Cognitive Function and Quality of Life in Vorinostat-Treated Patients after Matched Unrelated Donor Myeloablative Conditioning Hematopoietic Cell Transplantation

Myeloablative conditioning allogeneic hematopoietic cell transplantation (HCT) puts patients at greater risk for significant cognitive and quality of life decline compared with recipients of reduced-intensity conditioning or autologous HCT. Vorinostat, a histone deacetylase inhibitor, has been shown to have neuroprotective and neurorestorative effects in preclinical models of neurologic diseases. Thus, within the context of a myeloablative conditioning phase II clinical trial of vorinostat combined with tacrolimus and methotrexate for graft-versus-host disease prophylaxis, we conducted an ancillary study to evaluate feasibility of assessing associations between vorinostat and neurocognitive function and quality of life (ClinicalTrials.gov NCT02409134). Nine patients (mean age, 53 years; range, 36 to 66) underwent computerized neuropsychological testing (Cogstate) and completed surveys of mood (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), and quality of life (Functional Assessment of Cancer Therapy–General). Control cohorts from a separate concurrent longitudinal study (19 autologous and 18 allogeneic HCT patients, who matched the vorinostat patients on relevant medical and demographic variables) completed the same test battery. All allogeneic patients received busulfan-based myeloablative conditioning and were transplanted with HLA-matched unrelated donors. The total neurocognitive performance score of vorinostat patients did not change significantly across the study duration (ie, baseline, day 30, day 100, and day 160). Depression, anxiety, and quality of life also did not differ significantly across time. In univariate analyses (analysis of variance), vorinostat-treated patients showed no difference in neurocognitive function or quality of life compared with autologous and allogeneic control subjects. However, when medical variables were accounted for in a linear mixed effects regression model, the total neurocognitive performance of vorinostat-treated patients was comparable with autologous control subjects. Notably, autologous control subjects performed significantly better than allogeneic control subjects (estimate, .64; standard error, .23; P ≤ .01). Moreover, a smaller percentage of vorinostat-treated patients were classified as mildly, moderately, or severely impaired across neurocognitive domains as well as time points compared with both control cohorts. Thus, vorinostat may have neurorestorative or neuroprotective effects in the HCT setting. Accordingly, we recognize the need for a future, full-scale randomized controlled trial to further examine this hypothesis.     

螺旋CT导航多弹头射频消融肝癌的临床应用

目的 探讨并总结螺旋CT导航经皮肝穿刺多弹头射频消融肝癌的特点、安全性及临床近期疗效。方法 对20例肝细胞肝癌及多发肝转移瘤共32个瘤灶在螺旋CT导航下,配合自制穿刺定位定角器,进行了多弹头射频治疗,共消融49个靶位,通过对治疗前后及随访3-8个月的螺旋CT检查的比较及AFP、自觉症状等的改变进行对比观察。结果 20例患者,49个靶位,一次性穿刺及消融操作技术成功率达100％,复查螺旋CT检查:术毕时20例(100％)瘤灶密度减低,其中15例(占75％)病灶内见散在气化影;术后2个月时,20例中的16例(占80％)瘤灶体积缩小10％-20％,增强扫描动脉期瘤灶不强化。另3例瘤灶体积缩小不明显,但动脉期不强化;1例瘤灶略显增大,系邻近门静脉一侧,消融不彻底,病灶呈偏向门静脉一侧生长,动脉期轻度强化;术后6个月时,20例中的8例(占40％)瘤灶体积缩小达20％-30％,动脉期不强化。1例于治疗术后6.5个月死于肝、脑、肺多发转多。术后1个月复查血AFP,20例中13例(占65％)下降,下降值40-210μg/ml,平均下降135.6μg/ml,其中有2例降至正常范围。治疗后2个月内所有患者自觉症状均明显改善。无手术死亡,术中及术后不良反应轻微,无重要并发症发生。结论经皮多弹头射频消融术,是一种安全、可靠、微创的局部疗法,具有较高的临床应用价值。采?     

金丝桃苷对耐长春新碱结肠癌HCT8/VCR细胞耐药逆转作用

目的:探讨金丝桃苷对耐长春新碱结肠癌HCT8/VCR细胞的耐药逆转作用及其可能的作用机制。方法:分别以不同质量浓度(2.5~80 mg·L-1)的金丝桃苷及不同质量浓度(1.25~40 mg·L-1)的长春新碱作用于体外培养的HCT8和HCT8/VCR细胞48 h,采用噻唑蓝(MTT)比色法测定细胞生长抑制率,计算各组细胞金丝桃苷和长春新碱的半数抑制浓度(IC50)及金丝桃苷抑制率为5%的药物浓度;采用非毒性剂量金丝桃苷分别与不同质量浓度(1.25~40 mg·L-1)的长春新碱联合作用HCT8/VCR细胞,检测长春新碱的IC50,计算逆转倍数;采用流式细胞仪检测细胞凋亡率及线粒体膜电位变化,比色法检测含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-3,Caspase-9蛋白活性的变化。结果:金丝桃苷非细胞毒性剂量为0.82mg·L-1。0.82 mg·L-1金丝桃苷可使长春新碱对HCT8/VCR细胞的IC50从65.97 mg·L-1下降至9.94 mg·L-1,逆转倍数为6.63;与单独用长春新碱组比较,长春新碱与金丝桃苷联合用药组细胞凋亡率,Caspase-3,Caspase-9蛋白活性均显著提高(P0.01)。线粒体膜电位检测发现,与单独用长春新碱组及金丝桃苷组比较,长春新碱与金丝桃苷联合用药组低荧光强度相对细胞数所占比率显著提高(P0.01)。结论:长春新碱与金丝桃苷联合应用后可增强Caspase-3,Caspase-9蛋白活性,降低线粒体膜电位,提高HCT8/VCR细胞的凋亡率,从而产生耐药逆转作用。     

丹参多酚酸盐联合尼可地尔治疗冠心病心绞痛的临床研究

目的探讨丹参多酚酸盐联合尼可地尔治疗冠心病心绞痛的临床效果。方法选取2016年1月—2017年12月北京市和平里医院收治的146例冠心病心绞痛患者,随机分为对照组和治疗组,每组各73例。对照组口服尼可地尔片,5 mg/次,3次/d。治疗组在对照组基础上静脉滴注注射用丹参多酚酸盐,200 mg加入生理盐水250 mL中充分稀释后给药,1次/d。两组均连续治疗2周。观察两组的临床疗效,比较两组治疗前后硝酸甘油用量、心绞痛发作次数、每次持续时间。比较两组治疗前后低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、红细胞比容(HCT)、红细胞聚集指数(EAI)、肌钙蛋白T(c Tn T)、白细胞介素(IL)1β、IL-18、一氧化氮(NO)、超氧化物歧化酶(SOD)、西雅图心绞痛量表(SAQ)各项评分的变化情况。结果治疗后,对照组和治疗组患者的总有效率分别为82.19%、93.15%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者硝酸甘油用量较治疗前明显减少,心绞痛发作次数、每次持续时间均明显减少,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组硝酸甘油用量、心绞痛发作次数、每次持续时间均明显少于对照组,两组比较差异有统计学意义(P0.05)。两组治疗后LDL-C、HCT、EAI、cTnT、IL-1β、IL-18水平较治疗前均显著降低,但HDL-C、NO、SOD、SAQ评分升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组LDL-C、HCT、EAI、cTnT、IL-1β、IL-18水平显著低于对照组,HDL-C、NO、SOD、SAQ评分高于对照组,两组比较差异具有统计学意义(P0.05)。结论丹参多酚酸盐联合尼可地尔治疗冠心病心绞痛具有较好的临床疗效,可明显改善患者胸闷、胸部绞痛、心电图等症状体征,调节血脂代谢和血液流变学状态,抑制炎症反应,调控氧化应激,具有一定的临床推广应用价值。     

Two generation reproduction and teratogenicity studies of feeding cyadox in Wistar rats

To investigate the teratogenic potential and reproductive toxicity of cyadox, a growth promoting agent, Wistar rats (F₀) were fed with diets containing cyadox (0, 50, 150 and 2500 mg/kg) or olaquindox (150 mg/kg), approximately equivalent to cyadox 5, 15, 250 or olaquindox 15 mg/kg b.w./day across two generations. Half of the pregnant rats (F₀, F_1b) were subjected to caesarean section on gestational day 20 for teratogenic examination and the other half produced pups F_1a and F_2a, respectively. At the 250 mg/kg b.w./day cyadox group, body weights of F_1b pregnant rats and F_2a on day 21 after birth decreased; fetal body lengths and tail lengths decreased; the number of fetal resorptions increased significantly; litter weights, number of viable fetuses decreased; number of embryo resorptions increased significantly; number of liveborn F_1a, F_1b and F_2a decreased. No macroscopic or microscopic change of any significance was found in the reproductive organs. Significant increases in the incidence of cervial ribs or lumbar ribs in F_2a pups and significant increases of relative organ weight of testis and epididymis in F_1b were observed at the 250 mg/kg b.w./day cyadox group. The NOAEL for reproduction/development of cyadox for rats was estimated to be 150 mg/kg diet, which was equivalent to approximately 15 mg/kg b.w./day.     

小檗碱抑制HCT116细胞生长与Wnt/β-catenin信号的关系研究

目的研究小檗碱对结肠癌细胞的增殖抑制作用与Wnt/β-catenin信号的关系。方法结晶紫染色法检测小檗碱对HCT116细胞增殖的抑制作用,采用流式分析及West-ern blot研究小檗碱诱导HCT116细胞凋亡;Western blot检测β-catenin蛋白表达、RT-PCR法检测β-catenin mRNA表达,确定小檗碱对其表达的影响;采用外源性过表达β-cate-nin研究小檗碱抑制HCT116细胞增殖与β-catenin的关系。结果小檗碱处理组细胞较对照组细胞增殖明显受到抑制,并诱导HCT116细胞凋亡。小檗碱处理组全细胞、胞质及核内β-catenin蛋白水平均明显较对照组低。外源性过表达β-catenin能减弱小檗碱对HCT116细胞增殖的抑制作用。小檗碱处理组β-catenin mRNA表达明显受到抑制。结论小檗碱能抑制HCT116细胞增殖并抑制Wnt/β-catenin信号转导,其机制可能与下调β-catenin mRNA表达有关。     

人HCT116结肠癌细胞系中CD133+结肠癌干细胞分离及鉴定

目的 从人结肠癌细胞系(HCT116)中分离鉴定结肠癌干细胞,并观察其体外生物学特性.方法 利用RT-PCR、免疫荧光、流式细胞等技术检测HCT116细胞中CD133的表达情况;利用免疫磁珠分选技术分选CD133+细胞;采用无血清培养基培养分选后的CD133+细胞鉴定其体外增殖特性;采用含血清培养基诱导干细胞克隆球分化并采用免疫组化检测CK20表达情况鉴定其分化特性.结果 HCT116细胞系中存住CD133+细胞,免疫磁珠能有效的分选CD133+细胞,分选后的阳性含量为91.92%,分选后的阳性细胞具有典型干细胞的体外增殖、分化特性.结论 CD133+结肠癌干细胞在体外具有和普通干细胞类似的无限增殖、自我更新和分化能力,同时它们也表达ABCG2等耐药相火蛋白.     

RB but not R‐HCVAD is a feasible induction regimen prior to auto‐HCT in frontline MCL: results of SWOG Study S1106

Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto‐HCT ) is effective for younger patients with mantle cell lymphoma (MCL ). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyperCVAD /MTX /ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH ) versus rituximab plus bendamustine (RB ) in a randomized phase II trial to select a pre‐transplant induction regimen for future development. Patients had previously untreated stage III , IV , or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB , followed by auto‐HCT . Fifty‐three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2‐year progression‐free survival (PFS ) was 81% vs. 82% and overall survival (OS ) was 87% vs. 88% for RB and RH , respectively. RH is not an ideal platform for future multi‐centre transplant trials in MCL . RB achieved a 2‐year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL .     

Circadian Rhythmicity as a Predictor of Quality of Life in Allogeneic Hematopoietic Cell Transplant Patients

Context

Quality of life (QoL) is increasingly recognized as an important outcome of cancer treatment. Previous studies have examined clinical predictors of QoL, but with the increasing prevalence of wearable sensors that monitor sleep and activity patterns, further investigation into whether these behaviors are predictive of post-treatment QoL is now feasible. Among patients receiving aggressive cancer treatment such as hematopoietic cell transplantation (HCT), analysis of circadian rhythms (24-hour patterns of sleep and activity) via wearable sensors is limited.