Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer t...Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.展开更多
AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer...AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.展开更多
<strong>Introduction:</strong> Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the...<strong>Introduction:</strong> Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. <strong>Patients and Methods:</strong> This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. <strong>Conclusion:</strong> This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.展开更多
Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been fo...Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been found to be deregulated in multiple cancers,and its high expression was correlated with poor prognosis.However,so far,no information was reported about the expression of KLF8 in pancreatic cancer.In the present study,we investigated,possibly for the first time,the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival （OS） rate.Methods We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics.We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time.Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.Results KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9％ of the 68 cases had positive expression.KLF8 expression was not associated with sex,age,tumor location,lymph node stage,and metastasis stage,but was associated with tumor stage （P=0.04）.Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis.In univariate and multivariate models,KLF8 was a significant predictor of OS in pancreatic cancer.Conclusion Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.展开更多
Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been i...Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.展开更多
Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasi...Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.展开更多
Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts ...Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.展开更多
文摘Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.
基金Supported by The Shandong Province Natural Science Foundation of China, No. ZR2010HZ004the National Key Clinical Medical Specialties Foundation
文摘AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.
文摘<strong>Introduction:</strong> Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. <strong>Patients and Methods:</strong> This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. <strong>Conclusion:</strong> This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.
基金This study was supported by the National Natural Science Foundation of China，China Health Industry Research and Special Fund
文摘Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been found to be deregulated in multiple cancers,and its high expression was correlated with poor prognosis.However,so far,no information was reported about the expression of KLF8 in pancreatic cancer.In the present study,we investigated,possibly for the first time,the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival （OS） rate.Methods We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics.We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time.Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.Results KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9％ of the 68 cases had positive expression.KLF8 expression was not associated with sex,age,tumor location,lymph node stage,and metastasis stage,but was associated with tumor stage （P=0.04）.Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis.In univariate and multivariate models,KLF8 was a significant predictor of OS in pancreatic cancer.Conclusion Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.
基金The work was supported by the National Natural Science Foundation of China(81970360).
文摘Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.
基金grants from the National Institutes of Health awarded to Yang VW (CA084197)
文摘Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.
基金supported by the Science and Technology project of Henan Province(202102310142)the National Natural Science Foundation of China(32001806)。
文摘Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.
