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1.
Nanoscale Res Lett ; 15(1): 197, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052458

RESUMO

In this study, self-catalyzed ß-FeSi2 nanowires, having been wanted but seldom achieved in a furnace, were synthesized via chemical vapor deposition method where the fabrication of ß-FeSi2 nanowires occurred on Si (100) substrates through the decomposition of the single-source precursor of anhydrous FeCl3 powders at 750-950 °C. We carefully varied temperatures, duration time, and the flow rates of carrier gases to control and investigate the growth of the nanowires. The morphology of the ß-FeSi2 nanowires was observed with scanning electron microscopy (SEM), while the structure of them was analyzed with X-ray diffraction (XRD) and transmission electron microscopy (TEM). The growth mechanism has been proposed and the physical properties of the iron disilicide nanowires were measured as well. In terms of the magnetization of ß-FeSi2, nanowires were found to be different from bulk and thin film; additionally, longer ß-FeSi2 nanowires possessed better magnetic properties, showing the room-temperature ferromagnetic behavior. Field emission measurements demonstrate that ß-FeSi2 nanowires can be applied in field emitters.

2.
Commun Biol ; 3(1): 113, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157156

RESUMO

The tonic model delineating the serotonin transporter polymorphism's (5-HTTLPR) modulatory effect on anxiety points towards a universal underlying mechanism involving a hyper-or-elevated baseline level of arousal even to non-threatening stimuli. However, to our knowledge, this mechanism has never been observed in non-clinical cohorts exhibiting high anxiety. Moreover, empirical support regarding said association is mixed, potentially because of publication bias with a relatively small sample size. Hence, how the 5-HTTLPR modulates neural correlates remains controversial. Here we show that 5-HTTLPR short-allele carriers had significantly increased baseline ERPs and reduced fearful MMN, phenomena which can nevertheless be reversed by acute anxiolytic treatment. This provides evidence that the 5-HTT affects the automatic processing of threatening and non-threatening voices, impacts broadly on social cognition, and conclusively asserts the heightened baseline arousal level as the universal underlying neural mechanism for anxiety-related susceptibilities, functioning as a spectrum-like distribution from high trait anxiety non-patients to anxiety patients.

3.
Int J Cancer ; 145(8): 2209-2224, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30980673

RESUMO

The dynamic cell-cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are extracellular vesicles that actively participate in cell-cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the ß-catenin/Tcf-4-activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA-146a-5p (miR-146a) is the major miRNA in CRCSC exosomes and exosomal miR-146a promotes stem-like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR-146a expression in serum exhibits higher miR-146aHigh /NumbLow CRCSC traits, an increased number of tumor-filtrating CD66(+) neutrophils and a decreased number of tumor-infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome-mediated stemness expansion.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Exossomos/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas rab de Ligação ao GTP/genética , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Células HT29 , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Interferência de RNA , Microambiente Tumoral/genética , Proteínas rab de Ligação ao GTP/metabolismo
4.
Nat Cell Biol ; 21(5): 664, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30820041

RESUMO

In the version of Supplementary Fig. 6c originally published with this Article, the immunoprecipitation (IP) and immunoblotting (IB) tags in the top panel were mislabelled. In addition, in Supplementary Fig. 6e, the blot of the IP: Numb; IB: ß-Trcp panel for HCT15 was mistakenly duplicated for HCT116. The correct versions of these figures are shown below. An independent repeat of the experiments presented in Supplementary Fig. 6c and e, showing results that are consistent with those reported in the unprocessed blots, have been deposited in figshare ( 10.6084/m9.figshare.7570685 ).

5.
Cancers (Basel) ; 11(1)2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30626171

RESUMO

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(-)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during surgery. We found that the CTC count in PB but not IMV correlates with disease stages. Neoadjuvant chemotherapy did not lead to decreased CTC count in both types of blood samples. With cutoffs of four CTCs per 2 mL of blood, and serum carcinoembryonic antigen (CEA) level of 5 ng/mL, patients with non-metastatic disease were more likely to experience recurrence if they had high PB CTC count and high serum CEA concentration (odds ratio, 8.9). Our study demonstrates the feasibility of enumerating CTCs with a SACA chip in patients with colorectal cancer.

6.
PLoS One ; 12(7): e0181562, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28727754

RESUMO

Functional impairment of endothelial colony-forming cells (ECFCs), a specific cell lineage of endothelial progenitor cells (EPCs) is highly associated with the severity of coronary artery disease (CAD), the most common type of cardiovascular disease (CVD). Emerging evidence show that circulating microRNAs (miRNAs) in CAD patients' body fluid hold a great potential as biomarkers. However, our knowledge of the role of circulating miRNA in regulating the function of ECFCs and the progression of CAD is still in its infancy. We showed that when ECFCs from healthy volunteers were incubated with conditioned medium or purified exosomes of cultured CAD ECFCs, the secretory factors from CAD ECFCs dysregulated migration and tube formation ability of healthy ECFCs. It is known that exosomes influence the physiology of recipient cells by introducing RNAs including miRNAs. By using small RNA sequencing (smRNA-seq), we deciphered the circulating miRNome in the plasma of healthy individual and CAD patients, and found that the plasma miRNA spectrum from CAD patients was significantly different from that of healthy control. Interestingly, smRNA-seq of both healthy and CAD ECFCs showed that twelve miRNAs that had a higher expression in the plasma of CAD patients also showed higher expression in CAD ECFCs when compared with healthy control. This result suggests that these miRNAs may be involved in the regulation of ECFC functions. For identification of potential mRNA targets of the differentially expressed miRNA in CAD patients, cDNA microarray analysis was performed to identify the angiogenesis-related genes that were down-regulated in CAD ECFCs and Pearson's correlation were used to identify miRNAs that were negatively correlated with the identified angiogenesis-related genes. RT-qPCR analysis of the five miRNAs that negatively correlated with the down-regulated angiogenesis-related genes in plasma and ECFC of CAD patients showed miR-146a-5p and miR-146b-5p up-regulation compared to healthy control. Knockdown of miR-146a-5p or miR-146b-5p in CAD ECFCs enhanced migration and tube formation activity in diseased ECFCs. Contrarily, overexpression of miR-146a-5p or miR-146b-5p in healthy ECFC repressed migration and tube formation in ECFCs. TargetScan analysis showed that miR-146a-5p and miR-146b-5p target many of the angiogenesis-related genes that were down-regulated in CAD ECFCs. Knockdown of miR-146a-5p or miR-146b-5p restores CAV1 and RHOJ levels in CAD ECFCs. Reporter assays confirmed the direct binding and repression of miR-146a-5p and miR-146b-5p to the 3'-UTR of mRNA of RHOJ, a positive regulator of angiogenic potential in endothelial cells. Consistently, RHOJ knockdown inhibited the migration and tube formation ability in ECFCs. Collectively, we discovered the dysregulation of miR-146a-5p/RHOJ and miR-146b-5p/RHOJ axis in the plasma and ECFCs of CAD patients that could be used as biomarkers or therapeutic targets for CAD and other angiogenesis-related diseases.


Assuntos
Doença da Artéria Coronariana/metabolismo , Células Endoteliais/metabolismo , Retroalimentação Fisiológica/fisiologia , MicroRNAs/metabolismo , Biomarcadores/sangue , Caveolina 1/metabolismo , Linhagem da Célula , Movimento Celular/fisiologia , Células Cultivadas , Meios de Cultivo Condicionados/metabolismo , Células Progenitoras Endoteliais/metabolismo , Exossomos/metabolismo , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , RNA Mensageiro/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
7.
FASEB J ; 31(1): 47-59, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27663861

RESUMO

Membrane fusions that occur during vesicle transport, virus infection, and tissue development, involve receptors that mediate membrane contact and initiate fusion and effectors that execute membrane reorganization and fusion pore formation. Some of these fusogenic receptors/effectors are preferentially recruited to lipid raft membrane microdomains. Therefore, major constituents of lipid rafts, such as stomatin, may be involved in the regulation of cell-cell fusion. Stomatin produced in cells can be released to the extracellular environment, either through protein refolding to pass across lipid bilayer or through exosome trafficking. We report that cells expressing more stomatin or exposed to exogenous stomatin are more prone to undergoing cell fusion. During osteoclastogenesis, depletion of stomatin inhibited cell fusion but had little effect on tartrate-resistant acid phosphatase production. Moreover, in stomatin transgenic mice, increased cell fusion leading to enhanced bone resorption and subsequent osteoporosis were observed. With its unique molecular topology, stomatin forms molecular assembly within lipid rafts or on the appositional plasma membranes, and promotes membrane fusion by modulating fusogenic protein engagement.-Lee, J.-H., Hsieh, C.-F., Liu, H.-W., Chen, C.-Y., Wu, S.-C., Chen, T.-W., Hsu, C.-S., Liao, Y.-H., Yang, C.-Y., Shyu, J.-F., Fischer, W. B., Lin, C.-H. Lipid raft-associated stomatin enhances cell fusion.


Assuntos
Fusão Celular , Regulação da Expressão Gênica/fisiologia , Microdomínios da Membrana/fisiologia , Proteínas de Membrana/metabolismo , Animais , Células CHO , Cricetinae , Cricetulus , Células HEK293 , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Osteoclastos/fisiologia , Osteoporose
8.
BMC Cancer ; 16: 697, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27577936

RESUMO

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is a transmembrane tyrosine kinase receptor that is overexpressed in 25 to 30 % of human breast cancers and is preferentially localized in lipid rafts. Stomatin is a membrane protein that is absent from the erythrocyte plasma membrane in patients with congenital stomatocytosis and is the major component of the lipid raft. RESULTS: In a total of 68 clinical cases of HER2-positive breast cancer, the absence of stomatin expression was associated with a decreased 5-year survival (65 % vs. 93 %, p = 0.005) by survival analysis. For stage I-III HER2-positive breast cancer, the absence of stomatin expression was associated with a decreased 5-year disease-free survival (57 % vs. 81 %, p = 0.016) and was an independent prognostic factor by multivariate analysis. Negative stomatin expression predicts distant metastases in a hazard ratio of 4.0 (95 % confidence interval from 1.3 to 12.5). CONCLUSIONS: These results may suggest that stomatin is a new prognostic indicator for HER2-positive breast cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Proteínas de Membrana/biossíntese , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/biossíntese
9.
J Gen Virol ; 97(9): 2411-2420, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27435237

RESUMO

Increasing evidence suggests that human cytomegalovirus (HCMV) plays an oncomodulatory role in human cancers. In colorectal cancer (CRC), presence of HCMV in tumours has been associated with a poor outcome in elderly patients. This study aimed to investigate the association between HCMV and the outcome of non-elderly patients with CRC. In tumour samples, HCMV DNA was detected by PCR. Viral transcript and protein were detected by in situ hybridization (ISH) and immunohistochemical staining (IHC), respectively. Clinical, pathological and survival data were compared between patients with HCMV-positive and -negative tumours. Quantitative reverse transcription PCR (qRT-PCR) was used to analyse the expression levels of cellular signals related to CRC progression and metastasis. Among 89 CRC non-elderly patients aged <65 years, HCMV was detected in 31 (34.8 %) tumour samples by PCR. By ISH and IHC, viral transcript and protein specifically localized to the cytoplasm of neoplastic mucosal epithelium. Outcome analysis revealed a more favourable disease-free survival (DFS) rate in patients with HCMV-positive tumours (P<0.01), specifically in patients with stage III disease. In a multivariate Cox proportional-hazard model, tumoural presence of HCMV independently predicted a higher DFS rate (hazard ratio 0.22; 95 % confidence interval 0.075-0.66, P<0.01). By qRT-PCR, the tumoural levels of interleukin-1 were relatively lower in samples positive for HCMV. The results suggest that HCMV may influence the outcome of CRC in an age-dependent manner and possibly has a dual oncomodulatory effect. How the virus interacts with the tumour microenvironment should be further studied.


Assuntos
Neoplasias Colorretais/virologia , Citomegalovirus/isolamento & purificação , Neoplasias Colorretais/patologia , DNA Viral/análise , DNA Viral/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Gradação de Tumores , Reação em Cadeia da Polimerase , RNA Viral/análise , RNA Viral/genética , Análise de Sobrevida , Resultado do Tratamento , Proteínas Virais/análise , Proteínas Virais/imunologia
10.
J Gen Virol ; 97(1): 152-159, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26474568

RESUMO

Colorectal cancer (CRC) is amongst the leading causes of cancer-related mortality worldwide. Emerging evidence suggests that human cytomegalovirus (HCMV) exists in the tumour tissue of CRC and is associated with disease outcome. To study whether tumoral HCMV is related to viral reactivation in blood, tumour specimens and pre- and post-operative blood samples from CRC patients were collected prospectively. PCR and quantitative PCR were performed to detect HCMV DNA. HCMV IgG and IgM antibodies were measured using a microparticle enzyme immunoassay. Transcription of a spliced HCMV UL73 gene transcript was analysed by quantitative reverse transcription PCR. HCMV was detected in 42.2% (35/83) of the tumour samples, with a low median viral load (30.08, range 2.33-5704 copies per 500  ng genomic DNA). The vast majority (80/81, 98.8%) of the CRC patients were seropositive for HCMV IgG. HCMV DNA was positive in 11.3% (22/194) of the pre-operative and 8.9% (15/168) of the post-operative blood samples. However, presence of HCMV and its viral load in tumours were not associated with the detection or viral loads in blood samples. About 26.67% (8/30) of the HCMV-positive tumours with available RNA had detectable viral UL73 transcripts, whilst none of the blood samples were positive for viral RNA (P < 0.0001). Therefore, presence of HCMV in tumours does not correlate with the serological or viraemic status of CRC patients. Active viral gene transcription occurred in the tumour but not in the blood of CRC patients. HCMV reactivation in CRC patients is possibly due to virus-cancer interactions in the CRC tumour microenvironment.


Assuntos
Anticorpos Antivirais/sangue , Neoplasias Colorretais/complicações , Infecções por Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Transcrição Genética , Carga Viral , Replicação Viral , Idoso , Idoso de 80 Anos ou mais , Infecções por Citomegalovirus/virologia , DNA Viral/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Perfilação da Expressão Gênica , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos
11.
Colloids Surf B Biointerfaces ; 140: 567-573, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26705859

RESUMO

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Compostos Férricos/química , Campos Magnéticos , Camundongos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanopartículas/química , Nanopartículas/ultraestrutura , Propriedades de Superfície , Carga Tumoral/efeitos dos fármacos
12.
J Gen Virol ; 96(12): 3613-23, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26450180

RESUMO

Human cytomegalovirus (HCMV) has been increasingly detected in colorectal cancer (CRC), and genetic polymorphisms in HCMV affect its pathogenesis. This study aimed to investigate HCMV genetic polymorphisms in CRC and its correlation with the clinical outcomes. We performed PCR and sequencing of a viral immunomodulatory gene, UL144, in clinical isolates and CRC specimens. The nucleotide and amino acid sequences were aligned, and a phylogenetic tree was constructed. The clinical, pathological and survival data were compared among tumours with different UL144 genotypes. HCMV was detected in 49 (47.8 %) of the tumour specimens. Genotype A predominated in 43 samples (22/43; 51.2 %) with successful sequencing, followed by genotype B (13/43; 30.2 %) and genotype C (8/43; 18.6 %). The genotypic distribution was similar to that of the clinical isolates and those reported in other Asian populations. The amino acid sequence of genotype B was the most conserved. For stage II and III CRC patients with HCMV-positive tumours, disease-free survival (DFS) varied among the three major genotypes (P50.0046). The presence of genotype B virus in the tumours was associated with a shorter DFS and independently predicted tumour recurrence in a multivariate Cox proportional hazards model (hazard ratio, 5.79; 95 % confidence interval, 1.30­25.81; P50.021). By reverse transcription PCR, tumour samples with genotype B viruses had the highest rate of UL144 expression. Our results suggest that genetic polymorphisms of HCMV UL144 are associated with clinical outcome in CRC and that HCMV may play an immunomodulatory role in the tumour microenvironment of CRC.


Assuntos
Neoplasias Colorretais/virologia , Citomegalovirus/genética , Glicoproteínas de Membrana/genética , Polimorfismo Genético , Proteínas Virais/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Citomegalovirus/classificação , Citomegalovirus/isolamento & purificação , DNA Viral/genética , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência
13.
Cancer Biol Ther ; 16(11): 1641-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26436767

RESUMO

Our previous studies showed that colorectal tumor has high interleukin-4 receptor α (IL-4Rα) expression, whereas adjacent normal tissue has low or no IL-4Rα expression. We also observed that human atherosclerotic plaque-specific peptide-1 (AP1) can specifically target to IL-4Rα. In this study, we investigated the therapeutic efficacy and systemic toxicity of AP1-conjuagted liposomal doxorubicin. AP1 bound more strongly to and was more efficiently internalized into IL-4Rα-overexpressing CT26 cells than CT26 control cells. Selective cytotoxicity experiment revealed that AP1-conjugated liposomal doxorubicin preferentially killed IL-4Rα-overexpressing CT26 cells. AP1-conjugated liposomal doxorubicin administered intravenously into mice produced significant inhibition of tumor growth and showed decreased cardiotoxicity of doxorubicin. These results indicated that AP1-conjugated liposomal doxorubicin has a potent and selective anticancer potential against IL-4Rα-overexpressing colorectal cancer cells, thus providing a model for targeted anticancer therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/administração & dosagem , Peptídeos/administração & dosagem , Receptores de Interleucina-4/metabolismo , Animais , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Doxorrubicina/metabolismo , Doxorrubicina/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Peptídeos/metabolismo , Peptídeos/toxicidade , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
14.
Int J Colorectal Dis ; 30(12): 1617-26, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26206347

RESUMO

PURPOSE: Colorectal polyps are generally believed to be the precursors of colorectal cancers (CRC); however, the proportion and speed of progression differed widely in different subsets of polyps. Using microarray-based comparative genomic hybridization (aCGH) platform and CD133 immunostaining, we characterized colon polyps according to their association with CRC that developed in the same individual. PATIENTS AND METHODS: aCGH was performed to unveil genomic changes in 18 cancer-synchronous polyps (CSP), and 9 cancer-preceding polyps (CPP), together with their corresponding cancers and 16 cases of incidental polyps (IP), were examined for comparison. aCGH profiles were analyzed to determine the clonal relationship (CR) between the paired adenoma and carcinoma. CD133 expressions in each subset of polyps were quantified by immunohistochemistry (IHC) staining. RESULTS: Progressive genomic changes were observed from IP, CSP/CPP to CRC; they encompass an entire chromosomal region in IP and sub-chromosomal region in CSP/CPP and CRC. CR analyses demonstrated that 50 % of CSP and 67 % of CPP were clonally related to the concurrent or later developed carcinomas, respectively. The CD133 expression levels were significantly higher in CSP/CPP than those in IP (P < 0.0001) and even higher in CSP/CPP that were clonally related to their corresponding carcinomas than CSP/CPP that were unrelated (P < 0.05). CONCLUSIONS: There were more genomic changes in CSP/CPP than IP; more than half of the CSP/CPP were clonally related to the corresponding carcinomas. Genomic changes at sub-chromosomal regions and/or high CD133 expression were associated with CSP/CPP and highlighted their carcinogenic potential.


Assuntos
Antígenos CD/genética , Pólipos do Colo/genética , Glicoproteínas/genética , Peptídeos/genética , Antígeno AC133 , Adenoma/genética , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Carcinoma/genética , Pólipos do Colo/metabolismo , Hibridização Genômica Comparativa , Feminino , Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Peptídeos/metabolismo , Estudos Prospectivos , Fatores de Risco
15.
J Surg Res ; 199(2): 362-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26119272

RESUMO

BACKGROUND: Tumor initiating cells are a small subset of cancer cells responsible for tumor growth and recurrence. The status of tumor initiating cells was measured using the surface markers CD133 (prominin-1) and ESA (epithelial-specific antigen). The aims of this study were to investigate the significance of CD133(+)/ESA(+) cells in mesenteric venous blood (MVB) and tumor mass (TM) for overall survival (OS) and disease-free survival (DFS) in colorectal cancer (CRC) patients undergoing curative resection. MATERIALS AND METHODS: A total of 229 CRC patients undergoing curative resection were prospectively enrolled in the study. Using CD133 and ESA as surface markers, CD133(+)/ESA(+) cells were enumerated from MVB and TM using flow cytometry. RESULTS: We analyzed the presence of CD133(+)/ESA(+) cells in TM from 158 patients and found no correlation to patient DFS, OS, or clinical stage. In 135 patients, an analysis of CD133(+)/ESA(+) cells in MVB showed an inverse correlation with both DFS and OS (P = 0.014 and P = 0.008, respectively). It exhibited an increase-then-decrease pattern with the peak in stage II patients. A multivariate Cox analysis demonstrated that the status of CD133(+)/ESA(+) cells in MVB, but not the TM, was a significant prognostic factor for DFS and OS (P = 0.003 and P = 0.011, respectively). CONCLUSIONS: The status of CD133(+)/ESA(+) cells in MVB, but not in TM, could be a useful indicator for predicting tumor recurrence and a prognostic marker for CRC patients.


Assuntos
Antígenos CD/análise , Antígenos de Neoplasias/análise , Moléculas de Adesão Celular/análise , Neoplasias Colorretais/sangue , Glicoproteínas/análise , Células-Tronco Neoplásicas , Peptídeos/análise , Antígeno AC133 , Idoso , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taiwan/epidemiologia
16.
Neoplasia ; 17(3): 265-78, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25810011

RESUMO

Breast cancer resistance protein [BCRP/ATP-binding cassette subfamily G member 2 (ABCG2)] is a member of the ATP-binding cassette transporter family. The presence of ABCG2 on the plasma membrane in many kinds of human cancer cells contributes to multidrug resistance during chemotherapy, and it has been used as the side population marker for identifying cancer stem cells in lung cancers. We report here that, in addition to the membranous form, ABCG2 proteins are also found inside the nucleus, where they bind to the E-box of CDH1 (E-cadherin) promoter and regulate transcription of this gene. Increased expression of ABCG2 causes an increase of E-cadherin and attenuates cell migration, whereas knockdown of ABCG2 downregulates E-cadherin and enhances cell motility. In mice, xenografted A549 cells that have less ABCG2 are more likely to metastasize from the subcutaneous inoculation site to the internal organs. However, for the cancer cells that have already entered the blood circulation, an increased level of ABCG2, and correspondingly increased E-cadherin, may facilitate circulating cancer cells to colonize at a distant site and form a metastatic tumor. We propose a novel role for nuclear ABCG2 that functions as a transcription regulator and participates in modulation of cancer metastasis.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Caderinas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transporte Ativo do Núcleo Celular , Animais , Antígenos CD , Caderinas/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Modelos Animais de Doenças , Xenoenxertos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Modelos Biológicos , Proteínas de Neoplasias/genética , Células Neoplásicas Circulantes , Interferência de RNA , Transcrição Genética
17.
J Neurophysiol ; 113(6): 1842-9, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25540221

RESUMO

Testosterone is capable of altering facial threat processing. Voices, similar to faces, convey social information. We hypothesized that administering a single dose of testosterone would change voice perception in humans. In a placebo-controlled, randomly assigned, double-blind crossover design, we administered a single dose of testosterone or placebo to 18 healthy female volunteers and used a passive auditory oddball paradigm. The mismatch negativity (MMN) and P3a in responses to fearfully, happily, and neutrally spoken syllables dada and acoustically matched nonvocal sounds were analyzed, indicating preattentive sensory processing and involuntary attention switches. Results showed that testosterone administration had a trend to shorten the peak latencies of happy MMN and significantly enhanced the amplitudes of happy and fearful P3a, whereas the happy- and fearful-derived nonvocal MMN and P3a remained unaffected. These findings demonstrated acute effect of testosterone on the neural dynamics of voice perception. Administering a single dose of testosterone modulates preattentive sensory processing and involuntary attention switches in response to emotional voices.


Assuntos
Percepção Auditiva/efeitos dos fármacos , Emoções , Testosterona/farmacologia , Voz , Adulto , Atenção , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Distribuição Aleatória
18.
Acta Otolaryngol ; 135(2): 177-80, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25515966

RESUMO

CONCLUSION: The location of the foreign body did not correspond well to the location of pain reported by patients. When patients present with foreign bodies in the pharynx, in addition to recording the location of pain and foreign body sensation, clinicians should perform a comprehensive and thorough oropharyngeal examination to avoid misdiagnosis. OBJECTIVES: Physicians are often guided by patient-indicated locations of pharyngeal foreign bodies. In this study, we aimed to determine the correlation between the location of the subjective neck pain or foreign body sensation and the true location of the foreign body. METHODS: We prospectively studied 90 patients who had pharyngeal foreign bodies removed at MacKay Memorial Hospital. We divided the head and neck into 10 zones according to the superficial anatomy. Subjective location, examination findings, and actual foreign body location were recorded and compared. RESULTS: The overall subjective and true locations of the foreign body were poorly correlated (kappa 0.27, p = 0.003). The positive predictive value (PPV) for the midline neck was 68%, which was higher than that on either lateral side of the neck. PPV above cricoid cartilage level was 66%.


Assuntos
Corpos Estranhos/fisiopatologia , Cervicalgia/etiologia , Faringe/fisiologia , Sensação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Corpos Estranhos/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
19.
Cancers (Basel) ; 6(4): 2369-86, 2014 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-25521853

RESUMO

Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a "real-time biopsy" and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis.

20.
Nanoscale Res Lett ; 9(1): 497, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25246875

RESUMO

In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 µM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.

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