abstract：:Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responde...

journal_title：Nature medicine

authors： Tan DSW,Chong FT,Leong HS,Toh SY,Lau DP,Kwang XL,Zhang X,Sundaram GM,Tan GS,Chang MM,Chua BT,Lim WT,Tan EH,Ang MK,Lim TKH,Sampath P,Chowbay B,Skanderup AJ,DasGupta R,Iyer NG

更新日期：2017-10-01 00:00:00

abstract：:Basal cell carcinoma (BCC), the most common human cancer, results from aberrant activation of the Hedgehog signaling pathway. Although most cases of BCC are sporadic, some forms are inherited, such as Bazex-Dupré-Christol syndrome (BDCS)-a cancer-prone genodermatosis with an X-linked, dominant inheritance pattern. We ...

journal_title：Nature medicine

authors： Bal E,Park HS,Belaid-Choucair Z,Kayserili H,Naville M,Madrange M,Chiticariu E,Hadj-Rabia S,Cagnard N,Kuonen F,Bachmann D,Huber M,Le Gall C,Côté F,Hanein S,Rosti RÖ,Aslanger AD,Waisfisz Q,Bodemer C,Hermine O,Morice

更新日期：2017-10-01 00:00:00

abstract：:The bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins ...

journal_title：Nature medicine

authors： Dai X,Gan W,Li X,Wang S,Zhang W,Huang L,Liu S,Zhong Q,Guo J,Zhang J,Chen T,Shimizu K,Beca F,Blattner M,Vasudevan D,Buckley DL,Qi J,Buser L,Liu P,Inuzuka H,Beck AH,Wang L,Wild PJ,Garraway LA,Rubin MA,Barb

更新日期：2017-09-01 00:00:00

abstract：:The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAFamp) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or ...

journal_title：Nature medicine

authors： Xue Y,Martelotto L,Baslan T,Vides A,Solomon M,Mai TT,Chaudhary N,Riely GJ,Li BT,Scott K,Cechhi F,Stierner U,Chadalavada K,de Stanchina E,Schwartz S,Hembrough T,Nanjangud G,Berger MF,Nilsson J,Lowe SW,Reis-Filho JS

更新日期：2017-08-01 00:00:00

abstract：:With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived C...

journal_title：Nature medicine

authors： Crespo M,Vilar E,Tsai SY,Chang K,Amin S,Srinivasan T,Zhang T,Pipalia NH,Chen HJ,Witherspoon M,Gordillo M,Xiang JZ,Maxfield FR,Lipkin S,Evans T,Chen S

更新日期：2017-07-01 00:00:00

abstract：:The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes under...

journal_title：Nature medicine

authors： Bilkei-Gorzo A,Albayram O,Draffehn A,Michel K,Piyanova A,Oppenheimer H,Dvir-Ginzberg M,Rácz I,Ulas T,Imbeault S,Bab I,Schultze JL,Zimmer A

更新日期：2017-06-01 00:00:00

abstract：:Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; howev...

journal_title：Nature medicine

authors： Honeycutt JB,Thayer WO,Baker CE,Ribeiro RM,Lada SM,Cao Y,Cleary RA,Hudgens MG,Richman DD,Garcia JV

更新日期：2017-05-01 00:00:00

abstract：:Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematu...

journal_title：Nature medicine

authors： Romani L,Oikonomou V,Moretti S,Iannitti RG,D'Adamo MC,Villella VR,Pariano M,Sforna L,Borghi M,Bellet MM,Fallarino F,Pallotta MT,Servillo G,Ferrari E,Puccetti P,Kroemer G,Pessia M,Maiuri L,Goldstein AL,Garaci E

更新日期：2017-05-01 00:00:00

abstract：:Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors....

journal_title：Nature medicine

authors： Davies H,Glodzik D,Morganella S,Yates LR,Staaf J,Zou X,Ramakrishna M,Martin S,Boyault S,Sieuwerts AM,Simpson PT,King TA,Raine K,Eyfjord JE,Kong G,Borg Å,Birney E,Stunnenberg HG,van de Vijver MJ,Børresen-Dale AL,Ma

更新日期：2017-04-01 00:00:00

abstract：:Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine ...

journal_title：Nature medicine

authors： Misu H,Takayama H,Saito Y,Mita Y,Kikuchi A,Ishii KA,Chikamoto K,Kanamori T,Tajima N,Lan F,Takeshita Y,Honda M,Tanaka M,Kato S,Matsuyama N,Yoshioka Y,Iwayama K,Tokuyama K,Akazawa N,Maeda S,Takekoshi K,Matsugo S,

更新日期：2017-04-01 00:00:00

abstract：:Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutrition...

journal_title：Nature medicine

authors： Zee T,Bose N,Zee J,Beck JN,Yang S,Parihar J,Yang M,Damodar S,Hall D,O'Leary MN,Ramanathan A,Gerona RR,Killilea DW,Chi T,Tischfield J,Sahota A,Kahn A,Stoller ML,Kapahi P

更新日期：2017-03-01 00:00:00

abstract：:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of...

journal_title：Nature medicine

authors： Ghosh A,Smith M,James SE,Davila ML,Velardi E,Argyropoulos KV,Gunset G,Perna F,Kreines FM,Levy ER,Lieberman S,Jay HV,Tuckett AZ,Zakrzewski JL,Tan L,Young LF,Takvorian K,Dudakov JA,Jenq RR,Hanash AM,Motta AC,Murph

更新日期：2017-02-01 00:00:00

abstract：:Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how t...

journal_title：Nature medicine

authors： Papapetrou EP

更新日期：2016-12-06 00:00:00

abstract：:Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we identified a heart-enriched long noncoding (lnc)RNA, named cardiac-hypertrophy-associated epigenetic regulator (Chaer), whic...

journal_title：Nature medicine

authors： Wang Z,Zhang XJ,Ji YX,Zhang P,Deng KQ,Gong J,Ren S,Wang X,Chen I,Wang H,Gao C,Yokota T,Ang YS,Li S,Cass A,Vondriska TM,Li G,Deb A,Srivastava D,Yang HT,Xiao X,Li H,Wang Y

更新日期：2016-10-01 00:00:00

abstract：:Altered metabolism has been implicated in the pathogenesis of inflammatory diseases. NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multiple biological functions that may be of importance in inflammation and in the pathogenesis of human metabolic diseases, including diabetes. However, the mechanis...

journal_title：Nature medicine

authors： Moon JS,Nakahira K,Chung KP,DeNicola GM,Koo MJ,Pabón MA,Rooney KT,Yoon JH,Ryter SW,Stout-Delgado H,Choi AM

更新日期：2016-09-01 00:00:00

abstract：:Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal. In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threate...

journal_title：Nature medicine

authors： Theurl I,Hilgendorf I,Nairz M,Tymoszuk P,Haschka D,Asshoff M,He S,Gerhardt LM,Holderried TA,Seifert M,Sopper S,Fenn AM,Anzai A,Rattik S,McAlpine C,Theurl M,Wieghofer P,Iwamoto Y,Weber GF,Harder NK,Chousterman BG,

更新日期：2016-08-01 00:00:00

abstract：:The mechanisms responsible for the persistence of HIV-1 after many years of suppressive antiretroviral therapy (ART) have been only partially elucidated. Most of the studies investigating HIV-1 persistence have been performed with blood, although it is well known that germinal centers (GCs) within lymph nodes (LNs) se...

journal_title：Nature medicine

authors： Banga R,Procopio FA,Noto A,Pollakis G,Cavassini M,Ohmiti K,Corpataux JM,de Leval L,Pantaleo G,Perreau M

更新日期：2016-07-01 00:00:00

abstract：:Mutations in genes encoding splicing factors (which we refer to as spliceosomal genes) are commonly found in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations recurrently affect specific amino acid residues, leading to perturbed normal splice site and exon recognition. Spl...

journal_title：Nature medicine

authors： Lee SC,Dvinge H,Kim E,Cho H,Micol JB,Chung YR,Durham BH,Yoshimi A,Kim YJ,Thomas M,Lobry C,Chen CW,Pastore A,Taylor J,Wang X,Krivtsov A,Armstrong SA,Palacino J,Buonamici S,Smith PG,Bradley RK,Abdel-Wahab O

更新日期：2016-06-01 00:00:00

abstract：:CD4(+) T cells that express the forkhead box P3 (FOXP3) transcription factor function as regulatory T (Treg) cells and hinder effective immune responses against cancer cells. Abundant Treg cell infiltration into tumors is associated with poor clinical outcomes in various types of cancers. However, the role of Treg cel...

journal_title：Nature medicine

authors： Saito T,Nishikawa H,Wada H,Nagano Y,Sugiyama D,Atarashi K,Maeda Y,Hamaguchi M,Ohkura N,Sato E,Nagase H,Nishimura J,Yamamoto H,Takiguchi S,Tanoue T,Suda W,Morita H,Hattori M,Honda K,Mori M,Doki Y,Sakaguchi S

更新日期：2016-06-01 00:00:00

abstract：:Molecular targeted therapy has the potential to dramatically improve survival in patients with cancer. However, complete and durable responses to targeted therapy are rare in individuals with advanced-stage solid cancers. Even the most effective targeted therapies generally do not induce a complete tumor response, res...

journal_title：Nature medicine

authors： Bivona TG,Doebele RC

更新日期：2016-05-05 00:00:00

abstract：:Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumo...

journal_title：Nature medicine

authors： Camarda R,Zhou AY,Kohnz RA,Balakrishnan S,Mahieu C,Anderton B,Eyob H,Kajimura S,Tward A,Krings G,Nomura DK,Goga A

更新日期：2016-04-01 00:00:00

abstract：:Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) signaling pathway and a potent tumor suppressor in many types of cancer. To test a tumor suppressive role for PTEN in pre-B acute lymphoblastic leukemia (ALL), we induced Cre-mediated de...

journal_title：Nature medicine

authors： Shojaee S,Chan LN,Buchner M,Cazzaniga V,Cosgun KN,Geng H,Qiu YH,von Minden MD,Ernst T,Hochhaus A,Cazzaniga G,Melnick A,Kornblau SM,Graeber TG,Wu H,Jumaa H,Müschen M

更新日期：2016-04-01 00:00:00

abstract：:Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and id...

journal_title：Nature medicine

authors： Noll EM,Eisen C,Stenzinger A,Espinet E,Muckenhuber A,Klein C,Vogel V,Klaus B,Nadler W,Rösli C,Lutz C,Kulke M,Engelhardt J,Zickgraf FM,Espinosa O,Schlesner M,Jiang X,Kopp-Schneider A,Neuhaus P,Bahra M,Sinn BV,Eil

更新日期：2016-03-01 00:00:00

abstract：:Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the ing...

journal_title：Nature medicine

authors： Suárez-Zamorano N,Fabbiano S,Chevalier C,Stojanović O,Colin DJ,Stevanović A,Veyrat-Durebex C,Tarallo V,Rigo D,Germain S,Ilievska M,Montet X,Seimbille Y,Hapfelmeier S,Trajkovski M

更新日期：2015-12-01 00:00:00

abstract：:The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer...

journal_title：Nature medicine

authors： Miner JJ,Daniels BP,Shrestha B,Proenca-Modena JL,Lew ED,Lazear HM,Gorman MJ,Lemke G,Klein RS,Diamond MS

更新日期：2015-12-01 00:00:00

abstract：:Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...

journal_title：Nature medicine

authors： Janes H,Herbeck JT,Tovanabutra S,Thomas R,Frahm N,Duerr A,Hural J,Corey L,Self SG,Buchbinder SP,McElrath MJ,O'Connell RJ,Paris RM,Rerks-Ngarm S,Nitayaphan S,Pitisuttihum P,Kaewkungwal J,Robb ML,Michael NL,Mullins JI

更新日期：2015-10-01 00:00:00

abstract：:By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show h...

journal_title：Nature medicine

authors： Miller MA,Ganesan AP,Luckashenak N,Mendonca M,Eisenlohr LC

更新日期：2015-10-01 00:00:00

abstract：:Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging suite in a biosafety containment facility, we show th...

journal_title：Nature medicine

authors： Prideaux B,Via LE,Zimmerman MD,Eum S,Sarathy J,O'Brien P,Chen C,Kaya F,Weiner DM,Chen PY,Song T,Lee M,Shim TS,Cho JS,Kim W,Cho SN,Olivier KN,Barry CE 3rd,Dartois V

更新日期：2015-10-01 00:00:00

abstract：:The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a b...

journal_title：Nature medicine

authors： Ortega-Molina A,Boss IW,Canela A,Pan H,Jiang Y,Zhao C,Jiang M,Hu D,Agirre X,Niesvizky I,Lee JE,Chen HT,Ennishi D,Scott DW,Mottok A,Hother C,Liu S,Cao XJ,Tam W,Shaknovich R,Garcia BA,Gascoyne RD,Ge K,Shilatif

更新日期：2015-10-01 00:00:00

abstract：:Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidate the structures of four new host-protective molecules produced in neutrophil-endothelial cocultures and present in human and mouse tissues after sterile inflammation or infecti...

journal_title：Nature medicine

authors： Dalli J,Chiang N,Serhan CN

更新日期：2015-09-01 00:00:00

abstract：:The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but understanding of host-commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal...

journal_title：Nature medicine

authors： Geva-Zatorsky N,Alvarez D,Hudak JE,Reading NC,Erturk-Hasdemir D,Dasgupta S,von Andrian UH,Kasper DL

更新日期：2015-09-01 00:00:00

abstract：:Endothelial dysfunction is a critical factor in many cardiovascular diseases, including hypertension. Although lipid signaling has been implicated in endothelial dysfunction and cardiovascular disease, specific molecular mechanisms are poorly understood. Here we report that Nogo-B, a membrane protein of the endoplasmi...

journal_title：Nature medicine

authors： Cantalupo A,Zhang Y,Kothiya M,Galvani S,Obinata H,Bucci M,Giordano FJ,Jiang XC,Hla T,Di Lorenzo A

更新日期：2015-09-01 00:00:00

abstract：:Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, wit...

journal_title：Nature medicine

authors： Hanssen MJ,Hoeks J,Brans B,van der Lans AA,Schaart G,van den Driessche JJ,Jörgensen JA,Boekschoten MV,Hesselink MK,Havekes B,Kersten S,Mottaghy FM,van Marken Lichtenbelt WD,Schrauwen P

更新日期：2015-08-01 00:00:00

abstract：:Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encod...

journal_title：Nature medicine

authors： Li B,Li H,Bai Y,Kirschner-Schwabe R,Yang JJ,Chen Y,Lu G,Tzoneva G,Ma X,Wu T,Li W,Lu H,Ding L,Liang H,Huang X,Yang M,Jin L,Kang H,Chen S,Du A,Shen S,Ding J,Chen H,Chen J,von Stackelberg A,Gu L,Zhang J,

更新日期：2015-06-01 00:00:00

abstract：:Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of ...

journal_title：Nature medicine

authors： Bhang HE,Ruddy DA,Krishnamurthy Radhakrishna V,Caushi JX,Zhao R,Hims MM,Singh AP,Kao I,Rakiec D,Shaw P,Balak M,Raza A,Ackley E,Keen N,Schlabach MR,Palmer M,Leary RJ,Chiang DY,Sellers WR,Michor F,Cooke VG,Korn JM

更新日期：2015-05-01 00:00:00

abstract：:Much has been written about the advantages and disadvantages of various oncology model systems, with the overall finding that these models lack the predictive power required to translate preclinical efficacy into clinical activity. Despite assertions that some preclinical model systems are superior to others, no singl...

journal_title：Nature medicine

authors： Gould SE,Junttila MR,de Sauvage FJ

更新日期：2015-05-01 00:00:00

abstract：:In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...

journal_title：Nature medicine

authors： Marquard J,Otter S,Welters A,Stirban A,Fischer A,Eglinger J,Herebian D,Kletke O,Klemen MS,Stožer A,Wnendt S,Piemonti L,Köhler M,Ferrer J,Thorens B,Schliess F,Rupnik MS,Heise T,Berggren PO,Klöcker N,Meissner T,Ma

更新日期：2015-04-01 00:00:00

abstract：:One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotrop...

journal_title：Nature medicine

authors： Riebold M,Kozany C,Freiburger L,Sattler M,Buchfelder M,Hausch F,Stalla GK,Paez-Pereda M

更新日期：2015-03-01 00:00:00

abstract：:Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signalin...

journal_title：Nature medicine

authors： Yoda A,Adelmant G,Tamburini J,Chapuy B,Shindoh N,Yoda Y,Weigert O,Kopp N,Wu SC,Kim SS,Liu H,Tivey T,Christie AL,Elpek KG,Card J,Gritsman K,Gotlib J,Deininger MW,Makishima H,Turley SJ,Javidi-Sharifi N,Maciejewski

更新日期：2015-01-01 00:00:00

abstract：:Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interacti...

journal_title：Nature medicine

authors： Arruda AP,Pers BM,Parlakgül G,Güney E,Inouye K,Hotamisligil GS

更新日期：2014-12-01 00:00:00