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1.
Front Immunol ; 15: 1364799, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524124

RESUMO

Purpose: To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC). Methods: We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed. Results: A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved. Conclusion: The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.


Assuntos
Neoplasias Hipofaríngeas , Terapia Neoadjuvante , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Resultado do Tratamento , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Hipofaríngeas/patologia , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de Neoplasias
2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(1): 104-110, 2024 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38475958

RESUMO

OBJECTIVES: With the assistance of 3D visualization and real-time navigation technologies, the tumors in the parapharyngeal and lateral skull base should be removed through oral the approach with endoscopy. METHODS: The preoperative CT data of eight patients with parapharyngeal or lateral skull base soft tissue tumors were modeled, and the anatomical position relationship between the tumor and surrounding blood vessels and other important structures was reconstructed using 3D visualization technology, and preoperative design was performed. The intraoperative oral approach and real-time navigation guidance were adopted in the endoscopic resection of soft tissue tumors in the parapharyngeal and lateral skull base, and the clinical application value of this method was evaluated. RESULTS: The blood loss during the operation was controlled within 150 mL, and the average blood loss was approximately 125 mL. The incidence of postoperative complications was low, and patients could recover well through functional training. The oral approach did not leave any wounds nor scars on the patient's facial skin after the operation and had no effect on the patient's appearance. CONCLUSIONS: The combination of 3D visualization technology, intraoperative real-time navigation, and endoscopy provides a beautiful, safe, and minimally invasive surgical method for patients with parapharyngeal or lateral skull base tumors.


Assuntos
Neoplasias da Base do Crânio , Neoplasias de Tecidos Moles , Humanos , Neoplasias da Base do Crânio/cirurgia , Imageamento Tridimensional , Endoscopia/métodos , Base do Crânio/cirurgia
3.
Cell ; 186(20): 4454-4471.e19, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37703875

RESUMO

Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA sequencing map of the dynamics of human macrophage specification from PCW 4-26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart. They are the major immune population in the early epidermis, exhibit a polarized distribution along the dorsal-lateral-ventral axis, and interact with neural crest cells, modulating their differentiation along the melanocyte lineage. Through spatial and differentiation trajectory analysis, we also showed that proangiogenic macrophages are perivascular across fetal organs and likely yolk-sac-derived as microglia. Our study provides a comprehensive map of the heterogeneity and developmental dynamics of human macrophages and unravels their diverse functions during development.


Assuntos
Macrófagos , Humanos , Diferenciação Celular , Linhagem da Célula , Macrófagos/citologia , Microglia , Especificidade de Órgãos
5.
Clin Cancer Res ; 29(15): 2791-2799, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184934

RESUMO

PURPOSE: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. PATIENTS AND METHODS: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. RESULTS: Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. CONCLUSIONS: Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Humanos , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Radioisótopos do Iodo/efeitos adversos , Piridinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia
6.
Reprod Sci ; 30(6): 1746-1757, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36694081

RESUMO

Embryo implantation and decidualization are key steps in establishing a successful pregnancy. Defects in embryo implantation and decidualization can cause a series of adverse chain reactions which can contribute to harmful pregnancy outcomes, such as embryo growth retardation, preeclampsia, miscarriage, premature birth, and so on. Approximately 75% of failed pregnancies are considered to be due to embryo implantation failure or defects. Decidualization, characterized by proliferation and differentiation of uterine stromal cells, is one of the essential conditions for blastocyst implantation, placental formation, and maintenance of pregnancy and is indispensable for the establishment of pregnancy in many species. Embryo implantation and decidualization are closely regulated by estrogen and progesterone secreted by the ovaries. Many cellular events and molecular signaling network pathways are involved in this process. This article reviews the recent advances in the molecular mechanisms of estrogen- and progesterone-regulating uterine receptivity establishment, blastocyst implantation, and decidualization, in order to better understand the underlying molecular mechanisms of hormonal regulation of embryo implantation and to develop new strategies for preventing or treating embryo implantation defects and improving the pregnancy rate of women.


Assuntos
Decídua , Progesterona , Gravidez , Feminino , Camundongos , Animais , Progesterona/metabolismo , Decídua/metabolismo , Placenta/metabolismo , Implantação do Embrião/fisiologia , Estrogênios/metabolismo , Útero/metabolismo , Células Estromais/metabolismo
7.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 197-200, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38279443

RESUMO

The present study aimed to elucidate the role of MicroRNA-203b-3p (miRNA-203b-3p) in protecting the deterioration of laryngeal carcinoma through targeting ZNF324. Relative levels of miRNA-203b-3p and ZNF324 in laryngeal carcinoma tissues with different tumor node metastasis (TNM) staging and pathological grades were detected. Regulatory effects of miRNA-203b-3p on clonality, viability and 5-Ethynyl-2'- deoxyuridine (EdU)-positive ratio in M2E and TU212 cells were assessed. The binding relationship between miRNA-203b-3p and ZNF324 was evaluated by dual-luciferase reporter gene assay. The involvement of ZNF324 in cell phenotype changes of laryngeal carcinoma regulated by miRNA-203b-3p was explored by rescue experiments. MiRNA-203b-3p was downregulated in laryngeal carcinoma, especially in those with advanced TNM staging or pathological grade. Overexpression of miRNA-203b-3p reduced clonality, viability and EdU-positive ratio in M2E and TU212 cells. In addition, ZNF324 was upregulated in laryngeal carcinoma, which was negatively regulated by miRNA-203b-3p. ZNF324 was verified to be the target binding miRNA-203b-3p. Notably, overexpression of ZNF324 could partially reverse the inhibitory effects of miRNA-203b-3p on laryngeal carcinoma proliferation. MiRNA-203b-3p is downregulated in laryngeal carcinoma, which blocks laryngeal carcinoma cells to proliferate through targeting ZNF324 and thus alleviates cancer progression.


Assuntos
Carcinoma , Proteínas de Ligação a DNA , Neoplasias Laríngeas , MicroRNAs , Humanos , Carcinoma/metabolismo , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Ligação a DNA/metabolismo
8.
J Med Internet Res ; 24(8): e34126, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921135

RESUMO

BACKGROUND: Questionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders. OBJECTIVE: This study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo. METHODS: In this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation. RESULTS: A total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation. CONCLUSIONS: The questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.


Assuntos
Aprendizado de Máquina , Inquéritos e Questionários , Vertigem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Vertigem/diagnóstico
10.
Oncogene ; 41(24): 3316-3327, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35411035

RESUMO

GRB2-associated-binding protein 2 (Gab2) deletion has a preventive effect of on chronic liver inflammation and hepatocellular carcinoma. This study was aimed to elaborate Gab2-initiated immunoregulation during hepatocarcinogenesis. Compared to wild-type group, liver-specific overexpression of Gab2 mice (L-Gab2) displayed early hepatocarcinogenesis after 5-month diethylnitrosamine (DEN) induction, and accelerated tumor growth after 9-month DEN challenge. More myeloid-derived suppressor cells (MDSCs) were observed in DEN-challenged L-Gab2 mice than that in DEN-treated wild-type mice. Additionally, MDSCs activation-induced tumor angiogenesis capability and immunosuppression function were exceedingly activated in DEN-exposed L-Gab2 mice, which reflected in the increased platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF), and the decreased cytotoxic T lymphocytes. Mechanistically, DEN-challenged L-Gab2 mice produced more IL-6, and IL-6 depletion significantly deprived Gab2-overexpression-mediated tumor-promotion phenomena, accompanied by the impairment of MDSCs-initiated immunosuppression function. MDSCs isolated from IL-6-depleted L-Gab2 mice or inactivating MDSCs partly restored the immune function of cytotoxic T cells. Of note, MDSCs gene signatures had a significant association with the increased Gab2 or IL6 in hepatoma specimens. Collectively, L-Gab2 mice accelerated hepatoma progression possibly through activating IL-6-initiated the activation of MDSCs. This study provides a novel insights for exploring the role of Gab2 in autoimmune tolerance during hepatocarcinogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supressoras Mieloides , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/metabolismo , Humanos , Terapia de Imunossupressão , Interleucina-6/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos , Células Supressoras Mieloides/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Physiol Res ; 71(2): 285-295, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-35275699

RESUMO

Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. Emilin 1 plays a determinant role in fibers formation, but its role in the progression of GMC remains unclear. The present study was aimed to search for the predictive role and regulatory mechanism of Emilin 1 on GMC. Here, Protein and mRNA expression of Emilin 1 were decreased in GMC tissues compared to normal muscle tissues. Using the anslysis of target prediction, Emilin 1 was observed to be a potential downstream sponge of miR-491-5p. In comparison to Emilin 1, miR-491-5p showed a aberrant elevation in GMC tissues, which was further proven to have a negative correlation with Emilin 1. The direct binding of miR-491-5p to Emilin 1 mRNA was confirmed by luciferase reporter gene assay, and miR-491-5p mimics inhibited, while miR-491-5p inhibitor promoted the protein expression and secretion of Emilin 1 in contraction bands (CB) fibroblasts. Additionally, miR-491-5p mimics promoted the expression of cyclin-dependent kinase 2 and cyclin D1 and the proliferation of CB fibroblasts, which could be reversed by Emilin 1 overexpression. Mechanistically, miR-491-5p mimics possibly activated transforming growth factor beta1 (TGF-beta1)/Smad3 signal cascade via binding to 3'-untranslated region of Emilin 1 mRNA, thereby promoting the progression of fibrosis of CB fibroblasts. Collectively, miR-491-5p inhibited Emilin 1 expression, and subsequently promoted CB fibroblasts proliferation and fibrosis via activating TGF-beta1/Smad3 signal axis. MiR-491-5p might be a potentially effective biomarker for predicting GMC, providing a novel therapeutic strategy for GMC.


Assuntos
Contratura , MicroRNAs , Proliferação de Células , Contratura/patologia , Fibroblastos/metabolismo , Fibrose , Humanos , Glicoproteínas de Membrana , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/genética
12.
Bioengineered ; 13(3): 6650-6664, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35230214

RESUMO

Mitochondrial fission depends on dynamin-related protein 1 (Drp1) guanosine triphosphatase activity. Although there is some association between Drp1 and gastric cancer, the detailed mechanism remains largely unknown. In this study, the elevation of Drp1 was observed in human gastric carcinoma specimens including gastric mixed adenocarcinoma tissues, gastric intestinal-type adenocarcinoma tissues, and human gastric cancer cells compared to normal control, but not in diffuse gastric adenocarcinoma tissues. Gastric cancer patients with high Drp1 harbored advanced pathological stages and poor progression-free survival probability compared to those with low Drp1. Mdivi-1-mediated inactivation of Drp1 robustly inhibited cell viability and tumor growth but conversely induced cell apoptotic events in vitro and in vivo. Based on the Encyclopedia of RNA Interactomes Starbase, L22 ribosomal protein (RPL22) was recognized as the potential downstream oncogene of Drp1. Clinically, the significant correlation of Drp1 and RPL22 was also verified. Mechanistically, Drp1 inactivation did not affect the accumulation of RPL22 in gastric carcinoma. However, the intracellular distribution of RPL22 had an endonuclear location in Drp1-inactivated tumors. Of note, Drp1 inactivation notably reduced the expression of cytoplasmic RPL22 and increased its nuclear level in gastric cancer cells. Collectively, Drp1 had high levels in human gastric carcinoma specimens and could serve as a potential diagnostic and prognostic biomarker in gastric carcinoma. The Drp1 inactivation-mediated anti-proliferative and pro-apoptosis effects on gastric cancer were possibly associated with nuclear import of RPL22. This knowledge may provide new therapeutic tools for treating gastric carcinoma via targeting mitochondria-related ribosome pathway.


Assuntos
Dinaminas/genética , Proteínas Ribossômicas/genética , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Transcriptoma/genética
13.
Crit Rev Eukaryot Gene Expr ; 31(5): 51-57, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591390

RESUMO

The study explored the cross-talk between the microRNA miR-34a and prominin 1 in the development of laryngeal cancer (LC), which has an unacceptable high mortality rate. We predicted that miR-34a might target prominin 1. miR-34a and prominin 1 expression was analyzed with reverse transcription quantitative polymerase chain reaction. The correlation between miR-34a and prominin 1 was determined by linear regression analysis. miR-34a and prominin 1 overexpression and miR-34a inhibition were achieved in LC cells to analyze their relationship. The roles of miR-34a and prominin 1 in LC cell proliferation were studied with CCK-8 assay. The results showed miR-34a was downregulated, and prominin 1 was upregulated in LC. In addition, prominin 1 and miR-34a were inversely correlated across cancer tissue samples. In cancer cells, miR-34a overexpression downregulated prominin 1, while miR-34a knockdown upregulated prominin 1. Moreover, miR-34a overexpression reduced the enchaining effects of prominin 1 on LC cell proliferation. Therefore, miR-34a might suppress LC cell proliferation by targeting prominin 1.


Assuntos
Antígeno AC133/metabolismo , Proliferação de Células , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , MicroRNAs/metabolismo , Idoso , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Transcriptoma
14.
Pediatr Res ; 89(7): 1832-1839, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33007780

RESUMO

BACKGROUND: Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population. METHODS: In this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2-12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded. RESULTS: Patients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2-6 years). Drug-related adverse events occurred in <20% of patients in all groups. FFNS was well tolerated at both doses. CONCLUSIONS: This study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2-12 years), supporting its use in clinical treatment for AR children, including younger children aged 2-6 years. IMPACT: The aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2-6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2-6 years.


Assuntos
Androstadienos/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Administração Intranasal , Androstadienos/administração & dosagem , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Placebos , Resultado do Tratamento
15.
Front Cell Dev Biol ; 8: 566504, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330448

RESUMO

Histone demethylase PHF8 is crucial for multiple developmental processes, and hence, the awareness of its function in developing auditory organs needs to be increased. Using in situ hybridization (ISH) labeling, the mRNA expression of PHF8 in the zebrafish lateral line system and otic vesicle was monitored. The knockdown of PHF8 by morpholino significantly disrupted the development of the posterior lateral line system, which impacted cell migration and decreased the number of lateral line neuromasts. The knockdown of PHF8 also resulted in severe malformation of the semicircular canal and otoliths in terms of size, quantity, and position during the inner ear development. The loss of function of PHF8 also induced a defective differentiation in sensory hair cells in both lateral line neuromasts and the inner ear. ISH analysis of embryos that lacked PHF8 showed alterations in the expression of many target genes of several signaling pathways concerning cell migration and deposition, including the Wnt and FGF pathways. In summary, the current findings established PHF8 as a novel epigenetic element in developing auditory organs, rendering it a potential candidate for hearing loss therapy.

16.
Ann Transl Med ; 8(16): 993, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953793

RESUMO

BACKGROUND: Integrin subunit α 8 (ITGA8) methylation has been associated with the development of several cancers, but its contribution to breast cancer remains unclear. The present study aimed to investigate the methylation status of ITGA8, and the underlying regulatory mechanisms of ITGA8 methylation in breast cancer. METHODS: ITGA8 expression was investigated using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database and the Breast Cancer Gene-Expression Miner v.4.4 (bc-GenExMiner v4.4). The association between ITGA8 expression levels and the survival rate of breast cancer patients was evaluated using The Cancer Genome Atlas (TCGA) database and Gene Expression-based Outcome for Breast Cancer Online (GOBO): Gene Set Analysis. Methylation-specific PCR (MSP) was used to detect the methylation of ITGA8. Protein level of ITGA8 was determined by Western blot analysis. RESULTS: ITGA8 was expressed at low levels in human breast cancer cells compared to non-tumorigenic breast cells and breast tissue, and was upregulated in estrogen receptor (ER)-positive tissue compared with ER-negative tissue (P<0.01). ITGA8 gene expression was negatively associated with breast tumor stage and survival rate in all breast cancer patients. However, ER-positive patients with low ITGA8 expression showed poorer distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) rates than patients with high ITGA8 expression. This was not observed in the ER-negative population. Mechanistically speaking, hypermethylation of ITGA8 was discovered in ER-positive breast cancer cells. Administration of the methylation inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), significantly elevated protein expression of ITGA8 in ER-positive breast cancer cells compared to ER-negative cells. The positive association between ITGA8 status and methylation was also observed in clinical tissue specimens. When treated with 17-beta-estradiol, an antagonist of ERα, 5-aza-dC-induced upregulation of ITGA8 in ER-positive breast cancer cells was no longer observed. CONCLUSIONS: Low ITGA8 expression in ER-positive breast cancer might be caused by the hypermethylation of ITGA8, a process dependent on ERα. Our findings provide an important foundation for investigations into ITGA8-targeted treatment strategies for ER-positive breast cancer.

17.
Eur Arch Otorhinolaryngol ; 277(10): 2829-2838, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449029

RESUMO

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.


Assuntos
Refluxo Laringofaríngeo , Otolaringologia , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
18.
Aging (Albany NY) ; 12(7): 6240-6259, 2020 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276266

RESUMO

Esophageal carcinoma (EsC) is a clinically challenging neoplastic disease. Genistein, a natural isoflavone product, has anti-tumor properties. Through in vitro and in vivo studies, we found that genistein suppressed EsC cell proliferation in a time- and concentration-dependent manner. In addition, genistein markedly promoted apoptosis and arrested cell cycle at the G0/G1 phase in a concentration-dependent manner. Furthermore, high concentrations of genistein have no adverse effect on normal esophageal epithelial cells. Mechanistically, genistein treatment strikingly reduced the expression of cell cycle-associated genes, and up-regulated the expression of cell apoptosis-related genes in EsC cells. Additionally, genistein dramatically decreased epidermal growth factor receptor (EGFR) expression and attenuated its down-stream signaling molecules STAT3, MDM2, Akt and JAK1/2 phosphorylation, resulting in inhibited nuclear translocation of STAT3 and MDM2, thereby inhibiting the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways. In xenograft nude mice, genistein administration strikingly impaired tumor growth in a dose-dependent manner. Moreover, similar disturbances in molecular mechanisms were observed in vivo. Taken together, genistein suppressed the JAK1/2-STAT3 and AKT/MDM2/p53 signaling pathways by decreasing EGFR expression, leading to cell apoptosis, cell cycle arrest, and proliferation inhibition in EsC cells. Our findings suggest that genistein may be a promising alternative adjuvant therapy for patients with EsC.


Assuntos
Carcinoma , Neoplasias Esofágicas , Genisteína/farmacologia , Janus Quinase 1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma/tratamento farmacológico , Carcinoma/metabolismo , Carcinoma/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Camundongos , Fitoestrógenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J BUON ; 24(2): 813-818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128040

RESUMO

PURPOSE: The study was designed to analyze the risk factors related to postoperative recurrence of thyroid cancer to reduce the recurrence rate. METHODS: A total of 250 patients with thyroid cancer after operation were collected and divided into non-recurrent group (n=220) and recurrent group (n=30) according to whether the cancer recurred after operation or not. The postoperative recurrence rate of thyroid cancer was analyzed. The general condition, tumor characteristics, surgical approach, conditions of postoperative I131 treatment and pathological type of the two groups of patients were compared. The correlations of the postoperative recurrence of thyroid cancer with clinical risk factors were analyzed by means of Logistic regression analysis. RESULTS: The recurrence rate of thyroid cancer after operation was 12%, and the cumulative recurrence rates at 1, 2 and 3 years after operation were 3.20%, 6.00% and 10.40%, respectively. The recurrence rate in males was higher than that in females (p<0.05). The larger tumor diameter, the lower rate of lymph node metastasis and the lower level of tissue differentiation would eventually lead to the higher recurrence rate (p<0.01). Tumor diameter, lymph node metastasis and pathological type were correlated with the postoperative recurrence of thyroid cancer (p<0.05). CONCLUSION: Gender, tumor diameter, lymph node metastasis and pathological type are risk factors for recurrence after thyroidectomy.


Assuntos
Carcinoma Papilar/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Câncer Papilífero da Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Idoso , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Período Pós-Operatório , Fatores de Risco , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos
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