磷脂酰肌醇3激酶和蛋白激酶B在宫颈癌组织中的表达及意义

背景与目的:磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号转导通路具有重要的细胞调节功能,在肿瘤的发生发展中也发挥着重要的作用。但目前对宫颈癌中该通路的研究尚不充分。本研究拟检测不同宫颈病变组织中PI3K和Akt蛋白的表达,探讨PI3K/Akt信号转导途径与宫颈癌生物学行为的关系。方法:采用免疫组化SP法检测76例宫颈癌组织,21例宫颈上皮内瘤变组织,10例正常宫颈组织中PI3K、Akt蛋白的表达情况,并分析与宫颈癌临床病理因素的关系。结果:PI3K蛋白在正常宫颈组织中无表达,宫颈上皮内瘤变组织中表达率为42.9%,显著低于宫颈癌组织的69.7%(P<0.01)。Akt蛋白在正常宫颈组织和宫颈上皮内瘤变组织中的表达率分别为10.0%和52.4%,显著低于宫颈癌组织的75.0%(P<0.01)。PI3K和Akt蛋白的表达与宫颈癌患者临床分期、病理分级、淋巴转移有关(P<0.01),与年龄、原发灶大小、组织类型无关(P>0.05)。随着宫颈癌组织中PI3K表达的增强,Akt的阳性率增加。二者呈正相关(r=0.425,χ2=18.96,P<0.01)。结论:PI3K蛋白的高表达和Akt蛋白的高表达与宫颈癌细胞的增殖、浸润和转移有一定的相关性。     

血管内皮生长因子受体3与PI3K/AKT在胃癌组织中的表达及意义

 目的 观察血管内皮生长因子受体3（VEGFR-3）和磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B (PKB或Akt)在胃癌组织及相应癌旁组织中的表达情况。 方法 采用RT-PCR法检测36例胃癌及相应癌旁对照组织中VEGFR-3、PI3K、Akt mRNA 的表达;免疫组织化学法检测VEGFR-3、P-Akt蛋白的表达,并用图像分析方法测定平均吸光度值。 结果 1. RT-PCR 胃癌组织中VEGFR-3mRNA、PI3KmRNA、AktmRNA与癌旁对照组织的表达水平相比,差异有统计学意义(P<0.05),且VEGFR-3mRNA与PI3KmRNA、AktmRNA表达呈正相关 (P<0.05)。VEGFR-3 mRNA表达与TNM分期、浸润深度、淋巴结转移与远处转移有关(P<0.05)。2. 免疫组织化学 VEGFR-3、P-Akt蛋白在胃癌组织中的表达水平明显高于癌旁对照组织(P<0.05),且VEGFR-3、P-Akt蛋白表达水平呈正相关(P<0.05)。 结论 VEGFR-3阳性表达的胃癌患者可能更易发生淋巴结转移,VEGFR-3可作为评估患者预后的重要指标。VEGFR-3与PI3K/Akt的表达具有一定的相关性。     

磷脂酰肌醇3-激酶/蛋白激酶B与基质金属蛋白酶9在铂耐药上皮性卵巢癌中的表达及意义

目的 探讨磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)和基质金属蛋白酶9(MMP9)在铂耐药上皮性卵巢癌中的表达及临床意义.方法 使用酶联免疫吸附法分别检测PI3K、AKT及MMP9在38例铂类敏感卵巢癌(铂敏感组)和40例铂类耐药上皮性卵巢癌(铂耐药组)中的表达水平;分析各指标在铂耐药组内不同临床特征患者血清中的表达差异.结果 铂耐药组患者血清PI3K、AKT、MMP9水平均高于铂敏感组,差异均有统计学意义(P﹤0.05).组织学分级为G3级、病理类型为透明细胞癌的铂耐药组患者血清PI3K及AKT水平分别高于组织学分级为G1～2级及其他病理类型,差异均有统计学意义(P﹤0.05);临床分期为Ⅲ～Ⅳ期、有淋巴结转移以及有脉管浸润的铂耐药组患者血清MMP9水平分别高于临床分期为Ⅰ～Ⅱ期、无淋巴结转移以及无脉管浸润患者,差异均有统计学意义(P﹤0.05).PI3K与AKT表达呈正相关(r=0.472,P﹤0.05),PI3K与MMP9表达无相关性(r=0.187,P﹥0.05),AKT与MMP9表达呈正相关(r=0.431,P﹤0.05).结论 PI3K/AKT信号通路在上皮性卵巢癌铂耐药中起着重要作用,活化的AKT可能通过激活下游靶蛋白MMP9抑制细胞凋亡,降低细胞对化疗药物的敏感性.     

甲状腺乳头状癌PI3K/Akt信号转导通路mRNA和蛋白表达及其生物学意义的探讨

目的:探讨甲状腺乳头状癌(PTC)中PI3K mRNA、Akt mRNA、PI3K和Akt的表达与意义。方法:采用逆转录聚合酶链反应(RT-PCR)测定组织中PI3KmRNA和Akt mRNA的表达;应用免疫组化法测定组织中PI3K和Akt蛋白的表达。结果:PTC中PI3KmRNA表达量(90.3±5.06)和Akt mRNA的表达量(78.13±5.5)高于癌旁正常甲状腺组织(NAT)表达量37.74±10.63和14.82±5.63,P<0.05。免疫组化结果显示,甲状腺乳头状癌PI3K蛋白表达阳性率73.33%、Akt蛋白表达阳性率(83.33%)明显高于NAT组织蛋白表达阳性率33.33%和16.67%,P<0.05。PTC中PI3K和Akt蛋白表达与包膜浸润及淋巴结转移相关,P<0.05。结论:PTC中存在PI3K/Akt信号传导通路的异常激活,信号传导途径的激活水平与PTC浸润和局部转移有关。     

趋化因子受体CCR7与PI3K/Akt通路在胃癌组织中的表达及意义

目的 观察趋化因子受体CCR7和磷脂酰肌醇-3-激酶（PI3K）、蛋白激酶B（PKB或Akt）在胃癌组织中的表达情况,探讨CCR7与PI3K/Akt通路的关系。方法 采用RT-PCR法检测32例胃癌及相应癌旁对照组织中CCR7mRNA、PI3KmRNA、AktmRNA的表达;Western Blotting法检测CCR7、p-Akt蛋白的表达。结果 胃癌组织中CCR7mRNA、PI3KmRNA、AktmRNA与癌旁对照组织的表达水平相比,差异均有显著性（P〈0.001）,且CCR7mRNA与PI3KmRNA、AktmRNA表达呈正相关（P〈0.05）。CCR7、P-Akt蛋白在胃癌组织中的表达水平明显高于癌旁对照组织（P〈0.05）,两者表达与肿瘤TNM分期、浸润深度、分化程度、淋巴结转移与远处转移有关（P〈0.05）,并且CCR7、P-Akt表达水平呈正相关（P〈0.05）。结论 胃癌组织中高表达的CCR7可能通过PI3K/Akt通路促进胃癌的侵袭转移。     

3-磷酸肌醇依赖性蛋白激酶1在肿瘤发生发展及治疗中的作用

3-磷酸肌醇依赖性蛋白激酶1(PDK1)是磷脂酰肌醇3激酶-蛋白激酶B(PI3 K-Akt)通路的一个关键调节分子.PDK1可通过激活Akt,参与PI3K-Akt信号通路的活化,促进肿瘤的发生、发展及浸润转移.目前已经发现PDK1在头颈部肿瘤、多发性骨髓瘤、胰腺癌、食管癌、结肠癌等多种恶性肿瘤中高表达.抑制PDK1过表达可为恶性肿瘤的治疗找到新的突破点.目前已有多种PDK1抑制剂投入生产,发挥了抗肿瘤作用.     

PTEN/PI3K/Akt在非小细胞肺癌中的表达及其临床病理意义

背景与目的PTEN/PI3K/Akt信号通路的异常与一些恶性肿瘤的形成关系密切,本研究旨在探讨非小细胞肺癌(NSCLC)中PTEN、PI3K及Akt的表达及其临床意义。方法采用免疫组化SP法对61例NSCLC石蜡标本PTEN、PI3K及Akt蛋白表达进行研究,分析其与临床病理特征的关系。结果①PTEN在NSCLC中表达明显低于对照组;Akt、PI3K表达均明显高于对照组;②PTEN、PI3K表达与组织学类型、临床分期、淋巴结转移及生存率相关;Akt表达与临床分期、淋巴结转移及生存率相关;③Cox单因素分析显示对患者术后死亡有影响的因子有吸烟和PTEN阴性表达,且均为危险因子;④PTEN与PI3K、Akt蛋白阳性表达之间分别呈负相关;PI3K与Akt之间呈正相关。结论在NSCLC中,PTEN的缺失导致了PI3K/Akt表达上调,提示PTEN/PI3K/Akt信号通路在NSCLC的发生发展中可能起重要作用,并可作为NSCLC预后标志及分子治疗靶点。     

PI3K、Akt以及PTEN在胃肠道间质瘤中的表达及意义

目的:探讨PI3K、Akt以及PrEN的表达与GIST临床病理特征及预后的相关性,并探讨它们间的相互关系,以揭示其在GIST发生发展过程中的作用,为进一步的肿瘤靶点治疗提供理论依据.方法:选择临床病理资料完整、随访结果确切的中国医科大学附属盛京医院1990年-2007年2月手术切除、病理证实的GIST新鲜组织标本124例.男性64例、女性60例,平均年龄54.6岁.RT-PCR检测PI3K、Akt以及PTEN在GIST及对照组的mRNA水平.结果:PI3K mRNA水平随NIH分级表达上调(P＜0.05),PI3K的阳性表达率与黏膜受侵和肿瘤侵袭转移均显著相关(P＜0.05).Akt mRNA水平随NIH分级表达上调,其中在高、中危肿瘤组之间不明显,无统计学意义,其余各组有意义;Akt的阳性表达率与肿瘤侵袭转移和黏膜受侵显著相关,提示Akt的过表达促进了GIST的肿瘤侵袭转移.同时PTENmRNA随NIH分级表达下调(P＜0.05),随着肿瘤恶性程度的增加,PTEN的缺失率增高;PTEN的阳性表达率与肿瘤侵袭转移和黏膜受侵关系密切.结论:PI3 K/Akt与PTEN在GIST的发生发展中可能互相拮抗共同作用,PI3K、Akt蛋白阳性表达之间呈显著正相关(r =0.292.P=0.031);PI3K与PTEN蛋白阳性表达之间呈显著负相关(r=-0.412,P =0.036);PTEN与Akt蛋白阳性表达之间呈显著负相关(r=-0.386,P=0.024).     

非小细胞肺癌组织中表皮生长因子受体磷脂酰肌醇3激酶蛋白激酶B1及哺乳动物雷帕霉素靶蛋白mRNA表达及其临床意义

目的探讨磷脂酰肌醇3激酶/蛋白激酶B1/哺乳动物雷帕霉素靶蛋白(PI3K/Akt1/m TOR)通路与表皮生长因子受体(EGFR)基因的关系,及其PI3K/Akt1/m TOR通路导致EGFR-酪氨酸激酶抑制剂(TKI)耐药的具体机制。方法选择135例未经过放化疗或靶向药物治疗的非小细胞肺癌(NSCLC)患者的肿瘤组织标本,检测其EGFR、PIK3CA、Akt1和m TOR的mRNA表达水平,并进行相关性分析。结果 EGFR与Akt1、m TOR的表达水平呈正相关(r分别为0.342、0.320和0.281,均P<0.01),与PIK3CA基因无关。结论 EGFR基因表达与Akt1和m TOR相关,与PIK3CA无关,提示EGFR基因可能直接激活Akt及其下游通路,而不经过PI3K。     

胃癌PI3K和Akt及Survivin表达与临床病理特征及预后的相关性研究

目的   探讨胃癌组织中PI3K、Akt和Survivin表达与临床病理特征及预后的关系,为胃癌的诊断和预后评估提供理论依据。方法   采用免疫组化En Vision法检测75例胃癌组织中PI3K、Akt和Survivin表达,分析其表达与临床病理特征的关系;采用Spearman相关检验分析三者表达之间的关系;采用Kaplan-Meier法进行生存分析;采用Cox多因素回归模型分析影响胃癌预后的独立因素。结果  胃癌组织中PI3K、Akt和Survivin阳性表达率分别为73.3％（55／75）、38.7％ （29／75）和61.3％（46／75）。PI3K、Akt和Survivin表达与分化程度、TNM分期、淋巴结转移均有关（P＜0.05）,而与性别、年龄、肿块大小、治疗前CEA水平无关（P＞0.05）; PI3K与Akt、Survivin表达呈正相关（r=0.293,P＜0.05;r=0.450,P＜0.05）。Kaplan-Meier生存分析显示,PI3K、Akt、Survivin、分化程度、TNM分期及淋巴结转移与预后有关（P＜0.05）;Cox多因素回归分析显示,Survivin表达、淋巴结转移为影响胃癌预后的独立因素（P＜0.05）。结论  PI3K、Akt和Survivin表达与胃癌侵袭、转移密切相关,PI3K与Akt、Survivin之间可能存在协同作用,共同促进胃癌的恶性进展,Survivin是影响胃癌预后独立的因素之一。     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.