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BACKGROUND: Circular RNAs (circRNAs) belong to a class of covalently closed single stranded RNAs that have been implicated in cancer progression. Former investigations showed that hsa-circ-0013561 is abnormally expressed in head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of hsa-circ-0013561 during the progress of HNSCC still unclear. METHODS: Present study applied FISH and qRT-PCR to examine hsa-circ-0013561 expression in HNSCC cells and tissue samples. Dual-luciferase reporter assay was employed to identify downstream targets of hsa-circ-0013561. Transwell migration, 5-ethynyl-2'-deoxyuridine incorporation, CCK8 and colony formation assays were utilized to test cell migration and proliferation. A mouse tumor xenograft model was utilized to determine the hsa-circ-0013561 roles in HNSCC progression and metastasis in vivo. RESULTS: We found that hsa-circ-0013561 was upregulated in HNSCC tissue samples. hsa-circ-0013561 downregulation inhibited HNSCC cell proliferation and migration to promote apoptosis and G1 cell cycle arrest. The dual-luciferase reporter assay revealed that miR-7-5p and PDK3 are hsa-circ-0013561 downstream targets. PDK3 overexpression or miR-7-5p suppression reversed the hsa-circ-0013561-induced silencing effects on HNSCC cell proliferation and migration. PDK3 overexpression reversed miR-7-5p-induced effects on HNSCC cell proliferation and migration. CONCLUSION: The findings suggest that hsa-circ-0013561 downregulation inhibits HNSCC metastasis and progression through PDK3 expression and miR-7-5p binding modulation.
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BACKGROUND: Cancer-associated fibroblasts (CAFs) play an essential role in tumorigenesis and development of cancers. Nevertheless, the specific molecular mechanism of tumorigenesis and development in Laryngeal squamous cell carcinoma (LSCC) still unknown. METHODS: CAFs, CPFs and NFs were isolated and identified from laryngeal cancer, para-laryngeal cancer and normal tissues. Immunofluorescent staining, Rt-PCR and Western Blot were used to detect the expression of related proteins. Wound healing, migration, invasion and animal experiments were used to examine the ability of movement, migration, invasion and metastasis of LSCC. RESULTS: ROCK1, was highly expressed in CAFs and CAFs enhanced LSCC metastasis in vivo and vitro, and downregulation of ROCK1 in CAFs inhibited the migration and invasion of LSCC cells. While increasing ROCK1 expression in NFs promoted the migration and invasion of LSCC cells. Further studies revealed that epithelial-mesenchymal transition (EMT) and JAK2/STAT3/ERK1/2 pathway might play an essential role in promoting metastasis of LSCC. In addition, inhibition activity of ROCK1 or JAK2/STAT3/ERK1/2 signal molecules significantly reduced EMT and metastasis. CONCLUSIONS: CAFs-derived ROCK1 via JAK2/STAT3/ERK1/2 axis mediated EMT to promote LSCC metastasis and targeting ROCK1 might provide a potential treatment strategy for LSCC.
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BACKGROUND: Lymphangiogenesis has been reported to play crucial roles in the metastasis of thyroid cancer (THCA), but despite the significant research on lymphangiogenesis in THCA, the precise regulatory mechanism remains unclear. METHODS: Public databases including the Cancer Genome Atlas (TCGA), TIMER, and UALCAN were used to analyze and visualize the expression of TET3 and AHR in THCA, and the correlation between these molecules were used by TIMER. Additionally, RT-PCR and Western Blot were performed to determine the mRNA and protein expression of related proteins. Plate colony formation, wound healing, cell cycle, apoptosis, angiogenesis and transwell assay were used to examine the ability of proliferation, movement, lymphangiogenesis, migration and invasion of THCA cells. RESULTS: Analysis of the TCGA database revealed higher expression levels of TET3 and AHR in tumor tissue compared to normal tissue in THCA. Additionally, a strong correlation was observed between TET3 and AHR. UALCAN database demonstrated that high expression of TET3 and AHR was associated with advanced THCA TNM stages in THCA patients. Furthermore, TET3 activation accelerated THCA cell proliferation by inducing G2/M phase arrest and suppressing apoptosis, while AHR inactivation reduced THCA cell proliferation by decreasing G2/M phase arrest and promoting apoptosis in vitro. Notably, both TET3 and AHR significantly enhanced THCA cell lymphangiogenesis, migration and invasion. Moreover, TET3 activation and AHR inactivation regulated HIF-1α/VEGF signaling pathway, which ultimately, blocked the HIF-1α/VEGF in THCA cells and impaired their movement, migration and invasion abilities. CONCLUSIONS: The combined action of TET3 and AHR to promote lymphangiogenesis in THCA through the HIF-1α/VEGF signaling pathway, and targeting them might provide a potential treatment strategy for THCA.
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INTRODUCTION: The objective was to investigate the correlation between Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection in the development of benign thyroid lesions. MATERIAL AND METHODS: 29 cases of Hashimoto's thyroiditis (HT), 133 cases of thyroid adenoma, and 34 cases of HT with thyroid adenoma paraffin embedded tissue samples were used for EBV and HPV quantitative detection. RESULTS: None of the tissue samples carried HPV DNA. In HT tissue samples, the positive rate of EBV was 55.2% (16/29). In thyroid adenoma tissue samples, the positive rate was 37.6% (50/133). In HT combined with thyroid adenoma tissue samples, the positive rate of EBV was 67.6% (23/34). There was no correlation between EBV infection and clinical features such as age and gender. CONCLUSION: The occurrence and development of benign thyroid lesions are closely related to EBV infection. HT combined with thyroid adenoma may be more susceptible to EBV infection than simple HT and thyroid adenoma, which provides a new idea for the diagnosis and treatment of benign thyroid lesions.
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Infecções por Vírus Epstein-Barr , Doença de Hashimoto , Herpesvirus Humano 4 , Infecções por Papillomavirus , Neoplasias da Glândula Tireoide , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/virologia , DNA Viral/análise , Infecções por Vírus Epstein-Barr/complicações , Doença de Hashimoto/virologia , Herpesvirus Humano 4/isolamento & purificação , Papillomavirus Humano/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Neoplasias da Glândula Tireoide/virologiaRESUMO
Thyroid cancer, notably papillary thyroid cancer (PTC), is a global health concern with increasing incidence. Anoikis, a regulator of programmed cell death, is pivotal in normal physiology and, when dysregulated, can drive cancer progression and metastasis. This study explored the impact of anoikis on PTC prognosis. Analyzing data from GEO, TCGA, and GeneCards, we identified a prognostic signature consisting of six anoikis-related genes (ARGs): EZH2, PRKCQ, CD36, INHBB, TDGF1, and MMP9. This signature independently predicted patient outcomes, with high-risk scores associated with worse prognoses. A robust predictive ability was confirmed via ROC analysis, and a nomogram achieved a C-index of 0.712. Differences in immune infiltration levels were observed between high- and low-risk groups. Importantly, the high-risk group displayed reduced drug sensitivity and poor responses to immunotherapy. This research provides insights into anoikis in PTC, offering a novel ARG signature for predicting patient prognosis and guiding personalized treatment strategies.
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Anoikis , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Anoikis/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Prognóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Nomogramas , Perfilação da Expressão GênicaRESUMO
Poor blood glucose control is a common predisposing factor for parotid abscesses; however, extensive skin necrosis secondary to parotid abscesses has rarely been reported. In this article, we present the case of a 70-year-old man with poor glycemic control admitted to our hospital with swelling, congestion, and pain in the right parotid region that had gradually increased over 15 days prior to presentation. Based on the clinical, imaging, and laboratory findings, the patient was diagnosed with a giant parotid abscess with extensive skin necrosis caused by Klebsiella pneumoniae. The abscess responded poorly to long-term treatment with intravenous broad-spectrum antibiotics, and the patient underwent daily Bacillus exchange with blood glucose level management and electrolyte monitoring via routine blood tests. At the 3 month follow-up, complete resolution of the right parotid gland abscess and skin rupture was observed.
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Fibrovascular polyps (FVPs) are rare benign submucosal tumor-like lesions originating in the cervical esophagus and sporadically in the hypopharynx. In this article, we report a rare case of FVPs of the hypopharynx (hFVPs) with a mass measuring 16.0 × 4.0 × 1.8 cm in size, discussed its surgical strategy, and additionally reviewed relevant literature on important factors, such as age, sex, symptoms, size, treatments, and recurrence, associated with hFVPs.
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Spindle epithelial tumor with thymus-like differentiation of thyroid (SETTLE) is very rare neoplasm with 2 cellular forms, epithelial cell and spindle cell, and most reported cases have been in young people. An 11-year-old boy presented with painless swelling of the right neck lasting for more than 2 months. A tumor size measuring approximately 3 × 3 cm was resected, and intraoperative frozen pathology suggested a spindle cell tumor, which was confirmed as SETTLE by immunohistochemical staining and external hospital consultation. The immunohistochemical staining profile of the resected tumor tissue was as follows: cytokeratin (CK) (+), smooth muscle actin (weak+), vimentin (+), CK7 (focal+), B-cell lymphoma 2 (partial+), CD99 (-), calcitonin (+), galectin-3 (+), CK19 (+), and Ki-67 (10%+). Ultrasound at 1-year postoperative follow-up revealed no local recurrence of the lesion or lymph node metastasis in the thyroid gland. We summarized the disease characteristics of SETTLE among 6 cases reported to date and found that SETTLE is associated with a good prognosis and low postoperative recurrence rate. Thus, for this type of malignant thyroid tumor, diagnosis depends mainly on postoperative pathology and immunohistochemical staining and simple surgical resection is recommended.
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Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck squamous cell carcinomas (HNSCC). Rho-associated kinase1 (ROCK1) is considered to promote progression of numerous cancers, however, its role in LSCC is still unknown. Here, the expression level of ROCK1 is higher in LSCC tissues than non-tumor tissues, and the expression level of ROCK1 is positively correlated with advanced stage and poor survival prognosis. ROCK1 knockdown in TU686 and TU212 cells dramatically inhibits cellular proliferation, migration and invasion. Whereas the overexpression of ROCK1 reversed these changes. FAK signaling pathway plays an essential role in promoting LSCC progression. Inhibiting FAK activity with TAE226 observably impairs the tumor-promoting effects. In conclusion, ROCK1 promotes LSCC tumorigenesis and progression via the FAK signaling pathway, targeting the ROCK1 molecule may represent potential targets for clinical LSCC treatment.
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We previously found that the Rho-associated kinase 1 (ROCK1) activated Cancer-associated fibroblasts (CAFs) to promote LSCC metastasis. Accumulating evidence indicates that pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) is an oncogene; however, the crosstalk between ROCK1 and PYROXD1 in LSCC metastasis remains largely unknown. Here, we found that ROCK1 could target PYROXD1. The knockdown of ROCK1 expression reduces the expression of PYROXD1, while the knockdown of PYROXD1 expression did not alter the expression of ROCK1 indicating that ROCK1 is upstream of PYROXD1. Further, LSCC cells cocultured with PYROXD1 knocked-down CAFs exhibited lower proliferation, migration, invasion and metastasis abilities. Conversely, LSCC cells cocultured with PYROXD1-overexpressing CAFs showed opposite results. In conclusion, the crosstalk between ROCK1 and PYROXD1 regulated CAFs activation and promoted LSCC metastasis.
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One of the main clinical treatments for advanced nasopharyngeal carcinoma is chemotherapy, but systemic administration can cause serious adverse reactions. New type of nanomaterial which can actively targeting, imaging, and treating nasopharyngeal carcinoma at the same time to enhance the effect of chemotherapy, meanwhile monitoring the intracellular drug release process at the level of single cancer cell was urgently needed. GE11, an EGFR antagonist peptide, was used to target nasopharyngeal carcinoma which has positive expression of EGFR on its nucleus. GE11-modified graphene quantum dots (GQDs@GE11) were used as drug carriers for clinical chemotherapeutics cisplatin (CDDP) and doxorubicin (DOX). The emission spectrum of GQDs (460 nm) and the excitation spectrum of DOX (470 nm) have a good overlap, thus the transfer and release process of DOX can be sensitively detected by the fluorescence resonance energy transfer (FRET). CDDP was used to enhance the chemotherapy effect of nanoprobe, and the loading amount of DOX and CDDP on GQDs@GE11 nanoprobe were up to 67 and 50 mg/g, respectively. In vivo experiments have confirmed that GQDs@GE11/CDDP/DOX nanoprobe can be enriched to tumor site through specific targeting effect, and significantly inhibit tumor cell proliferation. This new type of targeted therapy fluorescent probe provides new ideas for the study of drug release process and the treatment of nasopharyngeal carcinoma.
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BACKGROUND: This study sought to establish a rat model of hypoparathyroidism by removing the rat parathyroid glands, and compare the effects of different transplantation sites and transplantation methods using a primary culture of parathyroid cells in vitro on the hormone secretion of the model rats. METHODS: Male Sprague Dawley (SD) rats were selected for in vivo parathyroid gland removal, and rats with abnormal postoperative water intake, weight gain, parathyroid hormone (PTH), and blood calcium ion concentration were selected as transplant recipients and divided into the model group, brachioradialis muscle cell transplantation group, gelatin sponge group, and subcutaneous transplantation group. The parathyroid tissue was removed and the primary cell culture was performed in vitro using homozygous SD rats as graft donors. When the parathyroid cells were able to secrete PTH, transplantation was performed, and the postoperative recovery of the PTH function of the rats with different transplantation sites and methods were observed. RESULTS: A recipient model with low PTH was successfully established, and parathyroid progenitor cells with obvious PTH secretion were obtained. Better secretion was observed in the brachioradialis cell group compare with other groups. CONCLUSIONS: The in vitro primary cell culture of the donor parathyroid cells combined with cell transplantation significantly improved the physiological function of the hypoparathyroid rats, and could potentially replace traditional clinical brachioradialis muscle tissue transplantation.
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Mutations in mitochondrial 12S rRNA (MT-RNR1) are the important causes of sensorineural hearing loss. Of these mutations, the homoplasmic m.1555A>G or m.1494C>T mutation in the highly conserved A-site of MT-RNR1 gene has been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. Since the m.1555A>G and m.1494C>T mutations are sensitive to ototoxic drugs, therefore, screening for the presence of these mutations is important for early diagnosis and prevention of deafness. For this purpose, we recently developed a novel allele-specific PCR (AS-PCR) which is able to simultaneously detect these mutations. To assess its accuracy, in this study, we employed this method to screen the frequency of m.1555A>G and m.1494C>T mutations in 200 deafness patients and 120 healthy subjects. Consequently, four m.1555A>G and four m.1494C>T mutations were identified; among these, only one patient with the m.1494C>T mutation had an obvious family history of hearing loss. Strikingly, clinical evaluation showed that this family exhibited a high penetrance of hearing loss. In particular, the penetrances of hearing loss were 80% with the aminoglycoside included and 20% when excluded. PCR-Sanger sequencing of the mitochondrial genomes confirmed the presence of the m.1494C>T mutation and identified a set of polymorphisms belonging to mitochondrial haplogroup A. However, the lack of functional variants in mitochondrial and nuclear modified genes (GJB2 and TRMU) in this family indicated that mitochondrial haplogroup and nuclear genes may not play important roles in the phenotypic expression of the m.1494C>T mutation. Thus, other modification factors, such as environmental factor, aminoglycosides or epigenetic modification may have contributed to the high penetrance of hearing loss in this family. Taken together, our data showed that this assay is an effective approach that could be used for detection the deafness-associated MT-RNR1 mutations.
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Alelos , Surdez/genética , Mitocôndrias/genética , Mutação/genética , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico/genética , Adulto , Idoso , Povo Asiático/genética , Audiometria , Sequência de Bases , Conexina 26 , Conexinas/genética , Análise Mutacional de DNA , Etnicidade/genética , Feminino , Genoma Mitocondrial , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Linhagem , tRNA Metiltransferases/genéticaRESUMO
BACKGROUND: Adrenomedullin has been identified as a tumor growth factor. However, few studies have reported its relationship with cancer survival. We evaluated the prognostic value of pretreatment plasma adrenomedullin levels in nasopharyngeal carcinoma (NPC). METHODS: Plasma adrenomedullin levels of 258 NPC patients and 100 healthy controls were determined using enzyme-linked immunosorbent assay. Adverse event was defined as tumor progression or death from any cause during 5-year follow-up. The relationships between plasma adrenomedullin levels and 5-year mortality, adverse event, tumor-free survival and overall survival were evaluated using multivariate analysis. RESULTS: Pretreatment plasma adrenomedullin levels were substantially higher in patients than in healthy subjects and were correlated highly with tumor classification, lymph node classification and tumor node metastasis stage positively. Adrenomedullin was identified as an independent predictor of 5-year mortality, adverse event, tumor-free survival and overall survival. Based on receiver operating characteristic curve analysis, pretreatment plasma adrenomedullin level had high predictive value for 5-year mortality and adverse event and had high diagnostic value for NPC. CONCLUSIONS: Adrenomedullin may be a reliable biomarker for predicting the long-term prognosis of patients with NPC and also has potential diagnostic utility for NPC.