ABSTRACT
We evaluated the effect of interferon-alpha2b as a chemosensitiser on HCT-15 cell line in treatment with doxorubicin. Chemosensitivity was determined by [3H]-thymidine incorporation and tetrazolium assays. The levels of expression of P-glycoprotein, Bcl-2 oncoprotein and HLA-ABC complex, and cell cycle/apoptosis analysis were determined by flow cytometry. Dox 50 ng/ml - IFN alpha 2b 500 IU/ml treatment inhibited cell proliferation (47.2 +/- 1.4%, p < 0.0001; MTT assay: 40.6 +/- 1.2%, p < 0.0001) and augmented the expression of P-170, Bcl-2 and HLA-ABC, while it didn't exert apoptosis, producing a slight G2/M arrest. A concentration of IFN-alpha2b, that by itself is not cytotoxic, can potentiate the efficacy of the anticancer drug. This effect is not due to a down-modulation of P-170. The absence of apoptosis and augmented levels of Bcl-2 expression suggests that this could be one of the mechanisms of drug resistance exerted by these cells.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Division/drug effects , Doxorubicin/toxicity , Drug Resistance, Multiple , Interferon-alpha/pharmacology , Membrane Proteins , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Adenocarcinoma , Cell Survival/drug effects , Colonic Neoplasms , Drug Resistance, Multiple/physiology , Drug Synergism , G2 Phase , HLA Antigens/analysis , HLA-A Antigens/analysis , HLA-C Antigens/analysis , Hemochromatosis Protein , Histocompatibility Antigens Class I/analysis , Humans , Interferon alpha-2 , Mitosis , Oncogene Protein v-cbl , Recombinant Proteins , Retroviridae Proteins, Oncogenic/genetics , Tumor Cells, CulturedABSTRACT
BACKGROUND: The use of telemedicine appears particularly promising in cardiovascular diseases; it may reduce the decisional time during an acute myocardial infarction, which is the greater part of the so-called "avoidable delay" and the inappropriate admission to the Emergency Department with the possibility of ruling out an acute pathology. The aim of our study was to show the diagnostic accuracy of a telecardiology service in the daily activity of general practitioners. METHODS: From February 1998 to February 1999, 150 general practitioners received a portable electrocardiographer (Card-Guard 7100) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for the reporting and interactive teleconsultation. RESULTS: During 1 year 3456 calls took place. At the time of the ECG recording 44% of patients were symptomatic. Chest pain was present in 669 patients (44%), dyspnea in 21%, palpitation in 18%, dizziness in 7%, and asthenia in 13%. ECG and teleconsultation solved all the problems for 2452 patients (71%) and further diagnostic tests were requested in 862 patients (25%); 142 patients (4%) were sent to the Emergency Department. Cardiological diagnosis was confirmed in 95 patients (73%), while anxiety or gastritis were presumed in 35 patients (27%). In the group of patients (n = 3314) for whom the cardiologist solved the problem without admission to the Emergency Department, there were 5 patients who were admitted to the Emergency Department for myocardial ischemia in the following 48 hours after the teleconsultation. Telecardiology service showed versus Emergency Department admission a sensitivity of 95%, a specificity of 97.5%, and a diagnostic accuracy of 92.5%. CONCLUSIONS: These data confirm a good diagnostic value to the service and a useful support to the general practitioners' activity.
Subject(s)
Electrocardiography/methods , Heart Diseases/diagnosis , Referral and Consultation , Telemedicine , Emergency Service, Hospital , Female , Humans , Male , Middle AgedABSTRACT
We have previously observed that acellular extracts from necrotic areas (NE) of the non-metastatic murine mammary adenocarcinoma M3, enhance in vitro cell detachment and spontaneous lung metastases. In the present study, using different proteinase inhibitors along with NE, only the calcium chelator EDTA could significantly abrogate the enhanced cell detachment from M3 produced by NE. The typical cleavage products of type IV collagenase were detected inside the tumor necrotic area, mainly in association with necrobiotic cells, as evaluated by Western blot analysis and immunohistochemical assays. Zymography revealed the presence of 72- and 92-kDa gelatinase/type IV collagenase in NE. Moreover, NE increased the in vitro invasive ability of cultured M3 cells. The use of specific antibodies against both 72- and 92-kDa type IV collagenases in the invasion assay showed that only the latter was able to revert the enhanced invasiveness to the baseline. It can be concluded that tumor necrosis is an important source of gelatinase/type IV collagenase, mainly in its 92 kDa form, and plays a major role in tumor invasion.
Subject(s)
Microbial Collagenase/analysis , Neoplasm Invasiveness , Neoplasms, Experimental/pathology , Pepsin A/analysis , Animals , Cell Adhesion/drug effects , Collagen/metabolism , Extracellular Matrix/metabolism , Female , Gelatinases , Mice , Mice, Inbred BALB C , Necrosis , Neoplasms, Experimental/enzymology , Protease Inhibitors/pharmacologyABSTRACT
Preference conditioning models were applied to the study of the motivational properties of opiate withdrawal. Conditioned place and taste aversions were produced by a single injection of an opiate antagonist in rats implanted with a morphine but not a placebo pellet. The hypothesis that withdrawal-produced jumping reflects the aversive properties of withdrawal was not confirmed. The use of central and peripheral administration of antagonists suggest that the aversive effects reflect antagonist activity in the brain.
