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More Than an Adipokine: The Complex Roles of Chemerin Signaling in Cancer.

Chemerin is widely recognized as an adipokine, with diverse biological roles in cellular differentiation and metabolism, as well as a leukocyte chemoattractant. Research investigating the role of chemerin in the obesity-cancer relationship has provided evidence both for pro- and anti-cancer effects. The tumor-promoting effects of chemerin primarily involve direct effects on migration, invasion, and metastasis as well as growth and proliferation of cancer cells. Chemerin can also promote tumor growth via the recruitment of tumor-supporting mesenchymal stromal cells and stimulation of angiogenes

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… Similarly, several studies have reported increased expression of chemerin in SCCOT tissues compared to adjacent non-cancerous tissues and in OSC cancer-associated myofibroblasts (CAMs) compared to adjacent tissue myofibroblasts (ATMs) [ 55 , 57 ]. … Abbreviations AKT | protein kinase B APC | APC regulator of Wnt signaling pathway ATM | adjacent tissue myofibroblast BCSC | breast cancer stem cell BE | Barrett’s esophagus BPH | benign prostatic hyperplasia CA125 | cancer antigen 125 CA 15-3 | cancer antigen 15-3 CAM | cancer associated myofibroblast …

Mesenchymal stem cells lineage and their role in disease development.

BackgroundMesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for differen

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… myofibroblasts in response to chemokine Cxcl4 secretion by activated platelets, eliciting BMF (Schneider et al. 2017 ) (Fig. 3 ). … The CA-MSCs are pluripotent cells that can differentiate into tumor microenvironment components, including fibroblasts, myofibroblasts, and adipocytes. …

The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy.

The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the "Trinity" in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the "Trinity" members in the tu

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… Molecule | Cell Type | Mechanism | Reference TGFβ | T reg | TGFβ from T reg activates SMA + myofibroblasts and their expression of CCR1 ligands to recruit MDSC | [ 109 ] CXCL12 | CAF | CXCL12 from FAP + CAF increases T cell exclusion and cancer growth | [ 110 ] Type I collagen | Myofibroblast | Type … Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15(+) Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy. Cancer Discov. 2020;10:232–253. doi: 10.1158/2159-8290.CD-19-0644. 46. …

Role of Chitinase 3-like-1 in Myelofibrosis via Fibroblast-Produced Extracellular Matrix Enhancement.

Cluster of differentiation 14+ monocytes produced spindle-shaped fibrocytes, similar to fibroblasts. Recent studies have reported that fibrocytes are crucial for the development and progression of primary myelofibrosis (MF); however, their functional role remains unclear. We compared monocytes and fibrocytes using RNA sequencing for gene expression profiles. We focused on chitinase 3-like-1 (CHI3L1), which causes inflammation, organ fibrosis, and extracellular tissue remodeling. We found higher CHI3L1 levels in patients with myeloproliferative neoplasm with MF than in those without MF. Further

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… Montgomery et al. ( 2017 ) revealed that CHI3L1 activates myofibroblasts, thereby promoting renal fibrosis in a mouse model of ischemia‐reperfusion injury. … CHI3L1 represents the missing link between fibrocytes and myofibroblasts and may serve as a novel therapeutic target for MF. …

AAV-DJ Enables Targeted Gene Modulation in Human Ovarian Cells.

STUDY QUESTION: Can adeno-associated viruses (AAVs) efficiently and safely transduce human primary granulosa cells and human ovarian stromal fibroblasts to modulate the expression of genes involved in follicle recruitment and ovarian microenvironment regulation? SUMMARY ANSWER: AAVs can efficiently transduce human primary granulosa cells and human ovarian stromal cells with low toxicity, with the serotype DJ (AAV-DJ) demonstrating superior performance. AAVs enable targeted modulation of ovarian genes such as AMHR2 in human primary granulosa cells and TGF β 1 in human ovarian stromal cells, su

Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver.

In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis.

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… differentiation. 113 In these experiments, CXCL4 was shown to induced myofibroblast differentiation of Gli1+ cells comparable to induction with TGF-β, a known stimulus for differentiation of MSCs into myofibroblasts. 113 Other cytokines Oncostatin M (OSM), is a pleiotropic cytokine belonging to the … Leptin-receptor-expressing bone marrow stromal cells are myofibroblasts in primary myelofibrosis. Nat Cell Biol. 2017;19(6):677–688. doi: 10.1038/ncb3530. 92. Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J. 2004;18(7):816–827. doi: 10.1096/fj.03-1273rev. 93. …

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinica

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia.

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-2

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… There are also reports that TGF-β released by tumor cells also allows AMSCs to differentiate into myofibroblasts. Created with Biorender.com . … Interestingly, it has also been shown that breast cancer-derived EVs induced tumor progression through AMSC differentiation into myofibroblasts, which contributed to extracellular matrix remodeling and angiogenesis [ 149 , 150 ] . …

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compar

Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.

CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic

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… Previous study reported that the origin of myofibroblasts in the kidney fibrosis was 50% arising from local resident fibroblasts and 35% from bone marrow [ 44 ]. … Another report showed that 60% of α-SMA-positive myofibroblasts derived from bone-marrow derived cells via the process of macrophage-myofibroblast transition [ 45 ]. The origin of myofibroblasts remains controversial. …

Acquired Platythorax, or Anteroposterior Flattening of the Chest Wall, as a Late Complication of Cyclophosphamide Treatment for Childhood Acute Lymphoblastic Leukemia, Presenting in a Young Man with Respiratory Failure.

BACKGROUND Acquired platythorax, or flattening of the chest with a reduction in the anteroposterior (AP) diameter, is very rare and the prognosis depends on the degree of the deformity, respiratory function, and on any underlying disease. Drug-induced pulmonary fibrosis is associated with pulmonary hypoplasia. A case of acquired platythorax is presented in a young man previously treated with cyclophosphamide in childhood. CASE REPORT A 20-year-old man began to experience cough, chest pain, and mild exertional dyspnea. He was admitted to the hospital at 23 years of age with respiratory failure.

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… Reddy et al. reported that depletion of the transcription factor PPARg in lung fibroblasts induced a profibrotic phenotype, and that activation of PPARg promoted dedifferentiation in lung myofibroblasts in an animal model in vivo [ 17 ]. … Reddy AT Lakshmi SP Zhang Y Reddy RC Nitrated fatty acids reverse pulmonary fibrosis by dedifferentiating myofibroblasts and promoting collagen uptake by alveolar macrophages FASEB J 2014 28 5299 310 25252739 10.1096/fj.14-256263 PMC4232282 18. …

Malignant Neoplasms Arising in the Cardiac Pacemaker Cavity: A Systematic Review.

Cancer is the abnormal proliferation of physiologically inadequate cells. Studies have identified the cardiac pacemaker pocket as a site of rare neoplasms. To evaluate the clinical outcomes, treatment, prognosis, and individualized management of tumors originating in the cardiac pacemaker pocket, a systematic review was conducted using case reports and case series available in the PubMed/Medline, Science Direct, Cochrane Central, LILACS, and Scientific Electronic Library Online (Scielo) databases. Pacemaker pocket tumors affected patients with a mean age of 72.9 years, with a higher incidence

Рецепт 1 в диабете и его хронические осложнения: механизмы сигнализации и новые терапевтические достижения.

Диабет моллюсков (DM) — системное метаболическое расстройство, характеризующееся хронической гипергликемией, которая может оказывать воздействие на почки, сетчатку, периферийные нервы и сердечно-сосудистую систему, что в конечном счете приводит к многочисленным хроническим осложнениям. 1 (PAR1) — G-белковый рецептор, приводимый в действие через каноническое декольте, например тромбинированный декольте и неканоническое декольте, например, декольте с помощью активированного белка C или матрицы Metalloproteinase-1. Эти режимы активации инициируют различные каналы подачи сигналов вниз по течению,

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… PAR1 is highly expressed in the fibrovascular membranes of proliferative diabetic retinopathy (PDR), particularly in vascular endothelial cells, CD45-positive leukocytes, and myofibroblasts, which are involved in angiogenesis and inflammation. … Under high-glucose conditions, kallikrein-related peptidase 8 (KLK8) is upregulated and proteolytically activates PAR1, promoting cardiac fibroblast-to-myofibroblast transition, collagen synthesis, and cell migration. …

Idiopathic pulmonary fibrosis: Current and future treatment.

ObjectivesIdiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma and architecture is destroyed, compliance is lost, and gas exchange is compromised in this debilitating condition that leads inexorably to respiratory failure and death within 3-5 years of diagnosis. This review discusses treatment approaches to IPF in current use and those that appear promising for future development.Data sourceThe data were obtained from the Randomized Controlled Trials and scientific studies published in En

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… Constant micro‐injuries to aging alveolar epithelium are believed to lead to disrupted epithelial–fibroblast communication, which culminates in recruitment and activation of myofibroblasts that produce collagen‐rich extracellular matrix. … Further, HuR knockdown reduced TGFβ‐driven morphological changes indicative of myofibroblast differentiation. 144 This link between HuR and myofibroblast transformation may indicate a potential new target for IPF treatment. …

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease.

AimTo assess the toxicity, tolerance, steroid-sparing capacity, effectiveness, and response rate to imatinib and dasatinib for the treatment of severe sclerotic chronic graft-vs-host disease (scGVHD).MethodsThis retrospective study analyzed 8 consecutive patients with severe refractory scGVHD who received salvage therapy with imatinib. Patients intolerant and/or refractory to imatinib received dasatinib treatment.Results7 patients discontinued imatinib treatment (1 achieved complete response, 5 were resistant and/or intolerant, and 1 developed grade IV neutropenia) and 1 patient achieved prolo

Bradyarrhythmias Associated with Oncologic Treatment-An Updated Review.

Background/Objectives: Bradyarrhythmias are an under-recognized component of cancer therapy-related cardiovascular toxicity. As survivorship improves and exposure to targeted and immune therapies increases, clinicians increasingly face clinically relevant sinus node dysfunction and atrioventricular (AV) conduction disease that may interrupt otherwise effective oncologic treatment. We aimed to synthesize evidence on the incidence, phenotype, mechanisms, and management of bradyarrhythmias across major anticancer drug classes. Methods: We performed a narrative review of PubMed and major clinical

Mesenchymal Stromal Cells in Neuroblastoma: Exploring Crosstalk and Therapeutic Implications.

Neuroblastoma (NB) is the second most common solid cancer in childhood, accounting for 15% of cancer-related deaths in children. In high-risk NB patients, the majority suffers from metastasis. Despite intensive multimodal treatment, long-term survival remains <40%. The bone marrow (BM) is among the most common sites of distant metastasis in patients with high-risk NB. In this environment, small populations of tumor cells can persist after treatment (minimal residual disease) and induce relapse. Therapy resistance of these residual tumor cells in BM remains a major obstacle for the cure of NB.

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… MSCs and CAFs MSCs were first associated with CAFs after BM-derived myofibroblasts were reported to accumulate in tumor stroma and to constitute up to 25% of stromal fibroblasts [ 80–83 ]. … Development of myofibroblasts from human bone marrow mesenchymal stem cells cocultured with human colon carcinoma cells and TGF beta 1 . In Vitro Cell Dev Biol Anim 36 : 77 – 80 10718362 10.1290/1071-2690(2000)036<0077:domfhb>2.0.co;2 81. …

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chroni

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… Based on the aforementioned literature observations, the main pathway towards IPF is the activation and proliferation of fibroblasts, as ECM components can only be over-expressed when myofibroblasts are formed. … For example, the upregulation of HDAC1 and 2 activity stimulates the TGF-β pathway as well as induces EMT [ 213 ] and ECM overproduction; and promotes fibroblast–myofibroblast transformation as well as cell migration. …

Advanced Diagnostic Techniques

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… (Not present in: hematopoietic cells, fibroblasts, neurons, chondrocytes, osteoblasts, myofibroblasts) Extracellular matrix Collagen: Cross-striated periodicity of 50 nm, 50- to 100-nm-thick. … Myofibroblastic tumors. (Not present in smooth muscle tumors and fibrosarcomas) Filaments, intermediate About 10 nm thick. Located in cytoplasmic matrix. Noncytokeratin: vimentin, desmin, neurofilaments, glial filaments. Impossible to distinguish them by EM. …