Sharon Ann O’Toole

Trinity College Dublin | TCD · Department of Obstetrics and Gynaecology

Background Considering the shared aetiology of Human Papillomavirus infections in oropharyngeal and cervical cancers and the possible role for sexual transmission, several key aspects of the relationship between cervical and oral infections merit investigation, including prevalence of concomitant oral HPV infection and type‐specific concordance wit...

Introduction: Cancer antigen 125 (CA125), the biomarker in common clinical use for ovarian cancer, is limited by low sensitivity for early disease and high false positives. The aim of this study was to evaluate several candidate biomarkers, alone or in combination, compared to CA125 in the prediction of malignant/borderline vs benign tumor status...

Despite the use of front-line anticancer drugs such as paclitaxel for ovarian cancer treatment, mortality rates have remained almost unchanged for the past three decades and the majority of patients will develop recurrent chemoresistant disease which remains largely untreatable. Overcoming chemoresistance or preventing its onset in the first instan...

Histone deacetylase 6 (HDAC6) is a unique histone deacetylating enzyme that resides in the cell cytoplasm and is linked to the modulation of several key cancer related responses, including cell proliferation and migration. The promising anti-cancer response of the first-generation HDAC6 catalytic inhibitors continues to be assessed in clinical tria...

Introduction/Background Circulating tumour cells (CTCs) play a crucial role in cancer dissemination and cellular extravasation leading to metastasis. There are only a limited number of CTCs per clinically/ethically allowed cancer patient`s blood draw and expanding this population of cells in vitro is crucial in order to provide a reliable number of...

Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infect...

Objective: The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods: We obtained 111 OC specimens from 2 univ...

Background: BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal/ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of ind...

ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours. In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in viv...

MAD2 is an intriguing protein, which has been associated with poor survival in cancer. Depending on the organ-specific cancer, either high expression or low expression levels have been correlated with low survival rates in patients. MAD2 is also a marker of contradiction. The normal function of MAD2 is to accumulate at kinetochores and generate a w...

Background: Detection and enumeration of Circulating Tumour Cells (CTCs) has been evaluated in many cancers such as breast cancer. However, the full prognostic and predictive power of CTCs for cancer cannot currently be harnessed, and the association between pathological complete response in patients receiving neoadjuvant chemotherapy for breast ca...

Objective Gynaecological cancer patients have a high risk of developing venous thromboembolism (VTE). There is limited information on patient experience and compliance with an extended low molecular weight heparin prophylaxis in this setting. The aim of this study was to assess patient compliance, satisfaction and experience with the extended low m...

The aim is to evaluate specific methylation markers for the triage of a HPV positive result in a HPV primary screening population. Host methylation factors have been shown to be hypermethylated in cervical cancer/pre-cancer and have the potential to triage women at high risk of cervical cancer. This study aims to investigate methylation of CADM1-M1...

EUROGIN 2018 poster. It has been well established that HPV screening for cervical cancer shows a greater sensitivity for the detection of CIN 2+ lesions in comparison to current cytological methods. While a negative HPV test is more reassuring than a negative cytology test for cervical cancer, a HPV positive result has a lower specificity for CIN 2...

Background: The aim of this study was to evaluate the clinical performance of the Cobas 4800 HPV test and the Aptima HPV assay for the detection of CIN2+ disease in women referred to colposcopy with minor cytological abnormalities. Methods: ThinPrep liquid-based cytology samples were collected from 562 women referred to colposcopy with minor cyt...

Background The aim of this study is to evaluate triage options for the management of women with a HPV positive primary screening test. Host methylation factors have repeatedly shown to be hypermethylated in cervical cancer/pre-cancer and have the potential to triage women at high risk of cervical cancer. This is part of a larger study within CERVIV...

Cervical screening has been a highly successful health promotion initiative. The way cervical screening is delivered is about to change dramatically, with the introduction of 'tests of risk' and 'tests of disease' based on primary HPV testing and the use of cell host response biomarkers. This article addresses the fundamental basis of this change i...

It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistan...

We have previously reported that myeloid differentiation primary response gene 88 (MyD88) is downregulated during all-trans retinoic acid (RA)-induced differentiation of pluripotent NTera2 human embryonal carcinoma cells (hECCs), whereas its maintained expression is associated with RA differentiation resistance in nullipotent 2102Ep hECCs. MyD88 is...

Objectives: The Aptima HPV assay (Hologic) which detects HPV mRNA has demonstrated high sensitivity for detection of CIN2+ and higher specificity than HPV DNA testing. This study compares two different HPV testing platforms kits; the Cobas HPV test (Roche) which detects DNA from 14 HR- HPV types including genotyping for HPV16 and 18 and the Aptima...

The aim of this study is to evaluate triage options to manage HPV positive women from a primary HPV cervical screening programme. Host methylation factors have repeatedly shown to be hypermethylated in cervical cancer and pre-cancer and have the potential to triage women at high risk of progression or who have CIN2+ precancerous lesions. In partner...

Introduction Gynaecological cancer is associated with some of the highest rates of venous thromboembolism (VTE) with some subtypes of ovarian cancer associated with rates as high as 20%. VTE prophylaxis is an important part of post-operative management in gynaecological cancer patient care. Despite the evidence base and guidelines recommending exte...

Introduction The close relationship between coagulation, thrombosis and cancer has long been established. Gynaecological cancers, in particular ovarian cancers, carry a high risk of thrombosis but coagulation activation is also thought to play a role in tumorigenesis and metastasis. In experimental animal models of metastasis, mice with a genetic p...

Introduction Increased thrombin production is associated with malignancy and is a marker for venous thromboembolism (VTE). Our group has shown that thrombin generation is increased in gynaecological malignancies. Although tumour derived Tissue Factor (TF) has been implicated, the precise mechanism by which thrombin production is increased is not fu...

Objective To investigate human papillomavirus (HPV) DNA testing and p16/Ki-67 staining for detecting cervical intraepithelial grade 2 or worse (CIN2+) and CIN3 in women referred to colposcopy with minor abnormal cervical cytology low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of undermined significance (ASC-US). The c...

Background: Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through...

Background: The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. Downregulation of MAD2, a key component of the spindle assembly checkpoint complex,...

Background: The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. Downregulation of MAD2, a key component of the spindle assembly checkpoint complex,...

Annually, ovarian cancer (OC) affects 240,000 women worldwide and is the most lethal gynaecological malignancy. Such mortality is predominantly associated with the development of an intrinsic and acquired resistance to chemotherapy, the lack of targeted therapies and the lack of biomarkers predicting therapeutic response. Our clinical data demonstr...

Cervical cancer is the third most common cancer affecting women worldwide. It is characterized by chromosomal aberrations and alteration in the expression levels of many cell cycle regulatory proteins, driven primarily by transforming human papillomavirus (HPV) infection. MYBL2 is a member of the MYB proto-oncogene family that encodes DNA binding p...

Many protocols used for measuring the growth of adherent monolayer cells in vitro are invasive, destructive and do not allow for the continued, undisturbed growth of cells within flasks. Protocols often use indirect methods for measuring proliferation. Microscopy techniques can analyse cell proliferation in a non-invasive or non-destructive manner...

Ovarian cancer is the seventh most common cancer in women and the most frequent cause of gynaecological malignancy-related mortality in women. Currently, no standardized reliable screening test exists. MicroRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumours. The...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Disseminated malignancy is responsible for the majority of cancer-related deaths and circulating tumour cells (CTCs) play a central role in metastasis. We and others have described the phenomenon of platelet cloaking of CTCs, where there is a potent dynamic interaction between c...

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically sign...

Ovarian cancer incidences and mortality rates in Ireland are among the highest worldwide. Biomarkers, including human epididymis protein 4 (HE4) and risk of malignancy (ROMA) index, may have utility in preoperative ovarian mass diagnosis. More accurate differentiation between benign and malignant masses would prevent fertility impairing surgery in...

The clinical performance of the cobas human papillomavirus (HPV) test for detection of high-grade disease in a colposcopy-referred population was compared with that of Hybrid Capture 2 (HC2). The overall agreement between the tests was 92.3%. Clinical sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 2 or greater...

Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2...

Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellul...

Autoantibodies represent an attractive biomarker for diagnostic assays principally due to the stability of immunoglobulin in patient serum facilitating measurement with conventional assays. Immune responses to tumorigenesis may facilitate detection of ovarian cancer in the early stages of the disease with identification of a panel of tumour specifi...

Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene mic...

Platelet adhesion to HIO-80 cells is minimal. Fluorescence microscopy image demonstrating that platelet adhesion to HIO-80 cells is minimal. HIO-80 cells and platelets were stained for actin [green], platelets were stained specifically for CD42a [red]. (TIF)

Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cel...

Epithelial ovarian carcinoma (EOC) is characterised by late diagnosis and recurrences, both of which contribute to the high morbidity and mortality of this cancer. Unfortunately, EOC has an innate susceptibility to become chemo-resistant. Specifically, up to 30% of patients may not respond to current standard chemotherapy (paclitaxel and platinum i...