首页 > 最新文献

Ernst Schering Foundation symposium proceedings最新文献

英文 中文
Asymmetric organocatalysis on a technical scale: current status and future challenges. 技术规模上的不对称有机催化:现状与未来挑战。
H Gröger
{"title":"Asymmetric organocatalysis on a technical scale: current status and future challenges.","authors":"H Gröger","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 2","pages":"141-58"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27547537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nucleophilic carbenes as organocatalysts. 亲核羰基作为有机催化剂。
F Glorius, K Hirano

N-Heterocyclic carbenes (NHC) have become an important class of organocatalysts and class of ligands for transition-metal catalysis. In organocatalyzed umpolung reactions, thiazolium salt-derived NHC have been used successfully for decades. Even so, during recent years there has been an increased interest in NHC-catalyzed transformations and many new reactions have been developed. This article focuses on the use of NHC in the conjugate umpolung of alpha,beta-unsaturated aldehydes.

n-杂环羰基(NHC)已成为一类重要的有机催化剂和一类重要的过渡金属催化配体。在有机催化的混合反应中,噻唑盐衍生的NHC已经成功使用了几十年。尽管如此,近年来人们对nhc催化的转化越来越感兴趣,并开发了许多新的反应。本文主要研究了NHC在α、β -不饱和醛共轭反应中的应用。
{"title":"Nucleophilic carbenes as organocatalysts.","authors":"F Glorius,&nbsp;K Hirano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>N-Heterocyclic carbenes (NHC) have become an important class of organocatalysts and class of ligands for transition-metal catalysis. In organocatalyzed umpolung reactions, thiazolium salt-derived NHC have been used successfully for decades. Even so, during recent years there has been an increased interest in NHC-catalyzed transformations and many new reactions have been developed. This article focuses on the use of NHC in the conjugate umpolung of alpha,beta-unsaturated aldehydes.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 2","pages":"159-81"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27547538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of the metabolic stress responses of apoptosis and autophagy in tumor suppression. 凋亡和自噬的代谢应激反应在肿瘤抑制中的作用。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_087
E White

Metabolic stress is an important stimulus that promotes apoptosis-mediated tumor suppression. Metabolic stress arises in tumors from multiple factors that include insufficient nutrient supply caused by deficient angiogenesis and high metabolic demand of unrestrained cell proliferation. The high metabolic demand of tumor cells is only exacerbated by reliance on the inefficient process of glycolysis for energy production. Recently it has become clear that tumor cells survive metabolic stress through the catabolic process of autophagy. Autophagy also functions as a tumor suppression mechanism by preventing cell death and inflammation and by protecting the genome from damage and genetic instability. How autophagy protects the genome is not yet clear but may be related to its roles in sustaining metabolism or in the clearance of damaged proteins and organelles and the mitigation of oxidative stress. These findings illuminate the important role of metabolism in cancer progression and provide specific predictions for metabolic modulation in cancer therapy.

代谢应激是促进细胞凋亡介导的肿瘤抑制的重要刺激物。肿瘤代谢应激的产生有多种因素,包括血管生成不足导致的营养供应不足和细胞无限制增殖的高代谢需求。肿瘤细胞的高代谢需求只会因依赖低效率的糖酵解过程而加剧。近年来,肿瘤细胞通过自噬的分解代谢过程在代谢应激中存活下来。自噬还作为一种肿瘤抑制机制,通过防止细胞死亡和炎症,保护基因组免受损伤和遗传不稳定。自噬如何保护基因组尚不清楚,但可能与它在维持代谢或清除受损蛋白质和细胞器以及减轻氧化应激中的作用有关。这些发现阐明了代谢在癌症进展中的重要作用,并为癌症治疗中的代谢调节提供了具体的预测。
{"title":"Role of the metabolic stress responses of apoptosis and autophagy in tumor suppression.","authors":"E White","doi":"10.1007/2789_2008_087","DOIUrl":"https://doi.org/10.1007/2789_2008_087","url":null,"abstract":"<p><p>Metabolic stress is an important stimulus that promotes apoptosis-mediated tumor suppression. Metabolic stress arises in tumors from multiple factors that include insufficient nutrient supply caused by deficient angiogenesis and high metabolic demand of unrestrained cell proliferation. The high metabolic demand of tumor cells is only exacerbated by reliance on the inefficient process of glycolysis for energy production. Recently it has become clear that tumor cells survive metabolic stress through the catabolic process of autophagy. Autophagy also functions as a tumor suppression mechanism by preventing cell death and inflammation and by protecting the genome from damage and genetic instability. How autophagy protects the genome is not yet clear but may be related to its roles in sustaining metabolism or in the clearance of damaged proteins and organelles and the mitigation of oxidative stress. These findings illuminate the important role of metabolism in cancer progression and provide specific predictions for metabolic modulation in cancer therapy.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"23-34"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27690206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 32
Cancer diagnostics using 1H-NMR-based metabonomics. 利用基于核磁共振的代谢组学进行癌症诊断。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_095
K Odunsi

For several solid human malignancies, currently available serum biomarkers are insufficiently reliable to distinguish patients from healthy individuals. Metabonomics, the study of metabolic processes in biologic systems, is based on the use of 1H-NMR spectroscopy and multivariate statistics for biochemical data generation and interpretation and may provide a characteristic fingerprint in disease. Here we review our initial experiences utilizing the metabonomic approach for discriminating sera from women with epithelial ovarian cancer (EOC) from healthy controls. 1H-NMR spectroscopic analysis was performed on preoperative serum specimens of 38 EOC patients, 12 patients with benign ovarian cysts and 53 healthy women. PCA analysis allowed correct separation of all serum specimens from 38 patients with EOC (100%) from all of the 21 premenopausal normal samples (100%) and from all the sera from patients with benign ovarian disease (100%). In addition, it was possible to correctly separate 37 of 38 (97.4%) cancer specimens from 31 of 32 (97%) postmenopausal control sera. ROC analysis indicated that the sera from patients with and without disease could be identified with 100% sensitivity and specificity at the 1H-NMR regions 2.77 parts per million (ppm) and 2.04 ppm from the origin (AUC of ROC curve = 1.0). These findings indicate that the 1H-NMR metabonomic approach deserves further evaluation as a potential novel strategy for the early detection of EOC.

对于一些实体人类恶性肿瘤,目前可用的血清生物标志物不足以可靠地区分患者和健康个体。代谢组学是研究生物系统中代谢过程的一门学科,它基于使用1H-NMR光谱和多元统计来生成和解释生化数据,并可能提供疾病的特征指纹。在这里,我们回顾了我们利用代谢组学方法区分上皮性卵巢癌(EOC)妇女血清与健康对照的初步经验。对38例EOC患者、12例良性卵巢囊肿患者和53例健康女性术前血清标本进行1H-NMR分析。PCA分析使38例EOC患者(100%)的所有血清标本与所有21例绝经前正常标本(100%)和所有良性卵巢疾病患者(100%)的血清标本正确分离。此外,38例(97.4%)癌症标本中有37例(97.4%)与32例(97%)绝经后对照血清中有31例(97%)可以正确分离。ROC分析表明,在h - nmr区域(起始点2.77 ppm和2.04 ppm),有病和无病患者的血清均能以100%的灵敏度和特异性进行鉴定(ROC曲线AUC = 1.0)。这些发现表明,作为早期发现EOC的潜在新策略,1H-NMR代谢组学方法值得进一步评估。
{"title":"Cancer diagnostics using 1H-NMR-based metabonomics.","authors":"K Odunsi","doi":"10.1007/2789_2008_095","DOIUrl":"https://doi.org/10.1007/2789_2008_095","url":null,"abstract":"<p><p>For several solid human malignancies, currently available serum biomarkers are insufficiently reliable to distinguish patients from healthy individuals. Metabonomics, the study of metabolic processes in biologic systems, is based on the use of 1H-NMR spectroscopy and multivariate statistics for biochemical data generation and interpretation and may provide a characteristic fingerprint in disease. Here we review our initial experiences utilizing the metabonomic approach for discriminating sera from women with epithelial ovarian cancer (EOC) from healthy controls. 1H-NMR spectroscopic analysis was performed on preoperative serum specimens of 38 EOC patients, 12 patients with benign ovarian cysts and 53 healthy women. PCA analysis allowed correct separation of all serum specimens from 38 patients with EOC (100%) from all of the 21 premenopausal normal samples (100%) and from all the sera from patients with benign ovarian disease (100%). In addition, it was possible to correctly separate 37 of 38 (97.4%) cancer specimens from 31 of 32 (97%) postmenopausal control sera. ROC analysis indicated that the sera from patients with and without disease could be identified with 100% sensitivity and specificity at the 1H-NMR regions 2.77 parts per million (ppm) and 2.04 ppm from the origin (AUC of ROC curve = 1.0). These findings indicate that the 1H-NMR metabonomic approach deserves further evaluation as a potential novel strategy for the early detection of EOC.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"205-26"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27691254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Defining personal nutrition and metabolic health through metabonomics. 通过代谢组学定义个人营养和代谢健康。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_097
S Rezzi, F-P J Martin, S Kochhar

A major charter for modern nutrition is to provide a molecular basis for health outcome resulting from different food choices and how this could be designed to maintain individual health free of disease. Nutrigenomic techniques have been developed to generate information at various levels of biological organization, i.e. genes, proteins, and metabolites. Within this frame, metabonomics targets the molecular characterization of a living system through metabolic profiling. The metabolic profiles are explored with sophisticated data mining techniques mainly based on multivariate statistics, which can recover key metabolic information to be further linked to biochemical processes and physiological events. The power of metabonomics relies on its unique ability to assess functional changes in the metabolism of complex organisms stemming from multiple influences such as lifestyle and environmental factors. In particular, metabolic profiles encapsulate information on the metabolic activity of symbiotic partners, i.e. gut microflora, in complex organisms, which represent major determinant in nutrition and health. Therefore, applications of metabonomics to nutrition sciences led to the nutrimetabonomics approach for the classification of dietary responses in populations and the possibility of optimized or personalized nutritional management.

现代营养学的一个主要章程是为不同食物选择导致的健康结果提供分子基础,以及如何设计这些食物以保持个人健康免受疾病的影响。营养基因组学技术已经发展到产生不同层次的生物组织信息,即基因、蛋白质和代谢物。在这个框架内,代谢组学通过代谢谱分析来针对生命系统的分子特征。利用基于多元统计的复杂数据挖掘技术探索代谢谱,可以恢复关键的代谢信息,进一步将其与生化过程和生理事件联系起来。代谢组学的力量依赖于其独特的能力来评估复杂生物体代谢的功能变化,这些变化源于多种影响,如生活方式和环境因素。特别是,代谢谱包含了复杂生物体中共生伙伴(即肠道微生物群)代谢活动的信息,这是营养和健康的主要决定因素。因此,代谢组学在营养科学中的应用导致了营养代谢组学方法用于人群饮食反应的分类和优化或个性化营养管理的可能性。
{"title":"Defining personal nutrition and metabolic health through metabonomics.","authors":"S Rezzi,&nbsp;F-P J Martin,&nbsp;S Kochhar","doi":"10.1007/2789_2008_097","DOIUrl":"https://doi.org/10.1007/2789_2008_097","url":null,"abstract":"<p><p>A major charter for modern nutrition is to provide a molecular basis for health outcome resulting from different food choices and how this could be designed to maintain individual health free of disease. Nutrigenomic techniques have been developed to generate information at various levels of biological organization, i.e. genes, proteins, and metabolites. Within this frame, metabonomics targets the molecular characterization of a living system through metabolic profiling. The metabolic profiles are explored with sophisticated data mining techniques mainly based on multivariate statistics, which can recover key metabolic information to be further linked to biochemical processes and physiological events. The power of metabonomics relies on its unique ability to assess functional changes in the metabolism of complex organisms stemming from multiple influences such as lifestyle and environmental factors. In particular, metabolic profiles encapsulate information on the metabolic activity of symbiotic partners, i.e. gut microflora, in complex organisms, which represent major determinant in nutrition and health. Therefore, applications of metabonomics to nutrition sciences led to the nutrimetabonomics approach for the classification of dietary responses in populations and the possibility of optimized or personalized nutritional management.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"251-64"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27691256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Estrogens, progestins, and risk of breast cancer. 雌激素,孕激素和乳腺癌的风险。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2007_059
M C Pike, A H Wu, D V Spicer, S Lee, C L Pearce

Obesity is associated with a decreased risk of breast cancer in premenopausal women but an increased risk in postmenopausal women, an effect that increases with time since menopause. Analysis of these effects of obesity shows that there is a ceiling to the carcinogenic effect of estrogen on the breast; increases in nonsex hormone-binding globulin-bound estradiol (non-SHBG bound E2) exceeding approximately 10.2 pg/ml have no further effect on breast cancer risk; this ceiling is lower than the lowest level seen during the menstrual cycle. This suggests that the effects of menopausal estrogen therapy (ET) and menopausal estrogen-progestin therapy (EPT) on a woman's breast cancer risk will greatly depend on her body mass index (BMI; weight in kilograms/height in meters squared, kg/m2) with the largest effects being in slender women. Epidemiological studies confirm this prediction. Our best estimates, per 5 years of use, of the effects of ET on breast cancer risk is a 30% increase in a woman with a BMI of 20 kg/m2 decreasing to an 8% increase in a woman with a BMI of 30 kg/m2; the equivalent figures for EPT are 50% and 26%. The analysis of the effects of estrogen also shows that even reducing the dose of estrogen in ET and EPT by as much as a half will have little or no effect on these risks. Reducing the progestin dose is likely to significantly reduce the risk of EPT: this is possible with an endometrial route of administration.

肥胖与绝经前妇女患乳腺癌的风险降低有关,但与绝经后妇女患乳腺癌的风险增加有关,这种影响随着绝经后的时间而增加。对肥胖的这些影响的分析表明,雌激素对乳房的致癌作用有一个上限;非性激素结合的球蛋白结合的雌二醇(非shbg结合的E2)超过约10.2 pg/ml对乳腺癌风险没有进一步的影响;这个上限低于月经周期的最低水平。这表明绝经期雌激素治疗(ET)和绝经期雌激素-黄体酮治疗(EPT)对女性乳腺癌风险的影响将在很大程度上取决于她的体重指数(BMI;体重单位为公斤/身高单位为米的平方(kg/m2),对苗条女性的影响最大。流行病学研究证实了这一预测。我们的最佳估计是,每使用5年,雌激素对乳腺癌风险的影响是BMI为20 kg/m2的女性增加30%,而BMI为30 kg/m2的女性增加8%;EPT的等效数字为50%和26%。对雌激素影响的分析还表明,即使将雌激素在ET和EPT中的剂量减少一半,对这些风险的影响也很小或没有影响。减少黄体酮的剂量可能会显著降低EPT的风险:这可能与子宫内膜给药途径。
{"title":"Estrogens, progestins, and risk of breast cancer.","authors":"M C Pike,&nbsp;A H Wu,&nbsp;D V Spicer,&nbsp;S Lee,&nbsp;C L Pearce","doi":"10.1007/2789_2007_059","DOIUrl":"https://doi.org/10.1007/2789_2007_059","url":null,"abstract":"<p><p>Obesity is associated with a decreased risk of breast cancer in premenopausal women but an increased risk in postmenopausal women, an effect that increases with time since menopause. Analysis of these effects of obesity shows that there is a ceiling to the carcinogenic effect of estrogen on the breast; increases in nonsex hormone-binding globulin-bound estradiol (non-SHBG bound E2) exceeding approximately 10.2 pg/ml have no further effect on breast cancer risk; this ceiling is lower than the lowest level seen during the menstrual cycle. This suggests that the effects of menopausal estrogen therapy (ET) and menopausal estrogen-progestin therapy (EPT) on a woman's breast cancer risk will greatly depend on her body mass index (BMI; weight in kilograms/height in meters squared, kg/m2) with the largest effects being in slender women. Epidemiological studies confirm this prediction. Our best estimates, per 5 years of use, of the effects of ET on breast cancer risk is a 30% increase in a woman with a BMI of 20 kg/m2 decreasing to an 8% increase in a woman with a BMI of 30 kg/m2; the equivalent figures for EPT are 50% and 26%. The analysis of the effects of estrogen also shows that even reducing the dose of estrogen in ET and EPT by as much as a half will have little or no effect on these risks. Reducing the progestin dose is likely to significantly reduce the risk of EPT: this is possible with an endometrial route of administration.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 1","pages":"127-50"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2007_059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27487550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Molecular imaging of tumor metabolism and apoptosis. 肿瘤代谢与凋亡的分子影像学研究。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_092
U. Haberkorn, A. Altmann, W. Mier, M. Eisenhut
{"title":"Molecular imaging of tumor metabolism and apoptosis.","authors":"U. Haberkorn, A. Altmann, W. Mier, M. Eisenhut","doi":"10.1007/2789_2008_092","DOIUrl":"https://doi.org/10.1007/2789_2008_092","url":null,"abstract":"","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":"49 1","pages":"125-52"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77559091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 24
In vivo characterization of progestins with reduced non-genomic activity in vitro. 体外非基因组活性降低的孕激素的体内表征。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_077
C. Otto, B. Rohde-Schulz, G. Schwarz, I. Fuchs, M. Klewer, H. Altmann, K. Fritzemeier
{"title":"In vivo characterization of progestins with reduced non-genomic activity in vitro.","authors":"C. Otto, B. Rohde-Schulz, G. Schwarz, I. Fuchs, M. Klewer, H. Altmann, K. Fritzemeier","doi":"10.1007/2789_2008_077","DOIUrl":"https://doi.org/10.1007/2789_2008_077","url":null,"abstract":"","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":"19 1","pages":"151-70"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77653428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
The interplay between MYC and HIF in the Warburg effect. Warburg效应中MYC和HIF的相互作用。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_088
C V Dang

c-MYC and the hypoxia-inducible factors (HIFs) are critical factors for tumorigenesis in a large number of human cancers. While the normal function of MYC involves the induction of cell proliferation and enhancement of cellular metabolism, the function of HIF, particularly HIF-1, involves adaptation to the hypoxic microenvironment, including activation of anaerobic glycolysis. When MYC-dependent tumors grow, the hypoxic tumor microenvironment elevates the levels of HIF, such that oncogenic MYC and HIF collaborate to enhance the cancer cell's metabolic needs through increased uptake of glucose and its conversion to lactate. HIF is also able to attenuate mitochondrial respiration through the induction of pyruvate dehydrogenase kinase 1 (PDK1), which in part accounts for the Warburg effect that describes the propensity for cancers to avidly take up glucose and convert it to lactate with the concurrent decrease in mitochondrial respiration. Target genes that are common to both HIF and MYC, such as PDK1, LDHA, HK2, and TFRC, are therefore attractive therapeutic targets, because their coordinate induction by HIF and MYC widens the therapeutic window between cancer and normal tissues.

c-MYC和缺氧诱导因子(hif)是许多人类癌症发生的关键因素。MYC的正常功能包括诱导细胞增殖和增强细胞代谢,而HIF,特别是HIF-1的功能包括对缺氧微环境的适应,包括厌氧糖酵解的激活。当MYC依赖性肿瘤生长时,低氧肿瘤微环境会提高HIF水平,从而致癌MYC和HIF通过增加葡萄糖的摄取并将其转化为乳酸来增强癌细胞的代谢需求。HIF还能够通过诱导丙酮酸脱氢酶激酶1 (PDK1)来减弱线粒体呼吸,这在一定程度上解释了Warburg效应,该效应描述了癌症在线粒体呼吸减少的同时大量摄取葡萄糖并将其转化为乳酸的倾向。因此,HIF和MYC共有的靶基因,如PDK1、LDHA、HK2和TFRC,是有吸引力的治疗靶点,因为它们由HIF和MYC协同诱导,扩大了癌症和正常组织之间的治疗窗口。
{"title":"The interplay between MYC and HIF in the Warburg effect.","authors":"C V Dang","doi":"10.1007/2789_2008_088","DOIUrl":"https://doi.org/10.1007/2789_2008_088","url":null,"abstract":"<p><p>c-MYC and the hypoxia-inducible factors (HIFs) are critical factors for tumorigenesis in a large number of human cancers. While the normal function of MYC involves the induction of cell proliferation and enhancement of cellular metabolism, the function of HIF, particularly HIF-1, involves adaptation to the hypoxic microenvironment, including activation of anaerobic glycolysis. When MYC-dependent tumors grow, the hypoxic tumor microenvironment elevates the levels of HIF, such that oncogenic MYC and HIF collaborate to enhance the cancer cell's metabolic needs through increased uptake of glucose and its conversion to lactate. HIF is also able to attenuate mitochondrial respiration through the induction of pyruvate dehydrogenase kinase 1 (PDK1), which in part accounts for the Warburg effect that describes the propensity for cancers to avidly take up glucose and convert it to lactate with the concurrent decrease in mitochondrial respiration. Target genes that are common to both HIF and MYC, such as PDK1, LDHA, HK2, and TFRC, are therefore attractive therapeutic targets, because their coordinate induction by HIF and MYC widens the therapeutic window between cancer and normal tissues.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"35-53"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27690207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 111
Mitochondria and cancer. 线粒体和癌症。
Pub Date : 2007-01-01 DOI: 10.1007/2789_2008_086
P Rustin, G Kroemer

Mitochondria contained in cancer cells exhibit two major alterations. First, they are often relatively resistant to the induction of mitochondrial membrane permeabilization (MMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. The mechanisms of MMP resistance have come under close scrutiny because apoptosis resistance constitutes one of the essential hallmarks of cancer. Second, cancer cell mitochondria often exhibit a reduced oxidative phosphorylation, meaning that ATP is generated through the conversion of glucose to pyruvate and excess pyruvate is then eliminated as the waste product lactate. This glycolytic mode of energy production is even observed in conditions of high oxygen tension and is hence called anaerobic glycolysis. Here, we discuss the molecular mechanisms accounting for inhibition of the mitochondrial apoptosis pathway in neoplasia and discuss possible mechanistic links between MMP resistance and anaerobic glycolysis.

癌细胞中的线粒体表现出两个主要的变化。首先,它们通常相对抵抗线粒体膜透性(MMP)的诱导,而线粒体膜透性是细胞凋亡内在途径的限速步骤。由于细胞凋亡抵抗是癌症的基本特征之一,因此MMP耐药的机制一直受到密切关注。其次,癌细胞线粒体经常表现出氧化磷酸化的减少,这意味着ATP是通过葡萄糖转化为丙酮酸而产生的,多余的丙酮酸随后作为乳酸废物被消除。这种能量产生的糖酵解模式甚至在高氧张力条件下也能观察到,因此被称为厌氧糖酵解。在这里,我们讨论了肿瘤中线粒体凋亡途径抑制的分子机制,并讨论了MMP耐药性与厌氧糖酵解之间可能的机制联系。
{"title":"Mitochondria and cancer.","authors":"P Rustin,&nbsp;G Kroemer","doi":"10.1007/2789_2008_086","DOIUrl":"https://doi.org/10.1007/2789_2008_086","url":null,"abstract":"<p><p>Mitochondria contained in cancer cells exhibit two major alterations. First, they are often relatively resistant to the induction of mitochondrial membrane permeabilization (MMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. The mechanisms of MMP resistance have come under close scrutiny because apoptosis resistance constitutes one of the essential hallmarks of cancer. Second, cancer cell mitochondria often exhibit a reduced oxidative phosphorylation, meaning that ATP is generated through the conversion of glucose to pyruvate and excess pyruvate is then eliminated as the waste product lactate. This glycolytic mode of energy production is even observed in conditions of high oxygen tension and is hence called anaerobic glycolysis. Here, we discuss the molecular mechanisms accounting for inhibition of the mitochondrial apoptosis pathway in neoplasia and discuss possible mechanistic links between MMP resistance and anaerobic glycolysis.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27694502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
期刊
Ernst Schering Foundation symposium proceedings
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1