EGFR突变NSCLC二线TKIs治疗优化选择

恶性肿瘤的治疗已经进入驱动基因指导下的个体治疗时代,肺癌患者应该进行多基因检测,特别是表皮生长因子受体（EGFR）基因突变。EGFR基因突变的非小细胞肺癌（NSCLC）患者,如果一线接受了化疗,二线应该选择表皮生长因子受体一酪氨酸酶抑制剂（EGFR—TKIs）。EGFR基因突变的NSCLC患者一线EGFR—TKIs治疗失败后,二线治疗应该是个体化合理选择,包括局部放疗、化疗和继续EGFR—TKIs。目前一代和二代EGFR—TKIs药物之间未见到显著疗效差别。第三代EGFR—TKIs是目前的EGFR—TKIs耐药后的最有希望的选择,特别是针对T790M突变耐药。     

PRL-3在宫颈鳞癌组织中的表达及临床意义

通过RT-PCR和Western blotting来检测45例宫颈鳞癌组织和20例正常宫颈组织中PRL-3的表达情况。RT-PCR和Western blotting结果均显示宫颈鳞癌组织中PRL-3的表达明显高于正常宫颈组织(P0.01),PRL-3的表达与宫颈鳞癌组织的分化程度及淋巴转移密切相关(P0.05),而与患者年龄、肿瘤直径无关(P0.05)。因此PRL-3可能参与了人类宫颈鳞癌的发生、发展,并与宫颈鳞癌的部分临床病理特征有关,将可能作为宫颈鳞癌靶向治疗的一个新的分子靶点。     

Meta-Analysis of Neuropsychological Symptoms of Adolescents and Adults with PKU

Phenylketonuria (PKU; OMIM 261600) is an autosomal recessive inborn error of phenylanaline metabolism. PKU is characterized by deficient or defective phenylalanine hydroxylase activity and persistantly increased levels of the essential amino acid phenylalanine in the circulation. The present article examines current understanding of the etiology of PKU, along with a meta-analysis examining neuropsychological and intellectual presentations in continuously treated adolescents and adults. Patients with PKU differed significantly from controls on Full-Scale IQ, processing speed, attention, inhibition, and motor control. Future research utilizing an integrative approach and detailed analysis of specific cognitive domains will assist both the scientist and clinician, and ultimately the patient.     

晚期非小细胞肺癌TKIs治疗：关注与思考

以表皮生长因子受体（EGFR）为靶点的酪氨酸激酶抑制剂（TKIs）对晚期非小细胞肺癌EGFR突变患者的治疗效果令人瞩目。本文分析总结近年国内外相关研究,指出低剂量TKIs的应用虽有待进一步证实,但优于标准剂量组,并从安全性、改善肿瘤血管结构和功能、与细胞毒化疗的关系三方面探讨大剂量TKIs的应用效果。进一步分析指出大剂量联合小剂量TKIs能够最大程度地防止或延迟耐药的发生,进而控制疾病的进展。从而,为晚期非小细胞肺癌EGFR突变患者的TKIs治疗选择提供参考。     

Association between intermale aggression and genetically-defined tryptophan hydroxylase activity in the mouse brain

The relationship between the genetically defined intensity of intermale aggression and the activity of brain tryptophan hydroxylase (TPH) has been studied in inbred mice. No association between the enzyme activity and the percentage of aggressive mice (reflecting the predisposition to aggressive reaction) was revealed. However, a significant positive interstrain correlation between brain TPH activity and accumulated attacking time (reflecting fight intensity) was identified. No correlation was found between TPH activity and the accumulated attacking time in segregating F2 (BALB × C57BL) mice. In conclusion, TPH is an important, but not the only factor controlling the intensity of intermale aggression in mice. © 1996 Wiley-Liss, Inc.     

Tyrosine hydroxylase activities in the brains of wild Norway rats and silver foxes selected for reduced aggressiveness towards humans

Tyrosine hydroxylase (TH) activity was measured in brains from Norway rats and silver foxes showing wild type aggressiveness and from their counterparts selected over 20-25 generations for reduced aggressiveness towards humans (tameness). TH activity in the brain stem and cortex was increased in tame animals of both species compared with aggressive counterparts. Selection increased hypothalamic TH activity in foxes, but decreased it in rats. There was no difference in TH activity in corpus striatum between the tame and aggressive animals. Fetal TH activity in the posterior part of the brain was higher in tame than aggressive rats at day 20 of embryogensis. Increased TH activity in the brain stem and cortex of adult aggressive rats was observed after treatment of their mothers with hydrocortisone on the days 16 and 18 of pregnancy. This elevation in TH activity was associated with attenuation of the defense behavior of aggressive rats. The data suggested that alterations in neural TH activity in tame rats and foxes may be part of the neurochemical basis of their behavioral phenotype which is developed by selection. © 1994 Wiley-Liss, Inc.     

Serotonin metabolism and serotonergic receptors in Norway rats selected for low aggressiveness to man

Selection of Norway rats (24–27 generations) for low aggressiveness to man resulting in the loss of aggressive responding to handling markedly influences the brain serotonergic system. In “domesticated” Norway rats levels of serotonin in the midbrain and hypothalamus and 5-hydroxyindole acetic acid in the hypothalamus were higher than in non-selected aggressive rats. The activity of the key enzyme in serotonin biosynthesis, tryptophan hydroxylase, in midbrain of rats with genetically determined lack of aggressiveness to man was higher than in aggressive animals, although there was no difference in tryptophan hydroxylase activity in the hypothalamus. B_max and K_D of [³H]spiperone-specific binding in frontal cortex membranes were increased in tame rats. No significant differences in B_max and K_D were found between “domesticated” and aggressive rats in [³H]serotonin binding in the frontal cortex.