Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells

Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line. Apoptosis was determined by staining with bisBenzimide and propidium iodide. A dose dependent increase of apoptosis was noted, reaching 61 and 43% with 8 μg/ml CBD and 15 μg/ml CBD-DMH, respectively, after a 24 h treatment. Prior exposure of the cells to γ-irradiation (800 cGy) markedly enhanced apoptosis, reaching values of 93 and 95%, respectively. Human monocytes from normal individuals were resistant to either cannabinoids or γ-irradiation. Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis. Our data suggest a possible new approach to treatment of AML.     

An Atypical Rare Case of Extracranial Craniopharyngioma

We present a case of a purely extracranial, infrasellar craniopharyngioma that initially presented as a mass in nose and nasopharynx. Craniopharyngiomas are usually located within the sella. Purely infrasellar craniopharyngiomas have only rarely been reported in the literature. A 55-year-old man presented with 8-month history of progressive headache and epistaxis. Rhinoscopy revealed polypoidal mass in both the nasal cavities and nasopharynx. Pre-operative biopsy suggested Craniopharyngioma. A battery of tests necessary for the diagnosis of Craniopharyngioma was done which excluded other possibilities. Surgical resection was done and histopathology thereafter was confirmatory of Craniopharyngioma. Adjuvant radiotherapy was given to the patient. The patient is doing well. The Rathke’s pouch arises from the roof of the primitive mouth and grows toward the brain at the fourth week of gestation. Normally, it loses its attachment with the stomadeum completely by the eighth week of gestation. The craniopharyngeal canal (CPC) extends from the floor of the sella to the vomer and may rarely give rise to ectopic craniopharyngiomas. This case shows that such ectopic tumors may arise anywhere along the CPC. We are documenting this case as an atypical rare case of craniopharyngioma probably originating from tooth primordia.     

“凤凰涅槃”通路与肿瘤的复发和转移

肿瘤放化疗导致肿瘤凋亡或死亡的同时,启动了凋亡或死亡通路中某些执行蛋白,使得濒死的肿瘤细胞释放大量的炎症介质至肿瘤微环境,从而促进临近的、残余的或静止期的肿瘤细胞再增殖,这种“凤凰涅槃”现象提示现行以诱导肿瘤细胞凋亡或死亡为主要目的治疗方案存在不足。因此,探索“凤凰涅槃”现象的根源,阐明肿瘤复发和转移的新机制将为肿瘤的防治提供新策略和新思路。     

肌肉减少症与肿瘤化疗

肌肉减少症是以肌肉体积减少、肌力下降和肌肉功能减退为主要特征的临床综合征。肌肉减少症作为一个独立 的疾病体已成为近几年研究的热点,其在肿瘤患者中的地位越来越受到临床医生的重视。肌肉减少症是肿瘤恶病质的一个 重要特征,严重影响患者的生活质量和降低患者的生存期。在肿瘤患者中,发生肌肉减少症的几个主要因素包括：①高耗能; ②厌食;③炎症;④代谢不平衡。为了解肌肉减少症与肿瘤化疗之间的关系,我们从以下几个方面进行综述：肌肉减少症 在肿瘤患者中如何诊断;肌肉减少症在肿瘤患者中的发病率如何;在肿瘤患者治疗中,肌肉减少症与化疗药物之间的关系 如何;肌肉减少症对肿瘤患者预后的影响如何;肌肉减少症的干预措施及其对肿瘤患者治疗结局的影响。随着对肌肉减少 症在肿瘤患者中研究的深入,肿瘤学专家可以借鉴目前研究取得的结果应用于临床,根据每个患者的具体情况制定出个体 化的用药方案、营养治疗或物理辅助治疗策略等,最终为改善患者的预后和提高其生活质量服务。     

2016年上海市恶性肿瘤发病和死亡情况与2002—2016年的变化趋势分析

背景与目的：上海市疾病预防控制中心每年更新上海市恶性肿瘤发病和死亡及其趋势的统计资料。分析2016年上海市恶性肿瘤发病和死亡的基本情况及其2002—2016年的变化趋势。方法：采用上海市疾病预防控制中心建立的人群基础肿瘤登记管理系统和死因登记系统收集的2002—2016年恶性肿瘤发病和死亡资料,按诊断或死亡年份、性别和年龄组分层分析,计算数量、构成比、粗率、年龄别率、年龄标准化率（标化率）等指标,同时计算不同分组的主要癌症类型的数量、构成比和率值。按性别划分的所有恶性肿瘤和各主要癌症类型的发病和死亡标化率采用Joinpoint回归模型计算年度变化百分比（annual percent change,APC）分析变化趋势。应用Segi’s 1960年世界标准人口计算发病和死亡的标化率。结果：2016年上海市恶性肿瘤新发病例和死亡人数分别为74 422例和37 010人,粗发病率为513.94/10万,标化发病率为231.58/10万,女性的标化发病率高于男性。粗死亡率为255.58/10万,标化死亡率为90.01/10万,男性的标化死亡率高于女性。年龄别发病和死亡的数量和率值随着年龄的增长而增加,年龄别发病的数量和率值分别在60~64岁组和80~84岁组达到高峰,年龄别死亡的数量和率值分别在80~84岁组和85岁及以上组达到高峰。按发病例数排序,前10位常见癌症类型的部位依次为肺、结直肠、甲状腺、胃、乳腺、肝脏、前列腺、胰腺、脑和中枢神经系统、膀胱。按死亡人数排序,前10位依次为肺、结直肠、胃、肝、胰腺、乳腺、胆囊、食管、前列腺和淋巴系统。按性别划分的发病和死亡的前10位常见癌症类型与按常见组合年龄段划分的前5位常见癌症类型差异较大。总体上,男性的标化发病率在2002—2009年维持稳定状态,在2009—2016年以年均1.16%的增速上升,女性的标化发病率在2002—2009年维持稳定状态,在2009—2016年以年均4.48%的增速上升。2002—2016年,男性的标化死亡率以年均1.35%的减速下降,女性的标化死亡率以年均1.31%的减速下降。不同性别和癌症类型的变化趋势各不相同。结论：尽管男性和女性的标化发病率略有上升,但是对应的标化死亡率正在下降。按性别或年龄分层的总体和常见癌症类型的现况和趋势反映了上海户籍人口在癌症危险因素、筛查技术应用和诊疗水平等方面的变化。以人群为基础的癌症发病和死亡资料可用于减少癌症负担。     

肿瘤患者“营养认知-食欲-功能”量表的编制及信效度分析

目的开发综合营养认知、食欲及机体功能等评价进行营养风险筛查的量表，并进行信效度验证。 方法 在文献回顾、患者访谈及项目组讨论的基础上确定量表维度、形成条目池，经过德尔斐专家咨询形成原始量表。选取首都医科大学附属北京世纪坛医院104例肿瘤患者进行调查，检验量表的信效度。 结果 最终形成的肿瘤患者营养认知-食欲-功能（nutrition belief-appetite-function， BAF）评估量表包括营养认知、食欲和功能指标3个维度，共13个条目。项目分析时发现各条目和总分的相关系数均＞0.3，各条目的决断值均达到预设标准，故不考虑删除条目。本量表的分半信度为0.750，各维度的分半信度为0.590～0.847；量表的Cronbachs α系数为0.806，各维度的Cronbachs α系数为0.631～0.866，营养认知和功能维度的系数未达到理想状态；量表的重测信度为0.784，各维度的重测信度为0.588～0.721。量表效度分析方面，各维度与总量表间得分的相关系数为0.539～0.890，均有显著性；结构性因子分析提取2个公因子，累计方差贡献率为56.36%，删除2个条目后得到营养认知和食欲及功能相关的两个维度；量表总分及各维度得分均与NRS 2002的显著正相关。 结论 编制的肿瘤患者BAF评估量表具有较好的信效度，可有效评估肿瘤患者的营养风险。     

肌肉减少症

肌肉减少症是一种肌肉量减少、肌肉强度下降、肌肉功能减退的综合征，在老年人、体力活动缺乏者、慢性 疾病患者、恶性肿瘤患者中发病率较高，肌肉减少症患者跌倒、衰弱、失能的风险明显增加，独立生活能力减退，直接影 响老年人生活质量和临床结局，早期认识肌肉减少症对延缓老年衰弱有积极意义。肌肉减少症原因可分为与年龄相关、营 养相关、活动性相关、疾病相关这几个类型。年龄、内分泌改变、慢性炎症、恶液质、营养不良、维生素D 缺乏等能引起 肌肉减少症的发生。欧洲肌肉减少症工作组最新的专家共识建议使用低肌力作为肌肉减少症的最主要参数，推荐的诊断流 程为：问卷筛查肌肉减少症高危人群 - 测量肌肉力量判断患病可能性 - 测量肌肉量确诊 - 测量躯体活动能力评估疾病严重程 度。随着研究的进展人们对肌肉减少症的机制认识越来越清晰，早期营养干预、积极的抗阻运动及合理的药物治疗等可明 显改善肌肉量和肌力，延缓老年人功能衰退，提高生活质量。随着老龄化的到来，人们对肌肉减少症的研究日益重视，发 病机制日渐清晰，但药物治疗方面证据仍不足。     

细胞因子在肿瘤相关性贫血中的作用机制研究进展

肿瘤相关性贫血是肿瘤发生发展过程中最常见的并发症,肿瘤患者的贫血类型呈多样性,因影响红细胞生成或消耗的因素众多,如：慢性失血、溶血、铁代谢紊乱、肾功能不全、造血功能障碍（骨髓抑制）、炎性反应因子数量的增加、肿瘤患者恶性消耗、促红细胞生成素相对不足等均可导致贫血。目前肿瘤相关性贫血的具体发生机制尚未完全清楚,但炎性反应因子在肿瘤相关性贫血发生发展过程中起着决定性作用,其中hePcidin、IL-6、TNF-α及EPO等细胞因子扮演着重要角色。改善肿瘤患者的贫血状态,可以改善患者症状,提高患者生活质量,改善患者认知能力,增强患者社会能力,成为临床医师越来越关注的焦点。     

头颈区黏膜淋巴瘤的WHO分类更新及诊断方法

2017年1月与9月，《WHO头颈肿瘤分类》（第4版）与《WHO造血淋巴组织肿瘤分类》（修订第4版）两本蓝皮书相继面世，笔者也有幸受邀参与了《WHO头颈肿瘤分类》（第4版）一书中淋巴造血组织肿瘤有关章节的编写工作，分别对这两个新分类中关于头颈区黏膜淋巴组织增生性疾病的内容更新、头颈区黏膜淋巴瘤的诊断方法以及该区域常见淋巴瘤类型的诊断与鉴别诊断要点作一简介。     

NF-κB诱捕ODN促进宫颈癌HeLa细胞凋亡的实验研究

目的 探讨NF-κB在正常宫颈组织、宫颈上皮内瘤变组织以及宫颈癌组织中的表达情况以及NF-κB诱捕ODN对宫颈癌HeLa细胞增殖、凋亡的影响。方法 选取2013年2月至2014年2月南京医科大学第二附属医院妇产科收治的42例宫颈癌患者,以及同期诊治的宫颈上皮内瘤样病变患者22例、正常宫颈组织12例,进行免疫组织化学检测NF-κB信号激活情况;在体外培养的宫颈癌HeLa细胞株中,分别转染NF-κB特异诱捕ODN和错义ODN,使用MTT和流式细胞技术检测细胞增殖、凋亡情况。结果宫颈癌组织中NF-κB的表达明显增加;使用NF-κB诱捕ODN阻断NF-κB信号激活能够显著抑制宫颈癌HeLa细胞增殖,并增强顺铂诱导的细胞凋亡。结论 NF-κB诱捕ODN可以通过阻断NF-κB信号活化,从而抑制细胞增殖并增强顺铂诱导的细胞凋亡,为宫颈癌治疗提供了新的作用靶点和治疗方向。     

放化疗联合脑转移瘤放疗治疗非小细胞肺癌脑转移的临床疗效分析

目的 分析化疗同期胸部三维放疗联合脑转移瘤放疗治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）单纯脑转移的疗效及影响预后的因素。方法 回顾性分析52例单纯脑转移且脑转移瘤及原发肿瘤均接受放疗的NSCLC患者的临床资料,Kaplan-Meier法计算生存率并行log-rank 检验,Cox回归模型行多因素预后分析。结果 全组患者中位随访时间为13.5个月（4～49个月）,中位生存期为13.0个月（95% CI：11.2～14.8）,1年、2年、3年生存率分别为53.8%、13.5%和3.8%。胸部原发肿瘤体积＜118 cm³组和≥118 cm³组的中位生存期分别为14.0个月（95% CI：11.6～16.4）和12.0个月（95%  CI：10.7～13.3）,1年生存率分别为66.7%和42.9%,2年生存率分别为20.8%和0,3年生存率分别为8.3%和0,两组总生存率比较差异有统计学意义（χ²=5.648,P=0.017）。胸部原发肿瘤放疗剂量（dose to PTV,DTPTV）≥66 Gy组和DTPTV＜66 Gy组的中位生存期分别为13.0个月（95%  CI：10.8～15.2）和14.0个月（95%  CI：10.8～17.2）,两组比较差异无统计学意义（χ²=0.064,P=0.80）。多因素预后分析显示,原发肿瘤体积是影响总生存率的独立预后因素。结论 化疗同期胸部三维放疗联合脑转移瘤放疗治疗NSCLC单纯脑转移取得较好疗效,原发肿瘤体积较小的患者生存获益更大。     

中国人群HBV基因型及亚型与肝细胞癌相关性的Meta分析

目的 探讨中国人群HBV基因型及亚型与肝细胞癌（以下简称“肝癌”）的相关性。方法 计算机检索文献,收集2007年1月至2017年2月公开发表的有关中国人群HBV基因型、亚型与肝癌相关性的病例对照研究,按纳入与排除标准筛选文献、评价质量并提取有效数据,采用RevMan 5.3进行Meta分析。结果 最终纳入中国人群HBV基因型与肝癌相关性研究37篇,其中病例组4 109例,对照组15 319例;HBV基因亚型（C1、C2、 B2）与肝癌相关性研究8篇,其中病例组931例,对照组5 793例;纳入文献质量评分均≥7分。Meta分析结果显示,携带HBV C基因型者罹患肝癌的风险较携带HBV B基因型高（OR=2.35,95%CI：1.93~2.87,P<0.001）;携带HBV C基因型与A/D基因型者罹患肝癌风险差异无统计学意义（OR=1.25,95%CI：0.20~7.82,P=0.81）;携带HBV C1亚型、HBV C2亚型者罹患肝癌的风险差异无统计学意义（OR=1.05,95%CI：0.66~1.68,P=0.82）,携带HBV C2亚型者罹患肝癌风险较HBV B2亚型者高（OR=1.77,95%CI：1.38~2.27,P<0.001）。结论 中国人群携带HBV C基因型者罹患肝癌风险较其他主要基因型高,携带HBV C1亚型和HBV C2亚型者罹患肝癌风险相当,但HBV C2亚型者罹患肝癌风险均较携带HBV B2亚型者高。     

基于三种CT图像勾画的非小细胞肺癌靶体积比较研究

目的 比较基于三维CT (3DCT)、四维CT (4DCT)和锥形束CT (CBCT)图像勾画所得非小细胞肺癌(NSCLC)靶区位置和体积差异。方法 31例周围型NSCLC患者,序贯完成胸部3DCT和4DCT扫描,基于3DCT制定放疗计划,放疗首次拍摄CBCT,并基于骨性标志配准校正。在3DCT、4DCT的50%时相、最大密度投影(MIP)、CBCT图像上勾画得到GTV_3D、GTV_4D50%、IGTV_MIP和IGTV_CBCT。对组间位移比较行Wilcoxon秩和检验,靶区位置及包含度比较行配对t检验,肿瘤三维运动相关性行Pearson法分析。结果 肺上叶组GTV_3D、GTV_4D50%、IGTV_MIP 与IGTV_CBCT比值分别为0.77、0.84和1.10(P=0.004、0.005、0.07);中下叶组比值分别为0.67、0.65和1.17(P=0.001、0.001、0.020)。全组患者GTV_4D50%与IGTV_CBCT比值与肿瘤三维运动呈负相关(P=0.012)。全组患者IGTV_CBCT对GTV_3D、GTV_4D50%、IGTV_MIP包含度分别为0.65、0.65和0.62,IGTV_CBCT对GTV_MIP包含度与IGTV_CBCT对GTV_3D或GTV_4D50%包含度差异无统计学意义(P=0.375、0.167),而GTV_3D、GTV_4D50%、IGTV_MIP对IGTV_CBCT包含度分别为0.47、0.49和0.67,IGTV_MIP对IGTV_CBCT包含度大于GTV_3D或GTV_4D50%对IGTV_CBCT包含度(P=0.000、0.000)。结论 CBCT图像包含的肿瘤运动信息量明显大于3DCT图像,但略小于4DCT的MIP图像。即使3DCT、4DCT与CBCT配准校正后也有可能导致较严重的脱靶,这是基于CBCT进行循证靶区和计划修正所需注意的。     

DNA repair gene polymorphisms and risk of adult meningioma,glioma, and acoustic neuroma

Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case–control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR_CT/TT = 3.5; 95% confidence interval: 1.8–6.9; P_trend .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P_trend .01); MUTYH rs3219466 (P_trend .02), and PCNA rs25406 (P_trend .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P_trend .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P_trend .03) and ERCC5 rs17655 (P_trend .05) variants and decreased for the PARP1 rs1136410 (P_trend .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P_trend .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma.     

The Risk of Helicobacter Pylori Infection and Atrophic Gastritis from Food and Drink Intake: a Cross-sectional Study in Hokkaido

One-hundred and fifteen subjects were diagnosed with Helicobacter pylori (HP) infection and 93 subjects with ‍atrophic gastritis (AG) from tests of HP antibodies or serum levels of pepsinogen I and pepsinogen II involving 210 ‍inhabitants, who participated in the health check-up program. Logistic regression analysis found that refreshing ‍(isotonic) beverages significantly reduced the risk of HP infection (odds ratio: 0.767, 95%C.I.: 0.616-0.956). A higher ‍frequency of intake for margarine (odds ratio: 1.413, 95%C.I.: 1.080-1.848), cheese (odds ratio: 1.416, 95%C.I.: ‍1.044-1.920), Tsukemono (odds ratio: 1.277, 95%C.I.: 1.000-1.631) or Cola-beverages (odds ratio: 1.471, 95%C.I.: ‍1.051-1.239) showed a significantly increased risk of AG. In addition, high serum values of â-carotene (odds ratio: ‍0.691, 95%C.I.: 0.498-0.958), linoleic acid (odds ratio: 0.594, 95%C.I.: 0.382-0.924), and ã-linolenic acid (odds: 0.987, ‍95%C.I.: 0.976-0.998) were found to reduce the risk of AG, but not HP infection. Furthermore, these results suggest ‍that a more frequent intake of margarine, Tsukemono (pickled vegetables), or Cola-beverages may be a risk factor ‍for AG, while foods rich in carotenes, such as, â-carotene and n-6PUFAs, such as ã-linolenic acid, may reduce the ‍risk of AG.     

A novel immunomodulatory and molecularly targeted strategy for refractory Hodgkin's lymphoma

Although Hodgkin''s lymphoma (HL) was one of the first human cancers to be cured by chemotherapy, no new agents other than brentuximab vedotin (Adcetris®, CD 30 directed antibody drug conjugate) have received US Food and Drug Administration (FDA) approval for HL since 1977. Subsets of young adult patients with HL continue to relapse, even after stem cell transplantation, warranting new approaches. Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). In-depth immunohistochemical and morphoproteomic analyses of this exceptional responder to targeted therapy have yielded potential insights into the biology of advanced HL. The PI3K/AKT/mTOR pathway is a commonly activated pathway in multiple tumor types including HL. The patient was treated using therapy based on mechanistic in vitro data demonstrating that combined histone deacetylase (HDAC) and mTOR inhibition act together on this pathway, resulting in inhibition of reciprocal feedback networks, leading to better anti-proliferative activity. The in vivo response signature from this patient''s tissue sample sheds light on immune dysregulation in HL. We describe the response signature achieved from targeting immune dysregulation in addition to targeting the key oncogenic PI3K/AKT/mTOR pathway. We also expand on the role of rapamycin analogs in oncology. This study supports a role for an immune-type pathogenesis that is amenable to immune modulating targeted therapy in refractory HL.Significance: We report an exceptional responder to molecularly targeted and immune modulator therapy in advanced Hodgkin''s lymphoma. The morphoproteomic/morphometric findings in this “unusual responder” patient''s relapsed HL that correlate best, as a response signature with the subsequent clinical remission following rapamycin (sirolimus) and vorinostat (SAHA) therapies, center on an immune dysregulation involving an imbalance between effector and functional T regulatory cells in addition to targeting the mTOR pathway. This underscores the need for an approach illustrated in our study – namely of focusing on pathogenetic mechanisms and combinatorial therapies that target both the pathogenesis and adaptive responses to contemplated therapies.     

Awareness and Attitude Relating to the Human Papilloma Virus and its Vaccines Among Pediatrics,Obstetrics and Gynecology Specialists in Turkey

Background: To determine the level of knowledge on human papillomavirus (HPV) infection and vaccination,and the attitude towards HPV vaccination in pediatricians, obstetricians and gynecologists (OBG). Materialsand Methods: Participants were administered a 40-question survey, investigating the demographic properties,the knowledge on the HPV infection-vaccination and attitudes towards vaccination. Results: The study enrolleda total of 228 participants (131 pediatricians and 97 OBGs). At a rate of 99.6%, the participants agreed with thefact that the HPV infection was the most common sexually transmitted disease and 33.8% of the participants hadthe opinion that the HPV vaccination should be administered only in women. The lowest level of HPV vaccinerecommendation was among the pediatrics specialists (59.4%, p=0.012). When asked whether they would havetheir daughters receive HPV vaccination, 79.5% of the participants answered favorably; this rate was 36.7%for the sons. At a rate of 59.5% of the participants thought that the HPV vaccine needed to be included in thenational vaccine schedule. Most of the participants (91.6%) had the idea that reduction of the vaccine costswould increase the vaccination frequency. Conclusions: We observed that the consideration of the costs and theprejudices relating to the inefficacy of vaccination as well as the inadequate level of knowledge were involved inthe physicians’ resistance to HPV vaccination. We believe that the healthcare professionals should be informedadequately to overcome false beliefs, thereby ensuring success of the HPV vaccine upon inclusion in the nationalvaccine schedule in the future.     

水蛭素对肝细胞癌HepG2细胞抑制作用机制探讨

目的 研究水蛭素对肝细胞癌（hepatocellular carcinoma,HCC,简称肝癌）HepG2细胞抑制作用及其抗肝癌的分子机制。方法 将含不同浓度（1 U/mL、2 U/mL、4 U/mL和8 U/mL）水蛭素的培养液作用于肝癌HepG2细胞,采用MTT法检测水蛭素对肝癌HepG2细胞增殖的影响,流式细胞仪检测水蛭素对肝癌HepG2细胞凋亡的影响,Transwell法检测水蛭素对肝癌HepG2细胞迁移、侵袭的影响,荧光定量PCR检测血管内皮生长因子（vascular endothelial growth factor,VEGF）基因的mRNA表达水平,Western blot检测VEGF基因的蛋白表达水平。结果 与空白对照组比较,肝癌HepG2细胞增殖抑制率随水蛭素浓度（1 U/mL、2　U/mL、4 U/mL和8 U/mL）增加及作用时间（24　h、48　h、72　h）延长而增加,呈剂量-时间依赖效应（P<0.05）。不同浓度（2 U/mL、4 U/mL和8 U/mL）水蛭素作用48 h后,肝癌HepG2细胞凋亡率分别为（28.37±1.16）%、（40.27±0.97）%、（76.17±1.5）%,细胞侵袭个数分别为（204±9）个、（163±6）个、（94±4）个,细胞迁移个数分别为（86±5）个、（54±7）个、（20±5）个,细胞凋亡率、侵袭及迁移个数随水蛭素浓度增加而增加,呈浓度依赖性（P<0.05）。VEGF mRNA、蛋白的表达量随水蛭素浓度增加而明显下调（P<0.05）。结论 水蛭素能抑制肝癌HepG2细胞增殖、凋亡、迁移及侵袭,其机制可能是通过下调VEGF表达。     

Genetic Screening for Familial Gastric Cancer

Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1) mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC). E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.