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Biomedical subjects

Enda McDermott

Publications and source records attributed to Enda McDermott.

11 recordsLinked to original sources
PubMed2007

Lipophilin B: A gene preferentially expressed in breast tissue and upregulated in breast cancer.

Lipophilin B (LPB), which is also known as BU101, is a secretoglobin which exists in vivo as a complex with the mammary-specific protein, mammaglobin A (MGA). The aim of our study was to investigate the expression of LPB in a panel of breast and nonbreast tissues and compare its expression with that of MGA. Using RT-PCR, LPB mRNA was detected in 16/25 (64%) of normal breast specimens, 23/30 (77%) of fibroadenomas, 102/156 (65%) of primary breast cancers and in 8/36 (22%) nonbreast tissues. Levels of expression of LPB mRNA were significantly higher in breast cancers compared to both normal breast tissues (p = 0.02) and nonbreast tissue (p < 0.001). In the primary breast cancers, expression of LPB mRNA was positively correlated with the estrogen receptor (p = 0.045) but inversely related to both tumor grade (p < 0.001) and proliferation rates (p = 0.0345). Compared to MGA, expression of LPB was more sensitive but less specific for breast cancer. Using Western blotting, LPB migrated with an approximate molecular mass of 7-8 kDa, the expected molecular mass of free LPB. Immunohistochemical analysis of breast cancers showed that LPB expression was predominantly confined to the cytoplasm of tumor cells. We conclude that expression of LPB is preferentially but not exclusively restricted to breast tissue. Since LPB was expressed relatively specifically in breast tissue and was significantly upregulated in breast carcinomas, it is a promising candidate biomarker for breast cancer.

Biomarkers, Tumor↗
PubMed2005

Mammaglobin a in breast cancer: existence of multiple molecular forms.

Existing serum-based markers for breast cancer all lack organ specificity. Mammaglobin A (MGA) is a 93 amino acid protein expressed almost exclusively in breast tissue. The aim of our study was to investigate the different forms of MGA protein in fibroadenomas and breast carcinomas. MGA protein was measured by Western blotting in 132 breast cancers, 29 fibroadenomas and 14 nonbreast tissues. MGA protein in breast tissue was found to exist in 2 main forms. These forms migrated with approximate molecular masses of 18 and 25 kDa. Both forms of MGA were detected more frequently in breast carcinomas compared to fibroadenomas. The high molecular weight form of MGA but not the low molecular weight form was found more frequently in hormone receptor-positive than in receptor-negative cancers. Furthermore, an inverse relationship was found between the high molecular weight form of MGA and both tumour grade and proliferation index. No significant correlation was found between the MGA proteins and either tumor size or nodal status. Our results show that MGA protein exists in 2 main forms in breast tissue. As the high molecular weight form correlated positively with hormone receptors and negatively with tumor grade and proliferation rate, its presence is likely to be associated with a favourable prognosis for breast cancer. As expression of MGA is almost breast specific, it is a promising marker for breast cancer. Its most immediate use is likely to be in detecting micrometastases from breast cancer.

Biomarkers, Tumor↗
PubMed2005

Unusual presentation of a giant parathyroid adenoma: report of a case.

Parathyroid adenomas account for most cases of primary hyperparathyroidism (1 degrees HPT). Certain symptoms and biochemical abnormalities alert the surgeon to their presence, since these benign tumors are rarely evident on physical examination. Moreover, because they are usually very small, preoperative localization using sestamibi scanning or ultrasonography is required to avoid bilateral neck exploration. Parathyroid adenomas rarely attain huge proportions. We report a case of a parathyroid adenoma measuring 8 x 5 x 3.5 cm and weighing 110 g; to our knowledge the greatest mass reported in the literature. Interestingly, despite its huge size it did not cause many of the hypercalcemic symptoms usually associated with larger adenomas, but rather it manifested with symptoms of local pressure, another unusual property of this atypical tumor.

Adenoma↗
PubMed2005

Hungry bones without hypocalcaemia following parathyroidectomy.

Hungry bone syndrome is a complication of parathyroid surgery where the correction of primary hyperparathyroidism is associated with rapid bone remineralization, causing severe and prolonged hypocalcaemia [1]. We present a case of hungry bones where although there was rapid bone formation, the serum calcium was maintained within normal limits owing to the development of secondary hyperparathyroidism.

Adenoma↗
PubMed2005

A survey of breast cancer awareness and knowledge in a Western population: lots of light but little illumination.

There are conflicting data on breast cancer awareness and knowledge in specific population groups. We assessed awareness and knowledge of breast cancer in the general Irish population to identify sources of information on breast cancer and determine factors associated with knowledge and awareness of the disease. Participants (n=2355, 53% female) completed a multi-part questionnaire. Most (81%) had seen or heard something about breast cancer in the recent past and knowledge of symptoms and treatment was good overall. However, 66% of females overestimated their risk of developing disease, 88% underestimated the age at which it was most likely to develop and 56% underestimated 5-year survival. Knowledge of incidence and survival was higher in males (Odds Ratio (OR) 1.3, 95% Confidence Interval (CI); 1.1-1.5), participants with higher education (1.5; 1.2-1.7) and those who received information from television (1.3; 1.1-1.5). Ignorance regarding incidence, outcome and risk makes it unlikely that the general public or at risk females could currently make informed decisions on a range of breast cancer issues.

Adult↗
PubMed2004

High preoperative CA 15-3 concentrations predict adverse outcome in node-negative and node-positive breast cancer: study of 600 patients with histologically confirmed breast cancer.

BACKGROUND: CA 15-3 is the most widely used serum marker in breast cancer. Currently, its main uses are in the surveillance of patients with diagnosed disease and monitoring the treatment of patients with advanced disease. METHODS: Preoperative CA 15-3 concentrations were measured prospectively in 600 patients with histologically confirmed breast cancer. Marker concentrations were related to patient outcome by both univariate and multivariate analysis. RESULTS: After a median follow-up of 6.27 years, patients with high preoperative concentrations of CA 15-3 (>30 units/L) had a significantly shorter overall survival pattern than those with low concentrations. As a prognostic factor, CA 15-3 was independent of tumor size, axillary node status, and patient age. As well as being prognostic in the total population of patients, CA 15-3 also predicted outcome in different subgroups of patients, including those with both node-negative and node-positive disease, those who were both estrogen receptor (ER)-negative and ER-positive, and those younger and older that 50 years of age. CA 15-3 was also predictive of outcome irrespective of the type of adjuvant therapy administered, i.e., whether adjuvant hormone therapy, adjuvant chemotherapy, or radiotherapy was administered. CONCLUSION: Assay of CA 15-3 is a relatively inexpensive, convenient, and noninvasive method for evaluating prognosis in newly diagnosed breast cancer patients.

Adult↗
PubMed2004

Gastric glomus tumor.

Gastric glomus tumors are rare neoplasms that may present with upper gastrointestinal symptoms, or may be discovered incidentally. They may mimic other tumors both grossly and microscopically. They are usually benign and, although the exceptional case with aggressive behavior cannot be reliably predicted, large size may be of prognostic importance. We describe a 3.8 cm gastric glomus tumor in a patient who also had adenocarcinoma arising in an adenoma of the rectum, and discuss the differential diagnosis and prognosis.

Adenocarcinoma↗
PubMed2004

Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.

BACKGROUND: Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated. MATERIALS AND METHODS: Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody. RESULTS: Plasma endostatin levels, in breast cancer patients, were significantly elevated (P = 0.015) in the post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76 etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival. CONCLUSIONS: Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.

Adult↗
PubMed2003

Expression of ADAM-9 mRNA and protein in human breast cancer.

The ADAMs (a disintegrin and metalloprotease) are membrane proteins containing both protease and adhesion domains and thus may be potentially important in cancer invasion and metastasis. The aim of our study was to investigate the distribution and potential clinical significance of ADAM-9 in breast cancer. ADAM-9 expression was measured using both reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. ADAM-9 mRNA was expressed more frequently in both breast carcinomas (72/110, 66%) and fibroadenomas (21/38, 55%) compared to normal breast tissue (6/25, 24%) (p = 0.0004, p = 0.028, respectively). Multiple forms of ADAM-9 protein were detected by Western blotting, i.e., at 124, 84 and 48 kDa under reducing conditions and at 115, 76, 55, 52 and 46 kDa under nonreducing conditions. The 84 and 55 kDa forms were detected more frequently in the primary cancers compared to normal breast tissue (p < 0.0001, p = 0.0002, respectively). In addition, relative levels of the 84 kDa mature form were significantly higher in the primary cancers than in the fibroadenomas (p = 0.003), while the reverse was found for the 124 kDa precursor form (p = 0.026). In the carcinomas, the 84 kDa form of ADAM-9 protein was expressed at higher levels in node-positive than node-negative cancers (p = 0.05) and correlated positively with HER-2/neu protein levels (r = 0.313, p = 0.016). This is the first report to describe expression of any ADAM in a large number of human carcinomas.

ADAM Proteins↗
PubMed2003

Caspase 3 in breast cancer.

PURPOSE: An inability to undergo apoptosis is widely thought to contribute to both tumorigenesis and tumor progression. One of the key mediators of apoptosis is the thiol protease caspase 3. In this investigation, caspase 3 mRNA and protein expression in breast cancer was examined. EXPERIMENTAL DESIGN: Caspase 3 was measured at the mRNA level using reverse transcription-PCR and at the protein level using both Western blotting and activity assays. Levels of apoptosis were determined using an ELISA, which detects nucleosomes released during DNA fragmentation. RESULTS: Relative levels of caspase 3 mRNA were similar in breast carcinomas (n = 103), fibroadenomas (n = 25), and normal breast tissues (n = 6). However, levels of both the precursor and active forms of caspase 3 were significantly higher in carcinomas compared with both fibroadenomas (P = 0.0188) and normal breast tissues (P = 0.0002). Levels of apoptosis were also highest in the carcinomas and correlated significantly with active caspase 3 levels (r = 0.481; P = 0.0003). In the carcinomas, expression of caspase 3 showed no significant relationship with either tumor size, tumor grade, nodal status, or steroid receptor status but was significantly higher in ductal carcinomas than in lobular carcinomas (P = 0.0188). CONCLUSIONS: We conclude that rates of apoptosis as measured by both caspase 3 activation and nucleosome release are higher in breast cancer than in nonmalignant breast tissue. This finding would appear to conflict with the widely held belief that apoptosis is reduced in malignancy. The proliferation:apoptosis ratio, however, may be higher in carcinomas than in the corresponding normal tissue.

Apoptosis↗