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Advances in Medical Sciences Mar 2022Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential.... (Review)
Review
BACKGROUND
Inflammatory myofibroblastic tumors (IMTs) are rare intermediate-grade neoplasms that have a high recurrence rate after excision and exhibit low metastatic potential. These tumors contain proliferating neoplastic, fibroblastic and myofibroblastic cells, and are also characterized by chronic inflammatory infiltration by lymphocytes, plasma cells, eosinophils, and histiocytes. They belong to the group of inflammatory spindle cell lesions. Some reactive lesions, such as inflammatory pseudotumors, may appear to be IMTs, which makes their differential diagnosis extremely difficult. The aim of this article is to compile the recent information on IMTs to aid in their diagnosis and treatment.
METHODS
We reviewed articles published between 2017 and 2021, which were selected from online medical databases. In addition, some earlier articles and latest scientific monographies were analyzed.
RESULTS
The terminology used for inflammatory spindle cell lesions seems to be confusing. The terms "inflammatory myofibroblastic tumors" and "inflammatory pseudotumors" are interchangeably used by many scientists. However, a detailed analysis of the development of terminology suggests that the term "inflammatory myofibroblastic tumors" should be used to refer to a neoplastic lesion.
CONCLUSIONS
IMTs are rare neoplasms, which have not been investigated in detail due to the difficulty in collecting a large number of cases. Thus, our knowledge about this disease remains unsatisfactory. Recently developed techniques such as next-generation sequencing and computer-aided histopathological diagnosis may be useful in understanding the etiopathology of IMTs, which will help in the selection of the most appropriate therapy for patients.
Topics: Diagnosis, Differential; Granuloma, Plasma Cell; Humans; Inflammation; Myofibroblasts
PubMed: 35219201
DOI: 10.1016/j.advms.2022.02.002 -
Aging and Disease Feb 2022Aging is a prominent risk factor for cardiovascular diseases, which is the leading cause of death around the world. Recently, cellular senescence has received potential... (Review)
Review
Aging is a prominent risk factor for cardiovascular diseases, which is the leading cause of death around the world. Recently, cellular senescence has received potential attention as a promising target in preventing cardiovascular diseases, including acute myocardial infarction, atherosclerosis, cardiac aging, pressure overload-induced hypertrophy, heart regeneration, hypertension, and abdominal aortic aneurysm. Here, we discuss the mechanisms underlying cellular senescence and describe the involvement of senescent cardiovascular cells (including cardiomyocytes, endothelial cells, vascular smooth muscle cells, fibroblasts/myofibroblasts and T cells) in age-related cardiovascular diseases. Then, we highlight the targets (SIRT1 and mTOR) that regulating cellular senescence in cardiovascular disorders. Furthermore, we review the evidence that senescent cells can exert both beneficial and detrimental implications in cardiovascular diseases on a context-dependent manner. Finally, we summarize the emerging pro-senescent or anti-senescent interventions and discuss their therapeutic potential in preventing cardiovascular diseases.
PubMed: 35111365
DOI: 10.14336/AD.2021.0927 -
Diagnostics (Basel, Switzerland) Dec 2021Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), requires a forensic age determination to ascertain their causal... (Review)
Review
Venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and pulmonary embolism (PE), requires a forensic age determination to ascertain their causal relationship with recent events, such as trauma or medical treatment. The main objective of this systematic review is to identify the current state-of-the-art immunohistochemical methods for age determination of fatal VTE. A literature search was performed through different databases, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Within the study, we have selected only cases represented by deceased patients for DVT and/or PTE in which thromboembolic material was collected during an autoptic examination and then subjected to a histological and an immunohistochemical investigation. Studies based on animal models were not included. We assessed bias risk. A database-based search produced a total of 19 articles. After excluding duplicate items from the selection, 14 articles were reviewed. Ten articles were excluded because they did not meet the inclusion criteria. The results have pointed out 4 studies that were included in the present analysis for a total of 157 samples of DVT and 171 PTE samples. These were analyzed using traditional histological and immunohistochemical techniques. The results must be interpreted with a critical eye because of their heterogeneity in terms of time, geography, and study design. The present review highlights the importance of associating specific immunohistochemical markers with a histological analysis for the timing of DVT/PTE fatal events. Further future experiences will hopefully endorse actual knowledge on the subject to increase the accuracy in the assessment of thrombus-embolus age.
PubMed: 34943633
DOI: 10.3390/diagnostics11122397 -
Frontiers in Immunology 2021Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the...
Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the peritoneal membrane. This process may be caused by a number of insults including pathological conditions linked to clinical practice, such as peritoneal dialysis, abdominal surgery, hemoperitoneum, and infectious peritonitis. All these events may cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy. Among the cellular processes implicated in these peritoneal alterations is the generation of myofibroblasts from mesothelial cells and other cellular sources that are central in the induction of fibrosis and in the subsequent functional deterioration of the peritoneal membrane. Myofibroblast generation and activity is actually integrated in a complex network of extracellular signals generated by the various cellular types, including leukocytes, stably residing or recirculating along the peritoneal membrane. Here, the main extracellular factors and the cellular players are described with emphasis on the cross-talk between immune system and cells of the peritoneal stroma. The understanding of cellular and molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.
Topics: Animals; Biomarkers; Cell Communication; Cytokines; Disease Susceptibility; Epithelial Cells; Humans; Immunity, Innate; Inflammation Mediators; Leukocytes; Peritoneal Dialysis; Peritoneal Fibrosis; Peritoneum; Peritonitis; Stromal Cells; T-Lymphocyte Subsets
PubMed: 33854496
DOI: 10.3389/fimmu.2021.607204 -
Investigative Ophthalmology & Visual... Apr 2021Interleukin (IL)-1α/IL-1β and transforming growth factor (TGF)β1/TGFβ2 have both been promoted as "master regulators" of the corneal wound healing response due to...
PURPOSE
Interleukin (IL)-1α/IL-1β and transforming growth factor (TGF)β1/TGFβ2 have both been promoted as "master regulators" of the corneal wound healing response due to the large number of processes each regulates after injury or infection. The purpose of this review is to highlight the interactions between these systems in regulating corneal wound healing.
METHODS
We conducted a systematic review of the literature.
RESULTS
Both regulator pairs bind to receptors expressed on keratocytes, corneal fibroblasts, and myofibroblasts, as well as bone marrow-derived cells that include fibrocytes. IL-1α and IL-1β modulate healing functions, such as keratocyte apoptosis, chemokine production by corneal fibroblasts, hepatocyte growth factor (HGF), and keratinocyte growth factor (KGF) production by keratocytes and corneal fibroblasts, expression of metalloproteinases and collagenases by corneal fibroblasts, and myofibroblast apoptosis. TGFβ1 and TGFβ2 stimulate the development of myofibroblasts from keratocyte and fibrocyte progenitor cells, and adequate stromal levels are requisite for the persistence of myofibroblasts. Conversely, TGFβ3, although it functions via the same TGF beta I and II receptors, may, at least in some circumstances, play a more antifibrotic role-although it also upregulates the expression of many profibrotic genes.
CONCLUSIONS
The overall effects of these two growth factor-cytokine-receptor systems in controlling the corneal wound healing response must be coordinated during the wound healing response to injury or infection. The activities of both systems must be downregulated in coordinated fashion to terminate the response to injury and eliminate fibrosis.
TRANSLATIONAL RELEVANCE
A better standing of the IL-1 and TGFβ systems will likely lead to better approaches to control the excessive healing response to infections and injuries leading to scarring corneal fibrosis.
Topics: Biomarkers; Cornea; Corneal Injuries; Humans; Transforming Growth Factor beta; Wound Healing
PubMed: 33825855
DOI: 10.1167/iovs.62.4.8 -
Frontiers in Oncology 2020The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor...
INTRODUCTION
The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor microenvironment (TME). Among the most abundant of these stromal cells are cancer-associated fibroblasts (CAFs). While their contribution to tumor progression is widely acknowledged, and various CAF-targeted treatments are under development, the relationship between CAF density and the clinicopathologic course of HNSCC has not been clearly defined. Here we examine the published evidence investigating the relationship of cancer-associated fibroblasts to local recurrence and indicators of prognostic significance in HNSCC.
METHODS
We conducted a meta-analysis of existing publications that compare the relationship between CAF density, local recurrence, and clinically significant pathologic criteria of disease development (T stage, nodal positivity, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation). Thirteen studies met the selection criteria, providing a total study population of 926 patients. Forest plots and risk ratios were generated to illustrate overall relationships.
RESULTS
Higher CAF density within the tumor microenvironment is associated with advanced T stage, nodal infiltration, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation (p <0.05). High CAF density is also associated with increased rates of local recurrence (p <0.001).
CONCLUSIONS
Across multiple studies, increased CAF density is correlated with histopathological criteria of poor prognosis in HNSCC. These findings highlight that CAFs may play a pivotal role in HNSCC development and progression. Staining for CAFs may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment. Understanding the mechanisms by which CAFs reciprocally interact with cancer cells will be crucial for optimization of TME-focused treatment of HNSCC.
PubMed: 33330034
DOI: 10.3389/fonc.2020.565306 -
Journal of the American Heart... Dec 2020Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are... (Meta-Analysis)
Meta-Analysis
Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are subdivided by classic umbrella terms, such as "fibroblasts," "myofibroblasts," "smooth muscle cells," "fibrocytes," "mesangial cells," and "pericytes." However, a discriminative marker-based subclassification has to date not been established. Methods and Results As a first effort toward a classification scheme, a systematic literature search was performed to identify the most commonly used phenotypical and functional protein markers for characterizing and classifying vascular mesenchymal cell subpopulation(s). We next applied immunohistochemistry and immunofluorescence to inventory the expression pattern of identified markers on human aorta specimens representing early, intermediate, and end stages of human atherosclerotic disease. Included markers comprise markers for mesenchymal lineage (vimentin, FSP-1 [fibroblast-specific protein-1]/S100A4, cluster of differentiation (CD) 90/thymocyte differentiation antigen 1, and FAP [fibroblast activation protein]), contractile/non-contractile phenotype (α-smooth muscle actin, smooth muscle myosin heavy chain, and nonmuscle myosin heavy chain), and auxiliary contractile markers (h1-Calponin, h-Caldesmon, Desmin, SM22α [smooth muscle protein 22α], non-muscle myosin heavy chain, smooth muscle myosin heavy chain, Smoothelin-B, α-Tropomyosin, and Telokin) or adhesion proteins (Paxillin and Vinculin). Vimentin classified as the most inclusive lineage marker. Subset markers did not separate along classic lines of smooth muscle cell, myofibroblast, or fibroblast, but showed clear temporal and spatial diversity. Strong indications were found for presence of stem cells/Endothelial-to-Mesenchymal cell Transition and fibrocytes in specific aspects of the human atherosclerotic process. Conclusions This systematic evaluation shows a highly diverse and dynamic landscape for the human vascular mesenchymal cell population that is not captured by the classic nomenclature. Our observations stress the need for a consensus multiparameter subclass designation along the lines of the cluster of differentiation classification for leucocytes.
Topics: Atherosclerosis; Humans; Mesenchymal Stem Cells; Muscle, Smooth, Vascular
PubMed: 33190596
DOI: 10.1161/JAHA.120.017094 -
Journal of Oral and Maxillofacial... 2019Oral Submucous Fibrosis (OSMF) is a chronic progressive scarring oral disease predominantly affecting people of South Asian origin. It is characterized by... (Review)
Review
Oral Submucous Fibrosis (OSMF) is a chronic progressive scarring oral disease predominantly affecting people of South Asian origin. It is characterized by juxtaepithelial inflammatory cell infiltration followed by fibrosis in the lamina propria and submucosa of the oral mucosa. The pathogenesis of the disease is not well established and a number of mechanisms have been proposed regarding the pathogenesis. A renewed interest has been shown in myofibrobasts which have been implicated to play a significant role in the pathogenesis of OSMF. The myofibroblast were initially identified by means of electron microscopy in granulation tissue of healing wounds as a modulated fibroblast exhibiting features of smooth muscle cells, with prominent bundles of microfilaments, dense bodies scattered in between, and gap junctions. The presence of myofibroblasts has successively been described in practically all fibrotic situations characterized by tissue retraction and remodeling. This review paper is an attempt to identify all the studies involving myofibroblasts and explaining the pathogenesis in a simplified manner.
PubMed: 31516233
DOI: 10.4103/jomfp.JOMFP_238_18 -
Gastroenterology Jan 2020Stenosis is a common complication of Crohn's disease (CD) that has no effective medical therapy. Development of antifibrotic agents will require testing in randomized...
BACKGROUND & AIMS
Stenosis is a common complication of Crohn's disease (CD) that has no effective medical therapy. Development of antifibrotic agents will require testing in randomized controlled trials. Computed tomography enterography- and magnetic resonance enterography-based technologies might be used to measure outcomes in these trials. These approaches have been validated in studies of patients with symptomatic strictures who underwent imaging evaluations followed by resection with histopathologic grading of the intestinal tissue for inflammation and/or fibrosis (the reference standard). Imaging findings have correlated with findings from quantitative or semiquantitative histologic evaluation of the degree of fibromuscular stenosis and/or inflammation on the resection specimen. However, it is not clear whether histologic findings are an accurate reference standard. We performed a systematic review of all published histologic scoring systems used to assess stenosing CD.
METHODS
We performed a comprehensive search of Embase and MEDLINE of studies through March 13, 2019, that used a histologic scoring system to characterize small bowel CD and assessed inflammatory and fibrotic alterations within the same adult individual. All scores fitting the criteria were included in our analysis, independent of the presence of stricturing disease, as long as inflammation and fibrosis were evaluated separately but in the same scoring system.
RESULTS
We observed substantial heterogeneity among the scoring systems, which were not derived from modern principles for evaluative index development. None had undergone formal validity or reliability testing. None of the existing indices had been constructed according to accepted methods for the development of evaluative indices. Basic knowledge regarding their operating properties were lacking. Specific indices for evaluating the important pathologic component of myofibroblast hypertrophy or hyperplasia have not been proposed.
CONCLUSIONS
In a systematic review of publications, we found a lack of validated histopathologic scoring systems for assessment of fibromuscular stenosis. Data that describe the operating properties of existing cross-sectional imaging techniques for stenosing CD should be questioned. Development and validation of a histopathology index is an important research priority.
Topics: Constriction, Pathologic; Crohn Disease; Fibrosis; Humans; Ileum; Magnetic Resonance Imaging; Reference Standards; Reproducibility of Results; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 31476299
DOI: 10.1053/j.gastro.2019.08.033 -
European Review For Medical and... Dec 2018Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence...
OBJECTIVE
Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence of a chronic inflammation that usually occurs during Inflammatory Bowel Disease (IBD). The relationship between inflammation and fibrosis in IBD remains still unclear and nevertheless the recent pharmacological progresses, currently the only resolutive therapeutic strategy is surgery, especially when complications (stricture, stenosis and obstruction of intestinal tracts) appear. As many different cellular types and molecular mechanisms are implicated in the pathogenesis of IBD, the identification of molecules able to counteract this process could be crucial.
MATERIALS AND METHODS
This is a literature review of several articles published on PubMed databases.
RESULTS
A number of researches suggest that Proliferator-Activated Receptor-gamma (PPAR-γ) has both anti-inflammatory and anti-fibrotic effects in many organs. PPAR-γ has been demonstrated to be able to downregulate pro-inflammatory cytokines production such as Interleukin (IL)-4,-5,-6 but also to interfere with profibrotic molecules as Platelet-Derived Growth Factor (PDGF), IL-1 and Transforming Growth Factor Beta (TGF-β), the main promoter of fibrosis. In preliminary clinical trials and in experimental models of intestinal fibrosis, natural and chemical PPAR-γ ligands have ameliorated the fibrotic process.
CONCLUSIONS
Since PPAR-γ could play a crucial role in the development of the disease, the research of new molecules, capable of ameliorating both inflammation and fibrosis lesions, as PPAR-γ agonists, could represent a valid and effective therapeutic approach for the prevention and treatment of IBD and intestinal fibrosis.
Topics: Fibrosis; Humans; Inflammation; Inflammatory Bowel Diseases; NF-kappa B; PPAR gamma
PubMed: 30575926
DOI: 10.26355/eurrev_201812_16652