Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 67.163
Filtrar
1.
Anticancer Res ; 39(11): 5903-5910, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704814

RESUMO

BACKGROUND: Gastric cancer (GC) exhibits heterogeneous clinical and molecular features, requiring the development of new biomarkers to further understand this disease. Our transcriptomic analysis detected overexpression of melanoma-associated antigen A6 (MAGEA6) in metastatic GC, leading us to determine the clinical significance of MAGEA6 in GC. MATERIALS AND METHODS: Fourteen GC cell lines and 230 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. Polymerase chain reaction array analysis was performed to identify coordinately expressed cancer-related genes, and immunohistochemistry (IHC) was used to detected MAGEA6 expression in situ. RESULTS: MAGEA6 mRNA levels were positively correlated with the expression of matrix metallopeptidase 9 mRNA. MAGEA6 mRNA levels were higher in GC tissues compared with those in normal adjacent tissues. Patients with high MAGEA6 expression had significantly worse prognosis. MAGEA6 protein levels in primary lesions predicted the likelihood of recurrence. CONCLUSION: Overexpression of MAGEA6 in GC tissues represents a promising biomarker for assessing the malignant phenotype of GC.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Gastrectomia/mortalidade , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/secundário , Carcinoma de Células em Anel de Sinete/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/secundário , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
2.
Anticancer Res ; 39(11): 6015-6023, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704827

RESUMO

BACKGROUND/AIM: We previously reported that expression of melanoma-associated antigen (MAGE)-D4 mRNA was a prognostic factor for esophageal squamous cell carcinoma (ESCC). The aim of this study was to validate the expression of MAGE-D4 in two additional patient cohorts, and to investigate its biological functions. MATERIALS AND METHODS: The role of MAGE-D4 in cell proliferation, adhesion, and migration was determined by gene knockdown experiments in the KYSE590 cell line. MAGE-D4 protein expression was analyzed in ESCC tissues by immunohistochemistry. A second validation cohort consisted of an ESCC mRNA dataset from The Cancer Genome Atlas. RESULTS: Knockdown of MAGE-D4 significantly decreased cell proliferation and migration. Expression of MAGE-D4 protein was significantly associated with disease-free survival. In the second validation cohort, high MAGE-D4 mRNA expression was associated with significantly shorter overall survival and disease-free survival. CONCLUSION: MAGE-D4 plays an important role in the malignant behavior of ESCC. MAGE-D4 was validated as a prognostic indicator in two independent ESCC patient cohorts.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Proteínas de Neoplasias/metabolismo , Idoso , Antígenos de Neoplasias/genética , Apoptose , Biomarcadores Tumorais/genética , Adesão Celular , Proliferação de Células , Estudos de Coortes , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Prognóstico , RNA Interferente Pequeno/genética , Taxa de Sobrevida , Células Tumorais Cultivadas
3.
Anticancer Res ; 39(11): 6249-6257, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704854

RESUMO

BACKGROUND/AIM: Therapeutic targeting of receptor protein tyrosine kinases (PTKs) has proven successful in treating cancer. However, reports about PTKs in treating prostate cancer are few. Elevated expression of the erythropoietin-producing hepatocellular receptor A2 (EPHA2) receptor tyrosine kinase, a transmembrane protein, is associated with poor prognosis of certain cancer types when the enzyme is dephosphorylated. This study investigated whether EPHA2 is useful in predicting the biochemical recurrence of prostate cancer. PATIENTS AND METHODS: Data from 241 patients who had undergone total prostatectomy between 2007 and 2011 were used. EPHA2 protein expression was categorized as high or low by two pathologists. The relationship was examined between EPHA2 expression level (high vs. low) and clinicopathological factors including biochemical recurrence. Correlations were examined between EPHA2, low-molecular-weight protein tyrosine phosphatase (LMW-PTP), E-cadherin, and Ki-67. RESULTS: EPHA2 expression was high in 121 (50.2%) and low in 120 (49.8%) patients. A log-rank test revealed early biochemical recurrence in the high-expression group. Gleason score, Ki-67 labeling index, and biochemical recurrence were more frequent in the high-expression group. Furthermore, multivariate analyses revealed that high EPHA2 expression was an independent prognostic factor for biochemical recurrence (hazard ratio=3.62, 95% confidence interval=2.39-5.61). Correlations between EPHA2 and both LMW-PTP and Ki-67 labeling index were positive, whereas EPHA2 and E-cadherin were negatively correlated. CONCLUSION: EPHA2 overexpression is predictive of aggressive prostate cancer behavior. EPHA2 may be a powerful prognostic biomarker for decision-making in postoperative follow-up after total prostatectomy, and regarding the need for palliative treatment. Additionally, it may be an important therapeutic target.


Assuntos
Biomarcadores Tumorais/metabolismo , Efrina-A2/metabolismo , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Análise de Variância , Caderinas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proteínas Tirosina Fosfatases/metabolismo , Curva ROC
4.
Anticancer Res ; 39(11): 6291-6297, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704859

RESUMO

BACKGROUND/AIM: Cyclins D1 and E play different roles in the cell cycle. Cyclin E promotes chromosome instability, whereas cyclin D1 regulates apoptosis of cells. This study evaluated the prognostic significance of G1 cyclins, p21 and pRb in tumor proliferation. PATIENTS AND METHODS: A total of 102 patients with colon cancer were operated on and staged according to TNM. Follow-up was 2 to 68 months (mean 38.3±16.7 months). Expression of cyclin E and D1 were evaluated using immunohistochemistry. RESULTS: Levels of cyclin E expression were correlated with cyclin D1 expression (p=0.038), p21 expression (p=0.047), and pRb expression (p=0.004). The 5-year survival rate along with prognosis of patients with advanced stage (III, IV) colon cancer and cyclin D1 positive tumors, were significantly worse (p=0.009). Statistically significant association was observed between tumor proliferative capacity Ki-67, cyclin D1 (p=0.009), pRb (p=0.031) and p21 (p=0.050). CONCLUSION: Cyclin D1 is highly expressed in advanced stage colon cancer patients, implying a potential prognostic value.


Assuntos
Neoplasias do Colo/metabolismo , Ciclina D1/metabolismo , Ciclina E/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fase G1 , Proteínas de Neoplasias/metabolismo , Proteínas Oncogênicas/metabolismo , Proteína do Retinoblastoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/química , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Ciclina D1/análise , Ciclina E/análise , Inibidor de Quinase Dependente de Ciclina p21/análise , Feminino , Seguimentos , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/análise , Prognóstico , Proteína do Retinoblastoma/análise , Taxa de Sobrevida
5.
Adv Exp Med Biol ; 1141: 241-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571167

RESUMO

Drug transporters are considered to be determinants of drug disposition and effects/toxicities by affecting the absorption, distribution, and excretion of drugs. Drug transporters are generally divided into solute carrier (SLC) family and ATP binding cassette (ABC) family. Widely studied ABC family transporters include P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance proteins (MRPs). SLC family transporters related to drug transport mainly include organic anion-transporting polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), organic cation/carnitine transporters (OCTNs), peptide transporters (PEPTs), and multidrug/toxin extrusions (MATEs). These transporters are often expressed in tissues related to drug disposition, such as the small intestine, liver, and kidney, implicating intestinal absorption of drugs, uptake of drugs into hepatocytes, and renal/bile excretion of drugs. Most of therapeutic drugs are their substrates or inhibitors. When they are comedicated, serious drug-drug interactions (DDIs) may occur due to alterations in intestinal absorption, hepatic uptake, or renal/bile secretion of drugs, leading to enhancement of their activities or toxicities or therapeutic failure. This chapter will illustrate transporter-mediated DDIs (including food drug interaction) in human and their clinical significances.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Interações de Medicamentos , Preparações Farmacêuticas , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transporte Biológico , Interações Alimento-Droga , Humanos , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos , Preparações Farmacêuticas/metabolismo
6.
Int J Nanomedicine ; 14: 7353-7362, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571856

RESUMO

Backgrounds: Profiting from the development of nanomaterials, photothermal therapy (PTT) has been discovered as efficient tumor ablation strategy for breast cancer. Materials and methods: Novel oxygen vacancy-rich tungsten bronze nanoparticles (NaxWO3) were synthesized through a simple pyrogenic decomposition process. TEM, XRD, UV-vis-NIR, photothermal conversion ability, and photothermal stability were performed. The viabilities of 293T and 4T1 cells after treating with 200 µg/mL NaxWO3 nanoparticles for 24 or 48 hrs were both above 80%, which proved the good biosafety and cytotoxicity of NaxWO3 in vitro. Two in vivo breast cancer models, namely percutaneous and intratibial 4T1 models were established and NaxWO3 (20 mg/kg) with power intensity of 1.5 W/cm2 980 nm laser photothermal treatment was used in vivo. Results: We successfully synthesized ~150 nm NaxWO3 nanoparticles with desirable PTT effects, as evidenced by the temperature increase from 25.8°C to 41.8°C in 5 mins under the irradiation of 980 nm laser (1 mg/mL). Also, cellular compatibility of NaxWO3 nanoparticles was found upon physiologic 293T cells, in contrast with significant cytotoxicity against breast cancer 4T1 cell in vitro dose-dependently. Besides, two in vivo breast cancer models showed the decent tumor ablation ability of NaxWO3 nanoparticles, demonstrating percutaneous 4T1 tumor elimination without recurrence during 2 weeks observation as well as intratibial breast cancer inhibition with decreased bone destruction and tumor volume after NaxWO3+PTT in vivo. Conclusion: For the first time, we developed a novel oxygen vacancy-rich tungsten bronze nanoparticles (NaxWO3) through a simple pyrogenic decomposition process for PTT. Both in vitro and in vivo experiments showed the good PTT ability and tumor ablation effects of synthesized NaxWO3 nanoparticles against breast cancer osteolytic bone metastasis. Additionally, our oxygen-deficient NaxWO3 nanoparticles will expand the research horizons of PTT nanomaterials.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias da Mama/patologia , Hipertermia Induzida , Nanopartículas/química , Fototerapia , Tungstênio/química , Animais , Neoplasias Ósseas/diagnóstico por imagem , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia , Distribuição Tecidual , Microtomografia por Raio-X
7.
Anticancer Res ; 39(10): 5361-5367, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570430

RESUMO

BACKGROUND/AIM: The mechanism responsible for B-cell translocation gene 1 (BTG1) down-regulation in breast carcinoma remains unknown. We examined the BTG1 expression status in breast carcinoma cells and investigated the mechanism underlying the observed alterations. MATERIALS AND METHODS: Four breast carcinoma cell lines (SK-BR-3, MDA-MB-231, T-47D, and MCF-7), and one normal mammary epithelial cell line (MCF-10A) were analyzed. BTG1 expression was examined using quantitative reverse transcription polymerase chain reaction (PCR) and western blot. Methylation status of the BTG1 promoter was analyzed using methylation-specific PCR (MSP). To investigate the effect of methylation on BTG1, the cells were treated with a demethylating agent. RESULTS: The carcinoma cells expressed significantly lower levels of BTG1 mRNA and protein than normal cells. The BTG1 promoter was highly methylated in the carcinoma cells. 5-aza-2-deoxycytidine significantly restored BTG1 expression. CONCLUSION: Down-regulation of BTG1 expression through epigenetic repression is involved in mammary carcinogenesis. BTG1 is a potential diagnostic marker and therapeutic target for breast carcinoma.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , Regulação para Baixo/genética , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Epigênese Genética/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , RNA Mensageiro/genética
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1548-1555, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607310

RESUMO

OBJECTIVE: To investigate the biological characteristics of ABCG2 and its effect on side population cells (SP cells) of multiple myeloma (MM) so as to find the way for reversing drug resistance. METHODS: The silence of ABCG2 expression was performed throngh interfering the MM cells by using siRNA. then the ratio of SP cell of MM, speed of cell proliferation and sensitivity of cells to chermotherapentic drugs before and after interference were compared, the biological functions of ABCG2 and its role in regulation of SP cells and PTEN/PI3K/AKT signaling pathway was clarified. RESULTS: siRNA interference could down regulate the expression of ABCG2 at both mRNA and protein level. After siRNA interference, the proliferation of multiple myeloma cells was decreased slightly, the expression of PTEN was increased, the activity of PI3K/AKT pathway was inhibited, and the ratio of SP cells was decreased. CONCLUSION: In multiple myeloma, down-regulation of expression ABCG2 can negatively regulate the expression of PTEN, the PI3K/AKT signaling pathway is inhibited,the ratio of SP decreased,and the response to drug is increased.


Assuntos
Mieloma Múltiplo , Células da Side Population , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Linhagem Celular Tumoral , Humanos , Proteínas de Neoplasias , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais
9.
Adv Exp Med Biol ; 1172: 189-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628657

RESUMO

Gasdermin is a recently identified family of pore-forming proteins consisting of Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME), and DFNB59. Gasdermin D (GSDMD) is a downstream effector of inflammasomes, which are supramolecular complexes that activate inflammatory caspases (-1, -4, and -5 in human and -1 and -11 in mouse). GSDMD contains a functionally important N-terminal domain (GSDMD-N), a C-terminal domain, and a linker in between that is recognized and cleaved by the activated inflammatory caspases. Upon cleavage, the GSDMD-N fragments translocate on the membrane and oligomerize to form membrane-embedded pores after specifically binding to acidic lipids such as phosphatidylinositol phosphates (PIPs), phosphatidic acid (PA), phosphatidylserine (PS), and cardiolipin. The pore exhibits strong membrane-disrupting cytotoxicity in mammalian cells by disrupting the osmotic potential and also serves as a gate for extracellular release of mature IL-1ß and IL-18 during pyroptosis. In this chapter, we review our current understanding of GSDM proteins in physiological and pathological cell death, with more focused discussions on its structural basis for GSDM activation and pore formation.


Assuntos
Proteínas de Neoplasias , Piroptose , Animais , Caspases/metabolismo , Ativação Enzimática , Humanos , Inflamassomos , Camundongos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Relação Estrutura-Atividade
10.
Cancer Immunol Immunother ; 68(10): 1597-1603, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31520110

RESUMO

BACKGROUND: Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated. METHODS: Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient's history of neoadjuvant chemotherapy and/or radiotherapy, and the patient's overall survival. RESULTS: ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival. CONCLUSIONS: Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.


Assuntos
Adenocarcinoma/terapia , Proteínas de Neoplasias/análise , Receptores de Superfície Celular/análise , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Endoteliais/química , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade
11.
Ann Hematol ; 98(11): 2541-2550, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493002

RESUMO

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE-IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.


Assuntos
Antígenos CD/biossíntese , Neoplasias do Jejuno , Linfoma de Células T Periférico , Proteínas de Neoplasias/biossíntese , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias do Jejuno/metabolismo , Neoplasias do Jejuno/mortalidade , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/terapia , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
12.
BMC Bioinformatics ; 20(1): 450, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477009

RESUMO

BACKGROUND: Mutational signatures are specific patterns of somatic mutations introduced into the genome by oncogenic processes. Several mutational signatures have been identified and quantified from multiple cancer studies, and some of them have been linked to known oncogenic processes. Identification of the processes contributing to mutations observed in a sample is potentially informative to understand the cancer etiology. RESULTS: We present here SigsPack, a Bioconductor package to estimate a sample's exposure to mutational processes described by a set of mutational signatures. The package also provides functions to estimate stability of these exposures, using bootstrapping. The performance of exposure and exposure stability estimations have been validated using synthetic and real data. Finally, the package provides tools to normalize the mutation frequencies with respect to the tri-nucleotide contents of the regions probed in the experiment. The importance of this effect is illustrated in an example. CONCLUSION: SigsPack provides a complete set of tools for individual sample exposure estimation, and for mutation catalogue & mutational signatures normalization.


Assuntos
Carcinogênese/genética , Genoma Humano , Mutação , Proteínas de Neoplasias/genética , Neoplasias/genética , Software , Carcinogênese/patologia , Análise Mutacional de DNA , Humanos , Taxa de Mutação , Neoplasias/patologia
13.
Int J Nanomedicine ; 14: 6197-6215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496681

RESUMO

Introduction and objective: Degradation of the extracellular matrix (ECM) changes the physicochemical properties and dysregulates ECM-cell interactions, leading to several pathological conditions, such as invasive cancer. Carbon nanofilm, as a biocompatible and easy to functionalize material, could be used to mimic ECM structures, changing cancer cell behavior to perform like normal cells. Methods: Experiments were performed in vitro with HS-5 cells (as a control) and HepG2 and C3A cancer cells. An aqueous solution of fullerene C60 was used to form a nanofilm. The morphological properties of cells cultivated on C60 nanofilms were evaluated with light, confocal, electron and atomic force microscopy. The cell viability and proliferation were measured by XTT and BrdU assays. Immunoblotting and flow cytometry were used to evaluate the expression level of proliferating cell nuclear antigen and determine the number of cells in the G2/M phase. Results: All cell lines were spread on C60 nanofilms, showing a high affinity to the nanofilm surface. We found that C60 nanofilm mimicked the niche/ECM of cells, was biocompatible and non-toxic, but the mechanical signal from C60 nanofilm created an environment that affected the cell cycle and reduced cell proliferation. Conclusion: The results indicate that C60 nanofilms might be a suitable, substitute component for the niche of cancer cells. The incorporation of fullerene C60 in the ECM/niche may be an alternative treatment for hepatocellular carcinoma.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Fulerenos/farmacologia , Fase G2/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Mecanotransdução Celular , Nanopartículas/química , Comunicação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Módulo de Elasticidade , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fulerenos/química , Humanos , Integrina alfa5beta1/metabolismo , Neoplasias Hepáticas/ultraestrutura , Mecanotransdução Celular/efeitos dos fármacos , Nanopartículas/ultraestrutura , Proteínas de Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
BMC Bioinformatics ; 20(1): 463, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500569

RESUMO

BACKGROUND: The Human Protein Atlas (HPA) aims to map human proteins via multiple technologies including imaging, proteomics and transcriptomics. Access of the HPA data is mainly via web-based interface allowing views of individual proteins, which may not be optimal for data analysis of a gene set, or automatic retrieval of original images. RESULTS: HPAanalyze is an R package for retrieving and performing exploratory analysis of data from HPA. HPAanalyze provides functionality for importing data tables and xml files from HPA, exporting and visualizing data, as well as downloading all staining images of interest. The package is free, open source, and available via Bioconductor and GitHub. We provide examples of the use of HPAanalyze to investigate proteins altered in the deadly brain tumor glioblastoma. For example, we confirm Epidermal Growth Factor Receptor elevation and Phosphatase and Tensin Homolog loss and suggest the importance of the GTP Cyclohydrolase I/Tetrahydrobiopterin pathway. Additionally, we provide an interactive website for non-programmers to explore and visualize data without the use of R. CONCLUSIONS: HPAanalyze integrates into the R workflow with the tidyverse framework, and it can be used in combination with Bioconductor packages for easy analysis of HPA data.


Assuntos
Análise de Dados , Armazenamento e Recuperação da Informação , Proteínas de Neoplasias/metabolismo , Software , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Humanos
15.
Cancer Sci ; 110(11): 3510-3519, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31487418

RESUMO

NOP2/Sun domain family, member 2 (NSUN2) is a nuclear RNA methyl-transferase catalyzing 5-methylcytosine formation. Evidence shows that NSUN2 is correlated with cell unlimited proliferation. However, its functional role in gallbladder carcinoma (GBC), which is the most common biliary tract malignancy and has a poor prognosis, remains to be determined. Here we found that NSUN2 was highly expressed in GBC tissues as well as cell lines. NSUN2 silencing repressed GBC cell proliferation and tumorigenesis both in vitro and in vivo. Conversely, upregulation of NSUN2 enhanced GBC cell growth and colony formation. We further discovered that RPL6 was a closely interacting partner with NSUN2. Silencing RPL6 resulted in insufficient NSUN2 translational level and accumulative NSUN2 transcriptional level. Exogenous expression of NSUN2 partially rescued the effect of RPL6 in gallbladder cancer progression. Taken together, our data provided novel mechanic insights into the function of NSUN2 in GBC, thus pointing to NSUN2 as a potential and effective therapeutic approach to GBC treatment.


Assuntos
Carcinoma/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Metiltransferases/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Ribossômicas/metabolismo , Animais , Carcinoma/patologia , Carcinoma/terapia , Linhagem Celular Tumoral , Proliferação de Células , Colecistite/metabolismo , Progressão da Doença , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Metiltransferases/antagonistas & inibidores , Camundongos , Camundongos Nus , Ensaio Tumoral de Célula-Tronco , Regulação para Cima
16.
Cancer Sci ; 110(11): 3533-3542, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31489722

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system. Surgical intervention is the preferred treatment for ccRCC, but targeted biological therapy is required for postoperative recurrent or metastatic ccRCC. Autophagy is an intracellular degradation system for misfolded/aggregated proteins and dysfunctional organelles. Defective autophagy is associated with many diseases. Mul1 is a mitochondrion-associated E3 ubiquitin ligase and involved in the regulation of divergent pathophysiological processes such as mitochondrial dynamics, and thus affects the development of various diseases including cancers. Whether Mul1 regulates ccRCC development and what is the mechanism remain unclear. Histochemical staining and immunoblotting were used to analyze the levels of Mul1 protein in human renal tissues. Statistical analysis of information associated with tissue microarray and The Cancer Genome Atlas (TCGA) database was conducted to show the relationship between Mul1 expression and clinical features and survival of ccRCC patients. Impact of Mul1 on rates of cell growth and migration and autophagy flux were tested in cultured cancer cells. Herein we show that Mul1 promoted autophagy flux to facilitate the degradation of P62-associated protein aggresomes and adipose differentiation-related protein (ADFP)-associated lipid droplets and suppressed the growth and migration of ccRCC cells. Levels of Mul1 protein and mRNA were significantly reduced so that autophagy flux was likely blocked in ccRCC tissues, which is potentially correlated with enhancement of malignancy of ccRCC and impairment of patient survival. Therefore, Mul1 may promote autophagy to suppress the development of ccRCC.


Assuntos
Autofagia , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Mitocôndrias/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Rim/enzimologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteólise , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/análise
17.
Cancer Sci ; 110(11): 3543-3552, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541611

RESUMO

Poly ADP-ribose polymerase inhibitors (PARPi) have shown promising therapeutic efficacy in triple-negative breast cancer (TNBC) patients. However, resistance ultimately develops, preventing a curative effect from being attained. Extensive investigations have indicated the diversity in the mechanisms underlying the PARPi sensitivity of breast cancer. In this study, we found that DNA damage binding protein 2 (DDB2), a DNA damage-recognition factor, could protect TNBC cells from PARPi by regulating DNA double-strand break repair through the homologous recombination pathway, whereas the depletion of DDB2 sensitizes TNBC cells to PARPi. Furthermore, we found that DDB2 was able to stabilize Rad51 by physical association and disrupting its ubiquitination pathway-induced proteasomal degradation. These findings highlight an essential role of DDB2 in modulating homologous recombination pathway activity and suggest a promising therapeutic target for TNBC.


Assuntos
Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Rad51 Recombinase/metabolismo , Reparo de DNA por Recombinação , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Reparo do DNA , Proteínas de Ligação a DNA/deficiência , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Ubiquitinação
18.
Medicine (Baltimore) ; 98(31): e16511, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374012

RESUMO

Blood-based biomarkers, such as carcinoembryonic antigen (CEA), and saliva-based biomarkers, such as mRNA, have emerged as potential liquid biopsies for non-invasive detection of many cancers. However, current tests typically use single type of biomarkers, and their sensitivity and specificity is often unsatisfactory.In this study, we developed a novel biomarker panel that measures both CEA level in blood and GREB1 and FRS2 levels in saliva to achieve high sensitivity and high specificity in detecting Non-Small Cell Lung Cancer (NSCLC).In the discovery phase, we achieved sensitivity of 96.67% and specificity of 93.33% for 30 NSCLC patients and 30 healthy controls. To further evaluate the prediction performance of our biomarker panel, we applied it to an independent set of 15 NSCLC cancer patients and 25 healthy controls. The sensitivity and specificity of our test reached 93.33% and 80.00% respectively.Our study discovered that the combined analysis of CEA and mRNA can be a novel liquid-biopsy technology for non-invasive detection of NSCLC.


Assuntos
Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal/análise , Idoso , Área Sob a Curva , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Feminino , Humanos , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Curva ROC , Saliva/enzimologia
19.
Medicine (Baltimore) ; 98(31): e16715, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374065

RESUMO

Chromosome 8 open reading frame 4 (C8orf4) is an activator of Wnt signaling pathway, and participates in the tumorigenesis and progression of many tumors. The expression levels of C8orf4 and ß-catenin were assessed via immunohistochemical staining in 100 cervical squamous cell carcinoma (CSCC) tissues, 50 high-grade squamous intraepithelial lesions (HSILs), 50 low-grade squamous intraepithelial lesions (LSILs), and 50 normal cervical tissues. Bisulfite sequencing polymerase chain reaction analysis was used to examine the methylation status of the C8orf4 locus in CSCC and normal cervical tissues. The expression rates of C8orf4 and ß-catenin were significantly higher in CSCCs or HSILs than in LSILs or normal cervical tissues (P < .05). C8orf4 expression was positively correlated with the poor differentiation of CSCCs (P = .009), and with aberrant expression of ß-catenin in CSCCs (P = .002) and squamous intraepithelial lesions (P < .001). The methylation rate of C8orf4 in CSCCs was significantly lower than that in normal cervical tissues (P = .001). The Cancer Genome Atlas genomics data also confirmed that the mRNA expression of C8orf4 was positively associated with the copy number alteration of C8orf4 (correlation coefficient = 0.213, P < .001), and negatively correlated with the methylation level of C8orf4 (correlation coefficient = -0.408, P < .001). In conclusion, the expressions of C8orf4 and ß-catenin were synergistically increased in CSCCs and HSILs and higher than those in LSILs and normal cervical tissues. The methylation level of C8orf4 is decreased in CSCCs and is responsible for the increased expression of C8orf4.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasia Intraepitelial Cervical/genética , Proteínas de Neoplasias/biossíntese , Neoplasias do Colo do Útero/genética , beta Catenina/biossíntese , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Reação em Cadeia da Polimerase , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Adulto Jovem , beta Catenina/genética
20.
Life Sci ; 234: 116788, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31445935

RESUMO

Livin is an important member of the human inhibitor of apoptosis proteins (IAPs) family. IAPs are proteins with antiapoptotic abilities, and their functions are different from the Bcl-2 (B-cell lymphoma-2) family proteins. However, the precise role of Livin in colon cancer progression remains unclear. The purpose of this study is to assess the effect of overexpression Livin in colon cancer cells and to examine its molecular mechanism. We demonstrated that Livin induced a colon cancer phenotype, including proliferation and migration, by regulating H2A.XY39ph (histone family 2A variant (H2AX) phosphorylated on the 39th serine site). We elucidated that Livin degraded Jumonji-C domain-containing 6 protein (JMJD6), which was mediated by the proteasome murine double minute 2 (MDM2), thereby regulating H2A.XY39ph. Above all, the overexpression of JMJD6 recovered H2A.XY39ph in colon cancer cells with a high level of Livin, thus inhibiting colon cancer malignancy progression. These results reveal a previously unrecognized role for Livin in regulating the tumor-initiating capacity in colon cancer and provide a novel treatment strategy in cancer via the interruption of H2A.XY39ph function and the interaction between H2A.XY39ph and JMJD6.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias do Colo/patologia , Histonas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas de Neoplasias/metabolismo , Mapas de Interação de Proteínas , Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Humanos , Proteínas Inibidoras de Apoptose/genética , Histona Desmetilases com o Domínio Jumonji/genética , Proteínas de Neoplasias/genética , Proteólise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA