FSP改性TiNbTaZr/Zn的表征和成骨诱导活性评价

目的: 探讨搅拌摩擦处理加工后的Ti-35Nb-2Ta-3Zr/ Zn（TNTZ/ Zn）复合材料是否具备诱导成骨的生物活性。方法: 通过搅拌摩擦处理,将Zn添加到TNTZ合金表面,设计对照组为TNTZ（未经FSP的TNTZ）,实验组为FSP（未加Zn加工的TNTZ）、TNTZ/Zn-0.5（0.5 mm预制孔）和TNTZ/Zn-1（1 mm预制孔）。使用扫描电子显微镜、X线衍射进行表征分析,检测共培养的大鼠骨髓基质干细胞（bone marrow stromal stem cells,BMSCs）的碱性磷酸酶（ALP）活性,实时定量 PCR 检测ALP活性,COL-1α、OPN和OCN基因的表达。采用 SAS 8.2软件包对数据进行统计学分析。结果: TNTZ/Zn-1组表面Zn纳米粒子分布较均匀,直径为70~80 nm。与TNTZ组相比,TNTZ/Zn-0.5和TNTZ/Zn-1组的ALP表达显著上调（P<0.05和 P<0.01）。相比于TNTZ组,TNTZ/Zn-0.5和TNTZ/Zn-1组的ALP活性、COL-1α、OPN和OCN基因表达增加,差异有统计学意义（P<0.05）。结论: 通过FSP成功将Zn整合到TNTZ合金表面,制备出纳米级微观结构。TNTZ/Zn复合材料可有效诱导成骨,是一种潜在的种植体材料。     

Perforation of metastatic melanoma to the small bowel with simultaneous gastrointestinal stromal tumor

The gastrointestinal tract (GIT) is a common site of metastases for malignant melanoma. These metastatic tumors are often asymptomatic. We describe a case of a 58-year-old male who presented with a sudden onset of generalized abdominal pain. The patient's past medical history was significant for lentigo melanoma of the right cheek. Laparotomy was performed and two segments of small bowel, one with a perforated tumor, the other with a non-perforated tumor, were removed. Histology and immunohistochemical staining revealed the perforated tumor to be a metastatic malignant melanoma and the non-perforated tumor was found to be a gastrointestinal stromal tumor (GIST). The patient was discharged 7 d postoperatively. To the best of our knowledge, this is the first reported case in the literature of a simultaneous metastatic malignant melanoma and a GIST. Surgical intervention is warranted in patients with symptomatic GIT metastases to improve the quality of life or in those patients with surgical emergencies.     

Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants

BACKGROUND AND AIMS: Resistance is a major challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). We investigated the mechanisms of resistance in patients with progressive GISTs with primary KIT mutations and the efficacy of the kinase inhibitor PKC412 for the inhibition of imatinib-resistant mutants. METHODS: We performed a cytogenetic analysis and screened for mutations of the KIT and PDGFRA kinase domains in 26 resistant GISTs. KIT autophosphorylation status was assessed by Western immunoblotting. Imatinib-resistant GIST cells and Ba/F3 cells expressing these mutant proteins were tested for sensitivity to imatinib and PKC412. RESULTS: Six distinct secondary mutations in KIT were detected in 12 progressive tumors, with V654A and T670I found to be recurrent. One progressive tumor showed acquired PDGFRA -D842V mutation. Amplification of KIT or KIT / PDGFRA was found in 2 patients. Eight of 10 progressive tumors available for analysis showed phosphorylated KIT. Two remaining progressive tumors lost KIT protein expression. GIST cells carrying KIT -del557-558/T670I or KIT -InsAY502-503/V654A mutations were resistant to imatinib, while PKC412 significantly inhibited autophosporylation of these mutants. Resistance to imatinib and sensitivity to PKC412 of KIT -T670I and PDGFRA -D842V mutants was confirmed using Ba/F3 cells. CONCLUSIONS: This study shows the high frequency of KIT/PDGFRA kinase domain mutations in patients with secondary resistance and defines genomic amplification of KIT / PDGFRA as an alternative cause of resistance to the drug. In a subset of patients, cancer cells lost their dependence on the targeted tyrosine kinase. Our findings show the sensitivity of the imatinib-resistant KIT -T670I and KIT -V654A and of PDGFRA -D842V mutants to PKC412.     

The stromal cell-derived factor-1alpha dependent migration of human cord blood CD34 haematopoietic stem and progenitor cells switches from protein kinase C (PKC)-alpha dependence to PKC-alpha independence upon prolonged culture in the presence of Flt3-ligand and interleukin-6

Addition of the inflammatory cytokine interleukin (IL)-6 to the culture medium of human cord blood haematopoietic stem and progenitor cells (HSPCs) has been shown to lead to an altered stromal cell-derived factor-1α-dependent migratory phenotype. This study investigated whether this effect was attributed to a differential engagement of protein kinase C (PKC) isotypes. The migratory activity of both Flt3-ligand and Flt3-ligand/IL-6 cultured cord blood HSPCs was PKC-α dependent on day 1, but PKC-α independent after 5 d of cultivation. PKC-α expression was not down-regulated in cells cultured for 5 d indicating a switch of signalling molecules directing cell migration.     

胃肠道间质瘤患者生存和预后因素综合分析

目的 探讨影响胃肠道间质瘤(GIST)患者生存和预后的因素.方法 复阅153例患者切片,以免疫组化法检测CD117、CD34、血小板衍生生长因子受体-α和Ki-67蛋白表达,结合临床病理特征和GIST生物学行为分级,分析影响GIST患者生存和预后的相关因素.采用卡普兰一迈耶(Kaplan Meier)法和Cox比例风险模型比较不同因素对生存的影响.结果 患者1、3、5年生存率分别为94.1%、7 6.3%和6 5.9%.单因素分析显示,患者预后与肿瘤直径(χ2=40.5 6 5,P＜0.01)、肿瘤部位(χ2=13.245,P＜0.01)、核分裂象数目(χ2=22.6 26,P＜0.01)、危险度分级(χ2=19.186,P＜0.01)、肿瘤有无坏死(χ2=28.6 6 5,P＜0.01)、手术方式(χ2 9.110,P＜0.01)和Ki 6 7指数(χ2=1 5.9 5 3,P＜0.01)有关.多因素分析表明,肿瘤直径＞10 cm、位于肠道、核分裂象数目＞10/50 HPF、危险度分级属高度危险性、肿瘤有坏死及Ki 6 7指数＞5%与预后呈明显负相关.且Ki 6 7指数、肿瘤大小及核分裂象数目是GIST预后的强预告因子.结论 GIST生物学行为分级法对评价GIST患者预后具有较好的临床价值;判断GIST患者预后需结合Ki-67指数和肿瘤部位等因素,为治疗提供依据.     

下消化道间叶源性肿瘤CT仿真内镜与病理的对照研究

目的 观察下消化道问叶源性肿瘤(GIMTs)的病理及免疫组化特点,对照研究其与CT仿真内镜(CTVE)诊断之间的关系,评价CTVE在下消化道GIMTs中的诊断价值.方法 收集74例下消化道GIMTs患者的手术病理标本,采用光镜观察其病理特点及良恶性状况,免疫组化法检测其CD117、CD34、α-平滑肌抗体(SMA)及S-100蛋白的表达,并与术前CTVE判定的病变部位及良恶性结果进行对照研究.结果 经病理及免疫组化检查,40例(54.1%)诊断为胃肠道间质瘤(GIST),其中恶性间质瘤16例(40%);33例(44.6%)诊断为平滑肌瘤;1例(1.4%)诊断为神经鞘瘤.发病部位位于空肠33例,回肠21例,大肠20例.免疫组化:CD117阳性38例,占51.4%;CD34阳性27例,占36.5%;SMA阳性46例,占62.2%,S-100阳性1例(1.4%).CTVE对病变部位准确定位69例(93.2%).其中大肠准确定位18例,符合率90.0%;空回肠准确定位51例,符合率94.4%.CTVE判断良恶性GIST的敏感性为84.2%,特异性为85.7%.结论 GIST是下消化道最常见的GIMTs,发病部位以小肠居多.CTVE能准确显示肿瘤的部位、形态、大小,可术前准确定位GIMTs,对其良恶性判断具有较高的敏感性和特异性,可为术前制定合理手术方案和治疗策略提供重要依据.

Abstract：

Objective To study the pathological and immunohistochemical features of alimentary tract mesenchymal tumors and compare with computed tomographic virtue endoscopy (CTVE) imaging technology to evaluate the diagnostic value of CTVE in alimentary tract mesenchymal tumors. Methods Seventy-four pathological specimens of alimentary tract mesenchymal tumors were collected. The pathological features and the expression of CD117, CD34, SMA and S-100 were observed by immunohistochemical method with light microscope. The pathological types and characteristics were determined by pathologists and compared with CTVE imaging technology. Results In the 74 cases of alimentary tract mesenchymal tumors,40 cases were diagnosed as stromal tumor with pathological and immunohistochemical methods (54. 1%).Sixteen of them were malignant, accounting for 40% of the stromal tumor while 33 cases were diagnosed as leiomyoma(44. 6%)and 1 case as schwannoma(1.4%) . In the 74 GIMTs cases ,33 were jejunum GIMTs,21 were ileum GIMTs and 20 were large intestine GIMTs. Immunohistochemistry assay in the 74 GIMTs cases showed that 51.4% GIMTs were positive for CD117, approximately 36. 5% were positive for CD34 , 62.2% were positive for smooth-muscle actin (SMA) and 1. 4% were positive for S-100 protein. In the 74 GIMTs cases,69 cases were diagnosed right in the accuracy for location with CTVE(93. 2%) with 51 cases in small intestinal (94. 4%) and 18 cases in large intestinal (90. 0%). The sensitivity and the specificity of CTVE to distinguish benign from malignant stromal tumors by CTVE characteristics were 84. 2% and 85. 7%respectively. Conclusions GIST is common in GIMTs and is often originated from the small intestinal. The immunohistochemistry has great value in diagnosing alimentary tract mesenchymal tumors. The CTVE imaging technology also has great value in diagnosing alimentary tract mesenchymal tumors which can show the localization, shape size and artery of the tumor clearly. The diagnostic sensitivity and specificity of CTVE are high to distinguish benign from malignant alimentary tract GISTs. CTVE plays an important role in guiding the clinical management of GISTs.     

Melatonin delays cell proliferation by inducing G1 and G2 /M phase arrest in a human osteoblastic cell line hFOB 1.19

Abstract: A recent prospective study indicated that melatonin supplements may reduce the progression of idiopathic scoliosis, the most common deformity of the spine. This form of scoliosis occurs during rapid skeletal growth. To date, however, there is no direct evidence regarding an antiproliferative effect of melatonin at the level of osteoblasts. Herein, we investigated whether melatonin inhibits cell proliferation in a normal human fetal osteoblastic cell line hFOB 1.19. MTT staining showed that at 1 mm concentrations, melatonin significantly inhibited osteoblast proliferation in time‐dependent manner. Flow cytometry demonstrated that melatonin significantly increased the fraction of cells in G₀/G₁ phase of the cell cycle, while simultaneously reducing the proportion in the G₂/M phase rather than the S phase. Western blot and real‐time PCR analyses further confirmed that melatonin’s inhibitory effect was possibly because of downregulation of cyclin D1 and CDK4, related to the G₁ phase, and of cyclin B1 and CDK1, related to the G₂/M phase. There was no downregulation of cyclin E, CDK2, and cyclin A, which are related to G₁/S transition and S phase. In addition, the trypan blue dye exclusion assay showed that cell viability was not changed by melatonin relative to control cells. These findings provide evidence that melatonin may significantly delay osteoblast proliferation in a time‐dependent manner and this inhibition involves the downregulation of cyclin D1 and CDK4, related to the G₁ phase, and of cyclin B1 and CDK1, related to the G₂/M phase.     

Stromal retinoic acid receptor beta promotes mammary gland tumorigenesis

Retinoic acid is a potent differentiation and antiproliferative agent of breast cancer cells, and one of its receptors, retinoic acid receptor β (RARβ), has been proposed to act as a tumor suppressor. In contrast, we report herein that inactivation of Rarb in the mouse results in a protective effect against ErbB2-induced mammary gland tumorigenesis. Strikingly, tissue recombination experiments indicate that the presence of Rarb in the stromal compartment is essential for the growth of mammary carcinoma. Ablation of Rarb leads to a remodeling of the stroma during tumor progression that includes a decrease in angiogenesis, in the recruitment of inflammatory cells, and in the number myofibroblasts. In agreement with this finding, we observed that a markedly reduced expression of chemokine (C-X-C motif) ligand 12 (Cxcl12) in the stroma of Rarb-null mice is accompanied by a decrease in the CXCL12/chemokine C-X-C receptor 4 (CXCR4)/ErbB2 signaling axis in the tumors. Relevance to the human disease is underlined by the finding that gene-expression profiling of the Rarb-deficient mammary stromal compartment identified an ortholog RARβ signature in human microdissected breast tissues that differentiates tumor from normal stroma. Our study thus implicates RARβ in promoting tumorigenesis and suggests that retinoid-based approaches for the prevention and treatment of breast cancer should be redesigned.     

DOG1、CD117和PDGFRA在胃肠道间质瘤中的表达及相关性

目的:探讨DOG1、CD117和血小板衍生生长因子受体α(PDGFRA)在胃肠道间质瘤(GISTs)诊断中的意义,并分析与其GISTs 临床病理因素和危险度的关系.方法:应用免疫组织化学Envision二步法检测63例GISTs及43例非GISTs间叶源性肿瘤患者中DOG1、CD117及PDGFRA的表达,并分析上述免...