Anti-HSP90 antibody promotes the anticancer effect of cisplatin by inhibiting human gastric cancer stem cells through internalizing eHSP90 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探索抗HSP90单克隆抗体28C10通过靶向肿瘤干细胞促进顺铂（cisplatin，DDP）对人胃癌细胞PAMC82恶性生物学行为的抑制效果及其可能的作用机制。方法: 28C10单独或与DDP联合处理人胃癌细胞PAMC82，采用不同实验方法检测该细胞的无血清成球能力、迁移和侵袭能力与克隆形成能力，CCK-8法检测28C10对PAMC82细胞恶性生物学行为和协同DDP抗癌能力的影响。采用细胞免疫荧光及流式细胞术检测PAMC82细胞中HSP90及eHSP90（extracellular HSP90）的表达、定位、eHSP90+亚群比例，以及28C10处理后对ALDH+、CD44+、eHSP90+细胞亚群的影响。采用WB实验检测28C10作用后PAMC82细胞中HSP90、干性相关蛋白以及PI3K/AKT/mTOR信号通路蛋白表达的变化。结果：胃癌细胞PAMC82膜表面表达eHSP90，具有2%~3%的eHSP90+细胞亚群，且eHSP90+细胞多为与ALDH+或CD44+共阳性细胞。28C10处理能显著抑制PAMC82细胞的成球、克隆形成、增殖、耐药、迁移及侵袭能力，而且和DDP联用的效果更明显（P<0.05或P<0.01）。流式细胞术分析发现28C10处理显著抑制PAMC82细胞的eHSP90+、ALDH+和CD44+亚群数量（均P<0.01）。免疫荧光实验发现28C10作用后eHSP90发生内吞，WB实验结果显示eHSP90、CD44、ALDH和干性相关蛋白OCT4、SOX2表达量均降低（P<0.05或P<0.01）。结论：抗HSP90单克隆抗体28C10可靶向胃癌PAMC82细胞的ALDH+、CD44+肿瘤干细胞相关亚群、内化eHSP90且降低细胞总HSP90的水平、抑制PI3K/AKT/mTOR信号通路，从而有效地抑制PAMC82细胞的干性、耐药和其他恶性生物学行为，协同DDP显著提高抗癌效果。

Anti-ENO1 antibody combined with metformin reverses the resistance of human non-small cell lung cancer A549 cells to cetuximab by targeting cancer stem cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the effect of anti-ENO1 (enolase 1) antibody and metformin (MET) treatment on the proliferation, migration, invasion and stemness of cetuximab (CTX) -resistant non-small cell lung cancer (NSCLC) cells through targeting cancer stem cells and the possible mechanism. Methods: 10 mmol/L MET combined with 40 μg/ml anti-ENO1 antibody was used to treat CTX(35 µg/ml)-resistant NSCLC A549 cells for 4 d, and the effects of combined treatment on A549 cells were detected with proliferation experiment, colony formation assay, migration and invasion experiments and methylcellulose ball formation experiment. In the meanwhile, FCM was used to detect the effects of CTX, MET and anti-ENO1 antibody single-drug treatment as well as the three-drug combination treatment on ALDH+ and CD44+ lung cancer stem cell subsets. Results: CTX combined with MET and anti-ENO1 antibody treatment significantly inhibited the proliferation, migration, invasion and self-renewal capacity of A549 cells. FCM analysis found that MET could significantly inhibit ALDH+ stem cell subpopulations, while anti-ENO1 antibody could significantly inhibit CD44+ stem cell subpopulations, and the three-drug combination treatment could simultaneously suppress ALDH+ and CD44+ stem cell subpopulations. Conclusion: MET and anti-ENO1 antibody respectively target ALDH+ and CD44+ cancer stem cell subsets, and the combined treatment of MET and anti-ENO1 antibody can effectively reverse the resistance of A549 cells to CTX, and thereby more effectively inhibiting stemness, proliferation, metastasis of A549 cells and tumor recurrence.

Factores de riesgo asociados a oclusiones venosas retinianas / Risk factors associated to retinal vein occlusion

RESUMEN Objetivos: Identificar los factores epidemiológicos, sistémicos y oculares de las oclusiones venosas retinianas. Métodos: Se realizó un estudio observacional descriptivo, transversal y prospectivo de los casos nuevos de oclusiones venosas retinianas que acudieron al Cuerpo de Guardia del Instituto Cubano de Oftalmología "Ramón Pando Ferrer", durante el período de marzo del año 2017 a marzo de 2018. Se estudiaron las variables epidemiológicas, los antecedentes patológicos sistémicos y los oculares. Los resultados se expresaron en frecuencias absolutas y relativas (variables cualitativas) y se calculó la media y la desviación estándar en las cuantitativas. Resultados: En el período se estudiaron 50 ojos de 50 pacientes diagnosticados con oclusión venosa retiniana. La edad promedio fue de 66 años (9,5 desviación estándar). Prevaleció la raza blanca (44 por ciento), sin predilección por sexo. Fueron más frecuentes la oclusión de la vena central de la retina (60 por ciento) y las formas no isquémicas de daño vascular (78 por ciento), así como la hipertensión arterial (78 por ciento), la obesidad (36 por ciento) y la diabetes mellitus (34 por ciento) como factores de riesgo sistémicos asociados, y el glaucoma crónico (24 por ciento) como factor ocular. Conclusiones: Las oclusiones venosas retinianas se presentan en edades avanzadas y asociadas a factores de riesgo sistémicos y oculares(AU)

ABSTRACT Objectives: Identify the epidemiological, systemic and ocular factors associated to retinal vein occlusion. Methods: A descriptive cross-sectional observational prospective study was conducted of the new cases of retinal vein occlusion presenting at the Emergency Service of Ramón Pando Ferrer Cuban Institute of Ophthalmology from March 2017 to March 2018. Analysis was performed of epidemiological variables and systemic and ocular pathological antecedents. Results were expressed as absolute and relative frequencies (qualitative variables), whereas quantitative variables underwent mean and standard deviation estimation. Results: Fifty eyes of 50 patients diagnosed with retinal vein occlusion were studied in the period. Mean age was 66 years (9.5 standard deviation). White skin color prevailed (44 percent) with no sex predominance. The most common disorders were central vein retinal occlusion (60 percent) and non-ischemic forms of vascular damage (78 percent), as well as arterial hypertension (78 percent), obesity (36 percent) and diabetes mellitus (34 percent) as associated systemic risk factors, and chronic glaucoma (24 percent) as an ocular factor. Conclusions: Retinal vein occlusion presents at advanced ages and is associated to systemic and ocular risk factors(AU)

Clinical features and ACADVL gene mutation spectrum analysis of 11 Chinese patients with very long chain acyl-CoA dehydrogenase deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of very long chain acyl-CoA dehydrogenase deficiency ( VLCADD ) and the correlations between its genotype and phenotype.</p><p><b>METHOD</b>Eleven patients diagnosed as VLCADD of Shanghai Jiaotong University School of Medicine seen from September 2006 to May 2014 were included. There were 9 boys and 2 girls, whose age was 2 d-17 years. Analysis was performed on clinical features, routine laboratory examination, and tandem mass spectrometry (MS-MS) , gas chromatography mass spectrometry (GC-MS) and genetic analysis were conducted.</p><p><b>RESULT</b>All cases had elevated levels of blood tetradecanoylcarnitine (C14:1) recognized as the characteristic biomarker for VLCADD. The eleven patients were classified into three groups: six cases in neonatal onset group, three in infancy onset group form patients and two in late onset group. Neonatal onset patients were characterized by hypoactivity, hypoglycemia shortly after birth. Infancy onset patients presented hepatomegaly and hypoglycemia in infancy. The two adolescent patients showed initial manifestations of exercise intolerance or rhabdomyolysis. Six of the eleven patients died at the age of 2-8 months, including four neonatal onset and two infant onset patients, with one or two null mutations. The other two neonatal onset patients were diagnosed since early birth through neonatal screening and their clinical manifestation are almost normal after treatments. Among 11 patients, seventeen different mutations in the ACADVL gene were identified, with a total mutation detection rate of 95.45% (21/22 alleles), including eleven reported mutations ( p. S22X, p. G43D, p. R511Q, p. W427X, p. A213T, p. C215R, p. G222R, p. R450H, p. R456H, c. 296-297delCA, c. 1605 + 1G > T) and six novel mutations (p. S72F, p. Q100X, p. M437T, p. D466Y, c. 1315delG insAC, IVS7 + 4 A > G). The p. R450H was the most frequent mutation identified in three alleles (13.63%, 3/22 alleles), followed by p. S22X and p. D466Y mutations which were detected in two alleles (9.09%, 2/22 alleles).</p><p><b>CONCLUSION</b>The ACADVL gene mutations were heterozygous in our patients. The mortality of neonatal onset form and infant onset form is much higher than the late onset form patients, suggesting a certain correlation between the genotype and phenotype was found. The earlier diagnosis and treatment of VLCADD are of vital importance for the improvement of the prognosis of the patients.</p>