原发性胃癌组织中的端粒及端粒酶表达

目的观察端粒（ＴＲＦ）及端粒酶在胃癌形成及发展中的作用。方法采用ＤＮＡ琼脂糖凝胶杂交技术及端粒重复扩增ＰＣＲ方法检测１７例早期胃癌、８９例进展期胃癌组织及邻近正常组织中的平均ＴＲＦ长度及端粒酶活性。结果早期、进展期胃癌的ＴＲＦ长度及端粒酶活性表达均显著短于或高于邻近胃组织（Ｐ＜０．０５～０．０１），且端粒酶活性的表达主要表现在ＴＲＦ缩短或延长的胃癌组织中，而ＴＲＦ缩短与胃癌的分化程度相一致。结论端粒及端粒酶的异常状态可能与胃癌的发生发展密切相关，端粒酶活性及端粒缩短可以作为胃癌的诊断标志     

端粒酶活性检测在妇科肿瘤早期诊断中的应用

目的　观察端粒酶活性在妇科肿瘤中的阳性率 ,探讨妇科肿瘤发生过程中端粒酶所起的作用及其在妇科肿瘤早期诊断及预后中的诊断价值。方法　用以PCR为基础的端粒重复序列扩增 (TRAP)法测定 83例妇科肿瘤标本及正常对照标本中的端粒酶活性　结果　在 6 2正常对照标本中发现 5例有端粒酶的活性表达 (8.1% ) ,在 83例子宫颈癌、卵巢癌、子宫内膜癌中端粒酶阳性率为 94 % ,和正常对照组比较 ,差异显著 (P <0 .0 0 1)。结论　端粒酶活化是妇科肿瘤中的普遍现象 ,检测端粒酶活性对早期诊断妇科肿瘤有一定意义。     

组织端粒酶活性与宫颈癌相关研究

目的为了了解宫颈组织端粒酶活性与宫颈癌的关系.方法在30例宫颈癌、72例宫颈CIN和16例正常宫颈新鲜组织中,端粒酶重复序列扩增法(TRAP)用于检测组织端酶活性.结果3组端粒酶活性阳性分别有22例,21例和1例(P＜0.01),平均端粒酶活性分别为1.362±0.768、0.4236±0.247和0.048±0.026(P＞0.01).结论组织端粒酶活性的异常表达与宫颈癌进展密切相关,且随病程的进展端粒酶平均活性程度逐渐升高.     

端粒酶活性热耐受程度的观察

端粒酶为一种核糖核蛋白，能重新填补染色体末端已缩短的端粒［１］。１９９４年ＴＲＡＰ方法建立以来［２］，人们对多种正常、良性病变及恶性肿瘤组织端粒酶活性进行检测，结果显示该酶活性存在于绝大多数恶性肿瘤及极少数良性病变组织中，正常人体细胞无端粒酶活性。故人们提出端粒酶活性可能成为恶性肿瘤诊断的标记物及肿瘤治疗的新靶点［３］，但对端粒酶活性的生物化学及分子生物学特性尚所知甚少。我们选择具有端粒酶活性的乳腺纤维腺瘤及乳腺浸润性导管癌各２例，观察良、恶性肿瘤端粒酶活性热耐受程度的差异，试图探讨和了解端粒酶…     

原发性肝癌及慢性肝脏病变端粒酶活性的研究

目的比较原发性肝细胞癌（ＨＣＣ）及其癌旁不同慢性病变组织端粒酶活性的异同,探讨端粒酶活性在恶性肿瘤诊断中的意义。方法用ＴＲＡＰ方法检测３８例ＨＣＣ及其癌旁不同慢性病变肝组织的端粒酶活性。同时以４例正常肝组织为对照。结果３８例ＨＣＣ中３２例显示端粒酶活性（８６８％）。端粒酶活性与ＨＣＣ的细胞分化、类型、大小及有无乙型肝炎病毒（ＨＢＶ）感染无关,但与病人血清中甲胎蛋白（ＡＦＰ）水平相关。端粒酶活性阴性组ＡＦＰ水平明显低于各阳性组（Ｐ＜００１）。正常肝（４例）、先天性胆管闭锁（４例）、肝小叶间纤维增生（２例）、慢性病毒性肝炎（２例）及未见明显病变肝组织（７例）均未见有端粒酶活性。２５例肝硬化中４例端粒酶呈弱活性。结论端粒酶活性见于大多数ＨＣＣ及个别肝硬化组织,其活性可能在ＨＣＣ的发生、发展中起重要作用,有希望成为恶性肿瘤诊断的标记物。     

利用人外周血白细胞端粒长度推断年龄

目的：探讨人外周咀白细胞端粒长度与供体年龄的关系,为法医学通过微量软组织推断年龄提供依据。方法：选取105例0～81岁健康人外周血样本,采用Southern印迹法检测其端粒限制性片段(terminal restriction fragment,TRF)平均长度,并作相关及回归分析。结果：外周血白细胞TRF长度随年龄增长逐渐缩短,并呈不均衡趋势;端粒DNA平均每年缩短51bp;得到推断年龄回归方程：Y=-16．539X 236．287±9．832。结论：人外周血白细胞TRF长度与年龄呈负相关,此规律为通过端粒DNA长度推断个体年龄提供了可能。     

星形细胞肿瘤中端粒酶与PTEN的表达及相关性

目的：研究星形细胞肿瘤中的端粒酶活性和PTEN表达,探讨其在星形细胞肿瘤发生发展过程中的相关性,方法：收集手术切除经病理证实的星形细胞肿瘤110例,8例正常脑组织作对照。用端粒酶原位杂交检测盒检测组织标本端粒酶活性,用LSAB法检测PTEN表达。结果：星形细胞肿瘤端粒酶活性和PTEN的阳性检出率分别为50％（55／110）和39．1％（43／110）,且随着肿瘤恶性程度的增加,端粒酶活性程度升高（P＜0．01）,端粒酶活性与PTEN表达有相关性（P＜0．01）,结论：端粒酶活性与星形细胞肿瘤的分化程度有关,提示端粒酶活性可能是星形细胞肿瘤恶性程度的重要标记物,PTEN蛋白可能对端粒酶的活性有调节作用。     

卵巢肿瘤组织中端粒酶活性的表达

目的分析端粒酶活性在卵巢肿瘤中的表达,探讨端粒酶活性作为卵巢肿瘤诊断肿瘤标记物的意义。方法取冰冻肿瘤组织,采用端粒重复序列扩增法（Telomeric Repeat Amplication Protocol）,结合银染,共测定了27例卵巢癌、5例良性卵巢肿瘤、22例卵巢癌癌旁组织以及12例正常卵巢组织中端粒酶活性,并分析其与组织分级、FIGO分期、病理类型以及有无转移的关系。PCR产物以采用聚丙烯酰胺凝胶电泳分析,以出现特征性的6-bp间隔的特征性阶梯状条带为阳性。出现〉100bp的条带为强阳性,出现〈99bp的条带为中低阳性。结果本实验共对66份标本进行了检测,12例正常卵巢组织中,仅有2例表达端粒酶活性;5例卵巢良性肿瘤中,1例表达端粒酶弱阳性。27例卵巢恶性肿瘤标本中,有23例表达端粒酶活性（其中强阳性16例）;在检测的22例卵巢上皮癌的癌旁组织中,有12例表达端粒酶弱阳性。卵巢恶性肿瘤的端粒酶活性表达阳性率显著高于卵巢良性肿瘤（P=0.0090）和正常卵巢（P=0.0000）。Ⅰ-Ⅱ期患者端粒酶活性阳性率71%,Ⅲ-Ⅳ期患者端粒酶活性阳性率90%（P=0.269）。而强阳性率Ⅲ-Ⅳ期明显高于Ⅰ-Ⅱ期（P=0.009）。在肿瘤类型和组织学分级中,端粒酶阳性表达率均没有显著差异。结论在卵巢恶性肿瘤组织中端粒酶活性有较高的表达率;早期和晚期卵巢肿瘤组织中端粒酶活性阳性率没有明显差异,但晚期卵巢肿瘤组织中的端粒酶活性程度较高;端粒酶活性有可能作为早期诊断卵巢肿瘤的标记物之一,并可以作为卵巢肿瘤判断预后的指标。     

6A8α-甘露糖苷酶表达对人鼻咽癌细胞CNE-2L2端粒酶活性和端粒长度的影响

探讨端粒长度与端粒酶活性在人鼻咽癌细胞CNE-2L2恶性行为改变前后的变化，建立研究恶性行为改变与端粒长度与端粒酶活性间关系的细胞模型。与6A8α-甘露糖苷酶表达正常的CNE-2L2细胞(野生型细胞W，转导空载体的细胞M及转导无关DNA片段的细胞S)相比，6A8α-甘露糖苷酶表达低下的细胞(AS)接种裸鼠皮下后的肿瘤性生长受抑。用Telo TAGGG Telomere Length Assay Kit及Telomerase PCR ELISA Kit分别测定端粒长度及端粒酶活性，用RT-PCR方法分析端粒重复序列结合因子(TRF)的转录水平。见AS细胞的端粒明显缩短(6．78Kb，W细胞为8．40Kb，M细胞为8．34kb，S细胞为9．56kb)，但端粒酶活性及端粒重复序列结合因子l和2(TRFl和2)的转录水平未见改变。实验表明，恶性行为降低的CNE-2L2细胞的端粒变短，但与端粒酶活性及TRF1／2无关，提示在CNE-2L2细胞中可能存在着端粒酶及TRF1／2以外的调节端粒长度的机制。这为研究肿瘤细胞恶性行为改变与端粒长度与端粒酶活性间关系提供了一个模型。     

端粒相关蛋白TIN2

TIN2(TRF1相互作用核蛋白2)是一重要的端粒相关蛋白。人TIN2蛋白包括N端,TRF1交互作用区(TRF1-Int)和C端3个结构域。它在TRF1复合物、TRF2复合物和Shelterin的功能中扮演关键角色,协同其它端粒蛋白维持端粒长度、结构和功能。TIN2与个体发育、细胞分化和肿瘤发生密切相关。     

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.     

Beta-endorphin and drug-induced reward and reinforcement

Although drugs of abuse have different acute mechanisms of action, their brain pathways of reward exhibit common functional effects upon both acute and chronic administration. Long known for its analgesic effect, the opioid beta-endorphin is now shown to induce euphoria, and to have rewarding and reinforcing properties. In this review, we will summarize the present neurobiological and behavioral evidences that support involvement of beta-endorphin in drug-induced reward and reinforcement. Currently, evidence supports a prominent role for beta-endorphin in the reward pathways of cocaine and alcohol. The existing information indicating the importance of beta-endorphin neurotransmission in mediating the reward pathways of nicotine and THC, is thus far circumstantial. The studies described herein employed diverse techniques, such as biochemical measurements of beta-endorphin in various brain sites and plasma, and behavioral measurements, conducted following elimination (via administration of anti-beta-endorphin antibodies or using mutant mice) or augmentation (by intracerebral administration) of beta-endorphin. We suggest that the reward pathways for different addictive drugs converge to a common pathway in which beta-endorphin is a modulating element. beta-Endorphin is involved also with distress. However, reviewing the data collected so far implies a discrete role, beyond that of a stress response, for beta-endorphin in mediating the substance of abuse reward pathway. This may occur via interacting with the mesolimbic dopaminergic system and also by its interesting effects on learning and memory. The functional meaning of beta-endorphin in the process of drug-seeking behavior is discussed.     

PTEN与信号转导及肿瘤

ＴＥＮ[1] (ｐｈｏｓｐｈａｔａｓｅａｎｄｔｅｎｓｉｎｈｏｍｏｌｏｇｙｄｅｌｅｔｅｄｏｎｃｈｒｏｍｏｓｏｍｅｔｅｎ)又名ＭＭＡＣ1 [2 ] (ｍｕｔａｔｅｄｉｎｍｕｔｉｐｌｙａｄａｎｃｅｄｃａｎｃｅｒ 1 )和ＴＥＰ1 [3 ] (ＴＧＦ -βｒｅｇｕｌａｔｅｄａｎｄｅｐｉｔｈｅｌｉａｌｃｅｌｌ -ｒｉｃｈｅｄｐｈｏｓｐｈａｔａｓｅ 1 ) (以下均称为ＰＴＥＮ) ,是 1 997年由 3个研究小组先后发现的一个具有双特异磷酸酶活性的抑癌基因。ＰＴＥＮ基因异常广泛存在于人类多种恶性肿瘤 ,如恶性神经胶质瘤、前列腺癌、子宫内膜癌、黑色素瘤等…     

Tobacco and alcohol and the risk of head and neck cancer

Summary We carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.     

Postinfectious immunodeficiency and autoimmunity: pathogenic and clinical values and implications

Autoimmunity is still a mystery of clinical immunology and medicine as a whole. The etiology and pathogenesis of autoimmune disorders remain unclear and, thus, are assessed as a balance between hereditary predisposition, triggering factors and the appearance of autoantibodies and/or self-reactive T cells. Among the immunological armamentarium, molecular mimicry, based on self-reactive T- and B-cell activation by cross-reactive epitopes of infectious agents, is of special value. Hypotheses regarding the possible involvement of molecular mimicry in the development of postinfectious autoimmunity are currently very intriguing. They provide new approaches for identifying etiological agents that are associated with postinfectious autoimmunity, paired microbial- and tissue-linked epitopes targeted for autoimmune reaction determination, postinfectious autoimmunity pathogenesis recognition and specific prevention, and therapy for autoimmune disorder development.     

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.     

类赖氨酰氧化酶2与肿瘤转移和发生

类赖氨酰氧化酶2(lysyl oxidase-like 2,LOXL2)是赖氨酰氧化酶(lysyl oxidase,LOX)基因家族的成员之一,其表达产物能促进胶原沉积.LOXL2的过表达能促进纤维化,并与肿瘤侵袭、转移及不良预后有关.目前大部分学者认为LOXL2是一种转移促进基因,也有实验支持其是一种肿瘤抑制基因.研究发现LOXL2可以通过激活Snail/Ecadherin通路或Src/FAK通路促进转移.LOXL2有望作为肿瘤生物标志物,用于预后判断,成为一个新的治疗靶点.