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Surgical Stress Promotes the Development of Cancer Metastases by a Coagulation-Dependent Mechanism in a Murine ModelSeth, Rashmi 07 September 2011 (has links)
Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.
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Surgical Stress Promotes the Development of Cancer Metastases by a Coagulation-Dependent Mechanism in a Murine ModelSeth, Rashmi 07 September 2011 (has links)
Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.
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Surgical Stress Promotes the Development of Cancer Metastases by a Coagulation-Dependent Mechanism in a Murine ModelSeth, Rashmi 07 September 2011 (has links)
Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.
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Surgical Stress Promotes the Development of Cancer Metastases by a Coagulation-Dependent Mechanism in a Murine ModelSeth, Rashmi January 2011 (has links)
Surgery precipitates a hypercoagulable state and has been shown to increase the development of cancer metastases in animal models, however mechanism(s) responsible for this are largely unknown. We hypothesize that the prometastatic effect of surgery may be secondary to postoperative hypercoagulable state. Surgical stress was induced in mice by partial hepatectomy or nephrectomy, preceded by intravenous injection of CT26-LacZ or B16F10-LacZ cells to establish pulmonary metastases with or without perioperative anticoagulation and their lung tumor cell emboli (TCE) were quantified. Fibrinogen and platelets were fluorescently labeled prior to surgical stress to evaluate TCE-associated fibrin and platelet clots. Surgery significantly increased metastases while anticoagulation with five different agents attenuated this effect. Fibrin and platelet clots were associated with TCE significantly more frequently in surgically stressed mice. Surgery promotes the formation of fibrin and platelet clots around TCE and this appears to be the mechanism for the increase in metastases seen following surgery.
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MMP-7 is Required for TGF-β and EGF Induced Migration and Invasion in Prostate Cancer CellsBolton, Clement, II 08 August 2018 (has links)
Prostate cancer micrometastasis allows cancer cells to vacate their original tumor sites and migrate to distant parts of the body via the bloodstream, lymphatic system, or by direct extension. Cells synthesize and secrete matrix metalloproteinases (MMPs) that degrade proteins of the surrounding extracellular matrix (ECM); thus allowing them to escape into the lymphatic or circulatory systems to invade other tissues. Transforming growth factor β (TGF-β) induces the migration and invasion of cancer cells and the expression of matrix metalloproteinases (MMPs), specifically MMP-2, and -9 in several malignancies. In this study, we examined the role of MMP-7, a known activator of MMP-2 and MMP-9, in TGF-β signaling in cell proliferation, migration, and invasion in prostate cancer cells. Basal expression levels of MMP7 mRNA, protein, and secreted protein were determined using RT-PCR, western blot analysis, and ELISA, respectively. Our data show that MMP7 mRNA and proteins were differentially expressed in several cell line models representing different stages of prostate cancer. TGF-β1 induces MMP-7 gene expression and protein levels 24 and 48 hours after treatment in PC3 cells. Our data also show that TGF-β induces cell migration and invasion in PC3 and E006AA cells; however, the selective knockdown of MMP7 expression using siRNA resulted in a significant decrease in control and TGFβ-induced cell migration and invasion in both PC3 and E006AA cells. MMP-7 knockdown also caused significant reduction in cell proliferation in PC3 cells. Our data suggest that MMP7 is essential for cell migration and invasion in prostate cancer cells indicating that it may be required for TGFβ-induced cancer metastases.
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Fatores prognósticos na ressecção de metástases hepáticas de câncer colorretalChedid, Aljamir Duarte January 2002 (has links)
OBJETIVO: Determinar o impacto de fatores prognósticos na sobrevida de pacientes com metástases hepáticas ressecadas e originadas de câncer colorretal. CASUISTICA E MÉTODOS: Foram analisados os prontuários de 28 pacientes submetidos a ressecção hepática de metástases de câncer colorretal de Abril /1992 a Setembro /2001. Foram realizadas 38 ressecções (8 pacientes com mais de uma ressecção no mesmo tempo cirúrgico e 2 pacientes submetidos a re-ressecções). Todos haviam sido submetidos previamente à ressecção do tumor primário. Utilizou-se um protocolo de rastreamento de metástases hepáticas que incluiu revisões clinicas trimestrais, ecografia abdominal e dosagem de CEA até completarem-se 5 anos de seguimento e, após, semestralmente. Os fatores prognósticos estudados foram: estágio do tumor primário, tamanho das metástases > 5cm, intervalo entre ressecção do tumor primário e surgimento da metástase <1 ano, CEA>100ng/ml, margens cirúrgicas <1cm e doença metastática extra-hepática. O estudo foi retrospectivo e a análise estatística foi feita através da curva de Kaplan-Meier, do log rank e da regressão de Cox. RESULTADOS: A morbidade foi 39,3% e a mortalidade operatória foi 3,6%.A sobrevida em 5 anos foi de 35%. Os fatores prognósticos independentes adversos foram: intervalo <1 ano entre ressecção do tumor primário e surgimento da metástase (p=0,047 e RR 11,56) e doença metastática extra-hepática (p=0,004 e RR=57,28). CONCLUSÕES: A ressecção hepática de metástases de câncer colorretal é um procedimento seguro com sobrevida em 5 anos acima dos 30%. Foram fatores prognósticos independentes adversos: doença metastática extra-hepática e intervalo<1ano entre ressecção do tumor primário e surgimento da metástase. / Prognostic factors following liver resection for hepatic metastases from colorectal cancer. BACKGROUND: To determine the impact of prognostic factors on survival of patients with metastases from colorectal cancer that underwent liver resection. METHODS: The records of 28 patients that underwent liver resection for metastases from colorectal cancer between April /1992 and September/2001 were retrospectively analized. Thirty-eight resections were performed (more than one resection in eight patients and two patients underwent re-resections). The primary tumor was resected in all the patients. A screening protocol for liver metastases including clinical examinations every three months, abdominal ultrassonography and CEA level until five years of follow-up and after every six months, was applied. The prognostic factors analized regarding the impact on survival were: Dukes C stage of primary tumor, size of metastasis > 5cm, a disease-free interval from primary tumor to metastasis < 1 year, CEA level > 100ng/ml, resection margins < 1cm and extrahepatic disease. The Kaplan-Meier curves, log rank and Cox regression were used for the statistical analysis. RESULTS: Perioperative morbidity and mortality were 39,3% and 3,6% respectively. The 5-year survival rate was 35%. The independent prognostic factors were: disease-free interval from primary tumor to metastasis < 1year (p=0,047; RR=11,56) and extrahepatic metastatic disease (p=0,004; RR=57,28). CONCLUSIONS: The liver resection for metastases from colorectal cancer is a safe procedure with more than 30% 5-year survival .Disease- free interval from primary tumor to metastasis < 1year and extrahepatic disease were independent prognostic factors.
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Fatores prognósticos na ressecção de metástases hepáticas de câncer colorretalChedid, Aljamir Duarte January 2002 (has links)
OBJETIVO: Determinar o impacto de fatores prognósticos na sobrevida de pacientes com metástases hepáticas ressecadas e originadas de câncer colorretal. CASUISTICA E MÉTODOS: Foram analisados os prontuários de 28 pacientes submetidos a ressecção hepática de metástases de câncer colorretal de Abril /1992 a Setembro /2001. Foram realizadas 38 ressecções (8 pacientes com mais de uma ressecção no mesmo tempo cirúrgico e 2 pacientes submetidos a re-ressecções). Todos haviam sido submetidos previamente à ressecção do tumor primário. Utilizou-se um protocolo de rastreamento de metástases hepáticas que incluiu revisões clinicas trimestrais, ecografia abdominal e dosagem de CEA até completarem-se 5 anos de seguimento e, após, semestralmente. Os fatores prognósticos estudados foram: estágio do tumor primário, tamanho das metástases > 5cm, intervalo entre ressecção do tumor primário e surgimento da metástase <1 ano, CEA>100ng/ml, margens cirúrgicas <1cm e doença metastática extra-hepática. O estudo foi retrospectivo e a análise estatística foi feita através da curva de Kaplan-Meier, do log rank e da regressão de Cox. RESULTADOS: A morbidade foi 39,3% e a mortalidade operatória foi 3,6%.A sobrevida em 5 anos foi de 35%. Os fatores prognósticos independentes adversos foram: intervalo <1 ano entre ressecção do tumor primário e surgimento da metástase (p=0,047 e RR 11,56) e doença metastática extra-hepática (p=0,004 e RR=57,28). CONCLUSÕES: A ressecção hepática de metástases de câncer colorretal é um procedimento seguro com sobrevida em 5 anos acima dos 30%. Foram fatores prognósticos independentes adversos: doença metastática extra-hepática e intervalo<1ano entre ressecção do tumor primário e surgimento da metástase. / Prognostic factors following liver resection for hepatic metastases from colorectal cancer. BACKGROUND: To determine the impact of prognostic factors on survival of patients with metastases from colorectal cancer that underwent liver resection. METHODS: The records of 28 patients that underwent liver resection for metastases from colorectal cancer between April /1992 and September/2001 were retrospectively analized. Thirty-eight resections were performed (more than one resection in eight patients and two patients underwent re-resections). The primary tumor was resected in all the patients. A screening protocol for liver metastases including clinical examinations every three months, abdominal ultrassonography and CEA level until five years of follow-up and after every six months, was applied. The prognostic factors analized regarding the impact on survival were: Dukes C stage of primary tumor, size of metastasis > 5cm, a disease-free interval from primary tumor to metastasis < 1 year, CEA level > 100ng/ml, resection margins < 1cm and extrahepatic disease. The Kaplan-Meier curves, log rank and Cox regression were used for the statistical analysis. RESULTS: Perioperative morbidity and mortality were 39,3% and 3,6% respectively. The 5-year survival rate was 35%. The independent prognostic factors were: disease-free interval from primary tumor to metastasis < 1year (p=0,047; RR=11,56) and extrahepatic metastatic disease (p=0,004; RR=57,28). CONCLUSIONS: The liver resection for metastases from colorectal cancer is a safe procedure with more than 30% 5-year survival .Disease- free interval from primary tumor to metastasis < 1year and extrahepatic disease were independent prognostic factors.
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Fatores prognósticos na ressecção de metástases hepáticas de câncer colorretalChedid, Aljamir Duarte January 2002 (has links)
OBJETIVO: Determinar o impacto de fatores prognósticos na sobrevida de pacientes com metástases hepáticas ressecadas e originadas de câncer colorretal. CASUISTICA E MÉTODOS: Foram analisados os prontuários de 28 pacientes submetidos a ressecção hepática de metástases de câncer colorretal de Abril /1992 a Setembro /2001. Foram realizadas 38 ressecções (8 pacientes com mais de uma ressecção no mesmo tempo cirúrgico e 2 pacientes submetidos a re-ressecções). Todos haviam sido submetidos previamente à ressecção do tumor primário. Utilizou-se um protocolo de rastreamento de metástases hepáticas que incluiu revisões clinicas trimestrais, ecografia abdominal e dosagem de CEA até completarem-se 5 anos de seguimento e, após, semestralmente. Os fatores prognósticos estudados foram: estágio do tumor primário, tamanho das metástases > 5cm, intervalo entre ressecção do tumor primário e surgimento da metástase <1 ano, CEA>100ng/ml, margens cirúrgicas <1cm e doença metastática extra-hepática. O estudo foi retrospectivo e a análise estatística foi feita através da curva de Kaplan-Meier, do log rank e da regressão de Cox. RESULTADOS: A morbidade foi 39,3% e a mortalidade operatória foi 3,6%.A sobrevida em 5 anos foi de 35%. Os fatores prognósticos independentes adversos foram: intervalo <1 ano entre ressecção do tumor primário e surgimento da metástase (p=0,047 e RR 11,56) e doença metastática extra-hepática (p=0,004 e RR=57,28). CONCLUSÕES: A ressecção hepática de metástases de câncer colorretal é um procedimento seguro com sobrevida em 5 anos acima dos 30%. Foram fatores prognósticos independentes adversos: doença metastática extra-hepática e intervalo<1ano entre ressecção do tumor primário e surgimento da metástase. / Prognostic factors following liver resection for hepatic metastases from colorectal cancer. BACKGROUND: To determine the impact of prognostic factors on survival of patients with metastases from colorectal cancer that underwent liver resection. METHODS: The records of 28 patients that underwent liver resection for metastases from colorectal cancer between April /1992 and September/2001 were retrospectively analized. Thirty-eight resections were performed (more than one resection in eight patients and two patients underwent re-resections). The primary tumor was resected in all the patients. A screening protocol for liver metastases including clinical examinations every three months, abdominal ultrassonography and CEA level until five years of follow-up and after every six months, was applied. The prognostic factors analized regarding the impact on survival were: Dukes C stage of primary tumor, size of metastasis > 5cm, a disease-free interval from primary tumor to metastasis < 1 year, CEA level > 100ng/ml, resection margins < 1cm and extrahepatic disease. The Kaplan-Meier curves, log rank and Cox regression were used for the statistical analysis. RESULTS: Perioperative morbidity and mortality were 39,3% and 3,6% respectively. The 5-year survival rate was 35%. The independent prognostic factors were: disease-free interval from primary tumor to metastasis < 1year (p=0,047; RR=11,56) and extrahepatic metastatic disease (p=0,004; RR=57,28). CONCLUSIONS: The liver resection for metastases from colorectal cancer is a safe procedure with more than 30% 5-year survival .Disease- free interval from primary tumor to metastasis < 1year and extrahepatic disease were independent prognostic factors.
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An individual patient data meta-analysis on characteristics, treatments and outcomes of Glioblastoma/ Gliosarcoma patients with metastases outside of the central nervous systemPietschmann, Sophie, von Bueren, André O., Kerber, Michael J., Baumert, Brigitta G., Kortmann, Rolf-Dieter, Müller, Klaus January 2015 (has links)
To determine the characteristics, treatments and outcomes of patients with glioblastoma multiforme (GBM) or gliosarcoma (GS) and metastases outside of the central nervous system (CNS).
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An investigation of Atf3, an adaptive-response gene, in breast cancer chemotherapy and stress response.Jalgaonkar, Swati 01 September 2016 (has links)
No description available.
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