cancers

癌症
  • 文章类型: Journal Article
    肥胖和肥胖相关蛋白(FTO),最早鉴定的mRNAN6-甲基腺苷(M6A)脱甲基酶,已知在几个生物过程中发挥关键作用。因此,FTO是抗癌治疗的有希望的靶标。了解FTO靶标的生物学功能和调节机制可以作为药物开发的指南。尽管在开发FTO抑制剂方面做出了巨大努力,到目前为止,还没有特异性的小分子抑制剂进入临床试验。在这份手稿中,我们回顾了FTO与各种癌症之间的关系,从药物化学和其他领域的角度开发了针对FTO靶标的小分子抑制剂,并描述了它们的结构优化过程和结构-活性关系,为他们未来的发展方向提供线索。
    [方框:见正文]。
    Adiposity and obesity-related proteins (FTO), the earliest identified mRNA N6-methyladenosine (m6A) demethylases, are known to play crucial roles in several biological processes. Therefore, FTO is a promising target for anticancer treatment. Understanding the biological functions and regulatory mechanisms of FTO targets can serve as guidelines for drug development. Despite significant efforts to develop FTO inhibitors, no specific small-molecule inhibitors have entered clinical trials so far. In this manuscript, we review the relationship between FTO and various cancers, the small-molecule inhibitors developed against FTO targets from the perspective of medicinal chemistry and other fields, and describe their structural optimization process and structure-activity relationship, providing clues for their future development direction.
    [Box: see text].
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    甲状腺结节(TNs)已成为中国最常见的内分泌疾病。细针抽吸(FNA)仍然是评估TN恶性肿瘤的标准诊断方法,尽管大多数FNA结果表明是良性疾病。平衡诊断准确性,同时减轻良性结节患者的过度诊断带来了重大的临床挑战。精确,非侵入性,和高通量筛查方法用于高风险TN诊断是非常需要的,但仍未被探索。开发此类方法可以提高超声成像等非侵入性方法的准确性,并减少由侵入性程序引起的良性结节患者的过度诊断。在这里,我们研究了掺杂金的锆基金属有机骨架(ZrMOF/Au)纳米结构在甲状腺疾病代谢谱中的应用。这种方法能够以高通量高效提取尿液代谢物指纹,低背景噪声,和再现性。利用偏最小二乘判别分析和四种机器学习模型,包括神经网络(NN),随机森林(RF),逻辑回归(LR),和支持向量机(SVM),我们使用诊断小组对甲状腺癌(TC)和低危TNs进行鉴别诊断的准确率提高(98.6%).通过对代谢差异的分析,确定良性结节和恶性肿瘤之间的潜在通路变化。这项工作探索了使用ZrMOF/Au辅助LDI-MS平台快速筛查甲状腺疾病的潜力,为甲状腺恶性肿瘤的无创筛查提供了一种潜在的方法。将这种方法与超声等成像技术相结合,可以增强非侵入性诊断方法用于恶性肿瘤筛查的可靠性。有助于防止不必要的侵入性手术,并降低良性结节患者过度诊断和过度治疗的风险。
    Thyroid nodules (TNs) have emerged as the most prevalent endocrine disorder in China. Fine-needle aspiration (FNA) remains the standard diagnostic method for assessing TN malignancy, although a majority of FNA results indicate benign conditions. Balancing diagnostic accuracy while mitigating overdiagnosis in patients with benign nodules poses a significant clinical challenge. Precise, noninvasive, and high-throughput screening methods for high-risk TN diagnosis are highly desired but remain less explored. Developing such approaches can improve the accuracy of noninvasive methods like ultrasound imaging and reduce overdiagnosis of benign nodule patients caused by invasive procedures. Herein, we investigate the application of gold-doped zirconium-based metal-organic framework (ZrMOF/Au) nanostructures for metabolic profiling of thyroid diseases. This approach enables the efficient extraction of urine metabolite fingerprints with high throughput, low background noise, and reproducibility. Utilizing partial least-squares discriminant analysis and four machine learning models, including neural network (NN), random forest (RF), logistic regression (LR), and support vector machine (SVM), we achieved an enhanced diagnostic accuracy (98.6%) for discriminating thyroid cancer (TC) from low-risk TNs by using a diagnostic panel. Through the analysis of metabolic differences, potential pathway changes between benign nodule and malignancy are identified. This work explores the potential of rapid thyroid disease screening using the ZrMOF/Au-assisted LDI-MS platform, providing a potential method for noninvasive screening of thyroid malignant tumors. Integrating this approach with imaging technologies such as ultrasound can enhance the reliability of noninvasive diagnostic methods for malignant tumor screening, helping to prevent unnecessary invasive procedures and reducing the risk of overdiagnosis and overtreatment in patients with benign nodules.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:核孔复合物(NPC)是复杂且动态的蛋白质结构,其跨越核膜并充当在细胞核和细胞质之间运输分子的看门人。NPC包含多达30种称为核孔蛋白(NUP)的不同蛋白质。然而,越来越多的研究表明,NPC在基因调控中起着重要作用,病毒感染,癌症,有丝分裂,遗传性疾病,肾脏疾病,免疫系统疾病,以及退化性神经和肌肉病变。
    目的:在这篇综述中,介绍了NPCs的结构和功能。然后我们描述了NPCs各组分的生理和病理作用,为将来的临床应用提供了方向。
    方法:本文综述了PubMed的相关文献。
    结论:这篇综述总结了目前关于NPCs在人体生理和病理学中的意义的研究。强调NPC相关疾病的机制基础。
    BACKGROUND: Nuclear pore complexes (NPCs) are sophisticated and dynamic protein structures that straddle the nuclear envelope and act as gatekeepers for transporting molecules between the nucleus and the cytoplasm. NPCs comprise up to 30 different proteins known as nucleoporins (NUPs). However, a growing body of research has suggested that NPCs play important roles in gene regulation, viral infections, cancer, mitosis, genetic diseases, kidney diseases, immune system diseases, and degenerative neurological and muscular pathologies.
    OBJECTIVE: In this review, we introduce the structure and function of NPCs. Then We described the physiological and pathological effects of each component of NPCs which provide a direction for future clinical applications.
    METHODS: The literatures from PubMed have been reviewed for this article.
    CONCLUSIONS: This review summarizes current studies on the implications of NPCs in human physiology and pathology, highlighting the mechanistic underpinnings of NPC-associated diseases.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    与病原体感染相关的癌症逐渐成为全球人类健康的重要威胁,研究病原体致癌机理具有重要意义。当前的机理研究依赖于动物和二维(2D)细胞培养模型,但是传统方法已被证明不足以快速模拟由新病原体引起的疾病。因此,研究重点已经转移到类器官模型上,可以在体外复制靶组织或器官的结构和遗传特征,为研究病原体诱导的致癌机制提供了新的平台。本文综述了类器官技术在四种病原体相关癌症研究中的应用:与幽门螺杆菌相关的胃癌,与乙型肝炎病毒或丙型肝炎病毒相关的肝癌,由大肠杆菌引起的结直肠癌,以及与人乳头瘤病毒有关的宫颈癌。这篇综述还提出了类器官技术在未来优化类器官模型和推进与病原体感染相关的癌症治疗方面的一些局限性。
    Cancers associated with pathogen infections are gradually becoming important threats to human health globally, and it is of great significance to study the mechanisms of pathogen carcinogenesis. Current mechanistic studies rely on animal and two-dimensional (2D) cell culture models, but traditional methods have been proven insufficient for the rapid modeling of diseases caused by new pathogens. Therefore, research focus has shifted to organoid models, which can replicate the structural and genetic characteristics of the target tissues or organs in vitro, providing new platforms for the study of pathogen-induced oncogenic mechanisms. This review summarizes the application of organoid technology in the studies of four pathogen-associated cancers: gastric cancer linked to Helicobacter pylori, liver cancer associated with hepatitis B virus or hepatitis C virus, colorectal cancer caused by Escherichia coli, and cervical cancer related to human papillomavirus. This review also proposes several limitations of organoid technology to optimize organoid models and advance the treatment of cancer associated with pathogen infections in the future.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    Ataxin-2(ATXN2)最初是在脊髓小脑共济失调2型(SCA2)的背景下发现的,但它已经成为各种神经退行性疾病的关键角色。这篇综述探讨了ATXN2在人类疾病中的多方面作用。揭示其不同的分子和细胞途径。ATXN2对疾病的影响超出了功能结果;它主要与各种RNA结合蛋白(RBP)相互作用,以调节疾病中转录后基因表达的不同阶段。随着研究的进展,还发现ATXN2在各种癌症的发展中起重要作用,包括乳腺癌,胃癌,胰腺癌,结肠癌,还有食道癌.这种全面的探索强调了ATXN2在疾病发病机理中的关键作用,值得科学界进一步研究。通过回顾ATXN2在疾病中的调节功能的最新发现,这篇文章帮助我们了解与这种有趣的蛋白质有关的一系列人类疾病的复杂分子机制。
    Ataxin-2 (ATXN2) was originally discovered in the context of spinocerebellar ataxia type 2 (SCA2), but it has become a key player in various neurodegenerative diseases. This review delves into the multifaceted roles of ATXN2 in human diseases, revealing its diverse molecular and cellular pathways. The impact of ATXN2 on diseases extends beyond functional outcomes; it mainly interacts with various RNA-binding proteins (RBPs) to regulate different stages of post-transcriptional gene expression in diseases. With the progress of research, ATXN2 has also been found to play an important role in the development of various cancers, including breast cancer, gastric cancer, pancreatic cancer, colon cancer, and esophageal cancer. This comprehensive exploration underscores the crucial role of ATXN2 in the pathogenesis of diseases and warrants further investigation by the scientific community. By reviewing the latest discoveries on the regulatory functions of ATXN2 in diseases, this article helps us understand the complex molecular mechanisms of a series of human diseases related to this intriguing protein.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    髓源性生长因子(MYDGF)是一种新型分泌蛋白,具有有效的抗凋亡和组织修复特性,存在于近140个人类组织和细胞系中。在口腔上皮和皮肤中丰度最高。最初,在骨髓来源的单核细胞和巨噬细胞中发现MYDGF用于心肌梗死后的心脏保护和修复。随后的研究表明,MYDGF在其他心血管疾病中起着重要作用(例如,动脉粥样硬化和心力衰竭),代谢紊乱,肾脏疾病,自身免疫性/炎症性疾病,和癌症。尽管基本机制尚未得到充分探索,MYDGF在健康和疾病中的作用可能涉及细胞凋亡和增殖,组织修复和再生,抗炎,和糖脂代谢调节。在这次审查中,我们总结了目前在了解MYDGF在健康和疾病中的作用方面的进展,专注于它的结构,功能和机制。图形摘要显示了MYDGF在不同器官和疾病中的当前作用(图。1).
    Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    DNA甲基转移酶(DNMT)在基因组DNA甲基化中起着至关重要的作用。在哺乳动物中,DNMT调节胚胎和成体细胞DNA甲基化的动态模式。DNMT的功能异常通常表明癌症,包括肿瘤抑制基因(TSG)的整体低甲基化和部分高甲基化,加速肿瘤的恶性,使病人的病情恶化,并显著加剧癌症治疗的难度。目前,核苷DNMT抑制剂如氮杂胞苷和地西他滨已被FDA和EMA批准用于治疗急性髓性白血病(AML),慢性粒单核细胞白血病(CMML),骨髓增生异常综合征(MDS)。因此,靶向DNMT是一种非常有前途的抗肿瘤策略。本文就DNMT抑制剂对肿瘤的治疗作用作一综述。旨在通过发现更多具有高活性的DNMT抑制剂,为癌症的治疗提供更多的可能性。高选择性,以及未来良好的药物特性。
    DNA methyltransferases (DNMTs) play a crucial role in genomic DNA methylation. In mammals, DNMTs regulate the dynamic patterns of DNA methylation in embryonic and adult cells. Abnormal functions of DNMTs are often indicative of cancers, including overall hypomethylation and partial hypermethylation of tumor suppressor genes (TSG), which accelerate the malignancy of tumors, worsen the condition of patients, and significantly exacerbate the difficulty of cancer treatment. Currently, nucleoside DNMT inhibitors such as Azacytidine and Decitabine have been approved by the FDA and EMA for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). Therefore, targeting DNMTs is a very promising anti-tumor strategy. This review mainly summarizes the therapeutic effects of DNMT inhibitors on cancers. It aims to provide more possibilities for the treatment of cancers by discovering more DNMT inhibitors with high activity, high selectivity, and good drug-like properties in the future.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    图像引导热消融(IGTA)是介入肿瘤学的重要治疗方式。它广泛用于治疗实体瘤,比如肝脏,肺,乳房,肾,和甲状腺癌。IGTA包括射频消融,微波消融(MWA),冷冻消融,和激光烧蚀。与其他能源相比,MWA具有消融体积大的优点,短消融时间,和低散热效果。MWA也可以诱导抗肿瘤免疫;然而,只有少数患者从中获得临床益处。基于这些数据,MWA和免疫治疗的结合已成为癌症治疗的一个有希望的新方向.本文就目前MWA与免疫治疗结合的研究现状作一综述。讨论了免疫激活的状况以及涉及MWA治疗各种恶性肿瘤的相关研究。
    Image-guided thermal ablation (IGTA) is an important treatment modality for interventional oncology. It is widely used for the treatment of solid tumors, such as liver, lung, breast, kidney, and thyroid cancers. IGTA include radiofrequency ablation, microwave ablation (MWA), cryoablation, and laser ablation. Compared with other energy sources, MWA has the advantage of a large ablative volume, short ablative time, and a low heat sink effect. MWA can also induce antitumor immunity; however, only a minority of patients derive a clinical benefit from it. Based on these data, the combination of MWA and immunotherapy has emerged as a promising new direction for cancer treatment. This review article focuses on current research on the combination of MWA and immunotherapy. The status of immune activation and related studies involving MWA for the treatment of various malignant tumors are discussed.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    由于抗肿瘤药物的大量副作用和不利的药代动力学特征,治疗癌症仍然具有挑战性。尽管近年来在理解肿瘤细胞的性质和作用方面取得了进展。生物材料的进步,如支架,植入物,个性化药物输送系统,量身定制的移植物,细胞表,和其他可移植材料,近年来,医疗保健和医学领域发生了重大变化。明胶是一种适应性很强的天然聚合物,由于其有利的特性,在医疗保健相关行业中得到广泛应用。包括生物相容性,生物降解性,负担能力,和可及的化学基团的存在。明胶在生物医学领域中用作生物材料,用于创建药物递送系统(DDS),因为它可以应用于各种合成程序。明胶纳米颗粒(NPs)已被广泛用作药物和基因的载体,专门针对癌症等患病组织,结核病,和艾滋病毒感染,以及治疗血管痉挛和再狭窄。这主要是由于它们的生物相容性和自然降解的能力。明胶具有需要更多阐明的多种潜在应用。本文综述了明胶及其衍生物在癌症诊断和治疗中的应用。生物材料和生物反应器的进步,加上对生物材料新兴应用的日益理解,在提高肿瘤治疗的疗效方面取得了进展。
    Treating cancer remains challenging due to the substantial side effects and unfavourable pharmacokinetic characteristics of antineoplastic medications, despite the progress made in comprehending the properties and actions of tumour cells in recent years. The advancement of biomaterials, such as stents, implants, personalised drug delivery systems, tailored grafts, cell sheets, and other transplantable materials, has brought about a significant transformation in healthcare and medicine in recent years. Gelatin is a very adaptable natural polymer that finds extensive application in healthcare-related industries owing to its favourable characteristics, including biocompatibility, biodegradability, affordability, and the presence of accessible chemical groups. Gelatin is used as a biomaterial in the biomedical sector for the creation of drug delivery systems (DDSs) since it may be applied to various synthetic procedures. Gelatin nanoparticles (NPs) have been extensively employed as carriers for drugs and genes, specifically targeting diseased tissues such as cancer, tuberculosis, and HIV infection, as well as treating vasospasm and restenosis. This is mostly due to their biocompatibility and ability to degrade naturally. Gelatins possess a diverse array of potential applications that require more elucidation. This review focuses on the use of gelatin and its derivatives in the diagnosis and treatment of cancer. The advancement of biomaterials and bioreactors, coupled with the increasing understanding of emerging applications for biomaterials, has enabled progress in enhancing the efficacy of tumour treatment.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    Endomucin(MUC14),由EMCN基因编码,是一种O-糖基化的跨膜粘蛋白,主要存在于静脉内皮细胞(EC)中,并在骨组织的H型血管中高度表达。其主要生物学功能包括通过血管内皮生长因子(VEGF)信号通路促进内皮生成和迁移,抑制炎症细胞与ECs的粘附。此外,它诱导血管生成并促进骨形成。由于Endomucin在上述方面的优异功能,为血管炎症相关疾病和骨疾病的治疗提供了新的研究靶点。根据目前对其功能的理解,子宫内膜蛋白的研究主要集中在上述两种疾病上。众所周知,癌症的进展与血管生成密切相关。最近发现子宫内膜蛋白在多种肿瘤中差异表达,并与生存率相关。子宫内膜蛋白在癌症中的生物学作用是不清楚的。本文介绍了Endomucin在血管炎症相关疾病和骨疾病中的研究进展,探讨了其在治疗中的应用价值和前景,并收集了子宫内膜蛋白在肿瘤中的最新研究情况,以期为拓展Endomucin的研究领域提供有意义的证据。
    Endomucin (MUC14), encoded by EMCN gene, is an O-glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory-related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory-related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号