Niall OHiggins - Academia.edu (original) (raw)
Papers by Niall OHiggins
Cancer Letters, 2009
The Breast Cancer Metastasis Suppressor 1 (BRMS1) belongs to an expanding category of proteins ca... more The Breast Cancer Metastasis Suppressor 1 (BRMS1) belongs to an expanding category of proteins called metastasis suppressors that demonstrate in vivo metastasis suppression while still allowing growth of the orthotopic tumor. Since BRMS1 decreases either the expression or function of multiple mediators implicated in resistance to chemotherapy (NF-κB, AKT, EGFR), we asked whether breast carcinoma cells expressing BRMS1 could be sensitized upon exposure to commonly used therapeutic agents that inhibit some of these same cellular mediators as BRMS1. In this report, we demonstrate that chemosensitivity of breast cancer cells is preserved in the presence of BRMS1. Further, BRMS1 does not change expression of AKT isoforms or PTEN, implicated in chemoresistance to common drug agents. Overall, our data with two different metastatic breast cancer cell lines indicates that BRMS1 expression status may not interfere with the response to commonly used chemotherapeutic agents in the management of solid tumors such as breast cancer. Since tumor protein expression analysis increasingly guides therapy decisions, our data may be of clinical benefit in disease management including profiling for BRMS1 expression before start of therapy.
British Journal of Cancer, 2006
Overexpression of HER2 is associated with an adverse prognosis in breast cancer. Despite this, th... more Overexpression of HER2 is associated with an adverse prognosis in breast cancer. Despite this, the mechanism of its transcriptional regulation remains poorly understood. PEA3, a MAP kinase (MAPK)-activated member of the Ets transcription factor family has been implicated in the transcriptional regulation of HER2. The direction of its modulation remains controversial. We assessed relative levels of PEA3 expression and DNA binding in primary breast cultures derived from patient tumours (n ¼ 18) in the presence of an activated MAPK pathway using Western blotting and shift analysis. Expression of PEA3 in breast tumours from patients of known HER2 status (n ¼ 107) was examined by immunohistochemistry. In primary breast cancer cell cultures, growth factors induced interaction between PEA3 and its DNA response element. Upregulation of PEA3 expression in the presence of growth factors associated with HER2 positivity and axillary lymph node metastasis (P ¼ 0.034 and 0.049, respectively). PEA3 expression in breast cancer tissue associated with reduced disease-free survival (Po0.001), Grade III tumours (Po0.0001) and axillary lymph node metastasis (P ¼ 0.026). Co-expression of PEA3 and HER2 significantly associated with rate of recurrence compared to patients who expressed HER2 alone (P ¼ 0.0039). These data support a positive role for PEA3 in HER2-mediated oncogenesis in breast cancer.
Thrombosis and haemostasis, 2004
Journal of Surgical Research, 2004
Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgica... more 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. 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. 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. 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.
The Journal of Clinical Endocrinology & Metabolism, 2004
Estrogen receptor (ER)-␣ and ER- function as transcription factors, and both interact with nucle... more Estrogen receptor (ER)-␣ and ER- function as transcription factors, and both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that coregulators are expressed in breast cancer and may be differentially recruited by ERs in the presence of estrogen and tamoxifen. ER- was found to be expressed more frequently in node-negative patients (P < 0.05). Expression of steroid receptor coactivator-1 (SRC-1) was associated with nodal positivity (P < 0.05) and resistance to endocrine treatment (P < 0.001). The spatial coexpression of ER-␣, ER-, and the coregulatory proteins was established using immunofluorescence. In both cell lines (MCF-7 and T47D) and in primary breast cancer cell cultures, -estradiol up-regulated ER- and coregulator protein expression and increased ER-␣/ER- interaction with the estrogen response element (ERE). 4-Hydroxy-tamoxifen (4-OHT) increased ER-␣ and silencing mediator for retinoid and thyroid receptors (SMRT) expression and increased ER-ERE binding. SRC-1 and SMRT were identified at the ER-ERE complex, and interactions between ER isoforms and coregulatory proteins were determined using immunoprecipitation. Both ER-␣ and ER- preferentially bound SRC-1 in the presence of -estradiol. Conversely, in cells treated with 4-OHT, ER-␣ and ER- bound SMRT. Differential recruitment of SRC-1 and SMRT by ER-␣ and ER- in the presence of -estradiol and 4-OHT may be central to the response of the tumor to endocrine treatment. (J Clin Endocrinol Metab 89: 375-383, 2004) Abbreviations: AIB1, Amplified in breast cancer coactivator; ER, estrogen receptor; ERE, estrogen response element; 4-OHT, 4-hydroxytamoxifen; SERM, selective ER modulator; SMRT, silencing mediator for retinoid and thyroid receptors; SRC-1, steroid receptor coactivator-1. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community.
Irish Journal of Medical Science, 2002
Irish Journal of Medical Science, 2002
Irish Journal of Medical Science, 1998
Introduction: Medullary carcinoma of the thyroid (MTC) is a rare tumour which occurs in both spor... more Introduction: Medullary carcinoma of the thyroid (MTC) is a rare tumour which occurs in both sporadic and hereditary forms. Mutations of the RET proto-oncogene have been identified in hereditary forms. The aim of our study was to confirm or exclude familial disease by examining for germline mutations in the RET proto-oncogene in patients with medullary thyroid carcinoma. Methods: Nine patients with medullary thyroid carcinoma and 4 of their children were studied. Peripheral blood was used to examine for mutations in the RET proto-oncogene. When this was not available, archival thyroid tissue was used. Results: Seven patients had clinically sporadic tumours, confirmed by mutational analysis of RET. Four children were at risk of being carriers of a mutated gene, as their fathers had histologically proven MTC and had tested positive for the mutation at codon 618 on exon 10 of the RET proto-oncogene. Three of these children carried the 618 mutation. To date, 2 have had a prophylactic thyroidectomy, the pathology of which revealed C-cell hyperplasia. One child had familial disease excluded by mutational analysis. One patient had a clinical diagnosis of MEN2B confirmed by detection of the 918 mutation on exon 16 of the RET proto-oncogene. Conclusions: RET proto-oncogene analysis is a reliable method of differentiating familial from sporadic MTC. Mutational information determines which family members of affected kindreds are at risk of developing the disease and can be used to affect clinical management.
International Journal of Cancer, 2000
Matrix metalloproteinases (MMP) types 2 and 9 (also known as gelatinase A and B) are thought to b... more Matrix metalloproteinases (MMP) types 2 and 9 (also known as gelatinase A and B) are thought to be causally involved in cancer invasion and metastasis. In normal as well as in malignant tissue, both these MMPs occur in multiple forms such as inactive precursors, active enzymes and enzyme-inhibitor complexes. Using newly developed quantitative activity assays, the levels of active MMP-2, total (active and activatable) MMP-2 and total MMP-9 were found to be significantly higher in breast carcinomas than in fibroadenomas. In addition, active MMP-2 and MMP-9 were detected more frequently in malignant than in benign breast carcinoma. These new quantitative activity assays are likely to be of use in studying the mechanism of action of both MMP-2 and -9, assessing their potential prognostic value in different cancers and in the design of MMP inhibitors for preventing cancer metastasis.
Journal of the American College of Surgeons, 2007
Evaluating the size of multifocal breast cancer for staging purposes is problematic. Historically... more Evaluating the size of multifocal breast cancer for staging purposes is problematic. Historically, the largest tumor focus in isolation has been used to stage multifocal disease and determine optimum adjuvant therapy. This study compared multifocal and unifocal breast cancer to determine if multifocal breast cancer presents at a higher stage. We performed a retrospective review of a prospectively collected database of 328 patients who underwent sentinel lymph node biopsy over a 7-year period. Clinical presentation and histopathologic features of multifocal breast cancer were compared with those of unifocal disease. Fifty-three (16%) patients presented with multifocal disease. Higher tumor grade was observed in the multifocal tumors compared with unifocal tumors (34% versus 20% grade III tumor, multifocal versus unifocal disease; p=0.03). Use of combined tumor focus diameter upstaged (pT status) 18 (34%) patients with multifocal tumors. There was no difference in nodal positivity based on pT status between largest and combined diameter multifocal disease. Combined tumor diameter in multifocal breast cancer does not correspond with an increase in sentinel node positivity and should not be used for staging purposes.
British Journal of Cancer, 2004
Breast Cancer Research, 2000
The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary... more The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix. Currently, at least 19 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high levels of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours
British Journal of Cancer, 2003
Surgery today, 2005
Parathyroid adenomas account for most cases of primary hyperparathyroidism (1 degrees HPT). Certa... more 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.
BMC cancer, Jan 23, 2006
The association of nipple discharge with breast carcinoma has resulted in numerous women undergoi... more The association of nipple discharge with breast carcinoma has resulted in numerous women undergoing exploratory surgery to exclude malignancy. The aim of this study was to determine whether pre-operative factors can identify those patients that are most at risk of carcinoma. All patients over a 14-year period (1991-2005) who had a microdochectomy or subareolar exploration for the evaluation of nipple discharge were assessed. Patient characteristics, pre-operative imaging and pathological findings were analysed. Of the 211 patients included in this study, 116 patients had pathological (unilateral, uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with pathological discharge and 2.4% (n = 2) of patients with non-pathological discharge were diagnosed with carcinoma. Overall, major duct excision resulted in the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in 39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 11...
Journal of Surgical Oncology, 1999
Irish Journal of Medical Science, 2002
International Journal of Cancer, 2005
Existing serum-based markers for breast cancer all lack organ specificity. Mammaglobin A (MGA) is... more 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.
Cancer Letters, 2009
The Breast Cancer Metastasis Suppressor 1 (BRMS1) belongs to an expanding category of proteins ca... more The Breast Cancer Metastasis Suppressor 1 (BRMS1) belongs to an expanding category of proteins called metastasis suppressors that demonstrate in vivo metastasis suppression while still allowing growth of the orthotopic tumor. Since BRMS1 decreases either the expression or function of multiple mediators implicated in resistance to chemotherapy (NF-κB, AKT, EGFR), we asked whether breast carcinoma cells expressing BRMS1 could be sensitized upon exposure to commonly used therapeutic agents that inhibit some of these same cellular mediators as BRMS1. In this report, we demonstrate that chemosensitivity of breast cancer cells is preserved in the presence of BRMS1. Further, BRMS1 does not change expression of AKT isoforms or PTEN, implicated in chemoresistance to common drug agents. Overall, our data with two different metastatic breast cancer cell lines indicates that BRMS1 expression status may not interfere with the response to commonly used chemotherapeutic agents in the management of solid tumors such as breast cancer. Since tumor protein expression analysis increasingly guides therapy decisions, our data may be of clinical benefit in disease management including profiling for BRMS1 expression before start of therapy.
British Journal of Cancer, 2006
Overexpression of HER2 is associated with an adverse prognosis in breast cancer. Despite this, th... more Overexpression of HER2 is associated with an adverse prognosis in breast cancer. Despite this, the mechanism of its transcriptional regulation remains poorly understood. PEA3, a MAP kinase (MAPK)-activated member of the Ets transcription factor family has been implicated in the transcriptional regulation of HER2. The direction of its modulation remains controversial. We assessed relative levels of PEA3 expression and DNA binding in primary breast cultures derived from patient tumours (n ¼ 18) in the presence of an activated MAPK pathway using Western blotting and shift analysis. Expression of PEA3 in breast tumours from patients of known HER2 status (n ¼ 107) was examined by immunohistochemistry. In primary breast cancer cell cultures, growth factors induced interaction between PEA3 and its DNA response element. Upregulation of PEA3 expression in the presence of growth factors associated with HER2 positivity and axillary lymph node metastasis (P ¼ 0.034 and 0.049, respectively). PEA3 expression in breast cancer tissue associated with reduced disease-free survival (Po0.001), Grade III tumours (Po0.0001) and axillary lymph node metastasis (P ¼ 0.026). Co-expression of PEA3 and HER2 significantly associated with rate of recurrence compared to patients who expressed HER2 alone (P ¼ 0.0039). These data support a positive role for PEA3 in HER2-mediated oncogenesis in breast cancer.
Thrombosis and haemostasis, 2004
Journal of Surgical Research, 2004
Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgica... more 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. 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. 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. 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.
The Journal of Clinical Endocrinology & Metabolism, 2004
Estrogen receptor (ER)-␣ and ER- function as transcription factors, and both interact with nucle... more Estrogen receptor (ER)-␣ and ER- function as transcription factors, and both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that coregulators are expressed in breast cancer and may be differentially recruited by ERs in the presence of estrogen and tamoxifen. ER- was found to be expressed more frequently in node-negative patients (P < 0.05). Expression of steroid receptor coactivator-1 (SRC-1) was associated with nodal positivity (P < 0.05) and resistance to endocrine treatment (P < 0.001). The spatial coexpression of ER-␣, ER-, and the coregulatory proteins was established using immunofluorescence. In both cell lines (MCF-7 and T47D) and in primary breast cancer cell cultures, -estradiol up-regulated ER- and coregulator protein expression and increased ER-␣/ER- interaction with the estrogen response element (ERE). 4-Hydroxy-tamoxifen (4-OHT) increased ER-␣ and silencing mediator for retinoid and thyroid receptors (SMRT) expression and increased ER-ERE binding. SRC-1 and SMRT were identified at the ER-ERE complex, and interactions between ER isoforms and coregulatory proteins were determined using immunoprecipitation. Both ER-␣ and ER- preferentially bound SRC-1 in the presence of -estradiol. Conversely, in cells treated with 4-OHT, ER-␣ and ER- bound SMRT. Differential recruitment of SRC-1 and SMRT by ER-␣ and ER- in the presence of -estradiol and 4-OHT may be central to the response of the tumor to endocrine treatment. (J Clin Endocrinol Metab 89: 375-383, 2004) Abbreviations: AIB1, Amplified in breast cancer coactivator; ER, estrogen receptor; ERE, estrogen response element; 4-OHT, 4-hydroxytamoxifen; SERM, selective ER modulator; SMRT, silencing mediator for retinoid and thyroid receptors; SRC-1, steroid receptor coactivator-1. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community.
Irish Journal of Medical Science, 2002
Irish Journal of Medical Science, 2002
Irish Journal of Medical Science, 1998
Introduction: Medullary carcinoma of the thyroid (MTC) is a rare tumour which occurs in both spor... more Introduction: Medullary carcinoma of the thyroid (MTC) is a rare tumour which occurs in both sporadic and hereditary forms. Mutations of the RET proto-oncogene have been identified in hereditary forms. The aim of our study was to confirm or exclude familial disease by examining for germline mutations in the RET proto-oncogene in patients with medullary thyroid carcinoma. Methods: Nine patients with medullary thyroid carcinoma and 4 of their children were studied. Peripheral blood was used to examine for mutations in the RET proto-oncogene. When this was not available, archival thyroid tissue was used. Results: Seven patients had clinically sporadic tumours, confirmed by mutational analysis of RET. Four children were at risk of being carriers of a mutated gene, as their fathers had histologically proven MTC and had tested positive for the mutation at codon 618 on exon 10 of the RET proto-oncogene. Three of these children carried the 618 mutation. To date, 2 have had a prophylactic thyroidectomy, the pathology of which revealed C-cell hyperplasia. One child had familial disease excluded by mutational analysis. One patient had a clinical diagnosis of MEN2B confirmed by detection of the 918 mutation on exon 16 of the RET proto-oncogene. Conclusions: RET proto-oncogene analysis is a reliable method of differentiating familial from sporadic MTC. Mutational information determines which family members of affected kindreds are at risk of developing the disease and can be used to affect clinical management.
International Journal of Cancer, 2000
Matrix metalloproteinases (MMP) types 2 and 9 (also known as gelatinase A and B) are thought to b... more Matrix metalloproteinases (MMP) types 2 and 9 (also known as gelatinase A and B) are thought to be causally involved in cancer invasion and metastasis. In normal as well as in malignant tissue, both these MMPs occur in multiple forms such as inactive precursors, active enzymes and enzyme-inhibitor complexes. Using newly developed quantitative activity assays, the levels of active MMP-2, total (active and activatable) MMP-2 and total MMP-9 were found to be significantly higher in breast carcinomas than in fibroadenomas. In addition, active MMP-2 and MMP-9 were detected more frequently in malignant than in benign breast carcinoma. These new quantitative activity assays are likely to be of use in studying the mechanism of action of both MMP-2 and -9, assessing their potential prognostic value in different cancers and in the design of MMP inhibitors for preventing cancer metastasis.
Journal of the American College of Surgeons, 2007
Evaluating the size of multifocal breast cancer for staging purposes is problematic. Historically... more Evaluating the size of multifocal breast cancer for staging purposes is problematic. Historically, the largest tumor focus in isolation has been used to stage multifocal disease and determine optimum adjuvant therapy. This study compared multifocal and unifocal breast cancer to determine if multifocal breast cancer presents at a higher stage. We performed a retrospective review of a prospectively collected database of 328 patients who underwent sentinel lymph node biopsy over a 7-year period. Clinical presentation and histopathologic features of multifocal breast cancer were compared with those of unifocal disease. Fifty-three (16%) patients presented with multifocal disease. Higher tumor grade was observed in the multifocal tumors compared with unifocal tumors (34% versus 20% grade III tumor, multifocal versus unifocal disease; p=0.03). Use of combined tumor focus diameter upstaged (pT status) 18 (34%) patients with multifocal tumors. There was no difference in nodal positivity based on pT status between largest and combined diameter multifocal disease. Combined tumor diameter in multifocal breast cancer does not correspond with an increase in sentinel node positivity and should not be used for staging purposes.
British Journal of Cancer, 2004
Breast Cancer Research, 2000
The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary... more The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix. Currently, at least 19 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high levels of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours
British Journal of Cancer, 2003
Surgery today, 2005
Parathyroid adenomas account for most cases of primary hyperparathyroidism (1 degrees HPT). Certa... more 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.
BMC cancer, Jan 23, 2006
The association of nipple discharge with breast carcinoma has resulted in numerous women undergoi... more The association of nipple discharge with breast carcinoma has resulted in numerous women undergoing exploratory surgery to exclude malignancy. The aim of this study was to determine whether pre-operative factors can identify those patients that are most at risk of carcinoma. All patients over a 14-year period (1991-2005) who had a microdochectomy or subareolar exploration for the evaluation of nipple discharge were assessed. Patient characteristics, pre-operative imaging and pathological findings were analysed. Of the 211 patients included in this study, 116 patients had pathological (unilateral, uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with pathological discharge and 2.4% (n = 2) of patients with non-pathological discharge were diagnosed with carcinoma. Overall, major duct excision resulted in the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in 39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 11...
Journal of Surgical Oncology, 1999
Irish Journal of Medical Science, 2002
International Journal of Cancer, 2005
Existing serum-based markers for breast cancer all lack organ specificity. Mammaglobin A (MGA) is... more 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.