FGF19在恶性肿瘤中的潜在临床价值及相关药物进展

成纤维细胞生长因子(FGF) 19是一种重要的激素样成纤维细胞生长因子,发挥调节细胞生理功能及代谢等作用。研究显示,在恶性肿瘤的发生和发展中FGF19扮演着重要角色。FGF19/成纤维细胞生长因子受体(FGFR) 4信号激活与癌症的发生和进展密切相关,是具潜力的抗肿瘤治疗靶点。靶向药物是抗肿瘤治疗的重要手段,靶向FGF19/FGFR4已成为近期的研究热点。靶向FGF19/FGFR4的策略大致分为两大类:靶向FGF19的治疗策略和靶向FGFR4的治疗策略。针对FGFR4的药物涵盖泛FGFR抑制剂、FGFR4特异性小分子抑制剂以及FGFR4特异性单克隆抗体等。FGFR4抑制剂的开发和设计等研究已取得重大进展,但仍面临诸多挑战。本文对FGF19的生理学功能、FGF19与肿瘤发生发展的关系、国内外相关研究进展以及FGF19相关药物进行详细综述,以期为基础科研及临床诊疗提供一定参考。     

FGF19/FGFR4信号通路在肝细胞癌中的研究进展

成纤维细胞生长因子19（FGF19）是成纤维细胞生长因子家族中的一员,通过与成纤维细胞生长因子受体4（FGFR4）结合,不仅参与胆汁酸、葡萄糖、脂质和能量代谢的调节,还与肝细胞癌的发生、发展和转移密切关系。研究发现,FGF19/FGFR4信号通路通过多种途径促进肝细胞癌细胞生存、增殖、侵袭与转移,阐明FGF19/FGFR4信号通路在肝细胞癌进程中的作用机制可为其靶向治疗提供依据。     

成纤维细胞生长因子受体5的研究进展

成纤维细胞生长因子受体5(fibroblast growth factor receptor 5, FGFR5)是FGFR5家族中的一个新型受体,是由胞外区、穿膜区及胞内区构成的穿膜受体。然而,与其他经典FGFRs不同,其胞内区缺乏信号转导所必须的酪氨酸激酶,这一特征决定了其生物学功能有别于其他FGFRs。FGFR5激活时可抑制细胞增殖,促进细胞黏附和融合,提示该蛋白是一个潜在的抑癌因子,其分子机制有待进一步研究阐明。研究表明,FGFR5在肿瘤及非肿瘤疾病的发生发展中扮演了独特的角色。     

FGF/FGFR信号通路在肺鳞癌靶向治疗中的研究进展

肺癌是目前世界上发病率和死亡率最高的恶性肿瘤之一。肺鳞癌是仅次于肺腺癌的非小细胞肺癌（NSCLC）最常见的组织学类型,与肺腺癌相比,肺鳞癌的靶向治疗进展明显滞后。FGF/FGFR信号通路的异常改变与很多肿瘤有关,特别是肺鳞癌。FGFR基因扩增、体错义突变、染色体异位是诱导该通路改变的常见机制,故该通路可能是靶向治疗的新方向。本文将对在NSCLC中,特别是肺鳞癌,FGFR的改变以及相关的抑制剂作一综述。     

FGFR抑制剂BGJ398对白血病细胞生物学行为及耐药的影响

背景与目的:成纤维细胞生长因子(fibroblast growth factor,FGF)家族成员能够调节细胞增殖、迁移和分化,在肿瘤性疾病的发生和转移等过程中发挥重要作用,FGF受体(FGF receptor,FGFR)抑制剂具有抗肿瘤活性.探讨FGFR抑制剂BGJ398对白血病耐药细胞株K562/ADM增殖、迁移、...     

靶向FGFR4的抗肿瘤药物研究进展

 成纤维细胞生长因子受体4（FGFR4）通过启动STAT3、MAPK和PI3K/AKT等信号级联,调节细胞的增殖、分化和转移。其基因突变、过表达或其配体分子过表达等异常信号转导在某些肿瘤的发生发展中发挥着重要的作用,表明FGFR4是此类肿瘤潜在的治疗靶标。靶向FGFR4的抗肿瘤药物或方法主要包括小分子抑制剂、单克隆抗体、配体捕获蛋白、短链RNA寡核苷酸适配体（shRNA）。本文回顾FGFR4异常的肿瘤及靶向FGFR4抗肿瘤药物的研究进展。     

非小细胞肺癌中 HGF/c-Met 信号通路与 EGFR-TKI 获得性耐药的关系

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）为首的靶向药物在晚期非小细胞肺癌患者治疗中取得巨大进展。然而,获得性耐药的出现是其不可避免的结果。肝细胞生长因子（HGF）／c-Met信号通路参与多种肿瘤细胞的形成、迁徙、血管生成等重要细胞进程。该信号通路的异常激活在EGFR-TKI 获得性耐药中发挥了重要作用。实验表明,HGF ／c-Met 信号通路抑制剂可使部分 EGFR-TKI获得性耐药患者临床获益。     

成纤维细胞生长因子受体3在乳腺癌中的研究进展

成纤维细胞生长因子受体3（FGFR3）在调节细胞的增殖、分化及血管形成中发挥重要作用。近年来,研究发现 FGFR3在乳腺癌发生发展和内分泌治疗耐药性乳腺癌中发挥一定的作用,并且与乳腺癌患者的预后密切相关。     

FGFR2基因多态性与乳腺癌相关性

成纤维细胞生长因子2型受体（FGFR2）在细胞的增殖、分化中起重要作用,其基因具有遗传多态性。近年研究表明,这种多态性与乳腺癌的发病风险以及临床病理因素具有相关性。     

Akt介导的信号通路在肿瘤淋巴管生成中的作用

肿瘤淋巴管生成不但为肿瘤的生长代谢提供营养物质,同时也是肿瘤淋巴结转移的重要条件。但是肿瘤淋巴管新生的分子机制十分复杂,需要多种生长因子、受体和信号通路的调控。Akt处于多条信号通路的重要交叉点,激活的Akt在肿瘤侵袭转移中具有十分重要的意义。血管内皮生长因子（vascular endothelial growth factor,VEGF）,成纤维细胞生长因子-2(fibroblast growth factor-2,FGF-2)、胰岛素样生长因子(insulin-like growth factor,IGF)、肝细胞生长因子（hepatocyte growth factor,HGF）等分子对淋巴管生成的促进作用都是直接或间接地通过Akt信号通路介导来实现的。     

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.     

Statistical challenges in preprocessing in microarray experiments in cancer

Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data are preprocessed. This article provides an overview of preprocessing methods, including summary algorithms and quality control metrics for microarrays. Some of the ramifications and effects that preprocessing methods have on the statistical results are illustrated. The discussions are centered around a microarray experiment based on lung cancer tumor samples with survival as the clinical outcome of interest. The procedures that are presented focus on the array platform used in this study. However, many of these issues are more general and are applicable to other instruments for genome-wide investigation. The discussions here will provide insight into the statistical challenges in preprocessing microarrays used in clinical studies of cancer. These challenges should not be viewed as inconsequential nuisances but rather as important issues that need to be addressed so that informed conclusions can be drawn.     

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.     

Hemoglobin in lymphogranulomatosis in children

The peculiarities of hemoglobin content and properties in lymphogranulomatosis were studied in children by different methods. In most patients the content of fetal hemoglobin and methhemoglobin was found to increase and the rate of ferricyanide oxidation of hemoglobin also increases. Simultaneously, the rate of non-homogenicity of basic hemoglobin fractions was observed to increase on account of immunologically different components.     

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.     

Sex hormones in women in rural China and in Britain

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.     

Temozolomide treatment in glioma--experiences in two university hospitals in Finland

Thirty-two patients with relapsing glioma were treated with temozolomide in two university hospitals in Finland. One patient (3%) had complete response and 9 (28%) partial response, with 8 patients (25%) showing stable disease. Median progression-free survival for these 18 patients (56%) was 7 months (range 2-11+). The remaining either had progressive disease (25%) or only clinical evaluation (19%). Karnofsky score improved in 34% of patients and decreased in 3%. Symptoms were alleviated in 44% and deteriorated in 9%. Grade 3-4 toxicity was detected in 9% of the patients. Only 4% of the days in treatment were spent in hospital. An average 1.8 neuroradiological investigations, 6.9 laboratory visits, and 5.3 visits to the oncologist were made. This study confirms that temozolomide has positive effects on the outcome of often heavily pretreated glioma patients. High drug costs are compensated by prolonged home care and even the possibility to maintain working capacity.