    Sugimura, Kazuro; Ishida, Tetsuya; Takemori, Masayuki; Kitagaki, Hajime; Tanaka, Yutaka; Yamasaki, Katsuhito; Shimizu, Tadafumi; Kono, Michio.

    1988-01-01

    Accurate preoperative staging of ovarian chocolate cysts is very important because recent hormonal therapy has been effective in low stage patients. However, it has been difficult to assess the preoperative stage of ovarian chocolate cysts. We evaluated the diagnostic potential of MRI in preoperative staging of 15 overian chocolate cysts. It was well known that the older the ovarian chocolate cyst was the more iron content it had. We examined the iron contents effect on T1 and T2 relaxation times in surgically confirmed chocolate cysts (stage II: 3 cases, stage III: 3 cases and stage IV: 9 cases by AFS classification, 1985) employing the 0.15-T MR system and 200 MHz spectrometer. There was a positive linear relation between T1 of the lesion using the MR system (T1) and T1 of the resected contents using the spectrometer (sp-T1); r = 0.93. The same relation was revealed between T2 and sp-T2; r = 0.87. It was indicated that T1 and T2 using the MR system was accurate. There was a negative linear relation between T1 and the iron contents ( r = -0.81) but no relation between T2 and the iron contents. T1 was 412 ± 91 msec for stage II, 356 ± 126 msec for stage III and 208 ± 30 msec for stage IV. T1 for stage IV was shorter than that for stage II and III, statistically significant differences were noted (p < 0.05). Thus, T1 was useful in differentiating a fresh from an old ovarian chocolate cyst. We concluded that T1 relaxation time using the MR system was useful for the staging of an ovarian chocolate cyst without surgery. (author)

  15. OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma - A critical appraisal

    NARCIS (Netherlands)

    van Haaften-Day, C; Shen, Y; Xu, FJ; Yu, YH; Berchuck, A; Havrilesky, LJ; de Bruijn, HWA; van der Zee, AGJ; Bast, RC; Hacker, NF

    2001-01-01

    BACKGROUND. Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel

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

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    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  18. Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer.

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    Lanfang Li

    Full Text Available Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1, an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients.We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer.The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375 and the protein (P = 0.0007 levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004 and omentum metastasis (P = 0.024. Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026.These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend

  19. Risk of borderline ovarian tumors among women with benign ovarian tumors

    DEFF Research Database (Denmark)

    Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

    2018-01-01

    tumors among women with a benign ovarian tumor. METHODS: This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals...... (CI) were calculated. RESULTS: Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors....... The risk for borderline ovarian tumors was primarily increased for women diagnosed with a benign ovarian tumor before 40years of age. The risk remained increased up to 9years after a benign ovarian tumor diagnosis. Finally, the associations did not change markedly when analyzed for the different histotypes...

  20. Proteomics Analysis for Finding Serum Markers of Ovarian Cancer

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    Yushan Cheng

    2014-01-01

    Full Text Available A combination of peptide ligand library beads (PLLB and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4 is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value 89.13±1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85±2.38 ng/mL. Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.

  1. Ovarian arteries supply to the pelvic lesions: angiographic identification and endovascular interventional management

    International Nuclear Information System (INIS)

    Wang Maoqiang; Liu Fengyong; Duan Feng; Wang Zhongpu; Wang Zhijun; Song Lei

    2006-01-01

    Objective: To investigate the frequency of the ovarian arteries (OVA) supply to the pelvic lesions and to evaluate the safety of transcatheter arterial embolization (TAE) of the OVA. Methods: Ninety-six patients referred for hypogastric-uterine arterial chemoembolization or embolization underwent selective ovarian arteriography,including pelvic malignancies in 63 cases, uterine fibroid in 17, and obstetric hemorrhage in 16 cases. Mean patient age was 46 years (range, 16-62 years). TAE supplementally was performed in patients with OVA supply to the pelvic lesions, using polyvinyl alcohol particles, gelatin sponge particles, and microcoils. The frequency of OVA supply to the pelvic lesions, the predictive factors, the technique and clinical significances of OVA embolization, were evaluated. Results: Bilateral OVA were catheterized selectively in 58 patients, and unilateral OVA in 38 patients. Thirty-three women (34.4%) had at least one ovarian artery supplying the pelvic lesions, including pelvic malignancies in 18, the fibroid in 5, and obstetric hemorrhage in 10 cases. The higher incidence of OVA supply to the pelvic lesions was observed in patients with obstetric disorders (χ 2 =6.73, P=0.009), with history of the pelvic surgery (χ 2 =3.55, P=0.04), with post embolization of the uterine arteries (χ 2 =6.80, P=0.009), and in patients with dysplasia of uterine artery bilaterally or unilaterally (χ 2 =3.40, P=0.04). Technical success of OVA embolization was achieved in the 33 cases, without severe complications related to the procedure. Persistent bleeding from the vagina was seen in 4 patients with obstetric hemorrhage after hypogastric-uterine arterial embolization, their bleeding ceased immediately after supplemental OVA embolization. Four patients developed transient symptoms of ovarian dysfunction after the hypogastric-uterine and OVA embolization. Conclusion: About 34% of the pelvic lesions can be supplied by OVA. Supplemental TAE of OVA is a safe and

  2. Prognostic importance of vascular endothelial growth factor-A expression and vascular endothelial growth factor polymorphisms in epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Smerdel, Maja; Waldstrøm, Marianne; Brandslund, Ivan

    2009-01-01

    INTRODUCTION: Vascular endothelial growth factors (VEGFs) play a central role in angiogenesis and consequently, in various steps of ovarian carcinogenesis. Gene polymorphisms within the VEGF system have revealed a correlation with prognosis in some malignancies. The aim of the present study...... was to examine the possible importance of 2 VEGF polymorphisms and VEGF-A expression in ovarian cancer. METHODS: We investigated 2 single nucleotide polymorphisms VEGF +405G/C and VEGF -460C/T by polymerase chain reaction and also analyzed VEGF-A expression by immunohistochemistry in 159 women with ovarian...... cancer. RESULTS: Vascular endothelial growth factor-A expression revealed a significant correlation with survival in a Cox proportional hazards regression model (P = 0.012). Germline polymorphisms were not correlated with clinicopathological parameters such as stage, type, and histology. Heterozygous...

  3. Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Annelisa M. Cornel

    2018-05-01

    Full Text Available Dendritic cell (DC vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of surmountable shortcomings, such as selection of utilized DC subsets, DC loading and maturation strategies, as well as tumor-induced immunosuppression may be targeted to maximize anti-tumor responses of DC vaccines. Generation of DC from CD34+ hematopoietic stem and progenitor cells (HSPCs may provide potential in patients undergoing allogeneic HSPC transplantations for hematologic malignancies. CD34+ HSPC from the graft can be genetically modified to optimize antigen presentation and to provide sufficient T cell stimulatory signals. We here describe beneficial (gene-modifications that can be implemented in various processes in T cell activation by DC, among which major histocompatibility complex (MHC class I and MHC class II presentation, DC maturation and migration, cross-presentation, co-stimulation, and immunosuppression to improve anti-tumor responses.

  4. Gestational Tubal Choriocarcinoma Presenting as a Pregnancy of Unknown Location following Ovarian Induction

    Directory of Open Access Journals (Sweden)

    Lawrence Hsu Lin

    2018-01-01

    Full Text Available The management of pregnancy of unknown location (PUL can be a challenging situation, since it can present as several different conditions. Here we describe a rare case of gestational choriocarcinoma arising in the fallopian tube after ovarian induction in an infertile patient. The patient received clomiphene for ovarian induction and had rising levels of human chorionic gonadotropin (hCG over nine months without sign of pregnancy. After referral to our center, the patient was diagnosed with a paraovarian tumor, which revealed a gestational choriocarcinoma arising in the fallopian tube; the final diagnosis was supported by pathological and cytogenomic analysis. Malignancies, such as gestational trophoblastic disease, should be in the differential diagnosis of PUL; the early recognition of these conditions is key for the proper treatment and favorable outcome.

  5. Changes in ovarian reserve and ovarian blood flow in patients with polycystic ovary syndrome following laparoscopic ovarian drilling.

    Science.gov (United States)

    Kamal, Nasser; Sanad, Zakaria; Elkelani, Osama; Rezk, Mohamed; Shawky, Mohamed; Sharaf, Abd-Elbar

    2018-04-10

    This prospective cohort study was conducted on 80 patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian stromal blood flow indices (Vascularization index: VI, flow index: FI, and vascularization flow index: VFI) were measured to explore the effect of LOD and to find out the correlation between serum AMH and different clinical, hormonal, and ultrasonic variables. There was a highly significant reduction of the serum AMH (p ovarian reserve parameters (AMH, OV and AFC) and ovarian stromal blood flow indices (VI, FI and VFI) with no observed correlation between AMH levels and Doppler indices.

  6. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    Science.gov (United States)

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Álvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; García-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; van Altena, Anne M; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; van den Ouweland, Ans M W; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; van Os, Theo A M; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Paillerets, Brigitte Bressac-de; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Åke; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

    2013-01-01

    TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduced estrogen receptor negative (ER-negative) (P=1.0×10−8) and BRCA1 mutation carrier (P=1.1×10−5) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10−14), increased low malignant potential ovarian cancer risk (P=1.3×10−15) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10−12) and BRCA1 mutation carrier (P=1.6×10−14) breast and invasive ovarian (P=1.3×10−11) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splice-variant. PMID:23535731

  7. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

    Science.gov (United States)

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Alvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; Altena, Anne Mvan; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkisza