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'Cancer' in all fields;
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Displaying Results 101 - 125 of 3656 on page 5 of 147
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Novel Microtubule targetting agents, pyrrolo-1,5,benzoxazepines induce apoptosis in multi-drug-resistant cancer cells
(2010)
LLOYD, DAVID; ZISTERER, DANIELA; WILLIAMS, DAVID; FAYNE, DARREN
Novel Microtubule targetting agents, pyrrolo-1,5,benzoxazepines induce apoptosis in multi-drug-resistant cancer cells
(2010)
LLOYD, DAVID; ZISTERER, DANIELA; WILLIAMS, DAVID; FAYNE, DARREN
Abstract:
PURPOSE: The development of multi-drug resistance (MDR) due to the expression of members of the ATPase binding cassette (ABC) transporter family is a major obstacle in cancer treatment. The broad range of substrate specificities associated with these transporters leads to the efflux of many anti-cancer drugs from tumour cells. Therefore, the development of new chemotherapeutic agents that are not substrates of these transporters is important. We have recently demonstrated that some members of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds are microtubule-depolymerising agents that potently induce apoptosis in several cancer cell lines and impair growth of mouse breast tumours. The aim of this current study was to establish if PBOXs were capable of inducing apoptosis in cancer cells expressing either P-glycoprotein or breast cancer resistance protein (BCRP), two of the main ABC transporters associated with MDR. METHODS: We performed in vitro studies to assess the effect...
http://hdl.handle.net/2262/40658
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The MyD88+ Phenotype Is an Adverse Prognostic Factor in Epithelial Ovarian Cancer.
(2014)
O'TOOLE, SHARON; O'NEILL, LUKE; GLEESON, NOREEN; O'BYRNE, KEN; O'LE...
The MyD88+ Phenotype Is an Adverse Prognostic Factor in Epithelial Ovarian Cancer.
(2014)
O'TOOLE, SHARON; O'NEILL, LUKE; GLEESON, NOREEN; O'BYRNE, KEN; O'LEARY, JOHN; SMYTH, PAUL
Abstract:
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 significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring ...
http://hdl.handle.net/2262/70461
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RanGTPase: A Candidate for Myc-Mediated Cancer Progression
(2013)
O'BYRNE, KEN
RanGTPase: A Candidate for Myc-Mediated Cancer Progression
(2013)
O'BYRNE, KEN
Abstract:
BACKGROUND: Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. METHODS: We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpress...
http://hdl.handle.net/2262/71221
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The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study.
(2013)
HUSSEY, JULIETTE; KENNEDY, MICHAEL
The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study.
(2013)
HUSSEY, JULIETTE; KENNEDY, MICHAEL
Abstract:
Background Breast cancer prognosis can be adversely influenced by obesity, physical inactivity and metabolic dysfunction. Interventions aimed at improving surrogate markers of breast cancer risk such as insulin resistance may result in improved breast cancer outcomes. The design of such interventions may be improved through increased understanding of metabolic presentation in this cohort. This cross-sectional study aimed to characterise the metabolic profile of breast cancer survivors relative to abdominal obesity and insulin resistance. A secondary aim was to compare measures of energy output across these groups. Methods Sixty-nine women (mean (SD) age 53.43 (9.39) years) who had completed adjuvant chemotherapy and radiotherapy for breast cancer were recruited. All measures were completed during one assessment conducted 3.1 (1.0) years post diagnosis. Body composition was measured by bioimpedance analysis and waist circumference (WC). Fasting (12 hour) blood samples were drawn to...
http://hdl.handle.net/2262/72477
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A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer
(2013)
BENNETT, KATHLEEN
A cohort study of metformin exposure and survival in patients with stage I-III colorectal cancer
(2013)
BENNETT, KATHLEEN
Abstract:
Background: Preclinical evidence suggests a beneficial effect of metformin in colorectal cancer. This study aimed to investigate associations between metformin exposure and colorectal cancer?specific survival using population-level data. Methods: Adult patients with stage I?III colorectal cancer diagnosed from 2001 to 2006 were identified from the National Cancer Registry Ireland. Use of metformin and other antidiabetic medications was determined from a linked national prescription claims database. Multivariate Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between prediagnostic metformin exposure (versus nonmetformin antidiabetic drugs) and colorectal cancer?specific mortality. Models were stratified by antidiabetic drug coprescription and intensity of metformin exposure. Results: The cohort included 207 diabetics who received metformin, 108 diabetics not exposed to metformin, and 3,501 nondiabetic patients. In multivari...
http://hdl.handle.net/2262/72468
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Lipid Rafts as Master Regulators of Breast Cancer Cell Function
(2011)
Babina, Irina S; Donatello, Simona; Nabi, Ivan R; Hopkins, Ann M
Lipid Rafts as Master Regulators of Breast Cancer Cell Function
(2011)
Babina, Irina S; Donatello, Simona; Nabi, Ivan R; Hopkins, Ann M
Abstract:
<p> <p>In: "Breast Cancer - Carcinogenesis, Cell Growth and Signalling Pathways". Editors: M. Gunduz, E. Gunduz. InTech, ISBN 978-953-307-714-7</p> </p> <p>This book chapter is also available at <a href="http://www.intechweb.org/books/show/title/breast-cancer-carcinogenesis-cell-growth-and-signalling-pathways">http://www.intechweb.org/books/show/title/breast-cancer-carcinogenesis-cell-growth-and-signalling-pathways</a></p>
<p> <p>Cancer is a leading cause of death in developed countries, and is on the rise in developing countries due in part to a lack of prophylactic screening and non-universal access to medical care (Jemal et al., 2011). Breast cancer is initiated when breast epithelial cells escape growth arrest and form a proliferating tumour mass. Numerous cellular mechanisms are dysregulated in breast tumour cells, including modified cell fate, altered protein signalling and trafficking, and enh...
https://epubs.rcsi.ie/surgart/10
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Investigating novel mechanisms of metastasis in endocrine resistant breast cancer.
(2014)
Bolger, Jarlath
Investigating novel mechanisms of metastasis in endocrine resistant breast cancer.
(2014)
Bolger, Jarlath
Abstract:
<p>Breast cancer is the commonest solid tumour in European females. Treatment of breast cancer using anti-oestrogenic agents provides a template for the development of targeted therapies, both in breast cancer and other neoplastic diseases. Tamoxifen remains the treatment of choice for pre-menopausal breast cancer patients who express an oestrogen receptor, while a newer class of drug, aromatase inhibitors, are the first-line treatment for post-menopausal patients. In spite of these advances, up to 25% of breast cancer patients will eventually develop a recurrent tumour and metastatic disease.</p> <p>The mechanism by which cancers can overcome this endocrine therapy is poorly understood. Cancer stem cell theory would suggest that there are sub-populations of cells within tumours that are highly tumourigenic and give rise to subsequent, resistant disease. However, this does not fully explain why some tumours may be initially steroid responsive, but can slowly adapt ...
https://epubs.rcsi.ie/phdtheses/133
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SPINK1 protein expression and prostate cancer progression.
(2014)
Finn, Stephen; Flavin, Richard
SPINK1 protein expression and prostate cancer progression.
(2014)
Finn, Stephen; Flavin, Richard
Abstract:
PURPOSE: SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer-specific survival. EXPERIMENTAL DESIGN: The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983-2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays. RESULTS: Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P < 0.01). SPINK1 overexpression was seen in 47 o...
http://hdl.handle.net/2262/75504
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Symptoms and problem clusters in cancer and non cancer patients in specialized palliative care - is there a difference?
(2014)
WALSH, THOMAS
Symptoms and problem clusters in cancer and non cancer patients in specialized palliative care - is there a difference?
(2014)
WALSH, THOMAS
Abstract:
CONTEXT: In clinical practice, some symptoms and problems frequently occur in combination, which may have consequences for symptom management. OBJECTIVES: Facing a growing number of non-cancer patients in palliative care, this study aimed to differentiate symptom clusters in the non-cancer population from those in cancer patients. METHODS: Inpatient data from the German Hospice and Palliative Care Evaluation between 2007 and 2011 were used for a cluster analysis of a 16-item symptom and problem checklist. An agglomerative hierarchical method was chosen. Coefficients from distance matrix ranging between 0 and 1 were calculated to indicate the interrelationship of clustered symptoms. RESULTS: The analysis identified five clusters in cancer patients: 1) nausea and vomiting (d = 0.000); 2) anxiety, tension, and feeling depressed (d = 0.125); 3) wound care and disorientation/confusion (d = 0.229); 4) organization of care and overburdening of family (d = 0.202); and 5) weakness, tired...
http://hdl.handle.net/2262/76569
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JNK regulates Fas receptor mediated apoptosis in prostate cancer cell lines
(2003)
Curtin, James
JNK regulates Fas receptor mediated apoptosis in prostate cancer cell lines
(2003)
Curtin, James
Abstract:
Prostate Cancer is a disease that primarily affects elderly men. The incidence of prostate cancer has been progressively increasing in the western world over the last two decades. Life expectancy and diet are believed to be the main factors contributing to this increase in prevalence. Prostate cancer is a slowly progressing disorder and patients often live for over 10 years after initially being diagnosed with prostate cancer. However, patients with hormone refractory prostate cancer have a poor prognosis and generally do not survive for longer than 2 or 3 years. Hormone refractory prostate cancer is responsible for over 200,000 deaths each year and current chemotherapeutic regimens are only useful as palliative agents. The long-term survival rate is poor and chemotherapy does not significantly increase this. Cell lines derived from hormone refractory tumours usually display elevated resistance to many cytotoxic drugs. The Fas receptor is a membrane bound protein capable of binding ...
http://hdl.handle.net/10468/2431
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MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells
(2016)
Nyhan, Michelle J.; O'Donovan, Tracey R.; Boersma, Antonius W. M.; Wiemer, Erik A....
MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells
(2016)
Nyhan, Michelle J.; O'Donovan, Tracey R.; Boersma, Antonius W. M.; Wiemer, Erik A. C.; McKenna, Sharon L.
Abstract:
Background: Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal. Methods: MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells. Results: MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines wit...
http://hdl.handle.net/10468/3686
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Oral cancer incidence and survival rates in the Republic of Ireland, 1994-2009.
(2016)
Ali, Hala; Sinnott, Sarah-Jo; Corcoran, Paul; Deady, Sandra; Sharp, Linda; Kabir, Zubair
Oral cancer incidence and survival rates in the Republic of Ireland, 1994-2009.
(2016)
Ali, Hala; Sinnott, Sarah-Jo; Corcoran, Paul; Deady, Sandra; Sharp, Linda; Kabir, Zubair
Abstract:
Oral cancer is a significant public health problem world-wide and exerts high economic, social, psychological, and physical burdens on patients, their families, and on their primary care providers. We set out to describe the changing trends in incidence and survival rates of oral cancer in Ireland between 1994 and 2009. Methods: National data on incident oral cancers [ICD 10 codes C01-C06] were obtained from the National Cancer Registry Ireland from 1994 to 2009. We estimated annual percentage change (APC) in oral cancer incidence during 1994–2009 using joinpoint regression software (version 4.2.0.2). The lifetime risk of oral cancer to age 79 was estimated using Irish incidence and population data from 2007 to 2009. Survival rates were also examined using Kaplan-Meier curves and Cox proportional hazard models to explore the influence of several demographic/lifestyle covariates with follow-up to end 2012.
Oral cancer is a significant public health problem world-wide and exerts h...
http://hdl.handle.net/10147/621147
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Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo
(2016)
Pidgeon, Graham; Lysaght, Joanne; O'Byrne, Ken; Gately, Kathy
Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo
(2016)
Pidgeon, Graham; Lysaght, Joanne; O'Byrne, Ken; Gately, Kathy
Abstract:
Background Baicalein is a widely used Chinese herbal medicine derived from Scutellaria baicalenesis, which has been traditionally used as anti-inflammatory and anti-cancer therapy. In this study we examined the anti-tumour pathways activated following baicalein treatment in non-small cell lung cancer (NSCLC), both in-vitro and in-vivo. Methods The effect of baicalein treatment on H-460 cells in-vitro was assessed using both BrdU assay (cell proliferation) and High Content Screening (multi-parameter apoptosis assay). A xenograft nude mouse model was subsequently established using these cells and the effect of baicalein on tumour growth and survival assessed in-vivo. Tumours were harvested from these mice and histological tissue analysis carried out. VEGF, 12-lipoxygenase and microvessel density (CD-31) were assessed by immunohistochemistry (IHC), while H and E staining was carried out to assess mitotic index. Gene expression profiling was carried out on corresponding RNA samples us...
http://hdl.handle.net/2262/80227
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Men's information-seeking behavior regarding cancer risk and screening: A meta-narrative systematic review
(2017)
Saab, Mohamad M.; Reidy, Mary; Hegarty, Josephine; O'Mahony, Máirín; Murphy, Mike;...
Men's information-seeking behavior regarding cancer risk and screening: A meta-narrative systematic review
(2017)
Saab, Mohamad M.; Reidy, Mary; Hegarty, Josephine; O'Mahony, Máirín; Murphy, Mike; Von Wagner, Christian; Drummond, Frances J.
Abstract:
Objective: Preventive strategies are known to reduce cancer risk and incidence and improve prognosis. Men seldom seek medical information about cancer prevention and risk reduction. The aim of this meta-narrative systematic review was to critically appraise evidence from qualitative, quantitative, and mixed-methods studies that explored men's information-seeking behaviors in relation to cancer prevention and risk reduction. Methods: MEDLINE, CINAHL Plus with Full Text, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, Education Full Text, and ERIC were systematically searched for studies published in English between January 1, 2006 and May 30, 2016. A total of 4117 titles were identified; of which, 31 studies were included (21 qualitative studies, 9 quantitative studies, and 1 mixed-methods study). The methodological quality of the studies was appraised by using different tools. Results: Most studies focused on screening for prostate (n = 18) and colorectal...
http://hdl.handle.net/10468/4837
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Investigation into mechanisms of metastasis in breast cancer and pancreatic cancer
(2017)
Moore, Gemma
Investigation into mechanisms of metastasis in breast cancer and pancreatic cancer
(2017)
Moore, Gemma
Abstract:
The aim of this project was to investigate mechanisms of metastasis in triple negative breast cancer (TNBC) and pancreatic cancer. Metastasis is the ability of a cell to spread to another location colonising a secondary site, which contributes to approximately 90% of cancers fatalities. Both TNBC and pancreatic cancer possess poor prognosis, limited therapeutic options and the risk of each becoming metastatic remains a major risk. This body of work aimed to investigate unique influences on the metastatic capabilities of both TNBC and pancreatic cancer cells. Three critical metastatic phenotypes were investigated, specifically anoikis resistance (anchorage independence), colony formation, proliferation and invasion. Metastasis was investigated through three approaches: i) microarray profiling was used to investigate genes that were differentially expressed in anoikis resistant conditions, ii) an indirect co-culture model that mimicked the tumour microenvironment was used to assess cr...
http://doras.dcu.ie/21876/
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Exploring breast cancer and screening awareness among Irish women with intellectual disabilities
(2018)
Reidy, Mary; Denieffe, Suzanne; Foran, Sinéad
Exploring breast cancer and screening awareness among Irish women with intellectual disabilities
(2018)
Reidy, Mary; Denieffe, Suzanne; Foran, Sinéad
Abstract:
Accessible Summary: We asked women with intellectual disabilities what they knew about breast cancer and screening programmes. We asked women what would put them off going to see a doctor whether they found something wrong with their breast. Most of those we asked knew that a lump was a warning sign for breast cancer. Most of those we asked did not know about the risk factors for breast cancer. Many women did not know much about the breast screening programme. Many women said they would be worried about what the doctor might find. Improving breast cancer and screening awareness is important for women with intellectual disabilities. Women with intellectual disabilities need to be taught more about breast cancer and screening. Abstract: Background: Internationally, it is known that there are gaps in cancer and screening awareness among women with intellectual disabilities. Little is known about this awareness among Irish women with intellectual disabilities. The aim of this study was ...
http://hdl.handle.net/10468/6175
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Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic
(2018)
Arooj, Parniya; Bredin, Emily; Henry, Michael T.; Khan, Kashif A.; Plant, Barry J.; Mur...
Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic
(2018)
Arooj, Parniya; Bredin, Emily; Henry, Michael T.; Khan, Kashif A.; Plant, Barry J.; Murphy, Desmond M.; Kennedy, Marcus P.
Abstract:
Background: In the investigation of lung cancer, current practice in many healthcare systems would support bronchoscopy regardless of CT findings in patients with hemoptysis. We sought to identify the cause, the diagnostic yield of CT and bronchoscopy and the requirement for bronchoscopy in at risk patients with hemoptysis with a normal CT scan through our rapid access lung cancer clinic (RALC). Methods: Initially, a chart review was performed on all patients with hemoptysis (2011–2012) and thereafter a prospective analysis was performed (2013–2016). Results: Our analysis represents the largest study to date in outpatients with hemoptysis. In our retrospective study, 155 patients reported hemoptysis. Causes were lower respiratory tract infections (RTIs) (47%) and lung cancer (16%). Our prospective study included 182 patients. The causes of hemoptysis were RTIs (50%) and lung cancer (18%). There were no false negative CT-scans for lung cancer. 47/57 present with lung cancer underwent...
http://hdl.handle.net/10468/6180
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BCL2 and BCL(X)L selective inhibitors decrease mitochondrial ATP production in breast cancer cells and are synthetically lethal when combined with 2-deoxy-D-glucose.
(2018)
Lucantoni, Federico; Düssmann, Heiko; Llorente-Folch, Irene; Prehn, Jochen HM
BCL2 and BCL(X)L selective inhibitors decrease mitochondrial ATP production in breast cancer cells and are synthetically lethal when combined with 2-deoxy-D-glucose.
(2018)
Lucantoni, Federico; Düssmann, Heiko; Llorente-Folch, Irene; Prehn, Jochen HM
Abstract:
<p>The original article is available at <a href="http://www.oncotarget.com">www.oncotarget.com</a></p>
<p>Cancer cells display differences regarding their engagement of glycolytic vs. mitochondrial oxidative phosphorylation (OXPHOS) pathway. Triple negative breast cancer, an aggressive form of breast cancer, is characterized by elevated glycolysis, while estrogen receptor positive breast cancer cells rely predominantly on OXPHOS. BCL2 proteins control the process of mitochondrial outer membrane permeabilization during apoptosis, but also regulate cellular bioenergetics. Because BCL2 proteins are overexpressed in breast cancer and targetable by selective antagonists, we here analysed the effect of BCL2 and BCL(X)L selective inhibitors, Venetoclax and WEHI-539, on mitochondrial bioenergetics and cell death. Employing single cell imaging using a FRET-based mitochondrial ATP sensor, we found that MCF7 breast cancer cells supplied with mitochon...
https://epubs.rcsi.ie/physiolart/147
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The use of nanotechnology for treatment of multidrug resistant ovarian cancer cells
(2019)
SAED, MELAD ELHADI
The use of nanotechnology for treatment of multidrug resistant ovarian cancer cells
(2019)
SAED, MELAD ELHADI
Abstract:
The traditional ovarian cancer treatment includes a combination of surgery and chemotherapy. However, the prognosis for ovarian cancer following treatment is very poor in the majority of ovarian cancer patients, especially patients with stage III or IV disease on diagnosis. Many patients respond well initially to chemotherapy but go on to develop the recurrent chemoresistant disease. To improve the efficacy of chemotherapy, nanotechnology has been used in the targeting and treatment of ovarian cancer and it has been employed in cancer treatment to overcome some of the limitations seen with traditional therapy. In addition to their non-toxicity, low cost and commercial availability, nanodiamonds have many other advantages that can be utilized in drug delivery. They can be functionalized with different types of anticancer therapeutic and they can be suspended easily in water, which is important for biomedical applications. In this thesis, we have developed a novel nanocarrier usi...
http://hdl.handle.net/2262/86330
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1,4-dihydroxy quininib attenuates growth of colorectal cancer cells and xenografts and regulates the TIE-2 signaling pathway in patient tumours
(2019)
O'Sullivan, Jacintha
1,4-dihydroxy quininib attenuates growth of colorectal cancer cells and xenografts and regulates the TIE-2 signaling pathway in patient tumours
(2019)
O'Sullivan, Jacintha
Abstract:
Colorectal cancer (CRC) is the second leading cause of cancer associated deaths in developed countries. Cancer progression and metastatic spread is reliant on new blood vasculature, or angiogenesis. Tumour-related angiogenesis is regulated by pro- and anti-angiogenic factors secreted from malignant tissue in a stepwise process. Previously we structurally modified the small anti-angiogenic molecule quininib and discovered a more potent anti-angiogenic compound 1, 4 dihydroxy quininib (Q8), an antagonist of cysteinyl leukotriene receptor-1 with VEGF-independent bioactivity. Here, Q8, quininib (Q1) and five structural analogues were assayed for anti-tumorigenic effects in pre-clinical cancer models. Q8 reduced clone formation of the human colorectal cancer cell line HT29-Luc2. Gene silencing of CysLT1 in HT29-Luc2 cells significantly reduced expression of calpain-2. In human ex vivo colorectal cancer tumour explants, Q8 significantly decreased the secretion of both TIE-2 and VCAM-1 exp...
http://hdl.handle.net/2262/89326
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2-Deoxy-D-Glucose inhibits aggressive triple-negative breast cancer cells by targeting glycolysis and the cancer stem cell phenotype
(2019)
O'Driscoll, Lorraine; Porter, Richard
2-Deoxy-D-Glucose inhibits aggressive triple-negative breast cancer cells by targeting glycolysis and the cancer stem cell phenotype
(2019)
O'Driscoll, Lorraine; Porter, Richard
Abstract:
Due to limited availability of pharmacological therapies, triple-negative breast cancer (TNBC) is the subtype with worst outcome. We hypothesised that 2-Deoxy-D-Glucose (2-DG), a glucose analogue, may hold potential as a therapy for particularly aggressive TNBC. We investigated 2-DG?s effects on TNBC cell line variants, Hs578T parental cells and their isogenic more aggressive Hs578Ts(i)8 variant, using migration, invasion and anoikis assays. We assessed their bioenergetics by Seahorse. We evaluated metabolic alterations using a Seahorse XF Analyzer, citrate synthase assay, immunoblotting and flow cytometry. We assessed the cancer stem cell (CSC) phenotype of the variants and 2-DG?s effects on CSCs. 2-DG significantly inhibited migration and invasion of Hs578Ts(i)8 versus Hs578T and significantly decreased their ability to resist anoikis. Investigating 2-DG?s preferential inhibitory effect on the more aggressive cells, we found Hs578Ts(i)8 also had significantly decreased oxidative p...
http://hdl.handle.net/2262/89378
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An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer
(2015)
O'Donnell, Charlotte; Mahmoud, Amr; Keane, Jonathan; Murphy, Carola T.; White, Dec...
An antitumorigenic role for the IL-33 receptor, ST2L, in colon cancer
(2015)
O'Donnell, Charlotte; Mahmoud, Amr; Keane, Jonathan; Murphy, Carola T.; White, Declan; Carey, Sinead; O'Riordain, Micheal G.; Bennett, Michael W.; Brint, Elizabeth K.; Houston, Aileen M.
Abstract:
Background: Despite the importance of inflammation in cancer, the role of the cytokine IL-33, and its receptor ST2, in colon cancer is unclear. The aim of this study was to investigate the role of IL-33, and its receptor isoforms (ST2 and ST2L), in colon cancer. Methods: Serum levels of IL-33 and sST2 were determined with ELISA. ST2 and IL-33 expression was detected with quantitative real-time PCR (qRT–PCR), western blotting and immunohistochemistry. ST2 expression in CT26 cells was stably suppressed using ST2-specific shRNA. Cytokine and chemokine gene expression was detected with qRT–PCR. Results: Human colon tumours showed lower expression of ST2L as compared with adjacent non-tumour tissue (P<0.01). Moreover, the higher the tumour grade, the lower the expression of ST2L (P=0.026). Colon cancer cells expressed ST2 and IL-33 in vitro. Functional analyses showed that stimulation of tumour cells with IL-33 induced the expression of chemokine (C–C motif) ligand 2 (CCL2). Knockdown...
http://hdl.handle.net/10468/8457
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Characterisation of circulating tumour cells in men with advanced prostate cancer and correlation with numbers of circulating and tissue-based inflammatory cells
(2019)
HAYES, BRIAN DERMOT
Characterisation of circulating tumour cells in men with advanced prostate cancer and correlation with numbers of circulating and tissue-based inflammatory cells
(2019)
HAYES, BRIAN DERMOT
Abstract:
Many men with prostate cancer present with advanced stage disease, and in these men treatment is directed towards improved survival and quality-of-life rather than cure. Exercise therapies are recognised to have benefits in quality-of-life, all-cause and cancer-specific mortality in cancer patients, and prostate cancer is no exception. Obesity and metabolic syndrome are encountered with increasing frequency in prostate cancer patients, either as pre-existing comorbidities or as a side-effect of androgen deprivation therapy. The systemic inflammatory milieu which underpins the obese state has profoundly negative effects on cancer survivorship, but new data show that control of obesity, including through managed exercise interventions, can improve outcomes. Circulating tumour cells (CTCs) derived from the primary tumour are considered an intermediate step in the metastatic cascade and therefore a potentially useful target for therapy. Interventions (including exercise) targeted at im...
http://hdl.handle.net/2262/89485
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Waist circumference and risk of liver cancer: a systematic review and meta-analysis of over 2 million cohort study participants
(2019)
Rahmani, J.; Kord Varkaneh, H.; Kontogiannis, V.; Ryan, Paul M.; Bawadi, H.; Fatahi, S....
Waist circumference and risk of liver cancer: a systematic review and meta-analysis of over 2 million cohort study participants
(2019)
Rahmani, J.; Kord Varkaneh, H.; Kontogiannis, V.; Ryan, Paul M.; Bawadi, H.; Fatahi, S.; Zhang, Y.
Abstract:
Purpose: Liver cancer is the sixth most common type of cancer worldwide, and waist circumference (WC) is associated with its risk beyond body mass index (BMI). This dose-response meta-analysis was performed to investigate the association between WC and the risk of incident liver cancer using prospective cohort studies. Methods: A comprehensive systematic search was conducted in MEDLINE/PubMed, Web of Science databases, Scopus, and Cochrane from inception to May 2019. Studies with retrospective or prospective cohort design that reported hazard ratio (HR), risk ratio, or odds ratio, and the corresponding 95% confidence intervals (CI) for liver cancer based on WC categories were included in this meta-analysis. Combined HRs with 95% CIs was estimated by DerSimonian and Laird random-effects models. Results: Associations between WC and liver cancer were reported in 5 articles with 2,547,188 participants. All studies were published between 2013 and 2019. Pooled results showed a strong sig...
http://hdl.handle.net/10468/8870
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?Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival?.
(2016)
Phelan, James
?Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival?.
(2016)
Phelan, James
Abstract:
Despite extensive efforts, cancer therapies directed at the Protein Kinase C (PKC) family of serine/threonine kinases have failed in clinical trials. These therapies have been directed at inhibiting PKC and have, in some cases, worsened disease outcome. Here we examine colon cancer patients and show not only that PKC Beta II is a tumour suppressor, but patients with low levels of this isozyme have significantly decreased disease free survival. Specifically, analysis of gene expression levels of all PKC genes in matched normal and cancer tissue samples from colon cancer patients revealed a striking down-regulation of the gene coding PKC Beta in the cancer tissue (n = 21). Tissue microarray analysis revealed a dramatic down-regulation of PKC Beta II protein levels in both the epithelial and stromal diseased tissue (n = 166). Of clinical significance, low levels of the protein in the normal tissue of patients is associated with a low (10%) 10 year survival compared with a much higher (...
http://hdl.handle.net/2262/90707
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