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Background: The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. Methods: A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Results: Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. Conclusions: The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.
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BACKGROUND: RING Finger Protein 115 (RNF115), a notable E3 ligase, is known to modulate tumorigenesis and metastasis. In our investigation, we endeavor to unravel the putative function and inherent mechanism through which RNF115 influences the evolution of thyroid carcinoma (THCA). METHODS: We analyzed RNF115 expression in THCA using the Cancer Genome Atlas (TCGA) database. The influence of RNF115 on the progression of THCA was evaluated using both in vitro and in vivo experimental approaches. The protein regulated by RNF115 was identified through bioinformatics analysis, and its biological significance was further explored. RESULTS: In both THCA tissues and cells, RNF115 showed elevated expression levels. Enhanced expression of RNF115 fostered cell proliferation, tumor growth, and the exacerbation of epithelial-mesenchymal transition (EMT) in THCA, while also promoting tumor lung metastasis. Bioinformatics analysis identified cyclin-dependent kinase 10 (CDK10) as a downstream target of RNF115, which was found to be ubiquitinated and degraded by RNF115 in THCA cells. Functionally, overexpression of CDK10 was found to counteract the promotion of malignant phenotype in THCA induced by RNF115. From a mechanistic perspective, RNF115 activated the Raf-1 pathway and enhanced cancer cell cycle progression by degrading CDK10 in THCA cells. CONCLUSION: RNF115 triggers cell proliferation, EMT, and tumor metastasis by ubiquitinating and degrading CDK10. The regulation of the Raf-1 pathway and cell cycle progression in THCA may be profoundly influenced by this process.
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Neoplasias Pulmonares , Neoplasias de la Tiroides , Ubiquitina-Proteína Ligasas , Humanos , Carcinogénesis/genética , Transformación Celular Neoplásica , Quinasas Ciclina-Dependientes , Neoplasias de la Tiroides/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
OBJECTIVE: This study evaluated the feasibility, stability, safety, and economy of cricothyroid membrane (CM)-inserted needle electrodes for recurrent laryngeal nerve monitoring. STUDY DESIGN: Parallel and controlled study. SETTING: Clinical research center for thyroid diseases of Shaanxi province. METHODS: A total of 64 patients in the needle electrodes group (104 recurrent laryngeal nerves [RLNs]) and 44 patients in the endotracheal tube (ETT)-based electrodes group (80 RLNs) underwent monitored thyroidectomy. The evoked electromyography (EMG) signals detected by the 2 electrodes were recorded and analyzed. The changes in EMG during Berry's ligament traction and tracheal displacement were compared. All patients underwent preoperative and postoperative laryngoscopy within 1 week. RESULTS: Both electrodes successfully recorded typical evoked laryngeal EMG waveforms from RLNs. The needle electrodes recorded relatively higher amplitudes and similar latencies compared to ETT-based electrodes. The evoked EMG signals attributed to needle electrodes could accurately predict the function of RLNs with 100% sensitivity and specificity. The reduction in the recorded amplitudes attributed to needle electrodes was higher than that observed with ETT-based electrodes during Berry's ligament traction or trachea displacement, whereas a similar increase in the latencies was recorded in the 2 groups. Particularly, Berry's ligament traction was more likely to lead to EMG amplitude reduction and latency prolongation. The needle electrodes group recorded 2 cases of minor bleeding on the CM. The needle electrodes were more cost-effective than ETT-based electrodes. CONCLUSION: The CM-inserted needle electrodes are feasible, stable, safe, and economical for RLN monitoring, and they provide an alternative novel intraoperative neural monitoring format for thyroid surgeons.
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Glándula Tiroides , Tiroidectomía , Humanos , Glándula Tiroides/cirugía , Estudios de Factibilidad , Monitoreo Intraoperatorio , Nervio Laríngeo Recurrente , Electrodos , ElectromiografíaRESUMEN
The incidence of papillary thyroid microcarcinoma ï¼PTMCï¼ increases rapidly. However, epidemiological and autopsy studies show that the prevalence of low-risk papillary thyroid microcarcinoma ï¼LR-PTMCï¼ is very high, but the mortality is very low. There is over-diagnosis and over-treatment for LR-PTMC. Active surveillance ï¼ASï¼ was adopted for LR-PTMCs instead of immediate surgery, and more than 70% of the lesions remained stable or shrank in clinical observation. Therefore, AS is recommended for LR-PTMCs in clinical guidelines of several academic organizations around the world. However, PTMC is not equal to low-risk cancer. The implementation of AS strategy requires a strict grasp of indications and full consideration of population characteristics to ensure the maximum benefit of patients. This paper summarizes the present clinical progress of active surveillance for adult LR-PTMC.
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Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Adulto , Espera Vigilante , Neoplasias de la Tiroides/patología , Carcinoma Papilar/patología , Incidencia , Tiroidectomía/efectos adversos , Estudios RetrospectivosRESUMEN
TRG-AS1 has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer is unknown. In this study, we determined breast cancer patients with disease free survival is longer in breast cancer patients with high TRG-AS1 expression. Moreover, TRG-AS1 was downregulated in breast cancer tissues and even lower in bone metastatic tumor tissues. Compared with parental breast cancer cell MDA-MB-231, TRG-AS1 expression was downregulated in MDA-MB-231-BO cells with strong bone-metastatic characteristics. Next, the binding sites of miR-877-5p on TRG-AS1 and WISP2 mRNA were predicted and result showed that miR-877-5p could bind to 3'UTR of TRG-AS1 and WISP2. Subsequently, BMMs and MC3T3-E1 cells were cultured in the conditioned media of MDA-MB-231 BO cells transfected with TRG-AS1 overexpression vector, shRNA and/or miR-877-5p mimics or inhibitor and/or overexpression vector and small interfering RNA of WISP2. TRG-AS1 silencing or miR-877-5p overexpression promoted MDA-MB-231 BO cell proliferation and invasion. TRG-AS1 overexpressing reduced TRAP positive cells, decreased TRAP, Cathepsin K, c-Fos, NFATc1 and AREG expression in BMMs, and promoted OPG, Runx2 and Bglap2 expression, and decreased RANKL expression in MC3T3-E1 cells. Silencing WISP2 rescued the effect of TRG-AS1 on BMMs and MC3T3-E1 cells. In vivo results showed that tumor volumes significantly decreased in mice injected with LV-TRG-AS1 transfected MDA-MB-231 cells. TRG-AS1 knockdown markedly reduced the number of TRAP+ cells and the percentage of Ki-67+ cells and decreased E-cadherin expression in xenograft tumor mice. In summary, TRG-AS1 acts an endogenous RNA, inhibited breast cancer bone metastasis by competitively binding with miR-877-5p to upregulate WISP2 expression.
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Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.
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Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Tiroides , Humanos , Apoptosis/fisiología , Autofagia/fisiología , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas Asociadas a Fase-S/genética , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , UbiquitinaciónRESUMEN
Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored. Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing. Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively. Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC's pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.
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Nasopharyngeal carcinoma occurs in many parts of the pars nasalis pharyngis, and the pathological type is mainly squamous cell carcinoma. Because of the special position of nasopharynx, breathing, pronunciation and daily life will be seriously affected. At present, the research direction of nasopharyngeal carcinoma is mainly to explore the law of tumor cell proliferation and migration, study the molecular mechanism, master its biological behavior and clinical significance, try to find therapeutic targets, and further improve the level of tumor treatment. However, the pathologic structure and molecular mechanism of nasopharyngeal carcinoma have not been fully elucidated. In this study, the Lentivirus-mediated EIF3C shRNA vector (L.V-shEIF3C) was constructed to down-regulate the expression of EIF3C in human pharyngeal squamous carcinoma cell FaDu and the human nasopharyngeal carcinoma cell 5-8F, it was found that down-regulation of EIF3C could significantly inhibit the cell proliferation, promote cell apoptosis, induce cell cycle arrest, and inhibit the formation and growth of tumors in mouse models. This study provides strong evidence that EIF3C is a key gene driving the development and progression of head and neck cancer, which is of great significance for the diagnosis, prognosis or treatment of tumors, suggesting that EIF3C may become a valuable therapeutic development and intervention target.
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Structural health and construction security are important problems in civil engineering. Regular infrastructure inspection and monitoring methods are mostly performed manually. Early automatic structural health monitoring techniques were mostly based on contact sensors, which usually are difficult to maintain in complex infrastructure environments. Therefore, non-contact infrastructure inspection and monitoring techniques received increasing interest in recent years, and they are widely used in all aspects of infrastructure life, owing to their convenience and non-destructive properties. This paper provides an overview of vision-based inspection and vision-laser-based monitoring techniques and applications. The inspection part includes image-processing algorithms, object detection, and semantic segmentation. In particular, infrastructure monitoring involves not only visual technologies but also different fusion methods of vision and lasers. Furthermore, the most important challenges for future automatic non-contact inspections and monitoring are discussed and the paper correspondingly concludes with state-of-the-art algorithms and applications to resolve these challenges.
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Algoritmos , Rayos Láser , Procesamiento de Imagen Asistido por ComputadorRESUMEN
BACKGROUND: The incidence of thyroid cancer is rising rapidly in China, but there are few studies on the risk factors of thyroid cancer in the Chinese Han population. METHODS: We performed this case-control study of 510 patients and 509 controls to for determine the linkage of VAV3 variants (rs17019602, rs7521681, rs4915076, and rs1777451) with thyroid cancer susceptibility by computing the odds ratio (OR) and 95% confidence intervals (CI). Multi-factor dimension reduction (MDR) analysis was conducted to assess interaction of VAV3 genetic variants. RESULTS: We found that rs7521681 was remarkably related to a higher risk of thyroid cancer (OR = 1.74, p = 0.012), whereas rs4915076 (OR = 0.66, p = 0.001) significantly decreased thyroid cancer susceptibility. Stratified analyses showed that rs4915076 had a protective role in thyroid cancer in both ages >45 years (OR = 0.70, p = 0.017) and age ≤45 years (OR = 0.63, p = 0.007). Rs17019602 could increase the susceptibility of thyroid cancer in men (OR = 4.76, p = 0.049). Rs7521681 was related to an increased risk of thyroid cancer in women (OR = 1.97, p = 0.012). Rs4915076 could protect individuals from thyroid cancer both in men (OR = 0.60, p = 0.031) and women (OR = 0.68, p = 0.010). Moreover, rs4915076 was the best single-locus model to predict thyroid cancer. Interestingly, the interaction model of rs17019602, rs7521681, rs4915076, rs1777451, and age was a candidate gene-environment model. CONCLUSION: Our results indicated VAV3 variants were associated with thyroid cancer, which provides a new sight into etiology of thyroid cancer.
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Predisposición Genética a la Enfermedad , Neoplasias de la Tiroides , Adulto , Alelos , Estudios de Casos y Controles , China/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-vav/genética , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/genéticaRESUMEN
Background: Thyroid cancer is the most common endocrine malignancy and the fastest growing cancer worldwide. Thyroid cancer has the largest genetic component of all cancers. Previous genome-wide association studies indicated that genetic polymorphism in PCNXL2 is related to thyroid cancer susceptibility in European populations. This study aims to determine the influence of PCNXL2 polymorphisms on thyroid cancer risk in Chinese individuals. Methods: This case-control study identified four polymorphisms in PCNXL2 among 510 thyroid cancer cases and 509 healthy controls. The associations of PCNXL2 polymorphisms with thyroid cancer susceptibility were detected by calculating odds ratios. Multifactor dimensionality reduction was performed to detect the impact of SNP (single nucleotide polymorphism)-SNP interactions on the risk of thyroid cancer. Results: The study showed that rs10910660 in PCNXL2 was related to thyroid cancer susceptibility. Rs12129938 played a protective role in thyroid cancer susceptibility. Stratification analysis indicated that rs10910660 increased thyroid cancer risk at age >45 years. Rs12129938 enhanced susceptibility to thyroid cancer at age >45 years, while this SNP decreased thyroid cancer risk at age ≤45 years. Rs4649295 was associated with lower susceptibility to thyroid cancer at age ≤45 years. An association was observed between rs6424270 and rs12129938 with decreased susceptibility to thyroid cancer in women. Rs10910660 was related to thyroid cancer risk in men. The combination of rs6424270, rs10910660, rs12129938 and rs4649295 was the best model to predict thyroid cancer. Conclusion: This study suggests that PCNXL2 polymorphisms are risk factors for thyroid cancer in the Chinese population.
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Predisposición Genética a la Enfermedad , Neoplasias de la Tiroides/genética , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Femenino , Estudio de Asociación del Genoma Completo , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores Protectores , Factores de Riesgo , Glándula Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/patologíaRESUMEN
Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628-5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3'UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.
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MicroARNs/metabolismo , ARN Largo no Codificante/genética , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Humanos , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Transducción de Señal , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patologíaRESUMEN
Kallikrein-associated peptidase 11 (KLK11) has emerged as a key tumor-associated protein that is implicated in a wide spectrum of tumor types. However, the detailed involvement of KLK11 in laryngeal squamous cell carcinoma (LSCC) has not been well studied. The aims of our work were to evaluate whether KLK11 plays a role in LSCC. We found that both the mRNA and protein expression of KLK11 were significantly lower in LSCC tissues than in normal tissues. Low expression of KLK11 was also observed in LSCC cell lines, and the up-regulation of KLK11 caused a significant inhibitory effect on the proliferation, colony formation and invasion of LSCC cells. On the contrary, the knockdown of KLK11 markedly accelerated the proliferative and invasive abilities of LSCC cells. Molecular mechanism research revealed that KLK11 overexpression decreased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and down-regulated the expression of active ß-catenin, leading to the inactivation of Wnt/ß-catenin signaling in LSCC cells. Furthermore, GSK-3ß inhibition markedly abrogated the KLK11-mediated suppressive effect on Wnt/ß-catenin signaling. Notably, the reactivation of Wnt/ß-catenin partially reversed KLK11-mediated tumor-inhibition effect in LSCC. In addition, the xenograft tumor assay demonstrated that the up-regulation of KLK11 retarded tumor formation and the growth of LSCC cells in vivo. Taken together, the findings of our work demonstrate that KLK11 exerts a tumor-inhibition role in LSCC by down-regulating Wnt/ß-catenin signaling. Our work highlights a pivotal role of KLK11 in LSCC progression and suggests it as an attractive anticancer target for LSCC treatment.
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Neoplasias de Cabeza y Cuello/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina Endopeptidasas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo , Animales , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
BACKGROUND: This study was designed to detect patients with early NSCLC with tentatively using the stem signatures associated autoantibodies (AAbs), and to evaluate its latent values in the early diagnosis and precise prognosis prediction. METHODS: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 458 cases were enrolled (training set = 401; validation set = 57). TCGA databases were used to analyze the distinct expressions and prognostic values of related genes. The optimal cut-off values were 11.60 U/ml for P53, 4.90 U/ml for MAGEA1, 3.85 U/ml for SOX2, and 7.05U/ml for PGP9.5. RESULTS: We found that the stem signatures associated antibodies of MAGEA1, PGP9.5, SOX2, and TP53 exhibited high expressions in NSCLC, negatively correlating with the overall survival (OS) (P < 0.05). In the test groups, the diagnosis sensitivity of P53, PGP9.5, SOX2, and MAGEA1 reached to 21.5%, 39.0%, 50.3%, and 35.0%, respectively, and the specificity reached to 98.7%, 99.4%, 92.2%, and 97.4%. The four candidates' panel gave a sensitivity of 71.8% with a specificity of 89%. In the validation group, the detection of the four antibodies in early diagnosis of NSCLC also exhibited high specificity and sensitivity, further consolidating their potential application. CONCLUSIONS: The detection regarding stem signatures associated antibodies could be used as effective tools in early NSCLC diagnosis, but not for localized screening of cancers, and their abnormal expression was in accordance with poorer survival.
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Autoanticuerpos/sangre , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/patología , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/patología , Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Autoanticuerpos/inmunología , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Pronóstico , Tasa de SupervivenciaRESUMEN
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumors in the world. Genetic variants have an important role in HNSCC progression. Our study is aimed at exploring the relationship between MIR17HG polymorphisms and HNSCC risk in the Chinese Han population. METHODS: We recruited 537 HNSCC cases and 533 healthy subjects to detect the correlation of six polymorphisms in MIR17HG with HNSCC susceptibility. The associations were evaluated by computing odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analysis. RESULTS: Our study revealed that rs7336610 (OR 1.77, 95%CI = 1.09-2.86, and p = 0.021) and rs1428 (OR 1.73, 95%CI = 1.07-2.81, and p = 0.025) are strongly associated with increased susceptibility to HNSCC in men. Besides, rs17735387 played a crucial protective role in stage III/IV HNSCC patients (OR 0.34, 95%CI = 0.12-0.95, and p = 0.040) compared with stage I/II. CONCLUSION: Our study firstly indicated that MIR17HG polymorphisms are significantly associated with HNSCC susceptibility, which suggests that MIR17HG has a potential role in the occurrence of HNSCC.
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Pueblo Asiatico/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/genética , Polimorfismo de Nucleótido Simple/genética , ARN Largo no Codificante/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Estudios de Casos y Controles , Femenino , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Probabilidad , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
Matrine is one of the major alkaloids extracted from Sophora flavescens Ait of the traditional Chinese medicine, was the main chemical ingredient of compounds of Kushen injection. The Matrine is considered as a promising therapeutic agent for curing nonsmall cell lung cancer (NSCLC), used either alone or combined with chemotherapeutic agents. In the present study, we focused on the possible roles of Matrine exerted on the self-renewal ability of stem-like cells of the NSCLC group, as well as the cytotoxicity of chemotherapeutic agents, in vitro and in vivo. Here we reported that Matrine inhibits cancer stem-like cell (CSC) properties through upregulation of Let-7b and suppression of the Wnt pathway. Overexpression of Let-7b suppressed the ability of tumorsphere formation, decreased Wnt pathway activation through inhibiting its transcriptional activity in lung CSCs. Further studies revealed that Let-7b directly targeted CCND1 and decreased its expression, whereas Matrine increased Let-7b levels and followed by inactivation of the CCND1/Wnt signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in lung CSCs. What is more, we found that Matrine increased Let-7b level in an endoribonuclease DICER1-dependent manner. And xenografts in nude mice evidenced that Matrine increased the sensitivity of lung CSCs to 5-FU and inhibited the accumulation of CCND1 in tumor tissues induced by 5-FU. Taken together, these data illustrate the role of Let-7b in regulating lung CSCs traits and DICER1/let-7/CCND1 axis in Matrine or in combination with 5-FU intervention of lung CSCs' expansion, helping to fulfill the anti-cancer action of Matrine.
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Alcaloides/farmacología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Ciclina D1/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Fluorouracilo/farmacología , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Quinolizinas/farmacología , Células A549 , Alcaloides/uso terapéutico , Animales , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Resistencia a Antineoplásicos/fisiología , Fluorouracilo/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Quinolizinas/uso terapéutico , MatrinasRESUMEN
BACKGROUND: Parathyroid protection and central neck dissection (CND) are basic points of thyroid cancer surgery and draw persistent concern. We aimed to evaluate the value of carbon nanoparticles (CNs) for parathyroid gland protection and CND in thyroid surgery for thyroid cancer patients. METHODS: A total of 386 consecutive thyroid cancer patients were enrolled in the retrospective study. Three hundred thirty-four patients using CNs intraoperatively were included in the CN group, and 52 patients without using CNs or any other helping agent were included in the control group. Intact parathyroid hormone (iPTH) was examined. Medical records and histopathologic reports were reviewed. Histopathologic examination was performed. RESULTS: There were no statistical significances in demographic and basic surgical information, preoperative iPTH, and serum calcium between the two groups (P > 0.05). In the CN group, the thyroid tissue and central neck lymph nodes were stained black by CNs, while the parathyroid glands were not. Histopathological examination showed that the carbon nanoparticles might accumulated in the subcapsular sinus of lymph nodes compared with the none-stained samples. The staining with CNs did not impact the histopathological examination. There were no significant differences in postoperative hypocalcemia and hypoPT at day 1, 1 month, and half year after surgery between the two groups, respectively. There was a big decline of iPTH level after surgery, whereas the perioperative decreasing amplitude of PTH was not statistically different between the CNs and control group (57.2 ± 28.6 vs 55.7 ± 27.8, P = 0.710). There were 43 patients occurring incidental parathyroidectomy in the CN group (43/334, 12.9%) and 7 patients in the control group (7/52, 13.5%), without significant difference (P = 0.907). There was no significant difference in the number of lymph nodes identified by pathology per patient between the CNs and control group regardless of unilateral and bilateral CND. CONCLUSIONS: Carbon nanoparticles help highlight parathyroid glands and lymph nodes in thyroidectomy, but generate no significant benefit for parathyroid glands protection and lymph node dissection. The value of carbon nanoparticles in thyroid cancer surgery should not be exaggerated and needs further evaluation.
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Cuidados Intraoperatorios/métodos , Disección del Cuello/efectos adversos , Coloración y Etiquetado/métodos , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Adulto , Carbono/administración & dosificación , Colorantes/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/prevención & control , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Nanopartículas/administración & dosificación , Disección del Cuello/métodos , Glándulas Paratiroides/lesiones , Pronóstico , Estudios Retrospectivos , Tiroidectomía/efectos adversosRESUMEN
BACKGROUND: To evaluate the efficacy of a sensitive, real-time tool for identification and protection for parathyroid glands during thyroidectomy. METHODS: Near-infrared (NIR) auto-fluorescence was measured intraoperatively from 20 patients undergoing thyroidectomy. Spectra were measured from suspicious parathyroid glands and surrounding neck tissues during the operation with a NIR fluorescence system. Fast frozen sections were performed on the suspicious parathyroid glands. Accuracy was evaluated by comparison with histology and NIR identification. Data were attracted for Fisher's linear discriminant analysis. RESULTS: The auto-fluorescence intensity of parathyroid was significantly higher than that of thyroid, fat and lymph node. The peak intensity of auto-fluorescence from parathyroid was 5.55 times of that from thyroid at the corresponding wave number. Of the 20 patients, the parathyroid was accurately detected and identified in 19 patients by NIR system, compared with their histologic results. One suspicious parathyroid did not exhibit typical spectra, and was proved to be fat tissue by histology. The NIR auto-fluorescence method had a 100% sensitivity of parathyroid glands identification and a high accuracy of 95%. The positive predictive value was 95%. The parathyroid gland have specific auto-fluorescence spectrum and can be separated from the other three samples through the Fisher's linear discriminant analysis. CONCLUSIONS: NIR auto-fluorescence spectroscopy can accurately identify normal parathyroid gland during thyroidectomy. The Fisher's linear discriminant analysis demonstrated the specificity of the NIR auto-fluorescence of parathyroid tissue and its efficacy in parathyroid discrimination.