高活性的人白细胞介素-3突变体的构建与表达

目的:在大肠杆菌中构建表达高活性的人白细胞介素-3(hIL-3)突变体。方法:通过定点突变的方法构建hIL-3突变体K116V和K116W的表达载体,并实现hIL-3突变体在大肠杆菌中的表达。对所得包涵体蛋白依次溶解、纯化、透析复性。用Westernblot检测hIL-3突变体的特异性。单溶液细胞增殖(MTS)测定hIL-3突变体的生物学活性。结果:hIL-3在大肠杆菌中高效表达,表达量占菌体总蛋白的40%以上,主要以包涵体的形式存在。将包涵体溶解在8mol/L脲中,经Ni-NTA-Sepharose柱纯化后纯度达90%以上。MTS法测定hIL-3突变体K116V的活性为野生型的5倍,K116W的生物学活性也有所增加。结论:获得了高活性的hIL-3突变体K116V,有望成为hIL-3的替代品,也证明了hIL-3第116位的赖氨酸残基对于hIL-3的生物学活性很重要。     

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.     

Sequence Analysis Demonstrates that VP6, NSP1 and NSP4 Genes of Indian Neonatal Rotavirus Strain 116E are of Human Origin

We have sequenced the genes encoding the inner capsid protein VP6 and the nonstructural proteins NSP1 and NSP4 of the Indian neonatal serotype P8[11]G9 human/bovine reassortant candidate vaccine rotavirus strain 116E. These three genes share a high degree of sequence and deduced amino acid homology with human prototype strain Wa. Our results confirm and extend those of previous RNA-RNA hybridization studies which suggested that these genes are of human origin, and will facilitate examination of the host immune response to 116E induced by natural infection and vaccination. This revised version was published online in July 2006 with corrections to the Cover Date.     

Metabolism and excretion study of DW116, a new fluoroquinolone, in rats

Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential. Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound,¹⁹F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were 28.6±2.7% and 36.4±1.8% of the administered dose and the corresponding biliary recoveries were 14.4±5.5% and 37.0±7.6%, respectively.     

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?     

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.

Midterm Outcomes of the Dissected Aorta Repair Through Stent Implantation Trial

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