子宫颈鳞状细胞癌中GDF-15与EMT相关蛋白的表达及相关性

目的检测子宫颈鳞状细胞癌组织中GDF-15及上皮-间质转化(epithelial-mesenchymal transition, EMT)相关蛋白E-cadherin、N-cadherin、vimentin的表达,探讨GDF-15在子宫颈鳞状细胞癌发生、侵袭中的生物学作用。方法采用免疫组化EliVision两步法检测85例子宫颈鳞状细胞癌组织及其配对癌旁子宫颈组织中GDF-15、E-cadherin、N-cadherin、vimentin的表达,分析GDF-15表达与子宫颈鳞状细胞癌临床病理特征的关系及GDF-15与EMT相关蛋白表达的相关性。结果与癌旁子宫颈组织相比,子宫颈鳞状细胞癌组织中GDF-15、N-cadherin和vimentin表达上调,E-cadherin表达下调,差异有统计学意义(P均0.05)。子宫颈鳞状细胞癌组织中GDF-15表达与N-cadherin和vimentin表达呈正相关(r_s=0.422,r_s=0.374),与E-cadherin表达呈负相关(r_s=-0.305)。结论 GDF-15与EMT相关蛋白在子宫颈鳞状细胞癌组织中异常表达,过表达GDF-15在子宫颈癌的发生、侵袭中发挥重要作用,可能与诱导子宫颈癌EMT有关。     

食管癌中TAZ介导食管癌上皮细胞-间充质转化的作用

目的探讨TAZ介导的上皮细胞-间充质转化(epithelial-mesenchymal transformation,EMT)在食管癌发生、发展中的作用。方法采用免疫组化SP法检测143例食管癌组织中TAZ蛋白与EMT相关指标蛋白的表达,并分析两者的相关性。结果食管癌组织中TAZ、vimentin蛋白表达高于癌旁组织,E-cadherin、CKpan的表达低于癌旁组织,差异均有统计学意义(P0.05)。食管癌组织中TAZ蛋白表达与表皮相关蛋白E-cadherin、CKpan的表达呈负相关(r_s=-0.180,P=0.032;r_s=-0.215,P=0.01);与间质相关蛋白vimentin的表达呈正相关(r_s=0.200,P=0.017)。结论食管癌组织中TAZ高表达,食管癌及癌旁组织中TAZ和EMT相关蛋白的表达差异均有统计学意义,且两者的表达有一定的相关性。TAZ可能参与食管癌的EMT过程,促进食管癌的发展侵袭。     

Snail在乳腺癌中的表达及其与上皮-间质转化的关系

目的研究Snail蛋白在乳腺癌组织中的表达,并探讨Snail蛋白及其调控的上皮-间质转化(EMT)与乳腺癌恶性生物学行为的相关性。方法采用免疫组织化学SP法检测20例正常乳腺组织、60例乳腺癌组织(非特殊性浸润性导管癌)及其中20例乳腺癌癌旁组织中Snail蛋白、上皮标记物E-cadherin蛋白、间质标记物Vimentin蛋白的表达;分析乳腺癌组织中3种蛋白表达强度的相关性,以及Snail蛋白表达与乳腺癌淋巴结转移的关系。结果①在正常乳腺组织、乳腺癌癌旁组织、乳腺癌组织中,Snail蛋白表达逐渐递增,其阳性率分别为0、30%、53.3%;Vimentin蛋白表达亦逐渐递增,其阳性率分别为0、40%、63.3%;E-cadherin蛋白表达则逐渐减少,其阳性率分别为100%、75%、56.7%;正常乳腺组织、乳腺癌癌旁组织与乳腺癌组织间3种蛋白的表达差异均具有统计学意义(均P0.05)。②Snail蛋白表达与Vimentin蛋白表达呈显著正相关(r=0.536、P=0.000);Snail蛋白表达与E-cadherin蛋白表达呈负相关(r=-0.413、P=0.001);3种组织中,E-cadherin和Vimentin蛋白两者的表达差异呈显著负相关(r=-0.526、P=0.000)。③Snail蛋白的表达与乳腺癌腋窝淋巴结转移呈正相关,差异有统计学意义(r=0.600、P=0.000)。结论锌指转录因子Snail可能通过参与调控EMT过程从而在乳腺癌的发生和侵袭过程中发挥重要作用,并推动乳腺癌的远处淋巴结转移。     

IL-8在胃癌组织上皮间质转化过程中表达增强

目的研究胃癌上皮间质转化(EMT)过程中趋化因子IL-8的调节机制与意义。方法用Western blot、酶联免疫吸附试验(ELISA)等技术,检测胃癌组织与正常组织中IL-8以及EMT相关基因(E-cadherin, vimentin, twist等)的表达,胃癌细胞系MGC-803对IL-8与胃癌细胞EMT的相关性进行分析和探讨。结果肿瘤组织中IL-8的表达水平(710.5±89.9)显著高于癌旁组织(510.5±85.5)(P0.001)。与正常组织相比,胃癌组织中IL-6、twist及vimentin表达水平明显高于正常胃黏膜组织(P0.05),而E-cadherin表达水平低于正常组织(P0.05)。IL-8因子的分泌与twist蛋白(P0.001)和vimentin蛋白(r=0.454,P0.001)表达水平呈显著正相关性,与E-cadherin蛋白表达水平呈显著负相关性(P0.001)。结论胃癌组织中趋化因子IL-8的表达量增强, IL-8与胃癌侵袭转移相关,同时IL-8的表达量也可作为胃癌侵袭转移患者预后判断的参考标准之一。     

Livin表达与胃癌上皮-间质转化的关系及临床意义

目的探讨Livin表达与胃癌上皮-间质转化(epithelial-mesenchymal transition,EMT)的关系及临床意义。方法采用免疫组化法检测110例胃癌及相应癌旁正常胃组织中Livin和EMT标志蛋白的表达,分析Livin表达与胃癌临床病理特征的关系及Livin表达与EMT标志蛋白表达的相关性。应用Western blot法检测8例新鲜胃癌组织中Livin和EMT标志蛋白的表达。结果胃癌组织中Livin阳性率(59. 1%)明显高于相应癌旁组织(8. 2%)(P 0. 05)。Livin表达与胃癌淋巴结转移相关(P 0. 001)。Western blot检测结果显示Livin在有淋巴结转移的胃癌组中表达高于无淋巴结转移组。胃癌组织中E-cadherin、vimentin和N-cadherin的阳性率分别为29. 1%、30. 9%和57. 3%。胃癌组织中Livin与E-cadherin的表达呈负相关(r=-0. 322,P=0. 001),与vimentin和N-cadherin的表达呈正相关(r=0. 276,P=0. 004; r=0. 216,P=0. 024)。Livin高表达的胃癌组织中,vimentin和N-cadherin亦高表达,而E-cadherin表达降低,反之亦然。结论 Livin表达与胃癌组织的EMT表型有关,并促进胃癌的转移。     

EphA2在乳腺癌中的表达及其与上皮间质转化的关系

目的　研究EphA2、上皮间质转化（EMT）在乳腺癌中的表达情况及意义,探讨EphA2与EMT在乳腺癌的侵袭与转移过程中的关系。 方法　采用免疫组织化学方法检测30例乳腺纤维瘤组织和110例乳腺癌中EphA2、E-钙黏蛋白（E-cadherin）、β-连环蛋白（β-catenin）、波形蛋白（vimentin）的表达情况,分析其与乳腺癌临床病理因素的关系及EphA2、E-cadherin蛋白、β-catenin蛋白、vimentin蛋白表达的相关性。 结果　在30例乳腺纤维瘤组织中EphA2、E-cadherin蛋白、β-catenin蛋白、vimentin蛋白阳性率分别为20%、90%、26.67%、13.33%,在110例乳腺癌中的阳性率分别为61.82%、34.54%、64.54% 、68.18%。EphA2的高表达、E-cadherin蛋白的低表达、β-catenin蛋白和vimentin蛋白的高表达与临床分期、淋巴结转移、组织学分级显著相关（P<0.05）,EphA2的高表达与E-cadherin蛋白的低表达呈负相关（P<0.05）,与β-catenin蛋白、vimentin蛋白的高表达呈正相关（P<0.05）。 结论　EphA2、E-cadherin蛋白、β-catenin蛋白、vimentin蛋白与乳腺癌的侵袭与转移有相关性;EphA2可能通过调控E-cadherin蛋白、β-catenin蛋白、vimentin蛋白的表达来促进EMT,进而在乳腺癌的侵袭和转移过程发挥重要作用。     

转移相关基因FMNL2参与胃癌侵袭转移的相关性分析

目的探讨转移相关基因FMNL2与胃腺癌上皮-间质转化(epithelial-mesenchymal transitions,EMT)的关系,为胃癌转移机制提供新线索。方法收集20例正常胃黏膜、92例胃腺癌、43例淋巴结转移癌组织进行免疫组化分析,比较3种组织标本中FMNL2和E-cadherin、CK、vimentin的阳性率,分析FMNL2表达与胃癌EMT的关系。结果FMNL2、vimentin在胃腺癌中的表达明显高于正常胃黏膜组织;在淋巴结转移癌中的表达高于胃腺癌组织(P0.05)。上皮标志物E-cadherin、CK在正常黏膜中的表达显著高于胃腺癌及淋巴结组织(P0.05)。相关性分析发现FMNL2与E-cadherin、CK呈负相关(r=-0.466,P=0.000,r=-0.327、P=0.000);与vimentin表达呈正相关(r=0.553,P=0.000)。结论 FMNL2与胃腺癌EMT相关,并可能通过EMT促进胃腺癌侵袭转移。     

PTEN与食管鳞状细胞癌上皮-间质转化的关系

目的探讨食管鳞癌组织和癌旁正常黏膜组织中PTEN表达与上皮-间质转化的关系。方法采用免疫组织化学技术检测95例食管鳞癌组织和癌旁正常黏膜组织中的PTEN、E-cadherin和vimentin蛋白的表达。结果食管鳞癌组织中PTEN、E-cadherin和vimentin阳性表达率分别为49.5%、40.0%、58.9%,与癌旁正常组织(89.5%、76.8%、29.4%)相比具有明显差异(P0.05)。食管鳞癌组织中PTEN蛋白与E-cadherin蛋白表达呈正相关(r=0.362,P=0.001),而与vimentin蛋白表达呈负相关(r=-0.208,P=0.018)。结论 PTEN的缺失表达伴随E-cadherin的表达下调和vimentin的表达上调。PTEN可能与食管鳞癌的上皮间质转化有关,并与食管鳞癌的发生及浸润转移相关。     

受体酪氨酸激酶EphA7在乳腺癌中的表达及其临床意义

目的观察受体酪氨酸激酶EphA7在乳腺癌和正常乳腺组织中的表达,探讨EphA7蛋白表达的临床意义。方法应用免疫组化En Vision法染色检测乳腺正常细胞系、乳腺癌肿瘤细胞系和150例浸润性导管癌组织中EphA7的表达,分析其表达与临床病理特征的相关性。结果 EphA7蛋白在乳腺癌细胞系和浸润性导管癌中表达丢失,其表达水平与患者年龄(r_s=-0.157,P=0.055)、肿瘤分级(r_s=-0.331,P0.001)呈负相关;与淋巴结转移(r_s=0.245,P=0.002)、TNM分期(r_s=0.217,P=0.008)、HER-2表达(r_s=0.179,P=0.028)呈正相关。结论 EphA7在多数乳腺癌细胞中表达丢失,可能在乳腺癌发生和转移中发挥重要作用。     

舌鳞状细胞癌中Survivin的表达及与上皮细胞-间质转化的关系

目的探讨Survivin在舌鳞状细胞癌(tongue squamous cell carcinoma,TSCC)中的表达及其与上皮细胞-间质转化(epithelial-mesenchymal transition,EMT)的关系。方法采用免疫组化EnVision法检测63例TSCC及相应癌旁正常组织中Survivin和EMT标志物的表达,分析Survivin表达与TSCC临床病理特征的关系及其与EMT标志物的相关性。应用Western blot法检测8例TSCC新鲜组织中Survivin、E-cadherin和N-cadherin的表达。结果TSCC组织中Survivin阳性率为81.0%,明显高于相应癌旁正常组织中(15.9%);Survivin表达与TSCC临床分期、病理分级及淋巴结转移有明显相关性。E-cadherin和N-cadherin在TSCC组织中阳性率分别为42.9%和69.8%;Survivin与E-cadherin的表达呈负相关,与N-cadherin表达呈正相关。Western blot实验结果也证实,Survivin和N-cadherin在TSCC组织中呈高表达,而E-cadherin呈低表达。结论Survivin表达与TSCC组织EMT标志物有关,Survivin可能通过诱导TSCC细胞发生EMT,从而促进TSCC的侵袭和转移。     

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.     

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.     

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.     

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.     

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.     

Muscle strength and serum testosterone,cortisol and SHBG concentrations in middle-aged and elderly men and women

Forty healthy males (M) and females (F) divided into two different age groups i.e. M50 years (range 44–57; n= 9), F50 years (range 43–54; n= 9), M70 years (range 64–73; n= 11) and F70 years (range 63–73; n= 11) volunteered as subjects for examination of muscle cross-sectional area (CSA) and maximal voluntary isometric force production characteristics of the leg extensor muscles and serum androgen and sex hormone binding globulin (SHBG) concentrations. The CSA in the male groups was greatly larger (P < 0.01) than in the female groups and both elderly groups demonstrated slightly (n.s.) smaller values in the CSA than the two middle-aged groups. Maximal force of 2854 ± 452 N in M50 was greater (P < 0.05) than that of 2627 ± 752 N recorded for F50 as well as the force of 2787 ± 843 in M70 was greater (P < 0.001) than that of 1849 ± 295 recorded for F70. The force between F50 and F70 differed significantly (P < 0.05) from each other. The maximal rate of force production in M50 was greater (P < 0.01) than in F50 as well as in M70 greater (P < 0.001) than in F70. Both middle-aged groups demonstrated greater (P < 0.05) values than the respective elderly groups of the same sex. The individual values in the CSA correlated with the values in maximal force both in the middle-aged subjects (r= 0.66; P < 0.01) and in the elderly subjects (r= 0.69; P < 0.01). The mean concentration of serum testosterone in M50 was slightly (n.s.) greater than in M70 and in F50 significantly (P < 0.05) greater than in F70. Serum SHBG levels were lower in the males (P < 0.01) than in the females and serum testosterone/SHBG ratio in M70 and in F70 were lower (P < 0.05) than in M50 and in F50, respectively. In the females significant positive correlations were observed between the individual values in serum testosterone concentration and the values both in the CSA (r= 0.46; P < 0.05) and in maximal force (r= 0.62; P < 0.01) as well as between serum testosterone/SHBG ratio and both the CSA (r= 0.55; P < 0.05) and maximal force (r= 0.68; P < 0.01). The present results imply that the decreasing basal level of blood testosterone over the years in aging people, especially in females, may lead to decreasing anabolic effects on muscles thus having an association with age-related declines in the maximal voluntary neuromuscular performance capacity in aging people.