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Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient's lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC.
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Linhagem da Célula/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Macrófagos/metabolismo , Adulto , Idoso , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Linhagem Celular Tumoral , Linhagem da Célula/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antígenos HLA-DR/genética , Humanos , Metástase Linfática/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Recidiva Local de NeoplasiaRESUMO
AIM: To explore the association between the determinant factors including HLA-DQB1*03, DRB1-*07, -*13 and high-risk HPV infection, the cervical squamous cell carcinoma (CSCC) pathogenesis among Chinese Uighur and Han population. MATERIALS & METHODS: HLA alleles were genotyped by PCR sequence-specific primers. RESULTS: HPV16 infection rate was significantly higher among the Uighurs and Hans with CSCC as compared with healthy controls, respectively. HLA-DQB1*03 significantly increased among Uighurs with CSCC, while HLA-DRB1*07 significantly increased among Hans with CSCC. Similar tendencies were observed for DQB1*03 with HPV16-positive Uighurs CSCC and DRB1*07 with HPV16-positive Hans CSCC. CONCLUSION: This study suggests that HLA-DQB1*03 and DRB1*07 alleles may influence the immune response to HPV16 infection and increase the risk of CSCC among the Uighurs and Hans in China.
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Alelos , Etnicidade/genética , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , China/epidemiologia , Feminino , Papillomavirus Humano 16 , Humanos , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/virologia , Medição de Risco , Análise de Sequência de DNA , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Macrófagos/metabolismo , Fator C de Crescimento do Endotélio Vascular/biossíntese , Análise de Variância , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptores de Superfície Celular/metabolismo , Fatores SexuaisRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressively malignant tumors with dismal prognosis. Profilin 2 (PFN2) is an actin-binding protein that regulates the dynamics of actin polymerization and plays a key role in cell motility. Recently, PFN2 have emerged as significant regulators of cancer processes. However, the clinical significance and biological function of PFN2 in ESCC remain unclear. METHODS: PFN2 protein expression was validated by immunohistochemistry (IHC) on tissue microarray from Chinese Han and Kazakh populations with ESCC. The associations among PFN2 expression, clinicopathological features, and prognosis of ESCC were analyzed. The effects on cell proliferation, invasion and migration were examined using MTT and Transwell assays. Markers of epithelial-mesenchymal transition (EMT) were detected by Western blot analysis. RESULTS: Compared with normal esophageal epithelium (NEE), PFN2 protein expression was markedly increased in low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and ESCC, increased gradually from LGIN to ESCC, and finally reached high grade in HGIN in the Han population. Similarly, PFN2 protein was more overexpressed in ESCC than in NEE in the Kazakh population. The results of Western blot analysis also showed that PFN2 expression was significantly higher in the ESCC tissue than in a matched adjacent non-cancerous tissue. PFN2 expression was positively correlated with invasion depth and lymph node metastasis. High PFN2 expression was significantly correlated with short overall survival (OS) (P = 0.023). Cox regression analysis revealed that PFN2 expression was an independent prognostic factor for poor OS in ESCC. Downregulation of PFN2 inhibited, rather than proliferated, cell invasion and migration, as well as induced an EMT phenotype, including increased expression of epithelial marker E-cadherin, decreased mesenchymal marker Vimentin, Snail, Slug and ZEB1, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Our findings demonstrate that PFN2 has a novel role in promoting ESCC progression and metastasis and portending a poor prognosis, indicating that PFN2 could act as an early biomarker of high-risk population. Targeting PFN2 may offer a promising therapeutic strategy for ESCC treatment.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Terapia de Alvo Molecular , Profilinas/metabolismo , Adulto , Idoso , Povo Asiático , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Linhagem Celular Tumoral , Movimento Celular , Forma Celular , Progressão da Doença , Transição Epitelial-Mesenquimal , Epitélio/metabolismo , Epitélio/patologia , Carcinoma de Células Escamosas do Esôfago , Etnicidade , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Fenótipo , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Prognóstico , Modelos de Riscos Proporcionais , RNA Interferente Pequeno/metabolismo , Curva ROC , Transfecção , Regulação para CimaRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC. METHODS: Multiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied. RESULTS: SLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro. CONCLUSIONS: Combined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.
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Proteínas de Transporte de Cátions/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/etnologia , Carcinoma/metabolismo , Carcinoma/terapia , Proliferação de Células , China , Estudos de Coortes , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , RNA Interferente Pequeno/metabolismo , Análise Serial de Tecidos , Resultado do Tratamento , Regulação para CimaRESUMO
Wearable flexible sensors are widely used in several applications such as physiological monitoring, electronic skin, and telemedicine. Typically, flexible sensors that are made of elastomeric thin-films lack sufficient permeability, which leads to skin inflammation, and more importantly, affects signal detection and consequently, reduces the sensitivity of the sensor. In this study, we designed a flexible nanofibrous membrane with a high air permeability (6.10 mm/s), which could be effectively used to monitor human motion signals and physiological signals. More specifically, a flexible membrane with a point (liquid metal nanoparticles)-line (carbon nanotubes)-plane (liquid metal thin-film) multiscale conductive structure was fabricated by combining liquid metal (LM) and carbon nanotubes (CNTs) with a polyurethane (PU) nanofibrous membrane. Interestingly, the excellent conductivity and fluidity of the liquid metal enhanced the sensitivity and stability of the membrane. More precisely, the gauge factor (GF) values of the membrane is 3.0 at 50% strain and 14.0 at 400% strain, which corresponds to a high strain sensitivity within the whole range of deformation. Additionally, the proposed membrane has good mechanical properties with an elongation at a break of 490% and a tensile strength of 12 MPa. Furthermore, the flexible membrane exhibits good biocompatibility and can efficiently monitor human health signals, thereby indicating potential for application in the field of wearable electronic devices.
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Metal organic frameworks (MOFs) have unique advantages in optimizing the ionic conductivity of battery separators because of their rich cavity structure and highly ordered and connected pores. In this study, we used a hydrothermal method to synthesize a functional material, Ag-MOF crystal, as a separator coating content, and then studied the properties and application effect of the MOF-Al2O3-blended coating applying to a polyethylene (PE) separator (MOFxAl1-x/PE). Results show that MOF0.08Al0.92/PE (MOF/Al2O3 = 0.08:0.92) used in NCM811||Li cells significantly not only improves the fast charge-discharge performance of the cells but also inhibits the growth of lithium dendrites during long-term charge-discharge cycling; the Li+ transference number (tLi+) of the MOF0.08Al0.92/PE composite separator is 0.61; the Li||separator||Li half-cell circulates stably for 1000 h at varying current density from 0.5 to 10 mA cm-2 and only produces low overpotentials, indicating that MOF0.08Al0.92 stabilizes lithium. The initial capacity of the NCM811||Li cell using the MOF0.08Al0.92/PE separator is 165.0 mA h g-1, its capacity retention is 70.67% after 300 cycles at 5 C, and the interface resistance of the cells only increases from 13.8 to 31.5 Ω, whereas the capacity retention of Al2O3/PE separator batteries is only 40.41% (62.2 mA h g-1) under the same conditions. During the charge-discharge cycling, the MOF-Al2O3 coating induces the lithium anode to quickly form a stable and dense solid-electrolyte interphase layer, promotes the uniform deposition of Li+, and inhibits the growth of lithium dendrites as well.
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OBJECTIVE: To explore the relevance between the promoter methylation status of Notch1 gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast. METHODS: Methylation status of Notch1 gene in human breast invasive ductal carcinoma (IDC, n = 89), ductal carcinoma in situ (DCIS, n = 20), atypical ductal hyperplasia (ADH, n = 11) and usual ductal hyperplasia (UDH, n = 20) were quantitatively evaluated by MALDI-TOF MS. The expression of Notch1 protein was detected by immunohistochemical stain (SP method). RESULTS: Positive expression rates of Notch1 protein in IDC and DCIS were 91.0% (81/89) and 75.0% (15/20), respectively, which were significantly higher than those of ADH (4/11) and UDH (30.0%, 6/20;P < 0.05). Notch1 protein expression was correlated significantly with lymph node metastasis, pathological grades and TNM stages of IDC. The mean methylation levels of Notch1 gene at CpG_3, CpG_4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS, ADH and UDH groups (P < 0.0083). In breast carcinomas, the mean methylation rates of Notch1 gene at CpG_4.5, CpG_10.11, and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis (P < 0.05); and the methylation rates at CpG_14.15.16 and CpG_18 loci in stage Iwere lower than that in stage II, further lower than that in stage III (P < 0.05); and that in CpG_1.2, CpG_12.13 loci in grade I (highly-differentiated group) were higher than that in grade II (moderate-differentiated group) and grade III (poorly-differentiated group) (P < 0.05); and the methylation rates at CpG_3, CpG_8 and CpG_14.15.16 loci in ER(+) PR(+) HER2(-) group were lower than that in ER(-) PR(-) HER2(+) group (P < 0.05). CONCLUSIONS: There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notch1 protein. This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1, and this change may have important significance in breast tumorigenesis and the development. Specific hypomethylation at CpG_3, CpG_ 4.5 and CpG_8 loci of Notch1 gene may play a role in the pathogenesis of breast carcinoma, suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Metilação de DNA , Receptor Notch1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Ilhas de CpG/genética , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Humanos , Hiperplasia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Regiões Promotoras Genéticas , Receptor Notch1/metabolismo , Adulto JovemRESUMO
In blood vessels, endothelial cells (ECs) grow along the direction of blood flow, while smooth muscle cells (SMCs) grow circumferentially along the vessel wall. To mimic this structure, a polycaprolactone (PCL) tubular scaffold with orthogonally oriented bilayer nanofibers was prepared via electrospinning and winding. ECs were cultured on the inner layer of the scaffold with axial nanofibers and SMCs were cultured on the outer layer of the scaffold with circumferential nanofibers. Fluorescence images of the F-actin distribution of ECs and SMCs indicated that cells adhered, stretched, and proliferated in an oriented manner on the scaffold. Moreover, layers of ECs and SMCs formed on the scaffold after one month of incubation. The expression levels of platelet-endothelial cell adhesion molecule 1 (PECAM-1) and a contractile SMC phenotype marker in the EC/SMC co-culture system were much higher than those in individual culture systems, thus demonstrating that the proposed biomimetic scaffold promoted the intercellular junction of ECs and preserved the contractile phenotype of SMCs.
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OBJECTIVES: This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3. RESULTS: Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2âweeks of treatment with CIK/DC-CIK cells in the treatment group (all Pâ<â.05). In addition, the results shown that 1-year overall survival was significantly prolonged (Pâ<â.0001) and quality of life was improved (Pâ=â.001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (Pâ=â.0003) as well as the levels of immunoglobulins were elevated (Pâ<â.00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (Pâ<â.00001). No fatal adverse reactions were noted (Pâ=â.04). CONCLUSIONS: It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.
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Imunidade Adaptativa/imunologia , Antineoplásicos/imunologia , Células Matadoras Induzidas por Citocinas/imunologia , Células Dendríticas/imunologia , Neoplasias Esofágicas/terapia , Idoso , Terapia Combinada , Neoplasias Esofágicas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8+ T cells, activated CD4+ memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.
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Solitary fibrous tumors (SFTs) can occur in several locations outside the pleura, but rarely in the sinonasal tract, and particularly not in the nasopharynx. Herein, we describe an unusual case of giant cell-rich SFT (GCRSFT) occurring in the nasopharynx. A 64-year-old man experienced dizziness and headache for more than 10 years with no obvious cause. Computed tomography (CT) scan showed a 3.9 cm × 2 cm tumor on the posterior lateral wall of the left nasopharynx, and angiography revealed a hypervascular tumor fed by branches of the left carotid artery. Hence, preoperative embolization was performed, and then the tumor was endoscopically resected. The symptoms were relieved after the resection, and postoperative head CT and video laryngoscopy showed that the tumor was completely resected. We next characterized the specific pathological characteristics of the resected tumor. Histologically, the tumor was characterized by varying cellular proliferation of cytologically bland spindle cells within a collagenous stroma, with prominent interspersed branching vessels. Mitotic activity was low (2/50HPF), and there was no evidence of pleomorphism or tumor necrosis. Moreover, multinucleated giant cells with deep nuclear staining and distributed in pseudovascular spaces were found within the tumor. We ruled out the possibility that our case was giant cell fibroblastoma (GCF) by immunohistochemical analysis, showing that the tumor cells were positive for CD34, CD99, STAT6, and BCL-2, and that the Ki-67 labeling index was 3%, indicating that our case was SFT and not GCF. The patient's condition is generally good after a 14-month follow-up. This report serves to broaden the morphologic spectrum of GCRSFT and will help clinicians and pathologists better understand this entity to prevent misdiagnosis.
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The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 (FGL2), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of FGL2 correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.
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Neoplasias Esofágicas/imunologia , Carcinoma de Células Escamosas do Esôfago/imunologia , Fibrinogênio/genética , Macrófagos Associados a Tumor/imunologia , Linfócitos B , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Técnicas de Cocultura , Bases de Dados Genéticas , Células Dendríticas , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Fator 7 de Crescimento de Fibroblastos/genética , Fator 7 de Crescimento de Fibroblastos/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Linfócitos do Interstício Tumoral/imunologia , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/imunologia , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neutrófilos , RNA Mensageiro , Células THP-1 , Microambiente Tumoral , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
OBJECTIVE: To study the efficacy of different anti-adhesion agents used in preventing tubal obstruction after recanalization. METHODS: Five hundred and eight patients with tubal obstruction were divided into 245 cases in control group, 108 cases in chitosan group; 113 cases in sodium hyaluronate group and 42 cases in lipiodol group. The patients in control group were injected with anti-inflammation agents after recanalization, while other groups were injected with chitosan, sodium hyaluronate or lipiodol at dose of 2 - 3 ml in every therapeutic group. The rate of location of tubal obstruction and tubal recanalization were recorded during operation. Then patients in every group were followed up on tubal patency after 3 months, and pregnancy rate after 12 months. RESULTS: Among 1016 fallopian tubes in 508 patients, there were 330 tubes occlusion at isthmus portion and 563 tubes occlusion at interstitial portion of fallopian tube. Thirty-seven fallopian tubes were ablated because of ectopic pregnancy, 86 fallopian tubes were unobstructed. (1) The recanalization rate were 95.7% (179/187) in chitosan group, 97.9% (191/195) in sodium hyaluronate group, 98.7% (75/76) in lipiodol group and 97.7% (425/435) in control group, which did not show statistical difference (P > 0.05). (2) The rates of tubal patency after 3 months of 91.7% (99/108) in chitosan group and 88.5% (100/113) in sodium hyaluronate group were significantly higher than 71.4% (30/42) in lipiodol group and 74.3% (182/245) in control group (P < 0.05). (3) The rates of intrauterine pregnancy after 12 months were 48.1% (52/108) in chitosan group and 41.6% (47/113) in sodium hyaluronate group, which were significantly higher than 23.8% (10/42) in lipiodol group and 24.1% (59/245) in control group (P < 0.05). CONCLUSION: Chitosan and sodium hyaluronate could be effective to prevent tubal obstruction after interventional recanalization and increase pregnancy rate.
Assuntos
Doenças das Tubas Uterinas , Histerossalpingografia , Animais , Doenças das Tubas Uterinas/cirurgia , Tubas Uterinas/cirurgia , Humanos , Taxa de Gravidez , Esterilização TubáriaRESUMO
OBJECTIVE: To investigate the polymorphism of HLA-DRB1 and DQB1 allele in esophageal squamous cell carcinomas of Kazakh in Xinjiang, and to characterize susceptible genes for the family of Kazakh esophageal squamous cell carcinoma. METHODS: HLA-DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0602 alleles were genotyped by sequence specific primers using polymerase chain reaction (PCR-SSP) in 200 Kazakh esophageal squamous cell carcinoma and 177 normal esophageal mucosa. RESULTS: The frequency of HLA-DRB1*1501, HLA-DQB1*0301, HLA-DQB1*0602 alleles in 200 Kazakh esophageal squamous cell carcinoma (0.455, 0.760 and 0.690) were significantly higher than that of 177 normal esophageal mucosa (0.232, 0.520, 0.554; OR = 2.78, 2.93, 1.80; P < 0.05). The frequency of HLA-DRB1*0901 between the carcinoma (0.105) and control groups (0.102) had no association (OR = 1.036, P > 0.05); The frequency of HLA-DQB1*0602 was higher in poor-differentiated squamous cell carcinomas (0.742) than that of well-differentiated tumors (0.597, P < 0.05). CONCLUSIONS: HLA-DRB1*1501, HLA-DQB1*0301, HLA-DQB1* 0602 may be susceptible to Kazakh esophageal squamous cell carcinoma. HLA-DQB1*0602 correlates with well-differentiated esophageal squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Glicoproteínas de Membrana/genética , Adulto , Idoso , Alelos , Carcinoma de Células Escamosas/patologia , China/etnologia , Suscetibilidade a Doenças , Neoplasias Esofágicas/patologia , Feminino , Frequência do Gene , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Li1.5Al0.5Ge1.5(PO4)3 (LAGP) is an inorganic solid electrolyte with a Na superionic conductor (NASICON) structure that provides a channel for lithium ion transport. We coated LAGP particles on one side of a polypropylene (PP) separator film to improve the ionic conductivity of the separator, and water-dispersed polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) on the other side to reduce the interfacial resistance between the separator and the lithium metal anode. The results show that the LAGP/PP/PVDF-HFP separator has a high ionic conductivity (1.06 mS cm-1) at room temperature (PP separator: 0.70 mS cm-1), and an electrochemical window of 5.2 V (vs. Li+/Li). The capacity retention of a NCM|LAGP/PP/PVDF-HFP|graphite full cell is 81.0% after 300 charge-discharge cycles at 0.2C. When used in a NCM|LAGP/PP/PVDF-HFP|Li half-cell system, the initial discharge capacity is 172.5 mA h g-1 at 0.2C, and the capacity retention is 83.2% after 300 cycles. More significantly, the surface of the Li anode is smooth and flat after 200 cycles. The interface resistance increased from 7 to 109 Ω after 100 cycles at 0.2C. This indicates that the synergistic effect of the asymmetric coated LAGP and PVDF-HFP is beneficial to inhibiting the growth of lithium dendrites in the battery and reduces the interface resistance.
RESUMO
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3), a member of the serine/threonine protein kinase family, is ubiquitously expressed and acts as an oncogene. However, the expression and exact molecular mechanism of MAP3K3 in ovarian carcinoma (OC) remain unclear. Here, we found that MAP3K3 protein was highly expressed in 70.5% of high-grade serous ovarian carcinoma (HGSOC) samples. MAP3K3 overexpression was significantly associated with the FIGO stage and chemotherapy response. Additionally, MAP3K3 overexpression was associated with reduced disease-free survival and overall survival. In vitro experiments showed that MAP3K3 overexpression promoted cell proliferation, inhibited apoptosis, and enhanced the migration and invasion of OC cells. Moreover, in vivo tumourigenesis experiments confirmed that silencing MAP3K3 significantly reduced the growth rate and volume of transplanted tumours in nude mice. Drug sensitivity experiments demonstrated that differential expression of MAP3K3 in OC cell lines correlates with chemotherapy resistance. Functionally, the MAP3K3 gene regulated the malignant biological behaviour of OC cells by mediating NF-κB signalling pathways, affecting the downstream epithelial-mesenchymal transition and cytoskeletal protein expression. Our results unveiled the role of MAP3K3 in mediating NF-κB signalling to promote the proliferation, invasion, migration, and chemotherapeutic resistance of OC cells, highlighting a potential new therapeutic and prognostic target.
Assuntos
MAP Quinase Quinase Quinase 3/metabolismo , NF-kappa B/metabolismo , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Análise Multivariada , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/enzimologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Fatores de Risco , Transdução de Sinais , Análise de SobrevidaRESUMO
Mitochondria, as primary energy generators and Ca2+ biosensor, are dynamically coupled to neuronal activities, and thus play a role in neuroplasticity. Here we report that respiratory neuroplasticity induced by daily acute intermittent hypoxia (dAIH) evoked adaptive changes in the ultrastructure and postsynaptic distribution of mitochondria in the pre-Bötzinger complex (pre-BötC). The metabolic marker of neuronal activity, cytochrome c oxidase (CO), and dendritic mitochondria were examined in pre-BötC neurons of adult Sprague-Dawley rats preconditioned with dAIH, which is known to induce long-term facilitation (LTF) in respiratory neural activities. We performed neurokinin 1 receptor (NK1R) pre-embedding immunocytochemistry to define pre-BötC neurons, in combination with CO histochemistry, to depict ultrastructural alterations and CO activity in dendritic mitochondria. We found that the dAIH challenge significantly increased CO activity in pre-BötC neurons. Darkly CO-reactive mitochondria at postsynaptic sites in the dAIH group were much more prevalent than those in the normoxic control. In addition, the length and area of mitochondria were significantly increased in the dAIH group, implying a larger surface area of cristae for ATP generation. There was a fine, structural remodeling, notably enlarged and branching mitochondria or tapered mitochondria extending into dendritic spines. Mitochondrial cristae were mainly in parallel-lamellar arrangement, indicating a high efficiency of energy generation. Moreover, flocculent or filament-like elements were noted between the mitochondria and the postsynaptic membrane. These morphological evidences, together with increased CO activity, demonstrate that dendritic mitochondria in the pre-BötC responded dynamically to respiratory plasticity. Hence, plastic neuronal changes are closely coupled to active mitochondrial bioenergetics, leading to enhanced energy production and Ca2+ buffering that may drive the LTF expression.
Assuntos
Dendritos/patologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hipóxia/enzimologia , Hipóxia/patologia , Mitocôndrias/patologia , Centro Respiratório/enzimologia , Trifosfato de Adenosina/biossíntese , Animais , Dendritos/ultraestrutura , Espinhas Dendríticas/patologia , Espinhas Dendríticas/ultraestrutura , Metabolismo Energético , Potenciação de Longa Duração , Mitocôndrias/ultraestrutura , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Receptores da Neurocinina-1/biossínteseRESUMO
Low-grade chondrosarcoma (LGC) is a very rare intracranial tumor, particularly in the sellar area. Herein, we describe an unusual case of LGC occurring in the sellar area. A 52-year-old man presented with diminution of vision for more than 3 months, but did not exhibit headaches reported in previous cases. MRI showed that the maximum size of the tumor was 7 cm on the left side of the saddle. We characterized the specific pathological characteristics. Histologically, the tumor had polypoid areas and a lobulated growth pattern under low-power examination. At high magnification, the tumor consisted of small cells with hyperchromatic nuclei in the cartilage matrix, with an alternating loose hypocellular zone and rich myxoid area. In our case, LGC needed to be distinguished from chordoma. Immunohistochemically, the tumor cells showed diffuse positivity for S-100 and vimentin, IDH1 was weakly cytoplasm positive. The Ki-67 labeling index was less than 5%. Additionally, AE1/3, EMA, and CK19 were negative, which could be used to exclude chordoma. This case report expands the literature on LGC and will help clinicians and pathologists better understand this entity.