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61.
Aldo Cannata Silvia Cantoni Antonio Sciortino Giuseppe Bruschi Claudio Francesco Russo 《Journal of the American College of Cardiology》2021,77(18):2323-2334
Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients. 相似文献
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目的 基于网络药理学和分子对接技术探究黄芪-赤芍配伍对治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的作用机制。方法 利用TCMSP,Pharmmaper数据库,筛选黄芪-赤芍治疗COPD的活性成分和潜在靶点;结合Genecards数据库挖掘的COPD相关靶点,对黄芪-赤芍药对与COPD靶点进行PPI网络构建,交互处理得到黄芪-赤芍药对治疗COPD的关键靶点,并进行GO分析和KEGG通路富集分析;并采用分子对接技术将主要活性成分与TNF-α(肿瘤坏死因子),IL-6(白细胞介素6)等进行分子对接;最后利用A549炎症细胞与人脐静脉内皮细胞缺氧损伤模型进行体外细胞实验对结果加以验证。结果 黄芪-赤芍药对中44个有效成分作用于COPD,核心成分为:槲皮素、山奈酚、丁子香萜、芍药苷、(2R,3R)-4-methoxyl-distylin、二氢异黄酮;黄芪-赤芍药对通过IL6、PTGS2、TNF等113个靶蛋白,调控Ras、PI3KAkt、IL-17等多条信号通路治疗COPD,且分子对接结果显示槲皮素、山奈酚、丁子香萜、芍药苷与IL-6、PTGS2、TNF大分子蛋白有良好的结合性,体外细胞试验证实,槲皮素与山奈酚均能减少IL-8,MMP-9炎症因子的分泌,具有不同程度的抗炎效果;芍药苷有明显的扩血管、抗血栓之效。结论 黄芪-赤芍药对治疗COPD具有多成分、多靶点、多通路、整体调节的作用特点。初步揭示了黄芪-赤芍药对通过抑制炎症反应、调节上皮细胞生长增强保护屏障等预测出黄芪-赤芍药对治疗COPD的潜在作用机制,以期为其活性成分的药效物质基础提供理论研究和思路。 相似文献
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66.
《Journal of thoracic oncology》2021,16(8):1379-1391
IntroductionBrain metastases (BMs) occur in 40% of patients with lung cancer. The activity of immunotherapy in these patients, however, remains controversial, as the cornerstone treatment is radiotherapy (RT). Because RT is associated with adverse events that may impair the quality of life, the possibility of substituting it with a single systemic approach is attractive. Therefore, we performed a systematic review and meta-analysis to evaluate the potential benefit of immune checkpoint inhibitors (ICIs) in patients with NSCLC with untreated BM (unBM).MethodsStudies that enrolled patients with NSCLC treated with ICIs and specifically allowed for unBM were identified by searching the EMBASE, PubMed, Cochrane, and other databases. The outcomes evaluated were intracerebral overall response rate (icORR) and intracerebral disease control rate (icDCR) for unBM, and grades 3 and 4 toxicity rate.ResultsWe included 12 studies with a total of 566 individuals in the final analysis. Anti–programmed cell death protein-1 therapy seems to be active in the central nervous system, with an icORR of 16.4% (95% confidence interval [CI]: 9.8%–24%; I2 = 33.17%) and an icDCR of 45% (95% CI: 33.4%–56.9%; I2 = 46.91%). In the meta-analysis for icORR (risk ratio = 1.26, 95% CI: 0.57–2.79) and icDCR (risk ratio = 0.88, 95% CI: 0.55–1.43) we did not observe any difference among patients with BM who were treated with RT before ICI start and those who were treated with ICI only.ConclusionsICI seems to be effective as a single treatment for active BM in selected patients with advanced NSCLC. 相似文献
67.
Pauline A. J. Mendelaar Jaco Kraan Mai Van Leonie L. Zeune Leon W. M. M. Terstappen Esther Oomende Hoop John W. M. Martens Stefan Sleijfer 《Molecular oncology》2021,15(1):116
Circulating tumor cells (CTCs) in the blood of cancer patients are of high clinical relevance. Since detection and isolation of CTCs often rely on cell dimensions, knowledge of their size is key. We analyzed the median CTC size in a large cohort of breast (BC), prostate (PC), colorectal (CRC), and bladder (BLC) cancer patients. Images of patient‐derived CTCs acquired on cartridges of the FDA‐cleared CellSearch® method were retrospectively collected and automatically re‐analyzed using the accept software package. The median CTC diameter (μm) was computed per tumor type. The size differences between the different tumor types and references (tumor cell lines and leukocytes) were nonparametrically tested. A total of 1962 CellSearch® cartridges containing 71 612 CTCs were included. In BC, the median computed diameter (CD) of patient‐derived CTCs was 12.4 μm vs 18.4 μm for cultured cell line cells. For PC, CDs were 10.3 μm for CTCs vs 20.7 μm for cultured cell line cells. CDs for CTCs of CRC and BLC were 7.5 μm and 8.6 μm, respectively. Finally, leukocytes were 9.4 μm. CTC size differed statistically significantly between the four tumor types and between CTCs and the reference data. CTC size differences between tumor types are striking and CTCs are smaller than cell line tumor cells, whose size is often used as reference when developing CTC analysis methods. Based on our data, we suggest that the size of CTCs matters and should be kept in mind when designing and optimizing size‐based isolation methods.
Abbreviations
- ACCEPT
- Automated CTC Classification, Enumeration, and PhenoTyping software
- BC
- breast cancer
- BLC
- bladder cancer
- CD
- computed diameter
- CEL
- cultured tumor cell (cell line)
- CK
- cytokeratin
- CRC
- colorectal cancer
- CTC‐L
- circulating tumor cells derived from cerebrospinal fluid (liquor)
- CTCs
- circulating tumor cells
- DAPI
- 4′6‐diamidino‐2‐phenylindole
- EMT
- epithelial–mesenchymal transition
- EpCAM
- epithelial cell adhesion molecule
- IQR
- interquartile range
- KW test
- Kruskal–Wallis test
- MWU test
- Mann–Whitney U test
- NCR
- nucleus/cytoplasm ratio
- P2A
- perimeter to area
- PC
- prostate cancer
- TIF
- tagged Image Format files
- TXT
- text file
- μm
- micrometer
- µm2
- square micrometers
68.
Emilie M.J. van Brummelen Sanne Huijberts Carla van Herpen Ingrid Desar Frans Opdam Robin van Geel Serena Marchetti Neeltje Steeghs Kim Monkhorst Bas Thijssen Hilde Rosing Alwin Huitema Jos Beijnen Rene Bernards Jan Schellens 《The oncologist》2021,26(4):290-e545
Lessons Learned
- Afatinib and selumetinib can be combined in continuous and intermittent dosing schedules, albeit at lower doses than approved for monotherapy.
- Maximum tolerated dose for continuous and intermittent schedules is afatinib 20 mg once daily and selumetinib 25 mg b.i.d.
- Because the anticancer activity was limited, further development of this combination is not recommended until better biomarkers for response and resistance are defined.
69.
指突状树突细胞肉瘤(interdigitating dendritic cell sarcoma,IDCS)是一种罕见的树突状细胞肿瘤,目前全球仅百余例报道,常以无痛性淋巴结肿大起病,侵袭性较强、预后较差[1-2]。骨髓增生异常综合征(myelodysplastic syndromes,MDS)为起源于造血干、祖细胞的恶性克隆性疾病,以单系或多系病态造血、易向白血病转化为特征,目前被认为是一种老年性疾病[3]。本研究报道1例同患IDCS和MDS的患儿,为国内外首次报道2种肿瘤同时发生,旨在探讨2种肿瘤的诊治要点,避免漏诊、误诊。 相似文献