GRIM-19的生物学活性及其与肿瘤关系的研究进展

干扰素/维甲酸联合应用诱导的细胞凋亡相关基因19(GRIM-19)是应用反义基因敲除法分离发现的一种新的细胞凋亡调节因子.GRIM-19存在于线粒体和细胞核中,在线粒体Ⅰ型呼吸过程中至关重要.GRIM-19参与细胞增生、凋亡调控过程,其表达水平降低或位点突变可以导致细胞的异常增生,同时,在病毒感染导致细胞癌变的过程中,GRIM-19可能是病毒癌基因结合的靶点.GRIM-19在肿瘤的形成和凋亡中发挥重要作用,可能成为一种新的肿瘤标记物,并可用于肿瘤早期筛选.     

GRIM-19在肿瘤及相关疾病中作用的研究进展

GRIM-19是一种新近发现的细胞死亡调控蛋白。笔者对其在肿瘤及相关疾病中所的起作用及机制进行综述，内容主要包括GRIM-19的细胞定位及其在细胞凋亡、呼吸链中的作用，以及其与病毒、细菌感染、各种恶性肿瘤的发生之间的关系。     

Livin与肿瘤的研究进展

凋亡抑制因子Livin是凋亡抑制蛋白家族的新成员。Livin在多种肿瘤组织中高表达,在细胞凋亡、细胞增生、细胞周期调控及参与肿瘤血管生成等过程中发挥重要作用,并且与化疗耐药性相关。大量研究表明,在许多恶性肿瘤组织中Livin异常表达与患者的预后密切相关,如肿瘤复发、生存期较短等。因此,以Livin为靶点的基因与免疫治疗也成为热点研究之一,为肿瘤的综合治疗提供了新的策略和方向。     

凋亡抑制因子Survivin与肿瘤关系研究进展(文献综述)

Survivin是一种细胞凋亡抑制因子 ,在转化细胞株和人体内几乎所有的恶性肿瘤中均有明显表达 ,而在这些恶性肿瘤周围的正常组织中均无表达。本文介绍了 Survivin的分子生物学结构、功能、作用机制、分布及其与各种肿瘤的关系     

survivin基因与肿瘤研究进展

目的 了解survivin基因在肿瘤研究中的作用。方法 采用文献回顾的方法，对survivin的分子结构。功能，作用机理，组织分布及其在肿瘤治疗中的作用进行综述。结果 survivin作为凋亡抑制蛋白（inhibitor of apoptosis protein,IAP）家族的新成员，独立于bcl-2，表达于几乎所有常见的人类恶性肿瘤组织，其表达与多种肿瘤患者预后不良密切相关。survivin通过直接抑制凋亡信号传导途径中最下游的效应分子caspase-3的活性而发挥其抑凋亡作用。抑制survivin的表达。以阻断其抑凋亡作用。可以达到治疗肿瘤的目的。结论 survivin广泛表达于多种人类恶性肿瘤组织，可作为预后不良的重要指标。并可作为抗肿瘤治疗中重要的新靶点。     

翻译控制肿瘤蛋白与肿瘤关系研究进展

翻译控制肿瘤蛋白(TCTP)是一种具有高度保守性和同源性的蛋白,广泛表达于所有真核有机体,其表达在转录和翻译水平受调节.在肿瘤中,TCTP参与调控细胞周期和增殖、抗凋亡以及肿瘤逆转,并与化疗耐药相关,有望成为抗肿瘤治疗靶标和肿瘤逆转靶标,为肿瘤治疗提供新思路.     

STK25的生物学特性及其与肿瘤关系的研究进展

Ⅲ生发中心激酶(GCK)是一类具有保守的丝/苏氨酸蛋白激酶特征的蛋白激酶家族,与p21活化蛋白激酶(PAK)家族同属于绝育20(Ste20)样激酶家族,参与了广泛的生物学效应,部分成员对外界的刺激可产生相应的应激反应,如细胞增殖、细胞死亡和细胞骨架重排等。STK25作为GCK家族第Ⅲ亚族(GCKⅢ)重要成员之一,参与上述的基本生理过程外,同时在能量代谢、肿瘤的发生与发展中发挥着重要作用。笔者将分别从STK25及家族部分成员的结构特点、分子生物学作用、能量代谢调节及抗肿瘤效应等方面一并进行综述,为最终将其应用于肿瘤的临床治疗提供借鉴。     

膀胱肿瘤的LOH及其与P53,RB关系的研究进展

对膀胱肿瘤的分子遗传学研究发现特杂色体位点上的杂合性丢失与肿瘤抑制基因Ｐ５３、ＲＢ有明显关系；并与膀胱肿瘤的分期、分级、预后有关。西文对近两年文献作一综述。     

P16基因与肿瘤关系的研究进展

Ｐ１６基因与肿瘤关系的研究进展于锡欣孟令详Ｐ１６基因，作为近年发现的对细胞周期有直接调节作用的负向调节基因，在多种肿瘤中普遍存在着改变（ａｌｔｅｒａｔｉｏｎ），已取代Ｐ５３，成为目前肿瘤基因研究的热点，现就Ｐ１６基因与肿瘤发生、治疗、预后的关系分别加...     

Bmi-1与干细胞及肿瘤干细胞关系的研究进展

多梳基因Bmi-1属PcG家族的一员,其可导致某些抑癌基因失活并为调节肿瘤干细胞的自我更新和分化所必需,可以作为肿瘤干细胞分选扩增的分子标记物.现在很多肿瘤都可以分离出致瘤能力强、有自我更新和分化潜能的细胞称为肿瘤干细胞,本文对Bmi-1基因在干细胞及肿瘤干细胞方面的研究进展进行综述.     

survivin和GRIM-19在前列腺癌组织中的表达

目的:探讨survivin和GRIM-19在前列腺癌组织中的表达及意义。方法:应用免疫组化、RT-PCR和Western印迹法检测survivin和GRIM-19在正常前列腺(NP)组织、良性前列腺增生(BPH)组织和前列腺癌(PCa)组织中的表达情况。结果:免疫组化结果显示survivin在NP、BPH和PCa组织中的表达率分别为6.25%、18.18%和90.62%(P<0.01);GRIM-19的表达率分别为87.50%、81.82%和9.37%(P<0.01)。半定量RT-PCR结果显示,在NP和BPH组织未检测到survivinmRNA表达,而PCa组织可检测到survivinmRNA高表达。Western印迹结果证实,在NP和BPH组织中有微量的survivin蛋白表达;而PCa组织可检测到survivin蛋白高表达;在NP和BPH组织中GRIM-19蛋白表达强阳性,而PCa组织中只有微量表达,两者比较差异均有显著性(P<0.01)。结论:survivin和GRIM-19的表达可能与PCa的发生密切相关。     

GRIM-19在肝细胞癌组织中的低表达及对其侵袭能力的影响

目的：检测GRIM-19在肝细咆癌（HCC）中的表达,分析其与HCC生物学行为的关系,并探讨GRIM-19对HCC侵袭能力的影响。方法：应用实时定量PCR技术检测83例HCC及其相对应的癌旁组织和8例正常肝组织中GRIM-19mRNA的表达,分析其与HCC临床病理因素之间的关系。用Westernblot法检测低侵袭力细胞株HL-7702、MHCC-97L和高侵袭力细胞株MHCC-97H、Huh-7中GRIM-19蛋白的表达。应用细胞转染技术将GRIM-19shRNA转入HL-7702和Huh-7,从而构建HL-7702和Huh-7的GRIM-19kd细胞系,并用Westernblot法检测转染效果。应用Transwell细胞迁移实验研究GRIM-19对HCC侵袭能力的影响。结果：实时定量PCR结果显示,83例HCC组织中有52例（62．65％）GRIM-19的表达低于相对应的癌旁组织（P〈O．01）,其表达水平也低于8例正常肝组织（P〈005）。GRIM-19的表达与HCC的TNM临床分期（P=O．011）、微血管浸润（P=O．047）和包膜浸润（P=O．013）密切相关。Westernblot显示HL-7702、MHCC-97L、MHCC-97H、Huh-7细胞系表达GRIM-19蛋白,且低侵袭力细胞株HL-7702、MHCC-97L中GRIM-19表达高于高侵袭力细胞株MHCC-97H、Huh-7。细胞侵袭实验显示GRIM-19低表达促进了HCC的侵袭能力。结论：GRIM-19在HCC的侵袭中起重要作用,可能为检测HCC的侵袭潜能提供新的研究思路。     

Plasmid-based Survivin shRNA and GRIM-19 carried by attenuated Salmonella suppresses tumor cell growth

Persistent activation of Survivin and its overexpression contribute to the formation, progression and metastasis of several different tumor types. Therefore, Survivin is an ideal target for RNA interference mediated-growth inhibition. Blockade of Survivin using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth. RNA interference does not fully ablate target gene expression, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Survivin-specific shRNA, we employed a combinatorial expression of Survivin-specific shRNA and gene associated with retinoid-interferon-induced mortality-19 (GRIM-19). Then, the GRIM-19 coding sequences and Survivin-specific shRNAs were used to create a dual expression plasmid vector and were carried by an attenuated strain of Salmonella enteric serovar typhimurium (S. typhimurium) to treat prostate cancer in vitro and in vivo. We found that the co-expressed Survivin-specific shRNA and GRIM-19 synergistically and more effectively inhibited prostate tumor proliferation and survival, when compared with treatment with either single agent alone in vitro and in vivo. This study has provided a novel cancer gene therapeutic approach for prostate cancer.     

GRIM-19和STAT3在乳腺癌组织中的表达及相关性

目的:通过研究干扰素/维甲酸联合应用诱导细胞凋亡相关基因19(GRIM-19)及其靶基因产物转录信号子与激活子3(STAT3)在乳腺癌组织与癌旁组织中的表达情况,探讨GRIM-19及其靶基因产物STAT3在乳腺癌中的表达及相关性。方法:采用western blot方法检测20例乳腺癌组织及其癌旁组织中GRIM-19与及下游基因STAT3的表达。结果:GRIM-19蛋白在乳腺癌组织中的表达明显低于癌旁组织(P=0.000),STAT3在乳腺癌组织中表达明显高于癌旁组织(P=0.000)。GRIM-19、STAT3表达呈负相关性(r=-0.67,P<0.001)。结论:GRIM-19在乳腺癌组织中低表达,而STAT3呈高表达,两者呈负相关。乳腺癌组织中GRIM-19低表达导致其对STAT3的抑制作用减弱。GRIM-19在乳腺癌组织中的低表达可能与乳腺癌的发生与发展密切相关。     

The clinicopathologic features of serum CA 19-9-positive colorectal cancers

The preoperative serum levels of carbohydrate antigen 19-9 (CA 19-9) were determined in 206 patients with colorectal cancer, 52 (25.2%) of whom were found to be positive. All of these patients had advanced cancers and significantly higher incidences of tumor invasion through the muscularis propria (91.3%) and lymph node involvement (54.5%). The incidences of liver metastasis and Dukes' stage D in the CA 19-9-positive group were 38.5% and 42.9%, respectively, significantly higher than those in the CA 19-9-negative group of 6.5% and 14.8%, respectively. Moreover, the incidence of liver metastasis in the CA 19-9-positive group patients with Dukes' stage D cancer was 95.2% (20/21); CA 19-9 showing higher specificity (81.7%) and a more positive predictive value (38.5%) for liver metastasis than the carcinoembryonic antigen (CEA). When a cutoff value of 160 U/ml was used, the specificity and positive predictive value reached 97.7% and 81.0%, respectively. An analysis of response operating characteristic (ROC) curves for liver metastasis revealed that CA 19-9 was more useful than CEA. The long-term survival of the CA 19-9-positive group patients was significantly worse than that of the CA 19-9-negative group patients (P < 0.0001), with no 1.25-year survivors in the former group when the cutoff value of 160U/ml was used. These results suggest that serum CA 19-9 as a useful preoperative indicator of liver metastasis and prognosis in colorectal cancer.     

CEA联合CA19-9检查在胆胰腺癌诊断中的价值

目的探讨CEA联合CA19-9检查在胆胰腺癌诊断中的价值。方法收集2012年8月至2015年7月贵州省人民医院肝胆外科收治的B超、CT、MRI等影像学检查提示胆道梗阻和胆道、胰腺占位,行CEA、CA19-9检查的患者800例,结合病理结果回顾性分析CEA联合CA19-9检查对胆胰腺癌诊断的准确率。结果单独CEA阳性(3.40μg/L)时,胆胰腺癌的诊断准确率为27.78%;单独CA19-9阳性(39.00 U/mL)时,胆胰腺癌的诊断准确率为35.43%;CEA和CA19-9均阳性时,胆胰腺癌的诊断准确率为85.71%;当提高阳性设定值CEA3.50μg/L,CA19-9200.00 U/mL时,胆胰腺癌的诊断准确率为95.42%。CEA和CA19-9同时阳性且持续升高时,依据之前的两组阳性设定值,胆胰腺癌的诊断准确率分别为95.91%和98.41%。结论 CEA联合CA19-9检查能够显著提高胆胰腺癌诊断的准确率,尤其当CEA3.50μg/L同时CA19-9200.00 U/mL,而且二者持续升高时。     

Interactions between diabetes and COVID-19: A narrative review

Diabetes, whether due to pancreatic beta cells insufficiency or peripheral resistance to insulin, has been suggested as a risk factor of developing severe acute respiratory disease coronavirus-2 (SARS-CoV-2) infections. Indeed, diabetes has been associated with a higher risk of infections and higher risk of developing severe forms of coronavirus disease 2019 (COVID-19) related pneumonia. Diabetic patients often present associated comorbidities such as obesity, hypertension and cardiovascular diseases, and complications of diabetes, including chronic kidney disease, vasculopathy and relative immune dysfunction, all of which make them more susceptible to infectious complications. Moreover, they often present low-grade inflammation with increased circulating interleukin levels, endothelial susceptibility to inflammation and dysfunction, and finally, hyperglycemia, which increases this risk. Additionally, corticosteroids, which count among the few medications which showed benefit on survival and mechanical ventilation requirement in COVID-19 pneumonia in large randomized controlled trials, are associated to new onsets of diabetes, and metabolic disorders in patients with previous history of diabetes. Finally, SARS-CoV-2 via the alternate effects of the renin-angiotensin system, mediated by the angiotensin-converting-enzyme 2, was also associated with insulin resistance in key tissues involved in glucose homeostasis, such as liver, skeletal muscles, and adipose tissue; and also, with impaired insulin secretion by pancreatic β-cells. In this work, we reviewed all elements which may help understand how diabetes affects patients with COVID-19, how treatments affect outcomes in patients with COVID-19, how they may cause new onsets of diabetes, and finally review how SARS-CoV-2 may inherently be a risk factor of developing diabetes, through immune-mediated diabetogenic mechanisms.     

Relationship between blood type and outcomes following COVID-19 infection

Since the onset of the COVID-19 pandemic, a concentrated research effort has been undertaken to elucidate risk factors underlying viral infection, severe illness, and death. Recent studies have investigated the association between blood type and COVID-19 infection. This article aims to comprehensively review current literature and better understand the impact of blood type on viral susceptibility and outcomes.