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Biomedical subjects

M J Duffy

Publications and source records attributed to M J Duffy.

At least 91 records · Page 5Linked to original sources

CA 125 as a tumour marker in epithelial ovarian cancer.

CA 125, a high molecular weight glycoprotein, was measured in sera from patients with epithelial ovarian cancer, patients with benign gynaecological disease and in patients with non-ovarian adenocarcinomas. High levels (greater than 35 U/ml) were found in 48/50 patients with active ovarian cancer but in only 3/26 patients who had an ovarian cancer previously diagnosed but who were apparently disease free. 6/23 patients with non-ovarian adenocarcinomas as well as 4/18 patients with benign gynaecological disease also had elevated levels. CA 125 levels were higher in serious than non-serous ovarian cancers and tended to increase with increasing stage. In all of 19 patients with ovarian cancer who responded to treatment CA 125 levels fell while 17/20 with progressive disease showed a rise. In 7/8 patients, serial determination of CA 125 showed a rise before the clinical detection of recurrence, the median lead-time being 3.5 months. We conclude that CA 125 is an excellent marker in the management of patients with epithelial ovarian cancers.

Antigens, Tumor-Associated, Carbohydrate↗

New cancer markers.

In recent years many new and improved cancer markers have become available. From a clinical point of view, the most useful of the new markers include CA 19-9 for pancreatic adenocarcinoma, CA 125 for epithelial ovarian cancer, CA 15-3 for breast cancer, prostate specific antigen for prostatic adenocarcinoma, placental alkaline phosphatase for testicular seminomas and neuron-specific enolase for small cell carcinoma of lung. None of these new markers are specific for cancer. Furthermore, none are organ specific, except prostate specific antigen for prostatic tissue. The main application of these markers is in monitoring patients with the specific malignancies indicated. Whether routine use of any of these new markers leads to higher quality of life or enhanced survival remains to be determined.

Antigens, Neoplasm↗

Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report.

Plasminogen activator is a serine protease which exists in two forms, known as tissue-type plasminogen activator and urokinase-type plasminogen activator. Here, we show that urokinase-type plasminogen activator activity in primary breast carcinomas correlates with both size of tumor and number of axillary nodes with metastases. Patients with primary carcinomas containing high levels of urokinase-type plasminogen activator activity had a significantly shorter disease-free interval than patients with low levels of activity. It is concluded that urokinase-plasminogen activator may be a new prognostic marker in breast cancer.

Biomarkers, Tumor↗

Tissue-type plasminogen activator, a new prognostic marker in breast cancer.

Plasminogen activator is a protease existing in two forms known as tissue-type and urokinase-type plasminogen activator. In this investigation, patients with breast cancers containing high levels of the tissue-type enzyme had a significantly longer disease-free interval and survival compared with patients with low levels of the enzyme. For the disease-free interval, the effect of tissue-type plasminogen activator was independent of tumor stage, grade, axillary node involvement, and estradiol receptor status. It is concluded that tissue-type plasminogen activator is a new prognostic marker in breast cancer.

Breast Neoplasms↗

Do proteases play a role in cancer invasion and metastasis?

The main difference between a benign and malignant tumor is the ability of the malignant form to invade normal tissue and spread or metastasize to distant sites throughout the body. It is the ability to form metastasis which makes cancer such a difficult disease to treat. Evidence suggesting that proteolytic enzymes are involved in cancer spread is as follows: proteases are involved in normal destructive events and tissue remodelling, correlations exist between different protease activities and metastatic potential in model tumor systems, inhibitors and antibodies against proteases inhibit metastasis in model systems and the finding of highest levels of protease activity at the invading front in tumors. The most likely mechanism by which proteases could mediate metastasis is by catalyzing degradation of the extracellular matrix and basement membranes. It is concluded that if proteases could be proved to play a role in the spread of human cancers, inhibition of these enzymes could open up new therapeutic approaches for the control of malignancy.

Humans↗

Tissue-type plasminogen activator in breast cancer: relationship with estradiol and progesterone receptors.

Plasminogen activator (PA) is an estradiol-inducible enzyme and therefore a potential marker for a functional estradiol receptor (ER) in human breast carcinomas. In this investigation tissue-type PA (t-PA) correlated significantly with both ER and progesterone receptors (PR) in human breast carcinomas. In contrast, neither total PA activity nor urokinase-like PA showed any significant correlation with either ER or PR. Other proteases such as a trypsin-like protease, a chymotrypsin-like protease, and cathepsin B also showed no correlation with ER and PR. It was concluded that the t-PA form of PA may be a marker for a functional ER in breast carcinoma and thus be of value in predicting hormone-dependent breast cancers.

Breast Neoplasms↗

Estradiol receptors in human breast carcinomas assayed by use of monoclonal antibodies.

Our aim here was to compare a new enzyme immunoassay for estradiol receptors (ER) in breast cancer with a standard assay involving radiolabeled estradiol. A significant correlation was obtained between the standard binding assay and immunoassay (rs = 0.945, p less than 0.001, n = 100). Immunoreactive ER were also found in endometrial carcinomas but not in lung carcinomas, malignant melanomas, or basal cell carcinomas. Patients with breast cancers containing immunoreactive ER survived significantly longer after operation than patients whose tumor lacked immunoreactive ER. This immunoassay for ER is simpler than the binding assay and requires less time and tissue.

Antibodies, Monoclonal↗

Multiple forms of plasminogen activator in human breast tumors.

Total plasminogen activator (PA) activity, tissue-type PA (t-PA) activity, urokinase-like PA activity, and immunoreactive t-PA were measured in benign breast tumors (fibroadenomas), primary breast carcinomas, axillary node metastases, and chest wall recurrences. Total PA activity did not differ significantly in the different types of tumors. However, benign tumors contained predominantly t-PA activity. Urokinase-like PA activity was significantly higher in the malignant tumors compared with the benign group. Both t-PA activity and immunoreactive t-PA were significantly lower in chest wall recurrences compared with primary carcinomas. The ratio of t-PA to urokinase activity was significantly decreased between stages 1 and 3 in the primary tumors. Also, immunoreactive t-PA levels were significantly lower in stages 2 and 3 compared with stage 1. No correlation was found between PA (either total or its different forms) and tumor grade, histological type, or the presence or absence of axillary node metastases.

Adenofibroma↗

Plasminogen activator and cancer.

Plasminogen activator is a protease which catalyses the conversion of the inactive plasminogen to the active plasmin. Most transformed cell lines and solid tumors produce elevated levels of plasminogen activator compared with nontransformed counterparts. This increased synthesis of plasminogen activator may play a role in tumorigenesis, cancer invasion and metastasis. Measurement of plasminogen activator in tumor extracts and body fluids may provide diagnostic and prognostic information. Finally, since plasminogen activator is an estradiol-inducible enzyme, its measurement in breast carcinomas might be a marker for a functional estrogen receptor.

Animals↗

CEA-like material in cytosols from human breast carcinomas. Correlation with biochemical and pathologic parameters.

CEA-like material was found in 51 of 62 primary human breast carcinomas and in only 2 of 12 fibroadenomas. Levels of carcinoma CEA-like material correlated weakly with cytoplasmic estradiol receptor levels, total cytosol estrogens, and cytosol progesterone. Levels of CEA-like material showed no significant correlation with carcinoma stage, grade, cellularity, size or histologic type. Levels, however, correlated inversely with lymphocyte infiltration.

Adenofibroma↗

Thyroid function in goitrous subjects with thyroxine binding globulin deficiency.

The co-existence of thyroxine binding globulin (TBG) deficiency and euthyroid goitre in the same family raised the possibility that the disorders might be related. However, although both disorders co-existed in some members of the family, other members had either but not both conditions. These observations exclude the possibility that goitre development was solely due to alterations in thyroid activity brought about by TBG deficiency. It is possible, however, that the defect in protein binding might have enhanced goitre development in predisposed individuals as the two largest goitres occurred in TBG deficient subjects. Of the conventional parameters used to assess thyroid hormone levels in TBG deficient subjects, only the free triiodothyronine index consistently reflected the euthyroid status of these patients as established by clinical examination and TSH levels.

Antibodies↗