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Research on individuals with a younger onset age of schizophrenia is important for identifying neurobiological processes derived from the interaction of genes and the environment that lead to the manifestation of schizophrenia. Schizophrenia has long been recognized as a disorder of dysconnectivity, but it is largely unknown how brain connectivity changes are associated with psychotic symptoms. Twenty-one adolescent-onset schizophrenia (AOS) patients and 21 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) was used to investigate local brain connectivity alterations in AOS. Regions with significant ReHo changes in patients were selected as "seeds" for further functional connectivity (FC) analysis and Granger causality analysis (GCA), and associations of the obtained functional brain measures with psychotic symptoms in patients with AOS were examined. Compared with HCs, AOS patients showed significantly increased ReHo in the right middle temporal gyrus (MTG), which was positively correlated with PANSS-positive scores, PSYRATS-delusion scores and auditory hallucination scores. With the MTG as the seed, lower connectivity with the bilateral postcentral gyrus (PCG) and higher connectivity with the right precuneus were observed in patients. The reduced FC between the right MTG and bilateral PCG was significantly and positively correlated with hallucination scores. GCA indicated decreased Granger causality from the right MTG to the left middle frontal gyrus (MFG) and from the right MFG to the right MTG in AOS patients, but such effects did not significantly associate with psychotic symptoms. Abnormalities in the connectivity within the MTG and its connectivity with other networks were identified and were significantly correlated with hallucination and delusion ratings. This region may be a key neural substrate of psychotic symptoms in AOS.
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BACKGROUND: Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms. METHODS: Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages. RESULTS: LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages. CONCLUSIONS: Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC.
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BACKGROUND: Nasopharyngeal carcinoma (NPC) is a subtype of head and neck cancer with dismal prognosis and high relapse rate. The role of long non-coding RNAs (lncRNAs) in NPC has become a research hotspot in recent years. This study aimed to interrogate the function and mechanism of lncRNA MSC antisense RNA 1 (MSC-AS1) in NPC. METHODS: MSC-AS1 level in NPC tissues and cells were detected by RT-qPCR. Function of MSC-AS1 in NPC cells was assessed by CCK-8, EdU, TUNEL, caspase-3 activity, and transwell invasion assay. Interaction of microRNA-524-5p (miR-524-5p) with MSC-AS1 and nuclear receptor subfamily 4 group A member 2 (NR4A2) was determined by RIP and luciferase reporter assays. RESULTS: MSC-AS1 was upregulated in NPC tissues and cells. Functional assays indicated that MSC-AS1 exacerbated cell proliferation, hindered apoptosis, and facilitated invasion and epithelial-to-mesenchymal transition (EMT) in NPC. Mechanistically, MSC-AS1 sequestered miR-524-5p to upregulate NR4A2 expression in NPC cells. Finally, NR4A2 was conformed as an oncogene in NPC, and overexpressed NR4A2 could restore MSC-AS1 knockdown-mediated inhibition on NPC progression. CONCLUSIONS: Our study firstly showed that lncRNA MSC-AS1 aggravated NPC progression by sponging miR-524-5p to increase NR4A2 expression, indicating MSC-AS1 as a novel target for the lncRNA-targeted therapy in NPC.
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Previous studies investigating the association between glutathione S-transferase M1 (GSTM1) null genotype and laryngeal cancer risk reported controversial results. Thus, a meta-analysis was performed to clarify the effect of GSTM1 null genotype on laryngeal cancer risk. A literature search was performed for all possible studies. We estimated summary odd ratio (OR) with its 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by ethnicity or the sample size. 24 individual case-control studies involving a total of 2,809 laryngeal cancer cases and 4,478 controls were finally included into this meta-analysis. Meta-analyses of total 24 studies showed the GSTM1 null genotype was significantly associated with increased laryngeal cancer risk (random-effects OR = 1.44, 95 % CI 1.19-1.73, P < 0.001). Subgroup analyses by ethnicity showed that the GSTM1 null genotype was associated with increased laryngeal cancer risk in both Caucasians (fixed-effects OR = 1.17, 95 % CI 1.04-1.33, P = 0.012) and Asians (random-effects OR = 1.89, 95 % CI 1.28-2.77, P = 0.001). Also, subgroup analyses by sample size also further identified this association above. The cumulative meta-analyses showed a trend of more obvious association between GSTM1 null genotype and increased risk of laryngeal cancer as information accumulated by year. Meta-analysis of available data suggests that GSTM1 null genotype contributes to increased laryngeal cancer risk in both Caucasians and East Asians.
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Predisposição Genética para Doença , Genótipo , Glutationa Transferase/genética , Neoplasias Laríngeas/genética , Humanos , Polimorfismo GenéticoRESUMO
Schizophrenia is a disorder resulting from aberrant brain networks and circuits. In the current study, we aimed to investigate specific network alterations in adolescent-onset schizophrenia (AOS) and to help identify the neurophysiological mechanisms of this adolescent disorder. We recruited forty-one subjects, including 20 AOS patients and 21 matched healthy controls (HCs), and we acquired brain images to examine the specific changes in functional network patterns using degree centrality (DC), which quantifies the strength of the local functional connectivity hubs. Whole-brain correlation analysis was applied to assess the relationships between clinical characteristics and DC measurements. The AOS group exhibited increased DC in the right inferior frontal lobe, right fusiform gyrus and right thalamus (p < 0.05, AlphaSim correction). Whole-brain correlation analysis found that the DC value in the right parahippocampus was positively correlated with PANSS-positive symptom scores (r = 0.80); DC in the right superior parietal lobe (SPL) was positively correlated with PANSS-negative symptom scores (r = 0.79); DC in the left precuneus was positively correlated with self-certainty (SC) scores (r = 0.70); and DC in the left medial frontal gyrus (MFG) was negatively correlated with self-reflectiveness (SR) scores (r = 0.69). We conclude that frontoparietal network and cortico-thalamo-cortical pathway disruptions could play key roles in the neurophysiological mechanisms underlying AOS. In AOS patients, the right parahippocampus and SPL are important structures associated with positive and negative symptoms, respectively, and the left precuneus and MFG contribute to deficits in cognitive insights.
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Preparações Farmacêuticas , Esquizofrenia , Adolescente , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico por imagemRESUMO
The aim of the present study was to compare the diagnostic performance of the main parameters derived from diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) regarding the detection and grading of hepatocellular carcinoma (HCC). A total of 78 patients diagnosed with HCC by biopsy were prospectively enrolled in the present study, and underwent routine magnetic resonance imaging (MRI), DWI, IVIM, DKI and contrast-enhanced MRI prior to surgery. Measurements, including mean diffusivity (MD), mean diffusional kurtosis (MK), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC), were compared with grading HCC using one-way ANOVA followed by the Student-Neuman-Keuls-q post-hoc test. Spearman's correlation coefficient was used to analyze the correlation between each parameter and pathological grade, while the diagnostic efficiency was evaluated using a receiver operating characteristic (ROC) curve. The 78 patients enrolled in the present study were grouped into highly (n=22), moderately (n=41) or poorly (n=15) differentiated HCC groups according to the criteria of Pathology and Genetics Tumors of the Digestive System. MK values differed significantly between different grades and decreased gradually with the degree of tumor differentiation. The MD, D and ADC values in the highly differentiated HCC group were significantly higher than those in the moderately or poorly differentiated HCC groups (all P<0.001), whereas no significant differences were observed in D* or f (P=0.502 and P=0.853, respectively). A significant correlation was observed between MK, MD, D and ADC, and HCC grades (r=0.705, r=0.570, r=0.423 and r=0.687, respectively). The comparison of the ROC curves of MK, MD, D, ADC, D* and f values for predicting highly differentiated HCC suggested that MK and D were the best indicators for predicting highly differentiated HCC, as the area under the ROC curve (AUC) of MK and D was significantly higher than that of ADC (Z=2.247 and 2.428, P=0.025 and 0.016, respectively), whereas non-statistically significant differences were observed in the AUC values between MK and D (Z=0.072; P=0.942). The DKI-derived MK and IVIM-derived D values had a similar diagnostic performance and were superior to ADC in discriminating the histological grade of HCC. In addition, the combination of MK and D values exhibited an improved diagnostic performance.
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At present, minimally invasive surgery is one of the primary strategies for the treatment of malignant pulmonary tumors. Although, there are some comparative studies between microwave ablation and radiofrequency for the treatment of malignant pulmonary tumors, there are few studies that have investigated the comparison between microwave ablation and cryoablation. The aim of the study was to retrospectively compare the efficacy and complications of microwave ablation (MWA) and cryoablation in the treatment of malignant pulmonary tumors. A retrospective analysis was performed on 48 patients with malignant lung tumors treated with MWA or cryoablation in The Third Hospital of Mianyang and The Affiliated Hospital of North Sichuan Medical College between June 2014 and June 2018. Of these patients, 29 received MWA and 19 received cryoablation. Intraprocedural pain was evaluated by using the visual analog scale (VAS). The intraprocedural pain, response rates, overall survival (OS) and complications rates were compared between the MWA group and cryoablation group. The results showed that the patients in the MWA group experienced more pain than those in cryoablation group as the MWA group VAS scores were much higher than those in cryoablation group (P<0.001). The overall response rate of the MWA group [21/29 (72.41%)] was not significantly different from the cryoablation group [14/19 (73.68%)] (P=0.92). The 6-, 12-, 24- and 36-month OS rates in the MWA group and cryoablation group were 92.72, 81.28, 64.54 and 54.91%, and 94.07, 81.13, 57.33 and 43.04%, respectively. No significant differences were found in the OS rate between the two groups (P=0.79). The complication rates in the MWA and cryoablation groups were 34.48 and 36.84%, respectively; there was no significant difference between the two groups (P=0.59). No patients died during the perioperative period. Cryoablation had a similar therapeutic effect compared with MWA in the treatment of pulmonary malignant tumors, but was associated with less pain.
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BACKGROUND: Family environment and life events have long been suggested to be associated with adolescent depression. The hippocampus plays a crucial role in the neural mechanism of major depressive disorder (MDD) through memory during stressful events. However, few studies have explored the exact neural mechanisms underlying these associations. Thus, the current study aimed to explore alterations in hippocampal functional connectivity (FC) in adolescent MDD based on resting-state functional magnetic resonance imaging and further investigate the relationship between hippocampal FC, environmental factors, and clinical symptom severity. METHODS: Hippocampal FC was calculated using the seed-based approach with the bilateral hippocampus as the seed for 111 adolescents with and without MDD; comparisons were made between participants with MDD and controls. We applied the Chinese version of the Family Environment Scale (FES-CV) and Adolescents Self-Rating Life Events Checklist (ASLEC) to evaluate family environment and life stress. Their relationship with hippocampal FC alterations was also investigated. RESULTS: We found that compared to controls, adolescents with MDD showed decreased connectivity between the left hippocampus and bilateral orbital frontal cortex (OFC) and right inferior temporal gyrus. In addition, the hippocampal-OFC connectivity was negatively correlated with conflict scores of the FES-CV in the MDD group and mediated the association between family conflict and depressive and anxiety symptoms. CONCLUSION: Our findings are novel in the field and demonstrate how family conflict contributes to MDD symptomatology through hippocampal-OFC connectivity; these findings may provide potential targets for personalized treatment strategies.
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BACKGROUND: To evaluate the role of high-resolution computed tomography (HRCT) in the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia and to provide experience in the early detection and diagnosis of 2019-nCoV pneumonia. METHODS: Seventy-two patients confirmed to be infected with 2019-nCoV from multiple medical centers in western China were retrospectively analyzed, including epidemiologic characteristics, clinical manifestations, laboratory findings and HRCT chest features. RESULTS: All patients had lung parenchymal abnormalities on HRCT scans, which were mostly multifocal in both lungs and asymmetric in all patients, and were mostly in the peripheral or subpleural lung regions in 52 patients (72.22%), in the central lung regions in 16 patients (22.22%), and in both lungs with "white lung" manifestations in 4 patients (5.56%). Subpleural multifocal consolidation was a predominant abnormality in 38 patients (52.78%). Ground-glass opacity was seen in 34 patients (47.22%). Interlobular septal thickening was found in 18 patients, 8 of whom had only generally mild thickening with no zonal predominance. Reticulation was seen in 8 patients (11.11%), and was mild and randomly distributed. In addition, both lungs of 28 patients had 2 or 3 CT imaging features. Out of these 72 patients, 36 were diagnosed as early stage, 32 patients as progressive stage, and 4 patient as severe stage pneumonia. Moreover, the diagnostic accuracy of HRCT features combined with epidemiological history was not significantly different from the detection of viral nucleic acid (all P >0.05). CONCLUSIONS: The HRCT features of 2019-nCoV pneumonia are characteristic to a certain degree, which when combined with epidemiological history yield high clinical value in the early detection and diagnosis of 2019-nCoV pneumonia.
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Ectopic thyroid tissue of nasopharynx is an uncommon phenomenon and papillary thyroid carcinoma arising from the tissue is extremely rare. The authors report a rare case of 16-year-old girl with papillary thyroid carcinoma of nasopharynx. Clinicians were ever confused by adenoid hypertrophy and solved the diagnostic dilemma by adequate examinations. In the case, we mainly emphasize that surgeons should be aware of and actively consider such a possibility of ectopic papillary thyroid carcinoma of nasopharynx in children and adolescents with long-term nasal obstruction, even if thyroid carcinoma is a rare tumor.
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Tonsila Faríngea/patologia , Carcinoma Papilar/diagnóstico , Coristoma/diagnóstico , Doenças Nasofaríngeas/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Feminino , Humanos , HipertrofiaRESUMO
ASAP1 helps regulate cellular structures such as actin cytoskeletal remodeling and focal adhesions that have a pivotal function in tumor progression. Overexpression of ASAP1 has proven to be a malignant indicator for a variety of tumors. To further determine the potential involvement of ASAP1 in laryngeal squamous cell carcinoma (LSCC), we evaluated the expression levels of ASAP1 by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry in tissue samples of 64 LSCC patients. We then analyzed and correlated the results with clinicopathological features. Furthermore, we used small interfering RNA (siRNA) to inhibit ASAP1 expression in vitro. The potential function of ASAP1 in invasiveness was evaluated in the Hep-2 LSCC cell line. Kaplan-Meier method was utilized to determine the association of ASAP1 expression with survival of patients. We showed that ASAP1 was upregulated in primary LSCC tumors and was correlated with lymph node metastasis and clinical tumor stage. Similarly, higher levels of ASAP1 were detected in the Hep-2 cell line compared to the 16 human bronchial epithelial (16HBE) cell line. ASAP1 expression was downregulated by lentiviral vector transfection containing siRNA in vitro. The invasive potential of these cells was found to be significantly suppressed, while expression levels of Rac1 and Cdc42 positively correlated with the inhibition of ASAP1 expression. In Kaplan-Meier overall survival curves, higher ASAP1 mRNA levels were found to be associated with a shorter progression-free survival trend. Based on these results, ASAP1 appears to contribute to the malignant mechanism of LSCC and may represent a significant prognostic marker for LSCC patients.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Laríngeas/genética , Invasividade Neoplásica/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/patologia , Estadiamento de Neoplasias , RNA Mensageiro/biossíntese , RNA Interferente PequenoRESUMO
miRNAs regulate gene expression and are key mediators of tumourigenesis. miR-129 has diverse effects in tumours, but its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. This article focuses on the role of miR-129-5p in LSCC. We show miR-129-5p is upregulated in primary LSCC tumours and correlated with advanced disease. Down-regulating miR-129-5p suppressed cell proliferation and migration, and caused cell cycle arrest in Hep-2 cell lines. Downregulation of miR-129-5p alone is sufficient to induce apoptosis both in vivo and in vitro. Moreover, the growth of LSCC xenograft exposed to miR-129-5p antisense oligonucleotides (ASO) in BALB/c mice was markedly inhibited. In addition, we found that miR-129-5p targeted adenomatous polyposis coli (APC) to release inhibition of Wnt signalling causing cell growth and tumourigenesis. Our results suggest miR-129-5p functions as an oncogene in LSCC by repressing APC and is a potential therapeutic target for LSCC.
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Proteína da Polipose Adenomatosa do Colo/metabolismo , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Laríngeas/metabolismo , MicroRNAs/metabolismo , Animais , Apoptose/genética , Carcinoma de Células Escamosas/genética , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Laríngeas/genética , Camundongos , Camundongos Endogâmicos BALB C , Oligonucleotídeos Antissenso/genéticaRESUMO
OBJECTIVE: To study the effect of anti-tumor peptide of tumstatin on tumor growth of human laryngeal squamous carcinoma in nude mice and the underlying mechanism. METHOD: Nude mice model bearing laryngocarcinoma were established by using human laryngeal squamous carcinoma cell line (Hep-II). The animals were given tumstatin or PBS for 10 consecutive days. The volumes of the subcutaneous tumor were observed. The microstructure in which the general 2-step immunohistochemical examination was adopted and ultra-micro-structural changes of carcinoma after administration of tumstatin were observed under light and electron microscopes for pathology examination. RESULT: The differences was statistically significant in the net mice weight, tumor weight, tumor volume and tumor weight/net mice weight between the treatment group and the control group (P<0.01). The restrained percentage of tumor was 51.58%. The necrosis and apoptosis of the tumor cells and the angiogenesis reduction were found under light and electron microscope in the treatment group. MVD of the treatment group was lower than that of the control group (P<0.01). CONCLUSION: Tumstatin can significantly restrain the development of laryngocarcinoma.
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Autoantígenos/farmacologia , Carcinoma de Células Escamosas/patologia , Colágeno Tipo IV/farmacologia , Neoplasias Laríngeas/patologia , Peptídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To study the apoptosis inducing effect of tumor necrosis factor related apoptosis-ligand (TRAIL) on human laryngeal squamous carcinoma Hep-2 cells and its effect mechanism. METHOD: The human laryngeal squamous carcinoma Hep-2 cell line was treated with different concentration of TRAIL in vitro. The inhibition ratio of tumor cells was determined by MTT colorimetric assay, the incidence of cell apoptosis was determined by flow cytometry method. The morphologic changes of laryngeal squamous carcinoma Hep-2 cell were observed with transmission electron microscope. RESULT: In vitro, all the different concentrations of TRAIL inhibited laryngeal squamous carcinoma cell's growth. The inhibited growth ratio showed significant concentration-dependence. The concentrations for inducing apoptosis-ratio(TRAIL 1, 10, 100 microg/L) determined by flow cytometry was (11.49 +/- 0.36)%, (22.31 +/- 0. 82)%, (59.64 +/- 1.10)% respectively in the study group, and (3.13 +/- 0.12)% in the control group, which was significantly different between these two groups (P < 0. 01). CONCLUSION: In vitro, TRAIL inhibited the growth of human laryngeal squamous carcinoma Hep-2 cells. The induced apoptosis of TRAIL shows significant concentration- independence. TRAIL inhibits the growth of human laryngeal squamous carcinoma Hep-2 cells trough inducing apoptosis.
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Apoptose/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Laríngeas/patologiaRESUMO
OBJECTIVE: To study the incentives of laryngeal cancer in Heilongjiang province. METHOD: A 1:One matched case control study was used to study the risk factors of laryngeal cancer in Heilongjiang province, distributing all tested staff by the same gender, age, urban and rural. Logistic regression models were used to analysis the relationship. RESULT: In single Logistic regression models, such habit as high levels of education, frequently consumption of sauerkraut, BBQ food, processed meats, the less physical activity, a relatively short time, smoking, irascible, and other factors would increase the risk of suffering from laryngeal cancer. But regular consumption of fresh vegetables, coarse grains, eggs, milk, and regular physical activity would reduce the risk of suffering from laryngeal cancer. The odds ratios (OR) were calculated using multiple Logistic regression models, ORs for the highest versus the lowest quintile of intake were 15.502 0 for high levels of education. 8.012 0 for smoking frequently. 7. 2680 for eating sauerkraut. 2.904 0 for eating BBQ food. 0.408 0 for exercise in protective factors. CONCLUSION: Potential risk factors for laryngeal cancer were eating sauerkraut. BBQ food and smoking frequently, but proper exercise may reduce the risk of laryngeal cancer.
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Neoplasias Laríngeas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Neoplasias Laríngeas/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: To study the expression of tumor necrosis factor related apoptosis induce ligand (TRAIL) receptors (DR4, DR5, DcR1, DcR2) in human laryngeal squamous cell carcinoma (LSCC). METHOD: The expression and distribution of DR4, DR5, DcR1, DcR2 were detected by immunohistochemical method in 68 patients of LSCC and 40 laryngeal normal tissues (LNT). RESULT: All of TRAIL receptors was observed in both tissues of LSCC and LNT. It was found that DR4, DR5 were overexpressed in the two tissues, indicating that there were no significant difference between the expressions of DR4 and DR5 in two tissues (P >0.05). DcR1 , DcR2 were over-expressed in LNT,were low expressed in LSCC (P <0. 05). Level of the TRAIL receptors DR5, DcR2 related with the degree of LSCC histological differentiation (P <0. 05). All receptors were not related with different clinical stage (P >0.05). CONCLUSION: TRAIL receptors expression is generally expressed in human LSCC and LNT. The expression level of TRAIL receptors is various, which may explain the anti-cancer effect of TRAIL. The TRAIL receptor DcR1, DcR2 may play an important role in the apoptosis regulation of LSCC.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Humanos , Neoplasias Laríngeas/patologia , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: To investigate the inhibitory effects of adenovirus transduced TFPI-2 gene on the growth of laryngeal squamous carcinoma. METHODS: Recombinant adenoviruses carrying human TFPI-2 gene were amplified and identified. The nude mouse model of laryngeal squamous carcinoma was established by intracutaneous injection of Hep-2 cells. Mice in the treated group were injected with recombinant adenoviruses with Ad-TFPI-2 (adenoviruses-TFPI-2) in peritumor tissue while mice in control group were injected with equivalent null plasmids. After treatment, the tumor weight and volume of tumor in each mouse were measured respectively. The morphological changes of tumor cells were observed using transmission electron microscope and proliferating cell nuclear antigen (PCNA) expression was examined using immunohistochemistry. RESULTS: The Ad-TFPI-2 virus titer was 2.8 x 10(12) PFU/ml after amplification. The average tumor weight and volume in Ad-TFPI-2 treated group were (1.20 +/- 0.34) cm3 and the volume (1.52 +/- 0.39) g, which were significantly lower than the tumor weight (2. 08 +/- 0.52) cm3 and (2.67 +/- 0.47) g in the control group (P < 0. 01). Apoptosis was observed in the tumors of Ad-TFPI-2 treated group. The PCNA index in Ad-TFPI-2 group was (54.9% +/- 12.4%), which was obviously lower than that (75.8% +/- 11.2%)in control group (P < 0.01). CONCLUSION: Peritumor injection of Ad-TFPI-2 can inhibit the growth of laryngeal squamous carcinoma in nude mouse model.
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Apoptose , Carcinoma de Células Escamosas/patologia , Glicoproteínas/genética , Neoplasias Laríngeas/patologia , Adenoviridae/genética , Animais , Carcinoma de Células Escamosas/genética , Vetores Genéticos , Células Hep G2 , Humanos , Neoplasias Laríngeas/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , TransfecçãoRESUMO
OBJECTIVE: To evaluate the inhibitory effect of endostatin on tumor growth of human laryngeal squamous carcinoma in nude mice and to explore the possible mechanism of the inhibition and the possible way of biological therapy. METHODS: Nude mice model bearing laryngocarcinoma was established by using human laryngeal squamous carcinoma cell line ( Hep-II). The animals were given endostatin (20 mg x kg(-1) x d(-1)) or PBS, for 21 consecutive days. The volumes of the subcutaneous tumor were observed. The microstructure in which the general 2-step immuohistochemical examination was adopted and ultra-microstructural changes of carcinoma after administration of endostatin were observed under light and electron microscopes for pathology examination. RESULTS: The differences were statistically significant for the net mice weight, tumor weight, and tumor volume and weight/net mice weight between the treatment group and the control group. The restrained percentage of tumor was 45.9%. The necrosis and apoptosis of the tumor cell and the angiogenesis reduction were found under light and electron microscope in the treatment group. The expression of MVD, PCNA and VEGF of the treatment group is lower than that of the control group, and T test showed that P < 0.01, P < 0.05, P < 0.05 respectively, the differences were statistically significant. CONCLUSIONS: These studies showed that endostatin could significantly restrain the development of laryngocarcinoma. The mechanism may be due to the effect of antiangiogesis.