RESUMO
The extracellular matrix (ECM) is a dynamic set of molecules produced by the cellular component of normal and pathological tissues of the embryo and adult. ECM acts as critical regulator in various biological processes such as differentiation, cell proliferation, angiogenesis, and immune control. The most frequent primary brain tumors are gliomas and by far the majority are adult astrocytic tumors (AATs). The prognosis for patients with these neoplasms is poor and the treatments modestly improves survival. In the literature, there is a fair number of studies concerning the composition of the ECM in AATs, while the number of studies relating the composition of the ECM with the immune regulation is smaller. Circulating ECM proteins have emerged as a promising biomarker that reflect the general immune landscape of tumor microenvironment and may represent a useful tool in assessing disease activity. Given the importance it can have for therapeutic and prognostic purposes, the aim of our study is to summarize the biological properties of ECM components and their effects on the tumor microenvironment and to provide an overview of the interactions between major ECM proteins and immune cells in AATs. As the field of immunotherapy in glioma is quickly expanding, we retain that current data together with future studies on ECM organization and functions in glioma will provide important insights into the tuning of immunotherapeutic approaches.
Assuntos
Astrocitoma , Matriz Extracelular , Microambiente Tumoral , Humanos , Matriz Extracelular/metabolismo , Microambiente Tumoral/imunologia , Astrocitoma/patologia , Astrocitoma/metabolismo , Astrocitoma/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Adulto , Animais , Proteínas da Matriz Extracelular/metabolismoRESUMO
The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN-GAA-Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by â¼1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells, A-196 increased FXN expression by up to 2-fold, an effect not seen in WT cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4-7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogs were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.
Assuntos
Metilação de DNA , Epigênese Genética , Fibroblastos/patologia , Ataxia de Friedreich/patologia , Inativação Gênica , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Proteínas de Ligação ao Ferro/metabolismo , Estudos de Casos e Controles , Fibroblastos/metabolismo , Ataxia de Friedreich/genética , Ataxia de Friedreich/metabolismo , Heterocromatina , Humanos , Proteínas de Ligação ao Ferro/antagonistas & inibidores , Proteínas de Ligação ao Ferro/genética , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , FrataxinaRESUMO
Calcific Aortic Valve Disease (CAVD) is the most common valvular heart disease in developed countries and in the ageing population. It is strongly correlated to median age, affecting up to 13% of the population over the age of 65. Pathophysiological analysis indicates CAVD as a result of an active and degenerative disease, starting with sclerosis and chronic inflammation and then leaflet calcification, which ultimately can account for aortic stenosis. Although CAVD has been firstly recognized as a passive event mostly resulting from a degenerative aging process, much evidences suggests that calcification arises from different active processes, involving both aortic valve-resident cells (valve endothelial cells, valve interstitial cells, mesenchymal stem cells, innate immunity cells) and circulating cells (circulating mesenchymal cells, immunity cells). Moreover, a role for the cell-derived "matrix vesicles" and extracellular matrix (ECM) components has also been recognized. The aim of this work is to review the cellular and molecular alterations occurring in aortic valve during CAVD pathogenesis, focusing on the role of ECM in the natural course of the disease.
Assuntos
Valvopatia Aórtica/genética , Estenose da Valva Aórtica/genética , Valva Aórtica/patologia , Calcinose/genética , Matriz Extracelular/genética , Doenças das Valvas Cardíacas/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/patologia , Estenose da Valva Aórtica/patologia , Calcinose/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Matriz Extracelular/patologia , Doenças das Valvas Cardíacas/patologia , HumanosRESUMO
The intricate relationships between innate immunity and brain diseases raise increased interest across the wide spectrum of neurodegenerative and neuropsychiatric disorders. Barriers, such as the blood-brain barrier, and innate immunity cells such as microglia, astrocytes, macrophages, and mast cells are involved in triggering disease events in these groups, through the action of many different cytokines. Chronic inflammation can lead to dysfunctions in large-scale brain networks. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are associated with a substrate of dysregulated immune responses that impair the central nervous system balance. Recent evidence suggests that similar phenomena are involved in psychiatric diseases, such as depression, schizophrenia, autism spectrum disorders, and post-traumatic stress disorder. The present review summarizes and discusses the main evidence linking the innate immunological response in neurodegenerative and psychiatric diseases, thus providing insights into how the responses of innate immunity represent a common denominator between diseases belonging to the neurological and psychiatric sphere. Improved knowledge of such immunological aspects could provide the framework for the future development of new diagnostic and therapeutic approaches.
Assuntos
Imunidade Inata , Transtornos Mentais/imunologia , Doenças Neurodegenerativas/imunologia , Animais , HumanosRESUMO
Malignant transformation is a multistep process in which several molecular entities become dysregulated and result in dysfunction in the regulation of cell proliferation. In past years, scientists have gradually dissected the pathways involved in the regulation of the cell cycle. The mitotic ubiquitin-conjugating enzymes UbcH10, has been extensively studied since its cloning and characterization and it has been identified as a constantly overexpressed factor in many types of cancer. In this paper, we have reviewed the literature about UbcH10 in human cancer, pointing out the association between its overexpression and exacerbation of cancer phenotype. Moreover, many recalled studied demonstrated how immunohistochemistry or RT-PCR analysis can distinguish normal tissues and benign lesions from malignant neoplasms. In other experimental studies, many of the consequences of UbcH10 overexpression, such as increased proliferation, metastasizing, cancer progression and resistance to anticancer drugs are reversed through gene silencing techniques. In recent years, many authors have defined UbcH10 evaluation in cancer patients as a useful tool for diagnosis and therapy. This opinion is shared by the authors who advertise how it would be useful to start using in clinical practice the notions acquired about this important moleculein the carcinogenesis of many human malignancies.
Assuntos
Biomarcadores Tumorais , Transformação Celular Neoplásica/metabolismo , Suscetibilidade a Doenças , Enzimas de Conjugação de Ubiquitina/metabolismo , Ciclo Celular , Transformação Celular Neoplásica/genética , Gerenciamento Clínico , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Técnicas de Diagnóstico Molecular , Terapia de Alvo Molecular , Especificidade de Órgãos , Reação em Cadeia da Polimerase , Prognóstico , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
DJ-1 deglycase is a protein with anti-oxidative and anti-apoptotic properties and its role in oncogenesis is controversial. Indeed in primary breast cancer and non-small-cell lung carcinoma, its higher expression was shown in more aggressive tumors while in other neoplasms (e.g., pancreatic adenocarcinoma), higher expression was related to better prognosis. Beclin has a relevant role in autophagy and cellular death regulation, processes that are well known to be impaired in neoplastic cells. DJ-1 shows the ability to modulate signal transduction. It can modulate autophagy through many signaling pathways, a process that can mediate either cell survival or cell death depending on the circumstances. Previously, it has been suggested that the involvement of DJ-1 in autophagy regulation may play a role in tumorigenesis. The aim of our study was to investigate the link between DJ-1 and Beclin-1 in glioblastoma through the immunohistochemical expression of such proteins and to correlate the data obtained with prognosis. Protein expression was assessed by immunohistochemistry and the immunoscores were correlated with clinicopathologic parameters. Kaplan-Meier survival curves were generated. A statistically significant association between DJ-1 score and recurrence (p = 0.0189) and between the former and Isocitrate Dehydrogenase 1 (IDH1) mutation (p = 0.0072) was observed. Kaplan-Meier survival curve analysis revealed that a higher DJ-1 score was associated with longer overall survival (p = 0.0253, ĸ2 = 5.005). Furthermore, an unexpected direct correlation (p = 0.0424, r = 0.4009) between DJ-1 and Beclin score was evident. The most significant result of the present study was the evidence of high DJ-1 expression in IDH-mutant tumors and in cases with longer overall survival. This finding could aid, together with IDH1, in the identification of glioblastomas with better prognosis.
Assuntos
Proteína Beclina-1/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteína Desglicase DJ-1/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Adulto JovemRESUMO
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system. In this paper, we review the main aspects in the field of vascular diseases (cerebral ischemia), of primitive and secondary neoplasms of Central Nervous System CNS, of CNS infectious diseases, of most common neurodegenerative diseases, in epilepsy and in demyelinating diseases (multiple sclerosis). Neuroinflammation phenomena are constantly present in all diseases; in every different pathological state, a variety of innate immunity cells responds to specific stimuli, differentiating their action, which can influence the blood-brain barrier permeability. This, in turn, undergoes anatomical and functional modifications, allowing the stabilization or the progression of the pathological processes.
Assuntos
Imunidade Inata , Sistema Nervoso/irrigação sanguínea , Sistema Nervoso/citologia , Animais , Barreira Hematoencefálica/patologia , Humanos , Sistema Nervoso/imunologiaRESUMO
The role of macrophages in the growth and the progression of tumors has been extensively studied in recent years. A large body of data demonstrates that macrophage polarization plays an essential role in the growth and progression of brain tumors, such as gliomas, meningiomas, and medulloblastomas. The brain neoplasm cells have the ability to influence the polarization state of the tumor associated macrophages. In turn, innate immunity cells have a decisive role through regulation of the acquired immune response, but also through humoral cross-talking with cancer cells in the tumor microenvironment. Neoangiogenesis, which is an essential element in glial tumor progression, is even regulated by the tumor associated macrophages, whose activity is linked to other factors, such as hypoxia. In addition, macrophages play a decisive role in establishing the entry into the bloodstream of cancer cells. As is well known, the latter phenomenon is also present in brain tumors, even if they only rarely metastasize. Looking ahead in the future, we can imagine that characterizing the relationships between tumor and tumor associated macrophage, as well as the study of circulating tumor cells, could give us useful tools in prognostic evaluation and therapy. More generally, the study of innate immunity in brain tumors can boost the development of new forms of immunotherapy.
Assuntos
Neoplasias Encefálicas/imunologia , Macrófagos/imunologia , Células Neoplásicas Circulantes/imunologia , Animais , Hipóxia Celular , Polaridade Celular , Progressão da Doença , Humanos , Ativação de Macrófagos , PrognósticoRESUMO
Hyperactivation of mammalian target of rapamycin (mTOR) signaling pathway occurs after an epileptogenic insult and, its inhibition prevents the development of spontaneous seizures. We have recently demonstrated that mTOR's inhibition by rapamycin (started before seizure onset), permanently reduces the development of spontaneous absence seizures in WAG/Rij rats, an animal model of absence epilepsy; furthermore, mTOR phosphorylation was increased in adult WAG/Rij rats' cortex, but not other brain areas. However, it was not clear whether this hyperphosphorylation was a cause or a consequence of absence seizure. Here, we have addressed this issue by analyzing immunohistochemically: (1) the brain levels of total and phosphorylated mTOR in young (before seizures) and adult WAG/Rij rats; (2) the proliferation of hippocampal neuronal stem/progenitor cells assessed by BrdU analysis at different ages. WAG/Rij rats have higher levels of total mTOR in several brain areas than Wistar rats; phospho-mTOR staining is higher in young WAG/Rij rats than control and adult WAG/Rij rats. Finally, the age-related decline in hippocampal neural progenitor cell proliferation rate was slower in WAG/Rij than Wistar rats. Our results support a role for persistent mTOR activation and consequent change in hippocampal progenitor cell proliferation during the epileptogenic process leading to the development of absence seizures in WAG/Rij rats.
Assuntos
Epilepsia Tipo Ausência/fisiopatologia , Hipocampo/patologia , Células-Tronco Neurais/patologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia Tipo Ausência/metabolismo , Epilepsia Tipo Ausência/patologia , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/fisiologiaRESUMO
Complete blood cell count-derived parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have recently shown to be highly sensitive biomarkers. Their usefulness has been proven as prognostic factors in several cancers, in the stratification of mortality in major cardiac events, as predictors and markers of infectious or inflammatory pathologies, and in many other conditions. Surprisingly, the study of these biomarkers in neurological diseases is somewhat limited. This paper aims to take stock of the data present in the literature regarding the complete blood cell count-derived ratios in this group of pathologies and to formulate a hypothesis, based on the most recent data concerning innate and acquired immunity, on which diseases of the nervous system could benefit in diagnostic and prognostic terms from the in-depth study of these new biomarkers.
Assuntos
Biomarcadores/sangue , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/patologia , Contagem de Células Sanguíneas/métodos , Plaquetas/patologia , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Linfócitos/patologia , Monócitos/patologia , Neutrófilos/patologia , Contagem de Plaquetas/métodos , PrognósticoRESUMO
In cardiac myxomas, the malignant transformation process, selecting incidental gene mutations and leading to loss of proliferation control, has not a so drastic effects in terms of growth rate of tumor mass, but frequently the particular location of lesion engrosses the high risk for health. For accurate cancer cell profiling, it is important to establish the embryologic origin of malignant cells and their initial commitments, above all, in the sight of therapeutic strategies and solutions. Here, we advance, for cardiac myxoma, the hypothesis of an origin from cardiac neural crest cells and we attempt to support it by an integrated discussion of current knowledge about embryological characteristics of neural crest cells and most recent studies focusing cardiac myxomas. We discuss the relationship between the basic plasticity of cardiac neural crest cells and some typical mutations arising in neoplastic lesions as well as the expression of typical cell markers of neural crests derivatives. Dysfunctions in proliferative and migratory programs, focused in other studies, are evaluated in the context of the topological and histopathological characteristics of cardiac myxomas.
Assuntos
Complexo de Carney/patologia , Proliferação de Células , Transformação Celular Neoplásica/patologia , Transição Epitelial-Mesenquimal , Neoplasias Cardíacas/patologia , Miocárdio/patologia , Crista Neural/patologia , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Complexo de Carney/genética , Complexo de Carney/metabolismo , Movimento Celular , Plasticidade Celular , Transformação Celular Neoplásica/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/metabolismo , Humanos , Masculino , Mutação , Miocárdio/metabolismo , Crista Neural/metabolismo , Transdução de SinaisRESUMO
Mycosis fungoides (MF) is a cutaneous malignant lymphoma with an extended clinical course. MF presents in series of dermatological manifestations, beginning with patches and plaques of the skin, and eventually evolving into tumours. Often MF can occur for extended periods without worsening of external symptoms, while the disease advances internally in organs such as lymph nodes, liver, spleen, lung, bone marrow, gastrointestinal tract, pancreas and kidney. The present report presents a clinical case in which gastrointestinal symptomatology occurred a decade after the first dermatological manifestation. Immunohistochemical analysis of the skin, along with small bowel biopsies revealed evidence of gastric T-cell lymphoma. To the best of our knowledge, the present study is the first to describe such a case in the literature.
RESUMO
In the adult, many embryologic processes can be co-opted by during cancer progression. The mechanisms of divisions, migration, and the ability to escape immunity recognition linked to specific embryo antigens are also expressed by malignant cells. In particular, cells derived from neural crests (NC) contribute to the development of multiple cell types including melanocytes, craniofacial cartilage, glia, neurons, peripheral and enteric nervous systems, and the adrenal medulla. This plastic performance is due to an accurate program of gene expression orchestrated with cellular/extracellular signals finalized to regulate long-distance migration, proliferation, differentiation, apoptosis, and survival. During neurulation, prior to initiating their migration, NC cells must undergo an epithelial-mesenchymal transition (EMT) in which they alter their actin cytoskeleton, lose their cell-cell junctions, apicobasal polarity, and acquire a motile phenotype. Similarly, during the development of the tumors derived from neural crests, comprising a heterogeneous group of neoplasms (Neural crest-derived tumors (NCDTs)), a group of genes responsible for the EMT pathway is activated. Here, retracing the molecular pathways performed by pluripotent cells at the boundary between neural and non-neural ectoderm in relation to the natural history of NCDT, points of contact or interposition are highlighted to better explain the intricate interplay between cancer cells and the innate and adaptive immune response.
RESUMO
Innate immunity plays a central role in neoplasms, including those affecting the central nervous system (CNS). Nowadays, tumors classification, especially that regarding gliomas, is based on molecular features such as mutations in isocitrate dehydrogenase (IDH) genes and the presence of co-deletion 1p/19q. Therapy, in most cases, is based on surgery, radiotherapy, and pharmacological treatment with chemotherapeutic agents such as temozolomide. However, the results of the treatments, after many decades, are not completely satisfactory. There is a class of drugs, used to treat cancer, which modulates immune response; in this class, the immune checkpoint inhibitors and vaccines play a prominent role. These drugs were evaluated for the treatment of gliomas, but they exhibited a poor outcome in clinical trials. Those scarce results could be due to the response of tumor-associated macrophage that creates imbalances between innate and adaptive immunity and changes in blood-brain barrier properties. Here, we have briefly reviewed the current literature on this topic, focusing on the possible role for innate immunity in the failure of immunotherapies against brain tumors.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/imunologia , Glioma/imunologia , Imunidade Inata/imunologia , Imunoterapia/métodos , Animais , Antineoplásicos Imunológicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia/tendências , Nivolumabe/farmacologia , Nivolumabe/uso terapêuticoRESUMO
The data of literature are discordant about the role of mast cells in different types of neoplasms. In this paper the authors propose the hypothesis that tumor-associated mast cells may switch to different polarization states, conditioning the immunogenic capacities of the different neoplasms. Anti-inflammatory polarized mast cells should express cytokines such as interleukin-10 (IL-10) and then mast cells number should be inversely related to the intensity of inflammatory infiltrate. On the contrary, when mast cells do not express anti-inflammatory cytokines their number should be directly related to the intensity of the inflammatory infiltrate. In this paper we briefly argue around feasible approaches, based on the retrospective studies of tumor tissue samples from neoplasms considered "immunologically hot" and neoplasms considered "immunologically cold", through immunohistochemistry and immunofluorescence techniques (confocal microscopy). The establishment of the actual existence of a polarization interchange of mast cells, could lead to a new vision in prognostic terms, useful to contrive new approaches in immunotherapy of tumors.
Assuntos
Citocinas/biossíntese , Mastócitos/imunologia , Modelos Imunológicos , Neoplasias/imunologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Neoplasias/análise , Contagem de Células , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoquímica , Inflamação , Linfócitos do Interstício Tumoral/química , Macrófagos/química , Mastócitos/metabolismo , Mastócitos/ultraestrutura , Microscopia Confocal , Neoplasias/química , Neoplasias/ultraestrutura , Inclusão em Parafina , Proteínas Proto-Oncogênicas c-kit/análise , Receptores de Superfície Celular/análise , Projetos de Pesquisa , Estudos RetrospectivosRESUMO
Cardiac myxomas are the most common benign cardiac tumor. We investigated the immunohistochemical properties of 11 surgically excised cardiac myxomas, in order to analyze the correlation between macrophages and mast cell populations and clinical parameters. CD68+/CD163-/iNOS- (M0) cells represent the most abundant macrophage phenotype; however, CD68+/CD163+ cells (M2) were also frequent. CD68+/iNOS+ (M1) elements were rare. Mast cells, defined as a population of c-kit (CD117)+ and/or tryptase+ cells were also detected. Statistical analysis showed significant correlations between c-kit (CD117)+ and tryptase, CD68 and erythrocyte sedimentation rate (ESR), ESR and red blood cell count (RBC), and prothrombin time and platelet count. The inverse correlation between RBCs in peripheral blood and ESR suggested that anemia associated with chronic inflammatory disease is a noncasual event in patients suffering from cardiac myxoma. Mechanical hemolysis may be only a minor component of anemia, according to the lack of correlation between echographic surface and RBCs. Moreover, tumor size did not correlate with ESR, showing that inflammatory state may depend from both tumor cells population and inflammatory infiltrate. In the future, modulation of macrophage polarization in cardiac myxomas might represent important therapeutic target.
Assuntos
Neoplasias Cardíacas/imunologia , Imunidade Inata/imunologia , Mixoma/imunologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Sedimentação Sanguínea , Contagem de Células , Feminino , Neoplasias Cardíacas/patologia , Humanos , Imuno-Histoquímica , Macrófagos , Masculino , Mastócitos , Pessoa de Meia-Idade , Mixoma/patologia , Estudos RetrospectivosRESUMO
Chordoid meningioma (CM) is a rare subtype of meningioma, which represents only 0.5% of all meningiomas. It is classified as Grade II according to the World Health Organization classification because of its tendency to relapse. Pathological and clinical characteristics have been studied in order to forecast the future evolution of the lesions. However, information about infiltration of macrophagic elements and mast cells is very scarce. The authors analyzed the immunohistochemical patterns of three cases and a relapse of CM, in order to verify whether infiltrating macrophages are in a polarized state and what would be the proportion between such elements and mastocytes. Results suggest that macrophages in CMs are mainly in a non-polarized or M2 state and their abundance might be associated with a major potential of relapse; additionally, there is an inverse correlation between the number of mast cells and macrophages. Further studies are requested in order to confirm these intriguing data.
Assuntos
Neoplasias Meníngeas/imunologia , Meningioma/imunologia , Recidiva Local de Neoplasia/imunologia , Adulto , Idoso , Contagem de Células , Humanos , Imunidade Inata , Macrófagos/imunologia , Mastócitos/imunologia , Pessoa de Meia-Idade , RecidivaRESUMO
The link between cerebral small vessel disease (CSVD) and epilepsy has been poorly investigated. Some reports suggest that CSVD may predispose to temporal lobe epilepsy (TLE). Aim of this study was to evaluate whether spontaneously hypertensive rats (SHRs), an established model of systemic hypertension and CSVD, have a propensity to develop TLE more than generalized seizures. To this aim, amygdala kindling, as a model of TLE, and pentylenetetrazole (PTZ)-induced kindling, as a model of generalized seizures, have been used to ascertain whether SHRs are more prone to TLE as compared to Wistar Kyoto control rats. While young SHRs (without CSVD) do not differ from their age-matched controls in both models, old SHRs (with CSVD) develop stage 5 seizures in the amygdala kindling model (TLE) faster than age-matched control rats without CSVD. At odds, no differences between old SHRs and age-matched controls was observed in the development of PTZ kindling. Enalapril pre-treatment prevented the development of CSVD and normalized kindling development to control levels in SHRs. No difference was observed in the response to pharmacological treatment with carbamazepine or losartan. Overall, our study suggests that uncontrolled hypertension leading to CSVD might represent a risk factor for TLE. Further experimental studies are needed to unravel other risk factors that, along with CSVD, may predispose to TLE.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Convulsões/fisiopatologia , Animais , Doenças de Pequenos Vasos Cerebrais/complicações , Estimulação Elétrica , Epilepsia do Lobo Temporal/complicações , Masculino , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Convulsões/complicações , Especificidade da EspécieRESUMO
A number of available studies have focused on the role of mastocytes and their angiogenic factors, such as tryptase expression, in cancer growth as a major research objective. Cardiac myxoma is a rare neoplasia and is the most common primary tumor of the heart. The cellular elements of cardiac myxoma have an endothelial phenotype; however, its histogenesis remains unclear. Currently, no available studies have correlated the pathological characteristics of cardiac myxomas, such as cell differentiation and vascularization, with the angiogenic factors of mast cells. The aim of the present study was to investigate the role of mast cell tryptases on the development of cardiac myxomas and examine the histogenesis of tumoral cells. A series of 10 cardiac myxomas were examined by immunohistochemical analysis for the presence of tryptase-positive mast cells. Statistical analysis of our data demonstrated that angiogenesis and the development of pseudovascular structures were correlated with the number of tryptase-positive mast cells. Therefore, we hypothesize that cardiac myxoma cells are endothelial precursors which are able to generate mature vascular structures. Further morphological and immunophenotypic analyses of tumoral cells may corroborate such a hypothesis.