HCCR-1 mRNA and protein expression in human colorectal carcinoma and adjacent mucosa

目的 探讨HCCR-1 mRNA及HCCR-1蛋白在人大肠癌、癌旁组织及远端正常肠黏膜组织中的表达,及其临床病理学意义.方法 应用RT-PCR方法检测84例大肠癌、癌旁组织及15例远端正常肠黏膜组织中HCCR-1 mRNA水平,应用Western blot技术检测84例大肠癌、癌旁组织及15例远端正常肠黏膜组织中HCCR-1蛋白的表达水平,应用免疫组化SP法检测84例大肠癌、癌旁组织及15例远端正常肠黏膜组织、30例管状及绒毛管状腺瘤组织中HCCR-1蛋白的表达,分析HCCR-1表达水平与大肠癌临床病理特征的相关性.结果 HCCR-1 mRNA在人大肠癌及癌旁肠黏膜组织中均有表达.HCCR-1蛋白在癌旁肠黏膜组织和管状及绒毛管状腺瘤组织的阳性率分别为38%(32/84)、30%(9/30),两者差异无统计学意义(P>0.05),在大肠癌中的阳性率为81%(68/84),明显高于癌旁肠黏膜组织和管状及绒毛管状腺瘤的阳性率(P<0.05).大肠癌HCCR-1蛋白的高表达与肿瘤浸润深度呈明显正相关(P=0.007),与肿瘤是否转移无关(P>0.05).结论 人大肠癌存在HCCR-1蛋白的高表达,其与大肠癌的恶变演进有关.HCCR-1 mRNA的表达可能影响大肠癌的发生、发展.     

Sonic hedgehog mRNA及其蛋白在大肠癌的表达及其临床意义

目的 探讨大肠癌中Hedgehog信号通路相关基因Sonic hedgehog(SHH)的表达及其临床意义.方法 应用RT-PCR及免疫组织化学法(Envison二步法)检测本院2008年12月至2009年4月收集的43例大肠癌组织和距离癌10 cm以上的癌旁组织的SHHmRNA及蛋白的表达情况,并与20例非肠癌患者的正常大肠组织对照,分析其与大肠癌患者临床和病理各变量的相关性.结果 凝胶成像分析显示阳性表达的样本SHH mRNA片段大小为280 bp,与理论值相符,未表达的样本则未见相应条带.大肠癌组织SHHmRNA表达阳性率为27.9%(12/43),与癌旁组织的18.6%(8/43)差异无统计学意义(P＞0.05),但均显著高于正常大肠黏膜的0%(0/20)(均P＜0.05).SHH mRNA在大肠癌组织的表达强度显著高于癌旁组织(P＜0.05),在正常大肠黏膜则未见其表达.免疫组织化学显示SHH蛋白在大肠癌组织和癌旁组织均有阳性表达,细胞膜及胞质内出现棕黄褐色颗粒,背景不着色;正常大肠黏膜阴性表达.SHH蛋白在大肠癌组织的表达阳性率显著高于正常大肠黏膜[25.6%(11/43)比0%(0/20),P＜0.05],在大肠癌组织与癌旁组织、癌旁组织与正常大肠黏膜的表达阳性率差异则无统计学意义(均P＞0.05).SHH蛋白的表达强度大肠癌组织＞癌旁组织＞正常大肠黏膜(均P＜0.05).大肠癌组织中的SHH mRNA和蛋白表达强度与患者的年龄、性别、临床分期、肿瘤部位、肿瘤浸润深度、病理分型等变量均无明显关系(均P＞0.05).结论 SHH mRNA和蛋白在大肠癌组织中表达显著增强,但与临床和病理各变量无关联.     

大肠癌中WIF-1和Wnt2b的表达及其临床意义

目的通过检测WIF-1与Wnt2b在正常大肠黏膜、大肠腺瘤、大肠癌中的表达及其与大肠癌生成、侵袭转移之间的关系,探讨WIF-1与Wnt2b之间的关系。方法应用免疫组化SP法检测WIF-1和Wnt2b蛋白在15例癌旁正常组织、18例大肠腺瘤和103例大肠癌组织中的表达。结果 (1)WIF-1蛋白在大肠癌中的阳性率明显低于癌旁正常组织和腺瘤;Wnt2b蛋白在大肠癌中的阳性率高于癌旁正常组织和腺瘤。(2)WIF-1在大肠癌中的表达与患者的年龄、性别、分化程度、浸润程度、淋巴转移和远处转移均无关系(P>0.05);Wnt2b在大肠癌中的表达与大肠癌的分化程度、Dukes分期、淋巴结转移和远处器官转移相关(P<0.05),而与患者的年龄、性别均无关(P>0.05)。(3)大肠癌中WIF-1与Wnt2b的表达呈负相关(r=-0.199,P<0.05)。结论 WIF-1在正常大肠组织中呈阳性表达,在大肠癌的发病机制中可能发挥一定作用;Wnt2b的表达与大肠癌的发生、侵袭转移有关,联合检测WIF-1和Wnt2b有助于大肠癌的诊断、预防和治疗。     

MiR-145-5p在大肠癌中的表达及与多药耐药的关系

目的 探讨大肠癌中miR-145-5p和多药耐药基因(MDR1)蛋白P-糖蛋白（P-gp）的表达及两者的关系。方法 分别在组织、细胞水平采用SP法、Real-time PCR法、Western blotting法检测50例大肠癌 (CRC)患者组织及30例癌旁正常组织患者中P-gp的表达,miR-145-5p的表达变化对MDR1 mRNA及P-gp的影响及两者与临床病理特征之间的相关性。结果 大肠癌组织中miR-145-5p表达量明显低于癌旁正常组织,MDR1 mRNA及P-gp的表达量明显高于癌旁正常组织(r=-0.403,P<0.01)。大肠癌细胞(HCT-15)中miR-145-5p 能够抑制MDR1 mRNA及P-gp的表达(P<0.05)。结论 MiR-145-5p对大肠癌多药耐药基因及蛋白的表达具有调控作用,参与了大肠癌的发生、发展及多药耐药。     

Expression and clinical significance of WIF-1 and Wnt2b in colorectal carcinoma

目的 过检测WIF-1与Wnt2b在正常大肠黏膜、大肠腺瘤、大肠癌中的表达及其与大肠癌生成、侵袭转移之间的关系,探讨WIF-1与Wnt2b之间的关系.方法 应用免疫组化SP法检测WIF-1和Wnt2b蛋白在15例癌旁正常组织、18例大肠腺瘤和103例大肠癌组织中的表达.结果 (1)WIF-1蛋白在大肠癌中的阳性率明显低于癌旁正常组织和腺瘤;Wnt2b蛋白在大肠癌中的阳性率高于癌旁正常组织和腺瘤.(2)WIF-1在大肠癌中的表达与患者的年龄、性别、分化程度、浸润程度、淋巴转移和远处转移均无关系(P>0.05);Wnt2b在大肠癌中的表达与大肠癌的分化程度、Dukes分期、淋巴结转移和远处器官转移相关(P<0.05),而与患者的年龄、性别均无关(P>0.05).(3)大肠癌中WIF-1与Wnt2b的表达呈负相关(r=-0.199,P<0.05).结论 WIF-1在正常大肠组织中呈阳性表达,在大肠癌的发病机制中可能发挥一定作用;Wnt2b的表达与大肠癌的发生、侵袭转移有关,联合检测WIF-1和Wnt2b有助于大肠癌的诊断、预防和治疗.     

HCCR-1、Bcl-2的表达与结直肠癌的相关性分析

目的:分析人宫颈癌癌基因-1(Human Cervical Cancer Oncogene-1,HCCR-1)、B淋巴细胞瘤-2(B-cell Lymphoma-2,Bcl-2)表达与结直肠癌(Colorectal Cancer,CRC)的关系.方法:回顾性分析2019年3月至2022年3月本院收治的CRC患者113例.采用免疫组织化学法对CRC组织和癌旁组织中的HCCR-1、Bcl-2蛋白表达情况进行检测.对比CRC组织与癌旁正常组织间HCCR-1、Bcl-2蛋白表达水平;对比不同临床特征CRC组织的HCCR-1、Bcl-2蛋白表达情况;分析CRC组织中HCCR-1、Bcl-2蛋白表达相关性.结果:CRC组织中HCCR-1、Bcl-2蛋白阳性率均显著高于癌旁组织(P<0.05).CRC组织中HCCR-1、Bcl-2的表达均与Dukes分期相关(P<0.05).HCCR-1与Bcl-2蛋白表达呈负相关(P<0.05).结论:HCCR-1、Bcl-2蛋白在CRC组织中存在过表达状态,与其临床病理特征显著相关,并能作为一种新的预后判断指标和治疗靶点,为疾病诊断、预后判断提供参考价值.     

口腔鳞癌组织中PTPRK基因的异常表达及甲基化分析

目的分析口腔鳞癌(oral squamous cell carcinoma,OSCC)中受体型蛋白酪氨酸磷酸酶K(protein tyrosine phosphatase,receptor type K,PTPRK)基因的甲基化状态及其mRNA和蛋白表达,探讨OSCC的发生、发展机制。方法收集OSCC组织57例及癌旁正常口腔黏膜组织41例,采用甲基化特异性PCR(methylation specific PCR,MSP)、RT-qPCR和免疫荧光染色分析OSCC组织及癌旁正常口腔黏膜组织中PTPRK基因甲基化状态、mRNA和蛋白的表达以及甲基化与临床病理特征之间的关系。结果 OSCC组织中PTPRK基因甲基化阳性率高于癌旁正常口腔黏膜(59. 65%vs 34. 15%,P 0. 05)。OSCC组织中PTPRK的mRNA和蛋白表达量明显低于癌旁正常口腔黏膜(mRNA水平:0. 53±0. 23 vs 1. 05±0. 08,P 0. 001;蛋白水平:0. 43±0. 21 vs 1. 02±0. 78,P 0. 01),OSCC组织中PTPRK基因mRNA的表达与PTPRK基因的甲基化状态相关(P 0. 01)。PTPRK基因的高甲基化状态与淋巴结转移、TNM分期及病理分级相关(P 0. 05)。结论 PTPRK基因启动子区Cp G岛高甲基化可能与OSCC的发生、进展相关,有可能成为OSCC早期诊断及药物治疗的分子靶点。     

乳腺癌和癌旁乳腺组织中Notch1基因mRNA及蛋白的表达

目的 检测Notch1基因mRNA及Notch1蛋白在人乳腺癌和癌旁乳腺组织中的表达,分析其临床病理学意义.方法 应用逆转录聚合酶链反应(RT-PCR)方法榆测60例乳腺浸润性导管癌和60例癌旁乳腺组织中Notch1基因mRNA,应用免疫组织化学SP法检测60例乳腺浸润性导管癌、30例导管原位癌及60例癌旁乳腺组织Notch1蛋白的表达,分析Notch1表达水平与乳腺癌临床病理特征的相关性.结果 Notch1基因mRNA在人乳腺浸润性导管癌及癌旁乳腺组织中均有表达.Notch1蛋白在癌旁乳腺组织和导管原位癌中的阳性牢分别为55%(33/60)、70%(21/30),二者差异无统计学意义(P>0.05),在乳腺浸润性导管癌中的阳性率为90%(54/60),明显高于癌旁乳腺组织和导管原位癌的阳性率(P<0.05).乳腺浸润性导管癌Notch1蛋白的高表达与肿瘤的淋巴结转移(P=0.006)、病理学分级(P=0.001)和TNM分期(P=0.022)均呈显著正相关.结论 乳腺浸润性导管癌存在Notch1蛋白的高表达.Notch1蛋白高表达与乳腺癌的恶变演进有关.Notch1基因的表达可能影响乳腺癌的发生、发展.     

SEL1L基因在食管癌中的表达及意义

目的探讨SEL1L（human Sel-1-like）mRNA及其蛋白在食管癌组织中的表达及其临床意义。方法应用免疫组织化学SP法检测90例手术切除的食管鳞状细胞癌、35例距癌灶边缘5am以上切缘的正常黏膜、60例癌旁黏膜及20例内窥镜活检的食管鳞状上皮不典型增生组织中SEL1L蛋白的表达;运用原位分子杂交技术检测上述癌组织、正常黏膜、癌旁黏膜中SEL1L mRNA的表达。结果（1）SEL1L mRNA在食管鳞状细胞癌的表达率为80．0％（72／90）,较正常黏膜的14．3％（5／35）和癌旁黏膜的16．7％（10／60）高（P〈0．01）;SEL1L mRNA在有淋巴结转移组的表达阳性率为92．7％（38／41）比无淋巴结转移组69．4％（34／49）高（P〈0．01）。（2）SEL1L蛋白在鳞状细胞癌的表达阳性率为87．8％（79／90）,在鳞状上皮不典型增生中的表达阳性率为90．0％（18／20）。分别较正常黏膜的14．3％（5／35）和癌旁黏膜的13．3％（8／60）高（P〈0．01）。SEL1L蛋白表达与患者性别、年龄、肿瘤位置、大小、分化程度、浸润深度、淋巴结转移及临床分期均无明显相关性（P〉0．05）。（3）食管鳞状细胞癌组织中SEL1L mRNA和SEL1L蛋白的表达呈明显正相关（r=0．492,P〈0．01）。结论（1）SEL1L蛋白表达的调控主要在转录水平,SEL1L蛋白表达水平的升高主要是相应转录水平上调的结果。（2）SEL1L蛋白过表达可能是食管鳞状细胞癌发生的早期表现,SEL1L蛋白的检测可作为识别食管癌高风险患者的生物标记物。     

结直肠异常隐窝灶中BAI1、VEGF蛋白表达及意义

目的观察BAI1、VEGF在结肠异型增生性异常隐窝灶(aberrant crypt foci,ACF)、管状腺瘤及腺瘤癌变中的表达。方法联合放大内镜窄带成像(narrow-band imaging,NBI)技术观察ACF,采用免疫组化法检测40例异型增生性ACF、40例结肠管状腺瘤伴异型增生、35例管状腺瘤癌变及32例结直肠正常黏膜标本中BAI1和VEGF的表达。结果 BAI1蛋白在结直肠正常黏膜、异型增生性ACF、结肠管状腺瘤伴异型增生及管状腺瘤癌变组中的阳性率逐步降低,分别为93.8%、72.5%、45%、11.4%,且异型增生性ACF组阳性率明显低于结直肠正常黏膜组(P0.05),结肠管状腺瘤伴异型增生组阳性率明显低于异型增生性ACF组(P0.05),管状腺瘤癌变组阳性率明显低于管状腺瘤伴异型增生组(P0.05);VEGF蛋白在结直肠正常黏膜、异型增生性ACF、管状腺瘤伴异型增生及管状腺瘤癌变组中的阳性率逐步升高,分别为9.4%、52.5%、62.5%、94.3%,且异型增生性ACF组阳性率明显高于结直肠正常黏膜组(P0.05),管状腺瘤癌变组阳性率明显高于异型增生性ACF组及管状腺瘤伴异型增生组(P0.05);在异型增生性ACF、管状腺瘤及管状腺瘤癌变过程中BAI1和VEGF表达呈负相关(rs=-0.656,P0.05)。结论 BAI1低表达与VEGF高表达可能在结直肠癌前病变中起一定作用,可能为结直肠肿瘤的早期诊治提供新的作用靶点。     

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.