Abstract:
:The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations.
journal_name
Proc Natl Acad Sci U S Aauthors
Wang Z,Shen Z,Li Z,Duan J,Fu S,Liu Z,Bai H,Zhang Z,Zhao J,Wang X,Wang Jdoi
10.1073/pnas.1510837112subject
Has Abstractpub_date
2015-08-11 00:00:00pages
9990-5issue
32eissn
0027-8424issn
1091-6490pii
1510837112journal_volume
112pub_type
杂志文章abstract::Glucocorticoids play a critical role in control of the cytokine response after immune challenge. Conversely, cytokines modulate glucocorticoid production by the hypothalamic-pituitary-adrenal axis. To define the potency and mechanism of interleukin-6 (IL-6) for augmentation of adrenal function, we exploited mice defic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.16.9317
更新日期:2000-08-01 00:00:00
abstract::The mannose receptor (MR) is an endocytic receptor involved in serum homeostasis and antigen presentation. Here, we identify the MR as a direct regulator of CD8(+) T-cell activity. We demonstrate that MR expression on dendritic cells (DCs) impaired T-cell cytotoxicity in vitro and in vivo. This regulatory effect of th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1605885113
更新日期:2016-09-20 00:00:00
abstract::gC1qR is one of the C1q receptors implicated in the regulation of innate and adaptive immunity. We found that gC1qR inhibits RIG-I and MDA5-dependent antiviral signaling. Double stranded RNA and virus trigger the translocation of gC1qR to the mitochondrial outer membrane leading to the interaction of gC1qR with the RI...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0811029106
更新日期:2009-02-03 00:00:00
abstract::In binocular rivalry, a subject views two incongruent stimuli through each eye but consciously perceives only one stimulus at a time, with a switch in perceptual dominance every few seconds. To investigate the neural correlates of perceptual dominance in humans, seven subjects were recorded with a 148-channel magnetoe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.6.3198
更新日期:1998-03-17 00:00:00
abstract::We have investigated whether the large (5- to 15-fold) stimulation of synthesis of growth hormone (somatotropin) observed upon exposure of a strain of rat pituitary (GH3) cells to dexamethasone (a synthetic glucocorticoid) arises from a stimulation of pregrowth hormone mRNA. A good agreement was observed between the s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.6.2357
更新日期:1977-06-01 00:00:00
abstract::In mammalian females, most genes on one X chromosome are transcriptionally silenced as a result of X chromosome inactivation. Whereas it is well established that some X-linked genes "escape" X inactivation and are expressed from both active (Xa) and inactive (Xi) X chromosomes, most models for the chromosomal control ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.13.7364
更新日期:1999-06-22 00:00:00
abstract::Expression systems based on the Escherichia coli arabinose operon P(BAD) promoter exhibit the all-or-nothing (autocatalytic) induction of expression that was first documented in the lac operon. Under conditions of subsaturating levels of inducer, some of the cells of the population are fully induced, whereas other cel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.122227599
更新日期:2002-05-28 00:00:00
abstract::The plasma membrane (PM) is composed of heterogeneous subdomains, characterized by differences in protein and lipid composition. PM receptors can be dynamically sorted into membrane domains to underpin signaling in response to extracellular stimuli. In plants, the plasmodesmal PM is a discrete microdomain that hosts s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1907799117
更新日期:2020-04-28 00:00:00
abstract::Proteopithecus sylviae is an archaic anthropoid from the late Eocene quarry L-41, Fayum Province, Egypt. The dentition of Proteopithecus is very primitive and does not closely resemble that of other, better known, primates from the Fayum (e.g., parapithecids and propliopithecids). The dental morphology, much of which ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.25.13760
更新日期:1997-12-09 00:00:00
abstract::Members of the voltage-gated-like ion channel superfamily have a conserved pore structure. Transmembrane helices that line the pore (M2 or S6) are thought to gate it at the cytoplasmic end by bending at a hinge glycine residue. Proline residues favor bending of alpha-helices, and substitution of proline for this glyci...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0408270101
更新日期:2004-12-21 00:00:00
abstract::Hydrogen/deuterium exchange followed by trapping of the labeled species in the aprotic solvent DMSO has been used to elucidate structure in both the burst-phase molten globule-folding intermediate of apomyoglobin and in an equilibrium intermediate that models the kinetic intermediate. Precise estimates can be made of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0409538102
更新日期:2005-03-29 00:00:00
abstract::Following antigen stimulation, naïve T cells differentiate into memory cells that mediate antigen clearance more efficiently upon repeat encounter. Donor-specific tolerance can be achieved in a subset of transplant recipients, but some of these grafts are rejected after years of stability, often following infections. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1910298116
更新日期:2019-11-19 00:00:00
abstract::Excitation of HbCO by a single 6-psec 530-nm pulse results in photodissociation with a first-order constant of 0.89 X 10(11) sec-1. The kinetics of photodissociation, monitored by following absorbance changes in the Soret band at 440 nm, are interpreted as corresponding to predissociation followed by a corssing into a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.2.573
更新日期:1978-02-01 00:00:00
abstract::The sparking of cut grape hemispheres in a household microwave oven has been a poorly explained Internet parlor trick for over two decades. By expanding this phenomenon to whole spherical dimers of various grape-sized fruit and hydrogel water beads, we demonstrate that the formation of plasma is due to electromagnetic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1818350116
更新日期:2019-03-05 00:00:00
abstract::A polar lipid containing about 20 per cent of the lipid soluble inositol has been purified from cells of Saccharomyces cerevisiae. This compound labeled with (3)H-inositol, (32)P(i), or (14)C glucose was isolated from aqueous pyridine extracts by means of paper chromatography. Unlabeled compound was obtained by a diff...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.64.3.1042
更新日期:1969-11-01 00:00:00
abstract::In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decame...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.022646999
更新日期:2002-02-05 00:00:00
abstract::Biosynthesis of sucrose-6-P catalyzed by sucrose-phosphate synthase (SPS), and the presence of sucrose-phosphate phosphatase (SPP) leading to the formation of sucrose, have both been ascertained in a prokaryotic organism: Anabaena 7119, a filamentous heterocystic cyanobacterium. Two SPS activities (SPS-I and SPS-II) w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.24.13600
更新日期:1996-11-26 00:00:00
abstract::Swarming bacteria move in multicellular groups and exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. We find that high densities promote bacterial survival, even ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0910934107
更新日期:2010-02-23 00:00:00
abstract::The heat-stable enterotoxin B (STB) of Escherichia coli is a 48-amino acid extracellular peptide that induces rapid fluid accumulation in animal intestinal models. Unlike other E. coli enterotoxins that elicit cAMP or cGMP responses in the gut [heat-labile toxin (LT) and heat-stable toxin A (STA), respectively], STB i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.8.3202
更新日期:1993-04-15 00:00:00
abstract::Seventeen monoclonal antibodies derived from fusions with spleen cells of mice immunized with established culture lines of renal cancers identified nine cell-surface antigenic systems. Six of the systems (gp160, S25, gp120r, gp120nr, gp115, and V1) represent antigens not previously described. The other three systems a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.8.5122
更新日期:1981-08-01 00:00:00
abstract::Little is known about the large ectodomain of MET, the product of the c-met protooncogene and receptor for hepatocyte growth factor/scatter factor (HGF/SF). Here, we establish by deletion mutagenesis that the HGF/SF and heparin-binding sites of MET are contained within a large N-terminal domain spanning the alpha-chai...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2034936100
更新日期:2003-10-14 00:00:00
abstract::Larval fishes suffer prodigious mortality rates, eliminating 99% of the brood within a few days after first feeding. Hjort (1914) famously attributed this "critical period" of low survival to the larvae's inability to obtain sufficient food [Hjort (1914) Rapp P-v Réun Cons Int Explor Mer 20:1-228]. However, the cause ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1323205111
更新日期:2014-06-03 00:00:00
abstract::Human X chromosome DNA was partially purified from a mouse-human hybrid cell line containing a single human chromosome, the X. Enrichment of such DNA was accomplished by two sequential reassociations of radiolabeled hybrid cell DNA with large excesses of mouse DNA. Unreassociated hybrid cell DNA was used as a probe fo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.12.6525
更新日期:1979-12-01 00:00:00
abstract::Antibiotic resistance in bacteria has emerged as a global challenge over the past 90 years, compromising our ability to effectively treat infections. There has been a dramatic increase in antibiotic resistance-associated determinants in bacterial populations, driven by the mobility and infectious nature of such determ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1717162115
更新日期:2018-12-18 00:00:00
abstract::Evidence is assembled from the literature to support the argument that myocardial infarction and death results from narrowing of coronary arteries-a process that may result from various causes, as discussed in this paper. Angiotensin and hypertension are suggested as among the chief components of such processes. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.7.1813
更新日期:1972-07-01 00:00:00
abstract::Estrogen receptor alpha (ERalpha) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ERalpha knockout mice advanced our knowledge of ERalpha functions, gene deletion using this method is global and potentially confounded by developmental consequences...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0603045103
更新日期:2006-07-05 00:00:00
abstract::Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients wit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1408523111
更新日期:2014-06-17 00:00:00
abstract::Sulfonated gallium(III) corroles are intensely fluorescent macrocyclic compounds that spontaneously assemble with carrier proteins to undergo cell entry. We report in vivo imaging and therapeutic efficacy of a tumor-targeted corrole noncovalently assembled with a heregulin-modified protein directed at the human epider...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0901531106
更新日期:2009-04-14 00:00:00
abstract::Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown tha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.7.2918
更新日期:1991-04-01 00:00:00
abstract::Iodine is an important nutrient and a significant sink of tropospheric ozone, a climate-forcing gas and air pollutant. Ozone interacts with seawater iodide, leading to volatile inorganic iodine release that likely represents the largest source of atmospheric iodine. Increasing ozone concentrations since the preindustr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1809867115
更新日期:2018-11-27 00:00:00