ABSTRACT
Adenomyosis(AM)is a common benign uterine disease that seriously affects the life quality of women.Because of the unclear or diffuse distribution of AM lesions,the treatment of uterine preservation is often ineffective.High intensity focused ultrasound(HIFU),as a new non-invasive treatment technology,is currently widely used in AM treatment.This paper will review the application of HIFU in AM,so as to provide certain clinical reference for the treatment of AM.
ABSTRACT
<p><b>BACKGROUND</b>Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdr1) gene is well-known for its ability to confering drug resistance. In this study, we meant to transplant the placenta mesenchymal stem cells (P-MSCs) moderated by mdr1 gene into a nude mice model radiated by γ-Co(60) and to explore the chemoprotection for bone marrow (BM) toxicity.</p><p><b>METHODS</b>Human P-MSCs were isolated from trypsin-digested term placentas and then transduced by with reconstructed retroviral vector containing mdr1 gene and green fluorescent protein (GFP) reporter gene. The integration and expression of mdr1 gene was observed indirectedly by the expression of GFP. A nude mice model was constructed after irradiation with a sublethal dosage of γ-Co(60). These irradiated mice were transplanted with mdr1-MSCs through the caudal vein and then received paclitaxel (PAC) intraperitoneal chemotherapy. The Peripheral peripheral blood (PB) of the nude mice was collected, and the PB cells counts and values were determined using an automatic analyzer.</p><p><b>RESULTS</b>After PAC treatment, mdr1-MSCs transplanted mice showed markedly improved survival upon compared to MSCs transplanted mice (85.7% vs. 57.1%). White blood cell (WBC) and red blood cell (RBC) counts as well as the hemoglobin (Hb) values were significantly increased in PAC treated mdr1-MSCs mice compared to PAC treated control mice when PAC chemotherapy had been finished (all P < 0.05), but the difference was not found in the plateltes (PLT) count (P > 0.05).</p><p><b>CONCLUSION</b>Human P-MSCs moderated by mdr1 gene when transplanted into nude mice may provide chemoprotection for hematopoietic toxicity.</p>
Subject(s)
Animals , Female , Humans , Mice , Pregnancy , Bone Marrow , Cell Differentiation , Genetics , Physiology , Cells, Cultured , Erythrocytes , Metabolism , Genes, MDR , Genetics , Physiology , Green Fluorescent Proteins , Genetics , Metabolism , Hemoglobins , Metabolism , Leukocytes , Metabolism , Mesenchymal Stem Cells , Cell Biology , Metabolism , Mice, Inbred BALB C , Mice, Nude , Placenta , Cell BiologyABSTRACT
<p><b>BACKGROUND</b>Most of gynecologic malignancies are sensitive to chemotherapy. Myelosuppression is the main dose-related toxicity of many chemotherapeutic drugs. The human multidrug resistance (mdr1) gene is well known for its ability to confer drug resistance. This study aimed to explore the feasibility of expression and resistance of mdr1 gene transduction into human placenta mesenchymal stem cells (P-MSCs) by retrovirus vector.</p><p><b>METHODS</b>Human P-MSCs were isolated from trypsin-digested term placentas, and their immunophenotypes and differentiation potential were evaluated. Human P-MSCs were transduced by reconstructed retroviral vector containing the mdr1 gene and green fluorescent protein (GFP) reporter gene. The integration and expression of the mdr1 gene were observed indirectly by the expression of GFP, and fluorescence-activated cell sorter was used to evaluate the functional activity of permeability glycoprotein (P-gp) encoded by the mdr1 gene. The stimulating test was made in vitro to show pleiotropic drug resistance of transfected cells.</p><p><b>RESULTS</b>The isolated, cultured and expanded P-MSCs expressed stem cell markers such as CD29, CD44 and CD73, and showed osteogenic and adipogenic differentiation potentials under appropriate conditions. The expression of P-gp in the non-transfected P-MSCs cells was (0.4 +/- 0.1)%, but increased to (28.1 +/- 4.7)% after gene transfection (P < 0.01). And positive staining of P-gp located mainly at cell membrane and cytoplasm. Accumulation and extrusion assays showed that P-gp expressed by the transfected cells had pump-functional activity and could efflux daunomycin out of cells. The analysis of cell survival confirmed that transfected P-MSCs had a characteristic of multidrug resistance with a significant increase in the resistance to anticancer agents.</p><p><b>CONCLUSIONS</b>Transfer and expression of human mdr1 gene mediated by retrovirus vector conferred P-MSCs drug resistance. It might provide a new alternative to chemoprotection strategies.</p>