肿瘤旋磁治疗机的基本原理与临床初步应用

ZCX-Ⅱ型旋磁治疗机由上下两对磁头组成,下磁头由电动马达驱动,而上磁头则是在下磁头耦合力的作用下而发生同步旋转,以达到人体组织纤维与磁力线发生相对运动,从而产生磁生物学效应的目的,属国际首创。随机选择的32例临床放弃治疗的晚期恶性肿瘤患者,使用ZCX-Ⅱ型肿瘤旋磁治疗机,采用不同的治疗参数进行治疗。结果观察,症状完全缓解率达28.1%,部分缓解率达65.6%,总有效率为93.8%1,年生存率为28.1%。治疗后所有患者的临床症状和体征均可得到不同程度的改善和缓解,且无任何严重地毒副作用。文中介绍了该设备的基本原理、使用方法和临床疗效,并对其临床相关问题进行简要讨论。     

Can abundant colloid exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration? Cytohistological correlation of 127 oncocytic (Hürthle cell) lesions

Objective:  The objective of the present study was to find out whether the presence or absence of certain cytological features can exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration (FNA) to minimize unnecessary surgery. Methods:  Over a 17‐year period, 127 hypercellular, oncocyte‐exclusive, lymphocyte‐absent aspirates obtained via ultrasound‐guided FNA with on‐site assessment had histology slides for review. The presence or absence of six cytological features (microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia, transgressing blood vessels and colloid) and one histological feature (macrofollicular component) were determined for each case independently by two cytopathologists. Results:  Histology showed 12 (9.4%) cases of Hashimoto thyroiditis, 23 (18.1%) oncocytic adenomatoid nodules in nodular goitre, 66 (52.0%) oncocytic adenomas and 26 (20.5%) oncocytic carcinomas (13 minimally invasive without angioinvasion, six minimally invasive with angioinvasion, seven widely invasive). Histologically, a macrofollicular component was present in seven of 26 (26.9%) oncocytic carcinomas, including one case with abundant thin colloid. A microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia and transgressing vessels were present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. Conclusions:  A macrofollicular component is frequently present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. None of the cytological features studied, including abundant colloid, can exclude oncocytic carcinoma. Oncocytic carcinoma can only be excluded by thorough histological examination of thyroidectomy specimens. A molecular marker is needed to triage oncocytic lesions in thyroid FNA.     

[F]Fluorodeoxyglucose positron emission tomography in advanced thyroid cancer

In recent years, [¹⁸F]Fluorodéoxyglucose-PET imaging has emerged as an important oncological imaging modality. In metastatic thyroid carcinoma (M1), [¹⁸F]FDG-PET has been shown to have a high sensitivity in non iodine-avid metastases and/or dedifferentiated tumours and may therefore provide real-time prognostic information. The use of [¹⁸F]FDG-PET is more controversial in M0 patients with low residual serum Tg values but is very sensitive in aggressive histotypes such as tall cell variants of papillary thyroid carcinomas.     

Akt activation through the phosphorylation of erythropoietin receptor at tyrosine 479 is required for myeloproliferative disorder-associated JAK2 V617F mutant-induced cellular transformation

The disruption of Janus kinase 2 (JAK2) signaling regulation by its point mutation, V617F, is involved in various myeloproliferative disorders (MPDs). JAK2 V617F mutant induced constitutive activation of Akt when erythropoietin receptor (EpoR) was coexpressed; however, the physiological role of Akt activation in MPDs has not been elucidated. LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, inhibited Akt activation and induced apoptotic cell death in cells expressing JAK2 V617F mutant and EpoR. Previously, it has been shown that the phosphorylation at Y479 in EpoR is critical for the interaction with PI3K, an upstream molecule of Akt. Hence, EpoR mutant with a point mutation of Y479F, which fails to activate Akt, is useful for addressing the role of Akt activation in JAK2 V617F mutant-induced tumorigenesis. Interestingly, under the expression of EpoR Y479F mutant, JAK2 V617F mutant failed to exhibit potent anti-apoptotic activity. In addition, JAK2 V617F mutant-induced phosphorylation of CREB and GSK-3β was significantly decreased in cells expressing EpoR Y479F mutant, resulting in the downregulation of Bcl-XL and Mcl-1 expression. Furthermore, compared with when nude mice were inoculated with cells expressing JAK2 V617F mutant and EpoR, the lifespan of nude mice inoculated with cells expressing JAK2 V617F mutant and EpoR Y479F mutant was effectively prolonged. Taken together, it was clarified that PI3K-Akt activation through the phosphorylation of EpoR at Y479 is required for oncogenic signaling of JAK2 V617F mutant and that targeted disruption of this pathway has therapeutic utility.     

The driver and passenger effects of isocitrate dehydrogenase 1 and 2 mutations in oncogenesis and survival prolongation

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key events in the development of glioma, acute myeloid leukemia (AML), chondrosarcoma, intrahepatic cholangiocarcinoma (ICC), and angioimmunoblastic T-cell lymphoma. They also cause D-2-hydroxyglutaric aciduria and Ollier and Maffucci syndromes. IDH1/2 mutations are associated with prolonged survival in glioma and in ICC, but not in AML. The reason for this is unknown. In their wild-type forms, IDH1 and IDH2 convert isocitrate and NADP⁺ to α-ketoglutarate (αKG) and NADPH. Missense mutations in the active sites of these enzymes induce a neo-enzymatic reaction wherein NADPH reduces αKG to D-2-hydroxyglutarate (D-2HG). The resulting D-2HG accumulation leads to hypoxia-inducible factor 1α degradation, and changes in epigenetics and extracellular matrix homeostasis. Such mutations also imply less NADPH production capacity. Each of these effects could play a role in cancer formation. Here, we provide an overview of the literature and discuss which downstream molecular effects are likely to be the drivers of the oncogenic and survival-prolonging properties of IDH1/2 mutations. We discuss interactions between mutant IDH1/2 inhibitors and conventional therapies. Understanding of the biochemical consequences of IDH1/2 mutations in oncogenesis and survival prolongation will yield valuable information for rational therapy design: it will tell us which oncogenic processes should be blocked and which “survivalogenic” effects should be retained.     

FAK在胃癌组织中的表达及与Hp-L型感染的关系

目的探讨局部黏着斑激酶(focal adhesion kinase,FAK)在胃癌组织中的表达意义及与幽门螺杆菌L型(Helicobacter pylori-L,Hp-L)感染的关系。方法 (1)应用免疫组织化学Elivision法检测120例胃癌组织及40例切缘正常胃粘膜组织(对照组)中FAK蛋白的表达情况,采用免疫组织化学和革兰染色法检测Hp-L型的感染情况;(2)采用逆转录多聚酶链反应(RT-PCR)技术检测40例新鲜胃癌组织及对应切缘正常胃黏膜组织(对照组)中FAK的mRNA表达。结果胃癌组FAK蛋白的表达阳性率高于对照组(P0.05),且FAK的高表达与分化程度、浸润深度、淋巴结转移和TNM分期有关(P0.05),与年龄、性别、肿瘤大小无关(P0.05);RT-PCR显示,肿瘤组织、远端正常对照组织的FAK表达量差异明显(P0.01)。胃癌组Hp-L型检出率72.5%(87/120)与对照组37.5%(15/40)有显著性差异(P0.05),与免疫组化Hp-L型抗原表达率65.0%(78/120)无显著性差异(P0.05),Hp-L检出阳性率为69.2%(83/120);胃癌组中Hp-L型感染阳性组的FAK表达阳性率高于Hp-L型阴性组(P0.05),且Hp-L型阳性率和FAK蛋白的表达呈正相关(r=0.291,P0.05)。结论FAK蛋白和mRNA在胃癌中的表达增加,且与胃癌的浸润、转移相关,其机制可能与幽门螺杆菌L型(Hp-L型)感染有关。     

Prevalence and clinicopathologic characteristics of gastric cardia cancer in South Korea

Background and Aim: Western reports have suggested that the prevalence of gastric cardia cancer (GCC) has been increasing, and indicated some differences between GCC and gastric noncardia cancer (GNCC). However, few studies have been conducted in Asia. The aims of this study were to estimate the prevalence of GCC and to evaluate differences of clinicopathologic characteristics between GCC and GNCC in South Korea. Methods: This study was single‐center case–control study. A total of 829 patients with gastric cancer and 270 controls were enrolled between 2003 and 2011. Baseline characteristics, Helicobacter pylori (H. pylori) infection status, and histologic characteristics were compared among three groups (GCC, GNCC, and control). Results: Sixty cases (7.2%) of gastric cancer were located in cardia. Multivariate analysis showed that male odds ratio (OR, 5.72; 95% CI, 1.72–19.07; p = .005) and cigarette smoking (OR, 5.38; 95% CI, 1.39–20.90; p = .015) were risk factors of GCC in comparison with control group, but H. pylori infection rate was not significant. In the case of GNCC, cigarette smoking (OR, 3.87; 95% CI, 1.81–8.29; p < .001), past alcohol intake (OR, 2.82; 95% CI, 1.28–6.20; p = .010), intestinal metaplasia (OR, 3.22; 95% CI, 2.00–5.17; p < .001), and H. pylori infection (OR, 3.06; 95% CI, 1.90–4.93; p < .001) were risk factors of GNCC. Gastroesophageal reflux disease symptoms were higher in the GNCC (21.2%) than control group (13.5%) (p = .008). However, in the case of GCC, they were similar between the GCC (12.7%) and control group (p = .872). According to multivariate analysis, history of H. pylori eradication (OR, 0.34; 95% CI, 0.19–0.61; p < .001) was associated with a protective effect on GNCC. GCC showed higher depth of invasion (p = .038) and frequent distant metastasis (p = .012) than GNCC. Conclusion: In this referral center based study, the prevalence of GCC was 7.2% in South Korea. Risk factors and clinicopathologic characteristics for GCC and GNCC were different, supporting that the pathophysiology is different in the development of GCC and GNCC.     

37 例老年胃癌合并胰腺受侵围手术期的临床治疗分析

目的:探讨老年胃癌合并胰腺受侵患者围手术期合并症及并发症发生率与其他老年胃癌患者间的差异,优化老年胃癌合并胰腺受侵患者围手术期临床治疗护理策略。方法:收集2005年2月至2009年10月前来我院治疗的37名年龄>65岁的老年胃癌合并胰腺受侵患者作为研究对象,设置相同年龄胃癌无胰腺受侵患者37例作为对照,收集详细临床资料,对两组间围手术期合并症发生情况进行卡方(x2)检验,通过采取不同临床治疗护理手段进一步施行干预(包括不同的手术方式及临床监测管理模式),再次采用x2检验比较两组术后并发症发生率,最后通过随访实现Kaplan-Meier生存分析。结果:老年胃癌合并胰腺受侵组(组Ⅰ)与老年胃癌无胰腺受侵组(组Ⅱ)术前总体合并症发生率并无显著统计学差异(P>0.05);各项合并症中仅有血红蛋白降低(<100g/L)、白蛋白降低(<35g/L)以及合并糖尿病的患病人数存有统计学意义(P=0.020,P=0.032,P=0.013);根据两组患病情况不同采取不同手术方式,两组死亡人数未见统计学意义(P>0.05);组Ⅰ术后并发症发生率为70.27%,低于组Ⅱ的86.49%,但两组未见明显统计学差异(P>0.05);比较两组功能性、心血管类并发症,两者间存在显著统计学差异(P=0.036,P=0.013);两组术后5年生存率比较无统计学差异(P=0.8308)。结论:需加强对老年晚期胃癌合并胰腺患者围手术期的临床治疗护理策略,采取适宜的手术治疗方式,可减少术后并发症及死亡的发生,提高患者生活质量。     

Partial Biological Characterization of Cancer Stem-like Cell Line (WJ<Subscript>2</Subscript>) of Human Glioblastoma Multiforme

To provide suitable models for human GBM cancer stem cells in vitro and in vivo, and investigate their biological characteristics, a new human GBM cancer stem-like cell line, WJ2, was established in this experiment through serial passages from adherent monolayer culture to nonadherent tumor sphere culture in turns; Its partial biological characteristics were studied through cell proliferation and tumor sphere assay; cell cycle distribution, side population, and CD133 phenotype were analyzed with FCM. The expressions of CD133, Nestin, and GFAP of cancer stem-like cells and xenograft tumor cells were detected with RT-PCR and immunohistochemistry. Biological characterization, side population, CD133 phenotype and CD133 Nestin, BCRP-1, Wnt-1 gene expression revealed the stemness of this cancer stem-like cell line. Tumorigenicity heterotransplanted in nude mice; histopathological characteristics of xenograft tumor, and expressions of CD133, Nestin, and GFAP of xenograft tumor cells indicated that xenograft tumors recapitulated the phenotype and biological characterization of human primary GBM. All findings of this experimental study suggested that WJ₂ cancer stem-like cell line could accurately mimic human GBM cancer stem cell in vitro and in vivo; it would be useful in the cellular and molecular studies as well as in testing novel therapies of CSC-based anti-cancer therapies for human GBM.     

可复制性单纯疱疹病毒在抗肿瘤方面的应用

单纯疱疹病毒是肿瘤生物治疗中常用的病毒载体之一,可复制性单纯疱疹病毒以其溶瘤效率高、特异性好、可行性强成为近年来研究的热点。其中对溶瘤性单纯疱疹病毒突变株G207的研究开展得早,其溶瘤效果、靶向性及安全性都得到了确认,这也带动了可复制性单疱病毒应用的发展,目前已研究出多种溶瘤单纯疱疹病毒突变株。本文就近几年可复制性单纯疱疹病毒在抗肿瘤方面的研究现状加以综述,以探讨其临床治疗肿瘤的潜在价值及可行性。