新疆维吾尔族霍奇金淋巴瘤与EB病毒感染的关系

目的 探讨新疆地区维吾尔族霍奇金淋巴瘤与EB病毒感染的关系.方法 对52例病理确诊为霍奇金淋巴瘤(Hodgkin's lymphoma)的维吾尔族病例用免疫组化检测EBV,并对其中的27例用原位杂交检测EBV编码的mRNA(Epstein Barr virus encoded mRNA,EBER).结果 EBV:52例HL中40例阳性(76.9%),其中结节硬化型23例,混合细胞型10例,富于淋巴细胞型5例,淋巴细胞减少型2例.EBV在≤14岁的儿童中阳性率为95%(19/20),在14岁以上年龄组阳性率为65.5%(21/32).EBER:22例阳性,阳性率为81.5%(22/27),其中结节硬化型10例,混合细胞型8例,富于淋巴细胞型4例,无淋巴细胞减少型.EBV在≤14岁的儿童中阳性率为88.9%(8/9),在14岁以上年龄组阳性率为77.8%(14/18).结论 新疆维吾尔族霍奇金淋巴瘤中有高水平EBV感染的现象,尤其是儿童;霍奇金淋巴瘤各亚型的EBV感染率无明显差异.     

EBER原位杂交检测中手工与BenchMark ULTRA自动化染色差异

正与EBV感染相关的疾病有鼻咽癌、NK/T细胞淋巴瘤、EBV相关性胃癌、淋巴上皮瘤样癌、霍奇金淋巴瘤、非霍奇金淋巴瘤等。原位杂交是检测组织EBV感染的金标准,与PCR和免疫组化相比,原位杂交具有高度灵敏性和特异性,组织定位明确。目前最常用的EBER原位杂交试剂分别有适用于手工和全自动免疫组化染色仪两种类型的试剂盒。本实验使用北京中杉金桥公司的手工检测试剂盒和罗氏EBER全自动检测试剂盒同时对淋巴瘤、EBV相关性胃癌、     

鼻腔鼻咽部淋巴瘤:319例会诊病例分析

目的探讨鼻腔鼻咽部淋巴瘤的临床特点、病理分型及类型构成。方法回顾性分析首都医科大学附属北京友谊医院病理科319例鼻腔鼻咽部淋巴瘤会诊病例的临床资料、病理组织学特征及免疫表型,按WHO(2008)分类标准进行病理诊断及分类,并对统计结果进行对比分析。结果 319例会诊病例中,3例(0.9%)诊断为霍奇金淋巴瘤混合细胞型,考虑肿瘤累及鼻咽,建议全身检查;316例均为非霍奇金淋巴瘤(99.1%),包含非霍奇金T和NK细胞起源淋巴瘤177例(56.0%)、B细胞起源淋巴瘤139例(44.0%)。发病率位于前两位的是NK/T细胞淋巴瘤鼻型160例(50.6%)、弥漫大B细胞淋巴瘤64例(20.3%)。NK/T细胞淋巴瘤发病率高于弥漫大B细胞淋巴瘤。≥60岁的患者106例(33.2%)诊断均为非霍奇金淋巴瘤,其中弥漫大B细胞淋巴瘤40例(37.7%)、NK/T细胞淋巴瘤36例(34.0%),弥漫大B细胞淋巴瘤与NK/T细胞淋巴瘤发病率无统计学意义。60岁的非霍奇金淋巴瘤患者210例(66.5%),其中NK/T细胞淋巴瘤124例(59.0%)、弥漫大B细胞淋巴瘤24例(11.4%),发病率差异有显著性。结论 316例鼻腔鼻咽部非霍奇金淋巴瘤中以NK/T细胞淋巴瘤最为多见,第二位是弥漫大B细胞淋巴瘤;≥60岁老人鼻腔鼻咽部淋巴瘤患者弥漫大B细胞淋巴瘤、NK/T细胞淋巴瘤最为多见,两者之间发病率差异无显著性。     

鼻NK/T细胞淋巴瘤--15年研究报道

目的 :探讨鼻NK/T细胞淋巴瘤 (原诊断为“中线恶性网织细胞增生症”)的临床病理及免疫表型特征、病变性质及其与EB病毒感染的关系。方法 :过去 15年中对近 2 0 0例“中线恶网”病例做了一系列研究 ,包括临床病理分析、LSAB法免疫组化染色作免疫表型分析、用PCR技术作T细胞受体β和γ链基因重排及EBV DNA检测、EBER原位杂交和原位末端标记DNA片段技术检测细胞凋亡。结果 :①鼻NK/T细胞淋巴瘤有特征性临床及病理形态学表现 ;②瘤细胞表达CD3ε:89 8% ;CD45RO :81 2 % ;CD5 6 :81 2 % ;TIA 1:10 0 %。不表达B淋巴细胞和组织细胞分化抗原 ;③TCR β链基因重排检出率为85 7% ,TCR γ链基因重排检出率为 94 45 % ;④EBV DNA检出率为 6 7 86 % ;EBER原位杂交阳性率为 90 6 3% ;⑤肿瘤组织中的凋亡细胞与Ki 6 7 呈明显正相关 (P <0 0 0 6 3) ,Ki 6 7 细胞数量变化与患者的平均生存期有明显关系 (P <0 0 2 )。结论 :“中线恶网”实为EB病毒相关、细胞毒性NK/T细胞淋巴瘤。     

非特指性外周T细胞淋巴瘤中EBER、 LMP1的表达及与预后的关系

目的 探讨非特指性外周T细胞淋巴瘤(peripheral T-cell lymphoma,not otherwise specified,PTCL-NOS)中EBER、LMP1的表达及与患者预后的关系.方法 采用原位分子杂交(in situ hybridization,ISH)技术和免疫组化法分别检测81例PTCL-NOS及59例对照组[48例血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)和11例结外NK/T细胞淋巴瘤(extranodal NK/T cell lymphoma,ENK/TCL)]中EBER和LMP1的表达,并分析EBER表达与PTCL-NOS患者临床病理特征及预后的关系.结果 (1)81例PTCL-NOS中,EBER阳性率为43.2％ (35/81);35例EBER阳性的PTCL-NOS病例中免疫组化得分1分+2分者共29例,占EBER阳性病例的82.9％(29/35),3分+4分者共6例,占17.1％ (6/35).EBER表达与PTCL-NOS患者年龄、性别、乳酸脱氢酶(lactate dehydrogenase,LDH)水平及临床分期均无明显相关性(P＞0.05).(2)81例PTCL-NOS组织中,LMP1蛋白阳性率为22.2％(18/81).LMP1蛋白表达与EBER表达具有一致性,但EBER阳性率明显高于LMP1 (P ＜0.05).(3)33例PTCL-NOS获得临床随访资料,随访时间1～63个月,中位生存期为23个月,总生存率为33.3％(11/33).Kaplan-Meier生存曲线分析显示,EBER阳性组的生存率明显低于EBER阴性组(P＜0.05).结论 EB病毒(EBV)感染可能是PTCL-NOS发生、发展中重要但非根本性的因素.EBER-ISH检测EBV感染具有较高的敏感性和特异性.EBV感染对PTCL-NOS患者的预后判断具有重要意义.     

非霍奇金淋巴瘤患者T细胞亚群、NK细胞检测的临床意义

目的：研究非霍奇金淋巴瘤（NHL）患者外周血T淋巴细胞亚群、NK细胞检测结果的变化与该病的关系及与慢性淋巴腺炎患者细胞免疫功能的不同变化。方法：采用流式细胞仪（FCM）检测非霍奇金淋巴瘤（NHL）患者、慢性淋巴腺炎及正常人外周血T淋巴细胞亚群比例、NK细胞的变化。结果：非雹奇金淋巴瘤患者与正常人比较总的T淋巴细胞、辅助性T淋巴细胞及CD4^＋／CD8^＋比值明显下降（P〈0．05），细胞毒性T淋巴细胞明显升高（P〈0．05），NK细胞则无明显变化（P〉0．05）。非霍奇金淋巴瘤患者与慢性淋巴腺炎患者比较，细胞毒性T淋巴细胞、NK细胞明显升高（P〈0.05），而总的T淋巴细胞、辅助性T淋巴细胞无明显改变（P〉0．05），CD4^＋／CD8^＋比值略有下降但无明显统计学意义。结论：非霍奇金淋巴瘤患者细胞免疫功能明显受到抑制，T细胞亚群及NK细胞的检测对NHL的诊断、治疗、预后判断有一定的临床价值。     

肠道非霍奇金淋巴瘤与EB病毒、p53、p21ras的相关性

目的：研究肠道非霍奇金淋巴瘤（NHL）与EB病毒（EBV）感染p53、p21^ras蛋白表达及其相关性。方法：以SABC免疫组化方法检测瘤细胞p53、p21^ras基因的表达及EBV寡核苷酸探针（EBER）原位杂交。结果：19例肠道NHL好发部位小于肠下段和结肠，以单发瘤结节多见，常伴有表面溃疡形成。经免疫组化证实3例为T细胞淋巴瘤（15.79%），16例为B细胞淋巴瘤（84.21%）。依WHO分类，T细胞淋巴瘤为外周T细胞性（2／19例）和T／NK细胞性（1／19例）。EBV－EBER原位杂交3／19例有阳性表达，均为T细胞淋巴瘤，阳性细胞占肿瘤细胞的30％－80％。B细胞淋巴瘤未见阳性。p53的表达共有12例，占全部病例的63.16%，11例有p21^ras的表达，为57.9%，有8例同时检出p53和p21^ras的表达。结论；肠道淋巴瘤以B细胞淋巴瘤多发，并以惰性为多见，如为T细胞性淋巴瘤，提示多是侵袭性，且T细胞淋巴瘤与EBV相关性较高，而B细胞淋巴瘤无相关性。p53的表达与EBV感染无明显相关性，而p21^ras的表达与EBV感染似有关系。     

443例恶性淋巴瘤临床病理特征分析

目的：根据WHO(2008版)造血和淋巴肿瘤分类标准,探讨军事医学科学院附属医院恶性淋巴瘤的病理类型及分布特点。方法：收集2010年11月1日至2015年3月31日病理诊断443例恶性淋巴瘤,复习其临床资料、HE切片及免疫组织化学切片。按WHO(2008版)分类标准进行病理诊断及分类。结果：443例恶性淋巴瘤中霍奇金淋巴瘤11.06%(49/443),非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL)88.94%(394/443)。非霍奇金淋巴瘤中B细胞性淋巴瘤66.37%(294/443),T细胞性淋巴瘤22.35%(99/443)。非霍奇金淋巴瘤中,发病构成比居前5位分别为弥漫性大B细胞淋巴瘤41.53%(184/443)、滤泡性淋巴瘤11.06%(49/443),外周T细胞淋巴瘤5.64%(25/443),T淋巴母细胞白血病/淋巴瘤5.19%(23/443)、黏膜相关淋巴组织结外边缘区淋巴瘤4.74%(21/443)。HL中以结节硬化型经典型霍奇金淋巴瘤为多(4.51%,20/443)。恶性淋巴瘤患者中,男女比例为1.58∶1,中位年龄57岁(7~94岁)。霍奇金淋巴瘤和非霍奇金淋巴瘤起病部位均以颈部淋巴结为多。结论：443例淋巴瘤中,非霍奇金淋巴瘤发病远多于霍奇金淋巴瘤,非霍奇金淋巴瘤中以弥漫大B细胞淋巴瘤多见,霍奇金淋巴瘤中以结节硬化性霍奇金淋巴瘤多见。大部分淋巴瘤类型以男性发病为多,起病部位以颈部淋巴结为多。     

T细胞淋巴瘤中爱泼斯坦-巴尔病毒感染情况的研究

目的　通过检测不同类型T细胞淋巴瘤中爱泼斯坦 巴尔病毒 (EBV)基因编码产物EBERs的表达 ,探讨EBV与T细胞淋巴瘤的关系。方法　应用原位杂交的方法 ,对 6 0例经组织学和免疫组织化学确定的T细胞淋巴瘤中EBV编码的小RNAEBERs进行检测 ,并采用 1994年淋巴瘤REAL分类方案对 6 0例T细胞淋巴瘤进行分类 ,以进一步分析与EBV相关的T细胞淋巴瘤的临床病理特征。结果　发现 6 0例T细胞淋巴瘤中EBERs的检出率为 6 1.7% ,外周T细胞淋巴瘤的检出率为6 9 8%。结外淋巴瘤的检出率高于结内淋巴瘤 (P <0 .0 1)。EBERs在T细胞淋巴瘤中的血管中心性T细胞淋巴瘤、血管免疫母T细胞淋巴瘤、间变性大细胞淋巴瘤中的检出率分别为 17 18,2 2和 4 6 ,与外周T细胞淋巴瘤非特异型 (5 1.9% ,14 2 7)相比 ,差异有非常显著意义 (P <0 .0 1)。EBERs与T细胞淋巴瘤患者的性别、年龄和临床分期无关 (P <0 .0 5 )。结论　外周T细胞淋巴瘤与EBV感染有关 ,尤其是外周T细胞淋巴瘤中的血管中心性T细胞淋巴瘤、血管免疫母T细胞淋巴瘤和间变性大细胞淋巴瘤。     

不同类型霍奇金淋巴瘤EBV检测的原位杂交和免疫组化方法比较

目的 探讨EBER原位杂交和免疫组化EnVision两步法在检测不同类型霍奇金淋巴瘤(Hodgkin's lymphoma,HL)中EBV的表达和意义.方法 收集68例不同类型HL标本(结节硬化型38例、混合细胞型18例、淋巴细胞丰富型7例、淋巴细胞消减型5例),石蜡切片后,分别采用EBER原位杂交法检测EBV编码的mRNA(epstein barr encoded RNAs1,EBER1)以及免疫组化EnVision两步法检测EBV潜伏膜蛋白1(laten mbmbrane proteins,LMP1)在不同类型HL中的表达.结果 68例标本中,免疫组化EnVision两步法检测结果 总阳性率为36%(25/68),其中结节硬化型为23%(9/38),混合细胞型为66%(12/18),淋巴细胞丰富型和淋巴细胞消减型分别为28%(2/7)和40%(2/5);原位杂交检测结果 总阳性率为55%(38/68),其中结节硬化型为42%(16/38),混合细胞型为88%(16/18),淋巴细胞丰富型和淋巴细胞消减型分别为42%(3/7)和60%(3/5).结论 在对不同类型HL的EBV检测中,EBER原位杂交方法 比免疫组化EnVision两步法检出率更高,定位更清晰,同时也更具特异性和敏感性.     

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.