Search results for: ovarian%20cancer

Authors: Mahmoodreza Tahamtan

Abstract:

Malignant surface epithelial ovarian tumors(SEOT) account for approximately 90% of primary ovarian cancer. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Of the 35 cases of ovarian serous cystadenocarcinoma 30(85.7%)were diffusely positive(3+,4+),4 showed reactivity of < 50% of the tumor cells(1+,2+) and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors.

Keywords: WT1, ovary, malignant, epithelial tumors

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Authors: Amar Ranjan, Julieana Durai, Pranay Tanwar

Abstract:

Background &Introduction: Ovarian cancer is one of the most common malignant tumor in the female. 70% of the cases of ovarian cancer are diagnosed at an advanced stage. The five-year survival rate associated with ovarian cancer is less than 30%. The early diagnosis of ovarian cancer becomes a key factor in improving the survival rate of patients. Presently, CAl25 (carbohydrate antigen125) is used for the diagnosis and therapeutic monitoring of ovarian cancer, but its sensitivity and specificity is not ideal. The introduction of HE4, human epididymis protein 4 has attracted much attention. HE4 has a sensitivity and specificity of 72.9% and 95% for differentiating between benign and malignant adnexal masses, which is better than CA125 detection.  Methods: Serum HE4 and CA -125 were estimated using the chemiluminescence method. Our cases were 40 epithelial ovarian cancer, 9 benign ovarian tumor, 29 benign gynaecological diseases and 13 healthy individuals. This group include healthy woman those who have undergoing family planning and menopause-related medical consultations and they are negative for ovarian mass. Optimal cut off values for HE4 and CA125 were 55.89pmol/L and 40.25U/L respectively (determined by statistical analysis). Results: The level of HE4 was raised in all ovarian cancer patients (n=40) whereas CA125 levels were normal in 6/40 ovarian cancer patients, which were the cases of OC confirmed by histopathology. There is a significant decrease in the level of HE4 with comparison to CA125 in benign ovarian tumor cases. Both the levels of HE4 and CA125 were raised in the nonovarian cancer group, which includes cancer of endometrium and cervix. In the healthy group, HE4 was normal in all patients except in one case of the rudimentary horn, and the reason for this raised HE4 level is due to the incomplete development of uterus whereas CA125 was raised in 3 cases. Conclusions: Findings showed that the serum level of HE4 is an important indicator in the diagnosis of ovarian cancer, and it also distinguishes between benign and malignant pelvic masses. However, a combination of HE4 and CA125 panel will be extremely valuable in improving the diagnostic efficiency of ovarian cancer. These findings of our study need to be validated in the larger cohort of patients.

Keywords: human epididymis protein 4, ovarian cancer, diagnosis, benign lesions

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

Abstract:

Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: I. Ramalho, S. Campos, M. Dias

Abstract:

Introduction: Endometriosis may play a role in the pathogenesis of ovarian cancer (OC), however, the risk and prognosis have not been well established. The association between these two pathologies could have an important impact on prevention and early diagnosis of OC. Objective: To analyze the prevalence of endometriosis associated ovarian cancer and related clinical, epidemiological and histopathological issues. Design: We conducted a retrospective case series analysis of patients diagnosed with endometriosis and ovarian cancer in the Gynecology Department of Coimbra University Hospital Center since 2006 to 2015. Methods: We collected data from women diagnosed with ovarian cancer, with anatomopathology records reporting findings of endometriosis in ovarian cancer patients. Patients were retrieved from the pathological records and appropriate medical records were retrospectively reviewed. Statistical analysis was performed using SPSS 22.0. Results: Histological evidence of endometriosis was found in 17 out of 261 patients diagnosed with ovarian cancer (OC) (6.51%). The most usual symptoms were pelvic pain, abdominal distension, asthenia, ascites, weight loss and nausea. Mean age at diagnosis was 61.2 ± 15.1, 41-86 years old, 33.3% were pre-menopausal patients and cancer stage distribution was predominantly stage I (31.3%) and stage III (56.3%). OC occurred unilaterally in 14 patients and 2 patients were diagnosed with a synchronous ovarian and endometrial cancer. Regarding histological type, 10 OC were classified as clear cell carcinoma (CCC), 4 endometrioid carcinomas (EC) and 3 mixed type (clear cell and endometrioid). Four ovarian carcinomas presumably arose from endometriomas: 3 CCC and 1 EC. Conclusions: In accordance with previous studies, clear cell was the most common pathological type in endometriotic patients, followed by endometrioid carcinomas, and two rare synchronous ovarian and endometrial carcinomas were registered. Although endometriosis association to OC is uncommon, endometriosis should be managed with special care in order to early diagnosis.

Keywords: endometriosis, histology, observational study, ovarian cancer

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Authors: Abdelmaguid Ramzy, Mohamed Bahaa

Abstract:

Introduction: The effects of ovarian endometrioma on fertility outcomes with IVF have been always related to poor outcomes. Objective: To evaluate the effect of unilateral unoperated ovarian endometrioma < 2cm on the number of developing follicles and compare them with the contralateral ovary as a control. Design: Retrospective case control study. Setting: KasrEl-Aini IVF center. Patient(s): We studied 32 women with unilateral endometrioma who underwent their first IVF cycle. Methods: 32 Patients aged between 20-35 years selected for IVF who were diagnosed with one unilateral endometrioma (diameter <2 cm) and who did not undergo previous ovarian surgery were retrospectively identified. The number of follicles > 17 mm during folliculometry on the day of HCG trigger in the ovary that contained endometrioma were compared with those from the contralateral ovary. They were all hyperstimulated using long protocol with (225-300 IU) gonadotrophins. Primary outcome: The number of follicles > 17 mm during folliculometry on the day of HCG trigger. Result(s): The mean ± SD age, Day 3 serum FSH and LH were 27± 3.7 years, 5.8 ± 1.6 IU/ml and 4.5 ± 1.7 IU/ml respectively. There was no significant difference in the number of follicles > 17 mm on the day of HCG trigger in the ovary that contained endometrioma (4.4 ±2.5) and in the opposite ovary (4.5 ± 2.8) (P= 0.48). Conclusion: The presence of ovarian endometrioma in a controlled ovarian hyperstimulation cycle for IVF treatment is not associated with a reduced number of follicles > 17 mm during folliculometry on the day of HCG trigger.

Keywords: endometrioma, folliculometry, hyperstimulation, fertility

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Authors: M. Sunitha, B. Nithyavani, Mathew Yohannan, S. Thiruvieni Balajji, M. A. Rathi, C. Arul Raj, P. Ragavendran, V. K. Gopalkrishnan

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Establishment of an early and reliable biomarker for ovarian carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Carbonic anhydrases (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. In von Hippel-Lindau (VHL)-defective tumors, the cell surface transmembrane carbonic anhydrase (CA) CA XI and CA XII genes are overexpressed because of the absence of pVHL. These enzymes are involved in causing a hypoxia condition, thereby providing an environment for metastasis. Aberrant expression of the facilitative glucose transporter GLUT I is found in a wide spectrum of epithelial malignancies. Studying the mRNA expression of CA IX, CA XII and Glut I isozymes in ovarian cancer cell lines (OAW-42 and PA-1) revealed the expression of these hypoxia genes. Immunohistochemical staining of carbonic anhydrases was also performed in 40 ovarian cancer tissues. CA IX and CA XII were expressed at 540 bp and 520 bp in OAW42, PA1 in ovarian cancer cell lines. GLUT-1 was expressed at 325bp in OAW 42, PA1 genes in ovarian cancer cell lines. Immunohistochemistry revealed high to moderate levels of expression of these enzymes. The immuostaining was seen predominantly on the cell surface membrane. The study concluded that these genes CA IX, CA XII and Glut I are expressed under hypoxic condition in tumor cells. From the present results expression of CA IX, XII and Glut I may represent potential targets in ovarian cancer therapy.

Keywords: ovarian cancer, carbonic anhydrase IX, XII, Glut I, tumor markers

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Authors: Elham Vojoudi, Marzieh Mehrafza, Ahmad Hosseini, Azadeh Raofi, Maryam Najafi

Abstract:

Premature ovarian failure (POF) has become one of the main causes of infertility in women of childbearing age and the incidence of this disorder is increasing year by year. In these patients, poor ovarian response (POR) to gonadotropins reflects a diminished ovarian reserve (DOR) that gives place to few follicles despite aggressive stimulation. Up to now, egg donation is the only way to resolve infertility problems in POF patients. Therefore, some novel aspects such as activating (Akt signaling pathway) and inhibiting (Hippo-signaling) elements have been identified as IVA procedure that promotes primordial follicle activation. In this study, we used the newly developed technique (combination of in vitro activation of dormant follicles (IVA) and stem cell therapy) to promote ovarian follicle growth much more efficiently than the natural, in vivo process for women with POF. Transplantation of Warton Jelly-MSCs to the ovaries of POF patients rescued overall ovarian function. Participants (10 patients) were followed up monthly for a period of six months by hormonal (AMH, FSH, LH and E2), clinical (resuming menstruation), and US (folliculometry) outcomes after a laparoscopic operation. In summary, IVA/WJ-MSC transplantation may provide an effective treatment for POF.

Keywords: POF, in vitro activation, stem cell therapy, infertility

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Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

Abstract:

At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: Ae Ra Han, Taek Hoo Lee, Sun Zoo Kim, Hwa Young Lee

Abstract:

Introduction: Ovarian endometrioma is one of the important causes of poor ovarian reserve and up to half of them have recurred. However, the treatment for recurrence prevention has limited efficiency and repeated surgical management makes worsen the ovarian reserve. To find better management for recurrence prevention, we investigated risk factors and biomarkers for the recurrence of ovarian endometrioma. Methods: The medical records of women with the history of surgical dissection for ovarian endometrioma were collected. After exclusion of the cases with concurrent hysterectomy, been menopaused during follow-up, incomplete medical record, and loss of follow-up, a total of 134 women were enrolled. Immunohistochemical staining for progesterone receptor isoform B (PR-B) and nuclear factor kappa B (NFκB) was done with the fixed tissue blocks of their endometriomas which were collected at the time of surgery. Results: Severity of dysmenorrhea and co-existence of adenomyosis had significant correlation with recurrence of endometrioma. Increased PR-B (P = .041) and decreased NFκB (P = .036) immunoreactivity were found in recurrent group. Serum CA-125 level at the time of recurrence was higher than the highest level of CA-125 during follow-up in unrecurred group (55.6 vs. 21.3 U/mL, P = .014). Conclusion: We found that the severity of dysmenorrhea and coexistence of adenomyosis are risk factors for recurrence of ovarian endometrioma, and serial follow-up of CA-125 is effective to detect and prevent the recurrence. However, to determine the possibility of immunoreactivity of PR-B and NFκB as biomarkers for ovarian endometrioma, further studies of various races and large numbers with prospective design are needed.

Keywords: endometriosis, recurrence, biomarker, risk factor

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Authors: Kira Merigan

Abstract:

BACKGROUND- Fertility preservation (FP) measures are increasingly recognised as an important consideration for children and adolescents planned to undergo potentially damaging gonadotoxic therapy. Worldwide, there are very few documented cases of FP in young females by way of ovarian stimulation and oocyte cryopreservation.AIM – To report a case series of mature oocyte cryopreservation in 5post-pubertal adolescents aged 14-17 years old, with varied medical conditions requiring gonadotoxic treatment. SETTING-These cases took place via a multidisciplinary team approach at The Royal Children’s Hospital, a large tertiary centre in Melbourne, Australia. INTERVENTION– Ovarian stimulation and oocyte collection was performed as detailed in each case. RESULTS –Across the 5 patients, 3-28 oocytes were retrieved. We report pre-treatment workup, complications, and delays to treatment. CONCLUSION- Oocyte cryopreservation may be a safe alternative to ovarian tissue cryopreservation (OTC) in the adolescent population

Keywords: fertility preservation, adolescent, ovarian stimulation, oocyte cryopreservation

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Authors: D. Tohlob, E. Abo Hashem, N. Ghareeb, M. Ghanem, R. Elfarahaty, S. A. Roberts, P. Pemberton, L. Mohiyiddeen, W. G. Newman

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Gonadotropin stimulation is used in females undergoing assisted reproductive treatment for ovulation induction, but ovarian response is variable and unpredictable in these women. More effective protocols and individualization of treatment are needed to increase the success rate of IVF/ICSI cycles. We genotyped seven variants reported in previous studies to be associated with ovarian response (number of ova retrieved and total gonadotropin dose) in women undergoing IVF treatment including FSHR variants Asn 680 Ser (c.2039 A > G), Thr 307 Ala (c. 919 > A), -29 G > A, HRG c.610 C > T gene, BMP15 -9 C > G, AMH Ile 49 Ser (c.146 G > T), and AMHR -489A˃G in 118 Egyptian females attending Mansoura Integrated Fertility Center in Egypt, these females were undergoing their first cycle of controlled ovarian hyper stimulation for IVF/ICSI treatment. They were analyzed by TaqMan allelic discrimination assay in Manchester Center of Genomic Medicine. We found no evidence of any significant difference (p value < 0.05) in the number of eggs retrieved or the gonadotropin dose used between individuals in all genotypes except for HRG c.610 C > T gene polymorphism where regression analysis gives a p value of 0.04 with a fewer eggs number in TT genotyped females. These results indicate that these variants do not provide sufficient clinically relevant data to individualize the treatment protocols.

Keywords: controlled ovarian hyperstimulation, gene variants, ovarian response, assisted reproduction

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Authors: Nashi Khan, Amina Khalid

Abstract:

Aim: The purpose of this research was to find the psychiatric morbidity and level of sexual satisfaction among women with polycystic ovarian syndrome and their comparison with women with general medical conditions and to examine the correlation between psychiatric morbidity and sexual satisfaction among these women. Design: Cross sectional research design was used. Method: A total of 176 (M age = 30, SD = 5.83) women were recruited from both private and public sector hospitals in Pakistan. About 88 (50%) of the participants were diagnosed with polycystic ovarian syndrome (cases), whereas other 50% belonged to control group. Data were collected using semi structured interview. Sexual satisfaction scale for women (SSS-W) was administered to measure sexual satisfaction level and psychiatric morbidity was assessed by Symptom Checklist-Revised. Results: Results showed that participant’s depression and anxiety level had significant negative correlation with their sexual satisfaction level, whereas, anxiety and depression shared a significant positive correlation. There was a significant difference in the scores for sexual satisfaction, depression and anxiety for both cases and controls. These results suggested that women suffering from polycystic ovarian syndrome tend to be less sexually satisfied and experienced relatively more symptoms of depression and anxiety as compared to controls.

Keywords: level of sexual satisfaction, psychiatric morbidity, polycystic ovarian syndrome

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Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Faiqah Ramli, Syam Mohan, Noraziah Nordin, Hamed Karimian, Hapipah Mohd Ali

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Ovarian cancer is the most lethal gynecological malignancies. HME5, a prenylflavanoid has been isolated from local medicinal plant. This compound has been reported to possess a broad spectrum of biological activities including anticancer property. However, the potential of HME5 as an antiproliferative and cytotoxic agent on an ovarian cancer cells has not yet been investigated. In this present study, we examined the antiproliferative and cytotoxic effect of HME5 on Caov-3 (Human Ovarian Adenocarcinoma) cell line by using 3-[4,5-dimethylthizol-2-y]-2,5-diphenyltetrazolium bromide (MTT) assay, Acridine orange and propidium Iodide (AOPi) and cell cycle analysis study. HME5 has shown to inhibit Caov-3 in a time-dependent manner with the IC50 values of 5µg/ml, 2µg/ml and 1µg/ml after 24h, 48h and 72h treatment, respectively. Morphological study from AOPi analysis showed that HME5 induced apoptosis after 24 and 48h post-treatment. Nevertheless, HME5 exhibited cell cycle arrest at G1 phase as indicated in flow cytometry cell cycle profiling. In conclusion, HME5 inhibited proliferation of Caov-3 through induction of apoptosis and cell cycle arrest at G1 phase.

Keywords: apoptosis, prenylflavanoid, ovarian cancer, HME5

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Authors: Ghada E. Esheba, Ghufran Kheshaifaty, Kholoud Al-Harbi, Wafa'a Al-Harbi, Ala'a Al-Orabi, Moayad Turkistani

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Krukenberg tumor is a rare metastatic ovarian carcinoma that usually occurs in female between 30 - 40 year old and rarely seen after menopause. Stomach is the most common primary site. Histopathological features of krukenberg tumors appear as diffuse stromal proliferation, mucus-production, and numerous signet-cells and these tumors spread mostly by lymphatic route. Treatment and prognostic factors are not well established. This study describes a 34 year old female with a unilateral ovarian mass discovered accidentally during cesarean section delivery and it was misdiagnosed as luteoma of pregnancy, but histopathological examination showed a diffuse infiltration of the ovary and omentum by signet ring cells. These findings were not correlated with luteoma of pregnancy or any other types of primary ovarian tumors like surface epithelial tumor, sex cord stromal tumor or germ cell tumor. However, after the analysis of immunohistochemical results (negative CK7, positive CK20 and CDX-2), the finding was the diagnostic of metastatic krukenberg tumor. Two weeks later, the patient was evaluated and a large gastric tumor was found in her stomach and she underwent gastrectomy.

Keywords: CK7, CK20, CDX-2, Krukenburg tumor, metastatic ovarian tumor

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Authors: Viyango Pandian, Kumaresh Athiyappan

Abstract:

Pelvic congestion Syndrome (PCS) is usually seen in multiparous women who give history of chronic dull-aching pelvic pain. We report a case of a 17 year old unmarried female, who presented with acute onset of chronic dull-aching abdominal pain in the left iliac fossa, which particularly increased during menstruation and was finally diagnosed to be pelvic congestion syndrome. On ultrasonography, multiple tortuous and dilated veins were observed in the left adnexa. Both ovaries appeared normal in size, volume and echotexture. Computed tomography (CT) angiography was performed to precisely delineate the venous pathway and to assess any associated abnormality; which showed a dilated and tortuous left ovarian vein with an anomalous course around the left kidney and draining into the left renal vein. Clinical parameters and hormonal levels were within normal limits. This is a rare case of anomalous course of left ovarian vein associated with pelvic congestion syndrome.

Keywords: anomalous course of ovarian vein, computed tomography, pelvic congestion syndrome, ultrasonography

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Authors: Deirdre Mc Grath, Joanne Reid

Abstract:

Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has in relation to this study enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying program theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving program theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: ovarian cancer, exercise intervention, implementation, Co-design

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Authors: Mahmoodreza Tahamtan

Abstract:

Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Results: Of the 35 cases of ovarian serous cystadenocarcinoma, 30(85.7%) were diffusely positive (3+,4+),4 showed reactivity of < 50% of the tumor cells (1+,2+), and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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Authors: Deirdre Mc Grath, Joanne Reid

Abstract:

Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide, with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has, in relation to this study, enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying programme theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving programme theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: exercise, ovarian cancer, co-design, implementation

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Chia-Jung Li, Kuan-Hao Tsui

Abstract:

As women age, the quality of their oocytes deteriorates irreversibly, leading to reduced fertility. To better understand the role of Ferroptosis-related genes in ovarian aging, we employed a multi-omics analysis approach, including spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsies. Our study identified excess lipid peroxide accumulation in aging germ cells, metal ion accumulation via oxidative reduction, and the interaction between ferroptosis and cellular energy metabolism. We used multi-histological prediction of ferroptosis key genes to evaluate 75 patients with ovarian aging insufficiency and then analyzed changes in hub genes after supplementing with DHEA, Ubiquinol CoQ10, and Cleo-20 T3 for two months. Our results demonstrated a significant increase in TFRC, GPX4, NCOA4, and SLC3A2, which were consistent with our multi-component prediction. We theorized that these supplements increase the mitochondrial tricarboxylic acid cycle (TCA) or electron transport chain (ETC), thereby increasing antioxidant enzyme GPX4 levels and reducing lipid peroxide accumulation and ferroptosis. Overall, our findings suggest that supplementation intervention significantly improves IVF outcomes in senescent cells by enhancing metal ion and energy metabolism and enhancing oocyte quality in aging women.

Keywords: multi-omics, nutrients, ferroptosis, ovarian aging

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Authors: Dimitrios Binas, Marianna Konidari, Charis Bourgioti, Lia Angela Moulopoulou, Theodore Economopoulos, George Matsopoulos

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High grade ovarian epithelial cancer (OEC) is fatal gynecological cancer and the poor prognosis of this entity is closely related to considerable intratumoral genetic heterogeneity. By examining imaging data, it is possible to assess the heterogeneity of tumorous tissue. This study proposes a methodology for aligning, segmenting and finally visualizing information from various magnetic resonance imaging series in order to construct 3D models of heterogeneity maps from the same tumor in OEC patients. The proposed system may be used as an adjunct digital tool by health professionals for personalized medicine, as it allows for an easy visual assessment of the heterogeneity of the examined tumor.

Keywords: image segmentation, ovarian epithelial cancer, quantitative characteristics, image registration, tumor visualization

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

Abstract:

Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: Nayera E. Hassan, Salah Mostafa, Hamed Elkhayat, Kalled Hassan Sewidan, Sahar A. El-Masry, Manal Mouhamed Ali, Mones M. Abu Shady

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Pubertal growth is influenced by many factors including environmental and nutritional factors. Objective: To assess impact of nutritional status on pubertal staging, ovarian and uterine volumes among school girls. Method: Study was cross sectional and carried out on 1000 healthy school girls, aged 8-18 years selected randomly. They were categorized according to their ages into three groups: 8-12 years, 13-15 years and 16-18 years ±6 months, then according to their body mass index percentile to normal weight: (≥15-<85.), overweight (≥85-<95) and obese (≥95). All girls were subjected for physical, anthropometric (weight, height, body mass index), nutritional markers WAZ (weight/age Z score), HAZ (height/age Z score) and BMI-Z (body mass index Z score), pubertal assessment (Tanner stage) and pelvic transabdominal sonography (uterine and ovarian volumes). Results: Highly significant differences in ovarian and uterine volumes and nutritional markers (WAZ, HAZ and BMI-Z score) were detected among different grades of puberty in the two age groups (8-12 years, 13-15 years) coming in advance of obese girls (with increase of BMI); except HAZ in the second age group. Girls aged 16-18 years reached to final volume for the uterus and ovary with insignificant differences. Pubertal stage, ovarian and uterine sizes were highly significantly correlated with nutritional markers. Mean ages of onset: of puberty, menarche and complete puberty were, 11.65 + 1.84, 14.79 + 1.75 and 15.02 + 1.68 years respectively. Conclusion: Nutritional status has a crucial role in determining pubertal stage, ovarian and uterine volumes among Egyptian girls during the pubertal process.

Keywords: pubertal stage, nutritional markers, girls, ovarian and uterine volumes

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Authors: Arab M., Ait Abdallah M., Zeraoulia N., Boumaza H., Aoutia M., Griene L., Ait Abdelkader B.,

Abstract:

breast and ovarian cancer are respectively the first and fourth leading causes of cancer among women in Algeria. A family story of cancer in the most important risk factor, and in most cases of families with breast and /or ovarian cancer, the pattern of cancer family can be attributed to mutation in BRCA1/2genes. objectibes: the aim of our study in to investigate the spectrum of BRCA1/2 germiline mutation in familial breast and /or ovarian cancer and to determine the prevalence and the nature of BRCA1/2mutation in Algeria methods: we deremined the prevalence of BRCA1/2 mutation within a cohort of 161 probands selected according the eisinger score double stranded sanger sequencing of all coding exons of BRCA1/2including flanking intronic region were performed results: we identified a total of 23 distinct deleterious mutations (class5) 12 differents mutations in BRCA1(52%) and 11 in BRCA2(48%). 78% (18/23) were protein truncating and 22%(5/23) missens mutations.3 novel deleterious mutations have been identified, which have not been described in public mutation database. one new mutation were found in two unrelated patients. the overall mutation detection rate in our study is 28,5%(46/161).more over, an UVS c7783 located in BRCA2 is found in two unrelated probands and segregate in the 02 families/ conclusion: our results sugget of large spectrum of BRCA1/2 mutation in Algerian breast/ovarian cancer family. The nature and prevalence of BRCA1/2mutation in algerian families are ongoing in a larger study, 80 probands are to day under investigation. This study which may therefore identify the genetic particularity of Algerian breast /ovarian cancer.

Keywords: BRCA1/2 mutations, hereditary breast cancer, algerian women, prvalence

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Authors: Hyun-jin Kim, Gumgyung Gu, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min

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Background: Ovarian carcinoma is the fourth most common cause of cancer-related death in women worldwide. HE4, a novel marker for ovarian cancer could be used for monitoring recurrence or progression of disease in patients with invasive epithelial ovarian carcinoma. It is further intended to be used in conjunction with CA 125 to estimate the risk of epithelial ovarian cancer in women presenting with an adnexal mass. In this study, we aim to evaluate the analytical performance and clinical utility of HE4 assay using Architect i 2000SR(Abbott Diagnostics, USA). Methods: The precision was evaluated according to Clinical and Laboratory Standards Institute(CLSI) EP5 guideline. Three levels of control materials were analyzed twice a day in duplicate manner over 20 days. We calculated within run and total coefficient of variation (CV) at each level of control materials. The linearity was evaluated based on CLSI EP6 guideline. Five levels of calibrator were prepared by mixing high and low level of calibrators. For 43 women with adnexal masses, HE4 and CA 125 were measured and Risk of ovarian malignancy (ROMA) scores were calculated. The patients’ medical records were reviewed to determine the clinical utility of HE4 and ROMA score. Results: In a precision study, the within-run and total CV were 2.0 % and 2.3% for low level of control material, 1.9% and 2.4% for medium level and 0.5 % and 1.1% for high level, respectively. The linear range of HE4 was 14.63 to 1475.15pmol/L. Of the 43 patients, two patients in pre-menopausal group showed the ROMA score above the cut-off level (7.3%). One of them showed CA 125 level within the reference range, while the HE4 was higher than the cut-off. Conclusion: The overall analytical performance of HE4 assay using Architect showed high precision and good linearity within clinically important range. HE4 could be an useful marker for managing patients with adnexal masses.

Keywords: HE4, CA125, ROMA, evaluation, performance

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Ghada Esheba, Ebtisam Aljerayan, Afnan Al-Ghamdi, Atheer Alsharif, Hanan alzahrani

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Background: Primary ovarian neoplasms comprise a heterogeneous group of tumors of three main subtypes: surface epithelial, germ cell, and sex cord-stromal. The wide morphological variation within and between these groups can result in diagnostic difficulties. Gonadal sex cord-stromal tumors (SCST) represent one of the most heterogeneous categories of human neoplasms, because they may contain various combinations of different gonadal sex cord and stromal element. Aim: The aim of this work is to highlight the clinicopathological characteristics of SCST and to assess the value of alpha-inhibin and calretinin in the distinction between SCST and their mimics. Material and methods: This study was carried out on 100 cases using full tissue sections; 70 cases were SCST and 30 cases were histological mimics of SCST. The cases were studied using immunohistochemically using alpha-inhibin. In addition, an ovarian tissue microarray containing 170 benign and malignant ovarian neoplasms was also studied immunohistochemically for calretinin expression. The ovarian microarray included 14 SCST, 59 ovarian serous borderline tumors, 17 mucinous borderline tumors, 10 mucinous adenocarcinomas, 32 endometrioid adenocarcinomas, 34 clear cell carcinomas, and 4 germ cell tumors. Results: 99% of SCST examined using full tissue sections exhibited positive cytoplasmic staining for inhibin. On the contrary, only 7% of the histological mimics (P value < 0.0001). 86% of SCST in the tissue microarray were positive for calretinin with nuclear and/or cytoplasmic staining compared to only 7% of the other tumor types (P value < 0.0001). Conclusions: SCST have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment. Alpha-inhibin and calretinin are of great help in the diagnosis of sex cord-stromal tumors.

Keywords: calretinin, granulosa cell tumor, inhibin, sex cord-stromal tumors

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Authors: Lamia Bensissaid

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Goals: Endometriosis affects 6 to 10% of women of childbearing age. 17 to 44% of them have ovarian endometriomas. Medical and surgical treatments represent the two therapeutic axes with which PMA can be associated. Laparoscopic intraperitoneal ovarian cystectomy is described as the reference technique in the management of endometriomas by learned societies (CNGOF, ESHRE, NICE). However, it leads to a significant short-term reduction in the AMH level and the number of antral follicles, especially in cases of bilateral cystectomy, large cyst size or cystectomy after recurrence. Often, the disease is at an advanced stage with several surgical patients. Most have adhesions, which increase the risk of surgical complications and suboptimal resection and, therefore recurrence of the cyst. These results led to a change of opinion towards a conservative approach. Sclerotherapy is an old technique which acts by fibrinoid necrosis. It consists of injecting a sclerosing agent into the cyst cavity. Results : Recurrence was less than 15% for a 12-month follow-up; these rates are comparable to those of surgery. It does not seem to have a negative impact on ovarian reserve, but this is not sufficiently evaluated. It has an advantage in IVF pregnancy rates compared to cystectomy, particularly in cases of recurrent endometriomas. It has the advantages: · To be done on an outpatient basis. · To be inexpensive. · To avoid sometimes difficult and iterative surgery: · To allow an increase in pregnancy rates and the preservation of the ovarian reserve compared to iterative surgery. · of great interest in cases of bilateral endometriomas (kissing ovaries) or recurrent endometriomas. Conclusions: Ethanol sclerotherapy could be a good alternative to surgery.

Keywords: Endometrioma, Sclerotherapy, infertility, Ethanol

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Authors: Salina Yahya Saddik

Abstract:

The present study is designed to demonstrate the Ovarian Surface Epithelial cells (OSE) Estrogen Receptor α (ERα) and Progesterone Receptor (PR) during pregnancy and estrous cycle in rat. Moreover, determination of the levels of plasma progesterone, estradiol, FSH and LH were also made. The levels of plasma progesterone, estradiol, FSH and LH concentrations were determined on days 7 (n=5), 14 (n=5), and 21(n=5) of pregnancy in three groups of rats and during the estrous cycle (n=5) using ELISA kit. Immunohistochemical method for PR and ERα expression was also made on the ovary. During pregnancy, FSH and LH remained low except at term when LH levels began to increase from 16 ng/ml to 47 ng/ml. Progesterone levels significantly exceeded estradiol values in all pregnant rats with a peak value of 202 ng/ml on day 14. Elevated progesterone levels were associated negatively with LH and estradiol levels during pregnancy. The levels of estradiol surged significantly on day 21. Immunohistochemistry of the ovary showed low levels of OSE cells staining positive for ERα expression. ERα positive cells were absent on day 7 and 14 of pregnancy, only day 21 recorded a very low percentage of immunostaining (0.5%) within the nuclei of OSE cells. On the contrary, immunostaining of PR was not observed within the nuclei of OSE cells in all groups of study. In conclusions, these results may suggest that progesterone effect during pregnancy seems to be overriding the positive effect of estrogens on OSE cells. High progesterone levels may have a direct negative effect on gonadotropin production and thereby it might inhibit events leading to both follicular development and OSE proliferation. Understanding the factors affecting OSE proliferation may help elucidating the mechanism(s) of assisted diseases such as ovarian cancer.

Keywords: ovarian surface, pregnancy, gonadotropins, steroids

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Authors: Marcela Capcarova, Adriana Kolesarova, Marina Medvedova, Peter Petruska, Alexander V. Sirotkin

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The aim of this study was to determine the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS) and accumulation of Hsp70 in porcine ovarian granulosa cells after deoxynivalenol (DON) and zearalenone (ZEA) exposure in vitro. Porcine ovarian granulosa cells were incubated with DON/ZEA administrations as follows: group A (10/10 ng/mL), group B (100/100 ng/mL), group C (1000/1000 ng/mL), and the control group without any additions for 24h. In this study mycotoxins developed stress reaction of porcine ovarian granulosa cells and increased accumulation of Hsp70 what resulted in increasing activities of SOD and GPx in groups with lower doses of mycotoxins. High dose of DON and ZEA had opposite effect on GPx activity than the lower doses. Slight increase in TAS of porcine granulosa cells was observed after mycotoxins exposure. These results contribute towards the understanding of cellular stress and its response.

Keywords: deoxynivalenol, zearalenone, antioxidants, Hsp70, granulosa cells

Procedia PDF Downloads 215