COX-2在人肝细胞癌中的表达及其对耐药性的影响

目的探讨环氧合酶-2(COX-2)在肝细胞癌发生、发展中的作用以及COX-2对P-糖蛋白(P-gp)表达的影响。方法选择手术切除的52例肝癌标本为研究对象,应用RT-PCR、免疫组织化学分别检测COX-2 mRNA和COX-2蛋白在肝癌组织和正常肝组织中的表达。同时检测mdr 1mRNA和P-gp蛋白在肝癌组织中的表达情况,并分析COX-2与P-gp在肝癌组织中表达的相关性。结果正常肝组织中未见COX-2表达,中、低分化的肝癌组织表达阳性率高于高分化肝癌组织(P<0.01),在HBsAg阳性的肝癌组织中表达高于HBsAg阴性的肝癌组织(P<0.05),在合并肝硬化的肝癌组织中表达高于无肝硬化的肝癌组织(P<0.01)。mdr 1 mRNA在肝癌组织和正常肝组织中均有表达。同时表达COX-2和mdr1基因为42例,两者相关系数r=0.563(P<0.01)。结论 COX-2参与了以P-gp介导的肝癌的多药耐药机制。     

环氧化酶-2在肝细胞癌中的表达及临床意义

目的 观察环氧化酶-2(COX-2)在肝细胞癌(HCC,简称肝癌)中的表达特征.方法 应用免疫组织化学S-P法、逆转录聚合酶链反应检测重庆医科大学附属第二医院2005年10月至2007年6月手术切除并经病理切片证实的52例HCC标本、52例癌旁组织及10例正常肝组织中COX-2及其基因的表达情况.结果 COX-2/COX-2 mRNA在肝癌组织中的表达明显上调,与其在正常肝组织、癌旁组织中的表达相比差异有统计学意义(P<0.01).结论 (1)COX-2高表达参与了肝癌的发生和发展,其表达水平与肝癌的分化程度及是否合并乙型肝炎及肝硬化有关,与HCC组织的国际癌症病期分期、肿瘤大小、甲胎蛋白水平、大体类型及是否转移等无明显关系.(2)COX-2抑制剂有望为预防HCC的发生和发展提供一条新的途径.     

胃癌组织中COX-2蛋白的表达研究

目的探讨胃癌组织中环氧化酶-2(COX-2)表达及其与胃癌浸润转移的关系。方法应用免疫组化S-P法测定57例胃癌组织中COX-2蛋白的表达。结果COX-2在胃癌组织中阳性表达率为85.2%,正常胃粘膜组织中阳性表达率为28.1%,两者有显著性异(P<0.01);COX-2阳性表达与胃癌分化程度无关(P>0.05);与TNM分期、淋巴结转移显著相关(P<0.01)。结论COX-2表达与胃癌的转移、浸润等有关,可作为反映胃癌生物学行为的指标之一。     

核因子-κB、环氧合酶-2 mRNA在大肠癌中的表达及其与临床病理的关系

目的:探讨核因子-κB(NF-κB)、环氧合酶-2(COX-2)基因mRNA在大肠癌组织中的表达及与临床病理参数的关系.方法:采用SYBR Green Ⅰ实时定量RT-PCR技术检测58例手术切除的大肠癌及相应癌旁正常组织中NF-κB和COX-2 mRNA的表达.结果:NF-KB、COX-2 mRNA在大肠癌组织中的阳性表达率显著高于相应癌旁正常组织(P<0.01),且NF-κB、COX-2 mRNA在大肠癌组织表达量亦显著高于癌旁正常组(P<0.05).大肠癌浸润组织越深,NF-κB和COX-2 mRNA相对表达水平越高,且NF-κB mRNA的表达与大肠癌淋巴结转移有关.NF-κB与COX-2 mRNA表达呈正相关(r=0.417,P=0.001).结论:大肠癌组织中NF-κB和COX-2 mRNA高表达,两基因间表达水平呈正相关,且与大肠癌浸润程度、淋巴结转移有关.     

肝细胞肝癌中PED/PEA-15 mRNA及蛋白表达的临床意义

目的:探讨PED/PEA-15 mRNA及蛋白在肝癌组织、癌旁组织及正常肝组织中的表达情况及其临床意义.方法:应用半定量逆转录.聚合酶链反应检测40例肝细胞肝癌、相应癌旁组织和12例正常肝组织中PED/PEA.15基因的相对表达量.并通过免疫组化检测PED/PEA-15蛋白的表达.结果:半定量RT-PCR显示,PED/PEA-15基因在肝癌组织中均呈高表达,癌旁组织及正常肝组织呈低表达或不表达,相对表达量分别为1.201±0.301、0.64±0.101和0.565±0.077,PED/PEA-15 mRNA在肝癌组织中表达较癌旁组织、正常肝组织显著升高(P<0.01).免疫组织化学显示,肝癌组织、癌旁组织及正常肝组织中PED/PEA-15蛋白的表达率分别为72.5%、32.5%和16.7%.肝癌组织中PED/PEA-15蛋白表达较癌旁组织及正常肝组织显著升高(P<0.01).且PED/PEA-15 mRNA及蛋白的表达与肝癌病理分级、临床分期有关(P<0.05),而与发病年龄、性别、肿瘤大小、肿瘤数目差异无显著性(P>0.05).结论:PED/PEA-15 mRNA及蛋白在肝癌组织中表达水平明显升高,可能在肝癌的发生及发展过程中发挥重要作用.     

ABCG2在原发性肝细胞性肝癌中的表达及临床意义

目的:分析ABCG2(ATP-binding cassette superfamily G member2)在原发性肝细胞性肝癌(primaryhuman hepatocellular carcinoma,HCC)中的表达状况及其临床意义。方法:应用免疫组化S-P法和原位杂交的方法检测HCC150例﹑肝硬化50例﹑肝炎组织50例﹑正常肝组织10例中ABCG2蛋白及mRNA的表达情况。结果:HCC﹑肝硬化﹑肝炎和正常肝组织的ABCG2蛋白的阳性率分别是78.67%(118/150)﹑40.00%(20/50)﹑60.00%(30/50)和30.00%(3/10),四者之间差异有统计学意义(χ2=32.25,P<0.05)。ABCG2mRNA在HCC﹑肝硬化﹑肝炎和正常肝组织的阳性表达率分别是69.33%(104/150)﹑36.00%(18/50)﹑50.00%(25/50)和20.00%(2/10),差异有统计学意义(χ2=24.93,P<0.05)。结论:ABCG2在肝癌和肝炎组表达率增高,在肝硬化和正常肝组织表达率降低且ABCG2蛋白与有无转移有关,推测ABCG2参与肿瘤耐药,可能成为治疗HCC临床耐药的分子靶点。     

环氧合酶-2 mRNA在结肠癌组织表达的临床意义

目的探讨环氧合酶-2(cyclooxygenase-2,COX-2)在结肠癌组织中表达的临床意义。方法采用原位分子杂交方法检测63例结肠癌、22例结肠腺瘤、23例正常结肠粘膜组织中COX-2 mRNA的表达。结果COX-2 mRNA在结肠癌、结肠腺瘤及正常结肠粘膜组织中的表达阳性率分别为74.60%、72.73%、34.78%,癌及腺瘤组表达阳性率明显高于正常组,P<0.001。结肠癌组COX-2 mRNA的表达阳性率与性别、年龄、肿瘤大小、组织学类型等因素差异无统计学意义P>0.05,随着分化程度的升高其阳性表达率也升高,且有统计学意义P<0.05;另一方面也可见到当结肠癌已突破浆膜、有淋巴结转移和血管有浸润及远处有转移时组织中的阳性率虽高于未然组,但未见有统计学意义。结论COX-2虽参与了结肠肿瘤的发生、发展,却远非结肠癌恶变的早期指标。     

食管鳞癌组织中环氧合酶-2、p53蛋白的表达及临床病理学意义

目的:研究环氧合酶-2(COX-2)、p53基因在食管鳞癌组织中的表达及其临床意义.方法:采用免疫组化染色S-P法检测COX-2、p53蛋白在67例食管鳞癌组织及15例癌旁组织中的表达.结果:COX-2和p53在食管癌组织中的阳性表达率分别为73.5%(49/67)和64.2%(43/67),均高于癌旁组织(P<0.05).COX-2在高、中、低分化食管癌中的表达率逐渐降低(P<0.05);有嗜酒史者阳性表达率明显高于无嗜酒史者(P<0.05).p53高表达与食管癌淋巴结转移及嗜酒史有关(P<0.05).COX-2与p53表达具有相关性(r=0.249,P<0.05).结论:COX-2和p53均可能参与了食管癌的发生过程.不同分化食管鳞癌的COX-2表达率有差异,COX-2表达率与嗜酒可能相关.p53高表达与食管癌淋巴结转移及嗜酒史可能相关.     

COX-2与Fas蛋白在胃癌组织中的表达及意义

目的探讨COX-2和Fas蛋白在胃癌组织中的表达相互关系及意义。方法应用免疫组化方法检测了30例正常胃黏膜及82例胃癌组织中COX-2和Fas的表达情况。结果COX-2蛋白在胃癌组织中阳性表达率为63．4％,而在正常对照的胃黏膜组织中阳性率为13．3％,胃癌组织中COX-2蛋白阳性率显著高于正常胃黏膜(P＜0．001)。Fas在胃癌组织中阳性率为39．1％,在30例正常胃黏膜组阳性率为93．3％,正常胃黏膜组中Fas阳性率显著高于胃癌组织(P＜0．001)。COX-2与Fas的阳性表达在各性别组和各年龄组之间无显著差异,COX-2在有淋巴结转移和无淋巴结转移胃癌组间,低分化和高、中分化胃癌组间、TNM分期之间表达有显著差异。Fas在高、中分化胃癌组阳性表达率显著高于低分化胃癌组(P＜0．05)。而在TNM分期之间,有淋巴结转移和无淋巴结转移胃癌组间表达无显著性差异(P＞0．05)。胃癌组织中COX-2与Fas表达具有显著负相关(r_φ=-0．559,P＜0．001)。结论胃癌组织中存在COX-2的高表达与Fas低表达,且两者之间的表达强度具有显著等级负相关。     

胰岛素样生长因子结合蛋白-5在肝硬化、原发性肝癌患者肝组织和血清中的水平及临床意义

目的观察肝硬化、原发性肝癌患者肝组织和血清中胰岛素样生长因子结合蛋白-5(IGFBP-5)水平,探讨其与肝硬化、原发性肝癌的关系及其临床意义。方法取肝硬化组织、肝癌组织及癌旁正常组织各8例,采用实时RT-PCR技术检测IGFBP-5mRNA的表达水平;取肝硬化(21例)、原发性肝癌(14例)及正常对照者(14例)血清,采用ELISA法检测IGFBP-5水平,分析IGFBP-5在不同分组中水平的差异及其临床意义。结果肝硬化组肝组织中IG-FBP-5mRNA的表达及血清中IGFBP-5水平均较正常对照组降低(P均<0.05),与血清中升高的透明质酸(HA)、层粘连蛋白(LN)和肝功能无相关性。原发性肝癌组肝组织中IGFBP-5的表达及血清中IGFBP-5水平均高于正常对照组和肝硬化组(P均<0.05),与血清中升高的甲胎蛋白(AFP)和肝功能亦无相关性。结论在肝硬化发生后,肝组织表达和合成IGFBP-5减少,与其他细胞因子的调节有关,其可能与HA、LN互补作为诊断早期肝纤维化的一个无创指标;原发性肝癌患者肝组织中IGFBP-5表达增多,血清水平增高,其有可能作为一个潜在的诊断原发性肝癌的检测指标。IGFBP-5与肝硬化、原发性肝癌的关系值得进一步研究。     

Antiprotozoan and Antiviral Activities of Non-cytotoxic Truncated and Variant Analogues of Mussel Defensin

We previously reported the crucial role displayed by loop 3of defensin isolated from the Mediterranean mussel, Mytilusgalloprovincialis, in antibacterial and antifungal activities.We now investigated antiprotozoan and antiviral activities ofsome previously reported fragments B, D, E, P and Q. Two fragments(D and P) efficiently killed Trypanosoma brucei (ID₅₀ 4–12µM) and Leishmania major (ID₅₀ 12–45 µM) ina time/dose-dependent manner. Killing of T. brucei started asearly as 1 h after initiation of contact with fragment D andreached 55% mortality after 6 h. Killing was temperature dependentand a temperature of 4°C efficiently impaired the abilityto kill T. brucei. Fragments bound to the entire external epitheliumof T. brucei. Prevention of HIV-1 infestation was obtained onlywith fragments P and Q at 20 µM. Even if fragment P wasactive on both targets, the specificity of fragments D and Qsuggest that antiprotozoan and antiviral activities are mediatedby different mechanisms. Truncated sequences of mussel defensin,including amino acid replacement to maintain 3D structure andincreased positive net charge, also possess antiprotozoan andantiviral capabilities. New alternative and/or complementaryantibiotics can be derived from the vast reservoir of naturalantimicrobial peptides (AMPs) contained in marine invertebrates.     

Complementary and alternative approaches to pain relief during labor

This review evaluated the effect of complementary and alternative medicine on pain during labor with conventional scientific methods using electronic data bases through 2006 were used. Only randomized controlled trials with outcome measures for labor pain were kept for the conclusions. Many studies did not meet the scientific inclusion criteria. According to the randomized control trials, we conclude that for the decrease of labor pain and/or reduction of the need for conventional analgesic methods: (i) There is an efficacy found for acupressure and sterile water blocks. (ii) Most results favored some efficacy for acupuncture and hydrotherapy. (iii) Studies for other complementary or alternative therapies for labor pain control have not shown their effectiveness.     

Immunology and homeopathy. 1. Historical background

Homeopathy was born as an experimental discipline, as can be seen from the enormous amount of homeopathic data collected over more than two centuries. However, the medical tradition of homeopathy has been separated from that of conventional science for a long time. Conventional scientific wisdom dictates that homeopathy should have no effect above placebo but experiments on ultra-high dilutions of solutes together with some clinical data suggest the intriguing possibility that it might do in some circumstances. Today, an osmotic process between disciplines, previously seen as in conflict, is facilitated because over the last few decades homeopathy has initiated the methods of current medical science and a substantial number of experimental studies-at molecular, cellular and clinical levels-are available. One area of dialogue and of common progress is that of inflammation and immunity, probably because these are closely related to the traditional 'vital force' of the body's self-healing power. In a series of papers we review the historical origins of homeopathy, the laboratory and animal models related to the field of immunopharmacology, the clinical evidence in favor and against the use of homeopathy in the inflammatory diseases and the hypotheses regarding its action mechanism(s). Finally, we will enlighten the specific characteristics of the homeopathic approach, which places great emphasis on identifying a cure for the whole organism.     

Essential Oil of Betula pendula Roth. Buds

The essential oil of Betula pendula Roth. buds was obtainedusing both hydrodistillation and microdistillation techniquesand their chemical compositions were analyzed using both gaschromatography (GC) and gas chromatography–mass spectrometry(GC-MS). Overall, more than 50 compounds were identified representing80% and 92% for hydrodistillation and microdistillation, respectively.The main components (by hydrodistillation and microdistillation,respectively) found were -copaene (12% and 10%), germacreneD (11% and 18%) and -cadinene (11% and 15%) in the analyzedessential oils. The microdistillation technique proved to bea useful tool and compliant alternative when compared to hydrodistillation.     

Developing CAM Research Capacity for Complementary Medicine

This article describes initiatives that have been central to the development of complementary and alternative medicine (CAM) research capacity in the United Kingdom, Canada and the United States over the last decade. While education and service delivery are essential parts of the development of CAM, this article will focus solely on the development of research strategy. The development of CAM research has been championed by both patients and politicians, primarily so that we may better understand the popularity and apparent effectiveness of these therapies and support integration of safe and effective CAM in health care. We hope that the perspective provided by this article will inform future research policy.     

Natural health products, modulation of immune function and prevention of chronic diseases

The immune system is increasingly found to be involved in the development of several chronic illnesses, for which allopathic medicine has provided limited tools for treatment and especially prevention. In that context, it appears worthwhile to target the immune system in order to modulate the risk of certain chronic illnesses. Meanwhile, natural health products (NHPs) are generating renewed interest, particularly in the prevention and treatment of several chronic diseases. Over 20 scientists from fields related to immune function and NHPs were thus convened to establish the state of knowledge on these subjects and to explore future research directions. This review summarizes the result of discussions held during the symposium. It thus seeks to be thought provoking rather than to comprehensively cover such broad areas of research. Notably, a brief overview of the immune system is presented, including potentially useful targets and strategies to keep it in an equilibrated state, in order to prevent certain disorders. The pertinence and limitations of targeting the immune system to prevent chronic diseases is also discussed. The paper then discusses the usefulness and limitations of current experimental tools available to study the immune modulating effects of NHPs. Finally, a concise review of some of the most studied NHPs showing promising immunomodulatory activity is given, and avenues for future research are described.     

Complementary and alternative medicine for chronic prostatitis/chronic pelvic pain syndrome

To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990-2005 using the PubMed, Medline databases. Data from the articles were abstracted and pooled by subject. Keywords cross-searched with CP/CPPS included: complementary, alternative, integrative, therapies, interventions, nutrition, antioxidants, herbs, supplements, biofeedback and acupuncture. Listed articles with no abstracts were not included. Various CAM therapies for CP/CPPS exist including biofeedback, acupuncture, hyperthermia and electrostimulation. Additionally, a variety of in vitro and in vivo studies testing herbal and nutritional supplements were found. Saw palmetto, cernilton and quercetin were the most frequently tested supplements for CP/CPPS. Although many CAM therapies demonstrate positive preliminary observations as prospective treatments for CP/CPPS, further exploratory studies including more randomized, controlled trials are necessary for significant validation as treatment options for this complex disorder.     

Exercise and Life-Satisfactory-Fitness: Complementary Strategies in the Prevention and Rehabilitation of Illnesses

Moderate training of an endurance nature, but also other exerciseactivities, not only has a preventive effect on various illnessesand pre-illness states such as the metabolic syndrome and cancer,but is also effective in treating patients in the rehabilitationphase after illness, e.g. cardiovascular or cancer. Our investigationdemonstrates that even low level physical activity has a verygood preventive effect too, which is enhanced when it is accompaniedby mental activity and psychological well-being. In total, weinvestigated 13 000 people on the basis of socio-economic panelpolls with respect to life contentment, health status and leisure-timeactivities. Life contentment is positively linked to contentmentwith labor, which seems to be an essential aspect with regardto the increasing number of unemployed people in Europe. Thesecond important factor is health-promoting activities duringleisure time. Exercise, especially, has a significant influenceon life satisfaction as a feeling of physical fitness feelingis regarded as synonymous with good health. The results underlinethe psycho-neuroimmunological network, which stabilizes ourhealth and shows that different activities in older adults havea significant effect on the aging process and age-related illnesses.Besides the various activities that are important in this arena,namely muscle and mental mobility (‘brawn and brain’),a third component must be taken into consideration: life contentmentin the form of a successful retrospective view and a positiveoutlook, embedded in a psychosocial family environment (‘brood’)and integrated in a stress-free biotope, where life does makesense. Alternative and complementary strategies should be consideredin light of these three aspects when we think about additionalanti-inflammatory strategies in preventing diseases or treatingthem and their relapses. Sport has made a few healthy people ill, but sport has alsomade a good few of ill people healthy! (Gerhard Uhlenbruck,Aphorisms)     

Hibiscus sabdariffa affects ammonium chloride-induced hyperammonemic rats

Hibiscus sabdariffa (HS) is an edible medicinal plant, indigenous to India, China and Thailand and is used in Ayurveda and traditional medicine. Alcoholic extract of HS leaves (HSEt) was studied for its anti-hyperammonemic and antioxidant effects in brain tissues of ammonium chloride-induced hyperammonemic rats. Oral administration of HSEt (250 mg kg(-1) body weight) significantly normalizes the levels of ammonia, urea, uric acid, creatinine and non-protein nitrogen in the blood. HSEt significantly reduced brain levels of lipid peroxidation products such as thiobarbituric acid and reactive substances (TBARS) and hydroperoxides (HP). However, the administered extract significantly increased the levels of antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) in brain tissues of hyperammonemic rats. This investigation demonstrates significant anti-hyperammonemic and antioxidant activity of HS.