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1.
Pflugers Arch ; 476(8): 1235-1247, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38856775

RESUMO

To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.


Assuntos
Estimulação Elétrica , Laringe , Substância Cinzenta Periaquedutal , Proteínas Proto-Oncogênicas c-fos , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Substância Cinzenta Periaquedutal/metabolismo , Substância Cinzenta Periaquedutal/fisiologia , Estimulação Elétrica/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Laringe/fisiologia , Laringe/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Pressão , Bulbo/metabolismo , Bulbo/fisiologia , Ácido Glutâmico/metabolismo
2.
BMC Immunol ; 25(1): 7, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229027

RESUMO

BACKGROUND: Biomarkers that can predict outcome will improve the efficacy of treatment for HNSCC patients. In this regard, we retrospectively evaluated the prognostic effect of PD1, PD-L1, and CD45RO in tongue and larynx squamous cell carcinomas. METHODS: FFPE tissue blocks of 63 larynx and 40 tongue squamous cell carcinoma samples were selected, cut into 3 µm sections, and immunohistochemically stained for PD1, PD-L1, and CD45RO. The slides were evaluated by an expert pathologist, and results were analysed using Chi-square, univariate, and multivariable Cox regression methods. RESULTS: TC-PD-L1 expression (P = 0.001) and its expression intensity (P = 0.002) were significantly correlated with a higher percentage of PD-1 + tumor infiltrating lymphocytes. In univariate survival analysis, TC-PD-L1 and its expression intensity had a significant impact on both DFS (HR: 0.203; P = 0.003 and HR: 0.320; P = 0.005) and OS (HR: 0.147; P = 0.002 and HR: 0.322; P = 0.005). Based on the multivariate analysis, PD1 (DFS: HR: 3.202; P = 0.011, OS: HR: 2.671; P = 0.027) and TC-PD-L1 (DFS: HR: 0.174; P = 0.006, OS: HR: 0.189; P = 0.009) were found to be independent prognostic markers. In the second part, scoring systems were defined based on the expression status of PD1 and PD-L1. Patients with higher scores were expected to have longer DFS and OS. In multivariate analysis, the PD1/TC-PD-L1 (DFS: P = 0.001, OS: P = 0.003) scoring systems showed superior prognostic effects. Interestingly, at the highest levels of this score, none of the patients experienced recurrence or cancer-caused death. CONCLUSION: Collectively, this study suggests negative prognostic behaviour for TC-PD-L1 protein and introduces the PD-1/TC-PD-L1 scoring system as a strong prognostic marker in OS and DFS prediction of tongue and larynx HNSCC patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Laringe , Neoplasias da Língua , Humanos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Laringe/química , Laringe/metabolismo , Laringe/patologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Língua/química , Língua/metabolismo , Língua/patologia , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia
3.
Histochem Cell Biol ; 162(4): 287-297, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39031197

RESUMO

Mast cells (MCs) in rat airways have been classified into two subtypes: epithelial MCs and connective tissue MCs (CTMCs). However, the immunohistochemical characteristics, cellular morphology, and distribution of epithelial MCs in the upper airways remain unclear. The present study investigated the morphological characteristics and distribution of epithelial MCs using 5-hydroxytryptamine (5-HT) and other immunohistochemical markers in sectioned or whole-mount preparations of the rat larynx and trachea. A double immunofluorescence analysis revealed the colocalization of 5-HT immunoreactivity with c-kit, a stem cell factor receptor commonly used as a MC marker, in both epithelial MCs and CTMCs. Dopa decarboxylase, an enzyme involved in 5-HT synthesis, was detected in both subtypes, suggesting their ability to synthesize and release 5-HT. Tryptase and histidine decarboxylase (a biosynthetic enzyme of histamine), which are well-known mediators of MCs, were exclusive to CTMCs. Epithelial MCs were pleomorphic with long cytoplasmic processes, whereas CTMCs were round and lacked cytoplasmic processes. The density of epithelial MCs was significantly higher in the glottis and cranial part of the trachea than in the epiglottis and other parts of the trachea. The present results showed that the morphology and immunohistochemical characteristics of epithelial MCs were different from those of CTMCs in the rat larynx and trachea, and variform epithelial MCs were predominantly located at the entrance of the upper airways. Epithelial MCs may release 5-HT to regulate innate immune responses by modulating epithelial cell functions at the entrance gate of the upper airways.


Assuntos
Células Epiteliais , Imuno-Histoquímica , Laringe , Mastócitos , Traqueia , Animais , Mastócitos/metabolismo , Mastócitos/citologia , Ratos , Laringe/metabolismo , Laringe/citologia , Traqueia/citologia , Traqueia/metabolismo , Masculino , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Serotonina/metabolismo , Serotonina/análise , Ratos Wistar , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas c-kit/análise
4.
Medicina (Kaunas) ; 59(6)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37374276

RESUMO

Background and Objectives: Even if they are cells of controversial origin (mesenchymal, perivascular, or fibroblastic), follicular dendritic cells (FDC) are present in all organs. The aim of this study was to establish the FDC expression pattern and its interrelation with HPV 18 expression in laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Fifty-six cases of LSCC were evaluated by simple and double immunostaining. The following score was used: 0 (negative or few positive cells), 1 (10-30% of positive cells), 2 (30-50% of cells), and 3 (over 50% of cells). Results: The expression of CD 21-positive cells with dendritic morphology (CDM) was noticed in the intratumoral area of conventional (well and poorly differentiated types and HPV 18 positive cases with a value of 2 for the score) and papillary types (HPV-18 negative cases with a score of 1). The highest value of 2 for the score of CDM in HPV-18 positive cases was found in the peritumoral area of well- and poorly-differentiated conventional LSCCs. A significant correlation was found between scores of CDM from the intratumoral area and those of the peritumoral area (p = 0.001), between CDM and non-dendritic morphology cells (NDM) of the intratumoral area (p = 0.001), and between HPV-18 status and peritumoral NDM cells (p = 0.044). Conclusions: The FDC and NDM cell score values of intratumoral and peritumoral areas may represent important parameters of LSCCs. This may contribute to a better stratification of laryngeal carcinoma cases and the individualized selection of clinical treatment protocols.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Laringe , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Papillomavirus Humano 18 , Carcinoma de Células Escamosas/patologia , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/patologia , Laringe/metabolismo , Laringe/patologia
5.
Dev Biol ; 473: 33-49, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33515576

RESUMO

Proliferation and differentiation of vocal fold epithelial cells during embryonic development is poorly understood. We examined the role of Hippo signaling, a vital pathway known for regulating organ size, in murine laryngeal development. Conditional inactivation of the Hippo kinase genes Lats1 and Lats2, specifically in vocal fold epithelial cells, resulted in severe morphogenetic defects. Deletion of Lats1 and Lats2 caused abnormalities in epithelial differentiation, epithelial lamina separation, cellular adhesion, basement membrane organization with secondary failed cartilage, and laryngeal muscle development. Further, Lats1 and Lats2 inactivation led to failure in differentiation of p63+ basal progenitors. Our results reveal novel roles of Hippo-Lats-YAP signaling in proper regulation of VF epithelial fate and larynx morphogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Laringe/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular , Proliferação de Células/fisiologia , Células Epiteliais/metabolismo , Epitélio/fisiologia , Feminino , Via de Sinalização Hippo , Laringe/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfogênese , Proteínas Serina-Treonina Quinases/fisiologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/fisiologia , Prega Vocal/metabolismo , Prega Vocal/fisiologia , Proteínas de Sinalização YAP
6.
Bull Exp Biol Med ; 173(4): 553-559, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36094593

RESUMO

In squamous cell carcinoma of the larynx, the population of epithelial cells in the tumor tissue is initially heterogeneous and, in addition to tumor cells invading the organ mucosa, includes normal epithelial cells of protein-mucous glands and cells of the stratified epithelium covering the mucous membrane. A search for differential markers to separate these subpopulations was carried out. The surface marker CD44 and cytokeratins 5 and 17 that are often used to verify carcinoma cells, are common markers for all epithelial cells of the larynx. In highly differentiated carcinoma, subpopulations of normal and tumor epithelial cells can be separated by the level of expression of cytokeratins 10 and 18 and nuclear markers Ki-67 and p63. However, in moderately differentiated carcinoma, tumor cells and normal cells of the basal layer of the stratified epithelium covering the mucous membrane of the larynx have similar phenotypes, which should be taken into account when conducting experimental studies.


Assuntos
Carcinoma de Células Escamosas , Laringe , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Células Epiteliais/metabolismo , Epitélio/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Laringe/metabolismo
7.
Niger J Clin Pract ; 25(9): 1424-1429, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36149200

RESUMO

Background: Identifying tumor markers that can be used to determine the biological behavior of tumors and predicting their prognosis may be helpful in choosing treatment strategies. Besides the differences in the embryological and histological anatomy of the larynx in this regard, the possibility of molecular causes that can explain the different clinical behaviors has always been a question for the scientific world. Aim: In this study, we aimed to investigate whether there were any immunohistochemically molecular differences among laryngeal carcinoma cases originating from two different anatomical regions of the larynx. Patients and Methods: The study group consisted of 43 patients. The rate of supraglottic cancers was 41.8%, while the rest had glotto-subglottic tumors. Ki67, ß-catenin, E-cadherin, and p53 were examined in pathology preparations obtained by laryngectomy surgeries. The data obtained were analyzed by comparing factors that may affect the prognosis of the disease and between tumors originating from the two different anatomical regions. Results: We did not see any statistically significant difference between groups for stage and grade of tumor, tumor recurrence rate, or lymphovascular or perineural invasion rated in terms of the investigated markers. In addition, there was no statistically significant difference between the two distinct groups in survival analysis. Conclusions: With these results, our study differs from some studies in the literature, and we think that this difference could be because the cases in our study consisted of advanced stage tumors and the groups investigated had similar survival rates.


Assuntos
Carcinoma , Neoplasias Laríngeas , Laringe , Biomarcadores Tumorais , Caderinas/metabolismo , Carcinoma/patologia , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringe/metabolismo , Laringe/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Proteína Supressora de Tumor p53 , beta Catenina/metabolismo
8.
Development ; 145(4)2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29386246

RESUMO

Congenital laryngeal webs result from failure of vocal fold separation during development in utero Infants present with life-threatening respiratory problems at birth, and extensive lifelong difficulties in breathing and voicing. The molecular mechanisms that instruct vocal fold formation are rarely studied. Here, we show, for the first time, that conditional inactivation of the gene encoding ß-catenin in the primitive laryngopharyngeal epithelium leads to failure in separation of the vocal folds, which approximates the gross phenotype of laryngeal webbing. These defects can be traced to a series of morphogenesis defects, including delayed fusion of the epithelial lamina and formation of the laryngeal cecum, failed separation of the larynx and esophagus with reduced and disorganized cartilages and muscles. Parallel to these morphogenesis defects, inactivation of ß-catenin disrupts stratification of epithelial cells and establishment of p63+ basal progenitors. These findings provide the first line of evidence that links ß-catenin function to the cell proliferation and progenitor establishment during larynx and vocal fold development.


Assuntos
Anormalidades Congênitas/genética , Laringe/anormalidades , Laringe/metabolismo , Células-Tronco/metabolismo , Prega Vocal/metabolismo , beta Catenina/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Imunofluorescência , Camundongos
9.
Cell Mol Life Sci ; 77(19): 3781-3795, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32253462

RESUMO

The larynx and vocal folds sit at the crossroad between digestive and respiratory tracts and fulfill multiple functions related to breathing, protection and phonation. They develop at the head and trunk interface through a sequence of morphogenetic events that require precise temporo-spatial coordination. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as specification of the laryngeal field, epithelial lamina formation and recanalization as well as the development and differentiation of mesenchymal cell populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding congenital laryngeal disorders and the evaluation and treatment approaches in human patients. This review highlights recent advances in our understanding of the laryngeal embryogenesis. Proposed genes and signaling pathways that are critical for the laryngeal development have a potential to be harnessed in the field of regenerative medicine.


Assuntos
Doenças da Laringe/patologia , Laringe/metabolismo , Prega Vocal/metabolismo , Animais , Diferenciação Celular , Humanos , Doenças da Laringe/metabolismo , Laringe/crescimento & desenvolvimento , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais , Fator Nuclear 1 de Tireoide/metabolismo , Prega Vocal/crescimento & desenvolvimento
10.
Am J Physiol Lung Cell Mol Physiol ; 318(1): L89-L97, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31617735

RESUMO

Liquiritin apioside (LA), a main flavonoid component of licorice, reportedly suppresses cough responses to inhalation of aerosolized capsaicin [CAP; a stimulant to transient receptor potential vanilloid 1 (TRPV1)] in conscious guinea pigs via acting on peripheral nerves. However, the evidence of LA having a direct effect on airway sensory fibers is lacking. Considering the important role laryngeal chemoreceptors and mechanoreceptors play in triggering apnea and cough, we studied whether LA suppressed the apneic responses to stimulation of these receptors via directly acting on the superior laryngeal nerve (SLN). Intralaryngeal delivery of chemical [CAP, HCl, and distilled water (DW)] and mechanical [an air-pulse (AP)] stimulations was applied in anesthetized rat pups to evoke the apnea. These stimuli were repeated after intralaryngeal LA treatment or peri-SLN LA treatment to determine the direct effect of LA on the SLN. Our results showed that all stimuli triggered an immediate apnea. Intralaryngeal LA treatment significantly attenuated the apneic response to chemical but not mechanical stimulations. The same attenuation was observed after peri-SLN LA treatment. Owing that TRPV1 receptors of laryngeal C fibers are responsible for the CAP-triggered apneas, the LA impact on the activity of laryngeal C neurons retrogradely traced by DiI was subsequently studied using a patch-clamp approach. LA pretreatment significantly altered the electrophysiological kinetics of CAP-induced currents in laryngeal C neurons by reducing their amplitudes, increasing the rise times, and prolonging the decay times. In conclusion, our results, for the first time, reveal that LA suppresses the laryngeal chemoreceptor-mediated apnea by directly acting on the SLN (TRPV1 receptors of laryngeal C fibers).


Assuntos
Flavanonas/farmacologia , Glucosídeos/farmacologia , Laringe/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Animais , Apneia/tratamento farmacológico , Apneia/metabolismo , Tosse/tratamento farmacológico , Tosse/metabolismo , Feminino , Nervos Laríngeos/efeitos dos fármacos , Nervos Laríngeos/metabolismo , Laringe/metabolismo , Masculino , Fibras Nervosas Amielínicas/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/metabolismo
11.
Am J Physiol Gastrointest Liver Physiol ; 319(3): G412-G419, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32755305

RESUMO

A major component of gastric acid is hydrochloric acid (HCl), which can activate transient receptor potential vanilloid 1 (TRPV1). In the present study, we investigated how sustained laryngeal TRPV1 activation affects the frequency of the swallowing reflex. Experiments were carried out on 85 male Sprague-Dawley rats. The effects of short and sustained application of chemicals (3 µl of 0.1 N HCl or capsaicin) on the frequency of swallowing and on time-dependent changes in the occurrence of swallowing evoked by supralaryngeal nerve stimulation were determined. To evaluate vascular permeability of the larynx, Evans blue dye was intravenously injected after 5 or 60 min of sustained TRPV1 activation. SB366791 (a TRPV1 inhibitor) and Cap/QX-314 (a TRPV1-expressed neuronal inhibitor) significantly inhibited HCl/capsaicin-induced swallowing, but air flow-induced swallowing was not affected. Although the number of air flow-induced swallows followed by capsaicin stimulation was not affected within 5 min, it was significantly reduced by 60-min capsaicin or HCl application. The swallowing threshold associated with supralaryngeal nerve stimulation did not significantly change throughout the recording period. Evans blue dye concentrations in the larynx were significantly higher at 60 min in the 10-5 M capsaicin group than in the control group. Our results suggest that sustained TPRV1 activation not only desensitizes TRPV1 but also inactivates mechanoreceptors, which may be attributed to increases in vascular permeability and edema, as part of an inflammatory process.NEW & NOTEWORTHY Although a transient receptor potential vanilloid 1 (TRPV1) inhibitor or TRPV1-expressed neuronal inhibitor significantly inhibited HCl/capsaicin-evoked swallowing, air flow-induced swallowing was not affected. The number of air flow-induced swallows was significantly reduced within 60 min of TRPV1 activation. Evans blue dye concentration in the larynx increased 60 min after capsaicin application. TPRV1 activation not only desensitizes TRPV1 but also inactivates mechanoreceptors caused by increases in vascular permeability and edema.


Assuntos
Anestesia , Deglutição/efeitos dos fármacos , Laringe/metabolismo , Canais de Cátion TRPV/agonistas , Anilidas/farmacologia , Animais , Permeabilidade Capilar , Capsaicina/farmacologia , Cinamatos/farmacologia , Estimulação Elétrica , Nervos Laríngeos/fisiologia , Masculino , Mecanorreceptores/efeitos dos fármacos , Estimulação Física , Radiação , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV/antagonistas & inibidores
12.
Chem Senses ; 45(9): 823-831, 2020 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-33247587

RESUMO

The larynx plays a key role in airway protection via the laryngeal chemoreflex (LCR). This involuntary reflex can be evoked when hazardous substances activate mucosal receptors, which send signals to be processed within the brainstem. Although the LCR is meant to be protective, the reflex can become hyperstimulated, even to benign stimuli, which can result in pathological disorders, such as chronic cough and inducible laryngeal obstruction. In this review, we will outline the mechanism of the LCR and its associated pathological disorders.


Assuntos
Obstrução das Vias Respiratórias/metabolismo , Transtornos Respiratórios/metabolismo , Animais , Apneia/metabolismo , Tronco Encefálico/metabolismo , Células Quimiorreceptoras/metabolismo , Tosse/metabolismo , Humanos , Nervos Laríngeos/metabolismo , Laringe/metabolismo , Reflexo
13.
J Mater Sci Mater Med ; 31(12): 130, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252704

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) are well-known for tissue regeneration and bone repair. This study intended to evaluate the potential efficiency BMSCs in poly(lactide-co-glycolide) (PLGA) scaffolds for the treatment of laryngeal cartilage defects. BMSCs were isolated and identified, and added with 10 ng/mL transforming growth factor-beta1 (TGF-ß1) or/and 300 ng/mL CDMP1 to coculture with PLGA scaffolds. The chondrogenic differentiation, migration, and apoptosis of BMSCs were detected under the action of TGF-ß1 or/and CDMP1. After successful modeling of laryngeal cartilage defects, PLGA scaffolds were transplanted into the rabbits correspondingly. After 8 weeks, laryngeal cartilage defects were assessed. Levels of collagen II, aggrecan, Sox9, Smad2, Smad3, ERK, and JNK were detected. The TGF-ß1 or/and CDMP1-induced BMSCs expressed collagen II, aggrecan, and Sox9, with enhanced cell migration and inhibited apoptosis. In addition, laryngeal cartilage defect in rabbits with TGF-ß1 or/and CDMP1 was alleviated, and levels of specific cartilage matrix markers were decreased. The combined effects of TGF-ß1 and CDMP1 were more significant. The TGF-ß1/Smad and ERK/JNK pathways were activated after TGF-ß1 or/and CDMP1 were added to BMSCs or rabbits. In summary, BMSCs and PLGA scaffolds repair laryngeal cartilage defects in rabbits by activating the TGF-ß1/Smad and ERK/JNK pathways under the coaction of TGF-ß1 and CDMP1.


Assuntos
Cartilagem/metabolismo , Fator 5 de Diferenciação de Crescimento/metabolismo , Células-Tronco Mesenquimais/citologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Apoptose , Células da Medula Óssea/citologia , Diferenciação Celular , Movimento Celular , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Feminino , Laringe/metabolismo , Laringe/fisiologia , Masculino , Transplante de Células-Tronco Mesenquimais , Coelhos , Alicerces Teciduais
14.
Am J Forensic Med Pathol ; 41(4): 249-258, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32568883

RESUMO

Anaphylaxis is a serious reaction that may cause death in half an hour without diagnostic characteristic in autopsies. Mast cell (MC) degranulation combined with immunoglobulin E (IgE) plays the key roles in anaphylaxis. Unavailability of serum and instability of measured serum in postmortem diagnoses sometimes limit the opinion of medical experts. Allergic tissues are more accessible than serum, and there is a little research on degranulated mast cells and IgE in different human tissues, whereas we hardly know whether the expression will keep stable over the increasing postmortem interval (PMI). In this research, we examined the mast cell counts and degranulation rates and gE contents in human throat, lung, and intestine tissues and preliminarily investigated the correlation of these markers with PMI in anaphylaxis-associated death. Allergic samples showed a significant increase in mast cell degranulation accompanied by an increase in IgE levels than the control group, but the expression was not significantly correlated with increasing PMI only in throat tissues. Elevated mast cell degranulation combined with increased IgE levels may be a reliable biomarker for forensic diagnosis of human tissues due to IgE-mediated allergic sudden death.


Assuntos
Anafilaxia/patologia , Degranulação Celular , Imunoglobulina E/metabolismo , Mastócitos/patologia , Faringe/patologia , Mudanças Depois da Morte , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Laringe/metabolismo , Laringe/patologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Faringe/metabolismo , Adulto Jovem
15.
Bull Exp Biol Med ; 169(6): 802-805, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33108559

RESUMO

We analyzed the association of the level of mRNA expression of the main endocytosis receptor LRP1 and actin-binding proteins (ezrin, profilin-1, cofilin-1, and adenylyl cyclase-associated protein 1) with the development and metastasis of laryngeal and laryngopharyngeal squamous cell carcinoma. The mRNA expression was evaluated in paired tissue samples using quantitative reverse transcription real-time PCR (RT-qPCR) and SYBR Green reagents. The study included 38 patients with stage T1-4N0-1M0 laryngeal and laryngopharyngeal squamous cell carcinoma and 10 patients with chronic hyperplastic laryngitis or grade II-III epithelial dysplasia. The expression of LRP1 in patients with laryngeal and laryngopharyngeal squamous cell carcinoma depended on the stage of the tumor process. Against the background of low expression of LRP1 mRNA, the relationship between cofilin 1 and profilin 1 expression became stronger (r=0.08; p=0.05) and a correlation between cofilin 1 and esrin expression (r=0.7; p=0.05) appeared. Studies on a larger patient cohort are required to make a definite conclusion on the role of LRP1 in the development of laryngeal and laryngopharyngeal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/genética , Cofilina 1/genética , Proteínas do Citoesqueleto/genética , Neoplasias Laríngeas/genética , Laringite/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Neoplasias Faríngeas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Laringite/metabolismo , Laringite/patologia , Laringe/metabolismo , Laringe/patologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Faríngeas/metabolismo , Neoplasias Faríngeas/patologia , Faringe/metabolismo , Faringe/patologia , Profilinas/genética , Profilinas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais
16.
Bull Exp Biol Med ; 169(4): 504-507, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32915364

RESUMO

We analyzed the expression of genes encoding proteins involved in cytoskeleton remodeling (RND3, SNAI1, vimentin, cofilin, adenylate cyclase-associated protein 1, ezrin, and profilin) depending on the level of expression of protein phosphatase 1B (PPM1B) mRNA on the example of squamous cell carcinoma of the larynx and hypopharynx. Against the background of a high level of PPM1B expression, a significantly high level of profilin expression was noted. Metastasis correlated with the level of snai1 expression, while relapse after combination treatment was negatively associated with the level of vimentin expression. The obtained new data can reflect molecular peculiarities of the tumor growth in squamous cell carcinoma of the larynx and hypopharynx.


Assuntos
Citoesqueleto/genética , Neoplasias de Cabeça e Pescoço/genética , Recidiva Local de Neoplasia/genética , Profilinas/genética , Proteína Fosfatase 2C/genética , RNA Mensageiro/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cofilina 1/genética , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hipofaringe/metabolismo , Hipofaringe/patologia , Laringe/metabolismo , Laringe/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Profilinas/metabolismo , Proteína Fosfatase 2C/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Vimentina/genética , Vimentina/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
17.
Biochem Biophys Res Commun ; 510(2): 205-210, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30691694

RESUMO

Postnatal organ-specific stem and progenitor cells are an attractive potential donor cell for tissue-engineering because they can be harvested autologous from the recipient and have sufficient potential to regenerate the tissue of interest with less risk for ectopic growth or tumor formation compared to donor cells from embryonic or fetal sources. We describe the generation of tissue-engineered larynx and trachea (TELT) from human and mouse postnatal organoid units (OU) as well as from human fetal OU. Mouse TELT contained differentiated respiratory epithelium lining large lumens, cartilage and smooth muscle. In contrast, human postnatal TE trachea, formed small epithelial lumens with rare differentiation, in addition to smooth muscle and cartilage. Human fetal TELT contained the largest epithelial lumens with all differentiated cell types as well as smooth muscle and cartilage. Increased epithelial cytokeratin 14 was identified in both human fetal and postnatal TELT compared to native trachea, consistent with regenerative basal cells. Cilia in TELT epithelium also demonstrated function with beating movements. While both human postnatal and fetal progenitors have the potential to generate TELT, there is more epithelial growth and differentiation from fetal progenitors, highlighting fundamental differences in these cell populations.


Assuntos
Epitélio/metabolismo , Laringe/fisiologia , Células-Tronco/metabolismo , Engenharia Tecidual/métodos , Traqueia/fisiologia , Animais , Cartilagem/metabolismo , Diferenciação Celular , Proliferação de Células , Cílios/metabolismo , Células Epiteliais/metabolismo , Epitélio/embriologia , Receptores ErbB/metabolismo , Humanos , Interleucina-2/genética , Queratina-14/metabolismo , Laringe/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Músculo Liso/metabolismo , Organoides/metabolismo , Mucosa Respiratória/metabolismo , Traqueia/metabolismo
18.
Am J Otolaryngol ; 40(1): 89-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30472132

RESUMO

PURPOSE: To build a murine model for tobacco smoke and electronic cigarette vapor exposure to characterize the inflammatory and immune responses in the larynx. MATERIALS AND METHODS: In this pilot study, twenty-four wild-type C57BL/6 mice were divided into four groups: smoke, vapor with nicotine, vapor without nicotine, and air only. Following daily exposure for 4 months, larynges were dissected and processed with cytokine detection arrays. Each laryngeal cytokine level between the four different groups was analyzed statistically by using statistical analysis software (SAS) to calculate the analysis of variance (ANOVA). RESULTS: IL-4 was the only cytokine found to achieve statistically significant different levels in this study, with elevated levels of IL-4 in the tobacco smoke and vapor with nicotine groups compared to the levels found in the vapor without nicotine and air only groups (p = 0.0418). While statistically non-significant, prominent findings revealed up-regulation of TGF-ß2 and TGF-ß3 in the smoke group, but near-normal levels of TGF-ß2 and TGF-ß3 and suppression of IL-10 in the vapor groups (p > 0.05). CONCLUSION: The potential utility of the murine model is established for studying the inflammatory and immune effects of tobacco smoke and vapor on the mammalian larynx. IL-4 levels in mice larynges were significantly elevated in the tobacco smoke and vapor with nicotine groups.


Assuntos
Interleucina-4/metabolismo , Laringe/efeitos dos fármacos , Nicotina/farmacologia , Fumar Tabaco/efeitos adversos , Fator de Crescimento Transformador beta/metabolismo , Vaping/efeitos adversos , Animais , Interleucina-10/metabolismo , Laringe/metabolismo , Laringe/patologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Fumaça/efeitos adversos
19.
Histopathology ; 72(7): 1102-1114, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29266325

RESUMO

AIMS: Malignant tumours from the upper aerodigestive tract are grouped collectively in the class of head and neck squamous cell carcinoma (HNSCC). The head and neck tumours were responsible for more than 500 000 cancer cases in 2012, accounting for the sixth highest incidence rate and mortality worldwide among all tumour types. Laryngeal squamous cell carcinoma (LSCC) possesses the second highest incidence rate among all HNSCC. Despite significant advances in surgery and radiotherapy during the last few decades, no treatment has been shown to achieve a satisfactory therapeutic outcome and the mortality rate of LSCC is still high, with a 5-year survival rate of 64%. Therefore, further investigations are required to identify the pathogenesis of LSCC. METHODS AND RESULTS: In order to search for new LSCC biomarkers, we have analysed the expression of the HMGA family members, HMGA1 and HMGA2, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. HMGA proteins are usually absent in the healthy adult tissues. In contrast, their constitutive expression is a feature of several neoplasias, being associated with a highly malignant phenotype and reduced survival. Here, we report HMGA2 overexpression in larynx carcinomas. Conversely, HMGA1 does not show any differences in its expression between normal and carcinoma tissues. Interestingly, HMGA2 overexpression appears associated with that of two HMGA1-pseudogenes, HMGA1P6 and HMGA1P7, acting as a sponge for HMGA1- and HMGA2-targeting microRNAs and involved in several human cancers. CONCLUSIONS: Therefore, HMGA2 overexpression appears to be a strong feature of larynx carcinoma, supporting its detection as a valid tool for the diagnosis of these malignancies.


Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Proteína HMGA2/genética , Neoplasias Laríngeas/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Feminino , Proteína HMGA1a/metabolismo , Proteína HMGA2/metabolismo , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Laringe/metabolismo , Laringe/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade
20.
Bull Exp Biol Med ; 166(2): 250-252, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30488206

RESUMO

The model of head and neck squamous cell carcinoma (HNSCC) was used to study the expression of genes encoding actin-binding proteins depending on the type of cell motility. The expression of SNAIL1 and CAPN2 mRNA in HNSCC tissue was higher than in specimens of dysplastic epithelium of the larynx and hypopharynx, which can be explained by activation of mesenchymal and amoeboid types of cell motility. In biopsy material of HNSCC patients with T1-2N0M0, expression of genes responsible for actin-binding proteins differed from that of patients with pretumor pathology of the larynx and hypopharynx: expression of FSCN was lower, while expressions of EZR and CAP1 were higher. The data attest that progression of HNSCC is associated with activation of both types of cell motility and with the changes in the expression of mRNA encoding cell motility proteins.


Assuntos
Calpaína/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Fatores de Transcrição da Família Snail/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Calpaína/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Cofilina 1/genética , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hipofaringe/metabolismo , Hipofaringe/patologia , Laringe/metabolismo , Laringe/patologia , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Profilinas/genética , Profilinas/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Vimentina/genética , Vimentina/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
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