Cystatins and cathepsins in breast carcinoma Lah, T T; Kokalj-Kunovar, M; Drobnic-Kosorok, M ...
Biological chemistry Hoppe-Seyler,
07/1992, Letnik:
373, Številka:
7
Journal Article
Recenzirano
The increased expression of proteolytic systems is one of the characteristics of transformed and malignant cells and their evaluations in whole tumor homogenates were considered as possible ...diagnostic and/or prognostic factors. Abnormal intracellular distribution, increased activities and secretion of cysteine proteinases (CPs) cathepsin B (Cat B) and L (Cat L), were associated with tumor progression. In the present study of matched pairs of breast carcinoma and normal breast tissue, the activities of Cat B and Cat L in breast carcinoma homogenates were found to be 20 and 50 fold higher, respectively, than in normal tissues. In contrast, a decrease in total inhibitory activity of cysteine proteinase inhibitors (CPIs) was observed but an average ratio between tumor and normal tissues was only 0.75. One of the CPIs, stefin A, was also determined immunochemically. The activities of CPs and CPIs were compared to the increased levels of cathepsin D (Cat D) activities in individual patients, but no statistically significant correlations were found. We correlated CPs and CPIs with morphological and receptor data as well as the axillary lymph node metastases. There was no statistical correlation of CP and CPIs with the number of lymph node metastases. However, highly elevated levels of Cat B and Cat L and lowered CPI activities in tumor cytosols were often associated with poorly differentiated carcinomas and those with negative ER and PR values. We conclude that cysteine-dependent proteolysis may play an important role in breast tumors.
Low-level direct current (0.2-1.8 mA) was demonstrated to be an antitumor agent on two different murine tumor models (fibrosarcoma Sa-1 and melanoma B-16), and has been suggested for regional cancer ...treatment. Its antitumor effect was achieved by introduction of single or multiple-array needle electrodes (Pt-Ir alloy) in the tumor and (an)other electrode(s) subcutaneously in its vicinity. The electrode inserted in the tumor was made anodic (anodic electrotherapy, ET) or cathodic (cathodic ET). In control groups, animals were subjected to exactly the same procedures with needle electrodes inserted at usual sites without current. In single-stimulus ET performed after the tumors have reached approximately 50 mm3 in volume with 0.2, 0.6, and 1.O mA for 30, 60, and 90 min, cathodic ET exhibited better antitumor effect than anodic ET. In both cases and at all ET durations, the antitumor effect depended proportionally on the current level applied. The antitumor effect was evaluated by following tumor growth and by microscopic estimation of the necrotization of the tumor area immediately after ET, and 24, 48, and 72 h posttreatment.
Necrotization produced by cathodic ET was observed to be immediate and extensive whereas anodic ET resulted in increased necrotization only at 24 h posttreatment. In both cases the extent of necrosis was significantly higher than in control and was centrally located (site of electrode), whereas in controls it was sporadic, distributed randomly over the whole tumor area. When current was delivered via multiple-array electrode ET, the antitumor effect was slightly better in cathodic ET compared to single-electrode ET. Employing cathodic multiple-array electrode ET and using higher currents, i.e., 1.0, 1.4, and 1.8 mA in melanoma B-16, 20% and 40% cures were achieved by 1.4 and 1.8 mA single-shot ET of 1 h duration, respectively, whereas in fibrosarcoma Sa-1 no cures were accomplished. In general, different susceptibility of the two tumor models to ET was noticeable. Comparing tumor growth and necrotization after the application of direct current (0.6 mA) and alternating current (0.0 mA mean, 0.6 mA RMS), it appeared that alternating current had no impact either on necrotization of tumor tissue or on tumor growth. ET was performed on normal tissues as well. In subcutaneous tissue, thigh muscle, and liver of healthy mice immediately after 1 h of treatment using 0.6 mA in both cathodic and anodic modes, local necrotization at the site of electrode insertion was evident, with signs of acute inflammation in the vicinity. In anodic ET, vacuolization around the electrode was noticed.
The major problem confronting the cytopathologist in interpretation of the pleomorphic aspiration biopsy sample (ABS) of nonepithelial lesions is to provide a reasonable differential diagnosis, since ...the presence of cellular pleomorphism alone does not always denote malignancy. One must be fully cognizant of a vast number of pathologic processes to make a correct interpretation. Some indication of the extent of the problem and the potential diagnostic pitfalls are outlined in selection of nonneoplastic processes and benign and malignant tumors of mesenchymal origin presenting as pleomorphic ABSs.
A case of thyroid carcinoma in a 38-year-old male with a high serum level of calcitonin is reported. The tumor was composed of polygonal argyrophilic cells, signet ring Alcian blue-positive cells, ...and a minority of amphicrine elements. The same polymorphic cellular component was seen at the ultrastructural level. Anticalcitonin immunoperoxidase revealed that the majority of cells were positive, including the amphicrine cells. In spite of calcitonin production it is felt that cases similar to the present one should be distinguished from "ordinary medullary" carcinoma and the terms "amphicrine" or "composite calcitonin and mucin-producing carcinoma" are proposed.
Imaging was performed with both pertechnetate and 131I in 58 patients with thyroid nodules. Pertechnetate concentrated in all 12 follicular carcinomas, in two out of seven papillary carcinomas, and ...in some benign nodules that did not accumulate 131I in the 24-hr images.
