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Esophageal squamous cell carcinoma is one of the most common cancer in China, and locally advanced stage remains a heterogeneous and complex disease. Its treatments are constantly evolving. To date, radiochemotherapy and surgery are involved in the comprehensive treatment of this disease. However, because of the specifical anatomical location of esophagus, its physiological function will be impaired after surgical resection. If similar survival is obtained in esophageal cancer, an organ preserving strategy without surgery is of great significance for improving the quality of life. As a non-invasive tumor treatment method, neoadjuvant therapy plays an important role in the comprehensive treatment of preserving the esophagus. Recently, there are studies investigating the role of organ preserving strategy in the comprehensive treatment of esophageal cancer with neoadjuvant therapy, and the recognition of these advances will provide reference value for the comprehensive treatment of esophageal cancer.
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The morbidity and mortality of lung cancer were the highest in malignant tumors. In recent years, with the update of clinical assistant examination technology and the popularization of physical examination, especially the development of CT examination, more and more lung cancer in early stage are found in the form of pulmonary nodules. Surgery treatment should be considering as the first choice for early lung cancer. At present, various 3D technologies have been widely used in the field of medicine, leading the thoracic surgery to the direction of minimal invasion and precision. This review focuses on the current application of 3D technology in the perioperative period of early lung cancer.
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OBJECTIVE: To study the effect of transplanting autologous bone marrow mesenchymal stem cells (BMSCs) at different time point after myocardial infarction on cardiac function, and to approach its mechanism. METHODS: Thirty healthy Taihu Meishan swine were prepared for myocardial infarction models, and divided into 6 experimental groups, with 5 animals in each group. BMSCs were transplanted into 3 groups through coronary artery at 3 hours, 2 weeks and 4 weeks after myocardial infarction, named G1, G2 and G4, respectively. Meantime, DMEM culture medium was injected in the control group at correspond periods. Each swine was examined by MRI and Doppler before infarction, before transplantation, and at 8 weeks after infarction, respectively, to observe the change of cardiac function. The VEGF values of blood serum in different periods after transplantation were detected. All swine hearts were harvested after 8 weeks (the experimental terminus), and the planting and differentiation of transplanted cells in cardiac muscle were detected by the method of immunity histochemistry. The density of blood vessels in cardiac muscle was acquired simultaneously. RESULTS: There was no statistic difference of cardiac function between G1 and its control groups. The groups of G2 and G4 could improve cardiac function compared to the control groups, and G4 was superior to G2 (P < 0.05). There was no statistics difference of the decreased absolute value of myocardial infarcted area between G1 and the control groups. The myocardial infarcted area of G4 was greater than G2 (P < 0.05). The value of blood serum VEGF rose obviously in the G2 and G4, while G1 and all control groups did not present any marked changes, the rising amplitude of G4 was larger than G2 (P < 0.05). There were not any planting and differentiation of transplanted stem cells in G1 and all control groups at 8 weeks after infarction, but G2 and G4 could display, especially in G4 group (P < 0.05). There was no statistic difference of the density of blood vessels in cardiac muscle between G1 and all control groups at 8 weeks after infarction, but the differences were significant in all experimental groups, which was superior in G4 group to G1 and G2 groups (P < 0.05).CONCLUSION: There is disparity of transplanting BMSCs at different time point after myocardial infarction on cardiac function. Transplantation in acute period of myocardial infarction has no significant effect, but transplantation in non-acute period can ameliorate cardiac function. The therapeutic effect of transplanted at 4 weeks is superior to other time point. The MRI can display the location and compass of infarct cardiac muscle, and reflect the variation of cardiac function.
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BACKGROUND: A great quantity of cell loss in early stage following stem cell transplantation can significantly affect transplantation effect. Presently, it is confirmed that overexpression of AKT1 gene significantly inhibit cell apoptosis. OBJECTIVE: To explore whether AKT1 gene overexpression can block stem cell apoptosis under hypoxic condition following pig autologous bone marrow mesenchymal stem cell (BMSC) transplantation, and the effect of repairing damaged myocardium. DESIGN, TIME AND SETTING: The randomized controlled animal study was performed at the Soochow University from August 2005 to February 2007.MATERIALS: A total of 24 healthy male Meishan pigs were supplied by the Animal Experimental Center of Soochow University. METHODS: The CDS (regulation domin of AKT1) AKT1-cDNA fragment was amplified. Lentivector Packaging Kit was used to transfect BMSCs after synthesized with pCDH1-AKT1 shuttling plasmid. Following BrdU labeling, models of myocardial infarction were constructed by occluding the distal left anterior descending coronary artery in pigs with gelatin sponge. 4 weeks later, pigs were randomly divided into four groups: the model control group, the DMEM group, the BMSCs group, and the AKT-transfected group. In model control group, there was no other injection after occluding the left anterior descending coronary artery. In the DMEM group, 5 mL DMEM was injected into the coronary artery. 5 mL BMSCs (1×10~7 cells) were infused into the coronary artery in the BMSCs group. 5 mL BMSCs transfected with the AKT1 gene were injected in the AKT-transfected group MAIN OUTCOME MEASURES: Western blot analysis and real time RT-PCR were used to test the plasmid. The cardiac function was evaluated by magnetic resonance image. Histological characteristics of the myocardium were observed using immunohistochemistry. Serum vascular endothelial growth factor and transforming growth factor β1 levels were determined by ELISA. RESULTS: AKT1-cDNA was cloned into pCDH1-MCS1-EF1-copGFP and the sequence was confirmed in comparison with the published one. AKT mRNA expression could be detected distinctly 24 and 48 hours after transfecting cells. The expression of AKT1 intensity in MSCs remained strong 2 weeks later with detected by real time RT-PCR and Western blot analysis. AKT1-mRNA transcriptional levels were 120 times of primary cells. Before the cell implantation, the left ventricular end-diastolic dimension increased and the stroke volume decreased in the myocardial infarction hearts. The cardiac function was significantly improved after cell implantation, and the implanted MSCs prevented the infarct region from thinning and expanding, improved contraction and increased perfusion in all groups relative to the control hearts. The left ventricular chamber size was smaller in the hearts with being transplanted cells than that in the control hearts. Moreover, the improvement was even markedly greater in AKT-transfected group (P < 0.05). Hematoxylin-eosin staining results showed that fibering was significant in the model control group and DMEM group. Island-like myocardium was observed in the infarct zone of the BMSCs group and AKT-transfected group, and plenty of small vessels-shape structure was detected in the AKT-transfected group. Immunohistochemistry demonstrated that Von Willebrand Factor (vWF) and Cx-43 expression was determined in the myocardium in the BMSCs group and AKT-transfected group, and the proportion of BrdU and Cx-43-positive cells to BrdU-positive cells was significantly greater in the AKT-transfected group compared with the BMSCs group 4 weeks following transplantation (P < 0.05). Following cell transplantation, vascular endothelial growth factor levels were gradually increased, peaked at 1 week, gradually decreased, and reached a normal level at 4 weeks. Transforming growth factor p1 levels were gradually reduced, and significantly less than the model control group, DMEM group 4 weeks later (P < 0.05), and significantly lower than that pretransplantation (P < 0.05).CONCLUSION: Using lentiviral vector to construct with AKT1 gene could stably make BMSCs overexpress AKT1. The BMSCs engraftment in host myocardium might improve the left ventricle function by attenuating the contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. AKT1 overexpression can significantly improve cardiac function following infarction.
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BACKGROUND: Mobilization of autologous bone marrow-derived mesenchymal stem cells (MSCs) for repair of myocardialnecrosis is a safe and effective method for treatment of ischemic cardiomyopathy. OBJECTIVE: This review serves to summarize the research progress in mobilization of bone marrow-derived MSCs for treatment of ischemic cardiomyopathy. RETRIEVAL STRATEGY: Using the terms "bone marrow stem cells, myocardial infarction", manuscripts that were published from December 1996 to December 2006 were retrieved from the PubMed database. Manuscripts were primarily screened. Inclusion criteria: studies on bone marrow-derived MSCs used for treatment of ischemic cardiomyopathy, and studies that were recently published or in high-impact journals. Exclusion criteria: repetitive studies. LITERATURE EVALUATION: The manuscripts primarily focused on the randomized controlled experiments of bone marrow-derived MSCs for treatment of ischemic cardiomyopathy. Among the 28 included manuscripts, 28 were review studies, and the remaining were clinical or basic experimental studies. DATA SYNTHESIS: Bone marrow-derived MSCs possess self-renewal, proliferative, and multi-directional differentiation potential. They can differentiate into cardiac-like cells under the regulation of appropriate cytokines. Previous studies have demonstrated that the stem cells in the bone marrow blood circulation can reach infarcted myocardium and are involved in the tissue regeneration. A great progress has been made in the study on bone marrow-derived MSCs used for treatment of ischemic cardiomyopathy. However, there exist some problems, such as, how to preserve the seeded cells, the mechanism underlying differentiation and proliferation in the in vitro culture of cells remains unclear, and the biomechanical performance of cardiac-like cells are not satisfactory. CONCLUSION: Mobilization of bone marrow-derived MSCs is easy, fast, less-injury, and without immunologic rejections in the autotransplantation for treatment of isehemic cardiomyopathy. However, there are still some unsolved problems.