Cancer pathophysiology

  • 文章类型: Journal Article
    癌症是一种多方面的疾病,经常与几种生物过程的失调有关。SLPI是参与调节免疫应答和抑制蛋白酶活性的多功能蛋白。SLPI作为蛋白酶的抑制剂,发挥抗菌性能,并通过核因子-κB(NF-κB)途径抑制促炎基因的转录。该蛋白质作为调节剂的作用已与各种类型的癌症有关。最近的研究表明,SLPI在癌细胞中的上调增强了上皮恶性肿瘤的转移能力,表明这种蛋白质的有害作用。此外,SLPI与其他促癌因子相互作用错综复杂,包括基质金属蛋白酶-2(MMP-2),MMP-9,NF-κB和Akt通路,和p53上调的细胞凋亡调节剂(PUMA)。本文综述了SLPI在癌症病理生理学中的作用。强调其在癌细胞和组织中的表达,它作为预后生物标志物的潜力,以及它作为癌症治疗靶点的治疗前景。SLPI在癌症中的作用机制,包括它的抗炎作用,细胞增殖和血管生成的调节,和肿瘤微环境的调节,已被调查。已经讨论了SLPI在癌症中的临床意义,包括其作为诊断和预后生物标志物的潜力,它在化学抗性中的作用,以及它在几种癌症中的治疗潜力,如肝细胞癌(HCC),结直肠癌(CRC),胰腺癌,头颈部鳞状细胞癌(HNSCC),卵巢癌(OvCa),前列腺癌(PC),胃癌(GC),乳腺癌,和其他癌症。此外,我们强调了SLPI在癌症中的重要性,这为癌症治疗的潜在靶点提供了新的视角。
    Cancer is a multifaceted disorder frequently linked to the dysregulation of several biological processes. The SLPI is a multifunctional protein involved in the modulation of immunological response and the inhibition of protease activities. SLPI acts as an inhibitor of proteases, exerts antibacterial properties, and suppresses the transcription of proinflammatory genes through the nuclear factor-kappa B (NF-κB) pathway. The role of this protein as a regulatory agent has been implicated in various types of cancer. Recent research has revealed that SLPI upregulation in cancer cells enhances the metastatic capacity of epithelial malignancies, indicating the deleterious effects of this protein. Furthermore, SLPI interacts intricately with other cancer-promoting factors, including matrix metalloproteinase-2 (MMP-2), MMP-9, the NF-κB and Akt pathways, and the p53-upregulated modulator of apoptosis (PUMA). This review provides an overview of the role of SLPI in cancer pathophysiology, emphasizing its expression in cancer cells and tissues, its potential as a prognostic biomarker, and its therapeutic promise as a target in cancer treatment. The mechanisms of SLPI action in cancer, including its anti-inflammatory effects, regulation of cell proliferation and angiogenesis, and modulation of the tumor microenvironment, have been investigated. The clinical implications of SLPI in cancer have been discussed, including its potential as a diagnostic and prognostic biomarker, its role in chemoresistance, and its therapeutic potential in several types of cancer, such as hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic cancer, head and neck squamous cell carcinoma (HNSCC), ovarian cancer (OvCa), prostate cancer (PC), gastric cancer (GC), breast cancer, and other cancers. In addition, we emphasized the significance of SLPI in cancer, which offers fresh perspectives on potential targets for cancer therapy.
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  • 文章类型: Journal Article
    癌症是全球高死亡率的原因,也是卫生系统的巨大负担。癌细胞具有独特的特性,例如高增殖速率,自我更新,转移,和治疗抗性,因此,癌症新诊断的发展是一项繁琐的任务。外泌体由几乎所有细胞类型分泌,并具有携带多种对细胞间通讯至关重要的生物分子的能力。因此,在癌症的发病和扩散中起着至关重要的作用。这些外泌体组分可用于开发用于各种癌症的诊断和预后目的的标志物。这篇综述主要强调了以下主题:外泌体结构和功能,外泌体的分离和表征策略,外泌体内容物在癌症中的作用,特别关注非编码RNA和蛋白质,外泌体,和癌症微环境的相互作用,癌症干细胞,以及基于外泌体的肿瘤诊断和预后。
    Cancer is a cause of high deaths worldwide and also a huge burden for the health system. Cancer cells have unique properties such as a high rate of proliferation, self-renewal, metastasis, and treatment resistance, therefore, the development of novel diagnoses of cancers is a tedious task. Exosomes are secreted by virtually all cell types and have the ability to carry a multitude of biomolecules crucial for intercellular communication, hence, contributing a crucial part in the onset and spread of cancer. These exosomal components can be utilized in the development of markers for diagnostic and prognostic purposes for various cancers. This review emphasized primarily the following topics: exosomes structure and functions, isolation and characterization strategies of exosomes, the role of exosomal contents in cancer with a focus in particular on noncoding RNA and protein, exosomes, and the cancer microenvironment interactions, cancer stem cells, and tumor diagnosis and prognosis based on exosomes.
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  • 文章类型: Journal Article
    癌症是一个全球性的问题,预计它将对我们持续的全球健康危机产生重大影响。随着人口老龄化,我们看到癌症发病率增加,但是在不同的地理区域和癌症类型的生存率上观察到相当大的差异。乳腺癌和前列腺癌都是全球发病率和死亡率的主要原因。尽管癌症统计数据表明乳腺癌和前列腺癌预防的某些领域有所改善,诊断,和治疗,这些统计数据清楚地表明需要改善我们对这种疾病的理解,危险因素,以及改善所有患者寿命和生活质量的干预措施,并希望为生活在发达国家和发展中国家的人们提供治疗。这份简明扼要的审查汇编了目前有关统计的资料,病理生理学,危险因素,以及与乳腺癌和前列腺癌相关的治疗方法。
    Cancer is a global issue, and it is expected to have a major impact on our continuing global health crisis. As populations age, we see an increased incidence in cancer rates, but considerable variation is observed in survival rates across different geographical regions and cancer types. Both breast and prostate cancer are leading causes of morbidity and mortality worldwide. Although cancer statistics indicate improvements in some areas of breast and prostate cancer prevention, diagnosis, and treatment, such statistics clearly convey the need for improvements in our understanding of the disease, risk factors, and interventions to improve life span and quality of life for all patients, and hopefully to effect a cure for people living in developed and developing countries. This concise review compiles the current information on statistics, pathophysiology, risk factors, and treatments associated with breast and prostate cancer.
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  • 文章类型: Journal Article
    目的:为了评估MMP-14在卵巢癌中的作用,进行了系统审查。
    方法:2020年3月,在Pubmed中进行了一项搜索,以MMP-14和卵巢癌作为搜索项。在排除不涉及MMP-14或卵巢癌或不涉及英语的参考文献后,发现的研究分为两类:基础研究和临床病理研究。
    结果:总计,发现94个参考文献,其中33个被排除。在纳入研究的参考列表中发现了另外两篇文章。根据全文,另有4人被排除在外。最终,59项研究被纳入审查,32项基础研究,19项临床病理研究。这两个类别都有8项研究。基础研究表明,MMP-14在卵巢癌的增殖过程中起着重要作用,入侵,血管生成和转移。在临床病理学研究中,MMP-14表达在大多数具有不良预后特征的肿瘤中发现,但这种免疫组织化学MMP-14测定似乎并不是预后的独立预测因子。
    结论:从这篇关于MMP-14在卵巢癌中的文献的系统综述中可以清楚地看出,MMP-14在卵巢癌的病理生理中起着各种重要作用。这些作用在病理生理学中的确切转化为MMP-14在卵巢癌临床病理研究中的重要性以及抗MMP-14药物的可能治疗作用需要进一步阐明。
    OBJECTIVE: In order to evaluate the role of MMP-14 in ovarian cancer, a systematic review was conducted.
    METHODS: In March 2020, a search in Pubmed was performed with MMP-14 and ovarian cancer as search terms. After exclusion of the references not on MMP-14 or ovarian cancer or not in English, the studies found were classified into two categories: basic research and clinicopathological research.
    RESULTS: In total, 94 references were found of which 33 were excluded. Two additional articles were found in the reference lists of the included studies. Based on the full texts, another 4 were excluded. Eventually, 59 studies were included in the review, 32 on basic research and 19 on clinicopathological research. 8 studies fell in both categories. The basic research studies show that MMP-14 plays an important role in ovarian cancer in the processes of proliferation, invasion, angiogenesis and metastasis. In clinocopathological research, MMP-14 expression is found in most tumours with characteristics of poor prognosis but this immunohistochemical MMP-14 determination does not seem to be an independent predictor of prognosis.
    CONCLUSIONS: From this systematic review of the literature concerning MMP-14 in ovarian cancer it becomes clear that MMP-14 plays various important roles in the pathophysiology of ovarian cancer. The exact translation of these roles in the pathophysiology to the importance of MMP-14 in clinicopathological research in ovarian cancer and possible therapeutic role of anti-MMP-14 agents needs further elucidation.
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  • 文章类型: Journal Article
    BACKGROUND: Exosomes are extracellular nanometric vesicles used by cells to communicate with each other. They are responsible for many pathological conditions, including tumors by transferring regulatory biomolecules that impact target cell activity. Because of their high concentration in exosomes compared with parental cells and the rest of exosomal content, specificity to the cell of origin, and their well-organized sorting mechanism, microRNAs (miRNAs) are thought to be the most potent exosomes cargo and used by scientists to track exosomes and to detect cell activity changes and prognosis in cancer early.
    OBJECTIVE: In this review, the results of studies examining the role of exosomes in cancer pathophysiology and their clinical potential are discussed in detail. Tumor-derived exosomes (TDEs) mediate the dynamic changes of cancer growth and invasion, including local microenvironment remodeling, distance metastasis, angiogenesis, and tumor-associated immunosuppression. They also contribute to hypoxia-induced tumor progression and cancer cell drug resistance. As a result of exosomes being present in all body fluids, it is possible to have early accessible and less-invasive diagnostic and prognostic measures by forming a table for each cancer type and its matched specific miRNAs. Under testing, available therapeutic uses of exosomes include interference of exosomes biogenesis, secretion, or uptake, and recruitment of exosomes as target-specific drug delivery vehicles, and immunostimulatory agents for both cancer patients and healthy population to avoid cancer development from the start.
    CONCLUSIONS: These data suggest that exosomes and exosomal microRNA are directly related to cancer progression mechanisms, and could be used in cancer early diagnosis, prognosis, and therapy.
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  • 文章类型: Journal Article
    It is well established that the role of the tumor microenvironment (TME) in cancer progression and therapeutic resistance is crucial, but many of the underlying mechanisms are still being elucidated. Even with better understanding of molecular oncology and identification of genomic drivers of these processes, there has been a relative lag in identifying and appreciating the cellular drivers of both invasion and resistance. Intercellular communication is a vital process that unifies and synchronizes the diverse components of the tumoral infrastructure. Elucidation of the role of extracellular vesicles (EVs) over the past decade has cast a brighter light on this field. And yet even with this advance, in addition to diffusible soluble factor-mediated paracrine and endocrine cell communication as well as EVs, additional niches of intratumoral communication are filled by other modes of intercellular transfer. Tunneling nanotubes (TNTs), tumor microtubes (TMs), and other similar intercellular channels are long filamentous actin-based cellular conduits (in most epithelial cancer cell types, ~15-500 µm in length; 50-1000+ nm in width). They extend and form direct connections between distant cells, serving as conduits for direct intercellular transfer of cell cargo, such as mitochondria, exosomes, and microRNAs; however, many of their functional roles in mediating tumor growth remain unknown. These conduits literally create a physical bridge to create a syncytial network of dispersed cells amidst the intercellular stroma-rich matrix. Emerging evidence suggests that they provide a cellular mechanism for induction and emergence of drug resistance and contribute to increased invasive and metastatic potential. They have been imaged in vitro and also in vivo and ex vivo in tumors from human patients as well as animal models, thus not only proving their existence in the TME, but opening further speculation about their exact role in the dynamic niche of tumor ecosystems. TNT cellular networks are upregulated between cancer and stromal cells under hypoxic and other conditions of physiologic and metabolic stress. Furthermore, they can connect malignant cells to benign cells, including vascular endothelial cells. The field of investigation of TNT-mediated tumor-stromal, and tumor-tumor, cell-cell communication is gaining momentum. The mixture of conditions in the microenvironment exemplified by hypoxia-induced ovarian cancer TNTs playing a crucial role in tumor growth, as just one example, is a potential avenue of investigation that will uncover their role in relation to other known factors, including EVs. If the role of cancer heterocellular signaling via TNTs in the TME is proven to be crucial, then disrupting formation and maintenance of TNTs represents a novel therapeutic approach for ovarian and other similarly invasive peritoneal cancers.
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  • 文章类型: Journal Article
    细胞间通讯对癌细胞组织和侵袭的生态系统至关重要。识别关键细胞货物及其不同的运输方式是理解癌细胞生长的基本机制的重要考虑因素。缝隙连接,外泌体,和凋亡小体作为介导细胞间转运的物理模式起关键作用。隧道纳米管(TNTs)-基于肌动蛋白的窄细胞质延伸-是独特的结构,有助于直接,长距离的细胞到细胞运输货物,包括microRNA,线粒体,和各种其他亚细胞成分。通过TNTs的货物运输发生在恶性细胞和基质细胞之间,并可能导致传播癌症表型的基因调控变化。更值得注意的是,这些不同分子的转移几乎总是在癌细胞自身之间的通讯中起着关键作用,以抵抗化疗导致的死亡并促进原发性致癌细胞的生长和转移。“系统生物学”的更传统的定义是复杂生物系统的计算和数学建模。这个概念,然而,现在在生物学中更广泛地用于各种环境,包括跨学科的研究领域,专注于生物系统内的复杂相互作用,以及这些相互作用如何引起这些系统的功能和行为。事实上,必须在其本地上下文中理解和重建组件,而不是单独检查它们。在适当的背景下评估癌症生态系统的长期目标是更好地诊断,分类,更准确地预测癌症治疗的结果。沟通对于肿瘤生态系统的发展和进化至关重要。这种相互作用导致癌症进展。作为肿瘤生态系统内细胞间通讯的关键介质,TNT是本文的中心主题。
    Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)-narrow actin-based cytoplasmic extensions-are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components. The transport of cargo via TNTs occurs between malignant and stromal cells and can lead to changes in gene regulation that propagate the cancer phenotype. More notably, the transfer of these varied molecules almost invariably plays a critical role in the communication between cancer cells themselves in an effort to resist death by chemotherapy and promote the growth and metastases of the primary oncogenic cell. The more traditional definition of \"Systems Biology\" is the computational and mathematical modeling of complex biological systems. The concept, however, is now used more widely in biology for a variety of contexts, including interdisciplinary fields of study that focus on complex interactions within biological systems and how these interactions give rise to the function and behavior of such systems. In fact, it is imperative to understand and reconstruct components in their native context rather than examining them separately. The long-term objective of evaluating cancer ecosystems in their proper context is to better diagnose, classify, and more accurately predict the outcome of cancer treatment. Communication is essential for the advancement and evolution of the tumor ecosystem. This interplay results in cancer progression. As key mediators of intercellular communication within the tumor ecosystem, TNTs are the central topic of this article.
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  • 文章类型: Journal Article
    Autotaxin, an ecto-lysophospholipase D encoded by the human ENNP2 gene, is expressed in multiple tissues, and participates in numerous critical physiologic and pathologic processes including inflammation, pain, obesity, embryo development, and cancer via the generation of the bioactive lipid lysophosphatidate. Overwhelming evidences indicate that the autotaxin/lysophosphatidate signaling axis serves key roles in the numerous processes central to tumorigenesis and progression, including proliferation, survival, migration, invasion, metastasis, cancer stem cell, tumor microenvironment, and treatment resistance by interacting with a series of at least six G-protein-coupled receptors (LPAR1-6). This review provides an overview of the autotaxin/lysophosphatidate axis and collates current knowledge regarding its specific role in pancreatic cancer. With a deeper understanding of the critical role of the autotaxin/lysophosphatidate axis in pancreatic cancer, targeting autotaxin or lysophosphatidate receptor may be a potential and promising strategy for cancer therapy.
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