P2X7受体与肿瘤发生发展关系的研究进展

P2X7受体作为嘌呤类受体家族中的一个重要成员,能够被细胞外ATP激活,从而参与细胞信号转导、细胞因子的分泌,介导细胞的生长与凋亡等细胞生物学功能的调控。近些年研究表明,P2X7受体的异常表达与多种肿瘤的发生发展密切相关,有望成为肿瘤靶向治疗的新型生物学标志物。本文结合国内外最新报导,对P2X7受体在肿瘤中的异常表达及相关致癌机制研究作一综述。     

癌痛患者外周血CD4+T淋巴细胞Thl/Th2漂移检测与分析

目的:观察癌痛患者外周血CD4+T淋巴细胞中的Th1/Th2漂移状态,探讨其与止痛治疗疗效的关系.方法:采用流式细胞术检测80例不同类型癌痛患者和20例无痛肿瘤患者外周血CD4+T淋巴细胞中IL-2/IL-6细胞因子水平.分析治疗前后、不同肿瘤、不同程度癌痛患者外周血CD4+T淋巴细胞表达Th1/Th2细胞亚群漂移状况.结果:癌痛患者存在Th1→Th2细胞亚群漂移现象,随着癌痛程度加重,Th1→Th2细胞亚群漂移逐渐增强,癌痛治疗效果差的治疗后Th1→Th2细胞亚群漂移进一步加强,而疗效显著者治疗后可逆转Th1→Th2细胞亚群的漂移状态.结论:免疫系统在癌痛的发生、发展中起重要作用,而细胞因子在免疫调节过程中发挥着重要作用.     

P2X7受体激活乳腺癌JNK/SAPK信号通路的研究进展

P2X7受体是ATP门控的离子通道,对二价阳离子有较强的选择性,属于嘌呤受体P2X家族。P2X7受体参与细胞信号转导、细胞因子的分泌等多种生理功能。近年研究发现P2X7受体通过增加氧化磷酸化及细胞内ATP的储备,介导细胞的存活与生长。在乳腺癌中P2X7受体表达异常,并能激活JNK/SAPK途径,诱导乳腺癌细胞凋亡。本文综述了P2X7受体与乳腺癌发生发展分子机制的相关研究。     

嘌呤受体P2Y2基因在恶性肿瘤中的研究进展

近年来恶性肿瘤的发病率逐年升高,严重影响了患者的生存质量及生存期.尽管随着放射治疗、化学治疗以及靶向治疗等治疗手段的不断发展,部分肿瘤患者获得了一定益处,但肿瘤细胞的远处转移以及肿瘤耐药的发生已经成为肿瘤患者转归过程中面临的巨大难题.因此,亟需寻找恶性肿瘤发生发展过程中相关靶向分子标志物,以阻断恶性肿瘤侵袭或耐药的发生,从而改善患者的生存质量并延长患者的生存期.嘌呤受体P2Y2(P2RY2)基因的表达产物为P2Y2受体,在人体内广泛表达,由细胞外的核苷酸腺苷三磷酸(ATP)/尿苷三磷酸(UTP)激活,诱导的嘌呤能信号转导可涉及多种生物学过程,如神经传递、肌肉收缩、伤口愈合,并可调控细胞的增殖、迁移和凋亡.研究证实P2RY2基因在多种恶性肿瘤中普遍表达,通过与肿瘤微环境中的相关信号分子或炎症物质相互作用,参与肿瘤细胞增殖的调控以及细胞迁移的诱导,并且近年来研究发现其与肿瘤耐药的发生密切相关,可能成为恶性肿瘤的潜在治疗靶点之一.本文对P2Y2受体在恶性肿瘤中的研究进展进行综述.     

疼痛对癌症患者抑郁和生活质量影响的研究

目的了解癌症患者疼痛和抑郁的发生率,疼痛对癌症患者生活质量的影响;探讨癌痛与肿瘤患者发生抑郁的相关性.方法以住院患者为主,采用癌症生活质量自评量表FACT-G、SDS抑郁自评量表、疼痛数字分级法(NRS)以及一般状况评定量表收集癌症患者相关资料.结果本研究入组患者236例,均为病理确诊的癌症患者,其中疼痛的发生率为64.4%,轻、中度痛占55.9%,重度痛占8.5%;抑郁的发生率为34.3%.不同程度的疼痛与身体状况、情感状况和功能状况的损害明显相关(P=0.001,0.047,0.008).疼痛与肿瘤患者的抑郁发生明显相关(P《0.001),癌症患者抑郁的发生率在无痛组、轻度痛组、中度痛组和重度痛组分别为14.3%,7.7%,60%,80%.结论癌症患者中约2/3发生疼痛,1/3发生抑郁.疼痛是影响癌症患者生活质量的主要因素;疼痛与抑郁的发生密切相关.     

嘌呤能配体门控离子通道7受体与宫颈癌关系的研究进展

嘌呤能配体门控离子通道7受体(P2X7R)是嘌呤受体家族中重要的一员,在人体多种组织和细胞中均有表达。研究表明,P2X7R与宫颈癌的发生发展有关,且其表达水平与疾病恶性程度密切相关。宫颈癌细胞中P2X7R低表达,可调节肿瘤细胞的生长与增殖,继而促进宫颈癌的转移与侵袭;通过转染获得高表达P2X7R的宫颈癌细胞系,可抑制肿瘤细胞增殖,并导致细胞凋亡。现就P2X7R研究进展及其与宫颈癌发生发展的关系进行综述,以期为靶向治疗宫颈癌等肿瘤性疾病提供新的研究方向。     

全国癌症止痛与姑息治疗培训班暨癌症急危重症治疗学术研讨会通知

为全面了解我国癌痛治疗现状,加强多学科学术交流,促进癌症疼痛治疗事业的发展,受《中国肿瘤》杂志社的委托,定于2004年8月13日~17日在济南举办“全国癌症止痛与姑息治疗培训班暨癌症急危重症治疗学术研讨会”。届时邀请全国著名癌痛专家介绍癌症疼痛发生机制、癌症疼痛的评估和诊断、癌症疼痛诊疗的新技术、WHO癌痛三阶梯方案的改进,癌痛的中医药治疗,癌痛的神经阻滞治疗,癌痛的心理治疗等国内外癌痛治疗的最新理念和方法。征文内容:1.癌痛发病率的调查与研究,癌痛发病原因的调查与研究,我国癌痛治疗存在的问题及对策,国家政策研究及其它…     

乳腺癌合并糖尿病患者肿瘤组织中Th17细胞含量测定

目的：分析乳腺癌及乳腺癌合并糖尿病患者肿瘤组织中Th17细胞含量,探讨Th17及糖尿病在乳腺癌发生发展中的意义。方法：收集2011年12月至2012年10月间18例乳腺癌非糖尿病和14例乳腺癌合并糖尿病患者乳腺癌改良根治术的手术切除组织标本,分为癌组织与癌旁组织2组,制成单细胞悬液;流式细胞术检测其中Th17细胞（ROR-γt淋巴细胞）比例。免疫组化法检测同一肿瘤组织中雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体2（HER-2）的表达。分析Th17细胞比例与被研究患者临床病理特征的关系。结果：乳腺癌非糖尿病患者肿瘤组织中Th17细胞表达与癌旁组织无明显差异（Z=-0．957,P=0．339〉0．05）;乳腺癌合并糖尿病患者肿瘤组织Th17细胞表达与癌旁组织存在差异（Z=-2．100,P=0．036〈0．05）;而乳腺癌非糖尿病与乳腺癌合并糖尿病患者肿瘤组织的Th17细胞表达无明显差异（Z=-0．912,P=0．337〉0．05）。结论：乳腺癌组织中有Th17细胞表达。有糖尿病的乳腺癌患者癌组织中Th17细晌含量高干痛軎绢织．     

雄激素受体与肝细胞癌

 在肝脏组织癌变过程中,雄激素及其受体可能起到重要作用。相关研究证实大多数肝细胞癌患者癌组织中都能检测到雄激素受体的表达,且雄激素受体的表达上调与肿瘤患者预后相关。最近研究表明雄激素受体通过各种途径参与肝细胞癌发生发展过程,以雄激素受体作为治疗靶点可能是肝细胞癌治疗的一种新疗法。     

癌痛的国内外治疗概况

癌痛是中晚期癌症患者的主要临床症状。世界卫生组织（WHO）据有关资料分析指出：70％的癌症晚期患者可出现显著的疼痛。并指出世界上每天约有350万~400万癌症患者忍受疼痛折磨，放在抗癌的同时积极采取有效止痛措施，缓解或减轻患者的疼痛是癌症治疗中的重要内容。近年来，国内外对癌痛的治疗措施有了迅速的发展，使癌痛的控制更方便和有效，从而改善了患者的健康状况，提高了生存质量。本文就作者所掌握的近年来国内外对癌痛治疗方面的情况作一简要介绍。一、癌痛的原因和机理1．癌症本身引起的疼痛包括原发肿瘤及转移瘤。由于肿瘤本身…     

P2X7受体与乳腺癌的发生和发展

 P2X7受体是腺甘三磷酸（ATP）门控的离子通道,对二价阳离子有较强的选择性,属于嘌呤能P2受体家族。P2X7受体参与细胞信号传导、细胞因子的分泌等多种生理功能。近几年研究发现P2X7受体通过增加氧化、磷酸化及细胞内ATP的储备,介导细胞的存活与生长。在乳腺癌中P2X7受体表达异常,活化的P2X7受体激活位于细胞质内的丝裂原活化蛋白激酶（MAPK）,后者受到刺激后磷酸化进入核内,引起细胞内一系列蛋白激酶的活化,进而影响乳腺癌的发生发展。     

前列腺癌干细胞相关肿瘤标志物的研究进展

前列腺癌(prostate cancer,PCa)是男性常见的恶性肿瘤。内分泌治疗是晚期前列腺癌的主要治疗方法,但该方法易使其发展成为激素难治性前列腺癌,且暂无切实有效的治疗方法。近年来的研究发现,前列腺癌干细胞在前列腺癌的发生、发展和转移中起着关键作用,因此前列腺癌干细胞的靶向治疗可能是根治前列腺癌的有效途径。靶向前列腺癌干细胞治疗需首先明确前列腺癌干细胞标志物,尤其是其特异标志物,才能更好地开展前列腺癌根治方案的研究。目前前列腺癌干细胞标志物的研究主要集中于CD44和CD133,但随着研究的不断深入其开始受到质疑,且发现了更多新的标志物,本文主要对前列腺癌干细胞领域研究较广和较新发现的肿瘤标志物进行综述。      

H89 enhances the sensitivity of cancer cells to glyceryl trinitrate through a purinergic receptor-dependent pathway

High doses of the organic nitrate glyceryl trinitrate (GTN), a nitric oxide (NO) donor, are known to trigger apoptosis in human cancer cells. Here, we show that such a cytotoxic effect can be obtained with subtoxic concentrations of GTN when combined with H89, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide.2HCl. This synergistic effect requires the generation of reactive oxygen species (ROS) from H89 and NO from GTN treatment that causes cGMP production and PKG activation. Furthermore, the GTN/H89 synergy was attenuated by inhibition of P2-purinergic receptors with suramin and competition with ATP/UDP. By down-regulating genes with antisense oligonucleotides, P2-purinergic receptors P2X3, P2Y1, and P2Y6 were found to have a role in creating this cytotoxic effect. Thus, H89 likely acts as an ATP mimetic synergizing with GTN to trigger apoptosis in aggressive cancer cells.     

肿瘤微环境在乳腺癌发生发展及治疗中的作用

乳腺癌是女性最常见的恶性肿瘤,且发病群体日趋年轻化.随着对其研究的不断深入,人们发现它的侵袭转移过程并非乳腺肿瘤细胞单方面的作用,而是乳腺癌与其所处的肿瘤微环境(tumor microenvironment,TME)相互作用而引起的.故应从乳腺肿瘤微环境中整体研究其发生发展,乳腺癌的治疗也应置于肿瘤微环境中综合考虑,这对寻找新的抗癌作用靶点意义重大.本文就肿瘤微环境中几种主要细胞和因子与乳腺癌发生发展的关系展开论述,并对乳腺癌新的抗癌作用靶点进行探索.     

Intrathecal injection of lentivirus‐mediated glial cell line‐derived neurotrophic factor RNA interference relieves bone cancer‐induced pain in rats

Bone cancer pain is a common symptom in cancer patients with bone metastases and the underlying mechanisms are largely unknown. The aim of this study is to explore the endogenous analgesic mechanisms to develop new therapeutic strategies for bone‐cancer induced pain (BCIP) as a result of metastases. MRMT‐1 tumor cells were injected into bilateral tibia of rats and X‐rays showed that the area suffered from bone destruction, accompanied by an increase in osteoclast numbers. In addition, rats with bone cancer showed apparent mechanical and thermal hyperalgesia at day 28 after intratibial MRMT‐1 inoculation. However, intrathecal injection of morphine or lentivirus‐mediated glial cell line‐derived neurotrophic factor RNAi (Lvs‐siGDNF) significantly attenuated mechanical and thermal hyperalgesia, as shown by increases in paw withdrawal thresholds and tail‐flick latencies, respectively. Furthermore, Lvs‐siGDNF interference not only substantially downregulated GDNF protein levels, but also reduced substance P immunoreactivity and downregulated the ratio of pERK/ERK, where its activation is crucial for pain signaling, in the spinal dorsal horn of this model of bone‐cancer induced pain. In this study, Lvs‐siGDNF gene therapy appeared to be a beneficial method for the treatment of bone cancer pain. As the effect of Lvs‐siGDNF to relieve pain was similar to morphine, but it is not a narcotic, the use of GDNF RNA interference may be considered as a new therapeutic strategy for the treatment of bone cancer pain in the future.     

ATP‐P2Y2‐β‐catenin axis promotes cell invasion in breast cancer cells

Extracellular adenosine 5′‐triphosphate (ATP), secreted by living cancer cells or released by necrotic tumor cells, plays an important role in tumor invasion and metastasis. Our previous study demonstrated that ATP treatment in vitro could promote invasion in human prostate cancer cells via P2Y2, a preferred receptor for ATP, by enhancing EMT process. However, the pro‐invasion mechanisms of ATP and P2Y2 are still poorly studied in breast cancer. In this study, we found that P2Y2 was highly expressed in breast cancer cells and associated with human breast cancer metastasis. ATP could promote the in vitro invasion of breast cancer cells and enhance the expression of β‐catenin as well as its downstream target genes CD44, c‐Myc and cyclin D1, while P2Y2 knockdown attenuated above ATP‐driven events in vitro and in vivo. Furthermore, iCRT14, a β‐catenin/TCF complex inhibitor, could also suppress ATP‐driven migration and invasion in vitro. These results suggest that ATP promoted breast cancer cell invasion via P2Y2‐β‐catenin axis. Thus blockade of the ATP‐P2Y2‐β‐catenin axis could suppress the invasive and metastatic potential of breast cancer cells and may serve as potential targets for therapeutic interventions of breast cancer.     

脂肪酸合成相关酶与乳腺癌的研究进展

乳腺癌是女性最常见的恶性肿瘤,随着肿瘤代谢研究的深入,脂代谢在乳腺癌发生发展中的作用越来越受到重视。内源性脂肪酸合成是肿瘤细胞脂肪酸的主要来源,也是肿瘤细胞的一个重要特征,靶向内源性脂肪酸合成治疗乳腺癌已经成为了一个研究热点。脂肪酸合成途径的相关酶包括ATP-柠檬酸裂解酶(adenosine triphosphate-citrate lyase,ACL)、乙酰辅酶A羧化酶1(acetyl-CoA carboxylase 1,ACC1)、脂肪酸合酶(fatty acid synthase,FASN)和硬脂酰辅酶A去饱和酶1(stearoyl-CoA desaturase-1,SCD1)在乳腺癌发生发展中发挥重要的作用,成为了乳腺癌治疗的新靶点。本文综述了ACL、ACC1、FASN和SCD1与乳腺癌的临床相关性及意义,在乳腺癌发生发展中的作用和分子机制及其抑制剂治疗乳腺癌的研究进展。     

GPD2 在非小细胞肺癌组织中的表达及临床意义

目的:研究GPD2在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达和临床意义,及GPD2基因对裸鼠成瘤能力的影响。方法:选取119例NSCLC肿瘤组织及配对正常组织,行GPD2免疫组化实验,并分析GPD2的表达与NSCLC患者临床病理特征的关系。使用ＲNA干扰慢病毒载体感染A549细胞,接种至裸鼠右侧腋窝,监测小鼠肿瘤生长情况,测量最终体积和重量。结果:肺癌患者肿瘤组织中GPD2的表达明显高于对照组(P＜0.01)。III/IV期组织中GPD2表达明显高于I/II期（P＜0.05）,同时GPD2在淋巴结转移患者中高表达（P＜0.05）。 shGPD2细胞形成肿瘤体积明显小于shCtrl细胞形成肿瘤体积,且肿瘤生长速度远低于shCtrl细胞形成的肿瘤。结论:GPD2蛋白在NSCLC组织中表达显著高于癌旁组织,其表达水平与患者TNM分期、淋巴结转移均显著相关,可能参与了NSCLC的发生、发展。     

Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

BACKGROUND: Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. METHODS: Primary tumors were obtained from 142 patients with axillary node-positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. RESULTS: After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). INTERPRETATION: Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the 'seed and soil' theory.