Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
1.
Front Oncol ; 11: 738144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737955

RESUMO

Many studies reported that microRNAs (miRNAs) target autophagy-related genes to affect carcinogenesis, however, autophagy-deficiency-related miRNA dysfunction in cancer development remains poorly explored. During autophagic progression, we identified miR-449a as the most up-regulated miRNA. MiR-449a expression was low in the tumor parts of CRC patient specimens and inversely correlated with tumor stage and metastasis with the AUC (area under the curve) of 0.899 and 0.736 as well as poor overall survival rate, indicating that miR-449a has the potential to be a prognostic biomarker. In the same group of CRC specimens, low autophagic activity (low Beclin 1 expression and high p62 accumulation) was detected, which was significantly associated with miR-449a expression. Mechanistic studies disclosed that autophagy upregulates miR-449a expression through degradation of the coactivator p300 protein which acetylates the transcription factor Forkhead Box O1 (FoxO1). Unacetylated FoxO1 translocated to the nucleus and bound to the miR-449a promoter to drive gene expression. Either activation of autophagy by the inducer or overexpression of exogenous miR-449a decreases the expression of target gene LEF-1 and cyclin D1, which lead to decreased proliferation, colony formation, migration, and invasion of CRC cells. Autophagy-miR-449a-tartet genes mediated suppression of tumor formation was further confirmed in the xenograft mouse model. In conclusion, this study reveals a novel mechanism wherein autophagy utilizes miR-449a-LEF1-cyclin D1 axis to suppress CRC tumorigenesis. Our findings open a new avenue toward prognosis and treatment of CRC patients by manipulating autophagy-miR-449a axis.

2.
Pathol Res Pract ; 217: 153288, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33276219

RESUMO

Microsatellite instability (MSI) is reflective of a deficient mismatch repair (dMMR) system, which is mostly associated with the methylation of mismatch repair (MMR) genes and BRAF mutations in sporadic colorectal cancers (CRCs). We performed a retrospective study to analyze the clinicopathological features of dMMR CRCs and their association with the BRAF V600E mutation. The incidence of dMMR CRCs in our cohort was 7.4 % (118/1603). Immunohistochemistry (IHC) revealed four common dMMR IHC patterns in 116 dMMR CRCs from 110 patients. dMMR type 1 (MLH1-/PMS2-) CRCs were the most frequent pattern, usually showing typical proximal location and MSI histology. The BRAF V600E mutation was almost exclusively observed in dMMR type 1 (32 of 72) and dMMR type 2 (PMS- only, 7 of 18) CRCs (p = 0.001). Patients with dMMR type 3 (MSH2-/MSH6-) CRCs were usually diagnosed at younger ages (p < 0.001) and had the strongest family history of Lynch syndrome-associated tumors (p = 0.002). dMMR type 3 CRCs frequently presented at advanced stages (p = 0.005) with perineural invasion (p = 0.021). We also found a significant positive association of dMMR type 1 and type 3 with advanced stages of CRC, whereas dMMR types 2 and 4 (MSH6- only) were usually diagnosed at early stages of CRC (p < 0.001). In conclusion, BRAF V600E mutations almost exclusively occurred in dMMR type 1 and 2 CRCs. Patterns of MMR protein expression display distinct associations with tumor staging and age at diagnosis.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/enzimologia , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/análise , Instabilidade de Microssatélites , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos
3.
Biochem Biophys Res Commun ; 530(3): 487-493, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32595041

RESUMO

Gout is an inflammatory arthritis caused by the phagocytosis of monosodium urate (MSU) crystal deposition in joints. NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome-dependent caspase-1 activation is implicated in the processing of interleukin-1ß (IL-1ß), which is the major effector cytokine in the acute inflammatory response of gout. Mechanisms underlying caspase-1 activation remain unclear. Epidermal growth factor receptor pathway substrate no. 8 (Eps8) is a signal transducer and actin filament organizer that plays a key role in lipopolysaccharide-stimulated phagocytosis in macrophages. Here, RAW264.7 macrophages that have no intact NLRP3 inflammasomes were used to investigate the role of Eps8 in MSU crystal-mediated caspase-1 activation. A kinetic study revealed that the induction of Eps8 expression by MSU crystals occurred before NLRP3, p46/p33 caspase-1, and mature IL-1ß in RAW 264.7 cells. In addition, actin cytoskeleton dynamics was required for Eps8 induction and caspase-1 activation in MSU crystal stimulation. Silencing Eps8 had no effect on the basal expression of p46/p33 caspase-1 and NLRP3, but nearly abolished MSU crystal-induced NLRP3 expression and caspase-1 activation. Furthermore, MSU crystals induced Eps8-pro-caspase-1 complex formation and Eps8 formed a stable complex with p33 caspase-1, but not with NLRP3. In summary, our results demonstrated for the first time the importance of Eps8 in MSU crystal-mediated caspase-1 activation without the involvement of NLRP3 inflammasomes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Caspase 1/metabolismo , Gota/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Úrico/metabolismo , Animais , Ativação Enzimática/efeitos dos fármacos , Gota/patologia , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Células RAW 264.7
4.
Asian J Surg ; 43(11): 1069-1073, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31974054

RESUMO

BACKGROUND: The metastatic pattern differs between colon cancer and rectal cancer because of the distinct venous drainage systems. It is unclear whether colon cancer and rectal cancer are associated with different prognostic factors based on the anatomic difference. METHODS: We assessed the prognostic factors and survival outcomes of patients with colorectal cancer who underwent pulmonary metastasectomy (PM), disaggregated by the location of primary colorectal cancer. The Cox proportional hazards model was used to identify variables that influenced the outcomes of pulmonary metastasectomy. RESULTS: Between 2008 and 2017, 179 patients underwent PM classified into colon cancer and rectal cancer groups based on the site of origin of metastasis. The median postoperative follow-up was 2.3 years (range, 0.1-10.6). The post-PM 5-year survival rate in the colon cancer and rectal cancer groups was 42.5% and 39.9%, respectively (p = 0.310). On multivariable Cox proportional hazards analysis, presence of previous liver metastasis [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.19-4.51; p = 0.013], numbers of tumors (≥2; HR, 6.56; 95% CI, 2.07-20.79; p = 0.001), and abnormal preoperative carcinoembryonic antigen (CEA) level (HR, 2.50; 95% CI, 1.34-4.64; p = 0.001) were independent prognostic factors in patients with metastatic rectal cancer. CONCLUSIONS: Prognostic correlates of post-PM survival differ between colon and rectal cancer. Rectal cancer patients have worse prognosis if they have a history of liver metastasis, multiple pulmonary metastases, or abnormal preoperative CEA. These results may help assess the survival benefit of PM and facilitate treatment decision-making.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Idoso , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Cirurgia Torácica Vídeoassistida
5.
Cancer Lett ; 472: 97-107, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875524

RESUMO

Many Aurora-A inhibitors have been developed for cancer therapy; however, the specificity and safety of Aurora-A inhibitors remain uncertain. The Aurora-A mRNA yields nine different 5'-UTR isoforms, which result from mRNA alternative splicing. Interestingly, we found that the exon 2-containing Aurora-A mRNA isoforms are predominantly expressed in cancer cell lines as well as human colorectal cancer tissues, making the Aurora-A mRNA exon 2 a promising treatment target in Aurora-A-overexpressing cancers. In this study, a selective siRNA, siRNA-2, which targets Aurora-A mRNA exon 2, was designed to translationally inhibit the expression of Aurora-A in cancer cells but not normal cells; locked nucleic acid (LNA)-modified siRNA-2 showed improved efficacy in inhibiting Aurora-A mRNA translation and tumor growth. Xenograft animal models combined with noninvasion in vivo imaging system (IVIS) analysis further confirmed the anticancer effect of LNA-siRNA-2 with improved efficiency and safety and reduced side effects. Mice orthotopically injected with colorectal cancer cells, LNA-siRNA-2 treatment not only inhibited the tumor growth but also blocked liver and lung metastasis. The results of our study suggest that LNA-siRNA-2 has the potential to be a novel therapeutic agent for cancer treatment.


Assuntos
Aurora Quinase A/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Isoformas de Proteínas/genética , Regiões 5' não Traduzidas/efeitos dos fármacos , Processamento Alternativo/genética , Animais , Aurora Quinase A/antagonistas & inibidores , Neoplasias Colorretais/patologia , Células HCT116 , Humanos , Camundongos , Metástase Neoplásica , Oligonucleotídeos/farmacologia , Isoformas de Proteínas/antagonistas & inibidores , RNA Mensageiro/genética , RNA Interferente Pequeno/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Cancer Manag Res ; 11: 7867-7875, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692488

RESUMO

PURPOSE: Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in colorectal cancer (CRC). Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been used to determine HER2-positive CRCs; however, the clinical utility of next-generation sequencing (NGS)-based techniques for determining HER2 status in CRC has been limited. Here, we detail our experience regarding the assessment of HER2 alterations in a CRC cohort. MATERIALS AND METHODS: We prospectively enrolled 73 CRC patients who underwent surgery and received adjuvant oxaliplatin treatment. We then examined HER2 alterations using the Oncomine Comprehensive Assay version 1, as well as clinical outcomes, in this cohort. RESULTS: Using the NGS-based assay, HER2 copy number gains in 12 of 73 CRCs were determined to range from 2.74 to 92.62. Of these 12 tumors, 6 had HER2 high-level copy number gain (92.6, 57.9, 57.0, 52.0, 35.2, and 8.42) and were all defined as HER2-positive CRC using HERACLES Diagnostic Criteria. Nevertheless, other 6 patients with low-level copy number gain (ranging from 2.74 to 3.04) and the remaining 61 patients without increase in HER2 copy number were all HER2-negative. Among the 6 HER2-positive CRCs, KRAS and PIK3CA mutations were detected in 1 (17%; G13D) and 2 (33.3%; 1 Q546R and 1 H1047R) patients, respectively. Moreover, 2 of the 6 (33.3%) HER2-positive patients had recurrent disease, while one patient had a partial response after anti-HER2 therapy. CONCLUSION: NGS-based tools could assist in the simultaneous detection of HER2 and other genomic alterations in patients with CRC. Only CRCs with HER2 high-level copy number gain were HER2-postive by current diagnostic criteria.

7.
BMJ Open ; 9(10): e028892, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601586

RESUMO

OBJECTIVES: This study aimed to determine colorectal cancer (CRC) risks among patients with gout through a follow-up study on a nationwide population-based cohort that included patients with gout and the general population in Taiwan. PARTICIPANT: From the Taiwan National Health Insurance Research Database, we identified 28 061 patients who were newly diagnosed with gout between 2000 and 2010 as the study cohort. We randomly selected 84 248 subjects matching in gender, age and baseline year as comparison cohort. The cohorts were followed up until CRC occurrence, withdrawal from the system of National Health Insurance, or Dec. 31, 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: Cumulative incidences and incidence rate ratios (IRRs) of CRC between two cohorts were examined. The Cox proportional hazards model was used to evaluate risk factors associated with CRC development. RESULTS: During the 13-year follow-up, the incidence rate of CRC development in the gout cohort reached 2.44 per 1000 person-years, which was higher than the 2.13 per 1000 person-years in the control cohort (IRR=1.15; 95% CI 1.04 to 1.26). After adjusting for age, gender, urbanisation status and comorbidities, including hypertension, diabetes and hyperlipidaemia, gout showed no significant association with increased risk of CRC occurrence (adjusted HR=1.03; 95% CI 0.93 to 1.14). CONCLUSIONS: Similar risks of CRC incidence were observed in patients with and without gout in Taiwan. Allopurinol and colchicine are commonly used as urate-lowering drug and anti-inflammation medication in Taiwan and had been shown to reduce the risk of CRC incidence. Thus, further pharmaco-epidemiological studies should be carried out to specifically assess the role of allopurinol in the relationship between gout and CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Gota/epidemiologia , Adulto , Idoso , Alopurinol/uso terapêutico , Colchicina/uso terapêutico , Comorbidade , Bases de Dados Factuais , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Gota/tratamento farmacológico , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
8.
Medicina (Kaunas) ; 55(4)2019 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-31013982

RESUMO

Background and objective: Risk of secondary prostate cancer after radiation therapy among patients with rectal cancer remains undetermined. Given an increased incidence of rectal cancer in younger people and improved survival for rectal cancer patients who received radiation therapy, the potential risk of secondary prostate cancer needs to be further investigated. Materials and Methods: Male patients (n = 11,367) newly diagnosed rectal cancer and who underwent abdominoperineal resection (APR) or low anterior resection (LAR) from 1 January, 1998 to 31 December, 2010 were identified from Taiwan National Health Insurance Research Database. The incidence and relative risk of secondary prostate cancer in study patients with (n = 1586) and without (n = 9781) radiotherapy within one year after rectal cancer diagnosis were compared using a competing-risks analysis. Results: Rectal cancer patients with radiotherapy were at a significantly decreased risk of developing prostate cancer, with a hazard ratio (HR) of 0.41 (95% confidence interval = 0.20⁻0.83) after adjustment for age. Analysis of the risk estimated for various follow-up lengths suggested that a decreasing HR was seen through the period followed-up and that there was a trend of decreasing prostate cancer risk with time after radiotherapy. Conclusions: Radiotherapy was significantly associated with decreased risk of secondary prostate cancer among rectal cancer patients, by a magnitude of 59%.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/epidemiologia , Radioterapia Adjuvante/efeitos adversos , Neoplasias Retais/epidemiologia , Neoplasias Retais/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taiwan/epidemiologia , Adulto Jovem
9.
EBioMedicine ; 43: 270-281, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30982765

RESUMO

BACKGROUND: In our preliminary screening, expression of miR-338-5p was found to be higher in primary colorectal cancer (CRC) with metastasis. The autophagy related gene- phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3) appeared to be targeted by miR-338-5p. Here, we provide solid evidence in support of PIK3C3 involved in miR-338-5p related metastasis of CRC in vitro and in vivo. METHODS: The potential clinical relevance of miR-338-5p and its target gene was analysed on benign colorectal polyps and primary CRCs by QPCR. Mouse spleen xenograft experiment was performed to examine the importance of miR-338-5p for metastasis. FINDINGS: PIK3C3 was one of target genes of miR-338-5p. In primary CRCs, expression of miR-338-5p is positively related to tumour staging, distant metastasis and poor patient survival. Patients with higher ratios of miR-338-5p/PIK3C3 also had significantly poor overall survival, supporting their significance in the progression of CRC. Over-expression of miR-338-5p promotes CRC metastasis to the liver and lung in vivo, in which PIK3C3 was down-regulated in the metastatic tumours. In contrast, overexpression of PIK3C3 in miR-338-5p stable cells inhibited the growth of metastatic tumours. Both migration and invasion of CRC in vitro induced by miR-338-5p are mediated by suppression of PIK3C3. Using forward and reverse approaches, autophagy was proved to involve in CRC migration and invasion induced by miR-338-5p. INTERPRETATION: MiR-338-5p induces migration, invasion and metastasis of CRC in part through PIK3C3-related autophagy pathway. The miR-338-5p/PIK3C3 ratio may become a prognostic biomarker for CRC patients. FUND: NCKU Hospital, Taiwan, Ministry of Science and Technology, Taiwan.


Assuntos
Autofagia/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Interferência de RNA , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Exp Mol Med ; 50(6): 1-14, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29884818

RESUMO

Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been implicated in many post-transcriptional processes, including RNA metabolism and mRNA splicing and translation. However, the role of hnRNP Q1 in tumorigenesis remains unclear. We previously performed RNA immunoprecipitation (RIP)-seq analysis to identify hnRNP Q1-interacting mRNAs and found that hnRNP Q1 targets a group of genes that are involved in mitotic regulation, including Aurora-A. Here, we demonstrate that altering the hnRNP Q1 level influences the expression of the Aurora-A protein, but not its mRNA. Stimulation with epidermal growth factor (EGF) enhances both binding between hnRNP Q1 and Aurora-A mRNA as well as the efficacy of the hnRNP Q1-induced translation of Aurora-A mRNA. The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways. In addition, we show that hnRNP Q1 up-regulates the translation of a group of spindle assembly checkpoint (SAC) genes. hnRNP Q1 overexpression is positively correlated with the levels of Aurora-A and the SAC genes in human colorectal cancer tissues. In summary, our data suggest that hnRNP Q1 plays an important role in regulating the expression of a group of cell cycle-related genes. Therefore, it may contribute to tumorigenesis by up-regulating the translation of these genes in colorectal cancer.


Assuntos
Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Sistema de Sinalização das MAP Quinases , Mitose , Proteínas de Neoplasias/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fator de Crescimento Epidérmico/genética , Células HCT116 , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Proteínas de Neoplasias/genética
11.
Sci Rep ; 7(1): 5823, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28725043

RESUMO

Downregulation of Mucin 2 (MUC2) expression is associated with early carcinogenesis events in colon cancer. MUC2 plays a role in the progression of colon cancer, and reduced MUC2 protein expression correlates with increased interleukin-6 (IL-6) expression. However, the interaction between MUC2 and IL-6 in colorectal cancer metastasis remains unclear. We systematically analyzed MUC2 and IL-6 expression and determined the survival of cancer patients with high or low MUC2 and IL-6 expression using the Oncomine and PrognoScan databases, respectively. This analysis identified downregulation of MUC2 and overexpression of IL-6 in colon cancer but not in normal colon tissue, and this expression pattern was correlated with poor survival of colon cancer patients. We examined the effects of MUC2 on colon cancer metastasis and used vector-mediated application of short hairpin RNA (shRNA) to suppress MUC2 expression. MUC2 suppressed the migration of colon cancer cells in vitro and dramatically diminished liver metastases in vivo. Treatment with IL-6 increased signal transducer and activator of transcription 3 (STAT3) phosphorylation, promoted checkpoint kinase 2 (Chk2) activation, attenuated cAMP response element-binding protein (CREB) phosphorylation, and suppressed E-cadherin protein expression in MUC2-silenced HT-29 cancer cells. Most importantly, MUC2 is a potential prognostic indicator for colon cancer.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Inativação Gênica , Interleucina-6/metabolismo , Neoplasias Hepáticas/secundário , Mucina-2/genética , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-6/genética , Estimativa de Kaplan-Meier , Macrófagos/metabolismo , Camundongos , Mucina-2/metabolismo , Transdução de Sinais
12.
Cancer Res ; 77(16): 4305-4316, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28652251

RESUMO

Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here, we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of COX-2-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2-induced tumor growth and cancer stemness. Genome-wide profile analysis revealed that genes regulated by DUSP2 were similar to those controlled by histone deacetylase. Indeed, treatment with novel histone deacetylase inhibitors abolished hypoxia-induced DUSP2 downregulation, COX-2 overexpression, cancer stemness, tumor growth, and drug resistance. Our findings illuminate mechanisms of cancer stemness and suggest new cancer therapy regimens. Cancer Res; 77(16); 4305-16. ©2017 AACR.


Assuntos
Hipóxia Celular/fisiologia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Fosfatase 2 de Especificidade Dupla/metabolismo , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Animais , Células CACO-2 , Linhagem Celular Tumoral , Regulação para Baixo , Células HCT116 , Células HT29 , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos SCID , Transdução de Sinais
13.
Oncotarget ; 8(21): 35165-35175, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-28422723

RESUMO

Colorectal mucinous adenocarcinoma (MAC) and serrated adenocarcinoma (SAC) share many characteristics, including right-side colon location, frequent mucin production, and various molecular features. This study examined the frequency of SAC morphology in MACs. We assessed the correlation of SAC morphology with clinicopathological parameters, molecular characteristics, and patient prognosis. Eighty-eight colorectal MACs were collected and reviewed for SAC morphology according to Makinen's criteria. We sequenced KRAS and BRAF, assessed CpG island methylator phenotype (CIMP) frequency, and analyzed DNA mismatch repair enzyme levels using immunohistochemistry in tumor samples. SAC morphology was observed in 38% of MACs, and was associated with proximal location (P=0.001), BRAF mutation (P=0.042), CIMP-positive status (P=0.023), and contiguous traditional serrated adenoma (P=0.019). Multivariate analysis revealed that MACs without both SAC morphology and CIMP-positive status exhibited 3.955 times greater risk of cancer relapse than MACs having both characteristics or either one (P=0.035). Our results show that two MAC groups with distinct features can be identified using Makinen's criteria, and suggest a favorable prognostic role for the serrated neoplastic pathway in colorectal MAC.


Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias Colorretais/patologia , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma Mucinoso/classificação , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismo , Idoso , Neoplasias Colorretais/classificação , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ilhas de CpG , Metilação de DNA , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sequência de DNA , Análise de Sobrevida
14.
Cell Death Dis ; 8(1): e2555, 2017 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-28079881

RESUMO

By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5'-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1. Overexpression of hnRNP Q1 promotes cell proliferation and tumor growth. HnRNP Q1/ΔRBD23-truncated mutant, which loses the binding ability and translational regulation of Aurora-A mRNA, has no effect on promoting tumor growth. The expression level of hnRNP Q1 is positively correlated with Aurora-A in colorectal cancer. Taken together, our data indicate that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A mRNA 5'-UTRs and regulates its translation, which increases cell proliferation and contributes to tumorigenesis in colorectal cancer.


Assuntos
Aurora Quinase A/genética , Carcinogênese/genética , Neoplasias Colorretais/genética , Ribonucleoproteínas Nucleares Heterogêneas/genética , Aurora Quinase A/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Masculino , Proteínas com Motivo de Reconhecimento de RNA , RNA Mensageiro/genética
15.
Int J Colorectal Dis ; 32(1): 155-157, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27844203

RESUMO

INTRODUCTION: Tension-free mesh repair is a widely used hernioplasty technique. However, mesh migration is a severe complication that may induce colon inflammation or perforation and can occur several months to several years following hernioplasty. CASE REPORT: We present a case where mesh migrated into the sigmoid colon 12 years postoperation and was mistaken for a colon tumor.


Assuntos
Colo Sigmoide/patologia , Neoplasias do Colo/diagnóstico , Herniorrafia/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera/patologia
16.
Oncotarget ; 7(47): 76852-76866, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27764771

RESUMO

MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis. By cell model and xenograft animal model, the enforced expression of miR-137 in colorectal cancer cells can inhibit cell proliferation and tumor formation, induce G2/M arrest, and lead to apoptosis. The expression pattern of miR-137 and Aurora-A or PTGS2 is negatively correlated in human colorectal cancer tissues and colon polyps. Those effects induced by overexpressed miR-137 can be rescued by the overexpression of Aurora-A. In summary, our study suggests that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the tendency toward to CRC formation through the impaired inhibitory effect of Aurora-A. The investigation of the regulatory mechanism of miR-137-mediated Aurora-A inhibition may shed new light on the early prognosis of cancer therapy for CRC in the future.


Assuntos
Aurora Quinase A/genética , Pólipos do Colo/genética , Neoplasias Colorretais/genética , Ciclo-Oxigenase 2/genética , Metilação de DNA , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias
17.
PLoS One ; 11(7): e0158844, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27383761

RESUMO

Colorectal cancer is the most common form of cancer in the world, and the five-year survival rate is estimated to be almost 90% in the early stages. Therefore, the identification of potential biomarkers to assess the prognosis of early stage colorectal cancer patients is critical for further clinical treatment. Dysregulated tyrosine phosphorylation has been found in several diseases that play a significant regulator of signaling in cellular pathways. In this study, this strategy was used to characterize the tyrosine phosphoproteome of colorectal cell lines with different progression abilities (SW480 and SW620). We identified a total of 280 phosphotyrosine (pTyr) peptides comprising 287 pTyr sites from 261 proteins. Label-free quantitative analysis revealed the differential level of a total of 103 pTyr peptides between SW480 and SW620 cells. We showed that cyclin-dependent kinase I (CDK1) pTyr15 level in SW480 cells was 3.3-fold greater than in SW620 cells, and these data corresponded with the label-free mass spectrometry-based proteomic quantification analysis. High level CDK1 pTyr15 was associated with prolonged disease-free survival for stage II colorectal cancer patients (n = 79). Taken together, our results suggest that the CDK1 pTyr15 protein is a potential indicator of the progression of colorectal cancer.


Assuntos
Proteína Quinase CDC2/metabolismo , Neoplasias Colorretais/metabolismo , Fosfoproteínas/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Fosfopeptídeos/metabolismo , Fosfotirosina/metabolismo , Prognóstico , Estudos Retrospectivos
18.
J Formos Med Assoc ; 115(8): 609-18, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27302557

RESUMO

BACKGROUND/PURPOSE: This study aims to examine the cost effectiveness of treating major cancers compared with other major illnesses in Taiwan. METHODS: We collected data on 395,330 patients with cancer, 125,277 patients with end-stage renal disease, and 50,481 patients under prolonged mechanical ventilation during 1998-2007. They were followed for 10-13 years to estimate lifetime survival functions using a semiparametric method. EuroQol five-dimension was used to measure the quality of life for 6189 cancer patients and 1401 patients with other illnesses. The mean utility values and healthcare costs reimbursed by the National Health Insurance were multiplied with the corresponding survival probabilities to estimate quality-adjusted life expectancies and lifetime costs, respectively. Data of 22,344 cancer patients under hospice care (considered as a comparison group) were used to conduct a cost-effectiveness analysis. Sensitivity analysis was conducted by assuming patients without treatment survived for 2 years with a quality of life value of 0.5. RESULTS: The costs of care for patients under prolonged mechanical ventilation and those with end-stage renal disease were US$41,780-53,708 per quality-adjusted life year (QALY) and US$18,222-18,465 per QALY, respectively, which are equivalent to 2.17-2.79 gross domestic product (GDP) per capita per QALY and 1.18-1.25 GDP per capita per QALY. The costs of care for the nine different cancers were less than 1 GDP per capita per QALY, with those of lung, esophagus, and liver cancers being the highest. Sensitivity analysis showed the same conclusion. Lifetime risks of six out of nine cancer sites show an increased trend. CONCLUSION: Cancer care in Taiwan seemed cost effective compared with that of other illnesses, but prevention is necessary to make the National Health Insurance more sustainable.


Assuntos
Análise Custo-Benefício , Gastos em Saúde , Neoplasias/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/economia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Neoplasias/terapia , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Sistema de Registros , Respiração Artificial/economia , Taiwan
19.
World J Surg ; 40(4): 895-905, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26711638

RESUMO

Literature about the risk of secondary cancer after radiation therapy (RT) of prostate and rectal cancer reveals contradictory results. We conducted a meta-analysis to examine whether the RT induces secondary rectal or prostate cancer in patients, respectively, with prostate or rectal cancer. All studies published in Medline or Pubmed up to March 3, 2015, containing RT of primary rectal or prostate cancer, and providing risk estimates of secondary prostate or rectal cancer were considered as eligible. Relative risk (RR) and standardized incidence ratios (SIR) were calculated using the random-effects model. Twenty studies met the inclusion criteria. 12 of them were from the Surveillance, Epidemiology, and End Results (SEER) database. For prostate cancer patients, pooled adjusted RRs or SIRs did not show an effect on the risk of secondary rectal cancer. However, notwithstanding the limitations of SEER-based studies, the subgroup of prostate cancer patients receiving external beam radiation therapy (EBRT) showed an increased risk of rectal cancer. For rectal cancer patients, pooled adjusted RR of prostate cancer was 1.12 (95 % CI, 0.44-2.8) and SIR was 0.40 (95 % CI, 0.29-0.55). All studies included in the SIR analysis of rectal cancer were derived from the SEER data source. Based on current evidence, RT for prostate cancer patients had no effect on rectal cancer incidence, except for patients who received EBRT therapy. However, compared with the general population, RT for rectal cancer is associated with a decreased prostate cancer risk as found in SEER-based studies.


Assuntos
Braquiterapia/estatística & dados numéricos , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/radioterapia , Neoplasias Retais/radioterapia , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/epidemiologia , Radioterapia/estatística & dados numéricos , Neoplasias Retais/epidemiologia , Fatores de Risco
20.
PLoS One ; 10(7): e0133755, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26207912

RESUMO

BACKGROUNDS AND AIMS: Life-expectancy of colon cancer patients cannot be accurately answered due to the lack of both large datasets and long-term follow-ups, which impedes accurate estimation of lifetime cost to treat colon cancer patients. In this study, we applied a method to estimate life-expectancy of colon cancer patients in Taiwan and calculate the lifetime costs by different stages and age groups. METHODS: A total of 17,526 cases with pathologically verified colon adenocarcinoma between 2002 and 2009 were extracted from Taiwan Cancer Registry database for analysis. All patients were followed-up until the end of 2011. Life-expectancy, expected-years-of-life-lost and lifetime costs were estimated, using a semi-parametric survival extrapolation method and borrowing information from life tables of vital statistics. RESULTS: Patients with more advanced stages of colon cancer were generally younger and less co-morbid with major chronic diseases than those with stages I and II. The LE of stage I was not significantly different from that of the age- and sex-matched general population, whereas those of stages II, III, and IV colon cancer patients after diagnosis were 16.57 ± 0.07, 13.35 ± 0.07, and 4.05 ± 0.05 years, respectively; the corresponding expected-years-of-life-lost were 1.28 ± 0.07, 5.93 ± 0.07 and 16.42 ± 0.06 years, significantly shorter than the general population after accounting for lead time bias. Besides, the lifetime cost of managing stage II colon cancer patients would be US $8,416 ± 1939, 14,334 ± 1,755, and 21,837 ± 1,698, respectively, indicating a big saving for early diagnosis and treatment after stratification for age and sex. CONCLUSIONS: Treating colon cancer at younger age and earlier stage saves more life-years and healthcare costs. Future studies are indicated to apply these quantitative results into the cost-effectiveness evaluation of screening program for colon cancers.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias do Colo/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Adenocarcinoma/economia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Doença Crônica/epidemiologia , Neoplasias do Colo/economia , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Comorbidade , Análise Custo-Benefício , Detecção Precoce de Câncer , Seguimentos , Humanos , Expectativa de Vida , Estadiamento de Neoplasias , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Taiwan/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA