Now showing items 41-60 of 82

    • A prospective study of patients with impending spinal cord compression treated with palliative radiotherapy alone

      O'Sullian, L.; Clayton-Lea, A.; McArdle, O.; McGarry, M.; Kenny, J.; Dunne, M.; O'Shea, E.; Small, C.; Moriarty, M.; Thirion, P. (Cambridge University Press, 2013)
      mpending malignant spinal cord compression (IMSCC) may be defined as compression of the thecal sac, without any visible pressure on the spinal cord itself. Although there is a perception that IMSCC patients have a better prognosis and less severe clinical symptoms than true malignant spinal cord compression (MSCC) patients, these factors have never been documented in the literature.
    • Mining methylome databases.

      O'Rourke, Colm J; Murphy, Therese M; Hollywood, Donal; Perry, Antoinette S; Prostate Molecular Oncology, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland. orourkco@tcd.ie (2013-02)
    • Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

      Perry, Antoinette S; O'Hurley, Gillian; Raheem, Omer A; Brennan, Kevin; Wong, Simon; O'Grady, Anthony; Kennedy, Anne-Marie; Marignol, Laure; Murphy, Therese M; Sullivan, Linda; et al. (2013-04-15)
      Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.
    • Manipulating the epigenome for the treatment of urological malignancies.

      O'Rourke, Colm J; Knabben, Vinicius; Bolton, Eva; Moran, Diarmaid; Lynch, Thomas; Hollywood, Donal; Perry, Antoinette S; Prostate Molecular Oncology, Institute of Molecular Medicine, Trinity College, Dublin, Ireland. (2013-05)
      Urological malignancies (cancers of the prostate, bladder, kidney and testes) account for 15% of all human cancers and more than 500,000 deaths worldwide each year. This group of malignancies is spread across multiple generations, affecting the young (testicular) through middle and old-age (kidney, prostate and bladder). Like most human cancers, urological cancers are characterized by widespread epigenetic insult, causing changes in DNA hypermethylation and histone modifications leading to silencing of tumor suppressor genes and genomic instability. The inherent stability yet dynamic plasticity of the epigenome lends itself well to therapeutic manipulation. Epigenetic changes are amongst the earliest lesions to occur during carcinogenesis and are essentially reversible (unlike mutations). For this reason, much attention has been placed over the past two decades on deriving pharmacological compounds that can specifically target and reverse such epi-mutations, either halting cancer on its developmental trajectory or reverting fully formed cancers to a more clinically manageable state. This review discusses DNA methyltransferase and histone deacetylase inhibitors that have been extensively studied in preclinical models and clinical trials for advanced and metastatic urological cancers.
    • DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

      Martin, Lynn M; Marples, Brian; Davies, Anthony M; Atzberger, Ann; Edwards, Connla; Lynch, Thomas H; Hollywood, Donal; Marignol, Laure; Radiation and Urologic Oncology, Prostate Molecular Oncology Research Group, Academic Unit of Clinical and Molecular Oncology, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland. (Elsevier Ireland Ltd, 2013-07-10)
      DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.
    • New targeted therapies for NSCLC.

      Carney, D (GreenCross Publishing, 2011)
    • An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its Diagnosis and the Role of Radiotherapy in its Management.

      Rock, Kathy; Rangaswamy, Guhan; O'Sullivan, Siobhra; Coffey, Jerome; Department of Radiation Oncology, St. Luke's Hospital, Rathgar, Dublin 6, Ireland. (Karger, 2011-10)
      BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin's lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no 'B' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.
    • Evolving progress in oncologic and operative outcomes for esophageal and junctional cancer: lessons from the experience of a high-volume center.

      Reynolds, John V; Donohoe, Claire L; McGillycuddy, Erin; Ravi, Naraymasamy; O'Toole, Dermot; O'Byrne, Ken; Hollywood, Donal; Department of Surgery, St James's Hospital and Trinity College, Dublin, Ireland. reynoljv@tcd.ie (Elsevier, 2012-05)
      Modern series from high-volume esophageal centers report an approximate 40% 5-year survival in patients treated with curative intent and postoperative mortality rates of less than 4%. An objective analysis of factors that underpin current benchmarks within high-volume centers has not been performed.
    • Quantification of organ motion during chemoradiotherapy of rectal cancer using cone-beam computed tomography.

      Chong, Irene; Hawkins, Maria; Hansen, Vibeke; Thomas, Karen; McNair, Helen; O'Neill, Brian; Aitken, Alexandra; Tait, Diana; Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, United Kingdom. (Elsevier, 2011-11-15)
      There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic (Σ) and random (σ) setup errors.
    • mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.

      Walsh, S; Flanagan, L; Quinn, C; Evoy, D; McDermott, E W; Pierce, A; Duffy, M J; UCD School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin, Ireland. (Elsevier, 2012-04)
      Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.
    • Perforation of colon cancer into a benign ovarian cyst.

      Walsh, S; Evoy, D; Cantwell, C P; Kroon, N; Sheahan, K; Gibbons, D; McDermott, E W; St. Vincent's University Hospital, Dublin , Ireland. siunwalsh@gmail.com (Informa Healthcare, 2012-04)
    • The effect of short term neo-adjuvant androgen deprivation on erectile function in patients treated with external beam radiotherapy for localised prostate cancer: an analysis of the 4- versus 8-month randomised trial (Irish Clinical Oncology Research Group 97-01).

      Daly, Patricia E; Dunne, Mary T; O'Shea, Carmel M; Finn, Marie A; Armstrong, John G; Department of Radiation Oncology, St. Luke's Hospital, Dublin, Ireland. trish_daly@eircom.net (Elsevier, 2012-07)
      Erectile dysfunction is a common consequence of external beam radiotherapy (EBRT) for prostate cancer. The addition of neo-adjuvant androgen deprivation (NAD) has an indeterminate additive effect. We examined the long-term effect on erectile function (EF) of two durations (4 months: arm 1 and 8 months: arm 2) of NAD prior to radiation (RT) for patients with localised prostate cancer from the Irish Clinical Oncology Research Group (ICORG 97-01) 4- versus 8-month trial. In this study we aimed to (1) analyse the overall effect on EF of NAD in an EBRT population, (2) compare the probability of retained EF over time in an EBRT population treated with either 4 or 8 months of NAD and (3) identify any variables such as risk group and age which may have an additive detrimental effect. This analysis provides unique long term follow up data.
    • In silico analysis and DHPLC screening strategy identifies novel apoptotic gene targets of aberrant promoter hypermethylation in prostate cancer.

      Murphy, Therese M; Sullivan, Linda; Lane, Caroline; O'Connor, Lisa; Barrett, Ciara; Hollywood, Donal; Lynch, Thomas; Lawler, Mark; Perry, Antoinette S; Prostate Molecular Oncology, Institute of Molecular Medicine, Trinity College, Dublin, Ireland. murphyth@tcd.ie (Wiley, 2011-01-01)
      Aberrant DNA methylation has been implicated as a key survival mechanism in cancer, whereby promoter hypermethylation silences genes essential for many cellular processes including apoptosis. Limited data is available on the methylation profile of apoptotic genes in prostate cancer (CaP). The aim of this study was to profile methylation of apoptotic-related genes in CaP using denaturing high performance liquid chromatography (DHPLC).
    • An unusual case of dyspnea in metastatic breast carcinoma.

      Cronin, Kathleen Ann; Twomey, Marie; O'Reilly, Maeve; Carney, Desmond N (Elsevier, 2011-02)
    • Multimodal management of retroperitoneal sarcoma

      Rangaswamy, Guhan; Gillham, Charles; St. Luke's Hospital, Rathgar, Dublin 6 (2012-05-03)
    • MicroRNAs as putative mediators of treatment response in prostate cancer.

      O'Kelly, Fardod; Marignol, Laure; Meunier, Armelle; Lynch, Thomas H; Perry, Antoinette S; Hollywood, Donal; Prostate Molecular Oncology Research Group, Academic Unit of Clinical and Molecular Oncology, Institute of Molecular Medicine, St James' Hospital & Trinity College, University of Dublin, James's Street, Dublin 8, Ireland. (2012-05-22)
      MicroRNAs (miRNAs) are an abundant class of noncoding RNAs that function to regulate post-transcriptional gene expression, predominantly by translational repression. In addition to their role in prostate cancer initiation and progression, recent evidence suggests that miRNAs might also participate in treatment response across a range of therapies including radiation treatment, chemotherapy and androgen suppression. The mechanism of this regulation is thought to be multifactorial and is currently poorly understood. To date, only a small number of studies have examined the functional role of miRNAs in response to prostate cancer treatment. Elucidating the role of miRNAs in treatment response following radiotherapy, chemotherapy and androgen suppression will provide new avenues of investigation for the development of novel therapies for the treatment of prostate cancer.
    • Transdermal hyoscine induced unilateral mydriasis.

      Hannon, Breffni; Jennings, Valerie; Twomey, Marie; O'Reilly, Maeve; Palliative Medicine Department, Our Lady's Children's Hospital, Dublin, Ireland. breffnilhannon@yahoo.co.uk (2012-03-20)
      The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.
    • Challenges in the Management of Pediatric Central Venous Access Devices in the Community.

      Wallace, Elaine; Twomey, Marie; O'Reilly, Maeve; Department of Palliative Medicine, Our Lady's Hospital for Sick Children , Crumlin, Dublin , Ireland. (2012-05-25)
      Central venous access devices (CVADs) play an essential role in the care of critically ill children. Significant challenges exist for teams in managing CVADs particularly in a community setting. The authors aimed to assess the experience of general practitioners (GPs) caring for children with CVADs. From 200 CVADs inserted in a pediatric hospital in 2009, 50 patients were randomly selected and 44 GPs were forwarded a questionnaire. Twenty (46%) GPs responded. The main reasons (n = 22) for using CVADs were medication administration (n = 11), nutrition (n = 6), and blood sampling (n = 5). Thirteen (65%) GPs had no education in CVAD management and 14 (70%) were unaware of existing guidelines. Those identified by GPs as having primary responsibility for care of CVADs in the community included hospital/pediatric teams (n = 9), parents (n = 3), GPs (n = 2), public health nurses (n = 1), and palliative care ("home care") teams (n = 1). The main challenges (n = 15) identified by GPs were lack of education (n = 4), line management difficulties (n = 3), infection risk (n = 3), infrequent exposure to CVADs (n = 3), and poor communication (n = 1). GPs felt that these challenges could be addressed through: education (n = 8), increased manpower and community support (n = 1), and improved communication (n = 1). This study highlights the inconsistency and challenges for GPs surrounding CVAD use in children. Further education and support is necessary to assist GPs in their use particularly when providing end-of-life care for children in the community.
    • A European survey relating to cancer therapy and neutropenic infections: Nurse and patient viewpoints.

      Leonard, Kay; Saint Luke's Radiation Oncology Centre, St James's Hospital, St James's Street, Dublin 8, Ireland. (2011-09-25)
      PURPOSE: Severe neutropenia and febrile neutropenia (FN) are the major causes of morbidity, treatment interruptions and dose reductions in patients undergoing chemotherapy. The European Oncology Nursing Society (EONS) conducted an European survey to evaluate nurse perspectives on prevention of infection and FN in this setting, and how much they educate their patients about this. A separate survey explored these issues in patients receiving chemotherapy. METHODS: 217 nurse participants were identified by EONS from the membership database and 473 cancer patients who were receiving/had received chemotherapy were identified through patient advocacy groups. Questionnaires were completed anonymously online for both surveys. RESULTS: More than 90% of the nurses agreed that preventing infections including FN is extremely/very important for a successful chemotherapy outcome and said that they, or other health professionals in their practice, advised patients about these issues. Most (90%) indicated that they favoured giving treatment to protect against FN and infections in chemotherapy patients at risk, rather than treating infection after it develops, but 82% expressed concern over patient concordance with measures employed. A substantial proportion of patients reported emergency room visits, hospitalization and/or chemotherapy delays or changes as a result of neutropenia, infection or FN. However, only 44% said that their infection risk was discussed with them before starting chemotherapy. CONCLUSIONS: Our findings indicate that nurses recognise the importance of reducing the risk of infection and FN in patients undergoing chemotherapy, as well as the need to educate patients. However, results of the patient survey suggest a need for better patient education.