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BACKGROUND: Effective treatment for severed acute radiation sickness (over 8 Gy) has not been obtained at present. Mesenchymal stem cells, which are shown to secrete hematopoietic cytokines and support hematopoietic progenitors, play an important role in cute radiation sickness. OBJECTIVE: To investigate the therapeutic potential of non-adherent bone marrow-derived stem cells in the treatment of acute radiation injury induced by 8.5 Gy X-ray irradiation, as wel as the mechanisms involved. METHODS: Non-adherent marrow-derived stem cells from the long bone of fetal limbs were col ected for analyzing surface antigens, cel cycle, osteogenic and adipogenic differentiation potential, and expressions of vascular endothelial growth factors and Annexin A2. After being exposed to 8.5 Gy total body irradiation, BALB/C mice were randomly assigned into transplantation group and control group. Mice in the transplantation group were given 3×106 CFDA-SE labeled human non-adherent bone marrow-derived stem cells, and those in the control group were given 0.3 mL normal saline. Then, the survival rate, peripheral white blood cells at different time, pathologic change and angiogenesis of the bone marrow were observed. RESULTS AND CONCLUSION: After X-ray irradiation, transplanted non-adherent mesenchymal stem cells appeared to have a homing to the site of injury. The survival rate of mice in the transplantation group was much higher than that in the control group. Compared with the control group, the white blood cells in the transplantation group decreased more slowly while recovered more rapid: the nadir appeared at day 14 after transplantation while it recovered within 30 days. The bone marrow of mice in the transplantation group regenerated more actively and had more hematopoietic islands than those in the control group on day 21. In addition, bone marrow angiogenesis of the transplantation group was more obvious than that of the control group. In conclusion, human fetal non-adherent bone marrow-derived stem cells could promote bone marrow angiogenesis in a mouse model of acute radiation injury, through which they could play an important role in tissue regeneration of acute radiation injury.
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Objective To study the expressions of miRNAlet7 and Ras in non-small cell lung cancer ( NSCLC),and their correlations with clinicopathological features and survival time.Methods In-situ hybridization was used to detect the expression of let7,and SP immunohistochemistry to measure HMGA2 in 68 NSCLC cases ( group A) and 20 cases with normal lungs ( group B).Results The positive rate of let7 in group A was lower than that in group B (39.7％ vs 63.2％ ) ( P ＜0.05).The positive rate of Ras in group A was higher than that in group B (66.2％ vs 25.0％ ) ( P ＜0.01 ).The positive rate of let7 was not related to the age,gender,histological type,cell differentiation,and clinical stages of cancer patients(P ＞0.05).The positive rate of Ras was related to smoking,sex,and histological type of cancer( P ＜0.01 ),and was not related to cell differentiation,lymphatic metastasis,and clinical stages of cancer ( P ＞0.05).There was an obvious negative correlation between let7 and Ras( r =-0.627,P ＜0.01 ).The 2-year survival rate of let7-positive group was higher than that of the let 7-negative group ( x2 =4.84,P ＜0.05).No statistically significant difference was found between Ras-positive and-negative groups ( P ＞0.05 ).Conclusions The lower level of let7 expression,and high level of Ras expression have much to do with the carcinogenesis of NSCLC.The level of let7-positive expression is closely related to prognosis; while Ras may act in cooperativity in the occurrence and development of NSCLC.
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Objective To investigate the influence of the lymph node micrometastasis and its clinicopathological features on postoperative disease-free survival rate for patients with gastric cancer.Methods The study included 120 patients with pT1-3NoMo gastric cancer. The relationships between clinicopathological features or carcinoembryonic antigen (CEA) positive expression and postoperative disease-free survival rate were analyzed. Results In clinicopathological factors, multivariate analysis identified CEA positive expression was significantly correlated with tumor diameter (P = 0.011 ),depth of tumor invasion (P= 0.027) and lymphatic vessel invasion (P= 0.001 ) in lymph node positively. The average postoperative follow-up was (53.14 ± 16.75) months. There was statistical correlation between the tumor diameter( P = 0.018 ) or depth of tumor invasion ( P = 0.015 ) and postoperative disease-free survival rate. The disease-free survival rate was 90.91% ( 80/88 ), 86.36% ( 19/22 )and 40.00% (4/10) for the lymph node CEA negative,isolated tumor cells (IT Cs) and micrometastasis,respectively. There was significant difference between micrometastasis and the lymph node CEA negative (P= 0.000) or ITCs (P = 0.009), however, the lymph node CEA negative and ITCs was no significant difference (P = 0.438 ). Lymph node micrometastssis of gastric cancer was detected in 10 patients who should belong to stage pN1,the restage rate was 8.33%(10/120). Conclusions If the patients were found micrometastasis in lymph node with high-risk stage pT1-3NoMo gastric cancer for whom chemotherapy may be recommended,because of its high recurrence and poor prognosis.
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Aim To study the inhibitory effects and its mechanisms of oridonin on human pancreas adenocarcinoma SW1990 cells.Methods Cell growth inhibition mediated by oridonin on SW1990cells was measured by MTT assay.The morphological changes were observed by Hoechst33258 fluorochrome staining and electron microscope.Cell cycle and apoptosis rate were analyzed by flow cytometry. The molecular mechanisms involved in the effects of oridonin on SW1990 cells were studied by RT-PCR.Results The growth of humen pancreas adenocarcinoma SW1990 cells was significantly inhibited by oridonin.Apoptosis morphological changes about chromatic agglutination and nuclear condensation were detected by Hoechst 33258 fluorochrome staining and electron microscope in oridonin treated SW1990 cells."Sub-G_1" phase peak and G_2/M growth arrest werer found with flow cytometry.The upregulating mRNA expression of p21 and downregulating mRNA expression of survivin were detected by RT-PCR.Conclusion The inhibitory effect of oridonin on human pancreas adenocarcinoma SW1990 cells through induced apoptosis and G_2/M growth arrest and the mechanisms may be through surviving-p21 co-regluation pathway.
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Idiopathic pulmonary fibrosis(IPF), with unknown pathogeny, is an interstitial lung disease.The pathological features are diffuse epithelial-cell lesion, fibroblast proliferation, myofibroblast differentiation and excessive extracellular matrix deposition.CXCR4 is the predominant chemokine receptor on fibrocytes;CXCL12 is the only ligand of CXCR4.A large number of studies have shown that CXCL12/CXCR4 biological axis plays an important role in the pathogenesis of idiopathic pulmonary fibrosis.Under the regulation of hypoxia, HIF-1α and PI3K-Akt-mTOR path, CXCL12/CXCR4 biological axis promotes lung fibroblast proliferation, myofibroblast differentiation and extracellular matrix deposition, resulting in development and progression of IPF.
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Objective Hirsutella sinensis (HS) is the anmorph of Ophiocordyceps sinensis (Cordyceps sinensis). O.sinensis and Panax notoginseng are two popular Chinese herbs, commonly used in traditional Chinese prescriptions for the treatment of various diseases. A combination of HS extract with P. notoginseng saponin (PNS) extract demonstrated more prominent lung-protective activity than the two herbs individually used in our preliminary studies. This study further investigated the action of their combination (HSPNS) on anti pulmonary fibrosis using a Bleomycin (BLM)induced mouse model. Methods BLM-treated Kunming mice was given HSPNS daily for 7, 14 or 28 d via ig administration. After treatment, following parameters were monitored using proper methods, respectively. Lung index, serum and lung malondialdehyde (MDA) and hydroxyproline (HYP) contents, lung superoxide dismutase (SOD) activity, transforming growth factor β1 (TGF-β1), and expression levels of collagen Ⅰ (Col- Ⅰ) and collagen Ⅲ (Col-Ⅲ). The lung biopsies were also dissected for semiquantitative histological analysis. Results The results indicated that HSPNS significantly reduced lung index, MDA and HYP contents, and expression levels of TGF-β1,Col- Ⅰ, and Col-Ⅲ. The combination also remarkably enhanced SOD activity compared with BLM-induced group.Moreover, the severe pulmonary fibrosis histopathological changes induced by BLM could be attenuated by HSPNS treatment. Conclusion These results suggest that HSPNS could significantly inhibit the progression of pulmonary fibrosis induced by BLM and its inhibitory effect might associate with its ability to scavenge free radicals, decrease TGF-β1 level, and inhibit collagen synthesis.
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Purpose To study the expression of livin and caspase-3 protein in pancreatic carcinoma and their correlation with clinicopathologic features and survivial time.Methods High-throughput tissue microarray technique and immunohistochemistry were used to detect the expression of livin and caspase-3 protein in 88 pancreatic carcinoma specimens without a history of chemo-radiation therapy and 11 non tumorous pancreatic tissues,and the relationship of these subjects was analyzed with Spearman rank correlation. Among these 88 cases, 54 cases were followed-up for 2 months to 6 years, whom were used for the prognosis analysis.Results In the 88 cases, the positive rate of livin was 76.1% (67/88); however, the positive expression of caspase-3 was 90.9%(10/11) in non-tumorous pancreatic tissue, which was much higher than that in the cancer (40.9%,36/88), with statistically significant differences(P＜0.01). There were significant relationships of livin protein expression with sex, TNM stage and lymph node metastasis (P＜0.05); the expression of caspase-3 protein expression was significantly related to sex, histological grade, TNM stage and lymph node metastasis (P＜0.01). Spearman rank correlation showed a significant correlation between livin and caspase-3 protein (P＜0.01). In 54 cases with followed-up data, univariant analysis revealed that both of livin protein expression and lymph node metastasis were related to the survival rate (P＜0.05), but caspase-3 protein expression, sex, age, tumor location, size, histological grade and TNM stage were unrelated to prognosis (P＞0.05). Furthermore,COX stepwise proportional hazards analysis showed that only livin status retained independent significance in prospecting prognosis of pancreatic carcinoma.Conclusions The expression of livin is associated with clinicopathologic features and prognosis in pancreatic carcinoma. High expression of livin protein indicates poor prognosis, which could become an independent index for the evaluation of prognosis.caspase-3 protein may be involved in the regulation of apoptosis and the progression of pancreatic carcinoma.
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Background and purpose:Unbalance of apoptosis regulation plays an important role in tumor initiation and progression.Survivin and caspase-3 all take part in the regulation of cell cycle and apoptosis.We investigated the role of survivin and caspase-3 in apoptosis of gastric carcinoma,as well as its relationship with the clinicopathologic features and the prognosis of gastric carcinoma by using tissue microarray.Methods:The gastric cancer tissue microarrays were composed of tissues from 100 cases of carcinoma of the stomach without a history of chemo-radiation therapy and 30 gastric tissues of control subject.The diameter of each specimen on tissue microarrays was 2.0 mm.Expressions of survivin,caspase-3 were investigated immunohistochemically on these tissue microarrays.Tumor cell apoptosis index was also examined by TUNEL method.Of the 100 cases,47 cases were followed-up from 14 months to 13 years,in which the prognosis was analyzed.Results:Two paraffin-embedded gastric carcinoma tissue microarrays were successfully constructed,including 114 and 116 tissue spots,respectively.Immunohistochemical analysis showed that survivin expression was positive in 78 cases(78%) in this series.In contrast,no expression of survivin in control tissues was detected(P
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Idopathic pulmonary fibrosis (IPF),with unknown pathogeny,is a interstitial lung disease. The pathological features are diffuse epithelial-cell lesion and excessive extracellular matrix deposition. Many investigators consider alveolar epithelial cells impairment and abnormal activation,fibroblast proliferation and myofibroblast differentiation as causes,resulting in excessive extracellular matrix disorganization of lung. Recently,it is believed that telomeres and telomerases might play a role in regulating the capacity of fibroblast proliferation and aberrant epithelial repair in IPF. The aim of this article is to review the telomeres,telomerases and their relationship with the idopathic pulmonary fibrosis,furthmore,to identify the etiology and pathogenesis of the idopathic pulmonary fibrosis and provide the study measure for establishing an effective treatment.