加味逍遥散联合三维适形放疗对原发性肝癌患者血清生长因子及免疫功能的影响

目的:观察加味逍遥散联合三维适形放疗对原发性肝癌(PLC)患者血清肝细胞生长因子(HGF)、转化生长因子-β1(TGF-β1)及免疫功能的影响。方法:选取90例PLC患者为研究对象,按照随机数字表法分为观察组和对照组,每组45例。对照组采用经肝动脉化疗栓塞术(TACE)联合三维适形放疗治疗,观察组在对照组基础上联合加味逍遥散治疗。对比2组中医证候疗效和实体瘤疗效,观察治疗前后血清HGF、TGF-β1及免疫功能指标的变化,记录不良反应发生情况。结果:观察组中医证候改善率97.78%,高于对照组的77.78%,差异有统计学意义(P<0.05)。观察组实体瘤疗效有效率略高于对照组,差异无统计学意义(P>0.05)。与治疗前比较,治疗后2组HGF水平均升高(P<0.05),TGF-β1水平均降低(P<0.05),观察组2项指标水平升高或降低幅度均大于对照组(P<0.05)。与治疗前比较,治疗后2组CD3^+、CD4^+、CD4^+/CD8^+、自然杀伤细胞(NK细胞)值均升高(P<0.05),观察组以上4项指标值均高于对照组(P<0.05)。2组治疗过程中均无严重不良反应发生。结论:加味逍遥散联合三维适形放疗治疗PLC可提高临床疗效,改善患者的免疫功能,调节机体血清相关因子。     

Activation of MET signaling by HDAC6 offers a rationale for a novel ricolinostat and crizotinib combinatorial therapeutic strategy in diffuse large B‐cell lymphoma

Some histone deacetylases (HDACs) promote tumor cell growth and pan‐ or selective HDAC inhibitors are active in some cancers; however, the pivotal HDAC enzyme and its functions in human diffuse large B‐cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, the interaction between HDAC6 and HR23B downregulated HR23B expression, thereby reducing the levels of casitas B‐lineage lymphoma (c‐Cbl), an E3 ubiquitin ligase for hepatocyte growth factor receptor (MET), which resulted in the inhibition of MET ubiquitination‐dependent degradation. In addition, enhanced HDAC6 expression and decreased HR23B expression were correlated with poor overall survival rates among patients with DLBCL. Taken together, these results establish an HDAC6–HR23B–MET axis and indicate that HDAC6 is a potent promoter of lymphomagenesis in DLBCL. Thus, a therapeutic strategy based on HDAC6 inhibitors in combination with MET inhibitors is promising. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium

Objective

To directionally-differentiate dermis-derived mesenchymal stem cells (DMSCs) into vascular endothelial cells (VECs) in vitro, providing an experimental basis for studies on the pathogenesis and treatment of vascular diseases.

肝细胞生长因子对人舌鳞癌 Tca8113细胞 VEGF-C 表达的影响及作用机制的初步研究

目的：研究 HGF 对人舌鳞癌 Tca8113细胞中 VEGF-C 表达的影响并探讨其作用机制。方法：体外培养 Tca8113细胞,应用 ELISA 方法测定不同浓度 HGF 作用下以及分别用 LY294002、U0126、SP600125、SB203580信号通路抑制剂阻断PI3K/Akt、P44/P22MAPK、JNK、P38MAPK 信号通路后 VEGF-C 的表达水平。结果：随着培养液中 HGF 浓度的增加,Tca8113细胞中 VEGF-C 的表达水平出现先增高后降低的趋势,当 HGF 浓度为40 ng/ml 时,VEGF-C 表达水平最高。PI3K/Akt 信号通路抑制剂（LY294002）和 P42/44MAPK 信号通路抑制剂（U0126）显著抑制了 HGF 刺激下 Tca8113的 VEGF-C 蛋白的表达（P ＜0．01）;而 JNK 信号通路抑制剂（SP600125）和 P38MAPK 信号通路抑制剂（SB203580）对 HGF 刺激下 Tca8113的 VEGF-C 蛋白的表达影响甚微（P ＞0．05）。结论：在人舌鳞癌 Tca8113细胞中,随着 HGF 浓度的增加,VEGF-C 的表达先增高后降低。PI3K/Akt 和 P44/P22MAPK 信号通路在口腔鳞状细胞癌淋巴转移中可能发挥作用。     

Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-α in bone marrow and peripheral blood of patients with multiple myeloma

Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-alpha (TGF-/ga) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-α, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-α (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-α and lactate dehydrogenase (P=.02), PB TGF-α and PB HGF (P=.002), BM TGF-α and CD38 (P=.046), BM TGF-α and BM HGF (P=.000), BM TGF-α and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.0018, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-α, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-α, and PDGF-AB in BM.     

Different doses of partial liver irradiation promotes hepatic regeneration in rat

The aim of this study is to investigate whether partial liver irradiation promotes hepatic regeneration in rat. Left-half liver of rat was irradiated to 10 Gy, and the Right-half to 0, 5, 10 and 15 Gy, respectively. Then, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were evaluated on 0 day, 15-day, 30-day, 45-day and 60-day after liver irradiation. Next, the serum HGF, NF-κB and TGF-β1 levels were also analyzed on 60-day after liver irradiation. Lastly, the cyclinD1 protein expression was appraised by western blots on 60-day after liver irradiation. ALT, AST and ALP levels were reduced compared with that of controls. The serum HGF, NF-κB and TGF-β1 levels, and the cyclinD1 protein expression in liver irradiation group were increased compared with that of controls group. However, hepatic regeneration of higher dose-irradiated cirrhotic liver was triggered a more enhanced regeneration, compared with that of higher doses group. In summary, these results suggest that different doses of partial liver irradiation promotes hepatic regeneration in rat.     

厄贝沙坦对老年非ST段抬高型心肌梗死患者血清肝细胞生长因子水平的影响

目的：观察厄贝沙坦对老年非ST段抬高型心肌梗死(NSTEMI)者血清肝细胞生长因子(HGF)水平的影响。方法选择2013年10月~2014年5月哈尔滨医科大学附属第四医院老年NESTMI患者38例,将入选患者中因各种原因不能服用厄贝沙坦的17例患者作为对照组,余21例为药物组。对照组给予硝酸酯药物、β受体阻滞剂、阿托伐他汀、拜阿司匹林、低分子肝素等常规治疗;药物组在此基础上给予常规治疗联合厄贝沙坦(150 mg/d)。分别于治疗前、治疗后第7天、治疗后第14天检测两组患者血清超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy);采用酶联免疫吸附试验检测血清中HGF含量。结果治疗后第14天时药物组血清hs-CRP及Hcy水平均较治疗前明显降低(P<0.05),且明显低于对照组(P<0.05);治疗后第7天两组患者血清HGF水平明显高于治疗前(P<0.05),但药物组明显低于对照组(P<0.05);两组患者治疗后第14天时HGF水平均较治第7天下降(P<0.05),但两组组差异无统计学意义(P>0.05)。结论老年非NSTEMI患者应用厄贝沙坦2周时可使血清中hs-CRP、Hcy水平明显下降,厄贝沙坦可降低老年NSTEMI患者血清HGF水平。     

食管鳞癌中肝细胞生长因子、血管内皮生长因子C及其受体3的表达及意义

目的:探讨肝细胞生长因子(HGF)、血管内皮细胞生长因子C(VEGF-C)和其受体3(VEGFR-3)在食管鳞癌中的表达水平及与食管鳞癌临床病理因素之间的关系.方法:采用RT-PCR技术检测25例食管正常黏膜、60例食管鳞癌组织中HGF、VEGF-C、VEGFR-3 mRNA的表达水平,并应用免疫组织化学法检测HGF、VEGF-C、VEGFR-3蛋白的表达水平并分析其与食管鳞癌临床病理因素之间的关系.结果:食管鳞癌组织中HGF、VEGF-C、VEGFR-3表达量明显高于食管正常黏膜组织,并且HGF、VEGF-C、VEGFR-3与食管鳞癌淋巴结转移、TNM分期呈正相关.结论:HGF、VEGF-C、VEGFR-3在食管鳞癌的发生发展中起到重要作用,三者可能协同作用在食管癌浸润生长、淋巴结转移及远处播散过程中起到一定作用.     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.