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'Cancer' in all fields;
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Displaying Results 226 - 250 of 3656 on page 10 of 147
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Stromal TRIM28-associated signaling pathway modulation within the colorectal cancer microenvironment
(2019)
Fitzgerald, Seán; Espina, Virginia; Liotta, Lance; Sheehan, Katherine M.; O’Grady, Anth...
Stromal TRIM28-associated signaling pathway modulation within the colorectal cancer microenvironment
(2019)
Fitzgerald, Seán; Espina, Virginia; Liotta, Lance; Sheehan, Katherine M.; O’Grady, Anthony; Cummins, Robert; O’Kennedy, Richard; Kay, Elaine W.; Kijanka, Gregor S.
Abstract:
Background Stromal gene expression patterns predict patient outcomes in colorectal cancer. TRIM28 is a transcriptional co-repressor that regulates an abundance of genes through the KRAB domain family of transcription factors. We have previously shown that stromal expression of TRIM28 is a marker of disease relapse and poor survival in colorectal cancer. Here, we perform differential epithelium-stroma proteomic network analyses to characterize signaling pathways associated with TRIM28 within the tumor microenvironment. Methods Reverse phase protein arrays were generated from laser capture micro-dissected carcinoma and stromal cells from fresh frozen colorectal cancer tissues. Phosphorylation and total protein levels were measured for 30 cancer-related signaling pathway endpoints. Strength and direction of associations between signaling endpoints were identified using Spearman’s rank-order correlation analysis and compared to TRIM28 levels. Expression status of TRIM28 in tumor epithe...
http://hdl.handle.net/10379/15614
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The relationship between the BMI-adjusted weight loss grading system and quality of life in patients with incurable cancer
(2019)
Daly, Louise; Dolan, Ross; Power, Derek; Ní Bhuachalla, Éadaoin; Sim, Wei; Fallon, Mari...
The relationship between the BMI-adjusted weight loss grading system and quality of life in patients with incurable cancer
(2019)
Daly, Louise; Dolan, Ross; Power, Derek; Ní Bhuachalla, Éadaoin; Sim, Wei; Fallon, Marie; Cushen, Samantha; Simmons, Claribel; McMillan, Donald C.; Laird, Barry J.; Ryan, Aoife
Abstract:
Background: Weight loss (WL) has long been recognized as an important factor associated with reduced quality of life (QoL) and reduced survival in patients with cancer. The body mass index (BMI)‐adjusted weight loss grading system (WLGS) has been shown to be associated with reduced survival. However, its impact on QoL has not been established. The aim of this study was to assess the relationship between this WLGS and QoL in patients with advanced cancer. Methods: A biobank analysis was undertaken of adult patients with advanced cancer. Data collected included patient demographics, Eastern Cooperative Oncology Group performance status, and anthropometric parameters (BMI and %WL). Patients were categorized according to the BMI‐adjusted WLGS into one of five distinct WL grades (grades 0–4). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐C30. The Kruskal–Wallis test and multivariate logistic regression analyses were u...
http://hdl.handle.net/10468/9333
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The clinicomolecular landscape of de novo versus relapsed stage IV metastatic breast cancer
(2020)
Seltzer, Sean; Corrigan, Mark; O'Reilly, Seamus
The clinicomolecular landscape of de novo versus relapsed stage IV metastatic breast cancer
(2020)
Seltzer, Sean; Corrigan, Mark; O'Reilly, Seamus
Abstract:
Background: de novo metastatic breast cancer (dnMBC) is responsible for 6–10% of breast cancer presentations with increasing incidence and has remained resistant to detection by mammography screening. Recent publications hypothesized that in addition to poor screening uptake, the presentation of dnMBC may be due to its unfavourable biology which remains unknown at the molecular level. Here we investigated the tumour biology of dnMBC in the form of clinicopathology, genomic alterations and differential gene expression to create a comparative landscape of de novo versus relapsed metastatic breast cancer (rMBC). Additionally, to address the current screening limitations, we conducted a preliminary biomarker investigation for early dnMBC detection. Methods: In this retrospective case-control study, gene expression and clinical data were accessed from the Cancer Genome Atlas (TCGA) for primary tumours of treatment-naïve patients with dnMBC (n = 17), rMBC (n = 49), and normal tissue (n = ...
http://hdl.handle.net/10468/9698
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Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells.
(2016)
Budanov, Andrei; Tsilioni, Irene; Flippidis, Aristotelis S.; Kerenidi, Theodora; Zarogi...
Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells.
(2016)
Budanov, Andrei; Tsilioni, Irene; Flippidis, Aristotelis S.; Kerenidi, Theodora; Zarogiannis, Sotirios G.; Gourgoulianis, Konstantinos I.
Abstract:
Objectives: Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. Design and methods: We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzymelinked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. Results: Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p=0.0001). The mean value (mean ? SEM) of Sesn2 in patients with MPEs was 0.54 ? 0...
http://hdl.handle.net/2262/91648
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Worry in Head and Neck Cancer Caregivers The Role of Survivor Factors, Care-Related Stressors, and Loneliness in Predicting Fear of Recurrence
(2017)
Maguire, Rebecca; Hanly, Paul; Balfe, Myles; Timmons, Aileen; Hyland, Philip; O’Sulliva...
Worry in Head and Neck Cancer Caregivers The Role of Survivor Factors, Care-Related Stressors, and Loneliness in Predicting Fear of Recurrence
(2017)
Maguire, Rebecca; Hanly, Paul; Balfe, Myles; Timmons, Aileen; Hyland, Philip; O’Sullivan, Eleanor; Butow, Phyllis; Sharp, Linda
Abstract:
Background Fear of recurrence (FOR) is a primary concern for both cancer survivors and their caregivers, yet little is known about what care-related factors exacerbate this worry. Objectives This study aimed to establish the role of care-related stressors—as distinct from survivor characteristics—in predicting FOR in head and neck cancer caregivers. Methods HNC survivor–caregiver dyads took part in a mailed survey. Survivors provided information on health and quality of life (using the Functional Assessment of Cancer Therapy Questionnaire). Caregivers provided sociodemographic information, impact of caring on their time and finances, as well as their level of social support (Oslo Support Scale), loneliness (3-point loneliness scale), and completed the Worry of Cancer Scale (to measure FOR). Results Data from 180 dyads were available for analysis. Multiple regression analysis was used to examine the role of caregiver stressors, social support, and loneliness while controlling for ...
http://mural.maynoothuniversity.ie/11580/
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Barriers to active self‐management following treatment for head and neck cancer: Survivors' perspectives
(2018)
Dunne, Simon; Coffey, Laura; Sharp, Linda; Timmons, Aileen Mary; Desmond, Deirdre; Goob...
Barriers to active self‐management following treatment for head and neck cancer: Survivors' perspectives
(2018)
Dunne, Simon; Coffey, Laura; Sharp, Linda; Timmons, Aileen Mary; Desmond, Deirdre; Gooberman-Hill, Rachael; O'Sullivan, Eleanor; Keogh, Ivan; Timon, Conrad; Gallagher, Pamela
Abstract:
Objective: Active self‐management practices may help head and neck cancer (HNC) survivors to deal with challenges to their physical, functional, social, and psychological well‐being presented by HNC and its treatment. This study investigates the factors perceived by HNC survivors to act as barriers to their active self‐management following primary treatment. Methods: In this qualitative study, 27 HNC survivors identified through 4 designated cancer centres in Ireland participated in face‐to‐face semistructured interviews. Interviews were audio‐recorded, transcribed, and analysed using thematic analysis. Results: Four themes (and associated subthemes) describing barriers to survivors' active self‐management were identified: emotional barriers (eg, fear of recurrence), symptom‐related barriers (eg, loss of taste), structural barriers (eg, access to appropriate health services), and self‐evaluative barriers (eg, interpersonal self‐evaluative concerns). Conclusions: This is the...
http://mural.maynoothuniversity.ie/12134/
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Activating Technology for Connected Health in Cancer: Protocol for a Research and Training Program
(2018)
Mountford, Nicola; Zubiete, Enrique Dorronzoro; Kessie, Threase; Garcia-Zapirain, Begon...
Activating Technology for Connected Health in Cancer: Protocol for a Research and Training Program
(2018)
Mountford, Nicola; Zubiete, Enrique Dorronzoro; Kessie, Threase; Garcia-Zapirain, Begonya; Nuño-Solinís, Roberto; Coyle, David; Munksgaard, Kristin B.; Fernandez-Luque, Luis; Romero, Octavio Rivera; Fernandez, Matilde Mora; Jimenez, Pedro Valero; Daly, Ailish; Whelan, Ruth; Caulfield, Brian
Abstract:
As cancer survival rates increase, the challenge of ensuring that cancer survivors reclaim their quality of life (QoL) becomes more important. This paper outlines the research element of a research and training program that is designed to do just that. Objective: Bridging sectors, disciplines, and geographies, it brings together eight PhD projects and students from across Europe to identify the underlying barriers, test different technology-enabled rehabilitative approaches, propose a model to optimize the patient pathways, and examine the business models that might underpin a sustainable approach to cancer survivor reintegration using technology. Methods: The program, funded under the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 722012, includes deep disciplinary PhD projects, intersectoral and international secondments, interdisciplinary plenary training schools, and virtual subject-specific education module...
http://mural.maynoothuniversity.ie/11286/
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Cancer survivors’ perspectives on adjustment-focused self-management interventions: A qualitative meta-synthesis
(2016)
Coffey, Laura; Mooney, Orla; Dunne, Simon; Sharp, Linda; Timmons, Aileen Mary; Desmond,...
Cancer survivors’ perspectives on adjustment-focused self-management interventions: A qualitative meta-synthesis
(2016)
Coffey, Laura; Mooney, Orla; Dunne, Simon; Sharp, Linda; Timmons, Aileen Mary; Desmond, Deirdre; O'Sullivan, Eleanor; Timon, Conrad; Gooberman-Hill, Rachael; Gallagher, Pamela
Abstract:
Purpose: Self-management interventions improve patient outcomes across a range of long-term conditions but are often limited by low uptake and completion rates. The aim of this paper was to conduct a meta-synthesis of qualitative studies exploring cancer survivors’ views and experiences of engaging with adjustment-focused self-management interventions in order to inform the development of future interventions targeting this population. Methods: Four electronic databases were systematically searched. Studies that used qualitative methods to explore cancer survivors’ views and experiences of engaging with adjustment-focused self-management interventions were included. A meta-ethnographic approach was used to synthesize the findings. Results: Thirteen studies met the inclusion criteria. Engaging with adjustment-focused self-management interventions enabled cancer survivors to gain emotional and informational support from peers and/or facilitators in an open, non-judgemental environm...
http://mural.maynoothuniversity.ie/10592/
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Molecular Evaluation of Enzalutamide Resistance in Prostate Cancer
(2020)
AIRD, JOHN
Molecular Evaluation of Enzalutamide Resistance in Prostate Cancer
(2020)
AIRD, JOHN
Abstract:
Prostate cancer is a leading cause of cancer related death in men. As prostate cancer cells are dependent on androgen receptor (AR) signalling for continued growth, anti-androgen therapy is initially effective in treating most patients with locally advanced or metastatic PCa. However, resistance to anti-androgen therapies inevitably develops in all patients leading to castration resistant prostate cancer (CRPC), which is currently incurable. In most cases of drug resistance, AR signalling is maintained despite castration levels of androgens. The molecular underpinnings for how this occurs and how it can be overcome have yet to be fully elucidated. Non-coding RNAs, initially thought to be redundant parts of the genome, are now known to be involved in the regulation of key cellular processes in human tumourigenesis and in the development of drug resistance. Long non-coding RNAs (lncRNAs) are non-coding RNAs > 200 nucleotides in length and over 100,000 have been identified in the h...
http://hdl.handle.net/2262/92526
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HAMLET and synthetic derivatives as pre-operative agents in the treatment of oral and oesophageal cancer
(2020)
Ghanim, Magda
HAMLET and synthetic derivatives as pre-operative agents in the treatment of oral and oesophageal cancer
(2020)
Ghanim, Magda
Abstract:
Oral and oesophageal cancers are aggressive tumours that are frequently diagnosed late, with high morbidity, mortality, and difficulties in surgical and therapeutic intervention. Novel imaging probes could assist in early diagnosis and alleviate treatment complications through demarking a clear margin for resection during surgery. A further need exists for effective and selective neoadjuvant therapies that reduce tumour size before surgery. This project addresses both issues by clarifying the mechanism of action of a class of natural anti-cancer protein-fatty acid complex agents derived from milk and by creating a synthetic polymer-fatty acid derivative as a probe for cancer cell identification. The novel probe was designed to be fluorescent and comprises natural component molecules found in milk and wheat. The probe s characteristics were investigated in SCC-9 cells - a squamous cell carcinoma of the tongue. The synthesised probe was shown to be non-toxic, and actively taken up, i...
http://hdl.handle.net/2262/93149
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Problems sleeping with prostate cancer: exploring possible risk factors for sleep disturbance in a population-based sample of survivors
(2019)
Maguire, Rebecca; Drummond, Frances J.; Hanly, Paul; Gavin, Anna; Sharp, Linda
Problems sleeping with prostate cancer: exploring possible risk factors for sleep disturbance in a population-based sample of survivors
(2019)
Maguire, Rebecca; Drummond, Frances J.; Hanly, Paul; Gavin, Anna; Sharp, Linda
Abstract:
Purpose: This study aimed to investigate the prevalence of sleeping problems in prostate cancer survivors and to explore the role of predisposing, precipitating and perpetuating factors in this process. Methods: Using a cross-sectional design, 3348 prostate cancer survivors between 2 and 18 years post diagnosis reported experiences of insomnia using the QLQC30, along with their sociodemographic characteristics, health status and treatment(s) received. The EQ5D-5L and QLQPR25 assessed survivors’ overall and prostate cancer–specific health-related quality of life. A hierarchical multiple regression analysis was constructed with three blocks: (1) predisposing (e.g. demographics at diagnosis), (2) precipitating (e.g. disease extent, treatment) and (3) perpetuating factors (e.g. side effects). Results: Nineteen percent of survivors reported significant problems sleeping. The final model accounted for 31% of the variance in insomnia scores (p < .001). In order of magnitude, associates ...
http://mural.maynoothuniversity.ie/13421/
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A randomised controlled trial of an adapted internet-delivered cognitive behavioural therapy (iCBT) with main carer access for depression and anxiety among breast cancer survivors: study protocol
(2021)
Richards, Derek
A randomised controlled trial of an adapted internet-delivered cognitive behavioural therapy (iCBT) with main carer access for depression and anxiety among breast cancer survivors: study protocol
(2021)
Richards, Derek
Abstract:
Background: Depression and anxiety are common problems among breast cancer survivors. Carer support is one of the most important determinants of women's psychological wellbeing. Survivors' distress can be alleviated by giving carers access to survivors' evidence-based treatment, which will help carers understand what survivors have been going through and help survivors feel more supported. Given the limited access to evidence-based treatments, an adapted internet-delivered cognitive behavioural therapy (iCBT) intervention for breast cancer survivors, but also open for carers' access, has the potential to decrease survivors' depression and anxiety symptoms and improve cancer-related communication and relationship quality between survivors and carers. Objectives: This study evaluates (1) the effectiveness of a guided iCBT intervention for depression and/or anxiety symptoms among breast cancer survivors with and without main carer access, and (2) the acceptabil...
http://hdl.handle.net/2262/94887
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Mechanically stimulated osteocytes promote the proliferation and migration of breast cancer cells via a potential CXCL1/2 mechanism
(2021)
Hoey, David
Mechanically stimulated osteocytes promote the proliferation and migration of breast cancer cells via a potential CXCL1/2 mechanism
(2021)
Hoey, David
Abstract:
Bone represents the most common site for breast cancer metastasis. Bone is a highly dynamic organ that is constantly adapting to its biophysical environment, orchestrated largely by the resident osteocyte network. Osteocytes subjected to physiologically relevant biophysical conditions may therefore represent a source of key factors mediating breast cancer cell metastasis to bone. Therefore, we investigated the potential proliferative and migratory capacity of soluble factors released by mechanically stimulated osteocytes on breast cancer cell behaviour. Interestingly the secretome of mechanically stimulated osteocytes enhanced both the proliferation and migration of cancer cells when compared to the secretome of statically cultured osteocytes, demonstrating that mechanical stimuli is an important physiological stimulus that should be considered when identifying potential targets. Using a cytokine array, we further identified a group of mechanically activated cytokines in the osteocy...
http://hdl.handle.net/2262/94945
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Extracellular vesicles in blood: are they viable as diagnostic and predictive tools in breast cancer?
(2020)
O'Driscoll, Lorraine
Extracellular vesicles in blood: are they viable as diagnostic and predictive tools in breast cancer?
(2020)
O'Driscoll, Lorraine
Abstract:
Extracellular vesicles (EVs), often described as mini-maps of their cells of origin, are found in the bloodstream and can be rich sources of cargo released from cancer cells. As such, they could be collected through minimally invasive methods and potentially used as biomarkers. However, the relatively complicated methodologies that separate the purest EVs are the least likely to be translated to the clinic, whereas simpler methods are non-selective for EVs. Notwithstanding this, research is underway to identify blood-based EV-associated diagnostic and predictive biomarkers for breast cancer. There is reason to be optimistic that some approaches will yield useful biomarkers. Thus, further studies with larger cohorts of appropriate samples are warranted.
http://hdl.handle.net/2262/95142
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Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells
(2006)
Stordal, Britta; Davey, Mary W.; Davey, Ross
Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells
(2006)
Stordal, Britta; Davey, Mary W.; Davey, Ross
Abstract:
Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these w...
http://doras.dcu.ie/2170/
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Identification of pancreatic cancer invasion-related proteins by proteomic analysis
(2009)
Walsh, Naomi; O'Donovan, Norma; Kennedy, Susan; Henry, Michael; Meleady, Paula; Cl...
Identification of pancreatic cancer invasion-related proteins by proteomic analysis
(2009)
Walsh, Naomi; O'Donovan, Norma; Kennedy, Susan; Henry, Michael; Meleady, Paula; Clynes, Martin; Dowling, Paul
Abstract:
Background – Markers of pancreatic cancer invasion were investigated in two clonal populations of the cell line, MiaPaCa-2, Clone #3 (high invasion) and Clone #8 (low invasion) using proteomic profiling of an in vitro model of pancreatic cancer. Materials and methods – Using 2D-DIGE followed by MALDI-TOF MS, two clonal sub-populations of the pancreatic cancer cell line, MiaPaCa-2 with high and low invasive capacities were incubated on matrigel 24 hours prior to analysis to stimulate cell-ECM contact and mimic in vivo interaction with the basement membrane. Results - Sixty proteins were identified as being differentially expressed (>1.2 fold change and p ≤ 0.05) between Clone #3 and Clone #8. Proteins found to have higher abundance levels in the highly invasive Clone #3 compared to the low invasive Clone #8 include members of the chaperone activity proteins and cytoskeleton constituents whereas metabolism-associated and catalytic proteins had lower abundance levels. Differential p...
http://doras.dcu.ie/2426/
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Development of taxane resistance in a panel of human lung cancer cell lines
(2008)
Breen, Laura; Murphy, Lisa; Keenan, Joanne; Clynes, Martin
Development of taxane resistance in a panel of human lung cancer cell lines
(2008)
Breen, Laura; Murphy, Lisa; Keenan, Joanne; Clynes, Martin
Abstract:
Using a selection process designed to reflect clinically relevant conditions, a panel of taxane-selected variants were developed to study further the mechanisms of resistance in lung cancer. Unlike continuous or pulse exposure to high concentrations of chemotherapeutic drugs which yield high resistance and often cross resistance, most variants developed here displayed low level resistance to the selecting drug with slight cross-resistance. Pulsing with taxol resulted in more highly resistant clones (up to 51.4-fold). Analysis of taxol and taxotere in the four major lung cancer cell types showed the taxanes to be more effective against NSCLC (with the exception of SKMES-taxane selected variants) than against the SCLC. Comparison of taxol and taxotere shows that taxol induces higher levels of resistance than taxotere. Further, in taxotere-selected cell lines, the cells are more resistant to taxol than taxotere, suggesting that taxotere may be a superior taxane from a clinical view. Ta...
http://doras.dcu.ie/4540/
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Development and application of novel analytical methods for molecularly targeted cancer therapeutics
(2011)
Roche, Sandra
Development and application of novel analytical methods for molecularly targeted cancer therapeutics
(2011)
Roche, Sandra
Abstract:
A detailed understanding of correlations of drug levels with drug action is an important aspect of the pre-clinical, clinical development and routine use of anti-cancer drugs. In furtherance of this important aim, the research in this thesis sought to develop and apply novel, highly sensitive, analytical methods to examine and understand correlations of drug levels with drug resistance mechanisms, therapeutic efficacy and side effects. LC-MS/MS is a state of the art analytical technique used to characterise and quantify both bio-molecules and pharmaceutical agents. Based on LC-MS/MS techniques, novel sensitive analytical methods were developed for the quantification of 1) tyrosine kinase inhibitor anti-cancer drugs to examine the interaction of these agents with drug resistance mechanisms, and 2) the multiple myeloma drug thalidomide as a pilot study to identify potential correlations between serum drug levels and toxicity/efficacy. Acquired resistance to chemotherapeutics throu...
http://doras.dcu.ie/16073/
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Tyrosine Kinase Inhibitors in Triple Negative Breast Cancer
(2010)
Corkery, Brendan Martin
Tyrosine Kinase Inhibitors in Triple Negative Breast Cancer
(2010)
Corkery, Brendan Martin
Abstract:
Basal-like breast cancers are generally negative for estrogen and progesterone receptor expression and HER-2 amplification (‘triple negative’ breast cancer, TNBC), and express basal cytokeratins 5/6, and EGFR (epidermal growth factor receptor). No targeted therapy options are currently approved for this subgroup of patients. The main aim of this study was to assess the potential role of selected inhibitors in TNBC, including the small molecule tyrosine kinases inhibitors of EGFR gefitinib and erlotinib, the monoclonal antibody against EGFR cetuximab, and the multi-target tyrosine kinase inhibitor dasatinib. Significantly higher EGFR expression was detected in TNBC compared to HER-2 positive breast cancer cell lines. EGF treatment stimulated phospho-EGFR which was inhibited by gefitinib. Sensitivity to gefitinib was associated with decreases in PMAPK and P-Akt, and G1 cell cycle arrest. Combined treatment with gefitinib and chemotherapy was more effective than either gefitinib or che...
http://doras.dcu.ie/15714/
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Challenges of drug resistance in the management of pancreatic cancer
(2010)
Sheikh, Rizwan; Walsh, Naomi; Clynes, Martin; O'Connor, Robert A.; McDermott, Ray
Challenges of drug resistance in the management of pancreatic cancer
(2010)
Sheikh, Rizwan; Walsh, Naomi; Clynes, Martin; O'Connor, Robert A.; McDermott, Ray
Abstract:
The current treatment of choice for metastatic pancreatic cancer involves single agent gemcitabine or combination of gemcitabine with capecitabine and erlotinib (tyrosine kinase inhibitor). Only 25-30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activations of DNA repair pathways, resistance to apoptosis, and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, over expression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target, and/or amplification of the target represent key challenges for treatment efficacy. Here we will review the ...
http://doras.dcu.ie/16057/
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Synthesis, characterization and biological evaluation of N-ferrocenylmethyl amino acid benzene carboxamide derivatives and N-ferrocenyl benzoyl amino alkane derivatives as anti-cancer agents.
(2012)
Butler, William E.
Synthesis, characterization and biological evaluation of N-ferrocenylmethyl amino acid benzene carboxamide derivatives and N-ferrocenyl benzoyl amino alkane derivatives as anti-cancer agents.
(2012)
Butler, William E.
Abstract:
The aim of this research was to explore the structure-activity relationship (SAR) of ferrocenyl-bioconjugates. A series of N-(ferrocenylmethylamino acid)-fluorinated-benzene carboxamide derivatives and a series of N-(ferrocenyl)-benzoyl-aminoalkane derivatives have been synthesised, structurally characterised and biologically evaluated for their anti-proliferative activity on various cancer cell lines, principally, the (estrogen receptor positive) MCF-7 breast cancer cell line. The anti-cancer effect of ferrocene is due to the generation of a reactive oxygenated species. As part of the primary SAR study, a series of N-(ferrocenylmethylamino acid)-fluorinated-benzene carboxamide derivatives have been synthesised, structurally characterised and biologically evaluated. This series involved the attachment of amino acids, such as glycine, L-alanine and β-alanine and also a fluorobenzoyl unit to a ferrocenylmethylamine moiety in order to enhance the bioavailability of the compounds thus ...
http://doras.dcu.ie/17496/
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Systemic delivery of therapeutic small interfering RNA using a pH-triggered amphiphilic poly-L-lysine nanocarrier to suppress prostate cancer growth in mice
(2012)
Guo, Jianfeng; Cheng, Woei Ping; Gu, Jingxia; Ding, Caixia; Qu, Xiaozhong; Yang, Zhenzh...
Systemic delivery of therapeutic small interfering RNA using a pH-triggered amphiphilic poly-L-lysine nanocarrier to suppress prostate cancer growth in mice
(2012)
Guo, Jianfeng; Cheng, Woei Ping; Gu, Jingxia; Ding, Caixia; Qu, Xiaozhong; Yang, Zhenzhong; O'Driscoll, Caitríona M.
Abstract:
Prostate cancer is associated with high mortality and new therapeutic strategies are necessary for improved patient outcome. The utilisation of potent, sequence-specific small interfering RNA (siRNA) to facilitate down-regulation of complementary mRNA sequences in vitro and in vivo has stimulated the development of siRNA-based cancer therapies. However, the lack of an effective siRNA delivery system significantly retards clinical application. Amphiphilic polycations with 'stealth' capacity have previously been synthesised by PEGylation of poly-l-lysine-cholic acid (PLL-CA). The benzoic imine linker between PEG and PLL-CA was designed to be stable at physiological pH but cleavable at lower pHs, consistent with the extracellular environment of tumours and the interior of endosomes/lysosomes. The selective hydrolysis of the PEG linker at these targeted sites should provide enhanced cellular uptake and endosomal escape while simultaneously ensuring prolonged blood circulation ...
http://hdl.handle.net/10468/932
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The role of Galectin-3 and Survivin in invasion and drug resistance in human cancer
(2003)
Linehan, Rasha
The role of Galectin-3 and Survivin in invasion and drug resistance in human cancer
(2003)
Linehan, Rasha
Abstract:
Galectin-3 is an apoptosis-related gene previously found to be over-expressed in invasive tumours and to cause in v itroinvasiveness and metastasis in colon, breast and thyroid follicular cancer cells. Galectin-3 over-expressing clones were obtained following stable transfection of galectin-3 cDNA into the non-invasive human lung carcinoma cell line DLKP. These clones exhibited increased invitro invasiveness and motility and altered cell adhesion properties, but did not exhibit a drug resistant phenotype. Survivin is an antiapoptotic gene highly expressed in all cancer types and during fetal development, but not in most normal adult tissue. To determine whether survivin over-expression plays a role in drug-resistance, transient transfections of survivin cDN into SKOV-3 ‘Tet off , MCF-7 'Tet off and DLKP cells, were carried out. All three transfections resulted in an overexpression of survivin mRNA, but not survivin protein. To further investigate the role o f galectin-3 and su...
http://doras.dcu.ie/18011/
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The expression of multiple drug resistance (MDR) associated proteins in invasive breast cancer
(2002)
Larkin, Anne-Marie
The expression of multiple drug resistance (MDR) associated proteins in invasive breast cancer
(2002)
Larkin, Anne-Marie
Abstract:
Despite the recent advances in the detection, treatment and management of breast cancer, with an increasing range of hormonal, cytotoxic and more recently MAb targeted drug regimes available in the clinic, between 40% and 50% o f patients diagnosed will eventually die from this disease. Identification of biological factors which can function as reliable markers of both prognosis and chemoresponsiveness will allow for more precise targeting of treatment for individual breast cancer patients. During the course of this thesis the expression of a panel of MDR associated proteins was correlated with patient and tumour characteristics and relapse and overall survival in a series of invasive breast carcinomas. In order to address the multifactorial nature o f this disease, expression of individual proteins was analysed in relation to other markers. The results presented show that MRP-1 protein at diagnosis is an independent prognostic factor for overall survival in node positive breast can...
http://doras.dcu.ie/18004/
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The effect of conjugated linoleic acid on the proliferation, migration and invasion of a murine mammary cancer cell line
(2002)
O'Connor, Áine
The effect of conjugated linoleic acid on the proliferation, migration and invasion of a murine mammary cancer cell line
(2002)
O'Connor, Áine
Abstract:
Conjugated Linoleic Acid (CLA), a polyunsaturated fatty acid, refers to a group of dienoic derivatives of linoleic acid that can be found in natural food sources, such as milk fat and the meat of ruminant animals. CLA has been shown to have anti-carcinogenic activity in many in vitro and in vivo studies. Previous studies have focused on the effects of dietary CLA on the prevention of tumour appearance, yet relatively little is known about the actual mechanism of CLA’s anti-cancer activity. The most lethal aspect of cancer is the ability of tumour cells to metastasise and form secondary tumours. The matrix metalloproteinases (MMPs), a multi-gene family of enzymes, which degrade components of the extracellular matrix (ECM) have been implicated as major role players in tumour invasion and metastasis. The aim of this study was to examine the effect of CLA on the proliferation, migration, invasion and MMP-9 expression of a murine mammary cancer cell line, 4T1, which is known to be highl...
http://doras.dcu.ie/18128/
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