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1.
J Transl Med ; 18(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000807

RESUMO

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.

2.
World J Clin Cases ; 7(23): 4163-4171, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832423

RESUMO

BACKGROUND: Gallbladder squamous cell carcinoma (GBSCC) is a rare subtype of malignancy and accounts for only 2%-3% of gallbladder malignancies. Due to its rapid development, most patients with GBSCC initially present with an advanced stage of the disease and hence a poor prognosis. The clinicopathological and biological features of SCC remain to be fully elucidated, owing to its uncommon occurrence. The majority of currently available data only described individual case reports or series analyses of trivial cases. CASE SUMMARY: A 64-year-old man was admitted for progressively poor abdominal distension and pain. Liver computed tomography (CT) showed infiltration of gallbladder carcinoma into the adjacent liver, and enlarged retroperitoneal lymph nodes. The patient underwent radical cholecystectomy. Part of the mass was grey and soft, and the neoplastic section showed a purulent-necrotic lesion. Hematoxylin and eosin staining revealed a moderately differentiated SCC. Immunohistochemical studies showed strong staining of the tumor for AE1/3 and CK5/6. Staining for CK19, CK7, and CAM5.2 was positive in the cytoplasm. Systemic chemotherapy was not administered because of the patient's poor physical condition. After five months, CT and magnetic resonance cholangiopancreatography showed multiple metastases in the liver and abdominal cavity. CONCLUSION: Squamous components of GBSCC may explain the complex biological behavior, and CD109 may be involved in the pathogenesis.

3.
Sci Rep ; 9(1): 8401, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182739

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.

4.
Hum Pathol ; 88: 7-17, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30537494

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a highly invasive disease with a poor long-term survival rate. Although there has been progress in understanding the pathogenesis of ESCC, there are currently no molecular biomarkers that are used in routine clinical practices to determine prognosis. Therefore, the aim of this study was to determine a small immunohistochemical panel that could predict the prognosis of patients with ESCC. Phospholipase C epsilon-1 (PLCE1), IKKα, IKBα, p65, and p53 were highly expressed in ESCC tissues. The high expression level of PLCE1, IKBα, and p53 showed a significant positive correlation with a short overall survival (P = .022, .009, and .024, respectively). This 3-biomarker panel (ie, PLCE1, IKBα, and p53) was found to be a predictor of ESCC, with a worse overall survival as each positive marker was added (hazard ratio, 1.553; 95% confidence interval, 1.166-2.067; P = .003). In another cohort (including 1922 esophageal endoscopic biopsy tissues), the lesions of 28 patients were aggravated. Three proteins (PLCE1, 12/28 [42.86%]; IKBα, 16/28 [57.14%]; p53, 16/28 [57.14%]) were immunoreactive in patients with progressive disease. Our study identified and validated that this immunohistochemical biomarker panel of 3 proteins, consisting of PLCE1, IKBα, and p53, is not only independently associated with an unfavorable outcome for ESCC patients but also able to predict disease progression to precancerous lesions.

5.
Obstet Gynecol ; 132(6): 1421-1429, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30399093

RESUMO

OBJECTIVE: To develop an effective, low-cost, single-visit cervical screening strategy incorporating a modified Pap test and visual inspection with acetic acid and Lugol's iodine for low-income settings. METHODS: We conducted a prospective cohort trial. Two low-income Muslim Uyghur communities in China's far western Kashi Prefecture served as pilot and validation study sites, respectively, and 4,049 women (aged 30-59 years) were screened. The conventional Pap test was modified using a cotton swab to collect cervical cells without scraping the cervix using an Ayre spatula, allowing visual inspection with acetic acid (and visual inspection with Lugol's iodine if visual inspection with acetic acid was negative) to be performed in a single visit. Results from both tests were available within 1-2 hours. Women positive for either or both underwent same-day biopsy that was shipped by a courier service to a central pathology laboratory. RESULTS: Single-visit screening incorporating both a modified Pap test and visual inspection achieved a sensitivity of 96.0% (95% CI 91.6-100), which was superior to Pap testing (76%, 95% CI 66.3-85.7; P<.001) or visual inspection with acetic acid-visual inspection with Lugol's iodine (48%, 95% CI 36.7-59.3; P<.001) alone in detecting cervical intraepithelial neoplasia (CIN) 2 or worse lesions. Rapid interpretation of both diagnostic procedures facilitated efficient same-day biopsy that achieved a negative predictive value of 98.2% in detecting CIN 2 or worse lesions. The increased sensitivity and minimized loss of follow-up allowed this approach to identify an extremely high prevalence of CIN 1 (2,741/100,000, 95% CI 2,238-3,245/100,000), CIN 2 or 3 (1,457/100,000, 95% CI 1,088-1,826/100,000), and cervical cancer (395/100,000, 95% CI 202-589/100,000) among these underscreened, at-risk women. CONCLUSION: Single-visit cervical screening with both a modified Pap test and visual inspection has greater sensitivity to detect high-grade CINs, reduces loss of follow-up, and could be an efficient low-cost strategy for low-resource settings.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias do Colo do Útero/diagnóstico , Ácido Acético , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , China , Corantes , Detecção Precoce de Câncer/economia , Feminino , Exame Ginecológico , Humanos , Iodetos , Pessoa de Meia-Idade , Teste de Papanicolaou , Projetos Piloto , Áreas de Pobreza , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal
6.
Mol Ther ; 26(12): 2751-2765, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30301667

RESUMO

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients.


Assuntos
Antígenos de Superfície/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Diferenciação Celular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Família Multigênica , Oncogenes , Prognóstico , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Mol Biol Rep ; 45(6): 2615-2623, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30341691

RESUMO

Hsa-MicroRNA-124a-3p (hsa-miR-124-3p) is involved in tumor progression in certain malignant tumors. However, its function and clinical implication in hepatocellular carcinoma (HCC) have not yet been illustrated. In this study, we explored the expression and prognostic value of hsa-miR-124-3p in patients with HCC. Hsa-miR-124-3p expression in HCC was analyzed in silico, which was subsequently confirmed by quantitative PCR in 155 HCC biopsy samples. Overall survival (OS) and disease-free survival in HCC patients was evaluated by Kaplan-Meier survival analysis, and univariate and multivariate Cox proportional hazard models were used. The in silico results demonstrated that hsa-miR-124-3p was reduced in cell lines and tissues of HCC, and hsa-miR-124-3p expression was lower in HCC tumor samples than in normal liver tissues. Moreover, a decrease in hsa-miR-124-3p expression was closely correlated with tumor diameter (≥ 5 cm) and number of lesions (multiple). Lower hsa-miR-124-3p expression was shown to be correlated with a shorter OS and poor prognosis in HCC. Our findings demonstrate that hsa-miR-124-3p might be a potential target for the diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
8.
Sheng Li Xue Bao ; 70(3): 269-280, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29926068

RESUMO

The present study was to investigate the role of the interaction between canonical transient receptor potential channel 1 (TRPC1) and calcium release-activated calcium modulator 1 (Orai1) in extracellular Ca2+-sensing receptor (CaR)-induced extracellular Ca2+ influx and nitric oxide (NO) production. Human umbilical vein endothelial cells (HUVECs) were incubated with CaR agonist Spermine [activating store-operated calcium channels (SOC) and receptor-operated calcium channels (ROC)] alone or in combination with the following reagents: CaR negative allosteric modulator Calhex231 plus ROC analogue TPA (activating ROC and blocking SOC), Ro31-8220 (PKC inhibitor that activates SOC and blocks ROC) or Go6967 (PKCs and PKCµ inhibitor that activates SOC and blocks ROC). The protein expressions and co-localization of TRPC1 and Orai1 were determined using immunofluorescent staining. The interaction between TRPC1 and Orai1 was examined by co-immunoprecipitation. We silenced the expressions of their genes in the HUVECs by transfection of constructed TRPC1 and Orai1 shRNA plasmids. Intracellular Ca2+ concentration ([Ca2+]i) was detected using Ca2+ indicator Fura-2/AM, and NO production was determined by DAF-FM staining. The results showed that TRPC1 and Orai1 protein expressions were co-located on the cell membrane of the HUVECs. Compared with Spermine+Ca2+ group, Calhex231+ TPA+Spermine+Ca2+, Ro31-8220+Spermine+Ca2+ and Go6976+Spermine+Ca2+ groups exhibited down-regulated protein expressions of TRPC1 and Orai1 in cytoplasm and decreased co-localization on the cell membrane. Co-immunoprecipitation results showed that the interaction between TRPC1 and Orai1 was reduced by Calhex231 plus TPA, Ro31-8220 or Go6976 addition in the Spermine-stimulated HUVECs. Double knockdown of Trpc1 and Orai1 genes significantly decreased [Ca2+]i level and NO production in all of the Spermine+Ca2+, Calhex231+TPA+Spermine+Ca2+, Ro31-8220+Spermine+Ca2+ and Go6976+Spermine+Ca2+ groups. These results suggest that TRPC1/Orai1 may form a complex that mediates Ca2+ influx and No production via SOC and ROC activation.


Assuntos
Cálcio/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Óxido Nítrico/metabolismo , Proteína ORAI1/metabolismo , Canais de Cátion TRPC/metabolismo , Benzamidas/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio , Membrana Celular , Cicloexilaminas/farmacologia , Inativação Gênica , Humanos , Indóis/farmacologia , RNA Interferente Pequeno , Receptores de Detecção de Cálcio/agonistas , Espermina/farmacologia
9.
Clin Exp Pharmacol Physiol ; 45(7): 675-682, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29575169

RESUMO

Synovial sarcoma (SS) is a mesenchymal malignant neoplasm showing characteristics of epithelial-mesenchymal biphasic differentiation. SS is of uncertain cellular origin; however, studies have suggested that SS originates from a somatic stem cell population. In this study, we aim to determine whether differential morphological features of the epithelial-mesenchymal transition (EMT) contributed to the tumourigenesis of SS invasion and metastasis. Twelve paraffin-embedded formalin-fixed tissue (FFPE) SS tissue specimens were obtained, and laser capture microdissection (LCM) with the ArcturusXT system and small chip method (SCM) were used to isolate and purify spindle and epithelial cells from SS specimens. The TRIzol method was used to extract RNA, and the mRNA levels of EMT-related genes in epithelial and spindle cells of SS specimens were measured using real-time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results show that collection of about 2 × 104 cells from FFPE samples using LCM was sufficient for qRT-PCR, with an efficiency of 75%. Compared with LCM, 72.2% (13 of 18) RNA samples were successfully extracted using SCM to isolate cells from FFPE SS tissues. In the 16 samples (11 spindle cell samples and 5 epithelial cell samples), Snail mRNA was significantly upregulated in spindle cell areas compared with that in epithelial cell areas (P = .001). Expression levels of the epithelial marker E-cadherin and the mesenchymal marker N-cadherin were not significantly different between epithelial and spindle cell areas. In spindle cells of recurrent SS samples, the mRNA levels of E-cadherin, N-cadherin, Snail, and Slug were higher in primary SS samples than in recurrent samples. Taken together, our results indicated that in SS samples, Snail mRNA was upregulated in spindle cell areas compared with that in epithelial cell areas and that the expression of EMT-related genes was increased in primary SS. LCM could be used to isolate and purify RNA from FFPE samples.


Assuntos
Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Microdissecção e Captura a Laser , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , Formaldeído , Humanos , Inclusão em Parafina , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recidiva , Fixação de Tecidos
10.
Future Oncol ; 14(20): 2005-2011, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29513033

RESUMO

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.


Assuntos
Alelos , Grupos Étnicos/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 Jovem
11.
Environ Sci Pollut Res Int ; 25(11): 11045-11053, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29411276

RESUMO

A novel quaternary ammonium polyethylene nonwoven fabric for removing chromium ions from water was prepared via radiation-induced grafting of glycidyl methacrylate and further modification with N,N'-dimethylethylenediamine. The structural and morphological characteristics of the adsorbent were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetry and differential thermogravimetry (TG/DTG), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The influences of several principal factors, including pH value, initial Cr(VI) concentration, contact time, and coexisting anions (including SO42-, CO32-, NO3-, PO43-, and Cl-), on adsorption performance were investigated via batch tests. The results showed that the optimum removal efficiency was 99.2% at pH 3 and the maximum adsorption quantity for Cr(VI) at 25 °C was 336 mg/g. The adsorption kinetic parameters were better fitted with the pseudo-second-order kinetic model, and the equilibrium data were described very well by the Freundlich isotherm model. Furthermore, the as-synthesized adsorbent exhibited excellent regeneration and recyclability while maintaining high adsorption performance after five adsorption/desorption cycles.


Assuntos
Compostos de Amônio/química , Cromo/química , Compostos de Epóxi/química , Íons/química , Metacrilatos/química , Águas Residuárias/análise , Adsorção , Cinética , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Águas Residuárias/química
12.
Oncotarget ; 8(13): 21526-21538, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28423526

RESUMO

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Macrófagos/imunologia , Neovascularização Patológica/patologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Ativação de Macrófagos/imunologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptores de Superfície Celular/imunologia
13.
Exp Mol Pathol ; 102(1): 15-21, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27939650

RESUMO

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.


Assuntos
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 Sexuais
14.
BMC Med Genomics ; 8: 69, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26503545

RESUMO

BACKGROUND: Synovial sarcoma (SS) is one of the most aggressive soft-tissue sarcomas and is noted for late local recurrence and metastasis. It is of uncertain histological origin and exhibits a biphasic histopathological form involving both the mesenchyme and epithelium. Thus, its diagnosis and therapy remain a huge challenge for clinicians and pathologists. This study aimed to determine whether differential morphological-associated genomic changes could aid in ascertaining the histogenesis of SS and to determine whether these sarcomas showed some specific mutated genes between epithelial and spindle cells that would promote tumor invasion and metastasis. METHODS: We conducted a comprehensive genomic analysis of mesenchymal and epithelial components in 12 formalin-fixed paraffin-embedded biphasic SS samples using the Illumina human exon microarray. Exome capture sequencing was performed to validate the single nucleotide polymorphism (SNP)-chip data, and de novo data were generated using a whole-exome chip with the Illumina exon microarray. Fisher's exact test based on PLINK analysis of the SNP-chip data. RESULTS: Here, the SNP-chip data showed that 336 SNPs had association P-values of less than 0.05 by chi-square test. We identified 23 significantly mutated genes between epithelial and spindle cell regions of SSs. Fifteen gene mutations were specific for the spindle cell component (65.2 %) and eight for the epithelial cell component (34.8 %). Most of these genes have not been previously reported in SS, and neuroguidin (NGDN), RAS protein activator like 3 (RASAL3), KLHL34 and MUM1L1 have not previously been linked to cancer; only one gene (EP300) has been reported in SS. Genomic analyses suggested that the differential SNPs in genes used for functional enrichment are mainly related to the inflammatory response pathway, adhesion, ECM-receptor interactions, TGF-ß signaling, JAK-STAT signaling, phenylalanine metabolism, the intrinsic pathway and formation of fibrin. CONCLUSIONS: This study investigated novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for SS. The identified pathways may be closely correlated with the pathogenic mechanisms underlying SS, and SS development is associated with morphological features.


Assuntos
Células Epiteliais/metabolismo , Exoma/genética , Genômica , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Sarcoma Sinovial/patologia , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma Sinovial/genética , Adulto Jovem
15.
Int J Clin Exp Pathol ; 8(4): 3636-47, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26097545

RESUMO

Renal cell carcinoma (RCC) accounts for approximately 3% of all new cancer cases. Although the classification of RCC is based mainly on histology, this method is not always accurate. We applied comparative genomic hybridization (CGH) to determine genomic alterations in 46 cases of different RCC histological subtypes [10 cases of clear cell RCC (CCRCC), 13 cases of papillary RCC (PRCC), 12 cases of chromophobe RCC (CRCC), 9 cases of Xp11.2 translocation RCC (Xp11.2RCC), 2 cases of undifferentiated RCC (unRCC)], and investigated the relationships between clinical parameters and genomic aberrations. Changes involving one or more regions of the genome were seen in all RCC patients; DNA sequence gains were most frequently (>30%) seen in chromosomes 7q, 16p, and 20q; losses from 1p, 3p, 13q, 14q, and 8p. We conclude CGH is a useful complementary method for differential diagnosis of RCC. Loss of 3p21-25, 15q, and gain of 16p11-13 are relatively particular to CCRCC vs. other types of RCC. Gain of 7p13-22, 8q21-24, and loss of 18q12-ter, 14q13-24, and Xp11-q13/Y are more apparent in PRCC, and gain of 8q21-24 is characteristic of type 2 PRCC vs. type 1 PRCC. Loss of 2q12-32, 10p12-15, and 11p11-15, 13p are characteristic of CRCC, and gain of 3p and loss of 11p11-15 and 13p are significant differentiators between common CRCC and CRCC accompanied by sarcomatous change groups. Gain of Xp11-12 is characteristic of the Xp11.2RCC group. Based on Multivariate Cox regression analysis, aberration in 5 chromosome regions were poor prognostic markers of RCC, and include the gain of chromosome 12p12-ter (P = 0.034, RR = 3.502, 95% CI 1.097-11.182), 12q14-ter (P = 0.002, RR = 5.115, 95% CI 1.847-14.170), 16q21-24 (P = 0.044, RR = 2.629, 95% CI 1.027-6.731), 17p12-ter (P = 0.017, RR = 3.643, 95% CI 1.262-10.512) and the loss of 18q12-23 (P = 0.049, RR = 2.911, 95% CI 1.006-8.425), which may provide clues of new genes involved in RCC tumorigenesis.


Assuntos
Carcinoma de Células Renais/genética , Aberrações Cromossômicas , Neoplasias Renais/genética , Adulto , Idoso , Hibridização Genômica Comparativa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Translocação Genética
16.
Biomed Environ Sci ; 28(4): 272-80, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25966753

RESUMO

OBJECTIVE: To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. METHODS: Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. RESULTS: ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. CONCLUSION: GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.


Assuntos
Arsênico/toxicidade , Extrato de Sementes de Uva/farmacologia , Fator 2 Relacionado a NF-E2/genética , Proantocianidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Animais , Antioxidantes/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Contagem de Espermatozoides , Testículo/citologia
17.
PLoS One ; 10(3): e0121448, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25822802

RESUMO

PURPOSE: To conduct a meta-analysis to evaluate the prognostic role of E-cadherin expression in bone and soft tissue sarcomas. METHODS: The PubMed, EMBASE, and Web of Science databases were searched using terms related to E-cadherin, sarcoma, and prognosis for all articles published in English before March 2014. Pooled effect was calculated from the available data to evaluate the association between negative E-cadherin expression and 5-year overall survival and tumor clinicopathological features in sarcoma patients. Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using a fixed-effects model. RESULT: Eight studies met the selection criteria and reported on 812 subjects. A total of 496 subjects showed positive E-cadherin expression (59.9%). Negative E-cadherin expression in bone and soft tissue sarcomas was correlated with lower 5-year overall survival (OR = 3.831; 95% CI: 2.246-6.534), and was associated with higher clinical stage (RR = 1.446; 95% CI: 1.030-2.028) and with male sex (RR = 0.678; 95% CI: 0.493-0.933). CONCLUSION: In the E-cadherin negative group, 5-year overall survival was significantly worse than in the E-cadherin positive group. However, further studies are required to confirm these results.


Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Caderinas/metabolismo , Sarcoma/metabolismo , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/mortalidade , Neoplasias Ósseas/patologia , Caderinas/genética , Regulação para Baixo , Feminino , Humanos , Masculino , Prognóstico , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Análise de Sobrevida , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 30(4): 327-32, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25330669

RESUMO

OBJECTIVE: To study the roles of stromal interaction molecule 2 (STIM2) and transient receptor potential canonical 3 (TRPC3) in extracellular Ca(2+)-sensing receptor (CaR)-induced extracellular Ca2+ influx and the production of nitric oxide (NO) in human umbilical vein endothelial cells (HUVEC). METHODS: (1) The interaction of STIM2 and TRPC3 was determined using the immunofluorescence technique. (2) The expressions of STIM2 and TRPC3 genes were silenced in HUVEC by transfection constructed STIM2 and TRPC3 RNA interference plasmids. The interference efficiency of STIM2, TRPC3 protein and mRNA levels were determined by Western blot and real time RT-PCR, respectively. (3) The second to fifth passage of HUVEC were divided into: STIM2-002 short hairpin RNA (STIM2-002 shRNA ) + spermine + Ca2+ group and TRPC3-004 short hairpin RNA (TRPC3-004 shRNA ) + spermine + Ca2+ group; control group (spermine + Ca2+ group) and vehicle+ spermine + Ca2+ group. The four groups of cells were incubated with CaR agonist spermine, the intracellular Ca2+ concentration ([Ca2+]i) was detected using the fluorescence Ca2+ indicator Fura-2/AM, and the production of NO was determined by DAF-FM (NO fluorescent probe) of each group in HUVEC. RESULTS: (1) Immunofluorescence technique results showed that STIM2 and TRPC3 proteinswere present in the cytoplasm of HUVEC. (2) The results of transfection constructed STIM2 and TRPC3 RNA interference plasmids demonstrated that shRNA targeted to the STIM2 and TRPC3 genes decreased STIM2 and TRPC3 mRNA levels by 88.2% and 74.0%, respectively (P < 0.05), simultaneously, the STIM2 and TRPC3 protein levels were decreased by 79.9% and 71.8%, respectively (P < 0.05). (3) Compared with spermine + Ca2+ group, the [Ca2+]i and the net NO fluorescence intensity of spermine + Ca(2+) + ShSTIM2-002 group, spermine + Ca(2+) + ShTRPC3-004 group and spermine + Ca2+ Vehicle group were not changed (P > 0.05). CONCLUSION: STIM2 and TRPC3 do not participate in CaR-mediated Ca2+ influx and NO production individually.


Assuntos
Cálcio/metabolismo , Moléculas de Adesão Celular/fisiologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Óxido Nítrico/metabolismo , Canais de Cátion TRPC/fisiologia , Células Cultivadas , Humanos , Molécula 2 de Interação Estromal
19.
Int J Clin Exp Pathol ; 7(9): 6165-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25337265

RESUMO

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. However, only some high risk human papillomavirus (HR-HPV)-infected women progress to cervical cancer, host immunogenetic factors human leukocyte antigen (HLA) may account for viral antigens presenting individually or together in the progression to cervical cancer. This study examined the association between the development of invasive cervical cancer (ICC) and the determinant factors including HLA-DRB1*1501 and DQB1*0602, HR-HPV infection among Chinese Uighur and Han populations. Blood samples, cervical swabs and biopsies were obtained from 287 patients with ICC (192 Uighurs and 95 Hans) and 312 healthy controls (218 Uighurs and 94 Hans). HPV DNA was detected by PCR and HLA-DRB1*1501 and DQB1*0602 alleles were performed using PCR-SSP method. HPV16 infection rates was significantly higher among Uighur and Han with ICC as compared to healthy controls (OR = 58.317; 95% CI: 39.663-85.744; OR = 33.778; 95% CI: 12.581-90.691; P < 0.05 for all). HLA-DRB1*1501 (OR = 0.305; 95% CI: 0.115-0.813; P < 0.05) and HLA-DRB1*1501-DQB1*0602 haplotype frequencies (OR = 0.274; 95% CI: 0.086-0.874; P < 0.05) were significantly reduced in Han ICC. The HLA-DQB1*0602 frequency significantly decreased among Uighur women with ICC (OR = 0.482; 95% CI: 0.325-0.716; P < 0.05). Similar tendencies were observed for DQB1*0602 with HPV16-positive ICC (OR = 0.550; 95% CI: 0.362-0.837; P < 0.05). This study suggests that HLA-DRB1*1501 and DQB1*0602 alleles may influence the immune response to HPV16 infection and decrease the risk of ICC among Uighurs and Hans in Xinjiang, China.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , DNA Viral/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Testes de DNA para Papilomavírus Humano , Papillomavirus Humano 16/genética , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Razão de Chances , Infecções por Papillomavirus/etnologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Fenótipo , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Fatores de Proteção , Fatores de Risco , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/virologia
20.
Asian Pac J Cancer Prev ; 15(18): 7941-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25292091

RESUMO

Catechol-O-methyltransferase (COMT) is involved in estrogen metabolism and is vital to estrogen-induced carcinogenesis, including that of ovarian cancer. Although many recent epidemiologic studies have investigated associations between the COMT rs4680 polymorphism and ovarian cancer risk, the results remain inconclusive. We therefore performed a meta-analysis to derive a more precise estimate of associations. Systematic searches of the PubMed, Embase, Web of Science, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese Biomedicine databases were undertaken to retrieve eligible studies. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the strength of the association. In total, 8 case-control studies involving 1,293 cases and 2,647 controls were included in the meta-analysis. Overall, the results showed no evidence of significant association between the COMT rs4680 polymorphism and ovarian cancer risk in any of the assessed genetic models. Subgroup analyses by ethnicity also did not reveal any significant association in any genetic model (p>0.05). In conclusion, our findings suggest that the COMT rs4680 polymorphism may not contribute to the risk of ovarian cancer.


Assuntos
Catecol O-Metiltransferase/genética , Predisposição Genética para Doença , Neoplasias Ovarianas/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Feminino , Humanos , Prognóstico , Fatores de Risco
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