ABSTRACT
Tumor microenvironment is composed by tumor cells,stromal cells,immune-inflammatory cells,extracellular matrix,soluble cytokine and so on.Previous studies focused on the biological behavior,genetic changes and related phenotypic changes of tumor cells,but tumor microenvironment is closely related with the tumor development and treatment resistance.In recent years,new studies have confirmed that tumor microenvironment is an important member of tumor,which play an important role in proliferation,invasion and proliferation of tumor cells.This article mainly introduces the tumor microenvironment features,tumor-associated macrophage and tumor-associated fibroblasts,which led to the radioresistance of tumor.
ABSTRACT
<p><b>OBJECTIVE</b>To establish red-green dual-color fluorescence glioma model in nude mice and to explore its practical values.</p><p><b>METHODS</b>CM-DiI-stained rat glioma C6 cells (C6-CM- DiI cells) expressing red fluorescence were inoculated into the brain of athymic nude mice expressing green fluorescence protein (NC-C57BL/6J-EGFP). Then the whole-body dual-color fluorescence imaging was detected dynamically. Finally whole brains of the tumor-bearing mice were removed and 5 µm thick serial frozen slices were made. Light microscopy, fluorescence microscopy and confocal laser scanning microscopy were performed to observe the transplanted tumor tissue structure and fluorescent cells.</p><p><b>RESULTS</b>Tumor mass with red fluorescence increased gradually under continuous in-vivo fluorescence imaging monitoring. Under the fluorescence microscope, cells with red, green and yellow fluorescence were observed in the frozen sections of transplanted tumor tissue and the mutual structural relationship among them could be defined. The tumor cells migration, implantation and cell fusion between transplanted tumor cells and host cells could be observed. It could be distinguished according to the fluorescence, that blood vessels of tumor-origin displayed red fluorescence, blood vessels of host-origin displayed green fluorescence and mosaic blood vessels appeared yellow fluorescence. It was depicted that host innate astrocytes and oligodendrocytes in the microenvironment at the tumor periphery could be activated and dedifferentiated into nestin-positive cells.</p><p><b>CONCLUSIONS</b>In contrast to traditional animal model, the dual-color fluorescence imaging of nude mouse models of glioma possesses enormous advantages in investigating tumor mass in-vivo fluorescence imaging, tumor cells migration and metastasis, tumor angiogenesis and reactive activation of host innate cells in the microenvironment at tumor periphery, thus, has highly practical application value.</p>
Subject(s)
Animals , Mice , Rats , Astrocytes , Metabolism , Brain Neoplasms , Metabolism , Pathology , Carbocyanines , Metabolism , Cell Fusion , Cell Line, Tumor , Cell Movement , Disease Models, Animal , Fluorescent Dyes , Metabolism , Glioma , Metabolism , Pathology , Green Fluorescent Proteins , Metabolism , Luminescent Proteins , Metabolism , Mice, Inbred C57BL , Mice, Nude , Microscopy, Confocal , Microscopy, Fluorescence , Neoplasm Transplantation , Neovascularization, Pathologic , Nestin , Metabolism , Oligodendroglia , MetabolismABSTRACT
The effects of cyclosporine A on matrix metalloproteinases(MMP)-2 and-9 expressions in the cardiac muscle of streptozocin-induced diabetic rats were investigated.The expressions of MMP-2 and MMP-9 mRNA and proteins in the cardiac muscle of diabetic rats were significantly upregulated,which could be decreasedby cyclosporine A(P＜0.05 or P＜0.01).The results suggest that cyclosporine A may effectively ameliorate the injuries of diabetic cardiomyopathy.
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Objective To study the autoimmune injuries on diabetic retinopathy(DR)and the protective effects of immunosuppre8sive therapy with eyelosporine A(CsA) on the DR of streptozotocin(STZ)-induced diabetic rats.Methods STZ-induced diabetic rats were randomly divided into 3 groups: group 1:diabetic group without any treatment;group 2:insulin-treated group;group 3:CsA-treated group which was further divided into 2 subgroups:subgroup A:CsA was given 1 week before hyperglycemia appeared and subgroup B:CsA was given one week after hyperglycemia appeared.Subgroup A and subgroup B were further subdivided into 3 groups respectively,based on the dose of CsA(1,4 and 8 mg·kg-1·d-1).As a control group,normal rats were also simultaneously monitored.The pathologic changes in the retina were investigated with HE stain and the deposition of immunoglobulins was detected with immunohistochemistry and immunofluorescent microscopy.Results After 8 week,the deposition of IgG, IgA and IgM was quite significant in the retina of diabetic rats.The data also suggested that insulin treatment had no effects on the DR.In contrast,with CsA intervention,the deposition of immunoglobulins on the retina of diabetic rats vanished.Conclusions Autoimmune injuries were shown,in the present study,to play a critical role in the pathogenesis of diabetic retinopathy.Immunosuppressive treatment with CsA showed protective effects by inhibiting the deposition of immunoglobulins in the retina of diabetic rats.