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Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in pro

Длинная и извилистая дорога: гомеостатические и беспорядочные микроэкологические ниши: обзор описательной части.

Микроэкологические ниши Haematopoiet были охарактеризованы как "приемники" крови и иммунной системы. Эти ниши меняются во время онтгении, при этом костный мозг становится доминирующим местом гематопоисиса в послеродовой жизни в стабильных условиях. Для определения структуры и функции различных микроэкологических ниш гематопоиета необходимо четко определить конкретные подмножества гематопоиетических стеблей и потомковых клеток во время офгении и понять их временной внешний вид и анатомическое позиционирование. Различные гематопоиетические и негематопоиетические клетки способствуют появлению гем

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… . 247 The inhibition of proliferation with the onset of senescence has been attributed, at least in part, to dysregulation of epigenetic control mechanisms (DNA methylation, histone modifications, chromatin reorganisation), metabolic changes (e.g., in autophagosome formation) and alterations in the secretome … bias in haematopoiesis, with loss of ASXL1 causing RNA polymerase II transcriptional deregulation and altering HSPC maintenance gene expression (e.g., VCAM1) in these bone marrow MSCs. 260 Ageing or senescent MSCs adopt a senescent-associated secretory phenotype which importantly incorporates into its secretome …

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

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… NOTCH1 mediates a switch between two distinct secretomes during senescence. Nat. Cell Biol. 2016;18:979–992. doi: 10.1038/ncb3397. 47. Passos J.F., Nelson G., Wang C., Richter T., Simillion C., Proctor C.J., Miwa S., Olijslagers S., Hallinan J., Wipat A., et al. … Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer. 2009;9:81–94. doi: 10.1038/nrc2560. 104. Campisi J., d’Adda di Fagagna F. Cellular senescence: When bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 2007;8:729–740. doi: 10.1038/nrm2233. 105. …

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

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… Separately, we have shown the ratio of Gas5 within cells and its secretome varies with the disease state [ 10 ]. Results from our RNA-FISH/IF analysis showed that Gas5 colocalized with tau in PS19 mice was disrupted with NPC86 treatment. …

An Overview of Current Research on Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Bibliometric Analysis From 2009 to 2021.

Background: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are important mediators of intercellular communication and participate in numerous physiological and pathological processes in the body. This study aims to introduce the research status, analyze the research hotspots, and predict the development trend through bibliometric analysis of MSC-EVs. Methods: We searched all relevant literature on MSC-EVs from 2009 to 2021 in the Web of Science. R-bibliometrix, VOSviewer, and CiteSpace software were used to visualize the quantitative analysis of the published literature, includ

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… In recent years, it has been demonstrated that the biological effects of MSCs largely depend on their secretome/EVs. …

The Fibronectin Expression Determines the Distinct Progressions of Malignant Gliomas via Transforming Growth Factor-Beta Pathway.

Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. We

Silencing SFRP1 in bone mesenchymal stem cells alleviates pediatric B-ALL-driven bone loss by activating Wnt/β-catenin signaling.

BackgroundBone loss is the most common skeletal complication of childhood acute lymphoblastic leukemia (ALL) and seriously affects the long-term survival quality of children. However, the mechanisms behind bone loss are complicated and need to be elucidated. This study seeks to examine the principal parameters influencing the osteogenic development of bone marrow mesenchymal stem cells (BMSCs) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) experiencing bone loss, and to identify viable ways for alleviating bone loss.MethodsFirstly, bone mass of adolescent B-ALL patients

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… Engineering a pro-osteogenic secretome through the transient silencing of the gene encoding secreted frizzled related protein 1 Int J Mol Sci 24 15 2023 [eng] 10.3390/ijms241512399 PMC10419110 37569774 14 You Y. Liu J. Zhang L. Li X. Sun Z. Dai Z. …

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety.

Multiple myeloma (MM) is the second most common haematological neoplasm of adults in the Western world. Overall survival has doubled since the advent of proteosome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. However, patients with adverse cytogenetics or high-risk disease as determined by the Revised International Staging System (R-ISS) continue to have poorer outcomes, and triple-refractory patients have a median survival of less than 1 year. Bispecific antibodies (BsAbs) commonly bind to a tumour epitope along with CD3 on T-cells, leading to T-cell activatio

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… Cyclophosphamide alters the tumor cell secretome to potentiate the anti-myeloma activity of daratumumab through augmentation of macrophage-mediated antibody dependent cellular phagocytosis. Oncoimmunology. 2021;10:1859263. doi: 10.1080/2162402X.2020.1859263. 41. …

Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy.

Plasmacytoid dendritic cells (pDCs) are multifaceted immune cells with a wide range of innate and adaptive immunological functions. They constitute the first line of defence against multiple viral infections and have also been reported to actively participate in antitumor immune responses. The clinical implication of the presence of pDCs in the tumor microenvironment (TME) is still ambiguous, but it is clear that pDCs possess the ability to modulate tumor-specific T cell responses and direct cytotoxic functions. Therapeutic strategies designed to exploit these qualities of pDCs to boost tumor-

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… Collapse of the Plasmacytoid Dendritic Cell Compartment in Advanced Cutaneous Melanomas by Components of the Tumor Cell Secretome. Cancer Immunol. Res. 2019;7:12–28. doi: 10.1158/2326-6066.CIR-18-0141. 40. …

Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process.

Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients' quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence,

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… The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015;522:106–110. doi: 10.1038/nature14492. 103. Brechbuhl H.M., Barrett A.S., Kopin E., Hagen J.C., Han A.L., Gillen A.E., Finlay-Schultz J., Cittelly D.M., Owens P., Horwitz K.B., et al. …

Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were

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… The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2 Mol. Cell 65 2017 730 742.e5 28212753 10.1016/j.molcel.2017.01.021 PMC5316415 70 Zhou M. Liu X. Li Z. Huang Q. Li F. Li C.-Y. …

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… Summary/conclusion : In summary, here we are showing a functional role for exosomes as part of the senescent secretome being mediators of paracrine senescence. … MiRokine expression decreased in cells in parallel to an increase in the secretome. The amount of miRokines per vesicle remained constant in large vesicles but increased in sEV after cytokine exposure. …

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidenc

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… Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in oa: A pilot study PLoS ONE 2018 13 e0194591 10.1371/journal.pone.0194591 29547667 PMC5856400 32. Yoneda T. Mechanisms of preferential metastasis of breast cancer to bone Int. J. …

Bone Loss, Osteoporosis, and Skeletal Fragility: Hidden Consequences of Cancer Cachexia.

Cancer cachexia (CC) is a devastating, multi-organ syndrome historically defined by the progressive wasting of skeletal muscle and adipose tissue. However, emerging evidence suggests that the skeletal system is also a major, yet underappreciated target of this catabolic state. While bone loss in oncology is primarily attributed to skeletal metastasis or cancer treatment-induced bone loss (CTIBL), clinical and preclinical data has increasingly demonstrated that tumor and host-derived systemic signals can drive severe bone deterioration even in non-metastatic disease. This review synthesizes cur

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… This discrepancy could be explained by differences in the tumor-derived secretome or in tumor growth kinetics; the shorter duration of the C26 model (~14 days) compared with HT-29 (~47 days) may indicate that bone resorption requires a longer time to develop than muscle wasting. …

Schwann Cell Activity in the Multiple Sclerosis Microenvironment.

Schwann cell (SC)-based therapy is currently being debated as an approach to promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). The main limitation of SC transplantation in MS patients is the short-term functional activity of SCs in the CNS environment. The goal of this study was to determine phenotypic, functional, and signaling changes in human SCs treated with CSF samples from MS patients in vitro, and to characterize the molecular mechanisms underlying SC injury response in the model MS mic

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… New insights into peripheral nerve regeneration: The role of secretomes. Exp. Neurol. 2022;354:114069. doi: 10.1016/j.expneurol.2022.114069. 70. Xiao J., Wong A.W., Willingham M.M., van den Buuse M., Kilpatrick T.J., Murray S.S. …

Biopsy Techniques for Musculoskeletal Tumors: Basic Principles and Specialized Techniques.

Biopsy is a pivotal component in the diagnostic process of bone and soft tissue tumors. The objective is to obtain adequate tissue without compromising local tumor dissemination and the patient's survival. This review explores contemporary principles and practices in musculoskeletal biopsies, emphasizing the critical role of diagnostic accuracy while also delving into the evolving landscape of liquid biopsies as a promising alternative in the field. A thorough literature search was done in PubMed and Google Scholar as well as in physical books in libraries to summarize the available biopsy tec

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… Liquid Biopsy in Chemoresistant Primary and Secondary Bone Tumors Recent research indicates that the tumor secretome, including DNA fragments from drug-resistant cells with mutations, is abundant in plasma, making blood-based liquid biopsy crucial [ 89 ]. …

An overview of cancer health disparities: new approaches and insights and why they matter.

Cancer health disparities remain stubbornly entrenched in the US health care system. The Affordable Care Act was legislation to target these disparities in health outcomes. Expanded access to health care, reduction in tobacco use, uptake of other preventive measures and cancer screening, and improved cancer therapies greatly reduced cancer mortality among women and men and underserved communities in this country. Yet, disparities in cancer outcomes remain. Underserved populations continue to experience an excessive cancer burden. This burden is largely explained by health care disparities, lif

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… Yoshimoto, S. et al. (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature, 499, 97–101. 186. Forslund, K. et al. ; MetaHIT consortium. (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. …

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy.

The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and

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… Computational reconstruction of the human skeletal muscle secretome. Proteins 2006;62:776–92. 10.1002/prot.20803 30. Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 2006;12:6–33. 31. Shephard RJ. …

The Role of Interleukin-1 in the Pathogenesis of Cancer and its Potential as a Therapeutic Target in Clinical Practice.

Interleukin-1 (IL-1) has long been known to be a key mediator of immunity and inflammation. Its dysregulation has been implicated in recent years in tumorigenesis and tumor progression, and its upregulation is thought to be associated with many tumors. Overexpression of the IL-1 agonists IL-1α and IL-1β has been shown to promote tumor invasiveness and metastasis by inducing the expression of angiogenic genes and growth factors. IL-1 blockers such as anakinra and canakinumab are already approved and widely used for the treatment of some autoimmune and autoinflammatory diseases and are currently

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… Yoshimoto S Loo TM Atarashi K Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome Nature 2013 499 7456 97 101 23803760 10.1038/nature12347 62. …

The potential of mesenchymal stem cells in the management of radiation enteropathy.

Although radiotherapy is effective in managing abdominal and pelvic malignant tumors, radiation enteropathy is still unavoidable. This disease severely affects the quality of life of cancer patients due to some refractory lesions, such as intestinal ischemia, mucositis, ulcer, necrosis or even perforation. Current drugs or prevailing therapies are committed to alleviating the symptoms induced by above lesions. But the efficacies achieved by these interventions are still not satisfactory, because the milieus for tissue regeneration are not distinctly improved. In recent years, regenerative ther

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… Martimianaki G Riminucci M Kalmanti M Study of oncogenic transformation in ex vivo expanded mesenchymal cells, from paediatric bone marrow Cell Prolif 2008 41 909 922 19040569 10.1111/j.1365-2184.2008.00559.x PMC6496314 Zimmerlin L Park TS Zambidis ET Donnenberg VS Donnenberg AD Mesenchymal stem cell secretome …