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BACKGROUND: The deep location of infratemporal fossa (ITF) combined with the abundant vascular plexus in it increased the difficulty of removing the mass in ITF through endoscope surgery approach. However, under appropriate circumstances, the excision of ITF tumors through a combined prelacrimal recess, Caldwell-Luc, and distal intraoral approach can be safely performed with minimal impact on the surrounding tissues. CASE PRESENTATION: The Department of Neurology received a 69-year-old male patient who had been experiencing headache, dizziness, and numbness from the mastoid region of his left ear to the corner of his mouth for a duration of 22 days. Cranial magnetic resonance imaging revealed the presence of a tumor located in the ITF. Following transfer to our department, surgical intervention was performed using a combined approach involving the prelacrimal recess, the anterior wall of maxillary sinus, and lateral ITF to successfully remove the tumor. Postoperative pathologic examination confirmed schwannoma as its nature. The patient was discharged in excellent condition without any functional impairment. CONCLUSIONS: On the basis of this case, the authors believe that this combined approach can offer a distinct endoscopic perspective and adequate surgical workspace, which is crucial for tumor removal while preserving the integrity of surrounding normal tissues. Moreover, the utilization of multiple small incisions has minimal impact on postoperative recovery.
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Objective: Differentiating 2 types of chronic rhinosinusitis with nasal polyps (CRSwNP) is important for the treatment. The current diagnostic methods using single indicators, including peripheral blood eosinophils and traditional sinus computed tomography (CT) scores, are not accurate. In this study, we aimed to investigate the diagnostic value of combining peripheral blood eosinophils and improved sinus CT scores for eosinophic chronic rhinosinusitis (ECRS). Study Design: Retrospective cohort. Setting: Tertiary medical center. Methods: We conducted a study involving 81 patients with CRSwNP. Peripheral blood samples were collected from the non-ECRS and ECRS groups. Improved three-dimensional volume image analysis and Lund-Mackay scoring system were performed to quantify the thickening of sinus mucosa. Multivariate binary logistic regression analysis was carried out to detect the predictive value of the scoring indicators. For significant indexes, receiver operating characteristic (ROC) curve analysis was applied. Results: The ECRS group had higher levels of blood eosinophil percentage and count, ethmoid sinus score, total sinus score, the ratio of ethmoid sinus score and maxillary sinus score, and the difference between ethmoid and maxillary score, compared to the non-ECRS group (P < 0.05). Binary logistic regression analysis demonstrated that both blood eosinophil percentage and the improved E - M score (subtraction of ethmoid and maxillary sinus scores) were significant predictors of ECRS diagnosis (P < .01). ROC curve analysis indicated that the combination of improved E - M score and blood eosinophil percentage had a higher diagnostic value compared to either factor alone (area under the curve = 0.874). Conclusion: Our study suggested the combination of improved total ethmoid sinus-maxillary score and blood eosinophil percentage is more accurate in predicting the diagnosis of ECRS.
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The study aimed at investigating the morphological characteristics and interconnected regularities of the cavernous sinus (CS) venous spaces using an expanded endoscopic endonasal transsphenoidal approach. Surgical dissections were performed for 15-colored silicon-injected human head specimens. The CS venous spaces were examined for their morphological and clinical characteristics using an expanded endoscopic endonasal transsphenoidal approach. The intracavernous course of the internal carotid artery (ICA) divided the CS venous spaces into four interconnected virtual compartments: medial, anteroinferior, posterosuperior, and lateral. The CS venous spaces had peculiar morphological characteristics; the medial compartment was C-shaped while the anteroinferior compartment resembled a boat's bow. The mean distances from the medial border of the inferior horizontal segment of cavernous ICA to the mid-line of the pituitary gland (PG) were 6.07 ± 1.61 mm (left) and 5.97 ± 1.89 mm (right); the mean distances from the medial border of the subarachnoid segment of cavernous ICA to the mid-line of the PG were 5.77 ± 1.16 mm (left) and 5.63 ± 1.17 mm (right); the mean distances from the medial border of the anterior vertical segment of cavernous ICA to the mid-line of the PG were 10.27 ± 1.74 mm (left) and 10.47 ± 1.90 mm (right). Morphological characteristics and the knowledge of the interconnected regularities of the CS venous spaces may help surgeons accurately locate the neurovascular structure, and thus may contribute to the effective prediction of tumor invasion and extension during endoscopic CS surgery.
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Seio Cavernoso , Neoplasias Hipofisárias , Seio Cavernoso/anatomia & histologia , Seio Cavernoso/patologia , Endoscopia , Humanos , Hipófise/patologia , Neoplasias Hipofisárias/patologia , SilícioRESUMO
BACKGROUND: Laryngeal neurilemmoma, especially recurrent laryngeal neurilemmoma, is a rare neural sheath tumor in head and neck. The most common symptom of laryngeal neurilemmoma is hoarseness or dysphonia, followed by dysphagia, dyspnea, and foreign body sensation. At present, surgical resection is the most effective treatment for this kind of tumor, thus making how to remove it become the most concerned problem of surgeons. CASE PRESENTATION: On February 18, 2021, a 64-year-old male presented to our clinic with recurrent sore throat and intermittent hoarseness for 3 years. The results of electronic laryngoscope and magnetic resonance imaging showed a 25×10×21 mm well-defined tumor in the left pyriform sinus without laryngeal cartilage destruction and enlarged lymph nodes. After the initial diagnosis of recurrent laryngeal neurilemmoma, to preserve the continuity of recurrent laryngeal nerve as much as possible, the authors determine to perform anatomical resection of recurrent laryngeal neurilemmoma with operating microscope under the monitoring of recurrent laryngeal nerve function. Finally, the patient recovered completely from hoarseness during postoperative follow-up. CONCLUSION: A complete diagnosis and treatment process of recurrent laryngeal neurilemmoma was presented by the case. Particularly, it shows the application of recurrent laryngeal nerve monitoring in the operation helps to protect the continuity of the recurrent laryngeal nerve, which lays a anatomical bases for the follow-up nerve repair.
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Laringe , Neoplasias de Bainha Neural , Neurilemoma , Rouquidão/etiologia , Rouquidão/cirurgia , Humanos , Laringe/patologia , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Nervo Laríngeo Recorrente/patologia , Nervo Laríngeo Recorrente/cirurgiaRESUMO
Long noncoding RNAs (lncRNAs) perform indispensable functions in cancer pathologies and are involved in the onset and progression of multiple cancers. Multiple platforms were performed to comprehensively analyze the head and neck squamous cell carcinoma (HNSCC) for determining molecular subtypes. Molecular subtypes were clustered and analyzed by the "ConsensusClusterPlus" R package. The Limma software was utilized to screen for differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO), were performed on the three database resources. Seventeen lncRNAs were determined as HNSCC-specific immune lncRNAs that were dysregulated. Our research identified and redefined two distinct molecular subtypes, C1 (230 samples) and C2 (269 samples). Moreover, the C1 subtype had a higher survival rate than the C2 subtype in HNSCC samples, as well as a prolonged median survival duration with activated immune response. 1531 DEGs, including 529 upmodulated genes and 1002 downmodulated genes, were identified in the above two subtypes. Functional enrichment analysis revealed that upmodulated genes in C2 were associated with tumorigenesis and development, while downregulated genes in C2 were associated with immune response. By comparing with the existing immunophenotyping group, it found that C1 had more overlaps with the existing Atypical and Basal, and C2 and Classical and Mesenchymal had a high degree of coincidence. On the basis of lncRNA, there were significant differences in the aspect of prognostic and immunological characteristics in the two identified molecular subtypes of HNSCC.
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BACKGROUND: Retropharyngeal abscesses are rarely reported in adults and occur mostly in patients with immunocompromised or as a foreign body complication. Admittedly, the treatment of retropharyngeal abscesses frequently involves surgical drainage to achieve the best results. However, when retropharyngeal abscesses occurred in a highly suspected patient with COVID-19, the managements and treatments should be caution to prevent the spread of the virus. CLINICAL PRESENTATION: On February 13, a 40-year-old male with retropharyngeal abscesses turned to our department complaining dyspnea and dysphagia. In addition, his chest CT scan shows a suspected COVID-19 infection, thus making out Multiple Disciplinary Team determine to perform percutaneous drainage and catheterization through left anterior cervical approach under the guidance of B-ultrasound. Finally, the patient recovered and was discharged from the hospital on February 27 after 14 days of isolation. There was no recurrence after half a year follow-up. CONCLUSIONS: By presenting this case, we aim at raising awareness of different surgical drainage methods and summarizing our experience in the management of retropharyngeal abscesses during the outbreak of COVID-19.
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COVID-19 , Pneumonia , Abscesso Retrofaríngeo , Adulto , Surtos de Doenças , Drenagem , Humanos , Masculino , Abscesso Retrofaríngeo/diagnóstico por imagem , Abscesso Retrofaríngeo/cirurgia , SARS-CoV-2RESUMO
IMPACT STATEMENT: Nasopharyngeal cancer is one of the most common malignant tumors in the head and neck. Identification of promising miRNA biomarkers might benefit a lot to the detection of nasopharyngeal carcinoma. A three-miRNA signature (has-miR-142-3p, has-miR-29c, and has-miR-30e) was obviously associated with the overall survival of nasopharyngeal carcinoma patients. The model has better clinical independence and has better clinical prediction effect when combined with clinical characteristics. Our results revealed that a three-miRNA signature was a potential novel prognostic biomarker for nasopharyngeal carcinoma.
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Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Área Sob a Curva , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/patologia , Prognóstico , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Invasion of pituitary growth hormone-secreting adenoma into surrounding tissues poses a challenge for complete resection in surgery, which is the main reason for recurrence of this type of cancer. Studies have shown that abnormal methylation of RASSF10 can promote the expression of MDM2 and regulate the tumor microenvironment by affecting the secretion of exosomes. In the present study, we aim to uncover the specific underlying mechanism of this effect. METHOD: Transwell co-culture assays was performed using GT1.1 cells or exosomes and RAW264.7 cells. RAW264.7 cells were collected for invasion, proliferation and apoptosis assays, RT-qPCR and western blotting. RNA-seq was performed and used to assess the potential molecular pathways of the effect of GT1.1 cell-exosomes on RAW264.7 cells. RESULTS: GT1.1 cells with reduced RASSF10 expression could promote the proliferation and migration of RAW264.7 cells, and promote their expression of osteoclast markers TRAP and CK. The effect of GT1.1 cell exosomes on the RAW264.7-cell phenotype was shown to be achieved through the RASSF10-MDM2 pathway. RNA-seq allowed the identification of PI3K-AKT, MAPK, and calcium signaling as important in this regulation system of RASSF10-MDM2. CONCLUSION: Our results indicate that GT1.1 cells activate PI3K-AKT, MAPK and calcium signaling via the RASSF10-MDM2 pathway, and promote the differentiation of RAW264.7 cells into osteoclasts through exosomes. This study may provide new ideas to aid in early diagnosis, prognostic assessment and treatment of aggressive pituitary adenomas.
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Adenoma/patologia , Exossomos/metabolismo , Hormônio do Crescimento/metabolismo , Invasividade Neoplásica/patologia , Neoplasias Hipofisárias/patologia , Proteínas Supressoras de Tumor/metabolismo , Adenoma/metabolismo , Animais , Neoplasias Ósseas/secundário , Diferenciação Celular , Movimento Celular , Proliferação de Células , Técnicas de Cocultura , Camundongos , Neoplasias Hipofisárias/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Células RAW 264.7 , Transdução de SinaisRESUMO
Allergic rhinitis (AR) is a worldwide highly prevalent nasal inflammatory disease with elusive mechanisms about the regulation of innate immune response. The roles and mechanisms of NLRP3, a typical inflammasome, in AR development remain unclear. Here we investigate the roles of NLRP3 inflammasome activation in the development and progression of AR and try to uncover its potential mechanisms underlying. Wildtype and NLRP3 knockout mice were applied to construct the ovalbumin (OVA)-induced AR model. Caspase-1 specific inhibitor Belnacasan and inflammasome activator ATP were used for adjuvant stimulation of AR-model mice respectively. We found that the production of IL-1ß and the activation of inflammasome were increased in both patients and mice with AR. NLRP3 deficiency markedly suppressed AR progression with reduced inflammatory response and epithelium pyroptosis in mice with AR. Furthermore, Caspase-1 inhibitor treatment in vivo ameliorated the development and progression of AR with favorable outcomes. Mechanistically, inflammation augments and nasal mucosa injury during AR were partially due to ASC-specks accumulation and subsequent cell pyroptosis. Our study reveals the previously unknown roles of NLRP3 inflammasome in promoting the development and progression of AR via enhancing inflammatory response and epithelium pyroptosis and thus provides a potential clue for allergic disease interventions.
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Epitélio/patologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Rinite Alérgica/patologia , Adolescente , Adulto , Idoso , Animais , Linhagem Celular , Progressão da Doença , Epitélio/metabolismo , Feminino , Humanos , Imunoglobulina E/sangue , Inflamação , Interleucina-1beta/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Ovalbumina/metabolismo , Rinite Alérgica/metabolismo , Adulto JovemRESUMO
Pituitary adenomas are the most common intrasellar tumors. Patients should be identified at an early stage so that effective treatment can be implemented. The study aims at detecting the potential biomarkers with diagnostic value of pituitary adenomas. Using a total of seven gene expression profiles (GEPs) of the datasets from the Gene Expression Omnibus (GEO) database, we first screened 1980 significant differentially expressed genes (DEGs). Then, we employed the prediction analysis for microarray (PAM) algorithm to identify 340 significant DEGs able to differ pituitary tumor from normal samples, which include 208 upregulated DEGs and 132 downregulated DEGs. DAVID database was used to carry out the enrichment analysis on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways. We found that upregulated candidates were enriched in protein folding and metabolic pathways. Downregulated DEGs saw a significant enrichment in insulin receptor signaling pathway and hedgehog signaling pathway. Based on the protein-protein interaction (PPI) network as well as module analysis, we determined ten hub genes including PHLPP, ENO2, ACTR1A, EHHADH, EHMT2, FOXO1, DLD, CCT2, CSNK1D, and CETN2 that could be potential biomarkers with diagnostic value in pituitary adenomas. In conclusion, the study contributes to reliable and potential molecular biomarkers with diagnostic value. Moreover, these potential biomarkers may be used for prognosis and new therapeutic targets for the pituitary adenomas.
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Adenoma/química , Biomarcadores Tumorais/análise , Neoplasias Hipofisárias/química , Adenoma/diagnóstico , Adenoma/genética , Algoritmos , Biomarcadores Tumorais/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/genética , Análise Serial de Tecidos , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND/AIMS: Nasopharyngeal cancer (NPC) is one of the common human malignant diseases all over the world, and chemotherapy remains the main therapy for NPC. However, the survival and life quality of NPC patients are still very poor. Thus, novel and selective anti-tumor agents are pressingly needed. Our previous study identified pectolinarigenin as a novel effective anti-tumor drug candidate for NPC. In this study, we further investigated its anti-tumor activities and explored the potential molecular mechanism. METHODS: NPC C666-1 cells were cultured and treated by pectolinarigenin. Cell proliferation assay, colony formation assay, Transwell assay and wound healing assay were conducted and cell apoptosis was detected by flow cytometry. Mitochondrial transmembrane potential and ROS were also observed. NPC subcutaneous xenograft mice model was established to evaluate the anti-tumor effect of pectolinarigenin in vivo. RESULTS: We observed that treatment of pectolinarigenin inhibited cell viability and cell migration of NPC C666-1 cells in concentration- and time-dependent manner. Pectolinarigenin induced cell apoptosis in C666-1 cells detected by flow cytometry analysis, which was associated with the activation of mitochondrial-related apoptosis and the accumulation of reactive oxygen species (ROS). Pectolinarigenin also activated caspase signaling pathway. The in vivo experiment of subcutaneous xenograft mice model also indicated that the administration of pectolinarigenin could decrease the tumor growth of NPC and no severe toxicity was observed. CONCLUSIONS: Based on our findings, we conclude that pectolinarigenin could suppress the tumor growth of NPC, which verifies it as a new therapeutic agent for treating this devastating disease.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Animais , Carcinoma , Caspases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The aim of this study was to investigate the relationship between the morphological characteristics of the sphenoid sinus and endoscopic localization of the cavernous sinus (CS) using an extended endoscopic endonasal transsphenoidal approach. Thirty sides of CS in 15 adult cadaver heads were dissected to simulate the extended endoscopic endonasal transsphenoidal approach, and the morphology of the sphenoid sinus and anatomic structures of CS were observed. The opticocarotid recess (OCR), ophthalmomaxillary recess (V1V2R), and maxillomandibular recess (V2V3R) in the lateral wall of the sphenoid sinus were presented in 16 sides (53.3%), 6 sides (20%), and 4 sides (13.3%) of the 30 sides, respectively. OCR is a constant anatomic landmark in endoscopy and coincides with the anterior portion of the clinoidal triangle. The C-shaped internal carotid artery (ICA) in the lateral wall of the sphenoid sinus was presented in 11 sides (36.7%), the upper one-third of which corresponds to the middle portion of the clinoidal triangle, and the lower two-thirds of which correlates to the supratrochlear triangle, infratrochlear triangle, and ophthalmic nerve in CS, around which the medial, lateral, and anteroinferior interspaces are distributed. From a front-to-behind perspective, the C-shaped ICA consists of inferior horizontal segment, anterior vertical segment, clinoidal segment as well as partial subarachnoid segment of the ICA. OCR and C-shaped ICA in the lateral wall of the sphenoid sinus are the 2 reliable anatomic landmarks in the intraoperative location of the parasellar region of CS.
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Seio Cavernoso/anatomia & histologia , Cirurgia Endoscópica por Orifício Natural/métodos , Seio Esfenoidal/anatomia & histologia , Adulto , Pontos de Referência Anatômicos/anatomia & histologia , Cadáver , Artéria Carótida Interna/anatomia & histologia , Humanos , Mandíbula/irrigação sanguínea , Artéria Maxilar/anatomia & histologia , Nariz , Nervo Oculomotor/anatomia & histologia , Artéria Oftálmica/anatomia & histologia , Nervo Oftálmico/anatomia & histologia , Nervo Óptico/anatomia & histologia , Seio Esfenoidal/irrigação sanguínea , Seio Esfenoidal/inervação , Nervo Trigêmeo/anatomia & histologia , Nervo Troclear/anatomia & histologiaRESUMO
AIMS: Nasopharyngeal carcinoma (NPC) is the most common primary malignancy of the nasopharynx. Due to its local recurrence and distant metastasis, conventional therapy is usually ineffective. MDA-7/IL-24 (melanoma differentiation associated gene 7), a member of the IL10 family of cytokines, inhibits growth of various human cancer cells, but the underlying mechanism is largely unknown. There is no report of mda-7 in nasopharyngeal carcinoma. We aimed to investigate the role of MDA-7/IL-24 in NPC. METHODS: Immune defective adenoviral vector carrying the gene was produced, infected NPC CNE cells and observed its growth, cell proliferation, apoptosis and the effect of combination with chemotherapy. RESULTS: The results showed that (1) MDA-7/IL-24 inhibited NPC CNE cell growth and survival; (2) mda-7 induced cell apoptosis and death; (3) MDA-7/IL-24 in collaboration with chemotherapy induced cell apoptosis significantly; (4) MDA-7/IL-24 induced cell apoptosis by down-regulation of anti-apoptosis molecules such as Bcl-2 and Bcl-xl and up-regulation of caspase 3. CONCLUSION: The results suggested that MDA-7/IL-24 had obvious therapeutic effect in NPC cells. It is verified that adenovirus mediated MDA-7/IL-24 represents a potentially important new approach to NPC therapy.
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BACKGROUND/AIMS: The pathogenic mechanisms underlying pituitary adenoma formation, progression, and invasion are poorly understood. To identify candidate tumor suppressor genes, we selected somatotroph adenomas as representative of pituitary adenomas. METHODS/RESULTS: We used genome-wide differential expression analysis in 15 invasive and 12 noninvasive somatotroph adenomas. HEPN1 reduction was more frequent in the invasive group, and this result was confirmed by qRT-PCR. To understand the function of HEPN1, the pituitary adenoma cell lines, GH3 and GT1.1, were stably transfected with short hairpin RNA (shRNA) targeting HEPN1 or ectogenic HEPN1 by lentivirus-mediated transfection. We found that HEPN1 overexpression in GH3 and GT1.1 cells inhibited cell proliferation, induced apoptosis, and attenuated invasive capacity, whereas HEPN1 silencing enhanced cell proliferation and invasion accompanied by decreased apoptosis. Western blot analysis revealed that HEPN1 overexpression decreased MMP-2, MMP-9, and Bcl-2 expression, but increased BAX, p53, and caspase-3 expression. In contrast, HEPN1 silencing increased MMP-2, MMP-9, and Bcl-2 expression, but decreased BAX, p53, and caspase-3 expression. CONCLUSION: Taken together, our results suggest that reduction of HEPN1 may play an important role in the progression of pituitary somatotroph adenomas. HEPN1 may thus be a candidate as a prognostic predictor or an anticancer therapeutic target for patients with somatotroph adenoma.
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Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Neoplasias Hipofisárias/metabolismo , Proteínas/metabolismo , Interferência de RNA , Animais , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Neoplasias Hipofisárias/patologia , Proteínas/antagonistas & inibidores , Proteínas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
The pathogenic mechanisms underlying pituitary somatotroph adenoma formation, progression are poorly understood. To identify candidate tumor suppressor genes involved in pituitary somatotroph adenoma tumorigenesis, we used HG18 CpG plus Promoter Microarray in 27 human somatotroph adenomas and 4 normal human adenohypophyses. RASSF3 was found with frequent methylation of CpG island in its promoter region in somatotroph adenomas but rarely in adenohypophyses. This result was confirmed by pyrosequencing analysis. We also found that RASSF3 mRNA level correlated negatively to its gene promoter methylation level. RASSF3 hypermethylation and downregulation was also observed in rat GH3 and mouse GT1.1 somatotroph adenoma cell lines. 5-Aza-2' deoxycytidine and trichostatin-A treatment induced RASSF3 promoter demethylation, and restored its expression in GH3 and GT1.1 cell lines. RASSF3 overexpression in GH3 and GT1.1 cells inhibited proliferation, induced apoptosis accompanied by increased Bax, p53, and caspase-3 protein and decreased Bcl-2 protein expression. We also found that the antitumor effect of RASSF3 was p53 dependent, and p53 knockdown blocked RASSF3-induced apoptosis and growth inhibition. Taken together, our results suggest that hypermethylation-induced RASSF3 silencing plays an important role in the tumorigenesis of pituitary somatotroph adenomas.
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Transformação Celular Neoplásica/genética , Metilação de DNA , Inativação Gênica , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Proteínas Monoméricas de Ligação ao GTP/genética , Animais , Apoptose/genética , Azacitidina/farmacologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Ilhas de CpG , Metilação de DNA/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Camundongos , Regiões Promotoras Genéticas , RNA Mensageiro/genética , Ratos , Proteína Supressora de Tumor p53/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine Selaginella doederleinii Hieron has been combined with radiotherapy for the treatment of human nasopharyngeal carcinoma in clinic in China. However, the detailed mechanism of anti-tumor effect of Selaginella doederleinii remains elusive. AIM OF THE STUDY: This study was designed to investigate the anti-tumor effect of ethanol extract of Selaginella doederleinii (SDE) on human nasopharyngeal carcinoma and its possible mechanisms. MATERIALS AND METHODS: Viability, apoptosis and protein expression of tumor cells were analyzed by MTT, Annexin V staining and Western blot, respectively. Formation of intracellular reactive oxygen species was determined using dichlorofluorescin fluorescence. The in vivo anti-tumor effect was evaluated by measuring tumor volume changes and TUNEL staining in nude mice. RESULTS: SDE significantly inhibited the growth and induced apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, SDE triggered the mitochondrial/caspase apoptotic pathway indicated by enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase cascade. Moreover, SDE provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N-acetyl cysteine almost completely blocked SDE-induced disruption of mitochondrial membrane potential, caspases activation and apoptosis. Furthermore, a transplantable nude mice model was utilized to estimate the effectiveness of SDE in vivo. The treated mice displayed decreased tumor size, which was associated with enhanced apoptotic cell death. CONCLUSIONS: These results, offering solid evidence of the induction of mitochondria-related apoptosis in tumor cells, provide the molecular theoretical basis of clinical application of Selaginella doederleinii for the treatment of human nasopharyngeal carcinoma.
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Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neoplasias Nasofaríngeas/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Selaginellaceae , Acetilcisteína/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/fisiologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/fisiopatologia , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Previous studies revealed that polydatin, a natural small compound, possessed protective effect against ischemia/reperfusion injury and inflammation. However, the action and molecular mechanism of its potent anti-cancer activity remain poorly understood. In the present study, polydatin significantly killed several human tumor cell lines in a dose- and time-dependent manner. The compound also dose-dependently caused mitochondrial apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, polydatin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt in CNE cells, while knock-down of CCAAT/enhancer-binding protein homologous protein (CHOP) dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of polydatin. Furthermore, polydatin provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting polydatin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in CNE cells. Taken together, these findings strongly suggest that polydatin might be a promising anti-tumor drug and our data provide the molecular theoretical basis for clinical application of polydatin.
Assuntos
Apoptose/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Glucosídeos/farmacologia , Mitocôndrias/metabolismo , Neoplasias Nasofaríngeas/patologia , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/farmacologia , Estresse Fisiológico , Sequência de Bases , Caspases/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Humanos , Neoplasias Nasofaríngeas/enzimologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente PequenoRESUMO
OBJECTIVE: To explore a simple and accurate method for localization of upper airway obstruction in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and provide instructions for surgical treatment. METHOD: Fifty OSAHS patients confirmed by PSG underwent acoustic rhinometric and pharyngometric assessment by Eccovision. The parameters were recorded, including nasal minimal cross-sectional area (NMCA), distance of MCA from the nostril (DCAN), minimum cross-sectional area at the nasal valve(MCA), nasal resistance (NR) and nasal volume from 0 to 6 cm from the nostril (NCV), as well as pharyngeal cross-sectional area (CSA) and volume from 4.8 to 15.0 cm. The sensitivity and specificity of acoustic rhinometry and pharyngometry on localization of airway obstruction was determined by a comprehensive imaging and endoscopic study. RESULT: In 50 cases with severe OSAHS, NMCA, DCAN, MCA, NCV, NR were (0.61 +/- 0.35) cm2, (2.06 +/- 0.12) cm, (0.87 +/- 0.12) cm2, (9.24 +/- 2.31)cm3 and (0.51 +/- 0.32)kPa/(L x min), respectively. Pharyngeal CSA and volume were statistically significantly lower than that in control group (P < 0.01). The value of DCAN was (2.06 +/- 0.12) cm, (9.50 +/- 4.08) cm, (13.10 +/- 2.52) cm in type I II, III patient, respectively. Compared with the control group, the difference was statistically significant. CONCLUSION: Acoustic rhinometry and pharyngometry is a simple and safe method in localization of airway obstruction in patients with OSAHS.
Assuntos
Cavidade Nasal/fisiopatologia , Rinometria Acústica , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To provide transnasal endoscopic optic canal decompression with the anatomic reference. METHOD: 15 samples of the adult corpse wet specimen (30 sides for the optic canal) were examined under the endoscope to scrutinize the regional anatomy of the optic canal. RESULT: distance between the spina nasalis anterior and the midpoint of optic canal medial wall is (61.02 +/- 5.83) mm, and the angle between spina nasalis anterior and the midpoint of optic canal medial wall is (45.1 +/- 4.81) degrees. The medial wall of optic canal is longest, with an average length of (11.61 +/- 1.58) mm; the lateral wall of optic canal is thickest, and the medial wall thinnest. 10 traumatic blind patient underwent endoscopic optic canal decompression with satisfactory outcome. CONCLUSION: The regional anatomy of the optic canal under endoscope is of importance to endoscopic optic canal decompression. Which is microinvasive with direct approach and clear view thus is widely used in clinical practice.