Efficacy of Bee Products(Anzer Honey,Pollen and Propolis)in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells:Cytotoxic,Genotoxic and Biochemical Studies

Background and Objective Although drugs are powerful therapeutic agents,they have a range of side effects.These side effects are sometimes cellular and not clinically noticeable.Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients.In this study,we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells“hTERT-HPNE”,and we aimed to improve these harmful effects by natural products.To benefit from the healing effect,we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey.Methods Cytotoxic and genotoxic effects of the drug were investigated by different tests,such as MTT,flow cytometry-apoptosis and comet assays.Anzer honey,pollen and propolis were analyzed by gas chromatography/mass spectrometry(G/C-MS).A total of 19 compounds were detected,constituting 99.9%of the samples.Results The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control(P<0.05).A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey,pollen and propolis in hTERT-HPNE cells(P<0.05).Conclusion This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells.In particular,Anzer honey,pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

Mast cell tryptase and carboxypeptidase A expression in body fluid and gastrointestinal tract associated with drug-related fatal anaphylaxis

AIM: To investigate the expression of mast cell tryptase and carboxypeptidase A in drug-related fatal anaphylaxis.METHODS: The expression of mast cell tryptase and carboxypeptidase A in 15 autopsy cases of drugrelated fatal anaphylaxis and 20 normal autopsy cases were detected. First, the expression of mast cell tryptase was determined in stomach, jejunum, lung, heart, and larynx by immunofluorescence. Different tissues were removed and fixed in paraformaldehyde solution, then paraffin sections were prepared for immunofluorescence. Using specific mast cell tryptase and carboxypeptidase A antibodies, the expression of tryptase and carboxypeptidase A in gastroenterology tract and other tissues were observed using fluorescent microscopy. The postmortem serum and pericardial fluid were collected from drug-related fatal anaphylaxis and normal autopsy cases. The level of mast cell tryptase and carboxypeptidase A in postmortem serum and pericardial fluid were measured using fluor enzyme linked immunosorbent assay(FEIA) and enzyme linked immunosorbent assay(ELISA) assay. The expression of mast cell tryptase and carboxypeptidase A was analyzed in drug-related fatal anaphylaxis cases and compared to normal autopsy cases.RESULTS: The expression of carboxypeptidase A was less in the gastroenterology tract and other tissues from anaphylaxis-related death cadavers than normal controls. Immunofluorescence revealed that tryptase expression was significantly increased in multiple organs, especially the gastrointestinal tract, from anaphylaxis-related death cadavers compared to normal autopsy cases(46.67 ± 11.11 vs 4.88 ± 1.56 in stomach, 48.89 ± 11.02 vs 5.21 ± 1.34 in jejunum, 33.72 ± 5.76 vs 1.30 ± 1.02 in lung, 40.08 ± 7.56 vs 1.67 ± 1.03 in larynx, 7.11 ± 5.67 vs 1.10 ± 0.77 in heart, P < 0.05). Tryptase levels, as measured with FEIA, were significantly increased in both sera(43.50 ± 0.48 μg/L vs 5.40 ± 0.36 μg/L, P < 0.05) and pericardial fluid(28.64 ± 0.32 μg/L vs 4.60 ± 0.48 μg/L, P < 0.05) from the anaphylaxis group in comparison with the control group. As measured by ELISA, the concentration of carboxypeptidase A was also increased more than 2-fold in the anaphylaxis group compared to control(8.99 ± 3.91 ng/m L vs 3.25 ± 2.30 ng/m L in serum, 4.34 ± 2.41 ng/m L vs 1.43 ± 0.58 ng/m L in pericardial fluid, P < 0.05).CONCLUSION: Detection of both mast cell tryptase and carboxypeptidase A could improve the forensic identification of drug-related fatal anaphylaxis.

Should mast cells be considered therapeutic targets in multiple sclerosis?

Mast cells are immune cells of the myeloid lineage that are found throughout the body,including the central nervous system.They perform many functions associated with innate and specific immunity,angiogenesis,and vascular homeostasis.Moreover,they have been implicated in a series of pathologies(e.g.,hypersensitivity reactions,tumors,and inflammatory disorders).In this review,we propose that this cell could be a relevant therapeutic target in multiple sclerosis,which is a central nervous system degenerative disease.To support this proposition,we describe the general biological properties of mast cells,their contribution to innate and specific immunity,and the participation of mast cells in the various stages of multiple sclerosis and experimental autoimmune encephalomyelitis development.The final part of this review is dedicated to an overview of the available mast cells immunomodulatory drugs and their activity on multiple sclerosis and experimental autoimmune encephalomyelitis,including our own experience related to the effect of ketotifen fumarate on experimental autoimmune encephalomyelitis evolution.

Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma

INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.

Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes

AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.

奥希替尼在老年非小细胞肺癌患者靶向治疗中的应用效果及对T细胞水平的影响

目的 探讨奥西替尼在老年非小细胞肺癌患者靶向治疗中的效果及对免疫水平的影响。方法 回顾性选择2018年1月至2020年12月老年非小细胞肺癌患者116例研究,根据治疗方法不同分为2组,各58例。对照组采用常规放化疗治疗,观察组在对照组基础上联合奥西替尼治疗,3个月治疗后评估患者效果,比较2组总有效率、T细胞水平(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、肿瘤标志物水平、不良反应发生率。结果 观察组治疗3个月总有效率为44.8%高于对照组25.9%(P<0.05);2组治疗后3个月CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平均低于治疗前(P<0.05);CD8^(+)水平高于治疗前(P<0.05);观察组治疗后3个月CD3^(+)(58.95±4.21)%、CD4^(+)(32.59±3.11)%、CD4^(+)/CD8^(+)(1.21±0.22)高于对照组(P<0.05);CD8^(+)(26.81±3.32)%低于对照组(P<0.05);观察组干预3个月后CA125(91±8)U/ml、CYFRA21-1(1.26±0.24)μg/L及癌胚抗原(CEA)水平(34±5)μg/L均低于对照组(P<0.05);2组不良反应发生率差异无统计学意义(P>0.05)。结论 奥西替尼用于老年非小细胞肺癌患者靶向治疗中,能获得较好的总有效率,对患者T细胞水平影响较小,可降低肿瘤标志物水平,未增加不良反应发生率,值得临床推广应用。

乌梅-防风药调控过敏性鼻炎Treg/Th17免疫平衡的分子机制研究

目的:探讨乌梅-防风药调控肥大细胞外泌体源性MMP9对过敏性鼻炎(AR)小鼠Treg/Th17免疫平衡的影响。方法:筛选乌梅与防风的潜在作用靶点,并与AR的风险基因取交集,GO分析与蛋白互作分析筛选出潜在作用靶点。建立AR小鼠模型,分离小鼠股骨中肥大细胞及外泌体。乌梅-防风药及外泌体治疗小鼠。评估各组小鼠行为学评分,检测小鼠鼻黏膜中Foxp3、RORγt的mRNA表达。敲减外泌体中MMP9表达后,观察AR小鼠的行为学评分和Foxp3、RORγt的mRNA表达。结果:生物信息学结果显示,乌梅-防风药可能通过肥大细胞外泌体源性IL-1β、MMP9作用于AR。相对于正常小鼠,AR小鼠Foxp3 mRNA表达降低,RORγt mRNA表达升高,MMP9表达升高(均P<0.05)。乌梅-防风药处理AR小鼠后,Foxp3 mRNA表达升高,RORγt与MMP9表达降低,但肥大细胞外泌体能进一步抵消乌梅-防风药的作用,敲减MMP9后肥大细胞外泌体作用减弱。结论:乌梅-防风药通过抑制骨髓源性肥大细胞外泌体源性MMP9调控AR小鼠Treg/Th17失衡。

替雷利珠联合化疗治疗非小细胞肺癌手术患者的效果

目的评价替雷利珠单抗在含铂双药化疗治疗的非小细胞肺癌手术患者中的应用效果。方法选取2022年1月—2023年12月收治的100例拟行手术治疗的非小细胞肺癌患者,根据随机数字表法将其分成两组。对照组50例患者在术前给予含铂双药治疗,观察组50例患者在其治疗基础上加用替雷利珠单抗治疗。比较两组临床疗效、无事件及无疾病生存率、生活质量改善情况、不良反应。结果观察组临床疗效(完全缓解率:20.00%vs.10.00%)及病理评估(主要病理学缓解率:46.00%vs.20.00%)优于对照组(Z=3.484,P<0.001;χ^(2)=7.664,P=0.006);Kaplan-Meier生存分析显示,观察组无事件生存率(84.00%vs.60.00%)及无疾病生存率(78.00%vs.60.00%)均高于对照组(χ^(2)=4.298,P=0.038;χ^(2)=4.783,P=0.029);在生活质量改善率方面,观察组(64.00%)较对照组高(42.00%),差异有统计学意义(χ^(2)=4.857,P=0.028);两组不良反应发生率(18.00%vs.22.00%)比较,差异无统计学意义(χ^(2)=0.250,P=0.617)。结论在含铂双药化疗治疗非小细胞肺癌手术患者中的实施替雷利珠单抗治疗可提高治疗效果,促进生活质量改善,且不会增加不良反应发生风险。

养肺益气汤联合载药微球支气管动脉化疗在非小细胞肺癌治疗中的临床效果分析

目的:分析养肺益气汤联合载药微球支气管动脉化疗治疗非小细胞肺癌的临床效果。方法:选择2020年1月—2023年1月启东市中医院肿瘤科收治的82例非小细胞肺癌患者,根据随机数表法分为化疗组、联用组,各41例。其中化疗组采用载药微球支气管动脉化疗治疗,而联用组采用养肺益气汤联合载药微球支气管动脉化疗治疗。比较两组肿瘤标志物、中医症候积分、毒副作用发生率。结果:治疗前,两组肿瘤标志物比较,差异无统计学意义(P>0.05);治疗后,两组肿瘤标志物均低于治疗前,且联用组低于化疗组,差异有统计学意义(P<0.05)。治疗前,两组中医症候积分比较,差异无统计学意义(P>0.05);治疗后,两组中医症候积分均低于治疗前,且联用组低于化疗组,差异有统计学意义(P<0.05)。联用组毒副作用总发生率低于化疗组,差异有统计学意义(P<0.05)。结论:在针对非小细胞肺癌进行治疗时,在载药微球支气管动脉化疗基础上予以养肺益气汤治疗能够进一步控制癌症病变,缓解各项临床症状,并降低毒副作用发生的可能性。

阿替利珠单抗不良反应94例文献分析

目的分析阿替利珠单抗发生不良反应(adverse reactions,ADRs)的临床特点与规律,为临床安全用药提供参考。方法搜索中国知网、维普、万方、Web of Science、PubMed数据库,收集关于阿替利珠单抗所致不良反应的报道文献并进行分析,研究时间为2022年4—8月。结果阿替利珠致不良反应报道共94例;其中男性56例(59.57%),女性38例(40.43%),男性占比较高;年龄(62.8±12.0)岁,中老年人居多;多数发生在用药后的90 d内(71例,71.0%);阿替利珠单抗致ADRs累及多个系统/器官,其中以神经系统损害(22例,22.0%)占比最多;3~4级严重ADRs占比最多(64例,64.0%);94例经治疗和(或)停药后,好转或治愈80例,死亡5例。结论阿替利珠单抗所致ADRs涉及不同性别与年龄段病人,累及多个系统/器官,临床使用应随时监测,警惕ADRs的发生,做到及时识别与治疗。

PD-1抑制剂联合抗血管生成药物治疗晚期NSCLC的疗效及安全性分析

目的探讨程序性死亡蛋白-1(PD-1)抑制剂联合抗血管生成药物治疗晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法选取我院2019年1月至2021年11月收治的137例晚期NSCLC患者作为研究对象,按治疗方法分为两组。PD-1抑制剂联合抗血管生成药物治疗者81例(联合组),PD-1抑制剂单药治疗者56例(单药组)。统计分析两组客观缓解率(ORR)、疾病控制率(DCR)、无进展生存时间(PFS)、总生存时间(OS)、血管内皮生长因子(VEGF)、肿瘤体积(TV)、预后生存曲线及毒副反应相关数据。结果联合组ORR和DCR显著高于单药组,差异有统计学意义(χ^(2)=4.219,3.583;P=0.040,0.045);联合组PFS和OS均显著长于单药组,差异有统计学意义(Z=7.017,5.778;P<0.001);两组治疗后VEGF和TV水平均明显下降(P<0.001),且治疗1、2个周期后联合组VEGF和TV水平均显著低于单药组,差异有统计学意义(P<0.001);两组Kaplan-Meier预后生存曲线比较差异有统计学意义(χ^(2)_(L)=5.338,P=0.027);两组患者恶心呕吐、头疼、疲劳、腹泻、皮疹、贫血、便秘、呼吸困难及关节痛发生率和Ⅲ级以上毒副反应发生率比较,差异无统计学意义(P>0.05)。结论PD-1抑制剂联合抗血管生成药物可抑制肿瘤微血管增生,缩小TV,提高ORR和DCR,延长PFS和OS,Ⅲ级以上毒副反应发生率低,毒副反应总体安全可控,有助于增加晚期NSCLC患者获益。

归脾汤加减联合免疫化学药物治疗气血亏虚型非小细胞肺癌疗效观察

目的:研究分析归脾汤加减联合免疫化学药物治疗气血亏虚型非小细胞肺癌(NSCLC)疗效。方法:选取2021年1月—2023年12月井冈山大学附属医院和峡江县人民医院收治的60例中医辨证为气血亏虚型的非小细胞肺癌患者作为本次研究对象,根据不同治疗方案进行分组,即对照组与观察组,各30例。2组患者均接受免疫化学药物、护胃、营养支持、镇痛等常规对症治疗。对照组实施免疫化学药物治疗,采用含替雷利珠单抗免疫化学药物治疗方案,治疗3个疗程,至疾病进展,或有不耐受毒性。观察组采用归脾汤加减联合免疫化学药物,治疗3个疗程。比较2组患者临床治疗效果、气血亏虚型中医证候积分、功能状态评分、生存质量评分及不良反应发生情况差异。结果:经不同用药方案治疗后,观察组临床治疗总有效率高于对照(P<0.05);观察组气血亏虚型中医证候积分低于对照组(P<0.05);观察组生活质量评分各条目得分均优于对照组(P<0.05);观察组肿瘤病人功能状态评分低于对照组(P<0.05);与对照组相比,观察组患者的周围神经损伤、免疫性肺炎、骨髓抑制、胃肠道反应及肝肾功能异常等不良反应发生率显著降低,差异具有统计学意义(P<0.05)。结论:采用归脾汤加减联合免疫化学药物治疗气血亏虚型非小细胞肺癌疗效显著,不仅能够有效缓解患者气血亏虚的症状,还能够降低西医治疗过程中的不良反应发生率,显著提升患者的生活质量。

屎肠球菌Ef026的体外益生特性研究

本试验旨在探究屎肠球菌Ef026的体外益生特性,挖掘其开发成饲用微生物制剂的潜力。通过对菌株的耐受性、细胞表面特性、抑菌作用、抗氧化作用及药敏试验,全面评价了其体外益生特性。结果显示:屎肠球菌Ef026在pH 3.0及0.3%的胆盐浓度下具有良好的耐受性;能够耐受70℃高温;具有极高的黏附性,其黏附指数为(38.00±1.67)%;对多种畜禽和水产养殖中常见病原菌具有一定的抑制作用;菌株完整细胞能够耐受2.0 mM H_(2)O_(2),同时还具有还原能力、DPPH·清除力、·O_(2)^(-)清除力和抗脂质过氧化能力;对常用抗生素具有不同程度的敏感性。屎肠球菌Ef026具有优良的体外益生特性,具有开发成饲用微生物制剂的价值。

基于RTCA技术研究抗体偶联药物的旁观者效应的检测方法

目的 利用实时无标记细胞分析(RTCA)系统评估抗体偶联药物(ADC)的旁观者效应。方法 采用RTCA系统监测抗原阳性细胞(Ag^(+))和抗原阴性细胞(Ag^(-))的共培养状态,观察Ag^(-)的细胞存活情况;采用重复实验验证结果的可靠性和一致性,并采用单因素方差分析比较不同细胞比例培养组在单个时间点的Ag^(-)存活率。结果 加入抗体偶联药物后,随着共培养时间的延长,Ag^(-)存活率下降;此外,在单个时间点(96 h)上,与0%Ag^(+)细胞的Ag^(-)细胞存活率相比,10%Ag^(+)细胞的Ag^(-)细胞存活率为89.07%(P=0.156),25%Ag^(+)细胞的Ag^(-)存活率为68.93%(P=0.0026),50%Ag^(+)、75%Ag^(+)和90%Ag^(+)细胞的Ag^(-)存活率分别为35.28%、13.99%和12.02%(P<0.0001)。在 Ag^(+)细胞比例为25%~90%时,旁杀伤效果显著;重复性结果显示不同Ag^(+)细胞的旁杀伤率的相对标准偏差(RSD)均小于30%。结论 结合RTCA技术和共培养方式的方法,可以更准确地模拟旁观者效应的生物学过程,为后续的抗体偶联药物开发提供有价值的参考。

阿美替尼、吉非替尼治疗EGFR突变局部晚期非小细胞肺癌的效果及预后

目的探讨阿美替尼、吉非替尼治疗表皮生长因子受体(EGFR)突变局部晚期非小细胞肺癌(NSCLC)的效果及预后。方法选取2019年3月至2022年9月确诊的100例EGFR突变局部晚期NSCLC,根据治疗方式不同分为A组(n=57)和B组(n=43),A组采用阿美替尼治疗,B组采用吉非替尼治疗,均持续治疗2个周期。比较2组的客观缓解率(ORR)和疾病控制率(DCR)、治疗前后血清EGFR水平和免疫球蛋白指标[免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)]、毒副反应发生率,所有患者随访12~42个月,绘制生存曲线,比较2组中位总生存期(OS)和中位无进展生存期(PFS)。结果A组ORR和DCR分别为28.07%和77.19%,B组分别为11.63%和44.19%,差异均有统计学意义(P<0.05)。治疗后,A组血清EGFR水平较B组低,IgM、IgA和IgG水平较B组高,差异有统计学意义(P<0.05)。A组<3级毒副反应发生率为71.93%,≥3级毒副反应发生率为21.05%,B组<3级毒副反应发生率为48.84%,≥3级毒副反应发生率为41.86%,差异有统计学意义(P<0.05)。A组中位OS和中位PFS分别为16.9个月和5.8个月,B组中位OS和中位PFS分别为10.5个月和4.0个月,差异有统计学意义(P<0.05)。结论与吉非替尼比较,阿美替尼治疗EGFR突变局部晚期NSCLC患者效果更好,可以更好控制病情发展,改善EGFR水平和免疫指标,提高患者生存率,且具有一定的安全性。

Personalized targeted therapy for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.

Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice

AIM: To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice. METHODS: AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts. Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS: Antisense S-ODN treatment led to reduced AFP gene expression. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction. CONCLUSION: Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.

Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation:Results from a retrospective study on 38 Chinese patients

BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.

Taxotere resistance in SUIT Taxotere resistance in pancreatic carcinoma cell line SUIT 2 and its sublines

AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020, S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT. Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and beta-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil (Ver) and indomethacin (IMC), respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2, the levels of beta-tubulin isotype II, III expressions in S-2/TXT were increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drug resistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions. The increases of beta-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.

健肝散体外对拉米夫定耐药株病毒表达抑制及增敏作用的研究

目的:探讨健肝散(JGP)对HepG2.2.15耐药株对拉米夫定(LMV)耐药的影响。方法:利用药物浓度递增冲击的方法,建立HepG2.2.15/LMV耐药细胞株模型,CCK8法检测耐药株、敏感株IC_(50)值,观察健肝散(JGP)含药血清对耐药株IC_(50)值影响;设置HepG2.2.15耐药株+正常大鼠血清组及HepG2.2.15耐药株+JGP含药血清组,荧光定量PCR检测两组细胞HBV-pgRNA表达水平,提取RNA后ELISA检测两组细胞上清HBsAg和HBeAg的表达水平。结果:①与HepG2.2.15细胞耐药株+正常大鼠血清组相比,HepG2.2.15细胞耐药株+JGP含药血清的IC_(50)值显著降低;②与耐药细胞株+正常血清组相比,健肝散含药血清可抑制HepG2.2.15 LMV耐药细胞株HBV-pgRNA的表达,差异有统计学意义(P<0.01);③与HepG2.2.15/LMV耐药细胞株添加正常血清组相比,JGP含药血清可抑制HepG2.2.15/LMV耐药细胞株HBsAg和HBeAg的表达,差异具有统计学意义(P<0.01)。结论:JGP体外可以增加耐药株对LMV敏感性,有效降低耐药株HBV的表达,对LMV耐药具有一定缓解作用。