奥沙利铂致急性血小板减少1例

<正>一、临床资料患者,63岁,男性,于2011年8月初体检时发现肝脏肿物,查相关抗原示CEA增高,后行PET/CT检查示乙状结肠不规则结节状高代谢病灶,考虑乙状结肠癌可能,病灶周围多发淋巴结转移,肝脏多发转移。肠镜检查示乙状结肠距肛门26²9cm见一大小约3×4cm菜花样肿物,病理活检示结肠低分化腺癌,KRAS基因检测野生型。后入组临床研究,行FOLFOX4方案化疗,用药方案:奥沙利铂85mg/m2,静脉滴     

Unexpected Seizure Attack in a Patient with Spinal Metastasis Diagnosed as Posterior Reversible Encephalopathy Syndrome

Seizure is a foreseeable risk in patients with brain lesion. However, seizure during treating non-brain lesion is not a familiar situation to neurosurgeon. Posterior reversible encephalopathy syndrome (PRES) is a relatively common situation after systemic chemotherapy. The aim of this study is to make neurosurgeons aware of this potential medical problem. A 52-year-old woman with advanced gastric cancer, presented with low back pain due to spinal metastasis at the 4th lumbar vertebra. Ten cycles of chemotherapy with FOLFOX (5-Fluoruracil/Oxaliplatin) had been completed 23 days ago. Two days before the planned operation, a generalized tonic clonic seizure occurred. She did not have a history of hypertension or seizure. The seizure was stopped with lorazepam 4mg. The brain magnetic resonance (MR) imaging showed high signal changes in both parieto-occipital lobes on the T2-weighted images, and these were partially enhanced, suggesting PRES. The surgery was preceded by treatment with an antiepileptic drug. The MR images, taken 1.5 months after the seizure, showed that the lesion was no longer present. At 3 month follow-up, no additional seizure attack occurred without any seizure medication. The possibility of a seizure attack should be considered if the patient has a history of chemotherapy.     

奥沙利铂联合替吉奥治疗老年晚期胃癌的临床观察

胃癌是我国常见的恶性肿瘤之一，60％以上发现时已属晚期。虽然手术是治疗胃癌的主要方法，但因晚期胃癌患者的患病时间长、预后差等特点使得其术后易转移复发，尤其是老年患者其机体的耐受能力较差，故治疗仍以保守治疗为主。我们对老年晚期胃癌患者予以奥沙利铂联合替吉奥治疗，取得了满意的疗效，现报告如下。     

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.     

奥沙利铂联合化疗治疗大肠癌临床护理

目的:探讨奥沙利铂联合化疗治疗大肠癌的不良反应及其临床护理措施。方法:回顾性分析40例大肠癌应用奥沙利铂联合化疗的临床资料。结果:40例患者均完成了4个周期的治疗,治疗过程中均出现感觉迟钝、手指(趾)麻木、胃肠道反应、骨髓抑制不同程度的不良反应,未发生严重的不良反应。结论:对大肠癌化疗期间做好饮食护理、心理护理,化疗前、中、后的护理,可使患者顺利完成化疗,提高生活质量。     

吉西他滨联合奥沙利铂或顺铂治疗非小细胞肺癌的临床疗效观察

目的：比较吉西他滨联合奥沙利铂与吉西他滨联合顺铂治疗非小细胞肺癌（ NSCLC）患者的临床效果。方法2013年6月＿2014年6月收治确诊的非小细胞肺癌患者68例,根据联合用药不同分为奥沙利铂组与顺铂组各34例。奥沙利铂组患者给予吉西他滨1000mg/ m2,d1、d8＋奥沙利铂130mg/ m2,d1,静脉滴注,3周为1个疗程;顺铂组给予吉西他滨1000mg/ m2,d1、d8＋顺铂25mg/ m2,d 1、2、3,静脉滴注,3周为1个疗程。2组均治疗2个疗程,随访6~24个月,比较2组临床疗效、近期不良反应、1年生存率。结果奥沙利铂组总有效率为41.2％（14/34）,顺铂组为35.3％（12/34）,2组比较差异无统计学意义（P ﹥0.05）。奥沙利铂组患者中位 PFS、OS 分别为24.5周、44.6周,顺铂组分别为18.2周、36.5周,2组中位 PFS 和中位 OS 比较差异无统计学意义（P ﹥0.05）。奥沙利铂组1年生存率为47.0％（16/34）,顺铂组为41.2％（14/34）,2组比较差异无统计学意义（P ﹥0.05）。2组患者不良反应主要表现为骨髓抑制、胃肠道反应和神经毒性等,以1~2级为主。奥沙利铂组1~2级神经毒性发生率为79.4％（27/34）,高于顺铂组35.3％（12/34）（P ＜0.01）,而3~4级不良反应发生率顺铂组为52.9％（18/34）,高于奥沙利铂组的20.6％（7/34）（P ＜0.01）,2组比较差异均有统计这意义（P ﹥0.05）。结论吉西他滨联合顺铂或奥沙利铂对非小细胞肺癌患者临床疗效相当,但联合奥沙利铂不良反应少,因而患者耐受性好,临床应用更安全。     

上调NDRG1表达降低奥沙利铂耐药结肠癌细胞的存活率

目的观察上调NDRG1表达对结肠癌细胞及奥沙利铂耐药结肠癌细胞的毒性作用并探讨其机制。方法以重组真核表达质粒pEGFP-NDRG1-N3转染HCT 116及奥沙利铂耐药的OHP-HCT 116结肠癌细胞,以实时定量(qRT)-PCR法和Western blot法检测转染效率。MTT法检测奥沙利铂对不同结肠癌细胞的毒性及验证OHP-HCT 116细胞的耐药性。给予奥沙利铂干预转染pEGFP-NDRG1-N3的HCT 116细胞及OHP-HCT 116细胞,MTT法检测细胞存活率,流式细胞术检测细胞凋亡率,Western blot法检测凋亡蛋白Bcl-2及p53蛋白水平变化。结果不同浓度奥沙利铂干预下的3株结肠癌细胞中HCT 116细胞对奥沙利铂最敏感,OHP-HCT 116细胞对奥沙利铂耐药得到验证。以不同浓度梯度奥沙利铂干扰转染pEGFP-NDRG1-N3的HCT 116细胞及OHP-HCT 116细胞,与MOCK及siNC组比较,在HCT 116细胞及OHP-HCT 116细胞,转染pEGFP-NDRG1-N3细胞的存活率下降(P<0.05),凋亡率升高(P<0.05),Bcl-2表达降低(P<0.05),p53表达升高(P<0.05)。结论上调NDRG1表达通过调控p53表达改善结肠癌细胞奥沙利铂耐药,提高化疗敏感性。     

Chronic Oral Administration of Magnesium-L-Threonate Prevents Oxaliplatin-Induced Memory and Emotional Deficits by Normalization of TNF-α/NF-κB Signaling in Rats

Antineoplastic drugs such as oxaliplatin (OXA) often induce memory and emotional deficits. At present, the mechanisms underlying these side-effects are not fully understood, and no effective treatment is available. Here, we show that the short-term memory deficits and anxiety-like and depression-like behaviors induced by intraperitoneal injections of OXA (4 mg/kg per day for 5 consecutive days) were accompanied by synaptic dysfunction and downregulation of the NR2B subunit of N-methyl-D-aspartate receptors in the hippocampus, which is critically involved in memory and emotion. The OXA-induced behavioral and synaptic changes were prevented by chronic oral administration of magnesium-L-threonate (L-TAMS, 604 mg/kg per day, from 2 days before until the end of experiments). We found that OXA injections significantly reduced the free Mg²⁺ in serum and cerebrospinal fluid (from ~ 0.8 mmol/L to ~ 0.6 mmol/L). The Mg²⁺ deficiency (0.6 mmol/L) upregulated tumor necrosis factor (TNF-α) and phospho-p65 (p-p65), an active form of nuclear factor-kappaB (NF-κB), and downregulated the NR2B subunit in cultured hippocampal slices. Oral L-TAMS prevented the OXA-induced upregulation of TNF-α and p-p65, as well as microglial activation in the hippocampus and the medial prefrontal cortex. Finally, similar to oral L-TAMS, intracerebroventricular injection of PDTC, an NF-κB inhibitor, also prevented the OXA-induced memory/emotional deficits and the changes in TNF-α, p-p65, and microglia. Taken together, the activation of TNF–α/NF–κB signaling resulting from reduced brain Mg²⁺ is responsible for the memory/emotional deficits induced by OXA. Chronic oral L-TAMS may be a novel approach to treating chemotherapy-induced memory/emotional deficits.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00563-x) contains supplementary material, which is available to authorized users.     

替吉奥联合奥沙利铂或奈达铂同步放疗治疗局部进展期食管鳞癌的临床观察

目的 比较替吉奥联合奥沙利铂（OXA）或奈达铂（NDP）同步放疗治疗局部进展期食管鳞癌的临床疗效和相关不 良反应。方法 选择局部进展期食管鳞癌患者72 例,随机分为观察组（38 例）和对照组（34 例）,两组均采用同步放化疗。观察组采用替吉奥联合OXA 治疗,OXA 剂量为130mg/m2,静脉滴注,d1,替吉奥40mg/m2,早晚各1 次口服,d1~14。对照组采用NDP,剂量为80mg/m2,静脉滴注,d1,其余治疗方法同观察组。两组患者放、化疗同时开始,3周为1 个疗程,共化疗2个疗程。比较两组患者治疗后的临床疗效、生存期及不良反应情况。结果 观察组和对照组近期总有效率分别为81.6%和82.4%,两组比较无统计学差异（P＞0.05）;观察组和对照组患者1、2、3 年生存率分别为86.8%、57.9%、28.9%和85.3%、55.9%、29.4%,两组比较均无统计学差异（均P ＞0.05）。观察组患者外周神经毒性反应发生率高于对照组（P＜0.05）;而在骨髓抑制、放射性食管炎及放射性肺炎等其他方面的不良反应发生率均类似于对照组,两组比较均无统计学差异（均P＞0.05）。结论在局部进展期食管癌同步放化疗中,替吉奥联合OXA 方案与替吉奥联合NDP 方案患者的近期有效率与远期生存率相当,有效性和耐受性都较好,值得进一步 前瞻性探索。