Abstract:
:Patient-derived xenografts (PDXs) and PDX-derived cells (PDCs) are useful in preclinical research. We performed a drug screening assay using PDCs and identified proteasome inhibitors as promising drugs for cholangiocarcinoma (CCA) treatment. Furthermore, we determined that phosphate and tensin homology deleted on chromosome ten (PTEN) deficiency promotes protein synthesis and proteasome subunit expression and proteolytic activity, creating a dependency on the proteasome for cancer cell growth and survival. Thus, targeting the proteasome machinery with the inhibitor bortezomib inhibited the proliferation and survival of CCA cells lacking functional PTEN. Therapeutic evaluation of PDXs, autochthonous mouse models, and patients confirmed this dependency on the proteasome. Mechanistically, we found that PTEN promoted the nuclear translocation of FOXO1, resulting in the increased expression of BACH1 and MAFF BACH1 and MAFF are transcriptional regulators that recognize the antioxidant response element, which is present in genes encoding proteasome subunits. PTEN induced the accumulation and nuclear translocation of these proteins, which directly repressed the transcription of genes encoding proteasome subunits. We revealed that the PTEN-proteasome axis is a potential target for therapy in PTEN-deficient CCA and other PTEN-deficient cancers.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Jiang TY,Pan YF,Wan ZH,Lin YK,Zhu B,Yuan ZG,Ma YH,Shi YY,Zeng TM,Dong LW,Tan YX,Wang HYdoi
10.1126/scitranslmed.aay0152subject
Has Abstractpub_date
2020-09-23 00:00:00issue
562eissn
1946-6234issn
1946-6242pii
12/562/eaay0152journal_volume
12pub_type
杂志文章abstract::A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unkn...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaf6786
更新日期:2017-03-29 00:00:00
abstract::Global investments in health information technology (HIT) in the form of electronic health record systems represent important new strategies to improve the quality and efficiency of health care. These potential benefits of HIT will not be achieved without direct attention to the use of health care information for clin...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3000764
更新日期:2010-02-10 00:00:00
abstract::Acquired lymphedema is a cancer sequela and a global health problem currently lacking pharmacologic therapy. We have previously demonstrated that ketoprofen, an anti-inflammatory agent with dual 5-lipoxygenase and cyclooxygenase inhibitory properties, effectively reverses histopathology in experimental lymphedema. We ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal3920
更新日期:2017-05-10 00:00:00
abstract::Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003293
更新日期:2012-03-07 00:00:00
abstract::MG53 promotes sarcolemmal repair in the mdx mouse model of Duchenne muscular dystrophy (Weisleder et al., this issue) and identifies a new protein therapeutic for muscle disease. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.3004082
更新日期:2012-06-20 00:00:00
abstract::Sustained viremia after acute HIV infection is associated with profound CD4+ T cell loss and exhaustion of HIV-specific CD8+ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiatin...
journal_title:Science translational medicine
pub_type: 临床试验,杂志文章
doi:10.1126/scitranslmed.aau0528
更新日期:2019-05-22 00:00:00
abstract::Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Curr...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau0965
更新日期:2018-12-05 00:00:00
abstract::Beginning with the 18th-century physician-scientist William Heberden, the elder, Science Translational Medicine introduces a new article series about historical figures whose transformational contributions to science, medicine, and society remain relevant today. ...
journal_title:Science translational medicine
pub_type: 历史文章,杂志文章
doi:10.1126/scitranslmed.aaa2250
更新日期:2015-05-13 00:00:00
abstract::A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinic...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa2406
更新日期:2015-09-23 00:00:00
abstract::The clinical application of cytokine therapies for cancer treatment remains limited due to severe adverse reactions and insufficient therapeutic effects. Although cytokine localization by intratumoral administration could address both issues, the rapid escape of soluble cytokines from the tumor invariably subverts thi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaw2614
更新日期:2019-06-26 00:00:00
abstract::Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used sev...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002573
更新日期:2011-11-02 00:00:00
abstract::Venetoclax is a specific B cell lymphoma 2 (BCL-2) inhibitor with promising activity against acute myeloid leukemia (AML), but its clinical efficacy as a single agent or in combination with hypomethylating agents (HMAs), such as azacitidine, is hampered by intrinsic and acquired resistance. Here, we performed a genome...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aax2863
更新日期:2019-10-30 00:00:00
abstract::Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction a...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal1669
更新日期:2017-06-07 00:00:00
abstract::Information provided to patients is thought to influence placebo and drug effects. In a prospective, within-subjects, repeated-measures study of 66 subjects with episodic migraine, we investigated how variations in medication labeling modified placebo and drug effects. An initial attack with no treatment served as a c...
journal_title:Science translational medicine
pub_type: 杂志文章,随机对照试验
doi:10.1126/scitranslmed.3006175
更新日期:2014-01-08 00:00:00
abstract::Whole-genome sequencing of patient DNA can facilitate diagnosis of a disease, but its potential for guiding treatment has been under-realized. We interrogated the complete genome sequences of a 14-year-old fraternal twin pair diagnosed with dopa (3,4-dihydroxyphenylalanine)-responsive dystonia (DRD; Mendelian Inherita...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002243
更新日期:2011-06-15 00:00:00
abstract::Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008517
更新日期:2014-04-16 00:00:00
abstract::Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decrea...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3007092
更新日期:2013-12-11 00:00:00
abstract::Systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) of the skin are autoimmune diseases characterized by inappropriate immune responses against self-proteins; the key elements that determine disease pathogenesis and progression are largely unknown. Here, we show that mice lacking immune inhibitory...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aax1159
更新日期:2019-12-11 00:00:00
abstract::The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing of exons of ATAD1, the gene encoding Thorase, in a cohort of patients wit...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aah4985
更新日期:2017-12-13 00:00:00
abstract::Long synthetic peptides (LSPs) have a variety of important clinical uses as synthetic vaccines and drugs. Techniques for peptide synthesis were revolutionized in the 1960s and 1980s, after which efficient techniques for purification and characterization of the product were developed. These improved techniques allowed ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3001387
更新日期:2010-09-22 00:00:00
abstract::Restoring reverse cholesterol transport ameliorates the B cell hyperexpansion and autoimmune disease found to be associated with accumulation of cholesterol in CD11c+ antigen-presenting cells. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.aal4997
更新日期:2017-01-25 00:00:00
abstract::Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we foun...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3010525
更新日期:2015-02-25 00:00:00
abstract::Children who survive preterm birth exhibit persistent unexplained disturbances in cerebral cortical growth with associated cognitive and learning disabilities. The mechanisms underlying these deficits remain elusive. We used ex vivo diffusion magnetic resonance imaging to demonstrate in a preterm large-animal model th...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3004669
更新日期:2013-01-16 00:00:00
abstract::The U.S.-Latin America Cancer Research Network strives to expand translational research capabilities and forge new collaborations. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad5859
更新日期:2015-12-23 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
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau1428
更新日期:2019-03-13 00:00:00
abstract::Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth ag...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal1321
更新日期:2017-09-06 00:00:00
abstract::Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents whil...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3009951
更新日期:2015-02-04 00:00:00
abstract::The elevation of carbon dioxide (CO2) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aat1662
更新日期:2018-09-05 00:00:00
abstract::Diabetic patients frequently suffer from continuous pain that is poorly treated by currently available analgesics. We used mouse models of type 1 and type 2 diabetes to investigate a possible role for the hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) ion channels as drivers of diabetic pain. Blocking or...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aam6072
更新日期:2017-09-27 00:00:00
abstract::An analysis of four regions in four countries suggests that the best way to mitigate disruption of the pharmaceutical industry is not to ignore or stem it but to sponsor initiatives that keep scientists engaged. ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aaa3679
更新日期:2015-05-06 00:00:00