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BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.
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BACKGROUND: Intersphincteric resection (ISR), the ultimate anus-preserving technique for ultralow rectal cancers, is an alternative to abdominoperineal resection (APR). The failure patterns and risk factors for local recurrence and distant metastasis remain controversial and require further investigation. AIM: To investigate the long-term outcomes and failure patterns after laparoscopic ISR in ultralow rectal cancers. METHODS: Patients who underwent laparoscopic ISR (LsISR) at Peking University First Hospital between January 2012 and December 2020 were retrospectively reviewed. Correlation analysis was performed using the Chi-square or Pearson's correlation test. Prognostic factors for overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using Cox regression. RESULTS: We enrolled 368 patients with a median follow-up of 42 mo. Local recurrence and distant metastasis occurred in 13 (3.5%) and 42 (11.4%) cases, respectively. The 3-year OS, LRFS, and DMFS rates were 91.3%, 97.1%, and 90.1%, respectively. Multivariate analyses revealed that LRFS was associated with positive lymph node status [hazard ratio (HR) = 5.411, 95% confidence interval (CI) = 1.413-20.722, P = 0.014] and poor differentiation (HR = 3.739, 95%CI: 1.171-11.937, P = 0.026), whereas the independent prognostic factors for DMFS were positive lymph node status (HR = 2.445, 95%CI: 1.272-4.698, P = 0.007) and (y)pT3 stage (HR = 2.741, 95%CI: 1.225-6.137, P = 0.014). CONCLUSION: This study confirmed the oncological safety of LsISR for ultralow rectal cancer. Poor differentiation, (y)pT3 stage, and lymph node metastasis are independent risk factors for treatment failure after LsISR, and thus patients with these factors should be carefully managed with optimal neoadjuvant therapy, and for patients with a high risk of local recurrence (N + or poor differentiation), extended radical resection (such as APR instead of ISR) may be more effective.
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BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disease characterized by high heterogeneity in clinical manifestation and prognosis. This study aimed to summarize clinical features of localized retroperitoneal CD and our experiences to improve the diagnosis and treatment of this disease. METHODS: Clinical data of 45 patients with localized retroperitoneal CD were retrospectively analyzed. The differences in clinical features between groups with and without paraneoplastic pemphigus (PNP) were compared. Survival was analyzed between groups depending on whether complicating with PNP, bronchiolitis obliterans (BO), gender, age and uni-centric CD (UCD)/multi-centric CD (MCD), respectively. RESULTS: Significant differences were observed between patient groups in the prevalence of retroperitoneal CD with PNP complicated with BO (P=0.010), the constituent ratios of initial symptoms (P<0.001) and the duration from appearance of the initial symptoms to being diagnosed (P=0.009). Among 45 cases, 43 tumors had clear margins and intact envelops and were completely resected, 40 patients were cured or significantly relieved, 3 patients were not significantly relieved, 2 patients received palliative surgical therapy and eventually relapsed and died after surgery. There were significant differences in the survival rate between groups depending on complication with BO, gender and age (≤40 and >40 years) (all P<0.05). CONCLUSIONS: Prompt and complete removal of the retroperitoneal CD tumor is critical to the management of this disease, as palliative resection tends to cause relapse and lead to a poor prognosis. Retroperitoneal CD patients with PNP may develop complications from BO leading to death. Complication with PNP, complication with BO, male gender and age ≥40 years were identified as prognostic risk factors for patients with localized retroperitoneal CD.
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TF/FVIIa (Tissue Factor/Active Coagulation factor VII) and EGFR (Epidermal Growth Factor Receptor) signaling both promote malignant progression of colorectal cancer. However, the crosstalk of these two signaling pathways in human colorectal cancer cells remains unclear. Here we detected the changes of mRNA profile in human colorectal cancer cell SW620 exposed to FVIIa. Microarray showed that mRNA levels of EGFR ligands were significantly upregulated. Western blot analysis confirmed the upregulation of EGFR ligands and the phosphorylation of EGFR at tyrosine-845 in colorectal cancer cells exposed to FVIIa. However, knockdown of TF by RNAi could block the upregulation of EGFR ligands induced by FVIIa stimulation. On the other hand, the expression of components of TF/FVIIa signaling was significantly upregulated in LoVo cells stimulated by EGF. However, the crosstalk between the two signaling pathways could not be detected in HT-29 colon cancer cells bearing wild-type KRAS. Taken together, our study suggest that the crosstalk between TF/FVIIa and EGFR signaling pathways in colon cancer cells depends on KRAS mutation.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Factor VIII/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Tromboplastina/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Receptores ErbB/genética , Receptores ErbB/metabolismo , Factor VIII/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Tromboplastina/genética , Células Tumorales CultivadasRESUMEN
Partridge Shank chicken is a valuable broiler breed in China. The first complete mitochondrial DNA (mtDNA) sequence of Partridge Shank chicken had been obtained using PCR amplification, sequencing and assembling. The complete mitochondrial genome was 16,788 bp in length, with the base composition of 30.2% for A, 23.7% for T, 32.5% for C and 13.5% for G. It exhibited the typical mitochondrial structure, including 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes, and a non-coding control region (D-loop region). The phylogenetic tree construced with maximum-likelihood (ML) method based on the complete chicken mitochondrial genomes showed that the 26 chicken breeds could be divided into two groups.
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BACKGROUND: Tissue factor (TF) is a significant risk factor for tumor growth and hepatic metastasis in patients with colorectal cancer (CRC). This study aimed to investigate whether hyperthermia has synergistic anti-tumor effects with TF knockdown in suppressing CRC progression and metastasis in vitro and in vivo. METHODS: Human colorectal cancer LOVO cells were treated by hyperthermia at 44°C for 2 hr or/and TF siRNA. Then the cells were subjected to colony formation assay. Apoptosis was analyzed by flow cytometry, confocal microscopy, and transmission electron microscopy. The cell migration and invasion abilities were analyzed by wound healing and matrigel assay. In addition, orthotopic nude mice model of CRC was established. RESULTS: Hyperthermia synergized with TF knockdown to reduce colony formation ability, induce apoptosis, and suppress the migration and invasion of LOVO cells in vitro. Moreover, hyperthermia in combination with TF depletion inhibited the growth and hepatic metastasis of CRC in orthotopic nude mice model. Mechanistically, the synergistic effects were at least partly mediated by inducing JNK mediated apoptosis and suppressing matrix metalloproteinases (MMPs) mediated invasion. CONCLUSIONS: Hyperthermia in combination with TF-targeted therapy could be a potential approach for CRC treatment.
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Neoplasias Colorrectales/terapia , Hipertermia Inducida , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/secundario , Tromboplastina/antagonistas & inhibidores , Animales , Apoptosis , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Femenino , Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , Ratones , Ratones Endogámicos BALB C , FN-kappa B/fisiología , Invasividad Neoplásica , ARN Interferente Pequeño/genéticaRESUMEN
BACKGROUND: MicroRNAs have been shown to offer great potential in both the diagnosis and prognosis of cancer. Despite the well-established role of the miR-17-92 in cancer formation and progression, the contribution of each individual miRNA remains to be characterized. Thus, we investigated whether deregulation of the miR-17-92 associated with colon cancer prognosis. METHODS: Expression levels of the miR-17-92 cluster and its paralogs were determined in 48 colon tumor and 48 paired normal tissues by real-time qRT-PCR. Associations with miRNA expression, age, sex, TNM staging, and survival prognosis were evaluated. RESULTS: MiR-17-92 cluster and its paralogs were significantly overexpressed in colon tumor. No significant associations were found between the deregulation of certain miRNAs and the clinical and pathologic characteristics observed in patients. Kaplan-Meier curves demonstrated significantly reduced overall survival in patients expressing high levels of miR-17. In multivariate Cox models, miR-17 overexpression (HR 2.67; P = 0.007) and TNM staging (HR 8.87; P = 0.002) were significantly associated with a risk of death. CONCLUSIONS: The miR-17-92 cluster and its paralogs were significantly elevated in patients with colon cancer, and heightened expression of miR-17 was associated with poor survival. Moreover, miR-17 and TNM staging were both identified as significant, but independent, prognostic biomarkers in colon cancer.
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Neoplasias del Colon/genética , Neoplasias del Colon/mortalidad , MicroARNs/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/patología , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Prospectivos , ARN Largo no Codificante , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
PURPOSE: Increased expression of tissue factor (TF) is associated with tumor invasion and metastasis in human colorectal cancer. We have previously observed that TF/FVIIa upregulates matrix metalloproteinase-7 (MMP-7) expression at the transcriptional level in colon cancer cells. MMP-7 overexpression is believed to play an important role in tumor invasion and metastasis. The aim of this study is to elucidate the molecular mechanisms by which TF/FVIIa induced MMP-7 expression and cell invasion in vitro. METHODS: Reverse transcription polymerase chain reaction, Western blot, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to determine the potential mechanism and signaling pathways by which TF/FVIIa induced MMP-7 expression and cell invasion in LoVo cells. Small interfering RNA (siRNA) and cell invasion assay was used to examine whether blocking c-Fos expression could abolish FVIIa-mediated upregulation of MMP-7 and cell invasion in vitro. RESULTS: The results showed that FVIIa induced the upregulation of MMP-7 both at the mRNA and protein levels in a time- and dose-dependent manner and increased the invasive behavior of LoVo cells. FVIIa enhanced the promoter activity of MMP-7, and the activator protein-1 (AP-1) binding site was responsible for the activation. Site mutation of the AP-1 binding site in the promoter almost completely abolished FVIIa-mediated response. Furthermore, ChIP assay confirmed that FVIIa promoted the direct binding of c-Fos with the MMP-7 promoter in vivo. FVIIa also induced the expression and nuclear accumulation of the AP-1 subunit c-Fos. siRNA-mediated knockdown of c-Fos eliminated FVIIa-stimulated MMP-7 expression and cell migration in vitro. In addition, selective mitogen-activated protein kinase (MAPK) kinase (MEK1/2) inhibitor (PD98059) and p38 MAPK inhibitor SB203580 suppressed MMP-7 upregulation induced by FVIIa. CONCLUSIONS: Our data suggest that a novel TF/FVIIa/MAPK/c-Fos/MMP-7 axis plays an important role in modulating the invasion of colon cancer cells and blockage of this pathway holds promise to treat colon cancer metastasis.
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Neoplasias del Colon/enzimología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Factor VIIa/metabolismo , Metaloproteinasa 7 de la Matriz/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Tromboplastina/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Sitios de Unión , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Activación Enzimática , Regulación Neoplásica de la Expresión Génica , Humanos , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 7 de la Matriz/metabolismo , Invasividad Neoplásica , Regiones Promotoras Genéticas/genética , Unión Proteica , Proteínas Proto-Oncogénicas c-jun/metabolismo , Factores de Tiempo , Factor de Transcripción AP-1/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
OBJECTIVE: To evaluate risk factors associated with morbidity and mortality in patients undergoing surgery for obstructing colorectal cancer. METHODS: One hundred and eleven patients who underwent emergency surgery for obstructing colorectal cancer from January 2001 to December 2009 were retrospectively reviewed. RESULTS: Forty-nine patients had obstruction proximal to the splenic flexure and 62 patients at or distal to the splenic flexure. The morbidity and mortality rates of the emergency surgery for malignant obstruction were 21.6% and 5.4%, respectively. Twenty-three patients received resection with primary anastomosis with intraoperative lavage for left-sided lesions. There was no difference in morbidity between right-sided cancer and left-sided cancer(P>0.05). Univariable analysis showed that complications rate was higher in patients with higher ASA score (3-4) and in those aged over 60 years. Multivariate logistic regression analysis revealed that ASA score(3-4) was an independent risk factor. CONCLUSIONS: Emergency surgery for obstructing colorectal cancer is associated with high rates of morbidity and mortality. Selection of the proper operation and intensive treatment after surgery are recommended in high risk patients.
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Neoplasias del Colon/cirugía , Obstrucción Intestinal/cirugía , Complicaciones Posoperatorias , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Blood coagulation factor VII (FVII) is physiologically synthesized in the liver and released into the blood. Binding of FVII to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FVII extrahepatically. However, little is known about FVII and CRC. We therefore hypothesized that CRC cells may synthese FVII, leading to tumor invasion and metastasis. METHODS: We detected the expression of FVII protein in 55 CRC specimens by immunohistochemical staining. The FVII mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FVIIa complex Western blotting assay. RESULTS: Extrahepatic synthesis of FVII was detected in the cytoplasm of 32 (58.2%) CRC specimens by immunohistochemistry, but not in normal mucosa. Liver metastasis (P = 0.003) and TNM staging (P = 0.005) were significantly correlated with FVII antigen expression. The positive ratios in stages I, II, III and IV were 33.3%, 40.0%, 52.4% and 87.5%, respectively. The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33 ± 2.88 vs. 1.47 ± 0.51, P = 0.03). Ectopic FVIIa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FVIIa complex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9 (4.7-fold) in a time-dependent and dose-dependent manner. CONCLUSIONS: Extrahepatic synthesis of FVII by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream effectors of TF/FVIIa signaling, facilitate the development of metastasis in colon cancer.
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Neoplasias Colorrectales/patología , Factor VII/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Movimiento Celular , Neoplasias Colorrectales/metabolismo , Factor VII/análisis , Factor VII/genética , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/secundario , Masculino , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , ARN Mensajero/análisis , Tromboplastina/fisiologíaRESUMEN
OBJECTIVE: To study the expression of coagulation factor VII(FVII)/tissue factor(TF)complex in colorectal carcinoma (CRC)and its correlation with clinicopathologic factor. METHODS: The expression of coagulation factor VII protein was studied by immunohistochemistry and Western blot.The expression of tissue factor and coagulation factor VII at the mRNA levels were evaluated by quantitative realtime RT-PCR in 45 cases of CRC. RESULTS: (1) FVII overexpression was ectopicly detected in CRC specimens at protein level by immunohistochemistry and Western blot, but not in adjacent non-cancerous mucosa of colorectum;(2)FVII protein mainly localized in the cytoplasm of colon cancer cells.The positive ratios of FVII protein expression in stages I, II, III and IV by immunohistochemistry assay were 33.3%, 40.0%, 64.7% and 80.0% respectively(P=0.001); (3)The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than that in CRC without hepatic metastasis.The relative expression was 5.33+/-2.88 and 1.47+/-0.51 respectively(P=0.03). Overexpression FVII gene was unrelated with tumor size, differentiation, depth of invasion, lymph node metastasis and TNM staging.There existed some relation between the gene and protein level by Spearman correlation, r=0.58, P=0.003;(4)The expression of TF mRNA in CRC significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging.The expression of tissue factor was a critical factor to predict liver metastasis by logistic regression analysis(P=0.001). CONCLUSION: Colorectal cancer can ectopicly synthesize coagulation factor VII.Tissue factor expression may play a role in the process of developing hepatic metastasis.The microenvironment of high dose FVII protein may promote tumor metastasis.
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Neoplasias Colorrectales/metabolismo , Factor VII/metabolismo , Neoplasias Hepáticas/secundario , Tromboplastina/metabolismo , Adulto , Anciano , Neoplasias Colorrectales/patología , Factor VII/genética , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tromboplastina/genéticaRESUMEN
OBJECTIVE: To investigate the clinical characteristics, surgical treatment and prognosis analysis of localized retroperitoneal Castleman disease (CD), and to improve the level of diagnosis and treatment of retroperitoneal Castleman disease with paraneoplastic pemphigus (PNP). METHODS: The clinical data of retroperitoneal CD with PNP from January 1993 to May 2009 were compared with CD without PNP retrospectively, including clinical features, tumor site, lab examination, surgical treatment, pathologic subtype and results of surgery. RESULTS: (1) Retroperitoneal Castleman disease more likely originated in para-kidney and iliac fossa with middle age of 36 years old, especially in left retroperitoneum. Of the 20 cases, 18 tumors (90%) were hyaline vascular variants and 2 were mixed variants. There was no statistical difference in gender, age, tumor site and pathological subtype between two groups. (2) Retroperitoneal CD with PNP more likely complicated with bronchiolitis obliterans (BO) and high level of serum CEA/CA242. (3) Retroperitoneal Castleman tumors had clear margin, intact envelop and were easily resectable, however the biological behavior of CD with PNP might tend malignant changing, invade adjacent blood vessel or seed locally, and eventually relapse after operation. (4) The 5-year survival rate of retroperitoneal CD with PNP was 42.8%, significantly lower than those without PNP. The average survival time was 30 months. Bronchiolitis obliterans and radical resection were the key effect in prognosis of retroperitoneal CD. CONCLUSIONS: Retroperitoneal CD with PNP has distinctive clinical features. Early diagnosis, prompt removal of tumor and termination secretion of causative antibody are critical to the management of this disease.
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Enfermedad de Castleman/diagnóstico , Enfermedad de Castleman/terapia , Adolescente , Adulto , Enfermedad de Castleman/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos/complicaciones , Pénfigo/complicaciones , Pronóstico , Espacio Retroperitoneal , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND AIMS: The extracellular interactions of plasma clotting factor VIIa (FVIIa) with tissue factor (TF) on the cell surface trigger intracellular signaling events involved in multiple physiological processes. TF expression is related to the metastatic potential of tumor cells and is a significant risk factor in the development of hepatic metastases in patients with colorectal cancer. At present, it is unclear how the interaction between TF and FVIIa influences the development of metastasis in colon cancer. MATERIALS AND METHODS: We used a stable LOVO cell line derived from colorectal adenocarcinoma for our model Western blot analysis, Northern blot analysis, polymerase chain reaction, and RNA inference (RNAi), and the Dual-Luciferase Reporter Assay System technology were utilized to determine if MMP7 can be up-regulated by the VIIa/TF complex. RESULTS: Northern blot analysis confirmed that the plasma clotting factor FVIIa/TF complex resulted in a marked increase in MMP7 expression in a time- and dose-dependent manner via the p38 pathway in vitro. The proximal promoter of the human MMP7 gene was cloned into a luciferase reporter construction (MMP7.luc1592). Upon treatment with FVIIa, reporter activity in LOVO cells was increased by 2.5-fold. TF RNAi almost completely abolished FVIIa-mediated MMP7.luc induction. Deletion constructs from MMP7.luc1592 further defined an active promoter region. INTERPRETATION: Taken together, these data provide evidence that expression of MMP7 in colon cancer may be regulated by FVIIa and TF at the transcriptional level. MMP7 may act as a downstream mediator of FVIIa/TF signal transduction to facilitate the development of metastasis in colon cancer.
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Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Factor VIIa/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Metaloproteinasa 7 de la Matriz/genética , ARN Neoplásico/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Northern Blotting , Western Blotting , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Inhibidores Enzimáticos/farmacología , Humanos , Imidazoles/farmacología , Metaloproteinasa 7 de la Matriz/biosíntesis , Reacción en Cadena de la Polimerasa , Piridinas/farmacología , Transcripción Genética , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVE: To assess the expression of Promatrilysin in LoVo colon cancer cell by FVIIa stimulation,and to investigate the effect of MAPKs signal transduction pathway on up-regulation of Promatrilysin. METHODS: (1) The expression of ProMMP-7 was detected by Western blot at different time points (0,2,4,6,9,12 and 24 h) and with different doses of (0,0.1,1,5,10,25 and 100 nmol/L) FVIIa stimulation. The change of ProMMP-7 expression was observed with 5 mg/L tissue factor (TF) antibody prior to 100 nmol/L FVIIa. (2) The activation of MAPKs (ERK, p38, JNK) signaling pathways were assessed at different time points after being stimulated with 100 nmol/L FVIIa and the changes of ProMMP-7 expression were detected after the special signal pathway inhibitors (PD98059,SB203580,SP600125) were applied,respectively. RESULTS: (1) The expression of ProMMP-7 in LoVo cells was up-regulated by FVII a in a time-effect dependent and dose-effect dependent manner,and markedly reached the peak level at h12, 5.5 folds that of the control group (P=0.006).The up-regulation of ProMMP-7 was completely inhibited by blockade with TF antibody. (2) A time-dependent phosphorylation of ERK1/2 and P38 in LoVo cells was induced with FVIIa incubation,reached the peak at min10,2.2 folds and 3.9 folds those of the control groups respectively, but not JNK. (3) The upregulation effect of ProMMP-7 was partially blocked after incubation of ERK1/2 inhibitors PD98059 and P38 inhibitors SB203580 prior to FVIIa, The expression of ProMMP-7 decreased by 32%+/-5% and 61%+/-10% respectively (P<0.05).whereas JNK inhibitors SP600125 did not have the effect. CONCLUSION: FVIIa induces tissue factor-dependent up-regulation of ProMMP-7 in LoVo cells. ERK1/2 and p38 signal pathways are not only involved in TF/FVIIa mediated signaling,but also related to the upregulation of MMP-7 in LoVo cells.
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Neoplasias del Colon/metabolismo , Precursores Enzimáticos/metabolismo , Factor VII/farmacología , Metaloendopeptidasas/metabolismo , Tromboplastina/farmacología , Antracenos/farmacología , Línea Celular Tumoral , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Humanos , Imidazoles/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 7 de la Matriz/metabolismo , Piridinas/farmacologíaRESUMEN
OBJECTIVE: To investigate the role of tissue factor expression in the invasive ability of human colon carcinoma cells and to analyze the correlation between tissue factor and MMP-2 and MMP-9. METHODS: HT-29 cells with sense-TFcDNA transfection and LoVo cells with antisense-TFcDNA transfection were implanted subcutaneously into nude mice as well as controls. The expressions of MMP-9 and MMP-2 at the protein and mRNA levels were detected by Western blot and RT-PCR respectively; Gelatin zymography was used for assay of the MMP-9 and MMP-2 activities in the supernatant cultured media of LoVo cells with antisense-TFcDNA transfection and controls. RESULTS: The expressions of MMP-9 and MMP-2 at the protein and mRNA levels in the group of HT-29 cells with sense-TFcDNA were significantly increased with untransfected HT-29 cells. The expression in the group of LoVo cells with antisense-TFcDNA had a significant decrease than that of the controls. The MMP-9 and MMP-2 activities of LoVo cells with antisense-TFcDNA were weakened because of the lower expression of tissue factor by gelatin zymography. The expression of MMP-9 and MMP-2 were closely correlated to the expression of tissue factor. CONCLUSION: Tissue factor can increase the invasive ability of human colon carcinoma cells. The partial mechanism is that TF can upregulate the expressions of MMP-9 and MMP-2. Tissue factor may be an inner agonist in the secretion of MMPs in colon carcinoma cells.
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Neoplasias del Colon/metabolismo , Metaloproteinasas de la Matriz/biosíntesis , Tromboplastina/biosíntesis , Animales , Línea Celular Tumoral , Neoplasias del Colon/patología , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasas de la Matriz/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Trasplante de Neoplasias , Tromboplastina/genética , TransfecciónRESUMEN
OBJECTIVE: To investigate the clinical diagnosis, treatment and immunohistochemical characteristics of rectal stromal tumors. METHODS: Immunohistochemical expression of CD117 was retrieved in 20 cases of mesenchymal tumors of the rectum. And we analyzed the immunohistochemical characteristics, clinical data of rectal stromal tumors, and the results retrospectively. RESULTS: Sixteen cases of rectal stromal tumors, 3 cases of leiomyosarcomas and 1 case of schwannoma were diagnosed. Histologically, 2 cases of GISTs were classified as benign, 1 as borderline and 13 as malignant. All of rectal stromal tumors (100%) were strongly positive for CD117, and 14 cases (88%) positive for CD34. The demographic profile of rectal stromal tumors showed a male predominance with average age of 60 years old. The main symptoms were urinary retention, constipation and abdominal pain. 14 cases were positive in digital rectal examination. The recurrence rate of local and radical resection in malignant stromal tumors was 4/4 and 3/6. 1, 3, 5-year survival rates were 89%, 64%, 48%, respectively. After operation mean survival time of was 47 months. CONCLUSIONS: The specific GIST constituted the majority of mesenchymal tumors in rectum. It usually showed malignant biological behavior. Invasion and recurrence were common. Earlier diagnosis and radical resection had better prognosis. Periodically following up can help to detect the recurrence timely.
Asunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias del Recto , Adulto , Anciano , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the effect of combined resection for the treatment of T(4) gastric cancer and to refine the indication for en bloc dissection. METHODS: Clinical data of 69 cases receiving combined resection were analyzed retrospectively, and compared with those of 45 cases undergoing palliative gastrectomy. RESULTS: Of 69 cases, 54 patients underwent curative combined resection, 15 patients underwent palliative combined resection, including 24 with transverse colectomy, 22 with pancreatico-splenectomy, 8 with left lateral lobectomy of liver, 6 with pancreatico-splenectomy and transverse colectomy, 5 with pancreaticoduodenectomy, 2 with cholecystectomy, 1 with splenectomy, 1 with phrenectomy. The total rate of lymph node metastasis was 88.4%; the operative mortality rate was 4.3%; the morbidity rate was 14.5%. The postoperatively 1-, 3-, 5-year survival rates of CR group and NCR group were 66.9%, 39.1%, 26.8% and 33.4%, 7.4%, 0% respectively (P < 0.01). The five year survival rate of curative resection group was 34.1%. CONCLUSIONS: An en bloc combined resection can cure some T(4) patients, and improve the five-year survival rate.