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1.
Environ Toxicol ; 39(1): 421-434, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37792549

RESUMEN

Papillary thyroid cancer (PTC) is a prevalent malignancy worldwide. Spleen tyrosine kinase (SYK) is a crucial enzyme that participates in various biological processes, including cancer progression. This study aims to uncover the biological function of SYK in PTC. SYK expression patterns in PTC were evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and western blot. Cell function assays were performed to assess the effects of SYK on PTC. Bioinformatics analysis was conducted to identify intriguing microRNA (miRNA) and circular RNA (circRNA). Dual-Luciferase Reporter or RNA immunoprecipitation assays were used to investigate the correlation among SYK, miR-377-3p, and hsa_circ_0006417. SYK was upregulated in PTC. Overexpression of SYK exhibited a positive correlation with tumor size, lymph node metastasis, and unfavorable disease-free survival. Functional assays revealed that SYK exerted tumorigenic effect on PTC cells through mTOR/4E-BP1 pathway. Mechanistically, hsa_circ_0006417 and miR-377-3p regulated SYK expression, offering modulating its tumor-promoting effects. Collectively, SYK acts as an oncogene in PTC through mTOR/4E-BP1 pathway, which is regulated by the hsa_circ_0006417/miR-377-3p axis, thereby providing a potential alternative for PTC treatment.


Asunto(s)
MicroARNs , ARN Circular , Quinasa Syk , Neoplasias de la Tiroides , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Quinasa Syk/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/metabolismo , Serina-Treonina Quinasas TOR , ARN Circular/genética
2.
Int J Surg ; 76: 163-170, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32173614

RESUMEN

BACKGROUND: Recurrence is still major obstacle to long-term survival in laryngeal squamous cell carcinoma (LSCC). We aimed to establish and validate a nomogram to precisely predict recurrence probability in patients with LSCC. METHODS: A total of 283 consecutive patients with LSCC received curative-intend surgery between 2011 and 2014 at were enrolled in this study. Subsequently, 283 LSCC patients were randomly assigned to a training cohort (N = 171) and a validation cohort (N = 112) in a 3:2 ratio. According to the results of multivariable Cox regression analysis in the training cohort, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were evaluated by calibration curve and concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was performed to estimate clinical value of our nomogram. RESULTS: Six independent factors rooted in multivariable analysis of the training cohort to predict recurrence were age, tumor site, smoking, alcohol, N stage and hemoglobin, which were all integrated into the nomogram. The calibration curve for the probability of recurrence presented that the nomogram-based predictions were in good correspondence with actual observations. The C-index of the nomogram was 0.81 (0.75-0.88), and the area under curve (AUC) of nomogram in predicting recurrence free survival (RFS) was 0.894, which were significantly better than traditional TNM stage. Decision curve analysis further affirmed that our nomogram had a larger net benefit than TNM stage. The results were confirmed in the validation cohort. CONCLUSION: A risk prediction nomogram for patients with LSCC, incorporating readily assessable clinicopathologic variables, generates more accurate estimations of the recurrence probability when compared TNM stage alone, but still needs additional data before being used in clinical implications.


Asunto(s)
Neoplasias Laríngeas , Recurrencia Local de Neoplasia , Nomogramas , Adulto , Anciano , Área Bajo la Curva , Calibración , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Análisis de Regresión , Estudios Retrospectivos
3.
J Hematol Oncol ; 10(1): 32, 2017 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-28122647

RESUMEN

The emerging roles of microRNAs (miRs) have been deeply investigated in cancer. However, the role of miR-194 in human laryngeal squamous cell carcinoma (LSCC) is still unclear. Here, we have demonstrated that miR-194 is significantly downregulated in LSCC tissues and cells, and overexpression of miR-194 inhibits the proliferation, migration, invasion, and drug resistance in LSCC cells. Moreover, Wee1 is identified as a novel direct target of miR-194. Ectopic expression of Wee1 at least in part overcomes the suppressive impacts of miR-194 on the malignant phenotypes of LSCC. Overall, our study provides new sights into the role of miR-194/Wee1 axis in LSCC and suggests a novel miR-194/Wee1-based clinical application for LSCC patients.


Asunto(s)
Carcinoma de Células Escamosas/patología , Proteínas de Ciclo Celular/metabolismo , Neoplasias Laríngeas/patología , MicroARNs/fisiología , Proteínas Nucleares/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Biopsia , Proteínas de Ciclo Celular/antagonistas & inhibidores , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo , Invasividad Neoplásica , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores
4.
Mol Pharmacol ; 92(3): 240-245, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28119482

RESUMEN

Cdk5 and Abl enzyme substrate 1 (Cables1) is an adaptor protein that links cyclin-dependent kinase (Cdks) with nonreceptor tyrosine kinases and regulates the activity of Cdks by enhancing their Y15 phosphorylation. Emerging evidence also shows that Cables1 can interact with, for example, p53 family proteins, 14-3-3, and ß-catenin, suggesting that Cables1 may be a signaling hub for the regulation of cell growth. Abnormal expression of Cables1 has been observed in multiple types of cancers and other diseases. In this review, we summarize the characteristics of Cables1 and highlight the molecular mechanisms through which Cables1 regulates the development of cancer and other diseases. Finally, we discuss future challenges in demonstrating the role and potential application of Cables1 in cancer and other diseases.


Asunto(s)
Proteínas Portadoras/fisiología , Ciclinas/fisiología , Neoplasias/terapia , Fosfoproteínas/fisiología , Animales , Proteínas Portadoras/química , Proteínas Portadoras/genética , Ciclinas/química , Ciclinas/genética , Humanos , Fosfoproteínas/química , Fosfoproteínas/genética , Fosforilación , Proteína p53 Supresora de Tumor/fisiología
5.
Carcinogenesis ; 33(4): 810-7, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22301282

RESUMEN

Inhibitor of differentiation (Id)-1 and nuclear factor-kappa B (NF-κB) have been detected in many malignant tumors, and their presence has been correlated with the metastatic potential of these tumors. This study was undertaken to investigate the prognostic significance of the expression of Id-1 and the p65 subunit of NF-κB (NF-κB/p65) and the proteins' roles in the invasion process of nasopharyngeal carcinoma (NPC) cells. The messenger RNA (mRNA) and protein levels of Id-1 and NF-κB/p65 in normal nasopharyngeal epithelial cells and NPC cell lines were examined using reverse transcription-PCR and western blot analysis, whereas the mRNA and protein levels of Id-1 and NF-κB/p65 in clinical NPC specimens were determined by reverse transcription-PCR and immunohistochemistry. Short hairpin RNA (shRNA) was used to silence Id-1 and NF-κB/p65 to allow for the examination of matrix metalloproteinase (MMP)-9 expression and migratory capacity changes in CNE-2 cells. Multivariate Cox analysis revealed that elevated Id-1 expression was a significant independent predictor of the 5 year overall survival rate (hazards ratio = 16.720, P = 0.005). Furthermore, elevated expression of both Id-1 and NF-κB/p65 was associated with poor clinical survival (P = 0.049). Targeting Id-1 and NF-κB/p65 mRNA with shRNA in CNE-2 cells inhibited MMP-9 expression and decreased the migratory capacity of CNE-2 cells. In conclusion, Id-1 expression is a novel independent prognostic marker molecule that helps identify NPC patients with a poor prognosis. Additionally, combined analysis of Id-1 and NF-κB/p65 can be useful for identifying patients at risk for unfavorable clinical outcomes. Id-1 or/and NF-κB/p65 enhanced tumor cell migration, which is associated with the secretion of MMP-9.


Asunto(s)
Proteína 1 Inhibidora de la Diferenciación/metabolismo , FN-kappa B/metabolismo , Neoplasias Nasofaríngeas/patología , Secuencia de Bases , Línea Celular Tumoral , Cartilla de ADN , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Masculino , Metaloproteinasas de la Matriz/metabolismo , Persona de Mediana Edad , Neoplasias Nasofaríngeas/metabolismo , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
6.
Ai Zheng ; 23(11 Suppl): 1498-501, 2004 Nov.
Artículo en Chino | MEDLINE | ID: mdl-15566666

RESUMEN

BACKGROUND & OBJECTIVES: At present head and neck surgeons from many countries have different opinions on management of well-differentiated thyroid cancer (WDTC). We will discuss WDTC invading trachea surgical treatment and its clinical significance. METHODS: Retrospectively reviewed clinical data of 15 cases WDTC invading trachea, According to WDTC invading extent and grade, there were 3 kinds of surgical approaches: 1) end to end anastomosis; 2) tissue flap reconstruction; 3)larynx-tracheal dissociation. RESULTS: 15 cases underwent radical resection and reconstruct the defect of tracheal or larynx-tracheal dissociation. 2 cases received directly suture, 5 cases received sternocleidomastoid muscle flap reconstruction, 2 cases received pectorlis major muscle flap reconstruction, 2 cases received platysma flap reconstruction, 2 cases received free forearm flap with muticore titanium-board reconstruction, 2 cases received larynx-tracheal dissociation with larynx block out and tracheal fistula. 10 cases (10/15, 66.7%) received decannulation postoperation. Patients who were success fully decannulated could recover phonation and maintain airway breath. In the 5 patients who couldn't decannulate, underwent sternocleidomastoid muscle flap reconstruction, 1 underwent free forearm flap with muticore titanium-board reconstruction, 1 underwent pectorlis major muscle flap reconstruction, 2 underwent larynx-tracheal dissociation, but all of them could hardly utter voice by compress tracheostoma and needed permanent tracheostoma due to collapse of trachea. The recurrence rate of our group is 33.33%, 5 years survival rate is 88.89%. CONCLUSIONS: WDTC with trachea invading easily cause dyspnea or emptysis influencing on 5 years survival rate. We should take more actively surgical approach to resect all the tumor and involved organ, thus improve survival rate and reduce recurrence postoperation.


Asunto(s)
Adenocarcinoma Folicular/cirugía , Carcinoma Papilar/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Neoplasias de la Tráquea/patología , Adenocarcinoma Folicular/patología , Adulto , Anciano , Carcinoma Papilar/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Colgajos Quirúrgicos , Tasa de Supervivencia , Neoplasias de la Tiroides/patología , Neoplasias de la Tráquea/cirugía
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