MM, multiple myeloma

MM,多发性骨髓瘤
  • 文章类型: Journal Article
    在过去的二十年中,各种含硼药物已被批准用于临床。更多的人目前正在临床试验中。对含硼化合物的兴趣日益增加是由于其与生物靶标的独特结合特性;例如,硼取代可用于调节生物活性,药代动力学特性,和抗药性。从这个角度来看,我们旨在全面回顾硼化合物在药物发现中的现状,特别关注2015年至2020年12月的进展。我们将这些化合物分为显示抗癌的组,抗菌,抗病毒,抗寄生虫和其他活动,并讨论与每个活动相关的生物目标,以及潜在的未来发展。
    Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.
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  • 文章类型: Journal Article
    主要炎症性疾病的发生和发展,即,癌症,血管炎症,一些自身免疫性疾病与免疫系统密切相关。基于生物制品的免疫疗法正在对这些疾病发挥关键作用,而免疫调节剂的使用总是受到各种因素的限制,例如体内酶消化的敏感性,穿过生物屏障的穿透力差,和网状内皮系统的快速清除。药物递送策略对于促进其递送是有效的。在这里,我们回顾了针对主要炎症性疾病的免疫疗法的潜在靶标,讨论了免疫治疗中涉及的生物制剂和药物递送系统,特别强调了批准的治疗策略,最后提供了这一领域的观点。
    The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.
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  • 文章类型: Journal Article
    大量研究证实,长链非编码RNA(lncRNAs)广泛参与代谢和免疫等关键生理过程,与肿瘤的发生发展密切相关,心血管疾病,神经系统疾病,肾病,和其他疾病。lncRNAs作为生物标志物或干预靶标的应用可以为疾病的诊断和治疗提供新的见解。本文集中于lncRNAs作为药理学靶标的新兴研究,并回顾了lncRNAs从疾病编码的作用到作为候选药物的转变。包括临床前研究的现状和进展。已经总结了lncRNA调控的前沿策略,包括lncRNA相关药物的来源,比如基因技术和小分子化合物,和相关的交付方式。还讨论了lncRNA靶向药物临床试验的最新进展。这些信息将为基于lncRNA的药物的研发提供最新的参考。
    Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.
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  • 文章类型: Journal Article
    环状RNA(circularRNAs,circRNAs)是一类非常令人感兴趣的保守单链RNA分子,其通过前体mRNA反向剪接衍生自外显子或内含子序列。与典型的线性RNA不同,circRNAs形成共价闭合,连续的稳定环,没有5'端盖和3'末端聚(A)尾部,因此对外切核酸酶消化有抗性。大多数circRNAs是高度丰富的,并在不同物种中保守,具有组织或发育阶段特异性表达。circRNAs已被证明作为microRNA海绵发挥重要作用,基因剪接和转录的调节因子,RNA结合蛋白海绵和蛋白/肽翻译。新的证据表明,circRNAs在各种人类疾病中起作用,特别是癌症,并可能作为癌症治疗更好的预测生物标志物和治疗靶点。考虑到它们潜在的临床相关性,circRNAs已成为肿瘤病理领域新的研究热点。在本研究中,目前对生物发生的理解,特点,数据库,研究方法,生物学功能亚细胞分布,表观遗传调控,讨论了circRNAs的细胞外运输和降解。特别是,首先总结了circRNA研究中涉及的多个数据库和方法,以及确定circRNAs在肿瘤生长中潜在作用的最新进展,移民和入侵,这使得circRNAs更好的预测生物标志物,被描述。此外,提出了circRNAs在癌症患者管理中的临床应用的未来观点,这可以为将来的circRNAs提供新的见解。
    Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5\'end cap and 3\'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.
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  • 文章类型: Case Reports
    胃肠道的髓外浆细胞瘤(EMP)极为罕见。EMPs的临床表现多种多样,取决于肿瘤的位置和进展。在这里,我们报告了一个80岁的EMP累及直肠的病例,排便习惯改变的男性患者.计算机断层扫描证实了一个界限,等衰减质量具有明显的异质增强。患者接受腹腔镜手术切除,浆细胞瘤最终经病理证实。此外,我们对胃肠道EMP进行了文献综述,以获得进一步的研究。最后,我们发现影像学检查没有特异性。EMP的诊断仍取决于组织病理学。
    Extramedullary plasmacytoma (EMP) of the gastrointestinal tract is an extreme rarity. Clinical manifestations of EMPs are varied, depending on the position and progress of tumor. Here we report a case of an EMP involving rectum in an 80-year-old, male patient with a change of bowel habit. Computed tomography scanning confirmed a circumscribed, iso-attenuating mass with the obvious heterogeneous enhancement. Patient received the surgical resection by laparoscope and the plasmacytoma was finally confirmed by the pathology. Furthermore, we made a literature review about the EMP of gastrointestinal tract to get the further study. Finally, we found out there is no specificity in imaging examination. Diagnosis of EMP still depends on the histopathology.
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  • 文章类型: Journal Article
    由细胞周期的失调和细胞周期蛋白依赖性激酶(CDK)的活化引起的持续细胞增殖是癌症的标志。抑制CDK是开发抗癌药物的一个非常有前途和有吸引力的策略。特别是,第三代CDK抑制剂可以选择性抑制CDK4/6,通过抑制G1向S期的转变来调节细胞周期,在抗癌功效和一般毒性之间表现出完美的平衡。迄今为止,三种选择性CDK4/6抑制剂已获得美国食品和药物管理局(FDA)的批准,和15CDK4/6抑制剂正在临床试验中用于治疗癌症。从这个角度来看,我们讨论了CDK4/6在调节细胞周期和癌细胞中的关键作用,分析选择性抑制CDK4/6用于癌症治疗的基本原理,回顾了具有不同化学支架的高选择性CDK4/6抑制剂的最新进展,解释与CDK4/6抑制剂抵抗相关的机制,并描述克服这一问题的解决方案,并简要介绍了蛋白水解靶向嵌合体(PROTAC),一种用于降解CDK4/6的新的革命性技术。
    The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases (CDKs) is a hallmark of cancer. The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs. In particular, third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition, exhibiting a perfect balance between anticancer efficacy and general toxicity. To date, three selective CDK4/6 inhibitors have received approval from the U.S. Food and Drug Administration (FDA), and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers. In this perspective, we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells, analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment, review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds, explain the mechanisms associated with CDK4/6 inhibitor resistance and describe solutions to overcome this issue, and briefly introduce proteolysis targeting chimera (PROTAC), a new and revolutionary technique used to degrade CDK4/6.
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  • 文章类型: Journal Article
    多发性骨髓瘤(MM)是第二种无法治愈的血液恶性肿瘤。近年来,由于microRNA(miRNA)的兴起,许多学者参与了其在MM诊断中的价值研究,并获得了良好但不一致的结果。因此,为了确定miRNA在MM早期诊断中的作用,我们进行了荟萃分析.
    我们搜索了相关研究,包括PubMed,WebofScience,EMBASE,科克伦图书馆,中国国家知识基础设施(CNKI)和万方数据库截至2020年7月20日进行本元分析。为了提高准确性,使用诊断准确性研究2(QUADAS-2)的质量评估.我们还应用随机效应模型来总结敏感性和特异性,正似然比(PLR),负似然比(NLR),诊断比值比(DOR)和曲线下面积(AUC)来测量诊断值,和亚组分析用于发现潜在的异质性来源。
    我们最终从15篇文章中收集了32项研究,其中包括2053例MM患者和1118例健康对照。整体灵敏度,特异性,PLR,NLR,DOR和AUC分别为0.81、0.85、5.5、0.22、25和0.90。亚组分析显示,血浆类型样本量较大的microRNA簇下调可以对MM患者进行更好的诊断准确性。此外,未发现发表偏倚.
    循环miRNA可能是MM早期诊断的潜在非侵入性生物标志物。然而,多中心,更严格,需要更大规模的研究来验证我们的结论.
    UNASSIGNED: Multiple myeloma (MM) is the second incurable hematological malignancy. In recent years, due to the rise of microRNA (miRNA), many scholars have participated in the study of its value in the diagnosis of MM, and have obtained good but inconsistent results. Therefore, in order to determine the role of miRNA in the early diagnosis of MM, we performed this meta-analysis.
    UNASSIGNED: We searched for related studies including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Database as of July 20, 2020 to conduct this meta-analysis. To improve the accuracy, the quality assessment of Diagnostic Accuracy Study 2 (QUADAS-2) was used. We also applied random effects models to summarize sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) to measure diagnostic values, and subgroup analysis used to discover potential sources of heterogeneity.
    UNASSIGNED: We finally collected 32 studies from 15 articles that included a total of 2053 MM patients and 1118 healthy controls in this meta-analysis. The overall sensitivity, specificity, PLR, NLR, DOR and AUC were 0.81, 0.85, 5.5, 0.22, 25 and 0.90, respectively. Subgroup analysis shows that the down-regulation of microRNA clusters with larger samples size of plasma type could carry out a better diagnostic accuracy of MM patients. In addition, publication bias was not found.
    UNASSIGNED: Circulating miRNA could be a potential non-invasive biomarker for early diagnosis of MM. However, multi-center, more rigorous, and larger-scale studies are needed to verify our conclusions.
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  • 文章类型: Journal Article
    骨转移和多发性骨髓瘤(MM)都是恶性疾病,在影像学上可出现溶骨性,并且难以区分。虽然正电子发射断层扫描/计算机断层扫描(PET/CT)已被证明可用于诊断各种骨病变,PET/CT和组织病理学与这些疾病之间的相关性尚不清楚。这项回顾性研究调查了区分MM和骨转移的最佳截止标准摄取值(SUV)。
    新诊断的溶骨性病变(n=344)和疑似恶性肿瘤的患者接受了氟脱氧葡萄糖(FDG)PET/CT和活检/手术。FDG摄取和形态学变化(例如,软组织肿块形成)与病理结果进行比较。
    共评估了8896个溶骨性病变。MM溶骨性病变的SUVmax(1.6±0.7)明显低于骨转移灶的SUVmax(5.5±2.7;p=0.000)。鉴别MM和骨转移的最佳阈值SUVmax为2.65(敏感性86.1%,特异性94.7%;p=0.000)。软组织肿块骨病变的SUVmax高于单纯溶骨病变的SUVmax(p=0.000)。骨转移患者中软组织肿块(7%)的百分比高于MM患者(2%)。骨转移的平均SUVmax为5.5±2.7(0.4-30.4);原发性肿瘤的SUVmax为7.5±4.2(1.0-28.5)。骨转移的SUVmax与原发肿瘤的SUVmax显著相关(r=0.532;p=0.000)。
    FDGPET/CT是鉴别溶骨性病变的有价值的工具。SUVmax鉴别MM与骨转移的最佳临界值为2.65。骨转移的SUVmax与原发肿瘤的SUVmax之间的显着相关性有助于检测原发肿瘤。
    UNASSIGNED: Both bone metastases and multiple myeloma (MM) are malignant diseases that can appear osteolytic on imaging and are difficult to differentiate. While positron emission tomography/computed tomography (PET/CT) has been demonstrated useful for the diagnosis of various bone lesions, correlations between PET/CT and histopathology and these diseases are unclear. This retrospective study investigated the optimal cutoff standardized uptake value (SUV) to differentiate MM and bone metastasis.
    UNASSIGNED: Patients with newly diagnosed osteolytic lesions (n = 344) and suspected malignancy underwent both fluorodeoxyglucose (FDG) PET/CT and biopsy/surgery. FDG uptake and morphologic changes (e.g., soft tissue mass formation) were compared with pathological results.
    UNASSIGNED: A total of 8896 osteolytic lesions were evaluated. The SUVmax of MM osteolytic lesions (1.6 ± 0.7) was significantly lower than that of bone metastases (5.5 ± 2.7; p = 0.000). The best cutoff SUVmax for differentiating MM and bone metastasis was 2.65 (sensitivity 86.1%, specificity 94.7%; p = 0.000). The SUVmax of bone lesions of soft tissue mass was higher than that for pure osteolytic lesions (p = 0.000). A greater percentage of patients with bone metastasis had a soft tissue mass (7%) than did patients with MM (2%). The mean SUVmax of bone metastases was 5.5 ± 2.7 (0.4-30.4); that of primary tumors was 7.5 ± 4.2 (1.0-28.5). The SUVmax of bone metastases significantly correlated with the SUVmax of primary tumors (r = 0.532; p = 0.000).
    UNASSIGNED: FDG PET/CT is a valuable tool to differentiate osteolytic lesions. The best cutoff value of SUVmax for differentiating MM from bone metastasis is 2.65. The significant correlation between the SUVmax of bone metastasis and that of primary tumors is helpful for detecting primary tumors.
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  • 文章类型: Journal Article
    人类间充质基质细胞(MSC)在表型上与成纤维细胞共享其国际细胞和基因治疗学会(ISCT)标志物CD73、CD90和CD105的阳性表达。成纤维细胞通常作为来自活检的不需要的副产物被共分离,并且它们可以在培养物中快速过度生长MSC。的确,已经提出了许多其他表面标记,尽管尚未鉴定出独特的MSC特异性标记。定量PCR(qPCR)是一种精确的,高效、快速的基因表达分析方法。为了识别适合于准确的MSC表征的标记,利用qPCR。
    两种商业获得的骨髓(BM)衍生的MSC和hTERT永生化的BM-MSC系(MSC-TERT)在RNA提取之前在不同的氧水平下培养不同的天。连同先前从脐带来源的MSCs和MSC-TERT细胞培养在2D或3D中提取的RNA样品,对该异质样本集的18个候选MSC标记基因的表达水平进行了定量分析.将MSC中的表达水平与成纤维细胞中的表达水平进行比较以验证这些基因在MSC和成纤维细胞之间的分化能力。ISCT标记物都不能区分成纤维细胞和MSC。总共六个其他基因(ALCAM,CLIC1,EDIL3,EPHA2,NECTIN2和TMEM47)被鉴定为准确鉴定MSC的可能生物标志物。
    根据表达式级别的考虑,可靠性和特异性,活化的白细胞粘附分子(ALCAM)是改善MSC鉴定的生物标志物组的最佳候选物。
    UNASSIGNED: Human mesenchymal stromal cells (MSCs) phenotypically share their positive expression of the International Society for Cell and Gene Therapy (ISCT) markers CD73, CD90 and CD105 with fibroblasts. Fibroblasts are often co-isolated as an unwanted by-product from biopsy and they can rapidly overgrow the MSCs in culture. Indeed, many other surface markers have been proposed, though no unique MSC specific marker has been identified yet. Quantitative PCR (qPCR) is a precise, efficient and rapid method for gene expression analysis. To identify a marker suitable for accurate MSC characterisation, qPCR was exploited.
    UNASSIGNED: Two commercially obtained bone marrow (BM) derived MSCs and an hTERT immortalised BM-MSC line (MSC-TERT) have been cultured for different days and at different oxygen levels before RNA extraction. Together with RNA samples previous extracted from umbilical cord derived MSCs and MSC-TERT cells cultured in 2D or 3D, this heterogeneous sample set was quantitatively analysed for the expression levels of 18 candidate MSC marker genes. The expression levels in MSCs were compared with the expression levels in fibroblasts to verify the differentiation capability of these genes between MSCs and fibroblasts. None of the ISCT markers could differentiate between fibroblasts and MSCs. A total of six other genes (ALCAM, CLIC1, EDIL3, EPHA2, NECTIN2, and TMEM47) were identified as possible biomarkers for accurate identification of MSCs.
    UNASSIGNED: Justified by considerations on expression level, reliability and specificity, Activated-Leukocyte Cell Adhesion Molecule (ALCAM) was the best candidate for improving the biomarker set of MSC identification.
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