John J O'Leary's research while affiliated with Trinity College Dublin and other places
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Publications (351)
Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with...
Background
Information concerning the health-related quality-of-life (HRQoL) consequences of colposcopy is limited, particularly over time. In a longitudinal study, we investigated women’s HRQoL at 4, 8 and 12 months post colposcopy and the factors associated with this.Methods
Women attending colposcopy at two large hospitals affiliated with the na...
Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid bio...
Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines IL‐1β, IL‐1ra and IL‐18 are activated by the NOD‐, LRR‐ and NLRP3 inflammasome, furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved...
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...
Introduction:
Ovarian cancer patients are at high risk of thrombosis particularly during chemotherapy treatment however the mechanism is not understood. The aim of this study is to investigate the role of the activated protein C (aPC) pathway in the procoagulant activity observed in ovarian cancer patients undergoing neoadjuvant chemotherapy.
Pat...
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...
Background
Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer.
Methods
Participants (n = 61)...
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...
Objectives
To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy.
Methods
Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissec...
Background
Human papillomavirus (HPV) is considered the strongest epidemiologic risk factor for cervical cancer. However, it is not a sufficient cause given the high prevalence of transient infections. We examined the relationship between exposure to tobacco smoke, measured using urinary nicotine metabolite concentrations, and p16/Ki-67 co-expressi...
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: Circulating tumour cells (CTCs) are silent precursors of metastatic disease that utilise various mechanisms to survive in circulation and metastasise to distal sites. Classical CTC detection relies on EpCam affinity-based technologies; however, CTCs are highly heterogeneous and often undergo EMT. Recent research highlights the ability o...
Prostate cancer accounts for approximately 13.5% of all newly diagnosed male cancer cases. Significant clinical burdens remain in terms of ineffective prognostication, with overtreatment of insignificant disease. Additionally, the pathobiology underlying disease heterogeneity remains poorly understood. As the role of cancer stem cells in the perpet...
PurposeThe association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller–Payn...
[This corrects the article DOI: 10.1371/journal.pone.0054193.].
Background
Despite an epidemic increase in the prevalence of Human Papilloma Virus (HPV) related Oropharyngeal Squamous Cell Carcinomas (OPSCCs) in Northern America and parts of Europe, there is virtually no information about the natural history of these cancers. The lack of well–defined precursor lesions and limited data on oral HPV persistence an...
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...
Objective
The incidence of human papillomavirus-associated head and neck cancers (HPV-HNC) is increasing worldwide. Research in other clinical contexts has shown that healthcare professionals (HCPs) can find discussing HPV with patients challenging. However, limited research has been conducted in HNC. This study aimed to investigate barriers and fa...
Introduction
Prevalence rates of human papillomavirus positive (HPV+) head and neck cancers (HNC) have increased over the last decades. Communicating about HPV is an increasingly relevant part of HNC patient care. This systematic review was conducted to explore healthcare professionals’ (HCP) views and experiences of discussing HPV with HNC patient...
Significance:
Up until recently, metabolism has scarcely been referenced in terms of immunology. However, emerging evidence has shown that immune cells undergo an adaptation of metabolic processes, known as the metabolic switch. This switch is key to the activation, and sustained inflammatory phenotype in immune cells, which includes the productio...
Significance:
Reactive oxygen species (ROS) are often considered to be undesirable toxic molecules that are generated under conditions of cellular stress, which can cause damage to critical macromolecules such as DNA. However, ROS can also contribute to the pathogenesis of cancer and many other chronic inflammatory disease conditions, including ath...
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...
Introduction/Background
Endometrial cancer (EC) is the most common gynaecological malignancy. The mainstay of treatment is surgical resection. Currently, there are no sensitive and specific biomarkers for EC. Human Epididymis protein 4 (HE4) shows promise as a diagnostic and prognostic marker. We investigated the sensitivity of preoperative serum H...
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:
Rising incidence of HPV-positive head and neck cancers (HPV-HNC) means HPV infection is increasingly relevant to patient-provider consultations. We performed a systematic review to examine, in the context of patient-provider HNC consultations: discussions about HPV, attitudes towards discussing HPV and information needs.
Methods:
We s...
Aims:
Reactive oxygen species (ROS) are highly reactive molecules generated in different subcellular sites or compartments, including endosomes via the NOX2-containing nicotinamide adenine dinucleotide phosphate oxidase during an immune response and in mitochondria during cellular respiration. However, while endosomal NOX2 oxidase promotes innate i...
The role of soluble MICA and MICB in NKG2D expression and NK cell functions.
(A) Expression of NKG2D on NK cells post-treatment with recombinant MICA or MICB for 24 hours. (B and C) NK cells were also functionally analysed for CD107a expression and IFNy production. Results are expressed as a percentage of control in the presence of IgG control for...
Neutralising the NKG2D-NKG2DL axis inhibits NK cell functions.
(A) Quantifying the capacity of monoclonal antibodies to neutralise NKG2D receptor on NK cells and MICA and MICB ligands on tumour cell lines. PBMCs and tumour cell lines were incubated for 1 hour at room temperature in the presence or absence of 1μg/mL of respective mAb and subsequentl...
Tumour cell immune evasion is a principal hallmark of successful metastasis. Tumour cells in the vasculature adopt a platelet cloak that efficiently suppresses the innate immune system by directly inhibiting Natural Killer (NK) cells, which normally function to neutralise spreading cancers. Here we describe two novel mechanisms of tumour cell evasi...
Quantifying expression and function of CD112 and CD155 ligands on tumour cell lines.
(A) Quantifying CD112 and CD155 ligands on tumour cell lines using fluorescent mAb and flow cytometry (B) Monoclonal antibodies against CD155 or CD112 were used to block NK cell targeting of tumour cell lines. NK cells were co-incubated with tumour cells in the pre...
Representative gating strategy.
(A) Gating of tumour cell populations from free platelets. FSC/SCC plots of SKOV3 cells, platelets and cloaked SKOV3 cells demonstrates two distinct populations. (B) Tumour cell gate (P11) stained with CD42b APC antibody. Isotype control, SKOV3, platelet and cloaked SKOV3 samples demonstrate the low free platelet con...
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...
Background
To the authors’ knowledge, published studies reporting on the performance of the FocalPoint GS (FPGS) imaging system have yielded conflicting results to date. However, the results of the MAVARIC study indicated that the FPGS “No Further Review” (NFR) aspect of the technology demonstrated potential and warranted further investigation. The...
Abstract Toll-like receptor 7 (TLR7) is a pattern recognition receptor that recognizes viral RNA following endocytosis of the virus and initiates a powerful immune response characterized by Type I IFN production and pro-inflammatory cytokine production. Despite this immune response, the virus causes very significant pathology, which may be inflamma...
Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long te...
Responses to individual HPV infection and vaccination knowledge statements for all practitioners, according to whether they provided correct answers, provided wrong answers, indicated that they were unsure or did not respond1.
(DOCX)
Background
Primary care practitioners (PCP) play key roles in cervical cancer prevention. Human papillomavirus (HPV) knowledge is an important influence on PCPs’ cervical cancer prevention-related behaviours. We investigated HPV knowledge, and associated factors, among general practitioners (GPs) and practice nurses.
Methods
A survey, including fa...
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...
The use of two-photon 3D printing to create templates for fabricating reproducible and tunable metallic nanostructures is described. The approach allows the structure of the template to be designed specifically for particular applications, e.g., fluid flow control, surface enhanced Raman spectroscopy, metal enhanced fluorescence etc. Here, we show...
Reactive oxygen species (ROS) promote growth factor signalling including for VEGF-A and have potent angiogenic and tumourigenic properties. However, the precise enzymatic source of ROS generation, the subcellular localization of ROS production and cellular targets in vivo that influence tumour-promoting processes, are largely undefined. Here, using...
Abstract This study aims to detect high grade squamous intraepithelial cells (HSIL) by investigating HSIL associated biochemical changes in morphologically normal appearing intermediate and superficial cells using Raman spectroscopy. Raman spectra (n = 755) were measured from intermediate and superficial cells from negative cytology ThinPrep specim...
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...
Equation S1. Model equation to estimate the probability of indolent, significant and aggressive disease for each patient.
Fig. S1. Heatmaps for indolent, significant and aggressive disease type.
Fig. S2. Alternate layout of Fig. 1 information.
Table S1. Summary statistics for full Clinical Cohort.
Table S2. Cross tabulation of the known indolen...
Background: Globally, prostate cancer (PrCa) is the fourth most common cancer type. Obesity and inflammation have been shown to play significant roles in PrCa disease progression. Obesity and a high body mass index (BMI) are associated with increased PrCa-specific mortality in patients with advanced disease. Furthermore, proinflammatory cytokines c...
Some cervical cancer screening programmes are replacing cytology with human papillomavirus (HPV) DNA testing as the primary screening test. Concerns have been previously raised around the potential psychosocial impact of testing positive for HPV. We analysed socio-economic variations in anticipated adverse reactions to testing positive for HPV in w...
Introduction:
Classifying indolent prostate cancer represents a significant clinical challenge. We investigated whether integrating data from different omic platforms could identify a biomarker panel with improved performance compared to individual platforms alone.
Methods:
DNA methylation, transcripts, protein, and glycosylation biomarkers were...
There is an unmet need for methods to help in the early detection of cervical precancer. Optical spectroscopy-based techniques, such as Raman spectroscopy, have shown great potential for diagnosis of different cancers, including cervical cancer. However, relatively few studies have been carried out on liquid-based cytology (LBC) pap test specimens...
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...
Raman spectroscopy is a powerful tool that has the potential to be used as a screening method for cervical cancer. It is a label free, low cost method providing a biochemical fingerprint of a given sample. The objective of this study was to address patient to patient variability contributed by hormonal effects due to the menstrual cycle, the use of...
The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irrespective of the infecting strain. Reactive oxygen species are ancient processes that protect plants, fungi and animals against invading pathogens including bacteria. However, in mammals reactive oxygen species production p...
Purpose:
Cost-effectiveness analyses (CEAs) of screening can be highly sensitive to the health-related quality of life (HRQoL) effects of screen tests and subsequent treatment. Accordingly, accurate assessment of HRQoL is essential. We reviewed the literature regarding HRQoL in cervical prevention and management in order to appraise the current ev...
It is widely accepted that cervical screening has significantly reduced the incidence of cervical cancer worldwide. The primary screening test for cervical cancer is the Papanicolaou (Pap) test, which has extremely variable specificity and sensitivity. There is an unmet clinical need for methods to aid clinicians in the early detection of cervical...
Background
Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical...
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...
Non-small cell lung cancer (NSCLC) accounts for a large proportion of
cancer deaths and is characterized by low treatment response rates and poor overall prognosis. In the absence of specific treatable mutations, cisplatin-based chemotherapy plays an important role in the treatment of this disease. Unfortunately, the development of resistance has b...
Objective:
To estimate prevalence of post-colposcopy physical after-effects and investigate associations between these and subsequent psychological distress.
Design:
Longitudinal survey.
Setting:
Two hospital-based colposcopy clinics.
Population:
Women with abnormal cytology who underwent colposcopy (±related procedures).
Methods:
Question...
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...
It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of t...
Background:
HPV-related oropharyngeal SCC represents a distinct subgroup of head and neck tumours. We analyse the expression of cytokeratin 7, a junctional biomarker with a SEQIKA fragment which stabilises HPV-16 E7 transcripts, in oropharyngeal SCCs.
Methods:
Archived tumour specimens and epidemiological data were collected from patients with o...
Prostate cancer is the second most common cancer in men worldwide. Gleason grading is an important predictor of prostate cancer outcomes and is influential in determining patient treatment options. Clinical decisions based on a Gleason score of 7 are difficult as the prognosis for individuals diagnosed with Gleason 4+3 cancer is much worse than for...
Resistance to neoadjuvant chemoradiation therapy (CRT) remains a critical barrier to the effective treatment of esophageal adenocarcinoma (EAC). Cancer stem-like cells (CSCs) are a distinct subpopulation of cells implicated in the resistance of tumors to anti-cancer therapy. However, their role in the resistance of EAC to CRT is largely unknown. In...
Reactive oxygen species (ROS) promote influenza pathogenicity by an unknown mechanism. Our aims were to determine 1) the site and enzymatic source of subcellular ROS generation and 2) the impact of ROS on the pathogenesis of virus infection. To do this, confocal microscopy was used to assess the subcellular distribution of viruses, toll-like recept...
In the era of primary vaccination against HPV and at the beginning of the low prevalence of cervical lesions, introduction of screening methods that can distinguish between low- and high-grade lesions is necessary in order to maintain the positive predictive value of screening. This case-control study included 562 women who attended cervical screen...
Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer-related deaths each year. Our group and others have previously demonstrated dysfunctional microRNA (miRNA or miR) expression in the context of thyroid cancer. The objective of the present study was to investigate the impact of synthetic manipula...
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...
Laser capture microdissection (LCM) allows microscopic procurement of specific cell types from tissue sections. Here, we present an optimized workflow for coupling LCM to LC–MS/MS including: sectioning of tissue, a standard LCM workflow, protein digestion and advanced LC–MS/MS. Soluble proteins extracted from benign epithelial cells, their associat...
Oncogenic mutations in BRAF are common in melanoma and thyroid carcinoma and drive constitutive activation of the MAPK pathway. Molecularly targeted therapies of this pathway improves survival compared to chemotherapy; however, responses tend to be short-lived as resistance invariably occurs. Cell line models of melanoma and thyroid carcinoma, +/-...
"Cancer stem cells" (CSCs) asymmetrically divide to drive tumorigenesis, a property that is lost upon differentiation. It is likely that elimination of CSC populations would dramatically enhance current cancer therapies. The switch between self-renewal and differentiation is controlled by several stemness signaling pathways, which have become the m...
Supporting Information
Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting pre-invasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providing uncertain evidence to support prophylactic vaccin...
Citations
... Indeed, FVIIa itself has been found to have a role in tumour pathogenesis, with overexpression increasing the migratory and invasive potential of breast cancer cells through PAR2 activation and the upregulation of βcatenin [90]. Members of the activated protein C pathway, a key anticoagulant pathway, are expressed in gynaecological tumours and also play a role in cancer pathogenesis [91]. These non-coagulation functions of the coagulation cascade postulates a role for these proteins in CTC mediated survival and metastatic potential in the circulation. ...
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... Recent studies of Smarcd1 focused on modulating H3K27me3 redistribution on the chromatin to regulate pluripotency-associated factor KLF4 in embryonic stem cells [9]. Smarcd1 has been reported downregulated in several human malignant tumors [10,11]. Hong and his colleagues demonstrated that the expression of Smarcd1 sensitized lung cancer cells to chemotherapy drug-induced apoptosis via the inhibition of miR-7 [10]. ...
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... In addition to these subunits, small GTPase Rac1 or Rac2 may be associated with NAPDH oxidase [18]. The contribution of NOX2 in respiratory viruses-induced ROS production has been confirmed [19][20][21][22][23]. NOX2 is a phagocytic enzyme, which is expressed in monocytes, neutrophils macrophages, as well as on air way epithelial cells [24]. ...
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... Whilst ROSs are small enough to diffuse through the cell, their localisation to specific compartments activate receptors and initiate specific redox signalling responses [142]. Endosomal compartments are vital sources of NADPH oxidase (NOX)-generated ROS species that are vital to initiating autophagic responses to oxidative stress [143,144]; endosome-localised NOX2 enzymes catalyse NADPH reduction that induces mitochondrial and nuclear DNA damage and apoptosis [138,145]. ROS-generating endosomes (also known as redoxosomes) can augment signalling of endocytosed receptors that can induce mitochondrial dysfunction-induced apoptosis and from lipids such as C2-ceramide [146,147]. NOX-generated ROSs have critical roles in oxidative inhibition of protein tyrosine phosphatases (PTPs) that are vital to insulin response. ...
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... For instance, tumor suppressor genes such as BRCA1, RASSF1A [45] or MLH1 [41,46]; cell adhesion genes as ICAM-1 [47] and CDH1 [48] and DNA repair genes PALB2 [49] are affected by DNA methylation. BRCA1 promoter methylation is reported in 10-15% of sporadic OvCa [7,[50][51][52][53]. It appears that a reversal of this phenotype can take place over time leading to changed methylation level in relapsed disease [54]. ...
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... As seen in studies with PTC and FTC, miR-222 is deregulated in ATC. While miR-222 is upregulated in ATC, miR-25 is found to be downregulated in ATC cell lines compared with benign thyroid cells [92]. ...
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... Indeed, it has been recently demonstrated in Rag knockout mice that H1N1 Influenza-A virus infection inhibits protein degradation at autophagosome-lysosome system level and precipitates α-syn accumulation [11]. Further experimental evidence showed that Influenza-A virus disrupts mitochondrial activity and increase oxidative stress [12,13], whereas hepatitis C virus impairs dopaminergic transmission and affects the blood-brain barrier (BBB) integrity [10]. Therefore, viral infections may intervene in cellular pathways critical for PD pathogenesis, probably contributing to the initiation of the disease [8,9,[14][15][16][17]. ...
... First-line chemotherapy with carboplatin and paclitaxel achieves an improved CR; however, recurrence occurs in 25% of patients with early stage disease and more than 80% of patients with advanced disease. 97 A majority of advanced ovarian cancer patients experience disease relapse within 2 years of the initial treatment of combination chemotherapy. 98 The heterogeneity of tumour cells leads to molecular variations in signalling pathways including oncogene activation, tumour suppressor inactivation and various pro-survival genetic mutations. ...
... biopsies of any areas of the cervical transformation zone that appear abnormal, or treatment to remove abnormal cervical cells) are associated with distress and anxiety in women before and during the procedure(s) [3]. Concerns around cancer, sex and fertility can also persist after coloposcopy and related interventions [4][5][6][7][8]. While is considerably less evidence on validated health-related quality-of-life (HRQoL) measures, particularly those that are typically used to impute quality-adjusted life years (QALYS) in health economic evaluations, such as the widely used EuroQol EQ-5D instrument [9]. ...
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... Previous studies have investigated HPV communication needs and gaps between HCPs and vaccine-eligible adolescent or HPV-related cancer patients [19][20][21][22][23][24][25]. Head and neck cancer (HNC) patients requires appropriate communication about HPV and high-quality information from healthcare providers [26]. ...
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