52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced... more
52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT. Determine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up. A single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4-6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention. 112 consecutive first round participants were recruited. Eight (7%)...
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Research Interests: Immunology, Biology, Epigenetics, Adolescent, Medicine, and 15 moreInflammatory Bowel Disease, Humans, Child, Female, Male, DNA methylation, Clinical Sciences, Adult, Age Factors, Disease Progression, Crohn Disease, Gene Expression Regulation, Gene expression profiling, Inflammatory Bowel Diseases, and Case Control Studies
Tumor-derived circulating DNA has been found in the plasma of cancer patients. Alterations include decreased strand stability, mutations of oncogenes or of tumor suppressor genes, microsatellite alterations, and hypermethylation of... more
Tumor-derived circulating DNA has been found in the plasma of cancer patients. Alterations include decreased strand stability, mutations of oncogenes or of tumor suppressor genes, microsatellite alterations, and hypermethylation of several genes. RNA has also been found circulating in the plasma of normal subjects and cancer patients. Tyrosinase mRNA has been extracted from the serum of melanoma patients and subjected to RT-PCR. Moreover, the presence of cell-free EBV-associated RNA has been reported in the plasma of patients with nasopharyngeal carcinoma. Human telomerase comprises two RNA subunits, telomerase RNA template (hTR) and its catalytic component, telomerase reverse transcriptase protein (hTERT). Expression of these subunits correlates with telomerase activity. Using RT-PCR, we investigated whether these RNA subunits were present in the serum of 18 patients with breast cancer, 2 patients with benign breast disease, and 21 normal subjects. The presence of amplifiable RNA w...
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Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal... more
Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decr...
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The roots of colorectal cancer date back to antiquity. In this short history of colorectal cancer we trace its clinical and research origins from ancient times through the dark ages, middle ages, to the scientific and medical advances of... more
The roots of colorectal cancer date back to antiquity. In this short history of colorectal cancer we trace its clinical and research origins from ancient times through the dark ages, middle ages, to the scientific and medical advances of the seventeenth to twentieth centuries and into the twenty-first century.
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K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer... more
K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients using a simple and rapid extraction technique and detected K-ras alterations with a PCR assay and subsequent product sequencing. Patients were followed up to determine their clinical outcome. We found K-ras mutations in the plasma of 17 patients (81%). In cases in which both plasma and pancreatic tissue were available, DNA mutations were similar in corresponding plasma and tissue samples. Plasma DNA alterations were found 5-14 months before clinical diagnosis in four patients. Mutant DNA was not found in the plasma of two patients with chronic pancreatitis or in five healthy controls. Our results indicate that K-ras mutations are often found in DNA isolated from the plasma of pancreatic cancer patients and that a noninvasive plasma-based assay ma...
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Research Interests: Medical Microbiology, Biology, Immunohistochemistry, Medicine, Molecular Diagnostics, and 15 moreColorectal cancer, Humans, Female, Male, Polymerase Chain Reaction, DNA methylation, CpG islands, Aged, Middle Aged, Carcinoma, National Cancer Institute, CpG island, Methyltransferase, Colorectal Neoplasms, and Microsatellite instability
Urokinase plasminogen activator (uPA) is a serine protease causally involved in cancer invasion and metastasis. Consistent with its role in cancer spread, uPA has been shown to be a prognostic marker in a variety of malignancies,... more
Urokinase plasminogen activator (uPA) is a serine protease causally involved in cancer invasion and metastasis. Consistent with its role in cancer spread, uPA has been shown to be a prognostic marker in a variety of malignancies, especially breast cancer. Approximately 20 different groups have shown that high levels of uPA in breast tumor tissue predict poor outcome. As a prognostic marker in breast cancer, uPA provides information that is independent of traditionally used factors such as tumor size, tumor grade, axillary node status and estrogen receptor status. Furthermore, uPA is prognostic in node-negative patients, and a clinical trial is currently under way to assess whether uPA and its inhibitor, plasminogen activator inhibitor-1, can differentiate between the majority of node-negative breast cancer patients who are cured by surgery from the minority who might benefit from adjuvant therapy. uPA is also prognostic in other malignancies, such as gastric, colorectal, esophageal, renal, endometrial, and ovarian cancers. uPA may thus be a prognostic indicator for multiple types of adenocarcinoma.
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Research Interests: Nonparametric Statistics, Gastroenterology, Medicine, Stents, Humans, and 12 moreJaundice, Clinical Sciences, Tumor necrosis factor-alpha, Gut, Bile Duct, Stent, Enzyme Linked Immunosorbent Assay, Interleukin, Inflammatory response, cholestasis, Pancreatic neoplasms, and Paediatrics and reproductive medicine
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Research Interests: Survival Analysis, Medicine, Colorectal cancer, Humans, Female, and 15 moreMale, American, Aged, Middle Aged, Carcinoma, Neoplasm Invasiveness, Adult, Colon cancer, Survival Rate, Retrospective Studies, Lymphovascular invasion, Neoplasm staging, Peritoneal Neoplasms, Medical and Health Sciences, and Colonic Neoplasms
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ship between disclosure, HRQOL, and medication adherence. Results: 92 IBD pts participated (62 CD/30 UC), evenly split between online and clinic sources. Mean±SD age was 37.5±12.6 yrs, 72% male, 95% Caucasian. Time since Dx was 8.7±8.9... more
ship between disclosure, HRQOL, and medication adherence. Results: 92 IBD pts participated (62 CD/30 UC), evenly split between online and clinic sources. Mean±SD age was 37.5±12.6 yrs, 72% male, 95% Caucasian. Time since Dx was 8.7±8.9 yrs, 70% experience a flare at least once/yr, 65% experience extra-intestinal Sx, 13% had an ostomy, and 50% were in remission at assessment. 38% stopped medication in the past yr without consulting their MD and 13% canceled at least 1 MD appt in the same time period. The IBD-DS demonstrated good reliability (α=0.74, split-half=0.75). Females were more likely to disclose IBD status (40.7±7.7 vs. 36.3±6.9). No other significant differences by demographic or clinical variables existed. 33% reported being afraid to tell others about their IBD, and 30% regretted previous disclosure. Disclosure was negatively correlated with all subscales on the IBDQ (all p<.01), with the largest association with emotional (r= -.47) followed by social functioning (r= -.46). Less disclosure was also related to increased systemic (r= -.45) and bowel symptoms (r= -.41). Only emotional function was predictive of disclosure (R Adjusted = .21, p<001). Decreased disclosure was a significant predictor of skipping medication in the past yr (Odds Adj = 1.10, p=.03), but not for missed MD visits (p=.89). Conclusions: IBD pts who disclose their illness to others report lower levels of social and emotional function, and increased IBD symptoms. Only emotional functioning was significantly predictive of increased disclosure. Concealment also related to reduced medication adherence in the past year. These findings suggest that discussing IBD with others may be related to poorer HRQOL. However, keeping IBD hidden may compromise medication adherence. Further investigation is warranted.
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AbstractAn automated system for analysis of colonoscopy videos is expected to complement the expertise and the experience of a medical professional in: (a) detecting lesions and (b) assessing the quality of a given procedure. Colonoscopy... more
AbstractAn automated system for analysis of colonoscopy videos is expected to complement the expertise and the experience of a medical professional in: (a) detecting lesions and (b) assessing the quality of a given procedure. Colonoscopy videos contain a significant number of ...
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Research Interests: Flow Cytometry, Cancer Research, Apoptosis, Medicine, Colorectal cancer, and 15 moreCell line, Humans, Colon cancer, Western blot, Transfection, Gastrointestinal Cancer, In Vitro Studies, Cell Proliferation, Treatment Response, Antineoplastic Agents, Enzyme Linked Immunosorbent Assay, Crystal Violet, Clusterin, Oxaliplatin, and Colorectal Neoplasms
The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if... more
The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2Gy, 5Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.018) and an increase in bridge formations (all p values &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.017) compared to bystander cells treated with media from unirradiated tissue (0Gy) at 24h. There was no significant difference between 2Gy and 5Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p=0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p=0.02) and mitochondrial membrane potential increased (p=0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring mitochondrial function through overexpression of MnSOD significantly rescues nuclear instability events; anaphase bridges and telomere length shortening.