Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 104
Filtrar
1.
Int J Med Robot ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33289238

RESUMO

BACKGROUND: We present our initial single-center experience with Senhance surgical robot-assisted colorectal surgery and examine its safety and feasibility. METHODS: From June 2019 to December 2019, patients who underwent Senhance surgical robot-assisted colorectal surgery in our hospital were retrospectively analyzed. We focused on the short-term outcomes. RESULTS: In total, 46 patients were enrolled in the study. Colorectal cancer was the most common indication for surgery (39 patients). The median total operation time was 283 min, and the median blood loss was 50 cc. Meanwhile, the median number of harvested lymph nodes was 20. Elderly age, advanced American Society of Anesthesiologists (ASA) stage, and right-sided colon surgery were associated with the occurrence of complications greater than grade III. CONCLUSION: Our findings demonstrate the feasibility and safety of the Senhance surgical robotic system in colorectal surgery. Care should be taken regarding the indications and patient selection. This article is protected by copyright. All rights reserved.

2.
Cancers (Basel) ; 12(11)2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33238621

RESUMO

BACKGROUND: The 5'-C-phosphate-G-3' island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. METHODS: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. RESULTS: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of BRAF, POLD1, MSH3, and SMAD4 mutations but lower frequencies of APC, TP53, and KRAS mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. CONCLUSIONS: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.

3.
J Gastrointest Surg ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201458

RESUMO

BACKGROUND: The effects of primary tumor location on colorectal liver metastasis (CRLM) and post-hepatic-metastasectomy overall survival (OS) are controversial. This study evaluated the difference in post-hepatic-metastasectomy OS among right-sided colon, left-sided colon, and rectal cancer groups. METHODS: In total, 381 patients who underwent curative-intent CRLM resection were enrolled. Patients were grouped based on the primary tumor location (right-sided, left-sided, and rectum). The Kaplan-Meier analysis and log-rank test were performed for survival analysis. The univariate and multivariate analyses of clinical and pathological factors were performed using the Cox proportional hazards model. RESULTS: Significant OS difference was noted among the three groups (log-rank, p = 0.014). The multivariate analysis revealed a 32% lower death risk in left-sided colon cancer compared with right-sided colon cancer (hazard ratio [HR] 0.68, p = 0.042), whereas no OS difference was noted between the rectal cancer and right-sided colon cancer groups. The left- versus right-sided OS advantage was noted only in the KRAS wild-type subgroup (HR 0.46, p = 0.002), and a rectal versus right-sided OS disadvantage was noted in the KRAS mutant subgroup (HR 1.78, p = 0.03). CONCLUSIONS: The CRLM post-hepatic-metastasectomy OS was superior in left-sided colon cancer than in right-sided colon cancer and was similar in rectal and right-sided colon cancer. The OS difference in different primary tumor locations is dependent on KRAS mutation status, with a decreased left- versus right-sided death risk noted only in KRAS wild-type colon cancer and an increased rectal versus right-sided death risk noted only in KRAS mutant colon cancer.

4.
Ann Surg Oncol ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32875464

RESUMO

BACKGROUND: Taiwan has witnessed a surge in the incidence of colorectal cancer (CRC), of which 40-60% metastasize. Continuous updating of cytoreductive strategies in metastatic CRC (mCRC) has contributed to median overall survival reaching 40 months. In this changing scenario, to standardize the approaches across Taiwan, a group of experts from the Taiwan Society of Colon and Rectal Surgeons (TSCRS) convened to establish evidence- and opinion-based recommendations for defining the criteria of "resectability" in mCRC. METHODS: Over the course of one-on-one consultations, lasting 30-40 min each, with 30 medical specialists (19 colorectal surgeons, 4 general surgeons, and 7 medical oncologists) from 16 hospitals in Taiwan followed by a 2-h meeting with 8 physician experts (3 general surgeons, 4 colorectal surgeons, and 1 thoracic surgeon), 12 key questions on cytoreduction were addressed. This was further contextualized based on published literature. RESULTS: The final consensus includes eight recommendations regarding the criteria for metastasis resection, role of local control treatment in liver potentially resectable patients, management of synchronous liver metastases, approach for peritoneal metastasis, place for resection in multiple-organ metastasis, and general criteria for resectability. CONCLUSIONS: mCRC patients undergoing R0 resection have the greatest survival advantage following surgery. Our role as a multidisciplinary team (MDT) should be to treat potentially resectable mCRC patients as rapidly and safely as possible, and achieve R0 resection as far as possible and for as long as possible (continuum of care). This TSCRS consensus statement aims to help build clinical capacity within the MDTs, while making better use of existing healthcare resources.

5.
J Gastrointest Surg ; 24(5): 1092-1100, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31140063

RESUMO

BACKGROUND OR PURPOSE: To compare the cost-performance between planned short-course radiation and upfront concurrent chemoradiation on metastatic rectal cancer. METHODS: A total of 75 patients with metastatic rectal cancer who underwent planned short-course radiation or upfront concurrent chemoradiation were enrolled. The Kaplan-Meier method was used to compute the survival rates. The χ2 test was used to compare baseline characteristics. The Cox proportional hazards model was applied to determine the prognostic influence of clinicopathological factors. RESULTS: The planned short-course radiation is superior to upfront concurrent chemoradiation in overall survival for the patients with metastatic rectal cancer (34.8 vs. 20.2 months, P = 0.010). The planned short-course radiation was an independent prognostic factor (P = 0.009, HR (95% CI) = 0.319(0.135-0.752)). The efficacy of radiation on downstaging was similar between planned short-course radiation and upfront concurrent chemoradiation. The total cost of concurrent chemoradiation is 4.52-fold more expensive than that of short-course radiation (340,142 vs. 75,106 NT dollars, respectively). CONCLUSIONS: Based on the impressive cost-performance of planned short-course radiation compared with upfront concurrent chemoradiation (better OS, modest downstaging and lower cost), planned short-course radiation should be the preferred radiation approach for managing metastatic rectal cancer.

6.
Am J Clin Oncol ; 43(1): 28-34, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693507

RESUMO

BACKGROUND: Both regorafenib and reduced-intensity FOLFOXIRI (riFOLFOXIRI) prolong survival in patients with metastatic colorectal cancer (mCRC). However, the sequence in which they should be administrated first in late-line treatment for refractory mCRC remains unclear. PATIENTS AND METHODS: This study was a single-center retrospective cohort study that reviewed data from patients at Taipei Veterans General Hospital, Taiwan, with mCRC refractory to fluorouracil, irinotecan, oxaliplatin, cetuximab (wild-type RAS), and bevacizumab. Patients were divided into 2 groups: a regorafenib-first group and a riFOLFOXIRI-first group. The Kaplan-Meier method and log-rank test were used to analyze survival, and a Cox proportional hazards model was used for univariate, multivariate, and subgroup analyses. RESULTS: A total of 136 and 55 patients followed a regorafenib-first or riFOLFOXIRI-first treatment strategy, respectively. At baseline, patient characteristics were similar between the groups, except for younger age in the riFOLFOXIRI-first group. The regorafenib-first group had better overall survival (13.8 vs. 10.7 mo, P=0.038), whereas patients in the riFOLFOXIRI-first group had a better partial response rate (P=0.005) but a higher rate of discontinuation due to adverse effects (P=0.004) and cross-over to regorafenib (P<0.001). Thus, no significant difference was observed in progression-free survival (regorafenib-first strategy: 3.17 mo; riFOLFOXIRI-first strategy: 4.97 mo; P=0.624). Regorafenib-first strategy, sex, and pathology were identified as independent prognostic factors. Subgroup analysis indicated that younger age, better performance status, stage IV disease, and mutant RAS gene favored the regorafenib-first strategy. CONCLUSION: Treatment with regorafenib-first followed by riFOLFOXIRI resulted in better overall survival when given as late-line treatment for patients with refractory mCRC.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Terapia de Salvação , Adenocarcinoma Mucinoso/secundário , Idoso , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano/administração & dosagem , Masculino , Oxaliplatina/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida
7.
Cancer Med ; 9(2): 476-486, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769227

RESUMO

BACKGROUND: We assumed that targeted next-generation sequencing (NGS) of mismatch repair-associated genes could improve the detection of driving mutations in colorectal cancers (CRC) with microsatellite instability (MSI) and microsatellite alterations at selected tetranucleotide repeats (EMAST) and clarify the somatic mutation patterns of CRC subtypes. MATERIAL AND METHODS: DNAs from tumors and white blood cells were obtained from 81 patients with EMAST(+)/MSI-high (MSI-H), 78 patients with EMAST(+)/microsatellite stable (MSS), and 72 patients with EMAST(-)/MSI-H. The germline and somatic mutations were analyzed with a 16-genes NGS panel. RESULTS: In total, 284 germline mutations were identified in 161 patients. The most common mutations were in EPCAM (24.8%), MSH6 (24.2%), MLH1 (21.7%), and AXIN2 (21.7%). Germline mutations of AXIN2, POLE, POLD1, and TGFBR2 also resulted in EMAST and MSI. EMAST(+)/MSI-H tumors had a significant higher mutation number (205.9 ± 95.2 mut/MB) than tumors that were only EMAST(+) or MSI-H (118.6 ± 64.2 and 106.2 ± 54.5 mut/MB, respectively; both P < .001). In patients with AXIN2 germline mutations, the number of pathological somatic mutations in the tumors was significantly higher than those without AXIN2 germline mutations (176.7 ± 94.2 mut/MB vs 139.6 ± 85.0 mut/MB, P = .002). CONCLUSION: Next-generation sequencing could enhance the detection of familial CRC. The somatic mutation burden might result from not only the affected genes in germline mutations but also through the dysfunction of downstream effectors. The AXIN2 gene might associate with hypermutation in tumors. Further in vitro experiments to confirm the causal relationship is deserved.

8.
BMC Cancer ; 19(1): 640, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253124

RESUMO

BACKGROUND: In the management of patients with RAS wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) therapies have demonstrated a clinical benefit, with longer survival. However, the correlation between the emergence of circulating RAS mutations and secondary resistance to anti-EGFR therapies requires further elucidation. In this study, we aim to examine evolutionary changes in RAS mutations through liquid biopsy in patients with mCRC during and after anti-EGFR therapy. METHODS: A total of 120 patients diagnosed with RAS wild-type mCRC will be enrolled in this study. Patients will receive a cetuximab-based infusional 5-fluorouracil regimen as first-line treatment. Cetuximab-based treatment is expected to continue until disease progression, intolerable toxic effects, or withdrawal of consent. Blood samples from enrolled patients will be collected before and then every 3 months during cetuximab-based treatment and also at disease progression. These blood samples will be evaluated for RAS resistance mutations by using the MassARRAY platform. The primary endpoint is the percentage of RAS mutations detected in circulating DNA from patients during cetuximab treatment. The correlation between the tumor response and survival outcomes of these patients and the emergence of circulating RAS mutations will be further analyzed. DISCUSSION: Liquid biopsy is a powerful technology that can represent tumor heterogeneity in a relatively noninvasive manner. Because RAS mutations play a major role in resistance to anti-EGFR therapy for mCRC, examining evolutionary changes in these mutations during such treatment through liquid biopsy would be useful. After comprehensively analyzing the emergence of circulating RAS mutations and its clinical relevance in this study, our results should provide practical guidance on anti-EGFR therapy for mCRC. TRIAL REGISTRATION: The date of trial registration ( NCT03401957 ) in this study was January 17, 2018.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas ras/genética , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Protocolos Clínicos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/secundário , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Biópsia Líquida , Mutação , Análise de Sobrevida , Resultado do Tratamento , Proteínas ras/sangue
9.
PLoS One ; 14(6): e0218436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31199857

RESUMO

Whether there are subsequent changes of metabolic profiles and microbiota status after partial colectomy remains unknown. We evaluated and compared long-term effects of microbiota status and metabolic profiles in early colorectal cancer (CRC) patients after curative colectomy to the controls. In this cross-sectional study, we analyzed metabolic syndrome occurrence in 165 patients after curative partial colectomy with right hemicolectomy (RH) or low anterior resection (LAR) and 333 age-sex matched controls. Fecal samples from some of those with RH, LAR, and controls were analyzed by next-generation sequencing method. The occurrences of metabolic syndrome were significantly higher in patients after RH, but not LAR, when compared with the controls over the long term (> 5 years) follow-up (P = 0.020). Compared with control group, RH group showed lower bacterial diversity (P = 0.007), whereas LAR group showed significantly higher bacterial diversity at the genera level (P = 0.016). Compared with the control group, the principal component analysis revealed significant differences in bacterial genera abundance after RH and LAR (P < 0.001). Furthermore, the Firmicutes to Bacteroidetes ratio was significantly lower in the RH group than the control group (22.0% versus 49.4%, P < 0.05). In conclusion, early CRC patients after RH but not LAR were associated with a higher occurrence of metabolic syndrome than the controls during long-term follow-up. In parallel with metabolic change, patients with RH showed dysbiosis with a tendency to decreased richness and a significant decrease in the diversity of gut microbiota.


Assuntos
Neoplasias Colorretais/metabolismo , Metabolismo Energético , Microbioma Gastrointestinal , Adolescente , Biomarcadores , Criança , Colectomia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Período Pós-Operatório
10.
J Cancer Res Clin Oncol ; 145(7): 1785-1794, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129768

RESUMO

PURPOSE: To investigate the associations between programmed cell death ligand-1 (PD-L1) on tumor cells (TCs) or PD-L1 on tumor-infiltrating immune cells (TIICs) and the microsatellite instability (MSI) status in colorectal cancer (CRC). METHODS: In total, 238 CRC patients were enrolled. PD-L1 expression and MSI status were studied by immunohistochemical staining and polymerase chain reaction. The χ2 test was used to compare characteristics. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards models were used to determine the prognostic influence of clinicopathological factors. RESULTS: Eighteen patients (7.6%) were had MSI-high (MSI-H) CRC. The number of patients with PD-L1 expression on TCs, stromal TIICs and intraepithelial TIICs was 13 (5.5%), 64 (26.9%) and 45 (18.9%), respectively. The MSI-H phenotype was significantly associated with younger age, right sidedness, mucinous component, high grade, stromal TIICs expressing PD-L1 (P = 0.042) and intraepithelial TIICs expressing PD-L1 (P < 0.001), but not TCs expressing PD-L1. PD-L1-expressing TCs were an independent marker of poor prognosis [hazard ratio (HR) = 3.387, P = 0.003], and PD-L1-expressing stromal TIICs were an independent marker of good prognosis (HR = 0.551, P < 0.001). CONCLUSIONS: PD-L1-expressing TCs were a marker of poor prognosis; in contrast, PD-L1-expressing TIICs were a marker of good prognosis. The MSI-H phenotype was associated with the presence of PD-L1-expressing TIICs, but not of PD-L1-expressing TCs.


Assuntos
Antígeno B7-H1/biossíntese , Antígeno B7-H1/imunologia , Neoplasias Colorretais/imunologia , Idoso , Neoplasias Colorretais/genética , Feminino , Humanos , Sistema Imunitário/patologia , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais
11.
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
12.
Int J Biol Markers ; 34(1): 47-53, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30854932

RESUMO

PURPOSE: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). MATERIALS AND METHODS: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. RESULTS: A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). CONCLUSIONS: In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-ß, PIK3CA, PTEN, AKT1, and high microsatellite instability.


Assuntos
Adenocarcinoma Mucinoso/secundário , Adenocarcinoma/secundário , Carcinoma de Células em Anel de Sinete/secundário , Neoplasias Colorretais/patologia , Cirurgia Colorretal/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Peritoneais/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/cirurgia , Idoso , Carcinoma de Células em Anel de Sinete/cirurgia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/cirurgia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
13.
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.

14.
Mol Oncol ; 12(10): 1706-1717, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30063110

RESUMO

Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogene, and its expression has been correlated with the prognosis of patients with cancer. In this study, we aimed to explore the relationship between ER stress-related ATF signaling and CIP2A. We found that CIP2A expression was positively correlated with ATF6 expression by analyzing publicly available RNA sequence data of patients with colorectal cancer (The Cancer Genome Atlas, TCGA). In addition, we demonstrated that tunicamycin-induced ER stress in vitro upregulated ATF6 and CIP2A. Mechanistically, we found that ATF6 directly bound to the CIP2A promoter and induced CIP2A gene expression, which contributed to colon cancer cell survival. Furthermore, knockdown of CIP2A reduced the viability of cells under ER stress. Most importantly, immunohistochemical analysis of a tissue microarray from a colon cancer patient cohort showed that higher expression levels of ATF6 and CIP2A were associated with a trend toward poor prognosis. Taken together, our results show that ER stress-related ATF6 upregulates CIP2A and contributes to the prognosis of colon cancer. Targeting CIP2A may disrupt ER stress-mediated colon cancer cell survival and thus improve the prognosis of patients with colon cancer.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Autoantígenos/metabolismo , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/metabolismo , Estresse do Retículo Endoplasmático , Proteínas de Membrana/metabolismo , Regulação para Cima , Idoso , Autoantígenos/genética , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Regiões Promotoras Genéticas/genética , Modelos de Riscos Proporcionais , Ligação Proteica , Estabilidade Proteica , Análise de Sobrevida , Transcrição Genética
15.
World J Surg Oncol ; 16(1): 128, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29976257

RESUMO

BACKGROUND: The incidence, site distribution, and mortality rates of patients with colorectal cancer differ according to gender. We investigated gene mutations in colorectal patients and wanted to examine gender-specific differences. METHODS: A total of 1505 patients who underwent surgical intervention for colorectal cancer were recruited from March 2000 to January 2010 at Taipei Veterans' General Hospital and investigated for gene mutations in K-ras, N-ras, H-ras, BRAF, loss of 18q, APC, p53, SMAD4, TGF-ß, PIK3CA, PTEN, FBXW7, AKT1, and MSI. RESULTS: There were significant differences between male and female patients in terms of tumor location (p < 0.0001) and pathological stage (p = 0.011). The female patients had significantly more gene mutations in BRAF (6.4 vs. 3.3%, OR 1.985, p = 0.006), TGF-ß (4.7 vs. 2.5%, OR 1.887, p = 0.027), and revealed a MSI-high status (14.0 vs. 8.3%, OR 1.800, p = 0.001) than male patients. Male patients had significantly more gene mutations in N-ras (5.1 vs. 2.3%, OR 2.227, p = 0.012); however, the significance was maintained only for mutations in BRAF (OR 2.104, p = 0.038), MSI-high status (OR 2.003 p = 0.001), and N-ras (OR 3.000, p = 0.010) after the groups were divided by tumor site. CONCLUSION: Gene mutations in BRAF, MSI-high status, and N-ras differ according to gender among patients with colorectal cancer.


Assuntos
Neoplasias Colorretais , Mutação , Proteínas Proto-Oncogênicas B-raf , Neoplasias Colorretais/genética , Feminino , Genes ras/genética , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Fatores Sexuais
16.
Int J Colorectal Dis ; 33(9): 1173-1181, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29869121

RESUMO

BACKGROUND: To investigate the clinicopathological features and prognostic significance of the BRAFV600E mutation in Asian patients with colorectal cancer. METHODS: We retrospectively reviewed the medical records of 1969 patients with colorectal cancer admitted to Taipei Veterans General Hospital for surgical treatment between 2000 and 2013. The measured endpoint was overall survival after surgery. The prognostic value of the BRAFV600E mutation was analyzed using the log-rank test and Cox regression analysis. RESULTS: The BRAFV600E mutation was detected in 106 (5.4%) patients and associated with female gender, abnormal cancer antigen (CA)19-9 at diagnosis, microsatellite status, right-sided primary tumors, mucinous histology, poor differentiation, and lymphovascular invasion. Metastatic patterns were more common in non-regional lymph node metastasis (20.8 vs. 7.4%, p = 0.06) and peritoneal seeding (41. vs. 21.2%, p = 0.04). Mutations were not prognostic in the overall survival of the entire study group but only in specific patients: age < 65, normal carcinoembryonic antigen at diagnosis, and stage IV disease. CONCLUSION: The BRAFV600E mutation was associated with distinct clinicopathological features and metastatic patterns. The overall survival rate was lower in selected colorectal patients with the BRAFV600E mutation.


Assuntos
Neoplasias Colorretais/genética , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Neoplasias Colorretais/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
17.
Sci Rep ; 8(1): 8503, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29844339

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

18.
PLoS One ; 13(5): e0197681, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795620

RESUMO

Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 ± 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 ± 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE-1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients' outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients' outcomes in univariate analysis.


Assuntos
Neoplasias Colorretais/patologia , Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Taxa de Sobrevida
19.
J Chin Med Assoc ; 81(9): 759-765, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29778550

RESUMO

BACKGROUND: The immunochemical fecal occult blood test (iFOBT) is an alternative method to colonoscopy that can be used for colorectal cancer (CRC) screening. If the iFOBT result is positive, a colonoscopy is recommended. In this retrospective study, we identify factors associated with negative colonoscopy and positive iFOBT results obtained during CRC screening. METHODS: We collected data for subjects who received a colonoscopy at Taipei Veterans General Hospital after receiving a positive iFOBT result during CRC screening from January 2015 to December 2015. Subjects' baseline data, medications, and co-morbidities as well as colonoscopy and histological findings were recorded. A negative colonoscopy result was defined as no detection of any colorectal neoplasia including non-advanced adenoma, advanced adenoma, and adenocarciona. Multivariate logistic regression analysis was conducted to identify the associated factors in screening subjects with positive iFOBT but negative colonoscopy results. RESULTS: 559 (46.3%) out of 1207 eligible study subjects received a colonoscopy with a negative result. Multivariate logistic regression analysis revealed that the use of antiplatelets [odds ratio (OR) = 0.654; 95% confidence interval (CI), 0.434-0.986], occurrence of hemorrhoid (OR = 0.595; 95% CI, 0.460-0.768), and the existence of colitis/ulcer (OR = 0.358; 95% CI, 0.162-0.789) were independent factors associated with negative colonoscopy but positive iFOBT results during CRC screening. The colon clean level, underlying diseases of gastrointestinal bleeding tendency (e.g., chronic kidney disease, cirrhosis), and the use of anticoagulant or nonsteroidal anti-inflammatory agents were not associated with negative colonoscopy and positive iFOBT results. CONCLUSION: The use of antiplatelet agents and the presence of hemorrhoids and colitis/ulcers were factors associated with negative colonoscopy and positive iFOBT results.


Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Sangue Oculto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/etiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
PLoS Biol ; 16(1): e2003714, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29337987

RESUMO

Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients' CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC. RPIA modulates cell proliferation and oncogenicity via activation of ß-catenin in colon cancer cell lines. Unlike its role in PPP in which RPIA functions within the cytosol, RPIA enters the nucleus to form a complex with the adenomatous polyposis coli (APC) and ß-catenin. This association protects ß-catenin by preventing its phosphorylation, ubiquitination, and subsequent degradation. The C-terminus of RPIA (amino acids 290 to 311), a region distinct from its enzymatic domain, is necessary for RPIA-mediated tumorigenesis. Consistent with results in vitro, RPIA increases the expression of ß-catenin and its target genes, and induces tumorigenesis in gut-specific promotor-carrying RPIA transgenic zebrafish. Together, we demonstrate a novel function of RPIA in CRC formation in which RPIA enters the nucleus and stabilizes ß-catenin activity and suggests that RPIA might be a biomarker for targeted therapy and prognosis.


Assuntos
Aldose-Cetose Isomerases/metabolismo , Aldose-Cetose Isomerases/fisiologia , beta Catenina/fisiologia , Polipose Adenomatosa do Colo/metabolismo , Adulto , Idoso , Animais , Animais Geneticamente Modificados , Carcinogênese , Linhagem Celular Tumoral , Núcleo Celular , Proliferação de Células/fisiologia , Transformação Celular Neoplásica , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Regiões Promotoras Genéticas/genética , Domínios Proteicos , RNA Mensageiro/genética , Ubiquitinação , Peixe-Zebra , beta Catenina/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA