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1.
J Surg Oncol ; 121(3): 538-546, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31853986

RESUMO

BACKGROUND: While the prognostic implications of positive circumferential resection margins (CRM) have been established for rectal cancer, its significance in colon cancer has not been well defined. The aim of the current study was to determine national rates for positive CRM in locally advanced colon cancer, associated factors, and survival impact. METHODS: The National Cancer Database was queried to identify patients with stage II-III adenocarcinoma of the colon (2004-2015). RESULTS: Positive CRM was identified in 9% of stage II and 12% of stage III patients. Factors associated with negative CRM included surgery in a high-volume facility, adequate lymph-node harvest, and negative distal/proximal margins. No difference in CRM rates was observed between surgical approaches, although having a positive CRM was significantly associated with higher conversion rates. Positive CRM was associated with significantly lower overall survival on both univariate and multivariable analysis. CONCLUSIONS: Positive CRM rates exceeded 10% nationally and have an adverse impact on survival. While several tumor characteristics were identified as independent risk factors, oncologic resections and surgery at high-volume centers were associated with lower rates of positive CRM. These findings emphasize the need for process improvement initiatives targeting modifiable factors, including adoption of appropriate oncologic techniques, standardized pathology reporting, and potential neoadjuvant strategies.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Margens de Excisão , Idoso , Neoplasias do Colo/patologia , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Estadiamento de Neoplasias , Fatores de Risco , Análise de Sobrevida , Estados Unidos/epidemiologia
2.
J Surg Res ; 245: 475-482, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31446189

RESUMO

BACKGROUND: The clinical characteristics of stage III colon cancer and the prognostic significance of tumor deposits were investigated, to construct a prognostic nomogram. METHODS: The data of patients were retrieved from the Surveillance, Epidemiology, and End Results database. Patients were randomized to a training or validation cohort. The Kaplan-Meier method was used to analyze survival rates. In the training cohort, a prognostic nomogram was established via Cox regression and then tested in the validation cohort. The accuracy and discrimination of the nomogram were assessed using concordance indices (C-indices) and calibration curves. RESULTS: Of the 9246 patients meeting the inclusion criteria, 1788 (19.3%) had tumor deposits. Patients with tumor deposits only showed similar survival rates to those with lymph node metastases only (P = 0.83). Compared with these, patients with both tumor deposits and lymph node metastases exhibited significantly worse survival (P < 0.01). In the multivariate Cox regression analyses, the following were identified as independent prognostic indicators and adopted to formulate the nomogram: tumor deposits, age, ethnicity, T stage, the number of positive regional lymph nodes, grade, and carcinoembryonic antigen. In the training cohort, the calibration curve showed good consistency, and the concordance index of the nomogram for predicting overall survival reaches 0.727 (95% CI: 0.71524-0.73876), superior to the concordance index of the American Joint Committee on Cancer staging system (0.594, 95% CI: 0.58224-0.60576). These results are supported in the validation cohort. CONCLUSIONS: Tumor deposits may be an independent prognostic factor for patients with stage III colon cancer after colectomy. The nomogram constructed herein accurately predicted overall survival.


Assuntos
Colectomia , Neoplasias do Colo/mortalidade , Nomogramas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
3.
Anticancer Res ; 39(11): 6291-6297, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704859

RESUMO

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


Assuntos
Neoplasias do Colo/metabolismo , Ciclina D1/metabolismo , Ciclina E/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fase G1 , Proteínas de Neoplasias/metabolismo , Proteínas Oncogênicas/metabolismo , Proteína do Retinoblastoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/química , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Ciclina D1/análise , Ciclina E/análise , Inibidor de Quinase Dependente de Ciclina p21/análise , Feminino , Seguimentos , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas/análise , Prognóstico , Proteína do Retinoblastoma/análise , Taxa de Sobrevida
4.
Cancer Sci ; 110(11): 3565-3572, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520559

RESUMO

Aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a second-line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty-two patients with metastatic colorectal cancer received aflibercept (4 mg/kg) plus FOLFIRI every 2 weeks. Seventy-eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma interaction. Plasma levels of biomarkers at baseline and at pre-dose 3 (day 1 of treatment cycle 3) were measured in all patients by ELISA. Relationships between these levels and efficacy endpoints were assessed. Ten potential biomarkers had a ±30% change from baseline to pre-dose 3 (adjusted P < .001), with the greatest changes occurring in placental growth factor (median: +4716%) and vascular endothelial growth factor receptor 1 (+2171%). Baseline levels of eight potential biomarkers correlated with overall survival in a univariate Cox regression analysis: extracellular newly identified receptor for advanced glycation end-products binding protein, insulin-like growth factor-binding protein 1, interleukin-8, kallikrein 5, pulmonary surfactant-associated protein D, tissue inhibitor of metalloproteinases 1, tenascin-C, and tumor necrosis factor receptor 2. None correlated with progression-free survival or maximum tumor shrinkage. Pre-dose 3 levels did not correlate with any efficacy endpoints. Preliminary data show that these eight biomarkers could be associated with overall survival. ClinicalTrials.gov identifier: NCT01882868.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Grupo com Ancestrais do Continente Asiático , Camptotecina/uso terapêutico , Neoplasias do Colo/sangue , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Fluoruracila/uso terapêutico , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Interleucina-8/sangue , Japão , Calicreínas/sangue , Leucovorina/uso terapêutico , Fator de Crescimento Placentário/sangue , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Proteína D Associada a Surfactante Pulmonar/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Neoplasias Retais/sangue , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Análise de Regressão , Tenascina/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
5.
J Surg Oncol ; 120(7): 1190-1200, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31536150

RESUMO

INTRODUCTION: Mucinous adenocarcinoma is a subtype of colonic adenocarcinoma associated with worse survival compared to nonmucinous adenocarcinoma. Prior studies on the effect of chemotherapy on survival in mucinous adenocarcinoma have shown mixed results. The aim of this study is to evaluate the effect of chemotherapy on the survival of patients with stage II and III mucinous adenocarcinoma. METHODS: The National Cancer Database was used to identify patients diagnosed with stage II or III nonmucinous adenocarcinoma or mucinous adenocarcinoma between 2004 and 2016. The primary outcome was overall survival. RESULTS: Fourteen thousand and three hundred patients with stage II mucinous colon adenocarcinoma and 16 741 patients with stage III mucinous colon adenocarcinoma were identified. There was no significant difference in survival between nonmucinous adenocarcinoma and mucinous adenocarcinoma patients in adjusted analysis for stage II disease (HR:1.00, 95%CI:0.98-1.02, P = .99), but there was a significant difference for stage III disease (HR:1.05, 95%CI:1.03-1.07, P < .001). In propensity-matched cohorts of patients with mucinous adenocarcinoma, chemotherapy was significantly associated with survival in stage II (HR:0.79, 95%CI:0.69-0.90, P < .001) and stage III disease (HR:0.56, 95%CI:0.52-0.60, P < .001). CONCLUSIONS: Patients with stage II or stage III mucinous adenocarcinoma of the colon who are given adjuvant chemotherapy have significantly improved survival compared to patients not given chemotherapy.


Assuntos
Adenocarcinoma Mucinoso/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Neoplasias do Colo/mortalidade , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
6.
Zhonghua Zhong Liu Za Zhi ; 41(9): 708-711, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550863

RESUMO

Objective: To investigate the effect of omeprazole on plasma concentration, efficacy and adverse reactions of capecitabine in patients with colon cancer. Methods: Seventy-two patients with colon cancer treated with capecitabine were analysed retrospective. The patients treated with capecitabine combined with omeprazole were identified as experimental group and the capecitabine treatment alone as control group.The differences of blood concentration and the side effects of capecitabine between these two groups were compared. Results: The plasma concentration of 5-Fluorouracilum in experimental group was (126.25±50.59) µg/ml, without significant difference of (123.09±56.70) µg/ml in control group (P=0.121). The incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and hand-foot syndrome in experimental group were 13.8%, 0%, 0% and 19.4%, respectively. In control group, the incidence of Ⅲ to Ⅳ degree bone marrow suppression, nausea, vomiting, diarrhea and the hand-foot syndrome were 11.1%, 0%, 0% and 19.4%, respectively, without significant difference of experimental group (P>0.05). The incidence of acid reflux and heartburn in the control group was 72.2%, significantly higher than 44.4% of the experimental group (P<0.05). The objective response rate (ORR) and progression-free survival time (PFS) in these two groups were 30.6% and 33.3%, and 8.0 month and 8.5 month, respectively, without significant difference (P>0.05). Conclusion: The intravenous omeprazole attenuates reflux and heartburn of colon cancer patients treated with capecitabine, without affecting its plasma concentration and side effects and has no impact on the PFS of these patients.


Assuntos
Capecitabina/efeitos adversos , Capecitabina/sangue , Neoplasias do Colo/tratamento farmacológico , Omeprazol/efeitos adversos , Omeprazol/sangue , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapêutico , China/epidemiologia , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Fluoruracila/administração & dosagem , Refluxo Gastroesofágico/induzido quimicamente , Refluxo Gastroesofágico/epidemiologia , Azia/induzido quimicamente , Azia/epidemiologia , Humanos , Omeprazol/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
7.
Dis Colon Rectum ; 62(10): 1212-1221, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31490830

RESUMO

BACKGROUND: Perineural invasion is associated with adverse oncological outcomes in colorectal cancer. However, data regarding the prognostic and predictive impact in colon cancer are scarce. OBJECTIVE: This study aims to clarify the role of perineural invasion in patients with nonmetastatic colon cancer. DESIGN: This study is a retrospective review of a prospectively maintained database. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with stage I to III colon cancer who underwent elective surgery at our tertiary center between 2004 and 2015 (n = 1145) were included. MEAN OUTCOME MEASURES: The primary long-term outcomes include disease-free survival, disease-specific survival, and overall survival. Differences were determined by multivariate Cox regression models adjusted for stage and potential confounders. RESULTS: Perineural invasion was identified in 215 patients (18.8%) and associated with emergency procedures, male sex, and advanced disease. Histopathological features including lymphatic and extramural vascular invasion, poor differentiation, and infiltrating tumor borders were correlated with perineural invasion. Compared with patients with perineural invasion-negative tumors, patients who had perineural invasion-positive tumors had worse disease-free, overall, and disease-specific survival (all p < 0.001). Moreover, patients with perineural invasion-positive node-negative disease had worse overall survival than patients with perineural invasion-negative node-positive disease (p < 0.001). After adjustment, perineural invasion remained significantly associated with worse disease-free survival (HR, 1.45; 95% CI, 1.03-2.03; p = 0.033), worse overall survival (HR, 1.75; 95% CI, 1.33-2.31; p < 0.001), and worse disease-specific survival (HR, 1.52; 95% CI, 1.00-2.30; p = 0.048). However, we did not find a significant predictive response with adjuvant chemotherapy in perineural invasion-positive node-negative tumors (HR, 2.10; 95% CI, 0.80-5.51; p = 0.122). The predictive value was only demonstrated in stage III disease with a significant impaired overall survival in patients with perineural invasion-positive tumors who did not receive adjuvant therapy (HR, 0.23; 95% CI, 0.13-0.40; p < 0.001). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Our study confirms the prognostic value of perineural invasion in stage I to II and III colon cancer. However, patients with node-negative disease and perineural invasion did not significantly benefit from adjuvant therapy. More information regarding postoperative treatment in node-negative perineural invasion-positive colon cancer is required. See Video Abstract at http://links.lww.com/DCR/A988. LA INVASIÓN PERINEURAL COMO FACTOR PRONÓSTICO NO PREDICTIVO EN EL CÁNCER DE COLON NO METASTÁSICO: La invasión perineural se encuentra asociada a resultados oncológicos adversos en casos de cáncer colorrectal. Sin embargo, los datos sobre el impacto pronóstico y predictivo en caso de cáncer de colon son pocos. OBJETIVO: Definir el papel de la invasión perineural en pacientes con cáncer de colon no metastásico. DISEÑO:: Revisión retrospectiva de una base de datos alimentada prospectivamente. AJUSTES: Centro hospitalario de atención terciaria. PACIENTES: Todos aquellos portadores de un cáncer de colon estadío I-III que se sometieron a cirugía electiva en nuestro centro entre 2004-2015 (n = 1145). PRINCIPALES RESULTADOS: Los resultados a largo plazo incluyeron la supervivencia sin enfermedad, la supervivencia específica de la enfermedad y la supervivencia general. Las diferencias se determinaron mediante modelos de regresión multivariantes de Cox, ajustados para el control de factores de confusión durante el análisis por estratificación. RESULTADOS: La invasión perineural fué identificada en 215 pacientes (18.8%) y se la asoció con procedimientos de emergencia, al género masculino y a la enfermedad avanzada. Las características histopatológicas que incluyeron la invasión vascular linfática y extramural, la diferenciación deficiente y los bordes tumorales infiltrantes se correlacionaron con la invasión perineural. Comparativamente con los tumores sin invasión perineural, los pacientes positivos a la invasión perineural tuvieron una peor supervivencia general, libre y específica de la enfermedad (todos p < 0.001). Asimismo, aquellos pacientes con invasion-perineural con ganglios negativos tuvieron una supervivencia global mucho peor que aquellos pacientes con ganglios positivos e invasión perineural negativa (p < 0.001). Después del ajuste, la invasión perineural se asoció significativamente con una peor supervivencia sin la enfermedad (HR, 1.45; IC 95%, 1.03-2.03; p = 0.033), supervivencia general (HR, 1.75; IC 95%, 1.33-2.31; p <0.001), así como con una peor supervivencia específica de la enfermedad (HR, 1.52; IC 95%, 1.00-2.30; p = 0.048). Sin embargo, no encontramos una respuesta predictiva significativa con quimioterapia adyuvante en los tumores acompañados de invasion-perineural con ganglios negativos (HR, 2.10; IC del 95%, 0.80-5.51; p = 0.122). El valor predictivo solo fué demostrado en aquellos casos de estadio III con un deterioro significativo de la supervivencia global en pacientes con tumores perineurales positivos a la invasión y que no recibieron tratamiento adyuvante (HR, 0.23; IC 95%, 0.13-0.40; p < 0.001). LIMITACIONES: Diseño retrospectivo. CONCLUSIÓN:: Nuestros resultados confirman el valor pronóstico de la invasión perineural en el cáncer de colon estadios I-II y III. Sin embargo, los pacientes con enfermedad ganglionar negativa e invasión perineural no se beneficiaron significativamente de la terapia adyuvante. Se requiere más información sobre el tratamiento postoperatorio en el cáncer de colon positivo para la invasión perineural con ganglios negativos. Vea el Resumen del video en http://links.lww.com/DCR/A988.


Assuntos
Neoplasias do Colo/patologia , Estadiamento de Neoplasias , Neoplasias do Sistema Nervoso Periférico/patologia , Idoso , Neoplasias do Colo/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias do Sistema Nervoso Periférico/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos
8.
Cancer Invest ; 37(8): 393-414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31502477

RESUMO

Colorectal cancer (CRC) is one of the most common malignancies. In recent decades, early diagnosis and conventional therapies have resulted in a significant reduction in mortality. However, late stage metastatic disease still has very limited effective treatment options. There is a growing interest in using viruses to help target therapies to tumour sites. In recent years the evolution of immunotherapy has emphasised the importance of directing the immune system to eliminate tumour cells; we aim to give a state-of-the-art over-view of the diverse viruses that have been investigated as potential oncolytic agents for the treatment of CRC.


Assuntos
Neoplasias do Colo/terapia , Terapia Viral Oncolítica/tendências , Vírus Oncolíticos/patogenicidade , Neoplasias Retais/terapia , Animais , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/virologia , Difusão de Inovações , Previsões , Interações Hospedeiro-Patógeno , Humanos , Terapia Viral Oncolítica/efeitos adversos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/virologia , Resultado do Tratamento
9.
Surgery ; 166(4): 639-647, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31399220

RESUMO

BACKGROUND: Current standards for lymph node harvest in colorectal cancer surgery may be inadequate. Higher lymph node yield may improve survival, but the number of lymph nodes needed to optimize survival is unknown. The objective of this study was to examine the relationship between lymph node yield and overall survival in patients undergoing colectomy for nonmetastatic colon adenocarcinoma. METHODS: The 2010 to 2014 National Cancer Database was queried for patients undergoing colectomy for nonmetastatic colon adenocarcinoma. Adjusted restricted cubic splines were used to model the nonlinear relationship between lymph node harvest and overall survival. Cox proportional hazard determined independent predictors of overall survival. RESULTS: A total of 261,423 patients were included. Restricted cubic splines demonstrated that the adjusted improvements in overall survival stabilized after 24 nodes. Patients were divided into: <12, 12 to 23, and ≥24 nodes. On survival analysis, patients with ≥24 nodes had better survival across all N stages compared to other groups (P < .001). Lymph node harvest ≥24 nodes was independently associated with improved overall survival compared to 12 to 23 nodes (hazard ratio 0.82; 95% confidence interval, 0.80-0.85). CONCLUSION: Lymph node harvest ≥24 nodes is associated with improved survival in colorectal cancer patients. These data may provide indirect evidence for a more extensive lymphadenectomy for colon cancer.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Colectomia/métodos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Linfonodos/patologia , Adenocarcinoma/cirurgia , Idoso , Colectomia/mortalidade , Neoplasias do Colo/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Coleta de Tecidos e Órgãos , Resultado do Tratamento
10.
Rev Col Bras Cir ; 46(3): e20192098, 2019 Aug 15.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31432981

RESUMO

OBJECTIVE: to evaluate the clinical and pathological differences between locally advanced colonic adenocarcinomas (LACA) with adhesions between adjacent organs or structures, and colonic adenocarcinomas with other clinical presentations. METHODS: we conducted a retrospective study from a convenience sample of patients with colonic adenocarcinoma, pathological stage pT3, distributed according to clinical and pathological characteristics in three groups: locally advanced tumors (LACA), pT3 tumors without adhesions or distant metastases (SF) and tumors with metastatic disease (M1). We evaluated clinical and pathological characteristics and the expression of seven immunohistochemical markers related to proliferation/apoptosis, cell invasion/migration and metastasis. RESULTS: we studied 101 patients: 30 LACA, 44 SF and 27 M1. Locally advanced tumors presented larger dimensions and were associated with increased lymphocyte infiltration rates, lower levels of bax expression, and CD 44v6 when compared with SF and M1 groups. We observed significant differences between LACA and M1 in relation to colonic location, histology, lymph node status and bax and CD44v6 expression. We found differences were observed between the three groups for tumor size and lymphocytic infiltrate. Survival was similar in the LACA and SF groups (p=0.66) and was lower in the M1 group (p<0.001). CONCLUSION: the data suggest that locally advanced colonic adenocarcinomas with adhesions between adjacent organs or structures represent a distinct entity.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Adenocarcinoma/mortalidade , Neoplasias do Colo/mortalidade , Humanos , Imuno-Histoquímica , Estudos Longitudinais , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida
11.
World J Gastroenterol ; 25(26): 3392-3407, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341364

RESUMO

BACKGROUND: DNA methylation, acknowledged as a key modification in the field of epigenetics, regulates gene expression at the transcriptional level. Aberrant methylation in DNA regulatory regions could upregulate oncogenes and downregulate tumor suppressor genes without changing the sequences. However, studies of methylation in the control of gene expression are still inadequate. In the present research, we performed bioinformatics analysis to clarify the function of methylation and supply candidate methylation-related biomarkers and drivers for colon cancer. AIM: To identify and analyze methylation-regulated differentially expressed genes (MeDEGs) in colon cancer by bioinformatics analysis. METHODS: We downloaded RNA expression profiles, Illumina Human Methylation 450K BeadChip data, and clinical data of colon cancer from The Cancer Genome Atlas project. MeDEGs were identified by analyzing the gene expression and methylation levels using the edgeR and limma package in R software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the DAVID database and KEGG Orthology-Based Annotation System 3.0, respectively. We then conducted Kaplan-Meier survival analysis to explore the relationship between methylation and expression and prognosis. Gene set enrichment analysis (GSEA) and investigation of protein-protein interactions (PPI) were performed to clarify the function of prognosis-related genes. RESULTS: A total of 5 up-regulated and 81 down-regulated genes were identified as MeDEGs. GO and KEGG pathway analyses indicated that MeDEGs were enriched in multiple cancer-related terms. Furthermore, Kaplan-Meier survival analysis showed that the prognosis was negatively associated with the methylation status of glial cell-derived neurotrophic factor (GDNF) and reelin (RELN). In PPI networks, GDNF and RELN interact with neural cell adhesion molecule 1. Besides, GDNF can interact with GDNF family receptor alpha (GFRA1), GFRA2, GFRA3, and RET. RELN can interact with RAFAH1B1, disabled homolog 1, very low-density lipoprotein receptor, lipoprotein receptor-related protein 8, and NMDA 2B. Based on GSEA, hypermethylation of GDNF and RELN were both significantly associated with pathways including "RNA degradation," "ribosome," "mismatch repair," "cell cycle" and "base excision repair." CONCLUSION: Aberrant DNA methylation plays an important role in colon cancer progression. MeDEGs that are associated with the overall survival of patients may be potential targets in tumor diagnosis and treatment.


Assuntos
Neoplasias do Colo/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Biologia Computacional , Simulação por Computador , Bases de Dados Genéticas/estatística & dados numéricos , Conjuntos de Dados como Assunto , Progressão da Doença , Epigênese Genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico
12.
BMC Cancer ; 19(1): 649, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266475

RESUMO

BACKGROUND: Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with clinicopathological parameters. METHODS: Quantitative RT-PCR and Westerns blots were used to examine EEF2K expression in primary tumor and the adjacent non-tumor tissues of CRC patients (n = 20). Kaplan-Meier curves and Cox regression analysis were used to assess the association between clinical outcomes of CRC patients and EEF2K protein expression determined by immunohistochemistry on tissue microarray (n = 151). RESULTS: EEF2K was significantly downregulated at both mRNA and protein levels in tumors of CRC patients. Univariate Cox regression analysis revealed that CRC patients with high tumor grade, advanced TNM staging and low EEF2K expression were associated with worse overall survival. Multivariate analysis further demonstrated that low EEF2K expression was an independent factor for predicting poorer overall survival in CRC patients (p = 0.014; Hazard ratio = 2.951; 95% confidence interval: 1.240-7.024). The 5-year survival rate was 82.8% in the EEF2K-high-expression group versus 63.9% in the EEF2K-low-expression group (p = 0.0118). The association of overall survival with EEF2K expression in CRC patients was verified in The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS: EEF2K is downregulated in CRC and its expression can be employed as a prognostic marker for CRC patients independent of TNM staging.


Assuntos
Neoplasias do Colo/metabolismo , Quinase do Fator 2 de Elongação/metabolismo , Neoplasias Retais/metabolismo , Idoso , Colo/metabolismo , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Regulação para Baixo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/metabolismo , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/metabolismo , Análise de Regressão , Taxa de Sobrevida , Resultado do Tratamento , Proteínas Supressoras de Tumor
13.
J Surg Oncol ; 120(3): 460-472, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276213

RESUMO

INTRODUCTION: Avoiding postoperative morbidity is essential in patients with advanced cancer. To further improve treatment in stage IV colorectal cancer, knowledge about risk factors which effect short- and long-term outcomes is important. METHODS: All stage IV colon and rectal cancer who underwent elective surgery between 2004 and 2015 were included (n = 345). We compared resectable colon and rectal patients, and unresectable colon and rectal cancer patients. RESULTS: Median follow-up duration was 22.2 (unresectable) and 56.7 months (resectable) with no difference in tumor location. Colon cancer patients were more often considered unresectable (P < .001). Rectal procedures were correlated with a higher morbidity rate and a longer surgical duration (P < .001). In the resectable cohort, obese patients, open procedures and prolonged surgery were independently associated with postoperative complications. Considering the palliative group, neoadjuvant treatment and age were correlated with worse outcomes. Morbidity was not associated with long-term outcomes in the resectable cohort. However, unresectable patients who developed respiratory (hazard ratio [HR]: 7.53) or cardiac (HR: 3.75) complications and patients with an American Society of Anesthesiologists-score III to IV (HR: 1.51) had an impaired survival. CONCLUSION: Our results emphasize the need for an adequate preoperative assessment to identify patients at risk for postoperative complications and impaired survival.


Assuntos
Neoplasias do Colo/cirurgia , Neoplasias Retais/cirurgia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Metástase Neoplásica , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Resultado do Tratamento
14.
Future Oncol ; 15(18): 2093-2106, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31257922

RESUMO

Aim: To investigate the association and prognostic value of ANKZF1 gene for survival in colorectal cancer, the mechanism of ANKZF1 level alteration and correlated signaling pathways ANKZF1 is involved. Patients & methods: The Cancer Genome Atlas COREAD dataset was analyzed by bioinformatical investigation. Results: High ANKZF1 expression is associated with poor overall survival (hazard ratio [HR]: 2.094; 95% CI: 1.188-3.689; p = 0.011) and recurrence-free survival (HR: 1.762; 95% CI: 1.021-3.042; p = 0.042) in colon cancer. Bioinformatical analysis showed ANKZF1 was upregulated by amplification and exon expression. ANKZF1 was associated with angiogenesis and cancer signaling pathways. Conclusion: High ANKZF1 is an independent factor of poor survival (overall survival and recurrence-free survival) in colon cancer by taking part in angiogenesis and some cancer signaling pathways.


Assuntos
Biomarcadores Tumorais , Proteínas de Transporte/genética , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Biologia Computacional/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
15.
Int J Clin Oncol ; 24(11): 1397-1405, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31332611

RESUMO

BACKGROUND: There are several methods for analyzing computed tomography (CT) images to evaluate chemotherapy efficacy in clinical studies. However, the optimal analysis method for each drug is still under debate. We conducted a pooled analysis using data from six phase II studies to evaluate four analysis methods in colorectal cancers (CRCs): morphological responses (MRs), early tumor shrinkage (ETS), depth of response (DpR), and response evaluation criteria in solid tumors (RECIST) ver.1.1. METHODS: We included 249 patients in this analysis. Pretreatments and findings of subsequent CT imaging were analyzed based on the MR, ETS, DpR, and RECIST ver.1.1. Differences in overall survival (OS) between the responders and non-responders according to each method were evaluated using survival analysis. RESULTS: The responders had significantly better hazard ratios (HRs) for OS, in terms of DpR (≥ median), ETS, objective response rate (ORR) [complete response (CR) + partial response (PR)], and disease control rate [CR + PR + stable disease (SD)]. Patients with right-sided colon cancers showed better HRs for DpR, but not for ETS and ORR. Contrastingly, patients with left-sided CRCs had better HRs for ETS, DpR, and ORR. MR was not associated with outcomes in this study, even in cases where bevacizumab was used. In patients with liver metastasis, ETS, DpR, and ORR showed better HRs, but not in those with lung metastasis. CONCLUSION: Early tumor shrinkage and DpR might be predictive markers only in left-sided CRCs with liver metastasis. Each imaging analysis has a different value based on the primary and metastatic sites.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Bevacizumab/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Análise de Sobrevida
16.
Oncol Rep ; 42(3): 923-936, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322253

RESUMO

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA­sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription­quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 (ITGA8) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin­mediated signaling pathway, and co­expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980­0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577­0.831; P<0.0085). Multivariate survival analysis indicated that integrin α (ITGA5) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Neoplasias do Colo/patologia , Integrinas/genética , MicroRNAs/genética , RNA Mensageiro/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Idoso , Estudos de Casos e Controles , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Curva ROC , Análise de Sequência de RNA , Taxa de Sobrevida
17.
Technol Cancer Res Treat ; 18: 1533033819853237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31159706

RESUMO

BACKGROUND: Non-coding RNAs are competing endogenous RNAs in the occurrence and development of tumorigenesis; numerous microRNAs are aberrantly expressed in colon cancer tissues and play significant roles in oncogenesis development and metastasis. However, large clinical and RNA data are lacking to further confirm the exact role of these RNAs in tumors. This study aimed to ascertain differential RNA expression between colon cancer and normal colon tissues. MATERIALS AND METHODS: RNA sequencing and clinical data of patients with colon cancer were procured from The Cancer Genome Atlas database; differentially expressed long non-coding RNA, differentially expressed messenger RNAs, and differentially expressed microRNAs were achieved using the limma package in edgeR to generate competing endogenous RNAs networks. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted with ggplot2 package, the Kaplan-Meier survival method was used to predict survival in patients with colon cancer. RESULTS: In total, 1174 differentially expressed long non-coding RNAs, 2068 differentially expressed messenger RNAs, and 239 differentially expressed microRNAs were generated between 480 colon cancer and 41 normal colon tissue samples. Three competing endogenous RNA networks were established. Gene Ontology analysis indicated that the genes of the up-regulated microRNA network were involved in negative regulation of transcription, DNA-template, and those of down-regulated microRNA network were involved in transforming growth factor ß receptor signaling pathways, response to hypoxia, cell migration, while Kyoto Encyclopedia of Genes and Genomes analyses of these networks turned out to be negative. Three long non-coding RNAs (AP004609.1, ARHGEF26-AS1, and LINC00491), 3 microRNAs (miRNA-141, miRNA-216a, and miRNA-193b) and 3 RNAs (ULBP2, PHLPP2, and TPM2) were detected to be associated with prognosis by the Kaplan-Meier survival analysis. Additionally, univariate and multivariate Cox regression analyses showed that the microRNA-216a of the competing endogenous RNA might be an independent prognostic factor in colon cancer. CONCLUSIONS: This study constructed the non-coding RNA-related competing endogenous RNA networks in colon cancer and sheds lights on underlying biomarkers for colon cancer cohorts.


Assuntos
Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Idoso , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/mortalidade , Biologia Computacional , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico
18.
J Surg Oncol ; 120(3): 431-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31187517

RESUMO

BACKGROUND AND OBJECTIVES: Primary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short-term outcomes, and five-year survival of patients undergoing nonpalliative surgery for PCL. METHODS: We performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis. RESULTS: We identified 2153 patients. Median patient age was 68. Diffuse large B-cell lymphoma accounted for 57% of tumors. 30- and 90-Day mortality were high (5.6% and 11.1%, respectively). Thirty-nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5-year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07-1.51; P = .01). CONCLUSIONS: Patients undergoing surgery for PCL have high rates of margin positivity and high short-term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Linfoma/mortalidade , Linfoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Big Data , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Adjuvante , Estudos Retrospectivos
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(6): 579-586, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31238638

RESUMO

Objective: To investigate the mortality of colorectal cancer and its trend from 1999 to 2015 in Tianjin, China, and to explore the mortality features in different populations in order to provide data for prevention and control strategies of colorectal cancer. Methods: Colorectal cancer mortality data between 1999 and 2015 were collected from Tianjin population - based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC). Population data of permanent residents were collected from Tianjin Municipal Public Security Bureau. The number of new cases and deaths, incidence [including crude incidence, age-adjusted standardized incidence and 95% confidence interval (95% CI)], and mortality (including crude mortality, age-adjusted standardized mortality and 95% CI) of colorectal cancer were calculated. Standardized incidence and mortality of colorectal cancer were calculated using the Segi's world standard population, adjusted with age and gender. JoinPoint regression and Cochran-Armitage trend test were used to determine the statistical significance of differences in mortality trend. Results: A total of 31 376 new onset cases and 14 893 death cases of colorectal cancer were observed in Tianjin from 1999 to 2015. Colorectal cancer incidence increased from 1999 to 2015 with a standardized rate from 9.66/100 000 to 15.36/100 000 [annual percent change(APC)=3.48%, Z=23.21, P<0.001]. Colorectal cancer mortality increased from 1999 to 2015 with a standardized rate from 5.18/100 000 to 6.11/100 000 (APC=1.24%, Z=5.69, P<0.001). Both showed an increasing trend. The death proportion of colon cancer increased (39.67% in 1999 and 50.33% in 2015), while the death proportion of rectal caner decreased (60.33% in 1999 and 48.57% in 2015). The median age of colorectal cancer onset fluctuated steadily around 66 years old (APC=0.16, T=1.75, P=0.100); the median age of death increased from 69 to 73 years old (APC=0.43, T=8.81, P<0.001). From 1999 to 2015, the mortality of colorectal cancer showed a downward trend (all P<0.05) in the age groups of <35 and 35-44 years, while an upward trend (all P<0.05) in the age groups of 45-54 years, 55-64 years and ≥ 65 years. Colorectal cancer mortality in males increased with a standardized rate of 5.53/100 000 in 1999 to 7.33/100 000 in 2015(APC=2.29%, Z=7.86, P<0.001), while colorectal cancer mortality in females flatted with a standardized rate of 4.83/100 000 in 1999 to 4.89/100 000 in 2015 (APC=0.10%, Z=-0.30, P=0.752). Colorectal cancer mortality increased with a standardized rate of 6.75/100 000 in 1999 to 7.33/100 000 in 2015 (APC=0.54%, Z=1.98, P=0.048) in urban areas and of 3.18/100 000 in 1999 to 4.38/100 000 in 2015 (APC=2.47, Z=6.46, P<0.001) in rural areas, whose differences were significant. Standardized mortality rate in rural area was lower but the rising velocity was faster as compared to urban area. Conclusions: Crude mortality and standardized mortality of colorectal cancer increase from 1999 to 2015 in Tianjin population. The people of elder, male and urban area have higher mortality. The mortality in people of male and rural area presents a faster rising state. Further efforts to reduce colorectal cancer mortality in Tianjin are needed to prevention and control of colorectal cancer.


Assuntos
Neoplasias Colorretais/mortalidade , Mortalidade/tendências , Adulto , Idoso , China/epidemiologia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/mortalidade , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/epidemiologia , Neoplasias Retais/mortalidade
20.
Technol Cancer Res Treat ; 18: 1533033819857737, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31242804

RESUMO

As a newly discovered cytokine, interleukin 9 was initially considered a T-lymphocyte growth factor. Interleukin 9 affects target cells by binding to a member of the γc-family of receptors and is involved in inflammation, autoimmune diseases, and other ailments. In recent years, mounting evidence reveals that interleukin 9 exerts antitumor effects, which has attracted considerable attention. Many previous studies were performed in vivo by establishing a mouse model of melanoma. Here, interleukin 9 protein and messenger RNA expression levels were both low in colon carcinoma tissue specimens, as assessed by immunohistochemistry and quantitative real-time polymerase chain reaction. In addition, interleukin 9 expression in these samples was correlated with TNM staging, Dukes staging, lymph node metastasis, and good prognosis, but not with gender, age, tumor size, tumor differentiation, and hepatic metastasis. In vivo, by establishing a mouse subcutaneous allograft model, we found that interleukin 9 overexpression inhibited tumor growth and resulted in longer survival time. Then, antitumor immune responses were increased by interleukin 9 as demonstrated by flow cytometry. Furthermore, interleukin 9 was shown to exert antitumor effects by regulating T-cell function and killing tumor cells in the tumor microenvironment. Overall, this study revealed that interleukin 9 exerts robust antitumor effects in colon cancer and transforms the tumor microenvironment in vivo.


Assuntos
Transformação Celular Neoplásica/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Interleucina-9/metabolismo , Microambiente Tumoral , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Interleucina-9/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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