Publications by authors named "Gerald C OʼSullivan"

Purpose: Electrochemotherapy (ECT) is the application of electric pulses to tumour tissue to render the cell membranes permeable to usually impermeant hydrophilic anti-cancer drugs, thereby enhancing cytotoxic effects. We sought to ascertain whether ECT can be an effective palliative treatment for cutaneous metastases of breast cancer.

Methods: This work reports data from the European Standard Operating Procedures for Electrochemotherapy trial (EudraCT Number: 2004-002183-18).

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Background And Study Aims: Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endoscopic delivery of this tumor permeabilizing treatment.

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Background: Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25 %. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict outcome.

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Many epithelial cancers, particularly gastrointestinal tract cancers, remain poor prognosis diseases, due to resistance to cytotoxic therapy and local or metastatic recurrence. We have previously shown that apoptosis incompetent esophageal cancer cells induce autophagy in response to chemotherapeutic agents and this can facilitate their recovery. However, known pharmacological inhibitors of autophagy could not enhance cytotoxicity.

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We have previously reported that most patients with esophagogastric cancer (EGC) undergoing potentially curative resections have bone marrow micrometastases (BMM). We present 10-year outcome data of patients with EGC whose rib marrow was examined for micrometastases and correlate the findings with treatment and conventional pathologic tumor staging. A total of 88 patients with localized esophagogastric tumors had radical en-bloc esophagectomy, with 47 patients receiving neoadjuvant (5-fluorouracil/cisplatin based) chemoradiotherapy (CRT) and the remainder being treated with surgery alone.

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Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth.

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Background: Changing work practices make it imperative that surgery selects candidates for training who demonstrate the spectrum of abilities that best facilitate learning and development of attributes that, by the end of their training, approximate the characteristics of a consultant surgeon.

Aims: The aim of our study was to determine the relative merits of components of a program used for competitive selection of trainees into higher surgical training (HST) in general surgery.

Methods: Applicants (N = 98, males 69, mean age 31 years [range 29-40]) to the Royal College of Surgeons in Ireland program for HST in general surgery between 2006 and 2008 were assessed.

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Background: Colorectal cancer is the second leading cause of cancer-related mortality and frequently presents with locally advanced or metastatic disease. Adenovirus (Ad) vectors are important gene delivery agents because they offer efficient and broad tissue transduceability. However, their ability to penetrate through multicell layers in colorectal cancers and maintain expression in colon tumor-related hypoxic conditions has yet to be analyzed.

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Background: The establishment of assessment reliability at the level of the individual trainee is an important attribute of assessment methodologies, particularly for doctors who have been failed. This issue is of particular importance for the process of competence assessment in the USA, UK, Australia and New Zealand.

Methods: We use data from 19 applicants for higher surgical training in 2008 at the Royal College of Surgeons in Ireland to compare: (i) the objective structured assessment of technical skills (OSATS) method; and (ii) a procedure-specific checklist to assess surgical technical skills in the excision of a sebaceous cyst task by two experienced senior surgeons.

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Background: Laparoscopic lavage has shown promising results in nonfeculent perforated diverticulitis. It is an appealing strategy; it avoids the complications associated with resection. However, there has been some reluctance to widespread uptake because of the scarcity of large-scale studies.

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Purpose: In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues.

Methods: Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined.

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Background: Laparoscopic skills are difficult to learn. We, therefore, assessed the factors involved in skill acquisition, maintenance, and loss in 2 prospective, randomized studies.

Methods: In study 1, 24 laparoscopic novices were randomly assigned to a control condition who performed the laparoscopic assessment task; Massed condition who trained on virtual reality (VR) simulation during 1 day or Interval condition who had the same amount of VR training distributed over 3 consecutive days.

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The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux.

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Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-κB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity.

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Purpose: The induction of systemic immune responses against antigenic targets that are over expressed by cancer cells represents a powerful therapeutic strategy to target metastatic cancer. We generated specific antitumor immune responses in a murine model of prostate cancer by oral administration of an attenuated strain of Salmonella typhimurium containing a plasmid coding for murine prostate stem cell antigen.

Materials And Methods: Trafficking of S.

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Background: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression.

Materials And Methods: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis.

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Background: Von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-α (HIF-α), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP)A2/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited.

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Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins.

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Preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. However, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. Clinical data relevant to treatment strategies may be generated prior to clinical trial through experimentation using intact patient tissue ex vivo.

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Cancer is one of the most wide-spread diseases of modern times, with an estimated increase in the number of patients diagnosed worldwide, from 11.3 million in 2007 to 15.5 million in 2030 (www.

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This video describes the use of patient tissue as an ex vivo model for the study of gene delivery. Fresh patient tissue obtained at the time of surgery is sliced and maintained in culture. The ex vivo model system allows for the physical delivery of genes into intact patient tissue and gene expression is analysed by bioluminescence imaging using the IVIS detection system.

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We investigated the cell-death mechanisms induced in esophageal cancer cells in response to the chemotherapeutic drugs, 5-fluorouracil (5-FU) and cisplatin. Chemosensitive cell lines exhibited apoptosis whereas chemoresistant populations exhibited autophagy and a morphology resembling type II programmed cell death (PCD). Cell populations that respond with autophagy are more resistant and will recover following withdrawal of the chemotherapeutic agents.

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