Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

探究自拟清肝降压饮早期干预高血压前期和原发性1级高血压

目的观察分析自拟清肝降压饮早期干预高血压前期和原发性1级高血压的疗效。方法选取我院于2010年1月至2012年12月收治的高血压前期和原发性1级高血压患者100例进行临床研究。结果治疗后,辅助清肝降压饮治疗的观察组患者的血压控制有效率为93.3%,明显优于对照组(P<0.05);观察组患者的证候有效率为98.1%,明显高于对照组(P<0.05)。结论自拟清肝降压饮早期干预高血压前期和原发性1级高血压有着良好的治疗效果,可以在临床上广泛推广。     

术中MR液体反转恢复序列在低级别神经胶质瘤切除术中的应用价值

目的探讨术中磁共振成像(intraoperative MRI,iMRI)中的液体反转恢复序列(fluid attenuated inversion recovery,FLAIR)在低级别神经胶质瘤(WHOⅠ~Ⅱ级)切除术中的应用价值,从而对是否存在残留肿瘤的诊断提供帮助。方法选取18例低级别神经胶质瘤(low-grade gliomas,LGGs)患者的术中MRI,查看FLAIR图像中手术腔周围是否存在高信号,并对术前或术后复查过MRI患者的图像进行分析,比较术区周边FLAIR信号的变化情况。结果低级别神经胶质瘤切除术中手术区域边缘iMRI的FLAIR表现:1)没有FLAIR异常信号7例;2)线状FLAIR高信号(linear FLAIR hyperintensity,LFH)7例;3)结节或片状FLAIR高信号(nodular or patchy FLAIR hyperintensity,NPFH)4例。接受iMRI分析的患者的手术切缘上无FLARI异常信号中的4例术后3个月复查MRI术区周围未见异常改变;出现LFH中有4例患者在术后3个月后复查MRI,异常信号强度减低或消失。而2例NPFH随即进行了第二次手术切除,并再次行术中MRI扫描,最终组织病理学为肿瘤残留,1例NPFH未进行二次手术,半年后复查,异常信号范围增大。结论经iMRI分析的手术区域切缘可能出现FLAIR高信号,出现线状FLAIR高信号时不应误认为是残余肿瘤,而出现结节或片状FLAIR高信号时可能是残余肿瘤。iMRI FLAIR在初步判断低级别神经胶质瘤切除术术区边缘是否存在残留肿瘤方面有一定的应用价值。     

71例肿瘤化疗致3~4级骨髓抑制的分析

目的：了解肿瘤科化疗致3~4级骨髓抑制不良反应的特点及相关因素，为临床合理用药提供参考。方法：选取某院2016年因化疗致3~4级骨髓抑制的住院肿瘤患者71例，分别从性别与年龄、药物种类、疾病类型、骨髓抑制类型及时间特点、化疗周期对抑制率的影响等多个因素进行回顾性分析。结果：3~4级骨髓抑制患者中男性多于女性，以41~60岁的中年人为主；药物以多西他赛、顺铂、吉西他滨为主，骨髓抑制的外周血象主要表现为白细胞及血小板下降；头颈部肿瘤所占比例最高，为67.7%；三系细胞开始下降时间和低值持续时间各不相同；白细胞及血小板最低值的发生率在化疗第4周期达到最大。结论：3~4级骨髓抑制的发生与多种因素有关，临床药师应该做好不良反应的报告和监测工作，减少反应的发生。