Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due t...Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.展开更多
AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study ...AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study was conducted on 140 subjects classified into two groups, 70 with T2D and 70 HS. Medical history and physical examination with anthropometric measurements were obtained from all subjects. Body fat percentage was determined by bioelectrical impendency analysis. Serum uc OC concentration was determined by enzyme immunoassay,while serum levels of insulin and hsC RP were obtained using high sensitivity enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment-IR. Lipid profile [triglycerides,total cholesterol(TC), high-density lipoproteins(HDL-c),low density lipoproteins(LDL-c), very low-density lipoproteins] was determined by spectrophotometry and standard formulas when applicable. RESULTS The T2D patient group showed significantly higher values of waist circumference, waist-to-hip ratio, systolic blood pressure(SBP), diastolic blood pressure(DBP),current smoking, and alcohol use when compared to the HS group(P < 0.05). We observed a significantly lower serum ucO C concentration in T2D than in HS(1.5 ± 1.4vs 2.3 ± 1.8, P < 0.05). In the whole study population,ucO C concentration was inversely correlated with body mass index(BMI)(r =-0.236, P < 0.05), fasting plasma glucose(r =-0.283, P < 0.01) and HDL-c(r =-0.255,P < 0.05); and positively correlated with LDL-c/HDL-c ratio(r = 0.306, P < 0.05) and TC/HDL-c ratio(r =0.284, P < 0.05). In the T2D group, serum uc OC concentration was inversely correlated with BMI(r =-0.310, P < 0.05) and body-fat percentage(r =-0.311,P < 0.05), and positively correlated with DBP(r = 0.450,P < 0.01). In HS group a positive correlation between serum levels of uc OC and SBP(r = 0.277, P < 0.05)was observed. CONCLUSION Serum uc OC is a potential marker for cardiovascular risk in Mexicans because it is related to adiposity parameters, blood pressure and lipid profile.展开更多
AIM To investigate the effects of sleeve gastrectomy plus trunk vagotomy(SGTV) compared with sleeve gastrectomy(SG) in a diabetic rat model.METHODS SGTV, SG, TV and Sham operations were performed on rats with diabetes...AIM To investigate the effects of sleeve gastrectomy plus trunk vagotomy(SGTV) compared with sleeve gastrectomy(SG) in a diabetic rat model.METHODS SGTV, SG, TV and Sham operations were performed on rats with diabetes induced by high-fat diet and streptozotocin. Body weight, food intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance(HOMA-IR), hepatic insulin signaling(IR, IRS1, IRS2, PI3 K and AKT), oral glucose stimulatedinsulin secretion, GLP-1 and ghrelin were compared at various postoperative times.RESULTS Both SG and SGTV resulted in better glucose tolerance, lower HOMA-IR, up-regulated hepatic insulin signaling, higher levels of oral glucose-stimulated insulin secretion, higher postprandial GLP-1 and lower fasting ghrelin levels than the TV and Sham groups. No significant differences were observed between the SG and SGTV groups. In addition, no significant differences were found between the TV and Sham groups in terms of glucose tolerance, HOMA-IR, hepatic insulin signaling, oral glucose-stimulated insulin secretion, postprandial GLP-1 and fasting ghrelin levels. No differences in body weight and food intake were noted between the four groups.CONCLUSION SGTV is feasible for diabetes control and is independent of weight loss. However, SGTV did not result in a better improvement in diabetes than SG alone.展开更多
AIM:To determine if other molecules reported to modulate AMP-dependent protein kinase(AMPK)activ-ity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism.ME...AIM:To determine if other molecules reported to modulate AMP-dependent protein kinase(AMPK)activ-ity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism.METHODS:Studies were performed with four hu-man colon cancer cell lines,Caco-2,HCT116,HT29 and SW1116.The compounds that were studied included A-769662,5-aminoimidazole-4-carboxamide-1-ribofu-ranoside,butyrate,(-)-epigallocatechin gallate(EGCG),KU-55933,quercetin,resveratrol and salicylates.The parameters that were measured were cell proliferation and viability,glucose uptake,lactate production and acidification of the incubation medium.RESULTS:Investigations with several molecules that have been reported to be associated with AMPK activa-tion(A-769662,5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside,EGCG,KU-55933,quercetin,resve-ratrol and salicylates)or AMPK inhibition(compound C)failed to reveal increased medium acidification and increased glucose uptake in colon cancer cells as previ-ously established with metformin and phenformin.The only exception was 5-aminosalicylic acid with which there were apparently lower glucose levels in the me-dium after incubation for 72 h.Further study in the absence of cells revealed that the effect was an artifact due to inhibition of the enzyme-linked glucose assay.The compounds were studied at concentrations that inhibited cell proliferation.CONCLUSION:It was concluded that treatment with several agents that can affect AMPK activity resulted in the inhibition of the proliferation of colon cancer cells under conditions in which glucose metabolism is not enhanced,in contrast to the effect of biguanides.展开更多
Positron emission tomography(PET) with ^(18)F-fluorodeoxyglucose(FDG) is a diagnostic tool to evaluate metabolic activity by measuring accumulation of FDG, an analogue of glucose, and has been widely used for detectin...Positron emission tomography(PET) with ^(18)F-fluorodeoxyglucose(FDG) is a diagnostic tool to evaluate metabolic activity by measuring accumulation of FDG, an analogue of glucose, and has been widely used for detecting small tumors, monitoring treatment response and predicting patients' prognosis in a variety of cancers. However, the molecular mechanism of FDG accumulation into tumors remains to be investigated. It is well-known that most cancers are metabolically active with elevated glucose metabolism, a phenomenon known as the Warburg effect. The underlying mechanisms for elevated glucose metabolism in cancer tissues are complex. Recent reports have indicated the potential of FDG-PET/CT scans in predicting mutational status(e.g., KRAS gene mutation) of colorectal cancer(CRC), which suggests that FDG-PET/CT scans may play a key role in determining therapeutic strategies by non-invasively predicting treatment response to anti-epidermal growth factor receptor(EGFR) therapy. In this review, we summarize the current findings investigating the molecular mechanism of ^(18)F-FDG accumulation in CRC.展开更多
文摘Hepatocellular carcinoma(HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.
文摘AIM To determine a potential relationship between serum undercarboxylated(uc OC) concentration and cardiovascular risk factors in type 2 diabetes(T2D) patients and healthy subjects(HS).METHODS A cross-sectional study was conducted on 140 subjects classified into two groups, 70 with T2D and 70 HS. Medical history and physical examination with anthropometric measurements were obtained from all subjects. Body fat percentage was determined by bioelectrical impendency analysis. Serum uc OC concentration was determined by enzyme immunoassay,while serum levels of insulin and hsC RP were obtained using high sensitivity enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment-IR. Lipid profile [triglycerides,total cholesterol(TC), high-density lipoproteins(HDL-c),low density lipoproteins(LDL-c), very low-density lipoproteins] was determined by spectrophotometry and standard formulas when applicable. RESULTS The T2D patient group showed significantly higher values of waist circumference, waist-to-hip ratio, systolic blood pressure(SBP), diastolic blood pressure(DBP),current smoking, and alcohol use when compared to the HS group(P < 0.05). We observed a significantly lower serum ucO C concentration in T2D than in HS(1.5 ± 1.4vs 2.3 ± 1.8, P < 0.05). In the whole study population,ucO C concentration was inversely correlated with body mass index(BMI)(r =-0.236, P < 0.05), fasting plasma glucose(r =-0.283, P < 0.01) and HDL-c(r =-0.255,P < 0.05); and positively correlated with LDL-c/HDL-c ratio(r = 0.306, P < 0.05) and TC/HDL-c ratio(r =0.284, P < 0.05). In the T2D group, serum uc OC concentration was inversely correlated with BMI(r =-0.310, P < 0.05) and body-fat percentage(r =-0.311,P < 0.05), and positively correlated with DBP(r = 0.450,P < 0.01). In HS group a positive correlation between serum levels of uc OC and SBP(r = 0.277, P < 0.05)was observed. CONCLUSION Serum uc OC is a potential marker for cardiovascular risk in Mexicans because it is related to adiposity parameters, blood pressure and lipid profile.
基金Supported by National Natural Science Foundation of China,No.81471019(to Hu SY)and No.81300286(to Liu SZ)Foundation for Outstanding Young Scientist in Shandong Province,No.BS2013YY031(to Liu SZ)+1 种基金Science and Technology Development Program of Shandong Province,No.2014GGE27485(to Liu SZ)Specialized Research Fund for the Doctoral Program of Higher Education of China,No.20130131120069(to Liu SZ)
文摘AIM To investigate the effects of sleeve gastrectomy plus trunk vagotomy(SGTV) compared with sleeve gastrectomy(SG) in a diabetic rat model.METHODS SGTV, SG, TV and Sham operations were performed on rats with diabetes induced by high-fat diet and streptozotocin. Body weight, food intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance(HOMA-IR), hepatic insulin signaling(IR, IRS1, IRS2, PI3 K and AKT), oral glucose stimulatedinsulin secretion, GLP-1 and ghrelin were compared at various postoperative times.RESULTS Both SG and SGTV resulted in better glucose tolerance, lower HOMA-IR, up-regulated hepatic insulin signaling, higher levels of oral glucose-stimulated insulin secretion, higher postprandial GLP-1 and lower fasting ghrelin levels than the TV and Sham groups. No significant differences were observed between the SG and SGTV groups. In addition, no significant differences were found between the TV and Sham groups in terms of glucose tolerance, HOMA-IR, hepatic insulin signaling, oral glucose-stimulated insulin secretion, postprandial GLP-1 and fasting ghrelin levels. No differences in body weight and food intake were noted between the four groups.CONCLUSION SGTV is feasible for diabetes control and is independent of weight loss. However, SGTV did not result in a better improvement in diabetes than SG alone.
基金Supported by The grants from the Alma Toorock Memorial for Cancer Research
文摘AIM:To determine if other molecules reported to modulate AMP-dependent protein kinase(AMPK)activ-ity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism.METHODS:Studies were performed with four hu-man colon cancer cell lines,Caco-2,HCT116,HT29 and SW1116.The compounds that were studied included A-769662,5-aminoimidazole-4-carboxamide-1-ribofu-ranoside,butyrate,(-)-epigallocatechin gallate(EGCG),KU-55933,quercetin,resveratrol and salicylates.The parameters that were measured were cell proliferation and viability,glucose uptake,lactate production and acidification of the incubation medium.RESULTS:Investigations with several molecules that have been reported to be associated with AMPK activa-tion(A-769662,5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside,EGCG,KU-55933,quercetin,resve-ratrol and salicylates)or AMPK inhibition(compound C)failed to reveal increased medium acidification and increased glucose uptake in colon cancer cells as previ-ously established with metformin and phenformin.The only exception was 5-aminosalicylic acid with which there were apparently lower glucose levels in the me-dium after incubation for 72 h.Further study in the absence of cells revealed that the effect was an artifact due to inhibition of the enzyme-linked glucose assay.The compounds were studied at concentrations that inhibited cell proliferation.CONCLUSION:It was concluded that treatment with several agents that can affect AMPK activity resulted in the inhibition of the proliferation of colon cancer cells under conditions in which glucose metabolism is not enhanced,in contrast to the effect of biguanides.
文摘Positron emission tomography(PET) with ^(18)F-fluorodeoxyglucose(FDG) is a diagnostic tool to evaluate metabolic activity by measuring accumulation of FDG, an analogue of glucose, and has been widely used for detecting small tumors, monitoring treatment response and predicting patients' prognosis in a variety of cancers. However, the molecular mechanism of FDG accumulation into tumors remains to be investigated. It is well-known that most cancers are metabolically active with elevated glucose metabolism, a phenomenon known as the Warburg effect. The underlying mechanisms for elevated glucose metabolism in cancer tissues are complex. Recent reports have indicated the potential of FDG-PET/CT scans in predicting mutational status(e.g., KRAS gene mutation) of colorectal cancer(CRC), which suggests that FDG-PET/CT scans may play a key role in determining therapeutic strategies by non-invasively predicting treatment response to anti-epidermal growth factor receptor(EGFR) therapy. In this review, we summarize the current findings investigating the molecular mechanism of ^(18)F-FDG accumulation in CRC.
