Juliana Cristina de Souza, Victor Coutinho Bastos, Núbia Braga Pereira, Adriana Abalen Martins Dias, Gleide Fernandes de Avelar, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes
{"title":"Angiogenesis in patient-derived xenografts of odontogenic myxoma","authors":"Juliana Cristina de Souza, Victor Coutinho Bastos, Núbia Braga Pereira, Adriana Abalen Martins Dias, Gleide Fernandes de Avelar, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes","doi":"10.1111/iep.12431","DOIUrl":"10.1111/iep.12431","url":null,"abstract":"<p>Previously, by employing 3D organotypic tissue culture and patient-derived xenograft (PDX) model, oral myxoma response to a MAPK/MEK inhibitor was observed. Gross examination of the tumour fragments obtained after 55 days of PDX grafting revealed increased capsule vascularization. Microscopic analyses showed blood capillaries intermixed with myxoma cells, but the origin of these capillaries, from mice or humans, was not established. This study aimed to investigate whether the endothelial cells observed in the myxoma PDX model are derived from the mouse or from the primary human tumour. Immunohistochemistry was performed on five tumour fragments from the PDX of myxoma after 55 days of implantation in mice. Immunopositivity for antibodies against human (HLA-ABC) and mouse (H2 Db/H2-D1) major histocompatibility complex class I (MHCI) was assessed in the endothelial cells. The endothelial cells in the PDX fragments revealed a membrane staining for the human MHCI protein in the PDX tumour and adjacent connective tissue capsule, indicating that capillaries were derived from the human tumour fragment. Considering the probable human origin of the endothelial cells from capillary blood vessels in the myxoma PDX, we conclude that this PDX model is an interesting model to study myxoma angiogenesis.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"65-69"},"PeriodicalIF":3.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9226372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mezgebe Gebrekiristos, Joshua Melson, Alice Jiang, Lela Buckingham
{"title":"DNA methylation and miRNA expression in colon adenomas compared with matched normal colon mucosa and carcinomas","authors":"Mezgebe Gebrekiristos, Joshua Melson, Alice Jiang, Lela Buckingham","doi":"10.1111/iep.12432","DOIUrl":"10.1111/iep.12432","url":null,"abstract":"<p>Dysregulation of DNA methylation patterns and non-coding RNA, including miRNAs, has been implicated in colon cancer, and these changes may occur early in the development of carcinoma. In this study, the role of epigenetics as early changes in colon tumorigenesis was examined through paired sample analysis of patient-matched normal, adenoma and carcinoma samples. Global methylation was assessed by genomic 5-methyl cytosine (5-mC) and long interspersed nuclear element-1 (LINE-1) promoter methylation by pyrosequencing. <i>KRAS</i> mutations were also assessed by pyrosequencing. Expression of miRNA, specifically, two microRNA genes—<i>miR-200a</i> and <i>let-7c</i>—was analysed using RT-qPCR. Differences in global methylation in adenomas were not observed, compared with normal tissue. However, LINE-1 methylation was decreased in adenomas (<i>p</i> = .056) and carcinomas (<i>p</i> = .011) compared with normal tissue. Expressions of miRNA, <i>miR-200a</i> and <i>let-7c</i> were significantly higher in adenomas than normal tissues (<i>p</i> = .008 and <i>p</i> = .045 respectively). Thus the significant changes in LINE-1 methylation and microRNA expression in precancerous lesions support an early role for epigenetic changes in the carcinogenic process. Epigenetic characteristics in adenomas may provide potential diagnostic and prognostic therapeutic targets early in cancer development at the adenoma stage.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 3","pages":"74-82"},"PeriodicalIF":3.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Orchestrated expression of vasculogenic mimicry and laminin-5γ2 is an independent prognostic marker in oral squamous cell carcinoma","authors":"Depanwita Saha, Debarpan Mitra, Neyaz Alam, Sagar Sen, Saunak Mitra Mustafi, Syamsundar Mandal, Biswanath Majumder, Nabendu Murmu","doi":"10.1111/iep.12430","DOIUrl":"10.1111/iep.12430","url":null,"abstract":"<p>Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin-5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin-5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin-5γ2 (<i>p</i> < .001) and MMP2 (<i>p</i> < .001). This pattern was mirrored by the significant upregulation of laminin-5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co-expression of VM and laminin-5γ2 was significantly associated with tumour grade (<i>p</i> = .010), primary tumour size (<i>p</i> < .001), lymph node metastasis (<i>p</i> = .001) and TNM stages (<i>p</i> < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin-5γ2 double-positive cohort displayed a significantly poorer disease-free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin-5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, <i>p</i> = .028] and OS [HR = 21.401, <i>p</i> = .033] in OSCC patients. Together, our findings imply that VM along with laminin-5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin-5γ2 coordination emerges as a critical prognostic biomarker for OSCC.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"54-64"},"PeriodicalIF":3.0,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9219510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Remifentanil reduces the proliferation, migration and invasion of HCC cells via lncRNA NBR2/miR-650/TIMP3 axis","authors":"Wei Liang, Jinyuan Ke","doi":"10.1111/iep.12429","DOIUrl":"10.1111/iep.12429","url":null,"abstract":"<p>Cancer cell hyperproliferation and metastasis are major causes of cancer-associated mortality. Although the use of anaesthetics and analgesics may affect cancer cell metastasis, the underlying molecular mechanism remains unclear. This study aimed to explore the mechanisms of action of remifentanil on hepatocellular carcinoma (HCC) progression. Cell viability was measured by the 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay. Quantitative real-time polymerase chain reaction and Western blotting were performed to assess the expression levels of long non-coding RNA (lncRNA) neighbour of BRCA1 gene 2 (NBR2), microRNA (miR)-650 and tissue inhibitor of metalloproteinase-3 (TIMP3) in HCC cells. Wound healing and transwell assays were employed to evaluate the migration and invasion of HCC cells respectively. The target relationships between miR-650 and NBR2/TIMP3 were confirmed by dual luciferase reporter assay. Remifentanil reduced the viability of HCC cells in a dose-dependent manner. Remifentanil treatment significantly increased the expression of lncRNA NBR2 and TIMP3, and repressed miR-650 expression in HCC cells. Decreased lncRNA NBR2 or increased miR-650 promoted the proliferation, migration and invasion of remifentanil-treated HCC cells. LncRNA NBR2 targeted miR-650, and miR-650 further targeted TIMP3. Moreover, miR-650 down-regulation or TIMP3 up-regulation reversed the effects of lncRNA NBR2 knockdown that caused an enhancement of cell viability, migration and invasiveness in remifentanil-treated HCC cells. Thus remifentanil reduces the proliferation, migration and invasion of HCC cells via the lncRNA NBR2/miR-650/TIMP3 axis in vitro.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"44-53"},"PeriodicalIF":3.0,"publicationDate":"2022-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna L. Gray, Nabina Pun, Amanda J. L. Ridley, Douglas P. Dyer
{"title":"Role of extracellular matrix proteoglycans in immune cell recruitment","authors":"Anna L. Gray, Nabina Pun, Amanda J. L. Ridley, Douglas P. Dyer","doi":"10.1111/iep.12428","DOIUrl":"10.1111/iep.12428","url":null,"abstract":"<p>Leucocyte recruitment is a critical component of the immune response and is central to our ability to fight infection. Paradoxically, leucocyte recruitment is also a central component of inflammatory-based diseases such as rheumatoid arthritis, atherosclerosis and cancer. The role of the extracellular matrix, in particular proteoglycans, in this process has been largely overlooked. Proteoglycans consist of protein cores with glycosaminoglycan sugar side chains attached. Proteoglycans have been shown to bind and regulate the function of a number of proteins, for example chemokines, and also play a key structural role in the local tissue environment/niche. Whilst they have been implicated in leucocyte recruitment and inflammatory disease, their mechanistic function has yet to be fully understood, precluding therapeutic targeting. This review summarizes what is currently known about the role of proteoglycans in the different stages of leucocyte recruitment and proposes a number of areas where more research is needed. A better understanding of the mechanistic role of proteoglycans during inflammatory disease will inform the development of next-generation therapeutics.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"34-43"},"PeriodicalIF":3.0,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39857078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"British Society for Matrix Biology Autumn 2021 Autumn Meeting: \"Extracellular Matrix and Rare Disease\"","authors":"","doi":"10.1111/iep.12421","DOIUrl":"10.1111/iep.12421","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 1","pages":"A1-A14"},"PeriodicalIF":3.0,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781645/pdf/IEP-103-A1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10597129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colonoscopy Audit Increases Detection of Sessile Serrated Polyps","authors":"A. Fraser","doi":"10.33696/pathology.2.030","DOIUrl":"https://doi.org/10.33696/pathology.2.030","url":null,"abstract":"Detection and removal of all adenomas at colonoscopy is associated with a reduced interval cancer rate [1,2]. This is consistent with the adenoma-carcinoma sequence for colorectal cancer. The identification of the serrated polyp cancer pathway has emphasized the importance of detection and removal of sessile serrated polyps. Serrated polyps are precursor lesions ac counting for 15% to 30% of colorectal cancers. They are overrepresented as a cause of interval cancers [3]. The detection of serrated polyps has been clearly linked to the risk of colorectal cancer in a prospective record linkage study in Sweden with a similar risk to tubular adenomas (HR of 1·77 (1·34-2·34) for sessile serrated polyps and 1·41 (1·30-1·52) for tubular adenomas) [4].","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"1 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79510843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Scafa, G. Santoro, V. Chiarella, N. Greco, Massimo Corsini, Manolo, Piccirilli
{"title":"Spinal Capillary and Cavernous Haemangiomas in Developmental Age: Our Experience","authors":"A. Scafa, G. Santoro, V. Chiarella, N. Greco, Massimo Corsini, Manolo, Piccirilli","doi":"10.33696/pathology.2.027","DOIUrl":"https://doi.org/10.33696/pathology.2.027","url":null,"abstract":"In 1863, Virchow proposed the first classification of vascular anomalies. He considered these lesions to be tumors (“angiomas”) and classified them into three categories (“simplex”, “cavernosum”, and “racemosum”) according to the microscopic appearance of the diseased vascular channels [2]. It was subsequently stated that angiomas could be either capillary, venous or arterial (with or without fistulae) based on the stage at which vascular morphogenesis was altered [3]. Setting aside Virchow’s hypothesis, Mulliken and Glowacki, in 1982, developed a new, “binary” classification model in which they distinguished true (1) vascular “hemangiomas”, characterized by cellular hyperplasia, from (2) vascular “malformations” which instead demonstrated vessel dysplasia with normal rates of cellular turnover. They also described the different biological behavior of the two “entities” in terms of tendency to spontaneous regression (present in vascular hemangiomas, absent in vascular malformations) [4]. This scheme was later embraced by the “International Society for the Study of Vascular Anomalies” (ISSVA) at the 1996 meeting in Rome [5], “expanded” at the 2014 ISSVA workshop in Melbourne, and last revised in 2018 (the updates were crucial to fully incorporate the genetic and histopathological advances in the knowledge of these lesions) [6,7]. Vascular tumors were divided into benign, borderline/locally aggressive, and malignant, and were also further sub-classified by pattern and location to include syndromic associations, such as PHACE (posterior fossa brain malformations, large facial hemangiomas, anatomical anomalies of the cerebral arteries, aortic coarctation and other cardiac anomalies, eye abnormalities) and LUMBAR (lower body congenital infantile hemangiomas and other skin defects, urogenital anomalies and ulceration, myelopathy, bony deformities, anorectal malformations and arterial anomalies, rectal anomalies) [7].","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"60 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77962303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Varying Presentations of EBV-associated Clinical Entities with Emphasis on EBV-Associated T- and NK-cell Lymphoproliferative Disorders of Childhood","authors":"Jonathan Y. Keow, N. Sangle","doi":"10.33696/pathology.2.028","DOIUrl":"https://doi.org/10.33696/pathology.2.028","url":null,"abstract":"The Epstein-Barr Virus (EBV) is an endemic human herpesvirus, with 90% of people demonstrating serological evidence of prior exposure to EBV. In most cases, primary infections of EBV generate mild or asymptomatic clinical courses, but may present as infectious mononucleosis if contracted during young adulthood. In a small percentage of cases, EpsteinBarr virus infection may manifest as a noncanonical reaction, yielding a wide variety of clinical manifestations.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"8 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73235964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuroprotective Effects of Khaya Anthotheca (Welw.) C.DC (Meliaceae) Decoction on Neurodegeneration Induced by Estrogen Depletion in Rats","authors":"Zemo Gamo Franklin, Djiogue Séfirin, S. Faustin, P. Anatole, Babiker Ali, Yousif, Awounfack Charline Florence, Djikem Tadah Rudig Nikanor, Njamen Dieudonne","doi":"10.33696/pathology.2.029","DOIUrl":"https://doi.org/10.33696/pathology.2.029","url":null,"abstract":"Background: Recently, we reported estrogen-like and anxiolytic effects of the decoction of Khaya anthotheca in ovariectomized rats. Rationale: The purpose of the present study was to assess the putative neuroprotective properties of the plant in ovariectomized rats. Methods: Thirty female Wistar rats were ovariectomized, while 6 were used as sham. After 14 days of endogenous hormonal decline, animals were randomly divided into six groups (n=6) and administered with distilled water, K. anthotheca decoction (125, 250 and 500 mg/kg doses) or estradiol valerate (1 mg/kg) for 28 days. Phytochemical analysis and antioxidant potential of the decoction were determined. Levels of oxidative stress biomarkers were determined in brain homogenates, while histopathological analysis was performed on brain sections, and expressions of neuroinflammation markers determined. Results: Polyphenols were detected in K. anthotheca, and the ferric reducing antioxidant power (FRAP) assay revealed antioxidant properties (635.50 ± 0.58 mg eq quercetin/g of dried decoction). Treatment with K. anthotheca decoction reduced MDA and increased GSH levels in brain homogenates (p<0.01). As estradiol valerate, the decoction, prevented neurodegeneration observed in cortices and hippocampi of untreated ovariectomized animals. Conclusions: Our results suggested that K. anthotheca is endowed with neuroprotective effects and warrant further studies, including other models of neurodegeneration and dementia.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"3 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89769227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}