自噬在肿瘤细胞死亡中的研究进展

自噬是细胞将自身的胞质蛋白和细胞器以形成自噬体的形式由溶酶体降解的过程,其既是细胞保守的自我防御机制,又是一种程序性细胞死T亡机制。诸多研究表明,自噬不仪参与机体多项生理功能的发挥,而且其功能的失调还与神经变性性疾病、自身免疫性疾病、肿瘤等多种疾病相关,但具体机制尚不明确,仍需进一步深入研究探讨。由此,本文综述了自噬的细胞学调控,以及其对细胞程序性死亡的影响和自噬诱导的细胞死亡在肿瘤发生发展中的作用机制,旨在为细胞自噬在肿瘤发生发展中的作用研究以及肿瘤治疗靶点的开发提供思路与线索。     

细胞自噬与肿瘤治疗

近年来,自噬与肿瘤的关系是一个重要的研究热点。有研究表明,自噬在肿瘤发生和转移的过程中起着双刃剑的作用,即自噬对肿瘤细胞具有抑制和促进的双重作用:在有些癌症中,可以通过诱导细胞自噬来促进肿瘤细胞的凋亡达到治疗肿瘤的作用;在有些癌症中,可以通过抑制细胞自噬达到治疗肿瘤的目的;自噬性细胞死亡也可能抑制血管生成,而肿瘤的生长和侵袭转移与新生血管形成密切相关;自噬也可以增强以细胞信号转导为靶点的抗肿瘤药物作用。本文即从以上4点出发,概述细胞自噬与肿瘤治疗的关系,也为肿瘤的治疗和预防提供新的思路。     

自噬研究新进展

自噬是广泛存在于真核细胞内的一种溶酶体依赖性降解途径,是细胞进行自我保护的一种重要机制,在维持细胞存活、更新、物质再利用和内环境稳定中起着重要作用.近年来,针对自噬的研究日益深入,本文对新提出来的受损自噬(frustrated au-tophagy)概念及意义、自噬与凋亡间分子联系的新发现,以及雷帕霉素靶蛋白(mamalian target of mpamycin,mTOR)自噬调节的新动态概述如下.     

细胞自噬与血脑屏障的关系研究进展

自噬对细胞具有一定的保护作用,但过度自噬则会导致细胞程序性死亡,称为Ⅱ型程序性细胞死亡。血脑屏障(BBB)在大脑与外周循环之间起保护作用,有助于分子和离子的流入和流出,以维持中枢神经系统的稳态。大量研究表明,细胞自噬在BBB功能中发挥着重要作用,一方面可对BBB的完整性起到损伤或保护作用,另一方面可影响药物、病原体等物质穿越BBB。因此,通过靶向自噬机制中的特定调节分子来调节自噬水平可能影响BBB的功能,进而影响中枢神经系统疾病的发生和发展。本文对细胞自噬与BBB之间关系的研究进展进行综述,以期为预防和治疗BBB损伤相关的疾病提供新思路。     

自噬对肿瘤放射治疗疗效的影响

自噬是一种重要的分解代谢过程,细胞消化和再循环自身的细胞质内容物以维持细胞稳态。自噬可以通过各种信号通路在肿瘤的发生发展中起到促进和抑制的双重作用。作为研究热点,自噬正被学者们从各个方面进行探索。然而,目前缺乏关于自噬与放疗关系的系统性总结。因此,笔者将从自噬对不同类型肿瘤放射敏感性和对放疗疗效的影响及自噬修饰用于改善肿瘤放疗疗效和预后的未来发展作一综述。     

α粒子辐射对ROS介导src激酶活性和自噬的影响

目的 通过检测人胚肾上皮细胞HEK293受不同剂量α粒子照射后,src激酶活性和细胞自噬系统的变化,探讨调控细胞自噬对高剂量辐射诱导细胞死亡的影响.方法 将人胚肾上皮细胞HEK293分为3组:0 cGy(对照)组、241Am α粒子照射低剂量(10 cGy)组和高剂量(300 cGy)组.应用免疫印迹实验检测细胞内源性蛋白LC3Ⅰ/Ⅱ和src激酶的变化;分子探针检测细胞内活性氧(ROS)水平;用ROS淬灭剂DMSO预处理照射细胞,并用免疫印迹法检测照射后src激酶的变化;使用自噬诱导剂雷帕霉素预处理照射细胞,以PI染色流式细胞术测定细胞死亡率.结果 与0 cGy相比,10 cGy α射线照射后LC3 Ⅰ/Ⅱ比例降低(=4.07,P＜0.05),胞质内具有绿色荧光点状GFP-LC3的细胞比例升高(t=12.29,P＜0.05),自噬被诱导;而300 cGy照射后,LC3Ⅰ/Ⅱ比例升高(t=2.93,P＜0.05),胞质内GFP-LC3形态无明显变化,自噬被抑制.与0 cGy相比,10和300 cGy照射后4h均能提升细胞内ROS水平(t=17.93、22.88,P＜0.05),且300 cGy比10 cGy照射诱发的ROS更多(t=15.76、22.66、14.22,P＜0.05).与0 cGy相比,10 cGy照射使src激酶419位酪氨酸磷酸化水平升高(t=5.66,P＜0.05),而300 cGy照射则降低其磷酸化水平(=4.67,P＜0.05).DMSO能够部分逆转高低剂量照射对src激酶活性的影响.辐照前以自噬诱导剂雷帕霉素处理细胞则能降低300 cGy照射诱发的细胞死亡率(t=12.14,P＜0.05).结论 高低剂量α粒子分别抑制和激活src激酶以及细胞自噬,ROS参与介导辐照对src激酶活性及自噬系统的影响.对自噬系统的干预能够降低细胞的辐射敏感性.     

光动力治疗与细胞自噬的研究进展

细胞自噬是真核生物中一种发现不久的普遍存在的生理现象,是涉及细胞自我消化的一系列生化过程。光动力治疗（photodynamic therapy,PDT）中,选择性聚集在快速增殖细胞（如肿瘤细胞）中的光敏剂分子经一定波长激光照射,产生有细胞毒作用的单态氧或氧自由基,靶向性地杀伤肿瘤细胞,引起肿瘤细胞死亡。PDT作用过程能够诱发一些细胞器如内质网、线粒体、细胞膜和溶酶体的损害,进而引起细胞凋亡和自噬的发生。对于一些接受低水平剂量的光动力作用细胞,其发生的自噬被认为与提高细胞在应激环境下的生存有着密切联系。然而,当凋亡受到抑制或是自噬水平无限制的持续上调时,自噬就成为了细胞死亡的一种途径。目前很多相关的实验技术已运用来检测细胞自噬的特征,本文就针对光动力治疗后引起自噬的一些相关问题做一详细综述。     

细胞自噬在病原体感染过程中的作用研究进展

细胞自噬是一种通过降解蛋白质和细胞器维持细胞内平衡的细胞机制。细胞自噬具有很多重要的生理功能,包括清除病原体的感染。但是由于细胞自噬在进化过程中具有高度的保守性,某些病原体通过进化,具有逃避细胞自噬的能力,甚至利用细胞自噬为病原体复制和发育提供有利条件。本文综述了细胞自噬与病原体相互作用的研究进展。     

自噬在非小细胞肺癌治疗中的研究进展

非小细胞肺癌（non-small-cell lung cancer,NSCLC）占所有肺癌的85%,是全球癌症相关死亡的主要原因,目前的治疗方法主要包括手术治疗、放疗、化疗、生物治疗等。然而化疗的缓解率不高且不良反应明显,靶向治疗只对特定人群有效,且容易出现耐药问题,因此,需要开发新的、更有效的NSCLC治疗方法。细胞自噬在NSCLC的病理生理过程中起着重要作用,作者通过分析自噬在肿瘤中发挥的双刃剑作用,对自噬相关基因进行研究,综述自噬在铂类耐药、表皮生长因子受体酪氨酸激酶抑制剂耐药及与免疫检查点抑制剂的联合应用中起到的重要作用,分析自噬在NSCLC治疗的应用前景,为NSCLC的新疗法的发展提供一些参考。     

γ射线照射诱导大鼠肝细胞线粒体自噬与再生的研究

目的 探讨线粒体自噬在细胞损伤后再生中的作用。方法 在体外利用γ射线照射诱导大鼠肝细胞损伤，在亚细胞水平上观察肝细胞的损伤修复情况与线粒体自噬的关系，并利用分子生物学技术进行DNA凋亡片段的分析和线粒体RNA的RT-PCR分析。结果 受损线粒体清除过程存在线粒体自噬，随着修复过程的进行细胞DNA凋亡程度下降，细胞自噬现象减少，细胞凋亡和线粒体自噬同时存在于损伤细胞中，通过RT-PCR分析发现肝组织的损伤修复与线粒体自噬后的线粒体再生有关。结论 线粒体自噬可能为组织的损伤修复提供某种分子信号，促使新的线粒体再生。     

Physiologic and pathologic calcifications and ossifications in the face and neck

The aim was to give a systematic presentation of physiologic and pathologic calcifications and ossifications in the face and neck with a special emphasis on clinical relevance. In a sometimes subacute setting one should recognize specific calcifications which often lead to important diagnoses such as fungal sinusitis or sclerosing labyrinthitis. In a more chronic situation intraocular calcifications in small children are pathognomonic for retinoblastoma. Juxtatumoral sclerosis of the laryngeal cartilage in laryngopharyngeal carcinoma is usually caused by tumor infiltration of the cartilage resulting in a higher tumor stage and, this way, has a major impact on the therapeutical strategy. Calcified lymph nodes are mainly unspecific but can be the result of tuberculosis or metastases of thyroid cancer. Cross-sectional imaging methods, most of all computed tomography, are ideally suited to reveal head and neck calcifications and ossifications, especially those which are clinically relevant.     

Head and neck infection and inflammation

This article discusses the imaging manifestations of infectious and inflammatory conditions of the head and neck. Special attention is paid to the sites, routes of spread, and complications of neck infections. Because the clinical signs and symptoms and the complications of these conditions are often determined by the precise anatomic site involved, anatomic considerations are stressed. Familiarity with the fascial layers, spaces of the neck, and the contents of each space is helpful for this discussion. The fascial layers of the neck are important barriers to infection, and once infection is established, the fascial layers play a part in directing its spread.     

Staging and surgical management of pancreatic and biliary cancer and inflammation

Management of benign and malignant diseases of the pancreas, liver, and biliary tract has made remarkable progress in the last two decades. Advances in minimally invasive surgery, interventional radiology, and diagnostic and therapeutic endoscopy have changed the treatment of common diseases such as cholelithiasis and more serious diseases such as pancreatic adenocarcinoma. Advances in biliary tract and pancreatic surgery have paralleled the advances in ultrasonographic imaging, CT, and MR imaging. This article outlines the surgeon's perspective on radiologic imaging and preoperative staging of benign and malignant biliary and pancreatic disease.     

The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings

Thyroid imaging approach is based on the preliminary clinical evaluation. Lesions that are smaller than 2 cm should be assessed with US, which is capable of discriminating masses as small as 2 mm and distinguishing solid from cystic nodules. US-guided FNAB provides tissue for cytologic examination of thyroid nodules. CT and MR imaging are indicated for larger tumors (greater than 3 cm diameter) that extend outside the gland to adjoining structures, including the mediastinum, and retropharyngeal region. Metastatic lymph nodes in the neck and invasion of the aerodigestive tract are also in the realm of CT and MR imaging. Thyroid nodules are categorized on scintigraphy as hot or cold nodules. Hot nodules are rarely malignant, whereas cold nodules have an incidence of 10% to 20% of malignancy. Calcifications (amorphous, globular, nodular, and linear) occur in adenomas and carcinomas and have no differential diagnostic features except for psammomatous calcifications, which are a pathognomonic finding in papillary carcinomas and a small percentage of medullary carcinomas. Papillary carcinoma is the most common malignant tumor (80%) followed by follicular (20% to 25%); medullary (5%); undifferentiated; anaplastic carcinomas (< 5%); lymphoma (5%); and metastases. Lymph node metastases are common in papillary carcinoma, 50% at presentation, and less common in follicular carcinomas. The metastatic nodes in papillary carcinoma may enhance markedly (hypervascular); show increased signal intensity on T1-weighted images (increased thyroglobulin content or hemorrhage); and reveal punctate calcifications. Localized invasion of the larynx, trachea, and esophagus occurs predominantly in papillary and follicular carcinomas; the incidence is less than 5%. Ectopic thyroid tissue may be encountered in the tongue (foramen cecum); along the midline between posterior tongue and isthmus of thyroid gland; lateral neck; mediastinum; and oral cavity. Goiter and malignant tumors, notably papillary carcinoma, may develop in ectopic thyroid tissue. Carcinomas may also arise in thyroglossal duct cysts, which develop from duct remnants between the foramen cecum and thyroid isthmus. Infectious disease of the thyroid gland is not common and the CT and MR imaging findings are similar as described under neck infection. Other types of inflammatory disorders including Hashimoto's thyroiditis, granulomatous thyroiditis, and Riedel's struma display no specific imaging features. Imaging studies may, however, be indicated to confirm a suspected clinical diagnosis and assess compromise of the airway (Riedel's struma). HPT is a clinical diagnosis in which hypercalcemia is the most important finding. Parathyroid hyperplasia, adenoma, and carcinoma represent underlying lesions. To relieve the patient's symptoms surgical extirpation is indicated. The surgical success rate without imaging is 95%. The indications for imaging studies vary but it is generally agreed that reoperation after a previous failed surgical attempt and suspicion of an ectopic parathyroid adenoma should be investigated by imaging. These consist of US, nuclear medicine studies, CT and MR imaging. US and technetium sestamibi scanning have the highest accuracy rate for localizing an adenomatous gland at and near the thyroid gland. Ectopic adenomas, particularly if they are located in the mediastinum, are preferrably investigated with CT and MR imaging with gadolinium and fat suppression. Carcinomas and parathyroid cysts are optimally evaluated by CT and MR imaging. On MR imaging adenomas are low in signal intensity on T1-weighted images, high in signal intensity on T2-weighted images, and enhance post introduction of gadolinium.     

幽门螺杆菌分泌与重组表达的VacA蛋白的分离纯化及其致细胞空泡效应与凋亡的对比研究

目的：分离纯化幽门螺杆菌分泌和重组表达的细胞空泡毒素抗原（ VacA）蛋白,并评价其致细胞空泡效应及致细胞凋亡效应。方法分别从幽门螺杆菌ATCC26695菌株培养上清和重组表达VacA蛋白的pQE30-VacA-E．coliM15基因工程菌中分离纯化VacA蛋白,经酸化后,以不同终浓度（5,10 ng／ml）分别与人胃腺癌AGS细胞共孵24 h,观察致空泡效应,并通过流式细胞术检测细胞凋亡。结果成功分离纯化出幽门螺杆菌分泌和重组表达的VacA蛋白;幽门螺杆菌分泌的VacA蛋白能显著引起AGS细胞的空泡样改变及凋亡（P＜0．01）,而重组表达的VacA蛋白致细胞空泡样改变及凋亡不显著（ P＞0．05）。结论幽门螺杆菌分泌的VacA蛋白有良好的空泡毒性及致凋亡效应,而重组表达的VacA蛋白无致空泡及凋亡效应,幽门螺杆菌分泌的VacA蛋白可用于VacA作用机制的研究。