非小细胞肺癌EGFR-TKIs治疗及PET分子成像的研究进展

表皮生长因子受体(epithelial growth factor receptor,EGFR)信号转导通路在非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)中发挥重要作用,尤其胞内酪氨酸激酶结构域的突变状态决定了目前NSCLC的靶向治疗。针对EGFR突变的分子靶向药物表皮生长因子受体酪氨酸激酶抑制剂(epithelial growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)已开发并应用于NSCLC的治疗。在治疗过程中,EGFR的突变状态随时间发生动态变化,因此精准掌握EGFR的突变状态是靶向治疗方案制定、优化的关键。PET分子成像可在细胞和分子水平,对在体生物活动的发生、发展过程进行实时成像,使实时、在体揭示EGFR的突变状态成为可能。因此,多种以TKIs为前体标记放射性核素作为靶向肿瘤突变EGFR胞内段分子成像探针的研究逐渐增多。本文就EGFR-TKIs在NSCLC治疗及相关PET分子成像方面的研究进展进行综述。     

抗-VEGF和抗-EGFR药物在进展期非小细胞肺癌治疗中的应用

化疗对非小细胞肺癌的疗效已到达平台期,研发更为有效、易耐受的治疗策略势在必行.肿瘤生物学分子机制研究孕育了分子靶向治疗.VEGF、EGFR相关信号通路在肿瘤发生、发展中发挥重要作用,是抗肿瘤药物的重要分子靶点.贝伐单抗联合化疗和小分子酪氨酸激酶抑制剂(埃罗替尼和吉非替尼)分别成为非小细胞肺癌的一、二线治疗方案.本文将综述多种抗-VEGF和抗-EGFR新药在进展期非小细胞肺癌治疗中的临床应用.     

肺癌EGFR突变与酪氨酸激酶抑制剂临床敏感性的关系

表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI)是近年来在临床中使用的一类新的小分子靶向药物,主要用于晚期非小细胞肺癌(NSCLC)的治疗,然而并非所有的NSCLC患者对TKI敏感。近期研究发现,在NSCLC治疗过程中,EGFR突变与TKI临床敏感性密切相关,通过检测肺癌EGFR突变状况可以预测TKI治疗的效果。     

EGFR突变种类与临床疗效关联

癌组织中表皮生长因子受体（epidermal growth factor receptor,EGFR）基因突变是应用靶向药物EGFR酪氨酸激酶抑制剂（tyrosine kinase inhibitor,TKI）治疗的一个重要相关因素及预测指标。对其突变的检测可以指导TKI类药物（TKIs）的最佳应用。该种突变常出现在非小细胞肺癌（NSCLC）中,尤其是在亚洲女性、肺腺癌、非吸烟者中,与非小细胞肺癌患者对TKIs治疗的敏感性密切相关。本文旨在探讨利用EGFR基因的已知突变热点的相关知识选择适合不同分子遗传学背景的群体或/和个体的＂个体化＂治疗方案,最终达到延长肺癌患者生存时间和提高生活质量的双重目的。     

EGFR 突变种类与临床疗效关联

癌组织中表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变是应用靶向药物EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗的一个重要相关因素及预测指标。对其突变的检测可以指导TKI类药物(TKIs)的最佳应用。该种突变常出现在非小细胞肺癌(NSCLC)中,尤其是在亚洲女性、肺腺癌、非吸烟者中,与非小细胞肺癌患者对TKIs治疗的敏感性密切相关。本文旨在探讨利用EGFR基因的已知突变热点的相关知识选择适合不同分子遗传学背景的群体或/和个体的"个体化"治疗方案,最终达到延长肺癌患者生存时间和提高生活质量的双重目的。     

肺癌分子靶向药物研究进展

本文就表皮生长因子受体(EGFR)酪氨酸激酶抑制剂、EGFR单克隆抗体、肿瘤血管生成因子(VEGF)受体抑制荆、内皮抑素以及一些多靶点药物等靶向药物在肺癌中的临床研究和应用进行综述。     

自噬与非小细胞肺癌EGFR-TKI耐药的研究进展

肺癌是目前世界上发病率和死亡率均居首位的恶性肿瘤,其中大多数是非小细胞肺癌(non-small cell lung cancer,NSCLC)。在对NSCLC的治疗中,酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)的应用已成为靶向表皮生长因子受体(epidermal growth factor receptor,EGFR)的重要治疗手段。但由于获得性耐药问题的出现,使得这类靶向药物的作用受到限制。近年来大量研究表明,除了基因突变等分子水平的因素外,细胞自噬(autophagy)在非小细胞肺癌EGFR-TKI靶向药物耐药中也发挥了重要的作用。该文重点就自噬与非小细胞肺癌EGFR-TKI靶向药物耐药的研究进展进行分析,旨在为解决自噬相关的EGFR-TKI耐药提供更多思路。     

EGFR家族受体的分子结构与药物作用机制

表皮生长因子受体(EGFR)及其同源蛋白HER2,HER3,HER4是调控细胞生长与分化的重要酪氨酸激酶受体.这些受体的突变或过表达将会引起激酶活性的失调,并导致包括肺癌与乳腺癌在内的各种癌症.因此,这些受体是治疗癌症的重要药物靶点.虽然目前对于EGFR激酶突变所引起的激酶活性失调及其致癌机制已有较深入的研究,但对于由EGFR或HER2过表达所引发的跨膜信号变化,相应的分子结构,以及由此导致的癌症发生与耐药性产生的分子机制则均不甚明了,在临床上也缺乏有效的靶向性药物或治疗窗口.本文将对EGFR家族受体的分子结构、跨膜信号传导机制,以及EGFR靶向药物的研究进行回顾和展望.     

EML4-ALK 融合基因在非小细胞肺癌中的研究进展

肺癌是发病率和死亡率最高的恶性肿瘤,分子靶向治疗以其特异性高、副反应轻的特点正日益受到关注。近年来临床研究发现EML4-ALK融合基因是除EGFR突变及KRAS突变之外的另-个重要的酪氨酸激酶抑制剂的作用靶点,该融合基因在年轻、不吸烟或少吸烟、腺癌、无EGFR和KRAS突变的非小细胞肺癌患者中发生率较高,且该融合基因阳性者对酪氨酸激酶抑制剂耐药,对于ALK抑制剂(如克唑替尼)则有良好的治疗反应,关于该药的临床试验表明:总有效率达57%(46例确定为部分缓解,1例确定为完全缓解),估计6个月无进展生存概率为72%,常见的副反应是1、2级胃肠道反应。该基因及该药的发现为非小细胞肺癌患者带来了希望。     

EGFR靶向的PET/SPECT分子成像研究进展

恶性肿瘤的发病率及死亡率逐年递增,分子靶向治疗为癌症治疗带来了新的革命,表皮生长因子受体(EGFR)在癌症发生、发展中发挥重要作用,针对EGFR的分子靶向治疗已成为近年研究热点。目前,已有多种EGFR分子靶向药物应用于临床,但总体有效率偏低。研究表明EGFR过表达和/或突变对治疗效果影响显著,因此治疗前准确评价肿瘤EGFR表达水平及突变状态显得尤为重要。分子成像能够实现活体细胞及分子水平生物学过程成像,并进行定性定量研究,使在体揭示EGFR表达状态成为可能。本文简述EGFR靶向分子成像的研究进展并对不同分子探针成像结果进行比较分析,对不同分子成像探针的功能进行评价,以期有益于EGFR靶向分子成像探针的研发及EGFR靶向分子成像研究。     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细