肝细胞癌中Wnt-5a、Ror2蛋白的表达及临床意义

目的探讨肝细胞癌(HCC)中Wnt-5a、Ror2蛋白表达的关系及临床意义。方法采用免疫组化SP法检测Wnt-5a及Ror2在62例HCC癌与癌旁组织中的表达。结果对比于癌旁组织,Wnt-5a在85.49%的HCC癌组织内表达明显减低或缺失(P0.001);Ror2在80.65%的HCC癌组织内表达明显减低或缺失(P0.001),两者表达呈正相关性(r=0.462,P=0.04);并且均相关于高的肿瘤分期(P0.05)、高的AFP水平(P0.05)以及高的Ki-67指数(P0.05)。结论 Wnt-5a和Ror2在HCC中可能发挥抑癌基因样作用,其减低或缺失表达可能与HCC的发生、发展有关。     

syndecan-1表达对肝细胞癌增殖、血管生成和转移的影响

目的探讨syndecan-1在肝细胞癌（hepatocellular carcinoma,HCC）表达的临床病理意义,及其与肿瘤转移、增殖和血管生成的关系。方法用免疫组织化学染色检测了syndecan-1在30例HCC原发癌组织、癌旁组织和肝内转移灶的表达,血管内皮生长因子（vascularendothelial growth factor,VEGF）和CD34-微血管密度（microvessel density,MVD）在原发灶和肝内转移灶的表达,及Ki-67在原发灶的表达。结果与HCC癌旁组织相比,syndecan-1在原发癌组织表达水平明显增高,syndecan-1在肝内转移灶表达水平明显下降（χ2=25.62,P〈0.001）。在HCC原发癌组织中,syndecan-1表达强度与Ki-67指数呈正相关（r=0.386,P〈0.05）。在肝内转移灶中,syndecan-1表达强度与CD34-MVD呈正相关（r=0.370,P〈0.05）。结论 HCC组织syndecan-1表达可能影响肿瘤转移、增殖和血管生成,提示syndecan-1在HCC生长和转移中的特殊作用可能为HCC有效治疗策略提供新思路。     

乳腺癌中Wnt/β-catenin信号通路相关蛋白的表达及意义

目的:本研究旨在探讨乳腺癌组织和细胞中Wnt/β-catenin信号通路相关蛋白Wnt-1和β-catenin的表达及意义。方法:选取我院于2015年1月~2017年1月间收治的150例乳腺癌患者作为研究对象。150例乳腺癌的肿瘤组织样本(实验组)来源于手术切除的、临床病理资料保存完整的乳腺癌石蜡切块;相应的临近非肿瘤组织样本(对照组)取自距离肿瘤组织0.5~1 cm的上述乳腺癌患者相应癌旁组织。采用real-tme PCR和Western blot法检测Wnt-1和β-catenin的表达情况。将乳腺癌细胞MCF-7分为3组:阴性对照组(MCF-7细胞)、激动剂组[MCF-7细胞+Wnt3a(1 mg/L)]和拮抗剂组[MCF-7细胞+DKK1(16μmol/L)]。采用real-time和Western blot检测Wnt-1和β-catenin表达情况。结果:与对照组相比,实验组患者Wnt-1和β-catenin的mRNA和蛋白表达量均升高(P0.05)。实验组患者肿瘤组织的Wnt-1表达阳性率和β-catenin表达阳性率均高于对照组(P0.05)。Wnt-1表达与乳腺癌患者肿瘤转移(x~2=5.352,P=0.021)、肿瘤分期(x~2=9.412,P=0.002)及肿瘤直径(x~2=9.412,P=0.002)密切相关(P0.05)。β-catenin表达与乳腺癌患者肿瘤转移(x~2=9.851,P=0.002)、肿瘤分期(x~2=5.661,P=0.017)密切相关(P0.05)。与对照组相比,激动剂组Wnt-1和β-catenin mRNA和蛋白表达量升高(P0.05);与对照组相比,拮抗剂组Wnt-1和β-catenin mRNA和蛋白表达量降低(P0.05)。结论:乳腺癌中Wnt/β-catenin信号通路相关蛋白Wnt-1和β-catenin表达上调,且其表达与肿瘤恶性状态密切相关。     

PDCD5通过Wnt/β-catenin通路抑制肾细胞癌侵袭转移及其机制研究

目的探讨肾细胞癌(RCC)患者PDCD5的表达水平及其参与调控RCC侵袭与转移的可能机制。方法利用免疫组化检测RCC标本与癌旁组织中PDCD5的蛋白表达水平,同时分析PDCD5与疾病分期、预后的相关性;利用transwell及划痕实验检测PDCD5对肾癌细胞系A498侵袭与转移的影响;利用Western blot检测A498细胞转染PDCD5后MMP2、MMP9、E-cadherin、N-cadherin及Wnt/β-catenin通路的变化。结果 (1)与癌旁组织相比,RCC标本中PDCD5明显下调(P0.001),且与疾病分期及预后正相关;(2)PDCD5明显抑制了肾癌细胞系A498的转移与侵袭能力(P0.01);(3)PDCD5通过抑制A498细胞系中MMP2、MMP9及N-cadherin的表达水平,增强E-cadherin的表达水平调控EMT转化,同时Wnt/β-catenin通路关键蛋白下调。结论 PDCD5通过调控Wnt/β-catenin通路影响肾细胞癌EMT转化,负性调控了RCC病人的侵袭与转移进程。     

β-catenin和wnt-1在食管癌组织中的表达及其临床意义

研究β-catenin和wnt-1在食管癌组织中的蛋白表达水平及其与肿瘤病理参数和预后的关系。选取40例具有完整病理资料、手术切除的食管癌蜡块标本和其中10例癌旁组织,应用免疫组化方法检测其β-catenin和wnt-1的蛋白表达水平,比较β-catenin和wnt-1蛋白在组织中的表达差异,及其与食管癌各种临床病理特征和预后的关系。结果显示,β-cate-nin的表达水平与临床分期有相关性（P〈0.05）;wnt-1的表达水平与细胞分化、预后有相关性（P〈0.05）;β-catenin、wnt-1的蛋白表达水平与性别、年龄无相关性（P〉0.05）。wnt-1和β-catenin作为Wnt信号通路的相关蛋白,与食管癌的发展和预后有一定关系。     

结直肠癌中FOXO3a表达及其与β-catenin、E-cadherin关系

目的探讨结直肠癌组织中FOXO3a的表达及其与Wnt信号通路中心蛋白β-catenin和该通路间接调节因子E-cadherin的关系。方法应用免疫组化SP法检测112例结直肠癌组织和103例正常肠黏膜组织中FOXO3a、β-catenin及E-cadherin蛋白的表达,分析三者表达与临床病理特征的关系以及FOXO3a与β-catenin、E-cadherin表达的相关性。结果 (1)FOXO3a在结直肠癌组织中的阳性率(57.14%)较正常肠黏膜组织(93.20%)明显降低(P<0.001),β-catenin在结直肠癌组织中的异常表达率(73.21%)较正常肠黏膜组织(2.91%)明显升高(P<0.001),E-cadherin在结直肠癌组织中的阳性率(70.54%)较正常肠黏膜组织(98.06%)明显降低(P<0.001)。(2)结直肠癌组织中FOXO3a、E-cadherin低表达以及β-catenin异常表达与肿瘤深层浸润、差分化、淋巴结转移和TNM高分期密切相关(P<0.05),与患者性别、年龄、肿瘤大小均无关(P>0.05)。(3)结直肠癌组织中FOXO3a的阳性表达与β-catenin的异常表达呈负相关(rs=-0.361,P<0.001),与E-cadherin的阳性表达呈正相关(rs=0.351,P<0.001)。结论 FOXO3a、E-cadherin表达降低与β-catenin异常表达可能在结直肠癌的发生、侵袭和转移过程中起重要作用,FOXO3a抑制结直肠癌发生、发展的作用机制可能与Wnt信号通路有关。     

E-cadherin的表达与肝细胞癌侵袭和转移的关系

目的研究上皮性钙黏蛋白（E-cadherin）在人肝细胞癌（HCC）中的表达情况,探讨其与肝癌的相关性。方法选择56例有完整随访资料的肝细胞癌及相应癌旁组织标本、20例正常肝组织标本,用RT-PCR方法检测E-cadherinmRNA的表达;用免疫组织化学方法检测E-cadherin的表达。结果①E-cadherin在肝细胞癌组织中的表达显著低于癌旁组织和正常组织（P〈0．05）,而在癌旁组织和正常组织中的表达无差异;②E-cadherin在肝癌组织中的表达与术后复发时间呈正相关（P〈0．05）,与病理分期呈负相关（P〈0．05）;③癌组织中E-cadherin表达与肝外转移呈负相关（P〈0．05）;④癌旁组织中E-cadherin表达与术后复发时间呈正相关（P〈0．05）。结论E-cadherin表达缺失或下调与肝癌的分化程度、侵袭转移能力和复发倾向相关,对肝癌临床转归的评估有一定指导意义。     

活化白细胞黏附分子、E-钙黏蛋白和β-连环蛋白在甲状腺乳头状癌中的表达及意义

目的通过对甲状腺乳头状癌(PTC)、结节性甲状腺肿和癌旁正常组织中活化白细胞黏附分子(ALCAM)、E-钙黏蛋白(E-cadherin)和β-连环蛋白(β-catenin)蛋白表达水平的检测,分析三者在PTC发生、发展过程中的作用及三者之间的相关性,探讨ALCAM、E-cadherin和β-catenin在PTC中的作用机制。方法采用免疫组织化学法、Western blotting法检测ALCAM、E-cadherin和β-catenin在PTC中的表达并分析三者的变化与临床病理特征的关系。结果 PTC组织中ALCAM的阳性率明显高于结节性甲状腺肿和癌旁正常组织(P0.05);PTC组织中E-cadherin的阳性表达率明显低于结节性甲状腺肿和癌旁正常组织(P0.05);PTC样本中β-catenin的异位表达率明显高于结节性甲状腺肿和癌旁正常组织(P0.05)。三者的阳性率在结节性甲状腺肿和癌旁正常组织中无明显差异(P0.05)。三者的异常表达与PTC淋巴结转移有关(P0.05),与患者年龄、性别、肿瘤大小无关(P0.05)。结论在PTC组织中ALCAM、β-catenin高表达,E-cadherin呈现低表达,三者的异常表达与淋巴结转移相关。三者在PTC的发生、发展和转移的过程中起重要的作用。     

结直肠癌组织中APC、β-catenin和COX-2的表达及临床意义

目的探讨结肠腺瘤性息肉病蛋白(adenomatous polyposis coli, APC)、β-catenin和COX-2在结直肠癌组织中的表达及与临床病理特征的关系。方法应用组织芯片联合全自动免疫组化EnVision两步法检测APC、β-catenin和COX-2在112例结直肠癌组织和癌旁正常结直肠组织中的表达。结果 APC在结直肠癌组织中低表达,与肿瘤分化程度相关(P0.05);β-catenin和COX-2在结直肠癌组织中高表达,与肿瘤分化程度、浸润深度、淋巴结转移及临床分期相关(P0.05);APC的表达与β-catenin、COX-2的表达呈负相关(r_s=-0.551,P0.01;r_s=-0.542,P0.01);β-catenin与COX-2的表达呈正相关(r_s=0.558,P0.01)。结论 APC、β-catenin和COX-2三者在结直肠癌的发生、发展中起重要作用,且β-catenin和COX-2的表达影响结直肠癌的侵袭及转移,其机制可能与APC、β-catenin和COX-2蛋白通过Wnt信号通路在结直肠癌中的作用相关。     

甲状腺乳头状癌组织中E-cadherin、β-catenin 和cyclinD1蛋白表达及意义

目的 探讨甲状腺乳头状癌组织中E-cadherin、β-catenin和cyclinD1蛋白表达对其发生、发展的影响.方法 应用免疫组化EnVision法检测36例甲状腺乳头状癌组织、27例甲状腺腺瘤旁组织E-cadherin、β-catenin 和cyclinD1的蛋白表达,同时分析三者表达水平的变化与其它病理参数的关系.结果 E-cadherin在甲状腺乳头状癌的表达下降,阳性率为30.56%(P<0.05),与肿瘤淋巴结转移相关(P<0.01);β-catenin在癌组织中细胞核/核周区呈强阳性表达,且表达率明显升高为80.56%(P<0.01),其异常表达与肿瘤淋巴结转移相关(P<0.01);cyclinD1在癌组织中的阳性表达率为72.22%(P<0.01),与肿瘤淋巴结转移有关(P<0.05).此外,E-cadherin的低表达与cyclinD1的过表达呈负相关(P<0.05),β-catenin的异位高表达与cyclinD1的过表达呈正相关(P<0.05).结论 E-cadherin表达缺失和β-catenin异位高表达可能通过诱导cyclinD1的过表达,进而影响甲状腺乳头状癌的发生和发展.     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.