Gene and microRNA expression reveals sensitivity to paclitaxel in laryngeal cancer cell line

Paclitaxel is a widely used chemotherapy drug for advanced laryngeal cancer patients. However, the fact that there are 20-40% of advanced laryngeal cancer patients do not response to paclitaxel makes it necessary to figure out potential biomarkers for paclitaxel sensitivity prediction. In this work, Hep2, a laryngeal cancer cell line, untreated or treated with lower dose of paclitaxel for 24 h, was applied to DNA microarray chips for gene and miR expression profile analysis. Expression of eight genes altered significantly following paclitaxel treatment, which was further validated by quantitative real-time PCR. Four up-regulated genes were ID2, BMP4, CCL4 and ACTG2, in which ID2 and BMP4 were implicated to be involved in several drugs sensitivity. While the down-regulated four genes, MAPK4, FASN, INSIG1 and SCD, were mainly linked to the endoplasmic reticulum and fatty acid biosynthesis, these two cell processes that are associated with drug sensitivity by increasing evidences. After paclitaxel treatment, expression of 49 miRs was significantly altered. Within these miRs, the most markedly expression-changed were miR-31-star, miR-1264, miR-3150b-5p and miR-210. While the miRs putatively modulated the mRNA expression of the most significantly expression-altered genes were miR-1264, miR-130a, miR-27b, miR-195, miR-1291, miR-214, miR-1277 and miR-1265, which were obtained by miR target prediction and miRNA target correlation. Collectively, our study might provide potential biomarkers for paclitaxel sensitivity prediction and drug resistance targets in laryngeal cancer patients.     

顺铂或奈达铂联合紫杉醇治疗宫颈癌的疗效比较

目的 对比分析顺铂或奈达铂与紫醇联合治疗宫颈癌的疗效。方法 选择2012年2月-2015年12月在宁强县天津医院进行诊治的宫颈癌患者160例,按照使用化疗药物的不同分为顺铂组和奈达铂组。顺铂组采取TP化疗方案,奈达铂组采取TN化疗方案,对比两组的疗效、化疗不良反应、住院时间和治疗费用。结果 顺铂组的有效率为79.26%,与奈达铂组的82.05%相比无明显差异;奈达铂组Ⅰ~Ⅳ级血红蛋白降低、白细胞减少的发生率均明显高于顺铂组（P<0.05）,但两组间Ⅲ~Ⅳ级血红蛋白降低、血小板和白细胞减少发生率无明显差异,奈达铂组Ⅰ~Ⅳ级和Ⅲ~Ⅳ级恶心、呕吐发生率均明显低于顺铂组（P<0.05）;奈达铂组患者的住院时间明显短于顺铂组（P<0.05）;奈达铂组的治疗费用与顺铂组相比无明显差异。结论 顺铂或奈达铂与紫杉醇联合应用于宫颈癌辅助化疗的疗效相似,奈达铂的胃肠道不良反应比顺铂更低,骨髓抑制尽管增加但仍可控,采用奈达铂化疗较顺铂缩短了住院时间,且住院费用并无明显增加,患者更易接受。     

2014-2016年北京大学肿瘤医院紫杉醇治疗乳腺癌的不良反应分析

目的 分析北京大学肿瘤医院紫杉醇治疗乳腺癌时发生的不良反应,提高对紫杉醇的认识,以便更好地发挥紫杉醇的治疗作用.方法 回顾并分析2014年7月—2016年12月北京大学肿瘤医院上报的81例紫杉醇治疗乳腺癌的不良反应.结果 发生紫杉醇不良反应的乳腺癌患者年龄以50~59岁居多,发生时间基本出现在输注30 min内,不良反应主要症状为胸闷憋气(88.89%)、骨髓抑制(77.78%)、皮肤瘙痒(33.33%)和血压下降(33.33%).51例为首次输注,16例发生不良反应的患者有过敏史.结论 应用紫杉醇化疗的乳腺癌患者先进行预处理方案及试验量输注,可减少不良反应发生.患者输注过程中应密切关注,出现不良反应积极对症处理.     

紫杉醇非注射给药系统研究进展

紫杉醇是从红豆杉中分离出的一种复杂的次生代谢产物,已成为世界公认的强活性广谱抗癌药物。紫杉醇水溶性差,口服生物利用度低,传统注射剂采用聚氧乙烯蓖麻油作为助溶剂,导致过敏反应发生率较高,临床使用前需进行预脱敏处理。因此,紫杉醇非注射给药系统的研究非常活跃,表明临床上对紫杉醇非注射剂型的需求巨大。综述了紫杉醇非注射给药系统的研究进展,包括口服给药系统、阴道给药系统、透皮给药系统、植入释药系统、鼻腔给药系统和吸入给药系统,为今后的研究和临床应用提供参考。     

Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit

Chemotherapeutics in the taxane and vinca-alkaloid classes sometimes produce a painful peripheral neuropathy for which there is no validated treatment. Experiments with rat models of paclitaxel- and vincristine-evoked pain suggest that these conditions may not respond to all of the analgesics that have efficacy in other models of painful peripheral neuropathy. We tested gabapentin as a potential analgesic for paclitaxel- and vincristine-evoked pain. We used a repeated dosing paradigm because there are precedents showing that repeated drug exposure may be necessary to demonstrate analgesia in neuropathic pain models. Gabapentin is believed to work via binding to voltage-gated calcium channels that contain the alpha-2-delta type-1 (alpha(2)delta-1) subunit, and the expression of this subunit is known to be increased in some painful peripheral neuropathy models. Thus we also examined whether the paclitaxel-evoked pain syndrome was accompanied by an alpha(2)delta-1 increase, and whether gabapentin had any effect on subunit expression. We found that the paclitaxel- and vincristine-evoked mechano-allodynia and mechano-hyperalgesia were significantly reduced by gabapentin, but only with repeated dosing. Paclitaxel-evoked painful peripheral neuropathy was associated with an increased expression of the alpha(2)delta-1 subunit in the spinal dorsal horn, but not in the dorsal root ganglia. The spinal cord increase was normalized by repeated gabapentin injections. Together, these findings suggest that repeated dosing with gabapentin may be beneficial in patients with chemotherapy-evoked painful peripheral neuropathy and that gabapentin's mechanisms of action may include normalization of the nerve injury-evoked increase in calcium channel alpha(2)delta-1 subunit expression.     

紫杉醇药涂球囊扩张治疗ASO患者疗效及SIRT7水平对术后血管再狭窄的预测

目的分析自身免疫性早发性卵巢功能不全(POI)患者血清免疫指标水平,筛选出较为特异的免疫性指标。 方法选取46例自身免疫性POI患者(POI组)和46例健康女性(正常组),比较两组体液免疫指标、自身免疫指标、抗心磷脂综合征指标、甲状腺功能指标水平。 结果与正常组比较,POI组孕产次、经期及月经周期减少,卵泡刺激素、黄体生成素升高,雌二醇、抗苗勒氏管激素降低;体液免疫指标κ轻链、λ轻链、免疫球蛋白G、免疫球蛋白M、免疫球蛋白E升高,补体4降低;抗心磷脂综合征指标抗心磷脂IgA抗体(ACA-IgA)、ACA-IgG、抗β2糖蛋白1 IgM抗体升高;甲状腺功能指标游离三碘甲状腺原氨酸、游离甲状腺素、促甲状腺素受体抗体、甲状腺过氧化物酶抗体升高(P＜0.05),上述指标阳性率两组间比较差异有显著性(P＜0.05)。POI组内与自身免疫指标阳性率比较,体液免疫指标阳性率和甲状腺功能指标阳性率差异均有显著性。 结论自身免疫性POI患者血清体液免疫指标和甲状腺功能指标更容易发生异常。     

多西他赛和紫杉醇致严重不良反应对比分析

目的：分析多西他赛和紫杉醇致严重不良反应的特点,为临床安全用药提供参考。方法收集2004年1月至2013年1月我省药品不良反应监测中心收到的多西他赛和紫杉醇引起的严重不良反应报告,比较2种药物所致严重不良反应临床表现及转归。结果共收集多西他赛和紫杉醇严重不良反应报告31份,涉及患者31例,不良反应33例次。31例患者中男性9例,女性22例;年龄31～76岁,平均年龄53岁。紫杉醇引起的严重不良反应17例次,主要临床表现为过敏性休克（70.59%）、过敏样反应（11.76%）、白细胞减少（11.76%）、骨髓抑制（5.88%）;多西他赛引起的严重不良反应16例次,主要临床表现为过敏样反应（31.25%）、骨髓抑制（18.75%）、白细胞减少（18.75%）、腹泻（6.25%）、过敏性休克（6.25%）、胃肠道出血（6.25%）、背痛（6.25%）、胸闷（6.25%）。停药及对症治疗后均好转或痊愈。结论多西他赛与紫衫醇致严重不良反应临床表现有所不同,与多西他赛相比,紫衫醇过敏性休克所占比例较高,使用时更应加强用药指导和监测。     

Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy

Background and Purpose

Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy.

Experimental Approach

The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay.

Key Results

PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg⁻¹) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT_1A antagonist WAY 100635, but not the CB₁ antagonist SR141716 or the CB₂ antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability.

Conclusions and Implications

Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT_1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN.     

紫杉醇热敏脂质体的制备与质量控制

目的：制备紫杉醇热敏脂质体,建立测定其含量、有关物质及溶血磷脂的方法,考察其含量、有关物质、溶血磷脂量以及体外溶血性。方法采用高效液相色谱（ HPLC）-紫外法检测制剂含量及有关物质,HPLC-电雾式检测器检测制剂中溶血磷脂单棕榈酰磷脂酰胆碱的量,并对检测方法进行验证;分光光度法测定体外溶血百分率。结果紫杉醇在60.39~181.17μg·mL-1范围内峰面积与浓度线性关系良好,回收率及精密度实验均符合要求;有关物质测定方法专属性、灵敏度和系统适用性均符合要求;溶血磷脂测定方法的专属性和灵敏度符合有关规定,在1.5~50.0μg·mL-1范围内峰面积与浓度线性关系良好,回收率、重复性均符合要求;3批自制紫杉醇热敏脂质体的含量在90.0%~110.0%之间,单个杂质含量均〈0.5%,总杂质含量均〈2.0%,体外基本不引起溶血。结论含量、有关物质及溶血磷脂检测方法均可用于紫杉醇热敏脂质体的质量评价,自制紫杉醇热敏脂质体各项指标均符合要求,且质量稳定。