Bim在克唑替尼诱导EML4-ALK融合基因阳性肺腺癌细胞株H2228凋亡中的作用机制

目的 探讨Bim在克唑替尼诱导EML4-ALK融合基因阳性肺腺癌细胞株H2228凋亡过程中的作用机制。方法 在不同时间点（24、48、72h）用不同浓度克唑替尼分别处理EML4-ALK阳性肺腺癌H2228细胞株和EML4-ALK阴性肺癌A549细胞株,采用MTT法检测克唑替尼作用72h的细胞增殖抑制情况;PI单染流式细胞仪检测经300nmol／L克唑替尼作用24、48和72h的细胞凋亡率;采用Western blotting法检测克唑替尼诱导前后Bim蛋白（Bim-EL、Bim-L和Bim-S）的表达水平,同时对促凋亡分子 Bid和抗凋亡分子 Bcl-2、Bcl-xL的蛋白水平进行联合检测;采用siRNA 技术“沉默”Bim 基因的表达,用流式细胞仪检测 siRNA“沉默”Bim基因后克唑替尼诱导H2228细胞株的凋亡率。结果 克唑替尼作用72h后,肺腺癌H2228细胞株和A549细胞株的细胞增殖抑制率均随着克唑替尼药物浓度的增加而逐渐升高,呈剂量依赖性。克唑替尼作用于H2228细胞72h的IC50值为335nmol／L。300nmol／L克唑替尼作用H2228 细胞株24、48、72h后的凋亡率分别为（19.19±0.61）％、（35.47±1.17）％、（43.58±4.84）％,作用A549细胞株的凋亡率分别为（12.71±0.1）％、（18.22±0.13）％、（19.36±0.45）％。随着克唑替尼（300nmol／L）作用时间的延长,细胞凋亡率亦随之增加,并呈时间依赖性（P＜0.05）。在凋亡细胞中发现Bim蛋白水平升高,以及抗凋亡蛋白 Bcl-2、Bcl xL表达降低,但促凋亡蛋白 Bid 在不同药物浓度及时间点的表达水平无明显变化。此外,经siRNA 技术“沉默”Bim 基因后,克唑替尼诱导的H2228细胞株凋亡率明显降低。结论克唑替尼通过下调抗凋亡蛋白 Bcl 2、Bcl xL及上调Bim的表达水平来发挥其诱导细胞凋亡作用,该过程可被Bim siRNA抑制。     

AKT信号通路在克唑替尼诱导的EML4-ALK阳性肺癌细胞凋亡迁移中的作用及机制研究

目的 探讨AKT信号通路在克唑替尼诱导的EML4-ALK阳性肺癌细胞凋亡迁移中的作用及机制研究.方法 培养人肺癌细胞株H2228,CCK8实验检测20、40、80、160、320、640 nmol/L的克唑替尼作用于细胞48 h后对细胞增殖的影响,计算半抑制浓度(IC50);300 nmol/L克唑替尼处理细胞24、48、72 h后,流式细胞仪检测细胞凋亡率,Transwell小室检测细胞迁移数;Western Blot检测Bcl-xL、Bcl-2、Bim、AKT、p-AKT蛋白表达.结果 克唑替尼能明显抑制人肺癌细胞株H2228增殖(P﹤0.01),根据IC50值选择300 nmol/L克唑替尼为研究对象;克唑替尼能明显促进细胞凋亡,抑制细胞迁移(P﹤0.01);克唑替尼能下调Bcl-xL、Bcl-2、p-AKT蛋白表达,上调Bim蛋白表达(P﹤0.01).AKT蛋白表达水平在克唑替尼作用的各个时间点间比较,差异无统计学意义(P﹥0.05).结论 克唑替尼通过AKT信号通路抑制人肺癌细胞株H2228迁移,并通过调节Bcl-xL、Bcl-2、Bim蛋白表达促进细胞凋亡.     

吉非替尼敏感性不同的非小细胞肺癌中miRNA-7表达的差异及临床意义

目的检测吉非替尼敏感性不同的非小细胞肺癌中miR-7的表达差异,并探讨其临床意义。方法采用吉非替尼(Gefitinib)药物大剂量冲击法诱导H827,建立耐吉非替尼肺癌细胞亚系H827-7/GR,有限稀释法将H827-7/GR细胞单克隆化,CCK-8法检测耐药前后细胞株及各单克隆细胞对吉非替尼的敏感性;RT-PCR方法检测H827、H827-7/GR和耐药单克隆细胞株以及其他对吉非替尼敏感性不同的肺癌细胞株A549、H358、H1299、H1650和H1975中miR-7的表达差异。结果 H827/GR耐药指数大于100;获得的6株耐药单克隆细胞株对吉非替尼的半生长抑制浓度(the half growth inhibition concentration,IC50)值不同;和吉非替尼敏感株H827相比,诱导的耐药细胞株H827/GR、耐药单克隆细胞株和吉非替尼耐药株A549、H358、H1299、H1650和H1975中miR-7的相对表达水平均降低(P<0.05)。结论在非小细胞肺癌中,耐药细胞中miR-7的相对表达水平均较敏感细胞系降低,提示miR-7的低表达可能与非小细胞肺癌耐药性相关,其可能是潜在的肺癌药物敏感性预测分子标志物。     

洛伐他汀克服非小细胞肺癌PC9细胞株吉非替尼耐药的体外研究

目的:研究联合洛伐他汀(lovastatin)和吉非替尼(gefi tinib)对体外诱导吉非替尼获得性耐药的非小细胞肺癌细胞株PC9细胞凋亡以及相关蛋白表达的影响,并探讨其可能的机制。方法:应用洛伐他汀联合吉非替尼处理耐吉非替尼的非小细胞肺癌PC9细胞株后,采用WST-1法检测不同药物处理对PC9细胞增殖的影响,Hoechst33342荧光染色法观察细胞凋亡形态,FCM法观察细胞凋亡状况,蛋白质印迹法检测凋亡相关蛋白的表达水平。结果:洛伐他汀联合吉非替尼可在体外诱导耐吉非替尼的PC9细胞凋亡,抑制其细胞增殖;洛伐他汀联合吉非替尼可诱导耐吉非替尼的PC9细胞中磷酸化表皮生长因子受体(phosphorylated epidermal growth factor receptor,p-EGFR)、磷酸化蛋白激酶B(phosphorylated protein kinase B,p-AKT)和磷酸化细胞外调节蛋白激酶1/2(phosphorylated extracellular signal-regulated kinase1/2,p-ERK1/2)蛋白表达水平明显下调。结论:在体外诱导吉非替尼获得性耐药的非小细胞肺癌细胞株PC9中,洛伐他汀可以克服吉非替尼耐药,两者具有良好的协同作用,提示两药联合对于出现吉非替尼耐药的非小细胞肺癌的临床治疗可能具有很大的应用潜力。     

EML4-ALK融合基因阳性非小细胞肺癌

 EML4-ALK基因融合能提高间变性淋巴瘤激酶（ALK）表达水平,激活ALK引起的肿瘤细胞生长、增殖、抗凋亡。EML4-ALK基因融合阳性肺癌常见于不吸烟的年轻女性腺癌患者,有着独特的临床特征。目前检测EML4-ALK融合基因常用方法有逆转录聚合酶链式反应技术、原位杂交免疫荧光和免疫组化技术。ALK抑制剂克卓替尼能够作用于该基因的传导通路并抑制其肿瘤活性。     

大黄素逆转非小细胞肺癌EGFR-TKI耐药的机制研究

目的 探讨大黄素逆转非小细胞肺癌（NSCLC）表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKI）耐药的作用机制。方法 应用持续诱导的方法构建NSCLC EGFR-TKI耐药细胞株HCC827／GR;应用MTS法检测大黄素（30μmol／L）、吉非替尼（1μmol／L）及两药联合处理HCC827和HCC827／GR细胞48h后细胞增殖能力的变化;应用Western blotting法检测HCC827和 HCC827／GR细胞中p EGFR、p-AKT、p-ERK1／2及p-MET蛋白表达水平的变化。结果 MTS法检测结果显示,经单药吉非替尼或大黄素处理后,HCC827／GR细胞增殖能力未减弱,而两药联合处理组的细胞增殖能力明显下降,差异有统计学意义（P＜0.05）。Western blotting检测结果显示,HCC827、HCC827／GR细胞中p-EGFR、p-ERK1/2明显表达,而p-AKT表达微弱;HCC827／GR 中p-MET表达水平较HCC827明显上调。经单药吉非替尼处理后,HCC827细胞株p-EGFR、p-ERK1/2表达水平下调,HCC827／GR细胞株p-EGFR表达明显下调;大黄素可显著下调HCC827／GR细胞株p-MET表达,但对p-EGFR、p-ERK1/2的表达无影响;而大黄素与吉非替尼两药联用可明显抑制HCC827／GR细胞株p-EGFR、p-ERK1/2以及p-MET的表达。结论 大黄素可以逆转NSCLC EGFR-TKI耐药,可能是通过抑制c-Met的活化来实现。     

mTOR 信号通路在 17-DMAG 克服 EML4-ALK 阳性肺癌细胞株H3122对alectinib耐药中的作用机制研究

目的 观察mTOR信号通路在17-DMAG克服旁路信号通路激活诱导棘皮动物微管相关蛋白样4与间变性淋巴瘤激酶（echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase,EML4-ALK）融合基因阳性肺癌细胞株H3122（以下简称“H3122细胞”）对alectinib耐药中的变化,并探讨其内在的调控机制。方法 加入100 ng/mL转化生长因子α（transforming growth factor-α,TGF-α）和100 ng/mL表皮生长因子（epidermal growth factor ,EGF）诱导H3122细胞对alectinib耐药,观察加入17-DMAG后上述耐药能否被克服。采用CCK-8法检测不同处理方式下H3122细胞增殖,流式细胞术检测细胞凋亡,蛋白质免疫印迹（Western blot）技术检测不同处理方式下细胞中ALK、EGFR及其磷酸化蛋白的表达,观察其下游mTOR信号通路关键蛋白及活化水平的表达情况。结果 alectinib作用72 h后H3122细胞增殖率随药物浓度升高而下降,IC₅₀为0.042 μmol/L;联合TGF-α或EGF后H3122细胞对alectinib耐药,IC₅₀ 远大于10 μmol/L;单药17-DMAG处理后H3122细胞增殖率随药物浓度升高而下降,IC₅₀为 0.245 μmol/L;联合TGF-α或EGF后H3122细胞增殖率亦被17-DMAG抑制,且呈剂量依赖性,IC₅₀分别为 0.251 μmol/L和0.301 μmol/L。经0.05 μmol/L alectinib作用72 h后H3122细胞凋亡率为（30.01±0.92）%,alectinib联合TGF-α或EGF后细胞凋亡率分别为（6.36±0.14）%和（6.13±0.21）%,显著低于alectinib单药处理（P＜0.001）;经0.3 μmol/L 17-DMAG单药或联合TGF-α、EGF作用72 h后H3122细胞凋亡率分别为（28.37±1.75）%、（26.69±1.2）%和（26.62±0.72）%,差异无统计学意义（P＞0.05）。alectinib可抑制H3122细胞中p-ALK、p-mTOR的表达,也可抑制mTOR上、下游关键蛋白的活化状态;EGF可明显增加细胞中p-EGFR、p-mTOR及mTOR上、下游关键蛋白的活化水平表达;alectinib可抑制p-ALK表达,但联合EGF后不能抑制mTOR及mTOR上、下游关键蛋白活化水平的表达;即使联合EGF后,17-DMAG亦能抑制H3122细胞中ALK、EGFR、mTOR信号通路蛋白及其活化状态蛋白的表达。结论 旁路信号通路激活介导EML4-ALK融合基因阳性肺癌细胞株H3122对alectinib耐药的方式具有可行性,mTOR信号通路在 17-DMAG克服旁路信号通路激活引起alectinib的获得性耐药过程中有一定作用。     

克里唑蒂尼：晚期 EML4-ALK 阳性非小细胞肺癌患者的潜在标准治疗

EML4-ALK为棘皮动物微管相关蛋白样4(echinoderm microtubule associated protein-like4,EML4)和间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)的融合基因,自在非小细胞肺癌(non-small cell lung cancer,NSCLC)首次被发现以来受到越来越多的关注,EML4-ALK最常见于从不/轻度吸烟的肺腺癌患者,EML4-ALK阳性NSCLC代表了NSCLC患者一个独特的亚型。所有EML4-ALK变体(variant)均具有生物学功能,其表达产物为嵌合酪氨酸激酶,可持续性促进细胞增殖,导致肿瘤的发生和转移。以EML4-ALK为靶点的ALK抑制剂克里唑蒂尼(crizotinib)治疗该亚型晚期NSCLC效果较佳。未来的挑战是寻找最佳的EML4-ALK检测方法,能简单、快速、灵敏和准确地鉴定出EML4-ALK阳性晚期NSCLC患者,以促使克里唑蒂尼早日成为晚期NSCLC患者的一线标准治疗。本研究对EML4-ALK在NSCLC患者中的突变情况、EML4-ALK的检测方法及克里唑蒂尼在治疗NSCLC中的潜在价值与临床应用进展作一综述。     

MAPK/ERK通路及泛素连接酶c-Cbl调控埃克替尼抑制肺癌HCC827细胞增殖和诱导细胞凋亡的研究

目的:研究MAPK/ERK通路及泛素连接酶c-Cbl调控埃克替尼抑制HCC827细胞增殖和诱导细胞凋亡的作用机制。方法:采用MTT法检测HCC827对埃克替尼的敏感性,AnnexinV-PI流式细胞术检测细胞凋亡,Westernblot检测相关蛋白表达,SPSS18.0进行统计学分析。结果:埃克替尼处理HCC827细胞24h的IC50为155.6μmol/L。埃克替尼诱导HCC827细胞早期凋亡并具有剂量依赖性。Westernblot结果显示埃克替尼可诱导p-EGFR和p-ERK下调并引起c-Cbl下调。结论:埃克替尼能够明显抑制HCC827细胞增殖,诱导细胞早期凋亡。其机制可能与c-Cbl参与的p-EGFR和p-ERK蛋白表达水平下调,从而抑制细胞增殖通路活化有关。     

IGF-1R旁路活化在EML4-ALK阳性非小细胞肺癌Alectinib继发耐药中的作用

摘 要：［目的］ 探讨胰岛素样生长因子-1（IGF-1）是否以旁路激活的方式诱导EML4-ALK融合基因阳性肺癌细胞株H3122对Alectinib的耐药,并进一步探讨旁路信号激活在 Alectinib耐药中的作用。［方法］ 通过外源性加入人胰岛素样生长因子1（hIGF-1）刺激H3122细胞株构建Alectinib耐药细胞株H3122-IGF-CR;通过CCK8法检测H3122细胞株及H3122-IGF-CR对不同浓度Alectinib的敏感性,并计算半数抑制浓度IC50和耐药指数;PE Annexin V/7-AAD双染法检测细胞凋亡情况;qRT-PCR检测亲本细胞中IGF-1R的表达情况;蛋白质印记法检测PI3K/AKT, Ras-Raf-MEK-ERK/MAPK信号通路的变化情况。［结果］ qRT-PCR结果显示IGF-1R在H3122细胞中ct值为20.90±0.06,内参ct值为12.48±0.12,ΔCt值＜12, 提示IGF-1R在H3122细胞株中高表达。H3122细胞的活力能被Alectinib抑制,且呈剂量依赖性,其IC50值为0.0173μmol/L;当加入50ng/ml或100ng/ml的hIGF-1刺激后,其对Alectinib敏感性降低,IC50为0.358μmol/L和0.4001μmol/L,耐药倍数为20.6倍和23.0倍。0.03μmol/L Alectinib单药处理48h后H3122细胞的凋亡率为（26.43±0.23）%,而Alectinib联合50、100、150ng/ml hIGF-1刺激48h后,凋亡率分别为（18.95±0.48）%、（15.90±0.16）%、（13.70±0.36）%,显著性低于Alectinib单药组（P<0.05）。外源性hIGF-1与IGF-1R结合后,明显增加细胞中p-IGF-1R及其下游p-AKT、p-mTOR、p-P70S6K、p-ERK的蛋白表达水平（P<0.05）。此外,联合应用IGF-1R抑制剂Linsitinib (OSI-906)可以抑制因hIGF-1配体导致的H3122耐药细胞的活力。［结论］ hIGF-1可通过旁路激活的方式诱导EML4-ALK阳性非小细胞肺癌H3122细胞对Alectinib耐药,其机制可能为激活了其下游信号通路PI3K/AKT,MAPK/ERK,初步证实 IGF-1R信号通路与Alectinib继发耐药相关。     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Increased apoptosis in cancer cells in vitro and in vivo by ceramides in transferrin-modified liposomes

Lysosomes are a promising therapeutic target for induction apoptosis in cancer cells due to lysosomal membrane permeabilization (LMP) leading to leakage of hydrolytic enzymes, especially the cathepsins, into the cytoplasm. We hypothesized that with the modification of the ceramide-loaded liposomes with transferrin (Tf), we would achieve both tumor targeting and increased delivery of lysosome-destabilizing agents, such as ceramides to lysosomes, to initiate LMP-induced apoptosis. We prepared Tf-modified (TL) and plain (PL) liposomes and loaded with short (C6)- or long (C16) N-acyl chain ceramides. Uptake, intracellular localization of liposomes, stability of the lysosomal membrane and release of cathepsin D were investigated on Hela cells by fluorescence microscopy and flow cytometry. Apoptosis was evaluated by binding of fluorescently-labeled Annexin V. Antitumor and pro-apoptotic effects of C6Cer-loaded Tf-liposomes were demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. TL were internalized specifically via the TfR-dependent endocytic pathway and localized within the endosome-lysosomal compartment. Ceramide-loaded Tf-liposomes significantly increased apoptosis compared with ceramide-free and ceramide-loaded non-modified liposomes. The treatment of cancer cells with TL led to increased LMP and cytoplasmic relocation of the intralysosomal cathepsin D. A strong antitumor and pro-apoptotic effect of C6Cer-loaded TL was also demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. The lysosomal accumulation of ceramides delivered by Tf-liposomes initiates the permeabilization of the lysosomal membranes required for the release of lysosomal cathepsins into the cytoplasm and initiation of the cancer cell apoptosis both in vitro and in vivo.     

Ringworm in animals in a farm in Assiut

Bericht über das Auftreten von Hautmykosen bei Tieren auf der Farm der Landwirtschaftlichen Fakultät der Universität Assiut. Von 70 Kälbern waren 42 pilzkrank, davon 22 durch T. mentagrophytes, 20 durch T. verrucosum. Von 180 Kühen waren 8 pilzbefalien, sämtlich durch T. mentagrophytes. Von 2 kranken Bullen wurde T. verrucosum isoliert. Auch die 3 Pferde und 2 Maultiere der Farm waren pilzinfiziert; Erreger war in diesen Fällen T. equinum. Auch ein Kalb war von T. equinum befallen. Die gleiche Pilzart wurde ferner von 3 Tierpflegern isoliert, die Pilzherde am Hals und an den Armen aufwiesen.     

Socioeconomic factors in cancer in Sweden

It is well known that certain cancers have shown clustering in socioeconomic groups, but limited data are available on recent results and time trends in such clustering. We determined standardized incidence ratios (SIR) for cancer, adjusted for age, period, region, parity and age at first childbirth among men and women in 6 socioeconomic groups based on the Swedish Family-Cancer Database. Persons had to be identified with the same socioeconomic status in the census of years 1960 and 1970, or of years 1960, 1970 and 1980; the comparison group was all people according to the same censuses. Cancers were followed from years 1970 to 1998 or from 1980 to 1998. Both increased and decreased SIRs were found, and a consistent pattern emerged, although the overall SIRs for cancer did not differ much, the lowest being for farmers (0.85) and the highest for professional men (1.07) and women (1.11). At individual sites, manual workers were at risk of tobacco-, alcohol- and occupation- and human papilloma virus-related cancers and at a decreased risk at most other cancers. Manual workers and farmers showed an excess of stomach cancer; professionals had an excess of melanoma and squamous cell skin cancer. Male and female SIRs correlated highly for manual and blue-collar workers and for professionals. The overall population-attributable fraction for selected sites was 16.7% for men and 10.9% for women and it was highest, over 50%, for lung cancer in both genders.     

Survey of changes in dietary preferences in cancer patients in China

Objective The aim of this study was to investigate the changes in dietary preferences in cancer patients in China and to determine the need for encouraging the adherence to a sensible diet among such patients.Methods A total of 468 cancer patients were interviewed using a self-designed questionnaire focusing on changes in the intake of specific foods. Data were analyzed using SPSS 16.0. Results Most patients completely avoided roosters and carp(73.1%), condiments(51.9%), and meat of aquatic species(40.4%). All other types of the specific foods were completely avoided by different subpopulations of the patients.Conclusion In addition to focusing on disease treatment, medical professionals need to help cancer patients overcome barriers associated with the customs of avoiding specific foods encompassed by the term ”fawu” and provide them with dietary guidance in order to prevent negative nutritional effects.     

Advances in cancer epidemiology in Japan

Epidemiologists in Japan have been performing calculations to estimate nationwide cancer incidence rates as well as 5‐year survival rates using population‐based cancer registry data. There have been remarkable changes in cancer incidence and/or mortality in cancers of the lung, liver and stomach, which were thought to be attributed to the changing impact of exposure to cigarette smoking, chronic hepatitis C virus infection and Helicobacter pylori infection, respectively. In systematic reviews providing evidence in risk/protective factors for cancer sites using case–control and cohort studies of the Japanese population, there were associations between cancer sites (esophagus, stomach, colo‐rectum, liver, pancreas, lung and breast) and various lifestyle factors. In the past 10 years, a hospital‐based case–control study at Aichi Cancer Center provided valuable evidence of gene‐environment interaction on the development of cancer [i.e., the effects of aldehyde dehydrogenase‐2 (ALDH2) polymorphism and heavy alcohol drinking on esophageal cancer, ALDH2 polymorphism and smoking on lung cancer, methylenetetrahydrofolate reductase polymorphism and heavy alcohol drinking on pancreatic cancer]. The database with stored DNA was also used and identified seven loci containing significant but low‐penetrance polymorphisms associated with the development of breast cancer. These findings together with established risk factors are likely to be useful to predict personalized breast cancer risk in East Asian women. In 2005, the Japan Multi‐Institution Collaborative Cohort (J‐MICC) study was launched to elucidate gene‐environment interactions as well as to confirm preclinical diagnostic biomarkers of cancer. J‐MICC, which has recruited 92,000 healthy individuals by the end of 2012, will follow the individuals until 2025.     

Foreign bodies in ENT in a teaching hospital in Eastern India

Objective

To evaluate the nature, common sites, modes of presentation of various foreign bodies (FB) in Ear, Nose and Throat (ENT).

Materials and methods

Observational retrospective study carried out at Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan. The study period was between Jan 2006 to Jan 2007. The information obtained from the hospital record books.

Results

Four hundred and eighty-two patients presented in the Department of Otorhinolaryngology of Vivekananda Institute of Medical Sciences, in the study period with FB in their ENT. Out of 482 pts, the commonest location of FB was to be in throat with 302 pts (62%) followed by ear with 119 pts (25%) and nose 61 pts (13%). Amongst the FB in throat the commonest was fish bone and the commonest site being tonsils. Artificial denture accounted for a significant number of 13 (4.3%). External auditory canal was the commonest site of FB lodgment in ear found in 118 patients (99.16%). Nasal FB were found in 61 patients; more common in pediatric age group (98.36%).

Conclusion

From this study we have found that FB lodgement is a very common complaint with which patients come to otolaryngologist. The commonest site of FB lodgement is in the throat. Most of the FB could be removed in emergency room (ER) with or without Local Anesthesia.     

整合素在急性白血病中的研究进展

急性白血病是一种早期造血干/祖细咆的恶性克隆性疾病.微小残留病和耐药被认为是其复发和难治的根源.近来,越来越多的证据显示白血病细胞通过与骨髓微环境中的基质细胞或细胞外基质相互作用促进其存活,并增强其对常规化疗药物的耐药.整合素是介导细胞与细胞外基质（细胞与非细胞成分）粘连的最主要黏附分子,在细胞增殖、存活等生物学过程中发挥关键作用,但作用机制尚不完全清楚.现就目前揭示的整合素及肿瘤微环境在急性白血病发生、发展中的作用进行综述.