Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1707

Search results for: ovarian cancer

1707 Role of Human Epididymis Protein 4 as a Biomarker in the Diagnosis of Ovarian Cancer

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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1706 Endometriosis-Associated Ovarian Cancer: Clinical and Pathological Pattern

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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1705 Expression of Hypoxia-Inducible Transmembrane Carbonic Anhydrases IX, Ca XII and Glut 1 in Ovarian Cancer

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

Abstract:

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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1704 Effects of New Anthraquinone Derivatives on Resistance Ovarian Cancer Cells and The Mechanism Investigation

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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1703 Evaluation of Brca1/2 Mutational Status among Algerian Familial Breast Cancer

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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1702 Utility of CK7, CK20 and CDX-2 as a Potential Panel in Differentiating Primary Ovarian Surface Epithelial Tumors from Metastatic Adenocarcinoma to the Ovary

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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1701 Exercise Intervention For Women After Treatment For Ovarian Cancer

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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1700 Automated 3D Segmentation System for Detecting Tumor and Its Heterogeneity in Patients with High Grade Ovarian Epithelial Cancer

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

Abstract:

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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1699 Exercise Intervention for Women After Treatment for Ovarian Cancer: Realist Evaluation of a Co-Designed Implementation Process

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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1698 A Prenylflavanoid, HME5 with Antiproliferative Activity in Human Ovarian Cancer Cells

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

Abstract:

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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1697 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers

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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1696 Update on Epithelial Ovarian Cancer (EOC), Types, Origin, Molecular Pathogenesis, and Biomarkers

Authors: Salina Yahya Saddick

Abstract:

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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1695 Construction of Ovarian Cancer-on-Chip Model by 3D Bioprinting and Microfluidic Techniques

Authors: Zakaria Baka, Halima Alem

Abstract:

Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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1694 The Role of Estradiol-17β and Type IV Collagen on the Regulation and Expression Level Of C-Erbb2 RNA and Protein in SKOV-3 Ovarian Cancer Cell Line

Authors: Merry Meryam Martgrita, Marselina Irasonia Tan

Abstract:

One of several aggresive cancer is cancer that overexpress c-erbB2 receptor along with the expression of estrogen receptor. Components of extracellular matrix play an important role to increase cancer cells proliferation, migration and invasion. Both components can affect cancer development by regulating the signal transduction pathways in cancer cells. In recent research, SKOV-3 ovarian cancer cell line, that overexpress c-erbB2 receptor was cultured on type IV collagen and treated with estradiol-17β, to reveal the role of both components on RNA and protein level of c-erbB2 receptor. In this research we found a modulation phenomena of increasing and decreasing of c-erbB2 RNA level and a stabilisation phenomena of c-erbB2 protein expression due to estradiol-17β and type IV collagen. It seemed that estradiol-17β has an important role to increase c-erbB2 transcription and the stability of c-erbB2 protein expression. Type IV collagen has an opposite role. It blocked c-erbB2 transcription when it bound to integrin receptor in SKOV-3 cells.

Keywords: c-erbB2, estradiol-17β, SKOV-3, type IV collagen

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1693 Blood Thicker Than Water: A Case Report on Familial Ovarian Cancer

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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1692 Performance Evaluation of the HE4 as a Serum Tumor Marker for Ovarian Carcinoma

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

Abstract:

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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1691 Concanavaline a Conjugated Bacterial Polyester Based PHBHHx Nanoparticles Loaded with Curcumin for the Ovarian Cancer Therapy

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

Abstract:

In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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1690 Induction of Cytotoxicity and Apoptosis in Ovarian Cancer Cell Line (CAOV-3) by an Isoquinoline Alkaloid Isolated from Enicosanthellum pulchrum (King) Heusden

Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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1689 Targeted Photodynamic Therapy for Intraperitoneal Ovarian Cancer, A Way to Stimulate Anti-Tumoral Immune Response

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

Abstract:

Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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1688 Therapeutic Potential of mAb KP52 in Human and Feline Cancers

Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

Abstract:

Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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1687 Studies on Induction of Cytotoxicity Through Apoptosis In Ovarian Cancer Cell Line (CAOV-3) by Chloroform Extract of Artocarpus Kemando Miq

Authors: Noor Shafifiyaz Mohd Yazid, Najihah Mohd Hashim, Hapipah Mohd Ali, Syam Mohan, Rosea Go

Abstract:

Artocarpus kemando is a plant species from Moraceae family. This plant is used as household utensil by the local and the fruits are edible. The plants’ bark was used for the extraction process and yielded the chloroform crude extract which was used to screen for anticancer potential. The cytotoxic effect of the extract on CAOV-3 and WRL 68 cell lines were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assays. Qualitative AO/PI assay was performed to confirm the apoptosis and necrosis process. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. In MTT assay, A. kemando inhibited 50% growth of CAOV-3 cells at 27.9 ± 0:03, 20.1± 0:03, 18.21± 0:04 µg/mL after 24, 48 and 72 hour, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with extract resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated A. kemando has potentially anticancer agent, particularly on human ovarian cancer.

Keywords: anticancer, Artocarpus kemando, ovarian cancer, cytotoxicity

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1686 Cytotoxic Activity of Extracts from Hibiscus sabdariffa Leaves against Women’s Cancer Cell Lines

Authors: Patsorn Worawattananutai, Srisopa Ruangnoo, Arunporn Itharat

Abstract:

Hibiscus sabdariffa (HS) leaves are vegetables which are extensively used as blood tonic and laxatives in Thai traditional medicine. They are popularly used as healthy sour soup for prevention of chronic diseases such as cancer. Therefore, the cytotoxic activity of different extracts of fresh and dried Hibiscus sabdariffa leaves were investigated via the sulforhodamine B (SRB) assay against three types of women’s cancer cell lines, namely the human cervical adenocarcinoma cell line (HeLa), the human ovarian adenocarcinoma cell line (SKOV-3), and the human breast adenocarcinoma cell line (MCF-7). Extraction methods were squeezing, boiling with water and maceration with 95% or 50% ethanol. The 95% ethanolic extracts of Hibiscus sabdariffa dry leaves (HSDE95) showed the highest cytotoxicity against all types of women’s cancer cell lines with the IC50 values in range 7.51±0.33 to 12.13±1.85 µg/ml. Its IC50 values against SKOV-3, HeLa and MCF-7 were 7.51±0.33, 9.44±1.41 and 12.13±1.85 µg/ml, respectively. In these results, this extract can be classified as “active” according to the NCI guideline which indicated that IC50 values of the active cytotoxic plant extracts have to be beneath 20 µg/ml. Thus, HSDE95 was concluded to be a potent cytotoxic drug for all women’s cancer cells. This extract should be further investigated to isolate active compounds against women’s cancer cells.

Keywords: breast adenocarcinoma, cervical adenocarcinoma, cytotoxic activity, Hibiscus sabdariffa, ovarian adenocarcinoma

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1685 Electrochemical Biosensor Based on Chitosan-Gold Nanoparticles, Carbon Nanotubes for Detection of Ovarian Cancer Biomarker

Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi

Abstract:

Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.

Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles

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1684 Effects of Some Characteristics of Gynecological Cancer Diagnosis and Treatment on Women's Sexual Life Quality

Authors: Buse Bahitli, Samiye Mete

Abstract:

The aim of the study was to evaluate the quality of sexual life of women with diagnosed gynecological cancer and receive treatment. The study was a descriptive and cross-sectional type, and it was carried out with 276 women. Information Form and Sexual Quality of Life Scale-Female (SQOL) form was used in the study. The data was evaluated using Mann-Whitney U and Kruskal-Wallis test. In the study, Sexual Quality of Life Scale-Female average score was 68.83 ± 21.17. The %43.1 of women was endometrial cancer, %30.8 was cervical cancer, %24.6 was ovarian cancer, and %1.4 was vulvar cancer. The average time to diagnosis of patients is 41.80 ± 47.64 months. There was no significant difference mean SQOL according to individual/sociodemographic characteristics like age, education. Gynecological cancer-related characteristics like gynaecological cancer type, treatment type, surgery type were found not to affect the mean score of SQOL. However, it was found that the difference was due to the higher SQOL score in the group with a diagnosis time of 25 months and over (X²KW= 6.356, p= 0.046). The reason of significant difference means SQOL according to diagnosis over time might be that women adapted to cancer diagnosis. While women with gynaecologic cancer are evaluating their sexual lives, it is necessary to evaluate them with good evaluation tools.

Keywords: gynecological cancers, sexuality, quality of sexual life, SQOL

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1683 Contribution of PALB2 and BLM Mutations to Familial Breast Cancer Risk in BRCA1/2 Negative South African Breast Cancer Patients Detected Using High-Resolution Melting Analysis

Authors: N. C. van der Merwe, J. Oosthuizen, M. F. Makhetha, J. Adams, B. K. Dajee, S-R. Schneider

Abstract:

Women representing high-risk breast cancer families, who tested negative for pathogenic mutations in BRCA1 and BRCA2, are four times more likely to develop breast cancer compared to women in the general population. Sequencing of genes involved in genomic stability and DNA repair led to the identification of novel contributors to familial breast cancer risk. These include BLM and PALB2. Bloom's syndrome is a rare homozygous autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia and is associated with breast cancer when in a heterozygous state. PALB2, on the other hand, binds to BRCA2 and together, they partake actively in DNA damage repair. Archived DNA samples of 66 BRCA1/2 negative high-risk breast cancer patients were retrospectively selected based on the presence of an extensive family history of the disease ( > 3 affecteds per family). All coding regions and splice-site boundaries of both genes were screened using High-Resolution Melting Analysis. Samples exhibiting variation were bi-directionally automated Sanger sequenced. The clinical significance of each variant was assessed using various in silico and splice site prediction algorithms. Comprehensive screening identified a total of 11 BLM and 26 PALB2 variants. The variants detected ranged from global to rare and included three novel mutations. Three BLM and two PALB2 likely pathogenic mutations were identified that could account for the disease in these extensive breast cancer families in the absence of BRCA mutations (BLM c.11T > A, p.V4D; BLM c.2603C > T, p.P868L; BLM c.3961G > A, p.V1321I; PALB2 c.421C > T, p.Gln141Ter; PALB2 c.508A > T, p.Arg170Ter). Conclusion: The study confirmed the contribution of pathogenic mutations in BLM and PALB2 to the familial breast cancer burden in South Africa. It explained the presence of the disease in 7.5% of the BRCA1/2 negative families with an extensive family history of breast cancer. Segregation analysis will be performed to confirm the clinical impact of these mutations for each of these families. These results justify the inclusion of both these genes in a comprehensive breast and ovarian next generation sequencing cancer panel and should be screened simultaneously with BRCA1 and BRCA2 as it might explain a significant percentage of familial breast and ovarian cancer in South Africa.

Keywords: Bloom Syndrome, familial breast cancer, PALB2, South Africa

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1682 Effect of Unilateral Unoperated Ovarian Endometrioma on Responsiveness to Hyperstimulation

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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1681 Rejuvenation of Premature Ovarian Failure with Stem Cells/IVA Technique

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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1680 Ovarian Surface Epithelium Receptors during Pregnancy and Estrus Cycle of Rats with Emphasis on Steroids and Gonadotropins Fluctuation

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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1679 Risk Factors and Biomarkers for the Recurrence of Ovarian Endometrioma: About the Immunoreactivity of Progesterone Receptor Isoform B and Nuclear Factor Kappa B.

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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1678 Palliative Performance Scale Differences between Patients Referred by Specialized Cancer Center and General Hospitals to the Palliative Care Center in Kuwait

Authors: Khalid Al Saleh, Najlaa AlSayed

Abstract:

Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

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