Abstract:
:The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.
journal_name
Proc Natl Acad Sci U S Aauthors
Voortman J,Lee JH,Killian JK,Suuriniemi M,Wang Y,Lucchi M,Smith WI Jr,Meltzer P,Wang Y,Giaccone Gdoi
10.1073/pnas.1008132107subject
Has Abstractpub_date
2010-07-20 00:00:00pages
13040-5issue
29eissn
0027-8424issn
1091-6490pii
1008132107journal_volume
107pub_type
杂志文章abstract::Trimeric class I virus fusion proteins undergo a series of conformational rearrangements that leads to the association of C- and N-terminal heptad repeat domains in a "trimer-of-hairpins" structure, facilitating the apposition of viral and cellular membranes during fusion. This final fusion hairpin structure is sustai...
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.0406696101
更新日期:2004-10-19 00:00:00
abstract::Brown adipose tissue (BAT) is present throughout life in rodents and plays an important role in energy balance. However, whereas BAT is clearly recognizable in the neonates of larger mammals (including dogs, cats, sheep, cattle, and humans), it is undetectable or present in only small quantities in adults of these spe...
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.88.23.10774
更新日期:1991-12-01 00:00:00
abstract::Amoebae of the cellular slime mold Dictyostelium discoideum possess an extensive and dynamic endomembrane system that includes many types of acidic vacuoles. A light membrane fraction from Dictyostelium, rich in vacuolar-type H(+)-ATPase, has been described [Padh, H., Lavasa, M. & Steck, T.L. (1989) J. Cell Biol. 108,...
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.89.17.8025
更新日期:1992-09-01 00:00:00
abstract::Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mys...
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.0400368101
更新日期:2004-03-30 00:00:00
abstract::Bacteria form colonies and secrete extracellular polymeric substances that surround the individual cells. These spatial structures are often associated with collaboration and quorum sensing between the bacteria. Here we investigate the mutual protection provided by spherical growth of a monoclonal colony during exposu...
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.1708954115
更新日期:2018-01-09 00:00:00
abstract::Secretions of the uterus support survival and growth of the conceptus (embryo/fetus and associated membranes) during pregnancy. Galectin-15, also known as OVGAL11 and a previously uncharacterized member of the galectin family of secreted beta-galactoside lectins containing a conserved carbohydrate recognition domain 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.0402669101
更新日期:2004-05-25 00:00:00
abstract::The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the generation of various brain rhythmic activities that can be modulated by benzodiazepines. Here, we assessed the contribution of alpha(2)GABA type A (GABA(A)) receptors to the effects of benzodiazepines on sleep and waking oscillatory pat...
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.0306975101
更新日期:2004-03-09 00:00:00
abstract::Protein interactions with the collagen triple helix play a critical role in collagen fibril formation, cell adhesion, and signaling. However, structural insight into sequence-specific collagen recognition is limited to an integrin-peptide complex. A GVMGFO motif in fibrillar collagens (O denotes 4-hydroxyproline) bind...
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.0808452105
更新日期:2008-11-25 00:00:00
abstract::Studies of natural killer (NK) cell function in vivo have been challenging primarily due to the lack of animal models in which NK cells are genetically and selectively deficient. Here, we describe a transgenic mouse with defective natural killing and selective deficiency in NK1.1(+) CD3(-) cells. Despite functionally ...
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.050588297
更新日期:2000-03-14 00:00:00
abstract::Discovering the visual features and representations used by the brain to recognize objects is a central problem in the study of vision. Recently, neural network models of visual object recognition, including biological and deep network models, have shown remarkable progress and have begun to rival human performance in...
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.1513198113
更新日期:2016-03-08 00:00:00
abstract::A procedure is described for selection of temperature-sensitive mutants affecting fatty-acid synthesis based upon radiation suicide of wild-type organisms by tritiated acetate selectively incorporated into fatty acids. At 37 degrees , two of the mutants extensively incorporate fatty-acid supplements provided in the me...
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.69.11.3105
更新日期:1972-11-01 00:00:00
abstract::Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questi...
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.1410767112
更新日期:2015-05-19 00:00:00
abstract::Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain. Failing human cardiomyocytes exhibit increased CaMKII and voltage-gated Ca(2+) ...
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.0913760107
更新日期:2010-03-16 00:00:00
abstract::Complex social behavior in Microtus voles and other mammals has been postulated to be under the direct genetic control of a single locus: the arginine vasopressin 1a receptor (avpr1a) gene. Using a phylogenetic approach, we show that a repetitive element in the promoter region of avpr1a, which reportedly causes social...
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.0602380103
更新日期:2006-07-18 00:00:00
abstract::Animal mitochondrial DNA (mtDNA) maintains a displacement loop (D loop) at the heavy strand origin of replication. These D loops represent sharply limited synthesis of heavy strands and provide a unique opportunity to examine the termination of DNA synthesis. Direct sizing at the nucleotide level indicates that the 3'...
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.78.10.6116
更新日期:1981-10-01 00:00:00
abstract::The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the pre...
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.72.8.3107
更新日期:1975-08-01 00:00:00
abstract::We prove theorems on the structure of the fundamental group of a compact riemannian manifold of non-positive curvature. In particular, a conjecture of J. Wolf [J. Differential Geometry, 2, 421-446 (1968)] is proved. ...
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.67.2.509
更新日期:1970-10-01 00:00:00
abstract::Histones play a crucial role in the organization of DNA in the nucleus, but their presence can prevent interactions with DNA binding proteins responsible for repair of DNA damage. Uracil is an abundant mutagenic lesion recognized by uracil DNA glycosylase (UDG) in the first step of base excision repair (BER). In nucle...
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.0914443107
更新日期:2010-03-09 00:00:00
abstract::The high-affinity receptor for human granulocyte/macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha subunit binds GM-CSF with low affinity, whereas the beta subunit does not bind GM-CSF by itself. The alpha and beta subunits together form the high-affinity GM-CSF rece...
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.88.12.5082
更新日期:1991-06-15 00:00:00
abstract::The earliest measurable parameter that shows density-dependent inhibition is the uptake of [(3)H]deoxyglucose by Balb 3T3 cells. The rate decreases even during the exponential phase of growth and reaches a minimum, about 8- to 10-times lower than maximum, as the culture approaches the saturation density. Cells transfo...
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.70.8.2374
更新日期:1973-08-01 00:00:00
abstract::Endoproteolytic processing of the human protein C (HPC) precursor to its mature form involves cleavage of the propeptide after amino acids Lys-2-Arg-1 and removal of a Lys156-Arg157 dipeptide connecting the light and heavy chains. This processing was inefficient in the mammary gland of transgenic mice and pigs. We hyp...
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.92.23.10462
更新日期:1995-11-07 00:00:00
abstract::Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showed that the central ...
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.2432220100
更新日期:2003-12-09 00:00:00
abstract::The signals required for rapid internalization of the bovine cation-dependent mannose 6-phosphate receptor have been localized to two distinct regions of the 67-amino acid cytoplasmic domain. One signal includes phenylalanine 13 and phenylalanine 18, while the other involves tyrosine 45. The former signal is more pote...
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.87.24.10010
更新日期:1990-12-01 00:00:00
abstract::A perversion in an otherwise uniform helical structure, such as a climbing plant tendril, refers to a kink that connects two helices with opposite chiralities. Such singularity structures are widely seen in natural and artificial mechanical systems, and they provide the fundamental mechanism of helical symmetry breaki...
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.1605621113
更新日期:2016-06-28 00:00:00
abstract::Lakes are considered the second largest natural source of atmospheric methane (CH4). However, current estimates are still uncertain and do not account for diel variability of CH4 emissions. In this study, we performed high-resolution measurements of CH4 flux from several lakes, using an automated and sensor-based flux...
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.2006024117
更新日期:2020-09-01 00:00:00
abstract::Opportunistic infections are often polymicrobial. Two of the most important bacterial opportunistic pathogens of humans, Pseudomonas aeruginosa and Staphylococcus aureus, frequently are coisolated from infections of catheters, endotracheal tubes, skin, eyes, and the respiratory tract, including the airways of people 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.0606756104
更新日期:2006-12-26 00:00:00
abstract::Operant conditioning techniques were used to assess how gender and song familiarity affect song discrimination in adult zebra finches (Taeniopygia guttata). Twenty-five males and females, divided into five cohorts, were trained to discriminate between conspecific songs at different times of year. Males discriminating ...
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.89.4.1368
更新日期:1992-02-15 00:00:00
abstract::The localization of calmodulin, a calcium-dependent modulator of many enzymes, was studied in rat liver, skeletal muscle, and adrenal slices. Calmodulin is found in liver cytoplasm, nucleus, and plasma membrane. Much of the cytoplasmic calmodulin is associated with glycogen particles presumably bound to enzymes involv...
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.77.1.366
更新日期:1980-01-01 00:00:00
abstract::Recently it has become apparent that N = 2 supersymmetric quantum field theory has something to do with cluster algebras. I review one aspect of the connection: supersymmetric quantum field theories have associated hyperkähler moduli spaces, and these moduli spaces carry a structure that looks like an extension of the...
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.1313073111
更新日期:2014-07-08 00:00:00
abstract::Despite their overall accuracy, errors in macromolecular processes, such as rRNA synthesis and ribosome assembly, inevitably occur. However, whether these errors are remediated and how this might be accomplished is not known. In previous work, we showed that a double mutant strain lacking both polynucleotide phosphory...
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.1231041100
更新日期:2003-05-27 00:00:00