OBJECTIVE: To investigate the role of uPA in early (pT1) breast cancer. METHODS: Immunohistochemistry (streptavidin-biotin-peroxidase system), using the Chemicon AB776 polyclonal antibody, which reacts with uPA-PA-1 and uPA-PAI-2 complexes, was performed. In addition, CD44std, Ki67, c-erb-B2, p53, ER and PR expression were studied on the same tissue samples by the same method. The results obtained were correlated with nodal invasion, with each other and with classical pathologic features such as histologic and nuclear grade by means of the Spearman test for nonparametric variables. RESULTS: The immunohistochemical reaction with uPA-PAI-1 and uPA-PAI-2 complexes was cytoplasmic and localized inside the tumor cells, with no, or only minimal reaction in the stromal cells. uPA-positivity detected by this method correlated significantly with ER expression (p = 0.031), PR expression (p = 0.030), favorable nuclear grade (p = 0.0087) and marginally with a low proliferation rate (p = 0.088), which was the opposite of the results reported by most other groups when studying either free uPA or uPA bound to its membrane receptor (uPAr) in similar tumors. CONCLUSION: From our results we conclude that uPA-PAI-1 and uPA-PAI-2 complexes are formed inside the tumor cells for the purpose of inactivating free or uPAr-bound uPA, which explains why our findings were the reverse of those obtained when studying these latter forms. A model incorporating our data and the present knowledge on the uPA-uPAr-PAI chain is proposed.

Breast Neoplasms↗

PubMedDate not supplied

Modulation of molecular marker expression by induction chemotherapy in locally advanced breast cancer: correlation with the response to therapy and the expression of MDR1 and LRP.

PURPOSE: To assess if molecular markers are able to predict the response to induction chemotherapy in locally advanced breast cancer, and if any variation in their expression is associated with the degree of axillary lymph node invasion. METHODS: Between 1995 and 1999, 48 patients with locally advanced breast cancer were submitted to induction chemotherapy at Fundación Tejerina--Centro de Patología de la Mama, Madrid, Spain. The patients carried either tumors larger than 5 cm in diameter with clinically positive axillary nodes, T4a or T4b tumors regardless of size, or inflammatory carcinomas. All received between 3 and 6 cycles of CAF standard polychemotherapy (Cyclophosphamide, Doxorubicin and 5-Fluorouracil) with the exception of one patient, who received CMF therapy (Cyclophosphamide, Methotrexate and 5-Fluorouracil), and another one, who received Taxotere-Doxorubicin. After completion of their induction chemotherapy scheme, 1 patient showed a "complete clinical response" (CCR, with disappearance of all clinical and radiological signs of tumor presence), 36 (75.0%) patients showed a "partial response" (PR, > 50%), 10 (20.8%) showed "no response" (NR, < 50%), and finally one progressed under treatment. Core biopsies were performed in all cases prior to treatment for histological diagnosis which allowed for the determination of the following parameters by means of immunohistochemistry: hormone receptors (ER and PR), oncogenes and tumor suppressor genes (c-erb-B2 and p53) and the proliferation marker Ki67. Initial tumor size, histologic and nuclear grade and histologic variety were also included as variables of the study. After chemotherapy, 37 patients were submitted to a rescue mastectomy at our center. The same aforementioned parameters were determined once again on the operative specimen, together with MDR1 expression (using two different antibodies) and LRP expression. As outcome variables, objective response to treatment and the presence of invaded axillary nodes were considered. RESULTS: Only the expression of the proliferation-associated Ki67 antigen, as well as nuclear grade were affected significantly (p < 0.05) by the previous chemotherapeutic treatment. All other studied parameters showed no significant change in expression. More disappointingly, even, none of the studied variables showed any significant power for predicting either an objective response to treatment, or the presence of invaded axillary nodes at surgery. Both outcome end-points were also unrelated to each other. Overexpression of the multidrug-resistance gene or the LRP gene, finally, showed no correlation whatsoever with the previous response to chemotherapy. CONCLUSION: According to these results, the parameters employed by us are of no practical use for predicting the response to treatment or the presence of invaded nodes at rescue surgery in locally advanced breast cancer. Clinical and surgical assessment remain thus the mainstay of treatment for this group of patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Clinical significance of the redefinition of the agent of amoebiasis.

Entamoeba histolytica is the pathogenic species of Entamoeba that causes amoebic dysentery and other invasive disease. The morphologically similar species, E. dispar, is non-pathogenic and accounts for about 90% of the previously estimated 500 million E. histolytica infections world-wide. Because of the recent redefinition of E. histolytica and E. dispar, and the limited number of drugs available to treat amoebiasis, a new approach to treatment of individuals carrying these parasites is necessary. A meeting of eminent scientists has recently agreed that on no account should prophylaxis against amoebiasis be given, and no treatment without symptoms should be administered. The expense of treating asymptomatic individuals, both monetary and at the risk of over-use of precious drugs, does not appear to be justified. It would seem wise that we preserve currently effective anti-amoebic drugs and avoid the development of drug-resistant E. histolytica.

Amebicides↗

PubMedDate not supplied

[The electroencephalographic analiotopogram in changes and modifications of the state of consciousness].

Explore the source record for details and available documents.

Alpha Rhythm↗