ABSTRACT
To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Cell-Penetrating Peptides , Chemistry , DNA , Chemistry , Drug Delivery Systems , HeLa Cells , Neoplasms , Drug Therapy , Particle Size , PlasmidsABSTRACT
<p><b>OBJECTIVE</b>To analyze the relationship between P-glycoprotein function in peripheral blood cells and primary multidrug resistance in breast carcinoma.</p><p><b>METHODS</b>P-gp function was investigated by flow cytometry in NK cells of 16 breast cancer patients treated with anthracyclines and taxanes. Among all the patients, 8 were in chemotherapy-sensitive group and 8 in chemotherapy-resistant group. P-gp function was determined by rhodamine 123 (Rh123)-ejection test. Mathematical model was established by a regression of the fluorescence-time curve. The efflux rate constants of the chemotherapy-sensitive and -resistant groups were compared.</p><p><b>RESULTS</b>There was no significant difference of Rh123 accumulation, retention or efflux between the two groups. The mathematical model of F(t) = F(0) · e(-kt) was established. K was the efflux rate constant, which was significantly different between the chemotherapy-sensitive and -resistant groups (P = 0.025). When k > 3.9 was used as diagnostic criterium for primary resistance, the sensitivity, specificity and accuracy were 75.0%, 100% and 87.5%, respectively.</p><p><b>CONCLUSION</b>P-glycoprotein function in peripheral blood cells is associated with primary multidrug resistance in breast carcinoma. The efflux rate constant may be a good predictor for chemotherapy sensitivity.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Blood , Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Metabolism , Pathology , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Killer Cells, Natural , Metabolism , Retrospective Studies , Rhodamine 123 , Metabolism , TaxoidsABSTRACT
<p><b>OBJECTIVE</b>To explore the value of flow cytometric immunophenotyping (FCI) in the diagnosis and differentiated diagnosis of lymphoma and explain the immunophenotypic features and differences of malignant lymphoma.</p><p><b>METHODS</b>Seventy four fresh samples of suspicious lymphoma were collected from Nov. 2004 to Aug. 2006. Each sample was individually evaluated by FCI. The results were analyzed and compared with the histopathological diagnosis.</p><p><b>RESULTS</b>Among the 74 cases, the FCI data consisted with the final morphological diagnosis in 61 cases (82.4%). For the diagnosis of B and T non-Hodgkin's lymphoma (NHL), thymoma, carcinoma and benign lesions of lymph node, the concordance between FCI data and morphological diagnosis were 93.5%, 100%, 100%, 100% and 81.3%, respectively.</p><p><b>CONCLUSION</b>Multi-parameter FCI analysis can provide important information and help for diagnosis of lymphoma. It is an assistant but necessary approach for the diagnosis and differential diagnosis of lymphoma.</p>