醫(yī)科大學精品課件：研究生專業(yè)英語

1、Tumor and aerobic glycolysis,Department of physiology and neurobiology Zhengzhou University Zhao Wenchao,Tumor,Robert A. Weinberg, et al. The Hallmarks of Cancer. Cell, 2000,1. Self-sufficiency in growth signals,2. Insensitivity to antigrowth signals,3. Evading apoptosis,4. Limitless replicative pot

2、ential,5. Sustained angiogenesis,6. Tissue invasion and metastasis,7. Aerobic glycolysis,Glucose,hexokinase,glucose-6-phosphate,fructose-6-phosphate,phosphoglucose isomerase,fructose l, 6 bisphosphate,glyceraldehyde-3-phosphate,dihydroxyacetone phosphate,aldolase,glyceraldehyde-3-phosphate dehydroge

3、nase,1, 3-biphosphoglycerate,phosphoglycerate kinase,3-phosphoglycerate,6-phosphofructokinase1,2-phosphoglycerate,phosphoglycerate mutase,phosphoenolpyruvate,enolase,pyruvate,pyruvate kinase,TCA,lactate,lactate dehydrogenase,Otto Heinrich Warburg,Lactate production increase,Glucose consumption incre

4、ase,Warburg effect,Aerobic glycolysis,Increased glycolysis,1. Response to hypoxia,1920s,1) In the early stage of tumor development, tumor cells are restricted in stroma without blood vessels due to intact basement menbrane,2) Diffusion of O2 for over 150m is impossible,3) No tumor cells can live 160

5、m away from blood vessels,Otto Heinrich Warburg,Lactate production increase,Glucose consumption increase,Warburg effect,Aerobic glycolysis,Increased glycolysis,1. Response to hypoxia,2. Provide matetials for proliferation,Glucose,glucose-6-phosphate,fructose l, 6 bisphosphate,glyceraldehyde-3-phosph

6、ate,dihydroxyacetone phosphate,3-phosphoglycerate,pentose phosphate pathway,ribose-5-phosphate,fatty acid,serine,Otto Heinrich Warburg,Lactate production increase,Glucose consumption increase,Warburg effect,Aerobic glycolysis,Increased glycolysis,1. Response to hypoxia,2. Provide materials for proli

7、feration,3. Provide acid microenvioment,3. Provide acid microenvioment,Activates matrix metalloproteinase (MMP,Otto Heinrich Warburg,Lactate production increase,Glucose consumption increase,Warburg effect,Aerobic glycolysis,Increased glycolysis,1. Response to hypoxia,2. Provide matetials for prolife

8、ration,3. Provide acid microenvioment,4. Provide energy rapidly,Glucose,hexokinase,glucose-6-phosphate,fructose-6-phosphate,phosphoglucose isomerase,fructose l, 6 bisphosphate,glyceraldehyde-3-phosphate,dihydroxyacetone phosphate,aldolase,glyceraldehyde-3-phosphate dehydrogenase,1, 3-biphosphoglycer

9、ate,phosphoglycerate kinase,3-phosphoglycerate,6-phosphofructokinase1,2-phosphoglycerate,phosphoglycerate mutase,phosphoenolpyruvate,enolase,pyruvate,pyruvate kinase,lactate,lactate dehydrogenase,Hexokinase, HK,1. Unidirection,Glucose,glucose-6-phosphate (G6P,2. Activity of HK is inhibited by G6P,3.

10、 Dependent of ATP, activity of HK is inhibited by ADP,4. Two forms: free and binding to mitochondrion,HK,HK,HK,HK,Most tissues,Low expression in fat, muscle, heart,Low expression in liver, kidney, intestine,liver, pancreas,Distribution,Km,0.02 mM,0.02 mM,0.02 mM,5 mM,tumor,HK,1. Overexpression in ca

11、ncer of breast, lung, gastrointestine, liver, pancreas, etc,2. Overexpression is positively related to poor prognosis, growth, migration, invasion,3. Higher expression in undifferentiated colon cancer than in differentiated ones,4. In the solid tumor, higher expression in central part than in border

12、,5. Increase in binding to mitochondrion in maligant tumor,Glucose,hexokinase,glucose-6-phosphate,fructose-6-phosphate,phosphoglucose isomerase,fructose l, 6 bisphosphate,glyceraldehyde-3-phosphate,dihydroxyacetone phosphate,aldolase,glyceraldehyde-3-phosphate dehydrogenase,1, 3-biphosphoglycerate,p

13、hosphoglycerate kinase,3-phosphoglycerate,6-phosphofructokinase1,2-phosphoglycerate,phosphoglycerate mutase,phosphoenolpyruvate,enolase,pyruvate,pyruvate kinase,lactate,lactate dehydrogenase,6-phosphofructokinase1, PFK1,fructose-6-phosphate,fructose l, 6 bisphosphate,1. Unidirection,2. PFK1 activity

14、 is inhibited by ATP, citrate, long-chain fatty acids, lactate and stimulated by ADP/AMP,3. PFK1 activity is stimulated by fructose 2, 6 bisphosphate,PFK2,fructose 2, 6 bisphosphate,Feed-forward,PFK1,M type,L type,P type,Muscle,Liver, kindey,Platelet,High expression in tumor,Less sensitive to ATP an

15、d citrate,More sensitive to 2,6FBP,PFK2,Poor prognosis and metastasis,Glucose,hexokinase,glucose-6-phosphate,fructose-6-phosphate,phosphoglucose isomerase,fructose l, 6 bisphosphate,glyceraldehyde-3-phosphate,dihydroxyacetone phosphate,aldolase,glyceraldehyde-3-phosphate dehydrogenase,1, 3-biphospho

16、glycerate,phosphoglycerate kinase,3-phosphoglycerate,6-phosphofructokinase1,2-phosphoglycerate,phosphoglycerate mutase,phosphoenolpyruvate,enolase,pyruvate,pyruvate kinase,lactate,lactate dehydrogenase,Pyruvate kinase, PK,PKL,PKR,PKM1,PKM2,liver and kidneys,erythrocyte,muscle, heart , brain,self-ren

17、ewing cells: stem cells, tumor cells,embryogenesis,PKM2,differentiation,PKM1/L/R,tumor,PKM2,dimer,PKM2,tetramer,Km,0.03 mM,0.46 mM,activity,high,low,tissue,normal cells,tumor,Glucose,glucose-6-phosphate,fructose l, 6 bisphosphate,glyceraldehyde-3-phosphate,dihydroxyacetone phosphate,3-phosphoglycera

18、te,phosphoenolpyruvate,pyruvate,PKM2,breast cancer, bladder carcinoma, colon cancer, esophageal squamous cell cancer, glioma, head and neck cancer, liver cancer, lung carcinoma, meningiomas, renal cell carcinoma,overexpression in tumors,increases in serum,patients with colon, breast, urological, lun

19、g, cervix, and gastrointestinal tumor,detected in the feces,patients with gastric and colorectal cancer,fructose l, 6 bisphosphate,dimer,tetramer,Tyrosine kinase,Inhibition the binding of 2,6FBP to PKM2,3-phosphoglycerate,Glucose,phosphoenolpyruvate,serine,Glucose transporter,sodium-dependent glucos

20、e transporter, SGLT,facilitative glucose transporter, GLUT,active,passive,SGLT,SGLT,SGLT1,SGLT2,SGLT3,SGLT4,SGLT5,SGLT6,small intestine, trachea, kidney, heart, colon,kidney,small intestine,small intestine, kidney,kidney,spinal cord, kidney, brain, small intestine,SGLT1,colorectal, head and neck, an

21、d prostate tumors,metastatic lesions of lung, pancreatic adenocarcinomas, and head and neck cancers,SGLT2,colorectal, gastrointestinal, head and neck, kidney tumors,metastatic lesions of lung, pancreatic adenocarcinomas, and head and neck cancers,GLUT,GLUT1-14,GLUT1,different expression in different

22、 cancers,high affinity for glucose and insensitive to insulin,erythrocytes, placenta, endothelial cells,GLUT2,lowest affinity for glucose, also transport fructose,liver, pancreatic islet cells, retina, stomach,overexpression in gastric tumors,was not detected in insulinomas or other types of islet c

23、ell tumors,GLUT3,overexpression in many tunors,brain, placenta, testes,means poor prognosis,highest affinity for glucose and insensitive to insulin,GLUT4,cardiac muscle, skeletal muscle, adipose,overexpression in gastric and breast cancer,GLUT5,kidneys, testes, small intestine, muscle, adipose tissu

24、e,overexpression in renal cell carcinoma, breast and prostate cancer,high affinity for glucose and sensitive to insulin,high affinity for fructose,GLUT8,testis, adrenal gland, liver, spleen and lung,overexpression in multiple myeloma,GLUT12,overexpression in breast cancer,heart, small intestine, skeletal muscle,Factors regulating expression of GLUTs, HK2, PFK1, PKM2,1. hypoxia,2. oncogene and tumor supressor gene,C-myc,p53,3. growth factors,EGF,4. hormones,estrogen,hypoxia-inducible factor-1, HIF-1,HIF-1,HI