The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies reveal...The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.展开更多
Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers i...Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.展开更多
A total of 12 indices of temperature extremes and 11 indices of precipitation extremes at 111 stations in southwestern China at altitudes of 285-4700 m were examined for the period 1961-2008. Significant correlations ...A total of 12 indices of temperature extremes and 11 indices of precipitation extremes at 111 stations in southwestern China at altitudes of 285-4700 m were examined for the period 1961-2008. Significant correlations of temperature extremes and elevation included the trends of diurnal temperature range, frost days, ice days, cold night frequency and cold day frequency. Regional trends of growing season length, warm night frequency, coldest night and warmest night displayed a statistically significant positive correlation with altitude. These characteristics indicated the obvious warming with altitude. For precipitation extreme indices, only the trends of consecutive dry days, consecutive wet days, wet day precipitation and the number of heavy precipitation days had significant correlations with increasing altitude owing to the complex influence of atmospheric circulation. It also indicated the increased precipitation mainly at higher altitude areas, whereas the increase of extreme precipitation events mainly at lowers altitude. In addition, the clearly local influences are also crucial on climate extremes. The analysis revealed an enhanced sensitivity of climate extremes to elevation in southwestern China in the context of recent warming.展开更多
The United States （U.S.） is facing a national opioid epidemic, and medical systems are in need of non- pharmacologic strategies that can be employed to decrease the public＇s opioid dependence. Acupuncture has emerg...The United States （U.S.） is facing a national opioid epidemic, and medical systems are in need of non- pharmacologic strategies that can be employed to decrease the public＇s opioid dependence. Acupuncture has emerged as a powerful, evidence-based, safe, cost-effective, and available treatment modality suitable to meeting this need. Acupuncture has been shown to be effective for the management of numerous types of pain conditions, and mechanisms of action for acupuncture have been described and are understandable from biomedical, physiologic perspectives. Further, acupuncture＇s cost-effectiveness can dramatically decrease health care expenditures, both from the standpoint of treating acute pain and through avoiding addiction to opioids that requires costly care, destroys quality of life, and can lead to fatal overdose. Numerous federal regulatory agencies have advised or mandated that healthcare systems and providers offer non-pharmacologic treatment options for pain. Acupuncture stands out as the most evidence-based, immediately available choice to fulfil these calls. Acupuncture can safely, easily, and cost-effectively be incorporated into hospital settings as diverse as the emergency department, labor and delivery suites, andneonatal intensive care units to treat a variety of commonly seen pain conditions. Acupuncture is already being successfully and meaningfully utilized by the Veterans Administration and various branches of the U.S. Military, in some studies demonstrably decreasing the volume of opioids prescribed when included in care.展开更多
The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in ...The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in arterial blood.P(v-a) CO_2 depends on the cardiac output and the global CO_2 production,and on the complex relationship between PCO_2 and CO_2 content.Experimental and clinical studies support the evidence that P(v-a) CO_2 cannot serve as an indicator of tissue hypoxia,and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO_2generated by the peripheral tissues.P(v-a) CO_2 can be replaced by the central venous-to-arterial CO_2 difference(△PCO_2),which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and,therefore,more easy to obtain at the bedside.Determining the △PCO_2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation(SCVO_2) > 70%associated with elevated blood lactate levels.Because high blood lactate levels is not a discriminatory factor in determining the source of that stress,an increased △PCO_2(> 6 mmHg)could be used to identify patients who still remain inadequately resuscitated.Monitoring the △PCO_2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and,thus,guiding the therapy.In this respect,it can aid to titrate inotropes to adjust oxygen delivery to CO_2 production,or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO_2 related to metabolic demand.The combination of P(v-a) CO_2 or △PCO_2 with oxygen-derived parameters through the calculation of the P(v-a) CO_2 or △PCO_2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.展开更多
基金The research in authors'lab has been supported by The University of Texas MD Anderson Cancer Center,KC180131 from Department of Defense Kidney Cancer Research Program,R01CA181196,R01CA190370,R01CA244144 from the National Institutes of Health(to BG)CPRIT Research Training Grant(RP170067)Dr.John J.Kopchick Research Award from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences(to PK).
文摘The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.
基金supported by the Andrew Sabin Family Fellow Award and Institutional Research Grant from the University of Texas MD Anderson Cancer Center,Grants from National Institutes of Health(CA181196 and CA190370)Anna Fuller Fund,and Ellison Medical Foundation(AG-NS-0973-13).
文摘Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.
基金National Natural Science Foundation of China, No.91025002 No.40725001+5 种基金 No.30970492 No.40971019 No. 11J0930003 The CAS Special Grant for Postgraduate Research, Innovation and Practice The Foundation from the State Key Laboratory of Cryosphere Science The Foundation from Lijiang City Government
文摘A total of 12 indices of temperature extremes and 11 indices of precipitation extremes at 111 stations in southwestern China at altitudes of 285-4700 m were examined for the period 1961-2008. Significant correlations of temperature extremes and elevation included the trends of diurnal temperature range, frost days, ice days, cold night frequency and cold day frequency. Regional trends of growing season length, warm night frequency, coldest night and warmest night displayed a statistically significant positive correlation with altitude. These characteristics indicated the obvious warming with altitude. For precipitation extreme indices, only the trends of consecutive dry days, consecutive wet days, wet day precipitation and the number of heavy precipitation days had significant correlations with increasing altitude owing to the complex influence of atmospheric circulation. It also indicated the increased precipitation mainly at higher altitude areas, whereas the increase of extreme precipitation events mainly at lowers altitude. In addition, the clearly local influences are also crucial on climate extremes. The analysis revealed an enhanced sensitivity of climate extremes to elevation in southwestern China in the context of recent warming.
文摘The United States （U.S.） is facing a national opioid epidemic, and medical systems are in need of non- pharmacologic strategies that can be employed to decrease the public＇s opioid dependence. Acupuncture has emerged as a powerful, evidence-based, safe, cost-effective, and available treatment modality suitable to meeting this need. Acupuncture has been shown to be effective for the management of numerous types of pain conditions, and mechanisms of action for acupuncture have been described and are understandable from biomedical, physiologic perspectives. Further, acupuncture＇s cost-effectiveness can dramatically decrease health care expenditures, both from the standpoint of treating acute pain and through avoiding addiction to opioids that requires costly care, destroys quality of life, and can lead to fatal overdose. Numerous federal regulatory agencies have advised or mandated that healthcare systems and providers offer non-pharmacologic treatment options for pain. Acupuncture stands out as the most evidence-based, immediately available choice to fulfil these calls. Acupuncture can safely, easily, and cost-effectively be incorporated into hospital settings as diverse as the emergency department, labor and delivery suites, andneonatal intensive care units to treat a variety of commonly seen pain conditions. Acupuncture is already being successfully and meaningfully utilized by the Veterans Administration and various branches of the U.S. Military, in some studies demonstrably decreasing the volume of opioids prescribed when included in care.
文摘The mixed venous-to-arterial carbon dioxide(CO_2)tension difference[P(v-a) CO_2]is the difference between carbon dioxide tension(PCO_2) in mixed venous blood(sampled from a pulmonary artery catheter) and the PCO_2 in arterial blood.P(v-a) CO_2 depends on the cardiac output and the global CO_2 production,and on the complex relationship between PCO_2 and CO_2 content.Experimental and clinical studies support the evidence that P(v-a) CO_2 cannot serve as an indicator of tissue hypoxia,and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO_2generated by the peripheral tissues.P(v-a) CO_2 can be replaced by the central venous-to-arterial CO_2 difference(△PCO_2),which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and,therefore,more easy to obtain at the bedside.Determining the △PCO_2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation(SCVO_2) > 70%associated with elevated blood lactate levels.Because high blood lactate levels is not a discriminatory factor in determining the source of that stress,an increased △PCO_2(> 6 mmHg)could be used to identify patients who still remain inadequately resuscitated.Monitoring the △PCO_2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and,thus,guiding the therapy.In this respect,it can aid to titrate inotropes to adjust oxygen delivery to CO_2 production,or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO_2 related to metabolic demand.The combination of P(v-a) CO_2 or △PCO_2 with oxygen-derived parameters through the calculation of the P(v-a) CO_2 or △PCO_2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism.
