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Biomedical subjects

N O'Higgins

Publications and source records attributed to N O'Higgins.

At least 55 records · Page 3Linked to original sources

Towards a high standard of surgical oncology throughout Europe.

To retain their role in co-ordinating the multidisciplinary management of cancer, surgeons must adapt to new developments in oncology. In addition to technical skill in operative surgery, all surgeons treating cancer patients must add new information in tumour biology, chemotherapy and radiotherapy to their range of knowledge. Such a broad approach is needed nowadays in order to give a valid clinical opinion and is indispensable in the planning of operative strategies. Although considerable differences in cancer treatment exist within Europe, centres of excellence can be defined. The European Society of Surgical Oncology is planning, with the co-operation of national surgical oncology groups, to devise Guidelines for Good Practice in Surgical Oncology which will be acceptable throughout Europe. Identification of centres for training, registration and accreditation of trainees and a system of continuing education for established surgical oncologists will be proposed. The aims of these proposals are (i) to promote excellence in treatment, (ii) to facilitate an exchange of information, (iii) to encourage participation in clinical trials, (iv) to improve education of medical and para-medical personnel about oncology and (v) to point the way to research opportunities. In medical practice abundant evidence exists that (a) a high standard of clinical care promotes educational activity, (b) good education stimulates research and (c) research in turn activates improvements in service and care. Because of its complexity and the need to involve many disciplines in its management, the treatment of patients with cancer requires a high standard of professional training and competence. Moreover, because of rapid developments in cancer research and treatment, mechanisms for continuing medical education for oncologists are essential.

Europe↗

Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer.

Results from model tumour systems suggest that either increased levels of certain metalloproteases (MMPs) or decreased levels of their inhibitors correlate with metastatic potential. In this study, levels of two MMPs, i.e. MMP-8 and -9, and their inhibitor tissue inhibitor of metalloprotease type 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in human breast tumours. Levels of MMP-8 and -9 correlated significantly with each other, but neither MMP correlated with urokinase plasminogen activator. Levels of both MMP-8 and -9 were also significantly related to levels of TIMP-1. In contrast, neither MMP correlated with plasminogen activator inhibitor. No relationship was found between MMP-8, MMP-9 or TIMP-1 and either tumour size or metastasis to axillary nodes. MMP-8 and -9 levels were inversely related to levels of oestrogen receptors. MMP-8 but not MMP-9 levels were also inversely correlated with progesterone receptor levels. It is concluded that the assay for MMP-8 and -9 described here will permit the evaluation of these proteases as prognostic markers in cancer.

Biomarkers, Tumor↗

Urokinase plasminogen activator as a prognostic marker in different subgroups of patients with breast cancer.

BACKGROUND: Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. Previously, uPA was shown to be an independent prognostic marker in breast cancer. The aim of this study were to evaluate uPA as a prognostic marker in different subgroups of patients with breast cancer. METHODS: Urokinase plasminogen activator was assayed by enzyme-linked immunosorbent assay in detergent extracts of human breast tumors. RESULTS: Using both disease free interval (DFI) and overall survival (OS) as end points, uPA was an indicator of prognosis in the following groups of patients: those with positive axillary nodes, those who were estrogen receptor (ER)-positive, women younger than 50 years of age, and women older than 50 years of age. For patients with negative axillary lymph nodes, uPA was a significant prognostic marker using DFI as an end point and was almost statistically significant (P = 0.055) using OS as end point. In patients who were ER-negative, uPA levels showed no significant relationship with patient outcome. CONCLUSIONS: Urokinase plasminogen activator is a significant prognostic marker in most of the major subgroups of patients with breast cancer and may be a marker for patients with negative axillary lymph nodes.

Animals↗

Assay of the c-erbB-2 oncogene encoded protein by ELISA and immunocytochemistry in human breast cancer.

The c-erbB-2 gene is amplified in a wide variety of different adenocarcinomas. Generally, gene amplification correlates with increased expression of the c-erbB-2 oncoprotein. Previous assays for the c-erbB-2 oncoprotein have been qualitative or semi-quantitative. In this investigation using human breast cancers, c-erbB-2 oncoprotein levels as measured by enzyme-linked immunosorbent assay (ELISA) correlated significantly with semi-quantitation by immunocytochemistry (r = 0.843, P < 0.0001, n = 97). The cut-off point for the ELISA which gave the strongest agreement with immunocytochemistry was 15 units/micrograms protein. It is concluded that detection of c-erbB-2 oncoprotein by ELISA is quantitative and objective.

Biomarkers, Tumor↗

Aspects of breast cancers.

Breast cancer is the commonest killing malignant disease of women in the European Community. The average annual age standardised mortality rate among the 12 EEC countries ranges from 28.5 to 13.7 per 100,000 females. In Ireland, breast cancer is treated primarily by general surgeons. At our Breast Institute at St. Vincent's Hospital where we see 100 patients with breast diseases weekly it is policy to recommend quadrantectomy, total axillary dissection and radiotherapy (QU.A.R.T.) for patients with T1 and T2 tumours if they are peripherally placed within the breast. Complete axillary dissection in early breast cancer provides accurate staging and virtually eliminates axillary recurrence and the dissection is standardised and audited in our unit. Audit of axillary dissection improves the lymph node yield and enhances the completeness of the procedure. Sophisticated mammography improves the detection of small tumours but even excellent mammography may fail to identify malignant disease. Screening programmes for early breast cancer detection should be based on clinical examination in addition to mammography and some 15% of our patients with palpable breast cancer had falsely negative mammograms. Before operation, extensive scintigraphy and sonography is carried out before primary treatment is undertaken. After treatment, clinical and biochemical surveillance is carried out. We have found the lysosomal protease, Cathepsin D to be a useful marker of progressive disease and prognosis in patients with breast cancer. Routine postoperative CEA and CA15.3 are also valuable markers and a high or rising CA15.3 often precedes clinical or investigative evidence of recurrence. In addition, assay of c-erB-2 protein by ELISA is also a simple, rapid quantitative prognostic guide in patients with breast cancer.

Biomarkers, Tumor↗

Enzyme-linked immunosorbent assay of c-erbB-2 oncoprotein in breast cancer.

Amplification or increased expression of the c-erbB-2 gene has previously been reported to be a prognostic marker for breast cancer. Gene amplification is usually measured by Southern blotting, whereas increased protein expression is usually detected by immunocytochemistry. We measured c-erbB-2 protein with an enzyme-linked immunosorbent assay (ELISA). High concentrations of oncoprotein were found in 25 of 161 (16%) primary breast cancers and in 3 of 6 (50%) breast cancer metastases. High concentrations were not found in normal breast tissue or benign breast tumors. In the primary cancers, high concentrations of c-erbB-2 protein were found more frequently (a) in estrogen receptor-negative tumors than in estrogen receptor-positive tumors, (b) in progesterone receptor-negative tumors than in progesterone-positive tumors, and (c) in axillary node-positive cancers than in node-negative cancers. Patients with tumors containing high amounts of the c-erbB-2 protein had a significantly shorter (P less than 0.001) disease-free interval and overall survival rate than did patients with low amounts. We conclude that assay of c-erbB-2 protein by ELISA is simple, rapid, and quantitative and offers important prognostic information in breast cancer.

Biomarkers, Tumor↗

Cathepsin D concentration in breast cancer cytosols: correlation with disease-free interval and overall survival.

Cathepsin D (CD) is an aspartyl protease implicated in cancer metastasis. In this study of 331 patients, we show that patients with primary breast carcinomas containing high concentrations of CD have a significantly shorter disease-free interval (chi-square = 4.28, P < 0.05) and overall survival (chi-square = 7.7, P < 0.01) than patients with low concentrations. CD as a prognostic marker for overall survival was equally valuable for women younger (chi-square = 4.39, P < 0.05) and older (chi-square = 3.97, P < 0.05) than 50 years. CD was also a significant prognostic marker for overall survival within the estradiol receptor (ER)-positive subgroup of patients (chi-square = 5.79, P < 0.025), but not in the ER-negative subgroup. Patients with tumors containing high concentrations of CD and low concentrations of ER had shorter disease-free intervals (chi-square = 15.1, P < 0.001) and lower overall survival (chi-square = 20.9, P < 0.001) than patients with high concentrations of ER but low concentrations of CD.

Biomarkers, Tumor↗

Cathepsin D concentration in breast cancer cytosols: correlation with biochemical, histological, and clinical findings.

Cathepsin D (CD, EC 3.4.23.5) is a lysosomal protease induced by estrogen in certain estrogen receptor (ER)-positive breast cancer cell lines but produced constitutively by ER-negative cell lines. Our aims in this investigation were to study the distribution of CD in human breast cancers and to relate its concentrations to various biochemical, histological, and clinical characteristics. The concentrations of CD were significantly higher in breast carcinomas than in either normal breast tissues or benign breast tumors. In primary carcinomas, CD concentrations did not correlate with the concentrations of ER or with the estrogen-inducible protease t-PA. However, CD concentrations did correlate weakly but significantly with both UK-PA antigen and UK-PA activity. Also, CD concentrations did not correlate with either tumor stage or axillary node status but did correlate significantly with tumor grade. Patients with cancers containing high concentrations of CD had a significantly shorter overall survival than did patients with low concentrations of the enzyme.

Breast Neoplasms↗

Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer.

Urokinase plasminogen activator (UK-PA) is a serine protease implicated in cancer invasion and metastasis. In this investigation, patients with breast cancers containing high levels of UK-PA antigen had significantly higher risk of early disease recurrence and shorter overall survival than did patients with low levels of the protein. In univariate analysis, UK-PA was a more powerful discriminator for disease-free interval than axillary node status, tumor size, or estradiol receptor. For overall survival, UK-PA as a prognostic marker, was of similar magnitude to axillary node status but stronger than that of tumor size or estradiol receptor. In multivariate analysis, for both disease-free interval and survival, UK-PA was an independent risk factor, being independent of tumor size, axillary node status, and estradiol receptor. UK-PA appears to be a new and independent prognostic marker in breast cancer.

Antigens, Neoplasm↗

An audit of road traffic accident victims requiring admission to hospital.

In this retrospective study, the case notes of all road traffic accident (RTA) victims admitted to one hospital during a 12 month period (1986-1987) were analysed. One hundred and twenty five patients were identified. The male/female ratio was 2:1 and the mean age was 34 years. The peak time of hospital arrival was midnight-1 am (18 cases, 15.6%) followed by the period 21.00-22.00 (10 cases, 18.6%. A total of 84 cases (73%) arrived between 17.00-8.00. The mean time spent in the accident and emergency department was 180 minutes. The severity of the victims' injuries was evaluated, using the Injury Severity Score (ISS). The mean ISS score was 9, with a range 1-75. There was a 33% mortality for patients with an ISS of 12 or more. Initial assessment of the RTA victims was performed by the SHO in 77% and by the registrar in 23% of cases. It is paramount that RTA victims with multiple injuries are rapidly transferred to an appropriate centre with the necessary expertise and facilities.

Abbreviated Injury Scale↗