Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response.

abstract：:Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date has relied heavily on reverse transcription polymerase chain reaction testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or subclinical infections have resulted in an unde...

journal_title：Science translational medicine

authors： Silverman JD,Hupert N,Washburne AD

更新日期：2020-07-29 00:00:00

abstract：:Adults with relapsed B cell acute lymphoblastic leukemia (B-ALL) have a dismal prognosis. Only those patients able to achieve a second remission with no minimal residual disease (MRD) have a hope for long-term survival in the context of a subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We ha...

journal_title：Science translational medicine

authors： Brentjens RJ,Davila ML,Riviere I,Park J,Wang X,Cowell LG,Bartido S,Stefanski J,Taylor C,Olszewska M,Borquez-Ojeda O,Qu J,Wasielewska T,He Q,Bernal Y,Rijo IV,Hedvat C,Kobos R,Curran K,Steinherz P,Jurcic J,Rosenbl

更新日期：2013-03-20 00:00:00

abstract：:In current clinical practice, uterine contractions are monitored via a tocodynamometer or an intrauterine pressure catheter, both of which provide crude information about contractions. Although electrohysterography/electromyography can measure uterine electrical activity, this method lacks spatial specificity and thus...

journal_title：Science translational medicine

authors： Wu W,Wang H,Zhao P,Talcott M,Lai S,McKinstry RC,Woodard PK,Macones GA,Schwartz AL,Cahill AG,Cuculich PS,Wang Y

更新日期：2019-03-13 00:00:00

abstract：:Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (~10% of all EGFR mutations) are generally assoc...

journal_title：Science translational medicine

authors： Yasuda H,Park E,Yun CH,Sng NJ,Lucena-Araujo AR,Yeo WL,Huberman MS,Cohen DW,Nakayama S,Ishioka K,Yamaguchi N,Hanna M,Oxnard GR,Lathan CS,Moran T,Sequist LV,Chaft JE,Riely GJ,Arcila ME,Soo RA,Meyerson M,Eck MJ,K

更新日期：2013-12-18 00:00:00

abstract：:Regulatory T cells (T(regs)) manipulated ex vivo have potential as cellular therapeutics in autoimmunity and transplantation. Although it is possible to expand naturally occurring T(regs), an attractive alternative possibility, particularly suited to solid organ and bone marrow transplantation, is the stimulation of t...

journal_title：Science translational medicine

authors： Feng G,Nadig SN,Bäckdahl L,Beck S,Francis RS,Schiopu A,Whatcott A,Wood KJ,Bushell A

更新日期：2011-05-18 00:00:00

abstract：:Although children represent 25% of the U.S. population and nearly 40% of the world's population, pediatric product development typically lags behind that targeted at adults. Here the authors describe the challenges and opportunities of pediatric product development and the unique issues that surround pediatric researc...

journal_title：Science translational medicine

authors： Connor E,Lombardi D,van den Anker J

更新日期：2009-10-14 00:00:00

abstract：:New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabb...

journal_title：Science translational medicine

authors： Diep BA,Le VT,Badiou C,Le HN,Pinheiro MG,Duong AH,Wang X,Dip EC,Aguiar-Alves F,Basuino L,Marbach H,Mai TT,Sarda MN,Kajikawa O,Matute-Bello G,Tkaczyk C,Rasigade JP,Sellman BR,Chambers HF,Lina G

更新日期：2016-09-21 00:00:00

abstract：:Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain. Mu opioid peptide (MOP) receptor agonists provide very effective pain relief. However, severe side effects limit their use in the clinical setting. Ago...

journal_title：Science translational medicine

authors： Ding H,Kiguchi N,Yasuda D,Daga PR,Polgar WE,Lu JJ,Czoty PW,Kishioka S,Zaveri NT,Ko MC

更新日期：2018-08-29 00:00:00

abstract：:Forty years ago, Judah Folkman predicted that tumor growth is dependent on angiogenesis and that inhibiting this process might be a new strategy for cancer therapy. This hypothesis formed the foundation of a new field of research that represents an excellent example of how a groundbreaking scientific discovery can be ...

journal_title：Science translational medicine

authors： Cao Y,Arbiser J,D'Amato RJ,D'Amore PA,Ingber DE,Kerbel R,Klagsbrun M,Lim S,Moses MA,Zetter B,Dvorak H,Langer R

更新日期：2011-12-21 00:00:00

abstract：:Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE...

journal_title：Science translational medicine

authors： Leary RJ,Kinde I,Diehl F,Schmidt K,Clouser C,Duncan C,Antipova A,Lee C,McKernan K,De La Vega FM,Kinzler KW,Vogelstein B,Diaz LA Jr,Velculescu VE

更新日期：2010-02-24 00:00:00

abstract：:Urea, the toxic end product of protein catabolism, is elevated in end-stage renal disease (ESRD), although it is unclear whether or how it contributes to disease. Urea can promote the carbamylation of proteins on multiple lysine side chains, including human albumin, which has a predominant carbamylation site on Lys(54...

journal_title：Science translational medicine

authors： Berg AH,Drechsler C,Wenger J,Buccafusca R,Hod T,Kalim S,Ramma W,Parikh SM,Steen H,Friedman DJ,Danziger J,Wanner C,Thadhani R,Karumanchi SA

更新日期：2013-03-06 00:00:00

abstract：:Lapatinib, a dual HER2/EGFR (human epidermal growth factor receptor 2/epidermal growth factor receptor) inhibitor, is a recently approved targeted therapy for metastatic breast cancer. Because lapatinib enhances the efficacy of the chemotherapeutic agent capecitabine in breast cancer patients, we tested whether lapati...

journal_title：Science translational medicine

authors： Dolloff NG,Mayes PA,Hart LS,Dicker DT,Humphreys R,El-Deiry WS

更新日期：2011-06-08 00:00:00

abstract：:The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting th...

journal_title：Science translational medicine

authors： Ter Horst KW,Lammers NM,Trinko R,Opland DM,Figee M,Ackermans MT,Booij J,van den Munckhof P,Schuurman PR,Fliers E,Denys D,DiLeone RJ,la Fleur SE,Serlie MJ

更新日期：2018-05-23 00:00:00

abstract：:Stimulator of interferon genes (STING) is a cytosolic receptor that senses both exogenous and endogenous cytosolic cyclic dinucleotides (CDNs), activating TBK1/IRF3 (interferon regulatory factor 3), NF-κB (nuclear factor κB), and STAT6 (signal transducer and activator of transcription 6) signaling pathways to induce r...

journal_title：Science translational medicine

authors： Fu J,Kanne DB,Leong M,Glickman LH,McWhirter SM,Lemmens E,Mechette K,Leong JJ,Lauer P,Liu W,Sivick KE,Zeng Q,Soares KC,Zheng L,Portnoy DA,Woodward JJ,Pardoll DM,Dubensky TW Jr,Kim Y

更新日期：2015-04-15 00:00:00

abstract：:Raman spectroscopy is an optical imaging method that is based on the Raman effect, the inelastic scattering of a photon when energy is absorbed from light by a surface. Although Raman spectroscopy is widely used for chemical and molecular analysis, its clinical application has been hindered by the inherently weak natu...

journal_title：Science translational medicine

authors： Thakor AS,Luong R,Paulmurugan R,Lin FI,Kempen P,Zavaleta C,Chu P,Massoud TF,Sinclair R,Gambhir SS

更新日期：2011-04-20 00:00:00

abstract：:Cancer-associated thrombocytosis and high concentrations of circulating transforming growth factor-β1 (TGF-β1) are frequently observed in patients with progressive cancers. Using genetic and pharmacological approaches, we show a direct link between thrombin catalytic activity and release of mature TGF-β1 from platelet...

journal_title：Science translational medicine

authors： Metelli A,Wu BX,Riesenberg B,Guglietta S,Huck JD,Mills C,Li A,Rachidi S,Krieg C,Rubinstein MP,Gewirth DT,Sun S,Lilly MB,Wahlquist AH,Carbone DP,Yang Y,Liu B,Li Z

更新日期：2020-01-08 00:00:00

abstract：:Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac arrhythmias. To elucidate the underlying mechanisms and discover potential chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte-specific expression of the human 2057del2 mutation in the gene encoding plakoglobin. A high-th...

journal_title：Science translational medicine

authors： Asimaki A,Kapoor S,Plovie E,Karin Arndt A,Adams E,Liu Z,James CA,Judge DP,Calkins H,Churko J,Wu JC,MacRae CA,Kléber AG,Saffitz JE

更新日期：2014-06-11 00:00:00

abstract：:Alzheimer's disease (AD) is hypothesized to be caused by an overproduction or reduced clearance of amyloid-β (Aβ) peptide. Autosomal dominant AD (ADAD) caused by mutations in the presenilin (PSEN) gene have been postulated to result from increased production of Aβ42 compared to Aβ40 in the central nervous system (CNS)...

journal_title：Science translational medicine

authors： Potter R,Patterson BW,Elbert DL,Ovod V,Kasten T,Sigurdson W,Mawuenyega K,Blazey T,Goate A,Chott R,Yarasheski KE,Holtzman DM,Morris JC,Benzinger TL,Bateman RJ

更新日期：2013-06-12 00:00:00

abstract：:Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we te...

journal_title：Science translational medicine

authors： Wee S,Vendruscolo LF,Misra KK,Schlosburg JE,Koob GF

更新日期：2012-08-08 00:00:00

abstract：:Each year, more than a half million people in the United States alone die from sepsis, a dire multisystem disease with highly inadequate treatment options. In a recent issue of Science, Puneet and colleagues provide compelling evidence that inhibiting sphingosine kinase 1--an enzyme that resides in immune cells and is...

journal_title：Science translational medicine

authors： O'Neill LA

更新日期：2010-06-16 00:00:00

abstract：:Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defens...

journal_title：Science translational medicine

authors： Achtman AH,Pilat S,Law CW,Lynn DJ,Janot L,Mayer ML,Ma S,Kindrachuk J,Finlay BB,Brinkman FS,Smyth GK,Hancock RE,Schofield L

更新日期：2012-05-23 00:00:00

abstract：:Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and ...

journal_title：Science translational medicine

authors： Pfeifer CG,Fisher MB,Carey JL,Mauck RL

更新日期：2015-10-21 00:00:00

abstract：:Heparin-based anticoagulant drugs have been widely used for the prevention of blood clotting during surgical procedures and for the treatment of thromboembolic events. However, bleeding risks associated with these anticoagulants demand continuous monitoring and neutralization with suitable antidotes. Protamine, the on...

journal_title：Science translational medicine

authors： Shenoi RA,Kalathottukaren MT,Travers RJ,Lai BF,Creagh AL,Lange D,Yu K,Weinhart M,Chew BH,Du C,Brooks DE,Carter CJ,Morrissey JH,Haynes CA,Kizhakkedathu JN

更新日期：2014-10-29 00:00:00

abstract：:Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced...

journal_title：Science translational medicine

authors： Dakin SG,Martinez FO,Yapp C,Wells G,Oppermann U,Dean BJ,Smith RD,Wheway K,Watkins B,Roche L,Carr AJ

更新日期：2015-10-28 00:00:00

abstract：:The inability to produce perfusable microvasculature networks capable of supporting tissue survival and of withstanding physiological pressures without leakage is a fundamental problem facing the field of tissue engineering. Microvasculature is critically important for production of bioengineered lung (BEL), which req...

journal_title：Science translational medicine

authors： Nichols JE,La Francesca S,Niles JA,Vega SP,Argueta LB,Frank L,Christiani DC,Pyles RB,Himes BE,Zhang R,Li S,Sakamoto J,Rhudy J,Hendricks G,Begarani F,Liu X,Patrikeev I,Pal R,Usheva E,Vargas G,Miller A,Woodson L,

更新日期：2018-08-01 00:00:00

abstract：:Myofibroblast-derived αvβ1 integrin has emerged as a critical mediator of transforming growth factor-β activation in experimental models of tissue fibrosis (Reed et al., this issue). ...

journal_title：Science translational medicine

authors： Dietz HC

更新日期：2015-05-20 00:00:00

abstract：:The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, caus...

journal_title：Science translational medicine

authors： Beatty PR,Puerta-Guardo H,Killingbeck SS,Glasner DR,Hopkins K,Harris E

更新日期：2015-09-09 00:00:00

abstract：:Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N'Djaména, as previously published. We developed a determi...

journal_title：Science translational medicine

authors： Zinsstag J,Lechenne M,Laager M,Mindekem R,Naïssengar S,Oussiguéré A,Bidjeh K,Rives G,Tessier J,Madjaninan S,Ouagal M,Moto DD,Alfaroukh IO,Muthiani Y,Traoré A,Hattendorf J,Lepelletier A,Kergoat L,Bourhy H,Dacheux L,

更新日期：2017-12-20 00:00:00

abstract：:Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. Photoreceptor cells are the primary cell type affected in many inherited diseases of retinal degeneration. Successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors ...

journal_title：Science translational medicine

authors： Vandenberghe LH,Bell P,Maguire AM,Cearley CN,Xiao R,Calcedo R,Wang L,Castle MJ,Maguire AC,Grant R,Wolfe JH,Wilson JM,Bennett J

更新日期：2011-06-22 00:00:00

abstract：:Retinal pigment epithelium (RPE) dysfunction and loss are a hallmark of non-neovascular age-related macular degeneration (NNAMD). Without the RPE, a majority of overlying photoreceptors ultimately degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement str...

journal_title：Science translational medicine

authors： Kashani AH,Lebkowski JS,Rahhal FM,Avery RL,Salehi-Had H,Dang W,Lin CM,Mitra D,Zhu D,Thomas BB,Hikita ST,Pennington BO,Johnson LV,Clegg DO,Hinton DR,Humayun MS

更新日期：2018-04-04 00:00:00