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11.
Fabrice Barlesi Edward B. Garon Dong-Wan Kim Enriqueta Felip Ji-Youn Han Joo-Hang Kim Myung-Ju Ahn Mary Jo Fidler Matthew A. Gubens Gilberto de Castro Veerle Surmont Qiao Li Anne C. Deitz Gregory M. Lubiniecki Roy S. Herbst 《Journal of thoracic oncology》2019,14(5):793-801
Introduction
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献12.
Keith P. Reber John D. Sivey Matthew Vollmuth Priyansh D. Gujarati 《Journal of labelled compounds & radiopharmaceuticals》2022,65(9):254-263
Parabens are antimicrobial additives found in a wide array of consumer products. However, the halogenated compounds formed from parabens during wastewater disinfection are a potential environmental concern. In order to identify these transformation products and investigate their mechanism of formation, a synthetic route to ethyl parabens labeled with the stable isotope carbon-13 at specific positions within the benzene ring was developed. This efficient two-step procedure starts from commercially available 13C-labeled phenols and involves (1) initial acylation of the phenol via a Houben–Hoesch reaction with trichloroacetonitrile followed by (2) a modified haloform reaction of the resulting trichloromethyl ketone to afford the corresponding 13C-labeled ethyl parabens in 65%–80% overall yield. The scope of the modified haloform reaction was also investigated, allowing for the synthesis of other parabens derived from primary or secondary alcohols, including 13C- and deuterium-labeled esters. In addition, 4-hydroxybenzoic acid can be formed directly from the common trichloromethyl ketone intermediate upon treatment with lithium hydroxide. This protocol complements existing methods for preparing 13C-labeled paraben derivatives and offers the specific advantages of exhibiting complete regioselectivity in the Houben–Hoesch reaction (to form the para-disubstituted product) and avoiding the need for protecting groups in the modified haloform reaction that forms the paraben esters. 相似文献
13.
《Saudi Pharmaceutical Journal》2022,30(6):669-678
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
15.
《Clinical Lymphoma, Myeloma & Leukemia》2020,20(8):e461-e467
IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed. 相似文献
16.
裴宇 《中国继续医学教育》2020,(13):131-133
目的探讨他克莫司联合308nm准分子激光在面部白癜风治疗中的应用效果。方法选取2017年2月-2019年2月医院84例面部白癜风患者为研究对象,根据入院单双号将受试者进行分组,其中对照组42例患者接受308nm准分子激光治疗,研究组42例患者在对照组的基础上联合他克莫司软膏治疗,比较两组患者治疗后1个月、3个月时的治疗总有效率以及治疗前后白斑面积与皮损区IL-17水平变化。结果研究组患者在治疗后1个月、3个月时的治疗总有效率均显著高于对照组(P<0.05),与治疗前相比,治疗后两组患者白斑面积及皮损区IL-17水平均显著减少,且研究组显著少于对照组(P<0.05)。结论他克莫司联合308nm准分子激光可有效缩小白斑面积,降低皮损区IL-17水平,疗效确切。 相似文献
17.
《药学学报(英文版)》2020,10(9):1634-1645
Systematic administration of anti-inflammatory cytokine interleukin 4 (IL-4) has been shown to improve recovery after cerebral ischemic stroke. However, whether IL-4 affects neuronal excitability and how IL-4 improves ischemic injury remain largely unknown. Here we report the neuroprotective role of endogenous IL-4 in focal cerebral ischemia–reperfusion (I/R) injury. In multi-electrode array (MEA) recordings, IL-4 reduces spontaneous firings and network activities of mouse primary cortical neurons. IL-4 mRNA and protein expressions are upregulated after I/R injury. Genetic deletion of Il-4 gene aggravates I/R injury in vivo and exacerbates oxygen-glucose deprivation (OGD) injury in cortical neurons. Conversely, supplemental IL-4 protects Il-4−/− cortical neurons against OGD injury. Mechanistically, cortical pyramidal and stellate neurons common for ischemic penumbra after I/R injury exhibit intrinsic hyperexcitability and enhanced excitatory synaptic transmissions in Il-4−/− mice. Furthermore, upregulation of Nav1.1 channel, and downregulations of KCa3.1 channel and α6 subunit of GABAA receptors are detected in the cortical tissues and primary cortical neurons from Il-4−/− mice. Taken together, our findings demonstrate that IL-4 deficiency results in neural hyperexcitability and aggravates I/R injury, thus activation of IL-4 signaling may protect the brain against the development of permanent damage and help recover from ischemic injury after stroke. 相似文献
18.
目的探讨负载 IL-4 和 BMP-2 的氧化石墨烯(graphene oxide,GO)-羧甲基壳聚糖(carboxymethyl chitosan,CMC)凝胶诱导巨噬细胞 M2 型分化及对 BMSCs 成骨分化的影响。方法取 CMC、GO 制备混合溶液后,分别添加 PBS、IL-4、BMP-2 或 IL-4+BMP-2,在交联剂作用下制备单纯或负载不同因子的 GO-CMC 凝胶支架;取单纯 GO-CMC 凝胶表征观测,包括大体、扫描电镜及傅里叶变换红外吸收光谱仪(Fourier transform infrared spectroscopy,FTIR)检测,以单纯 CMC 凝胶作为对照;取负载不同因子的 GO-CMC 凝胶行体外缓释实验。取 4~5 周龄 SPF 级 SD 雌性大鼠分离培养巨噬细胞,分别与单纯以及负载不同因子的 GO-CMC 凝胶培养,24 h 后行 CD206 免疫荧光检测巨噬细胞分化情况;取第 3 代大鼠 BMSCs 分别与单纯以及负载不同因子的 GO-CMC 凝胶成骨诱导培养,10 d 后行 ALP 染色观测早期成骨,21 d 行茜素红染色观测晚期成骨。结果大体观察 GO-CMC 凝胶呈棕色、半透明状;扫描电镜观察示,GO-CMC 凝胶孔径及孔壁厚度与单纯 CMC 凝胶相似,但内壁粗糙度增加;FTIR 检测显示 CMC 发生聚合形成凝胶。体外缓释实验示 3 种负载不同因子的 GO-CMC 凝胶缓释性能相似,均呈线性缓慢释放因子。CD206 免疫荧光检测示 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化,ALP 及茜素红染色示 GO-CMC 凝胶可诱导 BMSCs 成骨分化;其中负载 IL-4+BMP-2 的 GO-CMC 凝胶作用最显著(P<0.05)。 结论负载 IL-4 和 BMP-2 的 GO-CMC 凝胶可诱导巨噬细胞 M2 型分化,增强 BMSCs 成骨分化能力,为后期骨缺损修复及骨免疫调节研究提供了新的策略。 相似文献
19.
《Journal of tissue viability》2020,29(3):180-183
AimTo develop a treatment paradigm for chronic leg ulcers that incorporates new biomarkers of wound healing with currently available therapies.MethodsRecently published data on GM-CSF and MMP-13 as biomarkers of venous leg ulcer (VLU) healing status with accuracies of 92% and 78% respectively, was reviewed along with the wound bed preparation (WBP) theoretical framework for treatment of chronic wounds. The broad categories of wound treatments that align with the WBP concepts were identified. These were then considered in a hierarchical order that initially improves the wound bed and subsequently incorporates more complex advanced wound therapies. Identification of the non-healing status of the wound is the driver to advance through the different treatments.ResultsA point of care test of wound healing status is the key to the systematic use of currently available therapies for chronic leg ulcers in a timely fashion. The different therapies address – debridement, moisture control, bacterial contamination, protease inhibition, formation of granulation tissue, application of growth factors, application of matrix constructs, and application of cellular components. Progression through this hierarchical order of therapies is directed by the leg ulcer remaining in a non-healing state with the previous therapies having been implemented.ConclusionCombining a validated point of care test of wound healing with a systematic approach to wound therapies, has the potential to create a new paradigm of chronic leg ulcer treatment - biomarker directed wound therapy. 相似文献
20.
Regina K. Rowe David M. Pyle J. David Farrar Michelle A. Gill 《European journal of immunology》2020,50(10):1550-1559
Rhinovirus (RV) infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate DC antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 development. In this study, we investigate the effects of IgE-mediated stimulation on monocyte-driven, RV-induced T cell development utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 differentiation. This increase in RV-induced Th2 development was regulated by IgE-mediated inhibition of virus-induced type I IFN and induction of IL-10. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations—IgE-mediated stimulation and rhinovirus infection—may synergistically promote Th2 differentiation and allergic inflammation. 相似文献