Proliferation Of Myofibroblastic Cells Research Articles

Novel insights into biomarkers of progression in Desmoid tumor.

Desmoid tumor (DT) is a rare neoplasm characterized by the proliferation of myofibroblastic cells that infiltrates and invades adjacent tissues. Due to its locally aggressive and recurrent nature, DT often causes local symptoms and can be challenging to manage clinically. Therefore, identifying biomarkers that can predict the progression of DT and guide treatment decisions is critical. This review summarizes several biomarkers that have been implicated in active surveillance (AS) and the prediction of postoperative recurrence and attempts to elucidate their underlying mechanisms. Some of these novel markers could provide prognostic value for clinicians, and ultimately help facilitate optimal and accurate therapeutic decisions for DT.

Histological Changes in the Lung Tissue in Association with COVID-19: Review Article

Background: It has been shown that SARS-CoV-2 is a multi-systemic virus and can affect number of body systems including the respiratory tract, the gastro-intestinal tract, the liver, the kidney and the nervous system. Despite the high mortality rate, there is little literature on postmortem findings of this unique virus, perhaps due to its highly contagious nature, inadequate information on prevention, and a lack of robust infrastructure for appropriate management of infected cases at various centers throughout the world. Aim of the study: The aim of the current study was to review and list the main histological changes seen in patients died because of COVID-19. Methods: A systemic search was carried out including Google Scholar, PubMed, and MEDLINE and the Google search Engine in order to scan all available published articles dealing with histological changes affection the lung in patients with documented COVID-19. The following key words were used to accomplish the search mission: COVID-19, SARS-CoV-2, Lung Histology, Pulmonary Histology, Histopathology. The search was limited to articles written in English language. Any article published between the end of 2019 and the time of initiating the current work was reviewed. The information in the current review is totally based on reviewed articles that are mentioned in the section of references. Results: The main sources of lung tissues were Whole lung biopsy, Postmortem study, Core needle biopsy and Ultrasound based samples from autopsy. The exudative changes include injury to pneumocytes, congestion of capillaries, giant cell formations, dilation of alveolar ducts, thickening of capillaries, edema of interstitium and formation of hyaline membrane. The proliferative changes include hyperplasia of Type-2 pneumocytes with some reactive atypia with proliferation of myofibroblastic cells leading to granulation tissue formation, thickening of alveolar wall accumulation of alveolar macrophages, interstitial thickening which harbors collections of proliferating fibroblasts together with foci of hemorrhage and lymphocytic infiltration. Conclusion: The main histopathological changes in lung of patients with COVID-19 can be grouped into three main phases, exudative, proliferative and fibrotic phases in addition to changes involving vascular tissues, bronchi and bronchioles and the main changes are the diffuse alveolar damage seen in exudative and proliferative phases.

Cytokines Involved in the Progression of Liver Fibrosis by Influencing DNA Synthesis

Liver fibrosis is a pathological change in which the connective tissue in the liver proliferates abnormally, resulting in abnormal liver function or structure. Long-term liver fibrosis can develop cirrhosis or liver cancer, which poses a great threat to human health. This article reviews the cytokines closely related to liver fibrosis in recent years These cytokines affect the development of liver fibrosis mainly through processes that affect DNA synthesis. Platelet-derived growth factor promotes the division and proliferation of hepatic stellate cells by stimulating cellular DNA synthesis. Insulin-like growth factor, on the other hand, shows the proliferation of myofibroblastic cells in a manner that promotes the cell cycle to enter the DNA synthesis phase. Interleukin-6 promotes the progression of DNA synthesis in a manner that activates cyclins. We aim to find new approaches for the treatment of liver fibrosis by means of regulating DNA synthesis as the main approach by summarizing existing studies.

Oesophageal pseudotumor: a case report

Inflammatory pseudo tumor (IPT) also known as inflammatory myofibroblastic tumor (IMT) is a tumor like mass of inflammatory origin. It is a pseudo sarcomatous lesion that has been reported most commonly in liver, followed by lung, mesentery and omentum but very rarely seen in esophagus. Proliferation of myofibroblastic cells is more in IMT. In IPT it is more of an inflammatory reactive or regenerative entity and has an overlapping with immunoglobulin G4-related disease. Lesion often mimics malignancy. A 20 year old male patient with history of dysphagia, more for liquids, underwent CT thorax, showing dilated oesophagus, with a moderately contrast enhancing eccentric soft tissue density lesion involving mid and lower esophagus extending for a length of 6cm. Patient underwent right thoracotomy, and a 5x3x3cm hard lesion involving lower esophagus was excised. Histopathology pointed towards inflammatory myofibroblastic tumor or inflammatory pseudotumor. Proliferation of myofibroblastic cells is more in IMT. In IPT it is more of an inflammatory reactive or regenerative entity and has an overlapping with immunoglobulin G4-related disease. Lesion often mimics malignancy.

Generation and Activity of a Humanized Monoclonal Antibody That Selectively Neutralizes the Epidermal Growth Factor Receptor Ligands Transforming Growth Factor-αand Epiregulin

At least seven distinct epidermal growth factor (EGF) ligands bind to and activate the EGF receptor (EGFR). This activation plays an important role in the embryo and in the maintenance of adult tissues. Importantly, pharmacologic EGFR inhibition also plays a critical role in the pathophysiology of diverse disease states, especially cancer. The roles of specific EGFR ligands are poorly defined in these disease states. Accumulating evidence suggests a role for transforming growth factor α (TGFα) in skin, lung, and kidney disease. To explore the role of Tgfa, we generated a monoclonal antibody (mAb41) that binds to and neutralizes human Tgfa with high affinity (KD = 36.5 pM). The antibody also binds human epiregulin (Ereg) (KD = 346.6 pM) and inhibits ligand induced myofibroblast cell proliferation (IC50 values of 0.52 and 1.12 nM for human Tgfa and Ereg, respectively). In vivo, a single administration of the antibody to pregnant mice (30 mg/kg s.c. at day 14 after plug) or weekly administration to neonate mice (20 mg/kg s.c. for 4 weeks) phenocopy Tgfa knockout mice with curly whiskers, stunted growth, and expansion of the hypertrophic zone of growth plate cartilage. Humanization of this monoclonal antibody to a human IgG4 antibody (LY3016859) enables clinical development. Importantly, administration of the humanized antibody to cynomolgus monkeys is absent of the skin toxicity observed with current EGFR inhibitors used clinically and no other pathologies were noted, indicating that neutralization of Tgfa could provide a relatively safe profile as it advances in clinical development.

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy.

La fasciite nodulaire : à propos d’un cas et revue de la littérature

Among soft tissue tumors, nodular fasciitis is a relatively common tumor process, which occurs in the 30 first years of life. Nodular fasciitis is a benign tumor with a rapid proliferation of myofibroblastic cells, which develops at the expense of a muscular fascia in the subcutaneous tissue. Usual localizations are the trunk and upper limbs. Difficulty of diagnosis consists in the need to eliminate many differential diagnoses especially malignant tumor processes. From a clinical point of view, the rapid development of nodular fasciitis (from some days to some weeks) must fear a malignant process. This benign lesion, which does not recur (even if incomplete resection), may regress spontaneously. We report such a tumor located at the cubital fossa confirmed by a pathological examination.

Inflammatory Myofibroblastic Tumor of the Paratestis

Journal of Ultrasound in MedicineVolume 26, Issue 9 p. 1227-1230 Case Report Inflammatory Myofibroblastic Tumor of the Paratestis Sonographic Appearance With Pathologic Correlation Stylianos Megremis MD, PhD, Corresponding Author Stylianos Megremis MD, PhD efstel@med.uoc.gr First Department of Radiology Venizelio General Hospital, Iraklio, Crete, Greece.Address correspondence to Stylianos Megremis, MD, PhD, 23 Arsinois St, 71303 Iraklio, Crete, Greece.Search for more papers by this authorErini Papamitsaki MD, Erini Papamitsaki MD First Department of Radiology Venizelio General Hospital, Iraklio, Crete, Greece.Search for more papers by this authorPanagiotis Ieromonachou MD, Panagiotis Ieromonachou MD Department of Pathology, Venizelio General Hospital, Iraklio, Crete, Greece.Search for more papers by this authorEmmanouil Zois MD, PhD, Emmanouil Zois MD, PhD Department of Pathology, Venizelio General Hospital, Iraklio, Crete, Greece.Search for more papers by this author Stylianos Megremis MD, PhD, Corresponding Author Stylianos Megremis MD, PhD efstel@med.uoc.gr First Department of Radiology Venizelio General Hospital, Iraklio, Crete, Greece.Address correspondence to Stylianos Megremis, MD, PhD, 23 Arsinois St, 71303 Iraklio, Crete, Greece.Search for more papers by this authorErini Papamitsaki MD, Erini Papamitsaki MD First Department of Radiology Venizelio General Hospital, Iraklio, Crete, Greece.Search for more papers by this authorPanagiotis Ieromonachou MD, Panagiotis Ieromonachou MD Department of Pathology, Venizelio General Hospital, Iraklio, Crete, Greece.Search for more papers by this authorEmmanouil Zois MD, PhD, Emmanouil Zois MD, PhD Department of Pathology, Venizelio General Hospital, Iraklio, Crete, Greece.Search for more papers by this author First published: 01 September 2007 https://doi.org/10.7863/jum.2007.26.9.1227Citations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume26, Issue9September 2007Pages 1227-1230 RelatedInformation

Pseudosarcomatous and sarcomatous proliferations of the bladder

Pseudosarcomatous fibromyxoid tumor (PFT), postoperative spindle cell nodule (PSN), sarcoma, and sarcomatoid carcinoma of the bladder are frequently difficult to distinguish histopathologically with significant differences in disease-related outcomes. A retrospective review of our pathology registry over the last 25 years identified 7 PFT, 10 PSN, 18 primary bladder sarcomas, and 17 sarcomatoid carcinomas. Most patients with PFT, PSN, sarcoma, and sarcomatoid carcinoma were diagnosed between the ages of 50 to 60 years with PFT and PSN most commonly detected in women. A previous history of urological instrumentation and bladder cancer was present in all patients with PSN but none of the patients with PFT. Pseudosarcomatous fibromyxoid tumors were characterized by a tissue culture-like proliferation of myofibroblastic cells with focal atypia and overall cytoarchitectural features mimicking nodular fasciitis. Sarcomas and sarcomatoid carcinomas exhibited cellular atypia, mitotic activity with atypical mitosis, and the presence of necrosis. Transurethral resection was sufficient to control all PFT and PSN with no evidence of distant metastatic spread. In contrast, local recurrences and distant metastases frequently occurred in patients with primary sarcoma and sarcomatoid carcinoma despite aggressive surgical management, which was often combined with neoadjuvant chemotherapy (50% and 65% disease-specific mortality, respectively). Pseudosarcomatous fibromyxoid tumor and PSN have unique clinical and pathologic features that allow their distinction from primary bladder sarcoma and sarcomatoid carcinoma.

Atorvastatin Inhibits Hypercholesterolemia-Induced Calcification in the Aortic Valves via the Lrp5 Receptor Pathway

Calcific aortic valve disease is the most common indication for surgical valve replacement in the United States. The cellular mechanisms of valve calcification are not well understood. We have previously shown that cellular proliferation and osteoblastogenesis are important in the development of valvular heart disease. Lrp5, a known low-density receptor-related protein, plays an essential role in cellular proliferation and osteoblastogenesis via the beta-catenin signaling pathway. We hypothesize that Lrp5 also plays a role in aortic valve (AV) calcification in experimental hypercholesterolemia. We examined the effects of cholesterol and atorvastatin in Watanabe rabbits (n=54). Group I (n=18) received a normal diet, group II (n=18) a 0.25% cholesterol diet, and group III (n=18) a 0.25% (w/w) cholesterol diet with atorvastatin for the development of calcification. The AVs were examined for cellular proliferation, Lrp5/beta-catenin, and bone matrix markers. Bone formation was assessed by micro-computed tomography, calcein injection, and osteopontin expression. Low-density lipoprotein with and without atorvastatin was also tested in AV myofibroblasts for cellular proliferation and regulation of the Lrp5/beta-catenin pathway. Our results demonstrate that the cholesterol diet induced complex bone formations in the calcified AVs with an increase in the Lrp5 receptors, osteopontin, and p42/44 expression. Atorvastatin reduced bone formation, cellular proliferation, and Lrp5/beta-catenin protein levels in the AVs. In vitro analysis confirmed the Lrp5/beta-catenin expression in myofibroblast cell proliferation. Hypercholesterolemic AV calcification is attenuated by atorvastatin and is mediated in part by the Lrp5/beta-catenin pathway. This developmental pathway may be important in the signaling pathway of this disease.

The endothelin system and its role in pulmonary arterial hypertension (PAH)

Endothelin receptor antagonists represent a major advance in the treatment of PAH but much remains to be learned of their effectiveness in specific forms of pulmonary hypertension The endothelin system is emerging as an important mediator in pulmonary arterial hypertension (PAH) and the endothelin receptor antagonists represent a major advance in the treatment of this condition. PAH results from a massive proliferation of myofibroblast cells in the intima of small pulmonary arteries. Thickening of the media is also observed and abnormal proliferation of endothelial cells may result in plexiform lesions. The endothelin system has been extensively studied over the 15 years since its initial discovery by Yanagisawa and co-workers in 1988. It is clear that endothelin 1 (ET-1) is a key mediator of pulmonary vascular biology and pathophysiology. It is a powerful vasoconstrictor and proliferative cytokine. In the early 1990s ET-1 was identified as an important mediator of PAH. Plasma ET-1 levels were found to be elevated in patients with pulmonary hypertension and correlated with the raised pulmonary vascular resistance.1 Furthermore, expression of ET-1 mRNA and protein was increased in endothelial cells comprising vascular lesions in primary pulmonary hypertension.2 The availability of ET-1 receptor antagonists allowed testing of these compounds in experimental models. In rat models of experimental pulmonary hypertension—including pulmonary hypertension induced by chronic (2–3 weeks) hypoxia3 and by the alkaloid monocrotaline—ET-1 antagonists prevent the development of PAH. More compelling is the finding that ET-1 antagonists can partly reverse established PAH in experimental models.4 These observations suggest that ET-1 antagonists can potentially reverse established pulmonary vascular remodelling rather than simply prevent vasoconstriction.5 In clinical PAH the main component of the increased pulmonary vascular resistance is remodelling rather than vasoconstriction. However, in animal models the predominant lesion is medial hypertrophy rather than intimal thickening, and …

Aortic and mitral fenfluramine-phentermine valvulopathy in 64 patients treated with anorectic agents.

Few published studies of the pathology of fenfluramine-phentermine (fen-phen) valvulopathy, described by Connolly and colleagues in 1997, have appeared. To define temporal changes in the morphology of the stuck-on plaques and to determine whether the plaques progress or regress after cessation of fen-phen. The available clinical information and pathology material from 35 aortic valves (AVs) and 43 mitral valves (MVs) from 64 patients were reviewed. The valves fell into 3 groups: 17 AVs and 28 MVs had fen-phen lesions only, 2 AVs and 7 MVs had fen-phen changes associated with other valve diseases, and 16 AVs and 8 MVs had no fen-phen changes. Fenfluramine-phentermine-attributable dysfunction was regurgitation in all instances. Typical plaques showed proliferation of myofibroblastic cells with myxoid stroma. Small vascular channels and slight lymphocytic accumulations were often present. Deeper parts of some plaques had dense fibroelastic tissue underlying typical plaque. Considerable individual variation in the time course of anorectic agent use and the severity of fen-phen valvulopathy was observed. Possible plaque regression could not be assessed from this study. The observations suggest that in some patients fen-phen-induced plaques may continue to have surface proliferation despite drug withdrawal.

Hamartoma of the mitral valve with blood cysts: A rare tumor detected by echocardiography

A 16-year-old boy was submitted to a cardiac examination after an episode of faintness. A transthoracic echocardiogram was performed, which revealed a very mobile multicystic tumor attached to the mitral valve. A small solid mass adherent to the cysts was better defined by transesophageal echocardiography. The patient was submitted to cardiac surgery consisting of tumor resection and a mitral prosthesis implant. The surgery was successful. The tumor consisted of three bright red tense cysts with hematic content, each 1 to 2 cm in diameter. The cysts were coalescent and adherent to a solid mass attached to the posterior papillary muscle head. Histopathologic examination revealed a hamartoma with a cystic part composed of the proliferation of myofibroblast cells in a stroma with vessels, collagen, and elastin fibers. Valvular hamartoma with blood cysts is a very rare cardiac tumor both for its histopathology and its localization. (J Am Soc Echocardiogr 1998;11:832-6.)

External Biodegradable Supporting Conduit Protects Endothelium in Vein Graft in Arterial Interposition

The prevention of circumferential distension could reduce structural damage in arteriovenous grafts. We studied the effect of an external biodegradable supporting conduit on the endothelium and extracellular matrix in vein graft in a pig model. Cephalic vein control grafts (Group I) and jugular veins wrapped in a vicryl mesh tube (I.D. 4 mm) (Group II) were implanted into autologous carotid arteries (n = 14). The grafts were explanted after 1 and 24 hours and at 1 and 3 weeks and evaluated by ELISA for endothelial DNA synthesis and by immunohistoenzymic assays for cells and extracellular matrix. In group I an initial loss of endothelial and smooth muscle cells along with elastin breakdown was followed by an impaired endothelial regeneration and significant graft wall thickening. The elastic tissue was replaced by collagen type I and chondroitin sulfate accumulations, which included a disarray of alpha-smooth muscle actin positive cells. The endothelium was preserved in group II. After 3 weeks the circumferential elastin layers were densified, distended and separated from the endothelium by a neointimal growth of irregular thickness. Biodegradable perivenous conduit minimized endothelial injury and allowed the partial preservation of elastin fibers and smooth muscle cells in the arteriovenous graft. It did not however, prevent myofibroblastic cell proliferation and triggered a macrophagic reaction.

Effects of Topical Glaucoma Drugs on Fistuliezed Rabbit Conjunctiva

Conjunctival fibroblastic proliferation with contracting scar formation has been implicated as a possible cause of glaucoma filtering surgery failure. The effects of glaucoma medications on bulbar conjunctiva were evaluated in both eyes of 20 pigmented rabbits, with 5 rabbits per group each receiving singular topically applied daily doses of either 0.5% timolol, 1% epinephrine, 4% pilocarpine, or artificial tears in a masked fashion for 4 months. Posterior lip sclerectomies were performed in 16 rabbits-4 from each treatment group. The remaining four rabbits served as nonsurgical controls. Four additional rabbits, which had not received eye drops, were included as a nonmedicated control group, with one rabbit serving as a nonsurgical control. Immunostaining was performed to identify the presence of myofibroblasts in fistulized conjunctiva. Treated surgical eyes, regardless of medication, had higher myofibroblastic cell proliferation than treated nonsurgical eyes. Among fistulized eyes, all medications increased cell proliferation, with pilocarpine eliciting the most dramatic increase compared with all other groups.