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The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.
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Fibroblastos Asociados al Cáncer , Carcinoma de Células Escamosas , Exosomas , Neoplasias de Cabeza y Cuello , MicroARNs , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/patología , MicroARNs/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Exosomas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Línea Celular Tumoral , Hipoxia/metabolismo , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Both microRNA-21-5p (miR-21) and the tumor microenvironment, including hypoxia and cancer-associated fibroblasts (CAFs), play a vital role in head and neck squamous cell carcinoma (HNSCC), but whether there is an interaction and the specific regulatory mechanism between them in the process of metastasis is still unclear. In this study, we aimed to elucidate the connection and regulatory mechanism of miR-21, hypoxia, and CAFs in HNSCC metastasis. METHODS: The underlying mechanisms of hypoxia inducible factor 1 subunit alpha (HIF1α) regulating miR-21 transcription, promoting exosome secretion, CAFs activation, tumor invasion, and lymph node metastasis were determined through quantitative real-time PCR, immunoblotting, transwell, wound healing, immunofluorescence, ChIP, electron microscopy, nanoparticle tracking analysis, dual-luciferase reporter assay, co-culture model and xenografts experiments. RESULTS: MiR-21 promoted the invasion and metastasis of HNSCC in vitro and in vivo, whereas HIF1α knockdown inhibited these processes. HIF1α upregulated transcription of miR-21 and promoted the release of exosomes from HNSCC cells. Exosomes derived from hypoxic tumor cells were rich in miR-21, which induced NFs activation towards CAFs by targeting YOD1. Knockdown the expression level of miR-21 in CAFs prevented lymph node metastasis in HNSCC. CONCLUSION: Hypoxic tumor cell-derived exosomal miR-21 might be a therapeutic target to prevent or delay HNSCC invasion and metastasis.
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Fibroblastos Asociados al Cáncer , Neoplasias de Cabeza y Cuello , MicroARNs , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , MicroARNs/metabolismo , Metástasis Linfática/patología , Neoplasias de Cabeza y Cuello/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Microambiente TumoralRESUMEN
BACKGROUND: Cervical lymph node metastasis from unknown primary sites is a challenging clinical issue with a changing therapy model and unpredictable outcomes, which leads to the difficulty in selecting optimal treatments. Thus, it is valuable to analyze the clinical characteristics and outcomes of the patients who receive different management styles. METHODS: All patients with cervical lymph node metastasis from unknown primary sites were reviewed and no primary lesions were found. In addition, this work was funded by the Clinical Trial Fund Project of Tianjin Medical University Cancer Institute and Hospital (No. C1716). Specifically, we used univariate, multiple regression analysis to evaluate the factors associated with prognosis. RESULTS: 365 patients met the inclusion criteria, and the 2- and 5-year survival rates were 77.0% and 33.4%, respectively, with a median survival of 45 months. Gender, age, pathological type, nodal status, and necessary cervical lymph node dissection affected locoregional control. Distant metastasis was common in individuals with a pathological type of adenocarcinoma, poor differentiation, and advanced nodal status. Furthermore, patients who received induction chemotherapy had a better prognosis than those treated with postoperative chemotherapy. Multiple regression analysis showed that pathological grade, treatment models, and distant metastasis were associated with overall survival (OS) and progression-free survival (PFS). In addition, local recurrence exerted a significant influence on OS. Induction chemotherapy and postsurgical radiotherapy seemed to improve the prognosis of patients at the advanced stage compared with simple surgery and postsurgical chemotherapy. CONCLUSIONS: Pathological grade, treatment models, and distant metastasis were independent risk factors for prognosis. Induction chemotherapy or postoperative radiotherapy benefited patients at the advanced stage, and patients with adenocarcinoma, poor differentiation, and advanced nodal status should undergo induction chemotherapy in light of the increased risk of distant metastasis.
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Adenocarcinoma , Neoplasias Primarias Desconocidas , Neoplasias del Cuello Uterino , Humanos , Femenino , Metástasis Linfática/patología , Neoplasias Primarias Desconocidas/patología , Neoplasias Primarias Desconocidas/cirugía , Estudios Retrospectivos , Ganglios Linfáticos/patología , Escisión del Ganglio Linfático , Pronóstico , Adenocarcinoma/patología , Estadificación de Neoplasias , Tasa de Supervivencia , Recurrencia Local de NeoplasiaRESUMEN
Objective: We analysed the diagnostic performance of thyroglobulin in fine-needle aspiration (FNA-Tg) in the suspicious lateral cervical lymph nodes (CLNs) in patients with papillary thyroid cancer (PTC), proposed the best cutoff value and discussed the factors that may affect the diagnostic value of FNA-Tg. Methods: In the present study, a retrospective analysis of 403 patients with PTC with 448 suspected lateral CLNs metastasis from October 2019 to May 2021 was performed. The cutoff value according to the receiver operating characteristic (ROC) curve was determined, and the Wilcoxon rank-sum test was used to evaluate the correlation between FNA-Tg and factors. Results: According to the ROC curve, the cutoff value of FNA-Tg was 3.69 ng/ml (sensitivity, 92.48%; specificity, 75.00%). Patients who underwent total thyroidectomy were excluded. Compared with US and FNAC, the diagnostic performance of FNA-Tg was the greatest, especially for small CLNs (diameter ≤ 1 cm), cystic CLNs, and patients with Hashimoto's thyroiditis (HT). Moreover, FNA-Tg levels were correlated with the presence of HT (p = 0.003), the anti-thyroglobulin antibody (Tg-Ab) (p < 0.001), the ratio of metastatic lateral CLNs (p = 0.004) and Tg assay kits (p < 0.001). Conclusions: FNA-Tg measurement is sensitive enough for diagnosing lateral CLN metastases from PTC, but its diagnostic value is compromised by a number of factors.
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As water quality can be an indicator of public health, it cannot be ignored. We can regard the international image of a country as a kind of soft national power, which embodies the comprehensive strength of the country and plays a very important role in safeguarding the interests of a country. This article aims to study the changes in China's international image under mainstream media reports during the COVID-19 pandemic. This article is based on contaminated water and human health to study the concept of the international image, the optimization path of China's international image, and the SEIR model. The SEIR model is one of the classic infectious disease models. Because the virus infection rate in this model is constant, it is difficult to accurately determine the spread of new coronary pneumonia. To model and complete the pandemic trend prediction and other issues, this article proposes a virus infection rate prediction method based on the long short-term memory network (LSTM), and combines it with the SEIR model to establish a new crown pneumonia pandemic trend prediction model (LS-Net). The conclusion of this article shows that in the fight against the novel coronavirus infectious pneumonia pandemic, the Chinese people have demonstrated the style of a big country. I have unreservedly passed on my own experience in pandemic prevention and control to countries around the world, and dispatched medical teams to provide the world with Chinese "prescriptions." Chinese diagnosis and treatment programs are the crystallization of common wisdom of Chinese medicine and Western medicine to support the world. All countries fight the pandemic together. In this analysis, Pakistan, Kenya, and Nigeria hold 84%, 85%, and 75% of China's positive views, respectively, 61% of Russians also have a positive attitude toward China.
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COVID-19 , Pandemias , COVID-19/epidemiología , China/epidemiología , Humanos , Pandemias/prevención & control , Salud Pública , SARS-CoV-2RESUMEN
The water pollution affecting human health is a crisis and big test, which tests the mainstream news media's ability and level of communication to respond to major public opinions and public emergencies. The contaminated water is a crisis and a major test, which tests the ability and level of communication of major news outlets to respond to important common views and emergencies. It aims to understand the perception and attitude of the international mainstream media towards China during the contaminated water. The work sorted out the mainstream media's reporting of China from the contaminated water to the present and selected the New York Times, The Times, and the Guardian as examples. We could understand the changes in China's international image during the water pollution through these mainstream media reports on China. The results show that these media reports on water pollution in China mainly focused on negative public opinion, which accounted for more than 70% of the total number of reports. Western developed countries such as the United Kingdom and the United States are out of consideration for their national interests. Using mainstream media to create public opinion that is not conducive to China, advocating "neo-colonialism", "China threat theory" and other false statements, trying to limit China's influence, due to the difference in cognitive habits and the influence of British and American media hegemony also affects the country The communication and understanding between the two have brought obstacles.
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Macrodatos , Urgencias Médicas , China , Cognición , Humanos , Estados Unidos , Agua , Contaminación del AguaRESUMEN
Objective: The right cervical central lymph nodes include lymph nodes anterior to the right recurrent laryngeal nerve (LN-arRLN) and lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN), and are separated by the right recurrent laryngeal nerve (RLN). LN-prRLN is a common site of nodal recurrence after the resection of papillary thyroid carcinoma (PTC). However, the complexity in anatomical structure brings difficulties in determining the surgical scope, so it is necessary to assess the pattern and predictive factors of right cervical central lymph nodes, especially LN-prRLN metastasis in papillary thyroid carcinoma. Methods: A total of 562 diagnosed PTC patients who underwent right or total thyroidectomy were enrolled in this retrospective study. The clinicopathological features were collected, univariate and multivariate analyses were performed to determine predictive factors of the right central lymph node metastasis. Results: In this study, the metastatic rates of the right CLN, the LN-arRLN and the LN-prRLN were 59.6% (335/562), 51.8% (291/562) and 30.4% (171/562), respectively. And 22.6% (127/562) of patients had both LN-arRLN and LN-prRLN metastasis. Among patients without LN-arRLN metastasis, the rate of LN-prRLN metastasis was 16.2% (44/271), accounting for 25.7% of the LN-prRLN metastasis group. Factors associated with an increased risk of LN-arRLN metastasis include male, age below 55 years, tumor size > 1cm, extrathyroidal extension (ETE), clinical lymph nodes metastasis(cN1), lateral lymph node metastasis, and left CLN metastasis. In addition, ETE, lateral lymph node metastasis, and LN-arRLN metastasis were independent factors of LN-prRLN metastasis. The predictive factors of LN-prRLN in cN0 PTC were further explored, revealing that tumor size ≥1.5cm, ETE, and LN-arRLN metastasis were independent predictors of LN-prRLN metastasis in cN0 PTC. Conclusion: The LN-prRLN should not be ignored in surgery because of its high rate of metastasis. Our findings indicate that thorough dissection of central lymph nodes, especially LN-prRLN is crucial in clinical work.
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Carcinoma Papilar , Carcinoma , Neoplasias de la Tiroides , Carcinoma/patología , Carcinoma/cirugía , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Nervio Laríngeo Recurrente/patología , Estudios Retrospectivos , Factores de Riesgo , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugíaRESUMEN
Thyroglobulin (Tg) measurement in fine-needle aspiration (FNA-Tg) has proved to be an excellent tool to identify metastatic cervical lymph nodes (CLN) before or after surgery for papillary thyroid cancer (PTC). The diagnostic value of FNA-Tg for metastatic CLN in PTC patients is higher than that of ultrasound (US) and fine-needle aspiration cytology (FNAC), especially for small or cystic LN. The combination of FNAC and FNA-Tg can provide nearly 100% diagnostic sensitivity and specificity for CLN metastasis. However, the cutoff values of FNA-Tg for metastatic CLN have not been standardized, and the reported cutoff values of FNA-Tg range from 0.2 ng/ml to 77 ng/ml because of the differences in study samples, Tg measurement methods, Tg assays kits, etc. Serum anti-thyroglobulin antibody level, serum thyroglobulin level, the presence or absence of thyroid glands, and the characteristics of CLN may be factors affecting the accuracy of FNA-Tg. This review summarizes the recent research on the application of FNA-Tg in the diagnosis of metastatic LN in PTC and provides a reliable basis for the clinical diagnosis of cervical lymph node metastasis.
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Metástasis Linfática/diagnóstico , Tiroglobulina/sangre , Cáncer Papilar Tiroideo/sangre , Biomarcadores de Tumor/sangre , Biopsia con Aguja Fina , Humanos , Escisión del Ganglio Linfático , Sensibilidad y EspecificidadRESUMEN
Purpose: We aimed to develop a prognostic nomogram based on immunohistochemistry (IHC) biomarkers of patients with oral squamous cell carcinoma (OSCC). Methods: A total of 294 patients were enrolled in the study. The least absolute shrinkage and selection operator (LASSO) Cox regression model was performed to develop a combined IHC score (IHCs) classifier. Results: Five biomarkers, specifically c-Met, Vimentin, HIF-2α, VEGF-c, and Bcl-2 were extracted. Then, an IHCs classifier was developed, and patients were stratified into high- and low-IHCs groups. In the training cohort, the 5-year overall survival (OS) was 62.1% in low-IHCs group and 28.2% in high-IHCs group (P<0.001). The 5-year OS was 68.6% for the low-IHCs group and 28.4% for the high-IHCs group in the validation cohort (P<0.001). The area under the ROC curve (AUROC) of the combination of the IHCs classifier and TNM stage was 0.746 (95% CI: 0.658-0.833) in the training cohort and 0.735 (95% CI: 0.651-0.818) in the validation cohort, respectively. Conclusions: The nomogram could effectively predict the prognosis for patients with OSCC and may be employed as a potential tool to guide the individual decision-making process.
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BACKGROUND: Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. METHODS: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan-Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. RESULTS: The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. CONCLUSIONS: These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.
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Introduction: To assess the risk factor for the central lymph node (CLN) metastasis and investigated the surgery extent of lymph node dissection for patients with isthmic PTC (papillary thyroid carcinoma). Materials and Methods: A total of 669 patients with a single nodule of isthmic PTC were retrospectively reviewed. The propensity score matching was performed twice separately. 176 patients respectively from patients who underwent thyroidectomy plus bilateral central lymph node dissection (BCLND) and who underwent thyroidectomy plus unilateral central lymph node dissection (UCLND) were matched. 77 patients were respectively selected from patients who underwent thyroidectomy plus BCLND and who underwent thyroidectomy with no central lymph node dissection (NCLND) were matched. Results: Among all the patients who underwent BCLND, 81/177 (45.76%) was confirmed with histologically positive CLN metastasis, and the occult lymph node metastasis is 25.42%. A tumor size of 1.05 cm was calculated as the cutoff point for predicting CLN metastasis by ROC curve analysis with 177 patients who underwent BCLND. The 5-year recurrence-free survival (RFS) rates were 92.9% in the NCLND group and 100% in the BCLND group with P<0.05, while there was no statistical difference in 5-year RFS between the BCLND group and UCLND group (P=0.11). The multivariate logistic regression analysis identified that age<55, tumor size>1cm, capsule invasion and lymphovascular invasion were significantly associated with CLN metastasis, while only age and lymphovascular invasion were proved to be independent risk factors related to contralateral CLN metastasis. Conclusions: The thyroidectomy with NCLND could be insufficient for patients with isthmic PTC especially for those patients with high risk of central lymph node metastasis, considering that the rate of occult lymph node metastasis could not be ignored.
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Escisión del Ganglio Linfático , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto , Femenino , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Resultado del TratamientoRESUMEN
Metastasis and chemoresistance are major causes of poor prognosis in patients with esophageal squamous cell carcinoma (ESCC), manipulated by multiple factors including deubiquitinating enzyme (DUB). DUB PSMD14 is reported to be a promising therapeutic target in various cancers. Here, we explored the antitumor activity of Thiolutin (THL), the PSMD14 inhibitor, as a new therapy strategy in ESCC. Methods: Through 4-NQO-induced murine ESCC model, we investigated the expression of PSMD14 in esophageal tumorigenesis. Ubiquitin-AMC assay was performed to evaluate DUB activity of PSMD14 with THL treatment. The effect of THL on epithelial-to-mesenchymal transition (EMT), invasion, stemness and chemosensitivity was detected by using in vitro and in vivo experiments. Immunoprecipitation and in vivo ubiquitination assay were conducted to examine whether THL could impair the deubiquitination and stability of SNAIL regulated by PSMD14. Results: Compared with normal esophageal epithelium, PSMD14 was upregulated in 4-NQO-induced murine esophageal epithelium dysplasia and ESCC tissues. THL could significantly weaken DUB activity of PSMD14. Furthermore, the results of in vitro and in vivo assays showed that THL efficiently suppressed motility and stemness and increased sensitivity to cisplatin in ESCC. Mechanically, THL impaired the interaction between PSMD14 and SNAIL, then promoted the ubiquitination and degradation of SNAIL to inhibit EMT which plays a crucial role in ESCC metastasis, stemness and chemosensitivity. TCGA database analysis revealed that high concomitant PSMD14/SNAIL expression predicted shorter overall survival in esophageal cancer. Conclusion: Our findings demonstrate for the first time that suppression of PSMD14/SNAIL axis by THL could be a novel and promising therapeutic approach for ESCC clinical therapy.
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Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Transactivadores/metabolismo , Animales , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/patología , Pirrolidinonas/farmacología , Ubiquitinación/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The Delphian lymph node (DLN), also known as the prelaryngeal node, is one component of the central lymph node. The DLN has been well studied in laryngeal cancer, although its significance in papillary thyroid cancer (PTC) remains unclear. We retrospectively analyzed 936 patients with PTC who underwent thyroidectomy by a single surgeon in Tianjin Cancer Hospital from 2017 to 2019. Moreover, 250 PTC patients who underwent thyroidectomy by another surgeon in Tianjin Cancer Hospital from January 2019 to April 2019 were used as a validation cohort. Among the 936 patients with PTC, 581 patients (62.1%) had DLNs, of which 177 samples with metastasis (177/581, 30.5%) were verified. DLN metastasis was significantly correlated with sex, age, tumor size, bilateral cancer, multifocality, extrathyroidal extension, lymphovascular invasion and central and lateral neck lymph node metastasis. Multivariate analysis revealed that independent risk factors for DLN metastasis included age, gender, tumor size, extrathyroid extension, lymphovascular invasion and central lymph node metastasis, which determined the nomogram. In particular, tumor size was proven to be one of the most predominant single predictors. The diagnostic model had an area under the curve (AUC) of 0.829 (95% confidence interval, 0.804-0.854). The internal and external validations of the nomogram were 0.819 and 0.745, respectively. Our results demonstrate that DLN metastasis appears to be a critical parameter for predicting metastatic disease of the central compartments. Furthermore, this study provides a precise criterion for assessing DLN metastasis and has great clinical significance for treating PTC.
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Metástasis Linfática/diagnóstico , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adulto , Técnica Delphi , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Procesos Neoplásicos , Estudios Retrospectivos , Factores de Riesgo , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
Increasing evidence reveals a close relationship between deubiquitinating enzymes (DUBs) and cancer progression. In this study, we attempted to identify the roles and mechanisms of critical DUBs in head and neck squamous cell carcinoma (HNSCC). Methods: Bioinformatics analysis was performed to screen differentially expressed novel DUBs in HNSCC. Immunohistochemistry assay was used to measure the expression of DUB PSMD14 in HNSCC specimens and adjacent normal tissues. The level of PSMD14 in HNSCC tumorigenesis was investigated using a 4-NQO-induced murine HNSCC model. The function of PSMD14 was determined through loss-of-function assays. Chromatin immunoprecipitation, immunoprecipitation and in vivo ubiquitination assay were conducted to explore the potential mechanism of PSMD14. The anti-tumor activity of PSMD14 inhibitor Thiolutin was assessed by in vitro and in vivo experiments. Results: We identified PSMD14 as one of significantly upregulated DUBs in HNSCC tissues. Aberrant expression of PSMD14 was associated with tumorigenesis and malignant progression of HNSCC and further indicated poor prognosis. The results of in vitro and in vivo experiments demonstrated PSMD14 depletion significantly undermined HNSCC growth, chemoresistance and stemness. Mechanically, PSMD14 inhibited the ubiquitination and degradation of E2F1 to improve the activation of Akt pathway and the transcription of SOX2. Furthermore, PSMD14 inhibitor Thiolutin exhibited a potent anti-tumor effect on HNSCC in vivo and in vitro by impairing DUB activity of PSMD14. Conclusion: Our findings demonstrate the role and mechanism of PSMD14 in HNSCC, and provide a novel and promising target for diagnosis and clinical therapy of HNSCC.
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Enzimas Desubicuitinizantes/genética , Resistencia a Antineoplásicos/genética , Factor de Transcripción E2F1/genética , Células Madre Neoplásicas/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Proteínas Proto-Oncogénicas c-akt/genética , Factores de Transcripción SOXB1/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Transactivadores/genética , Animales , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/patología , Pronóstico , Pirrolidinonas/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Ubiquitinación/efectos de los fármacos , Ubiquitinación/genéticaRESUMEN
BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is a kind of squamous cell carcinoma of head and neck, and its incidence is on the rise in recent years. A variety of prognostic markers for OPSCC have been reported in many studies, but they are expensive or difficult to obtain. So, we retrospectively studied the prognostic significance of cytokeratin 19 soluble fragment (Cyfra21-1) in patients with OPSCC, in order to provide theoretical basis for accurate prognosis assessment. METHODS: A retrospective analysis of the clinicopathological data of 85 OPSCC patients with concurrent radiotherapy and chemotherapy (CRT) admitted from January 2010 to June 2017. Serum Cyfra21-1 levels were measured before treatment. Analyze the relationship between Cyfra21-1 and clinical pathological characteristics of patients. The receiver operating characteristic (ROC) curve was used to calculate the cut-off value of Cyfra21-1. The Cox proportional hazard model was used to conduct univariate and multivariate analysis of related prognostic factors, and to determine the factors related to overall survival (OS) and progression-free survival (PFS). RESULTS: The cutoff value for Cyfra21-1 was 2.93 ng/mL. The baseline data of patients in different Cyfra21-1 groups were balanced and comparable. In the univariate and multivariate analyses, it was found that Cyfra21-1 was associated with OS and PFS. A measurement of Cyfra21-1 ≥2.93 ng/mL indicated poor OS (P<0.001) and PFS (P=0.001). After adjusting for age and disease stage, Cyfra21-1 can independently affect the OS (HR =3.57, 95% CI: 1.60-7.99, P=0.002) and PFS (HR =2.89, 95% CI: 1.41-5.91, P=0.004) of patients with OPSCC treated with CRT. CONCLUSIONS: Pre-treatment Cyfra21-1 can be used as a prognostic marker for patients with OPSCC treated with CRT, which has important clinical significance.
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BACKGROUND: Oropharyngeal cancer (OPC) is a type of head and neck squamous cell cancer, the incidence of which has increased in recent years. Many studies have reported a variety of prognostic markers of OPC, but they are either expensive or difficult to obtain. Therefore, we retrospectively studied the prognostic value of circulating neutrophil count (CNC) in patients with OPC, with the aim of providing a theoretical basis for further prognostic stratification. METHODS: The clinicopathological data of 153 patients diagnosed with OPC from January 2010 to June 2017 were retrospectively analyzed. The CNC of each patient was measured before treatment. Then, the relationship between CNC and the clinicopathological characteristics of the patients was analyzed. The receiver operating characteristic (ROC) curve was used to calculate the cutoff value of CNC. The cox proportional hazards model was used to perform univariate and multivariate analysis of the relevant prognostic factors to determine the factors related to overall survival (OS) and progression-free survival (PFS). RESULTS: The cutoff value for CNC was 4.48. Neutrophilia was significantly associated with disease stage, P16 status, and the type of therapy. In the univariate and multivariate analyses, CNC was found to be correlated with OS and PFS. Increased neutrophil count was predictive of poor OS (P<0.001) and PFS (P=0.001). Neutrophil count was an independent risk factor for OS (HR =2.09, 95% CI: 1.25-3.51, P=0.005) and PFS (HR =1.78, 95% CI: 1.10-2.88, P=0.02) in patients with OPC. CONCLUSIONS: Pre-treatment CNC is an independent prognostic factor for OPC.
RESUMEN
A polyoxovanadium borate (H2 dap)6H[V12B16O54(OH)4] · 12H2O (dap=1,2-diaminopropane) with novel structure was hydrothermally synthesized and characterized by the single crystal X-ray diffraction. It crystallizes in triclinic system with space group Piand unit cell parameters a=19.027(4), b=16.142(3) Å, c=26.679(5) Å, α=90°, ß=101.06(3)°, γ=90°, V=8042(3) Å3, Z=4, Dc=1.962 g · cm(-3), µ=1.456 mm(-1), F(000)=4776, the final R1=0.0626, wR2=0.1927, S=1.003,for 7635 observed reflections with I>2σ(I). It is showed that the compound 1 is composed of V12B16 clusters unit and dap which is as a counter ion, and a two-dimensional layered structure is obtained by the effect of hydrogen bonding between the cluster units and dap, and between the layers via strong hydrogen bonds to form a three-dimensional supramolecular structure. The compound 1 were also characterized by IR, two-dimensional infrared (2D IR) correlation spectroscopy with magnetic and thermal perturbation, UV/Vis DRS spectra. The relationship between the structure and spectroscopy properties was discussed. The IR spectrum showed that the antisymmetric stretching vibration absorption peak νas (V-Oµ) and symmetric stretching vibration absorption peaks νs (V-Oµ) appeared at 775 and 683 cm(-1) respectively, whereas the vibration absorption peak in ν(B-O) of BO3 and the vibration absorption peak in ν(B-O) of BO4 appeared at 1350 and 1050 cm(-1) respectively. The response of the stretching vibrations of B-O and V-O was detected in the 2D IR correlation spectra with magentic perturbation. In addition, the response of the stretching vibrations of B-OH, B-O and V-O-V was detected in the 2D IR correlation spectra with thermal perturbation.