Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.

abstract：:Systemic toxicities have severely limited the clinical application of tumor necrosis factor (TNF) as an anticancer agent. Activity-on-Target cytokines (AcTakines) are a novel class of immunocytokines with improved therapeutic index. A TNF-based AcTakine targeted to CD13 enables selective activation of the tumor neovas...

journal_title：EMBO molecular medicine

authors： Huyghe L,Van Parys A,Cauwels A,Van Lint S,De Munter S,Bultinck J,Zabeau L,Hostens J,Goethals A,Vanderroost N,Verhee A,Uzé G,Kley N,Peelman F,Vandekerckhove B,Brouckaert P,Tavernier J

更新日期：2020-02-07 00:00:00

abstract：:The first EMBO workshop on Emerging Themes in Infection Biology was held last June in the South of France. It gathered scientists working on various pathogens from viruses and bacteria to larger eukaryotic fungi and parasites. Topics included not only the crosstalk between pathogens and their hosts but also the tools ...

journal_title：EMBO molecular medicine

authors： Caldeira S,Dumenil G

更新日期：2010-09-01 00:00:00

abstract：:Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...

journal_title：EMBO molecular medicine

authors： Christensen NR,De Luca M,Lever MB,Richner M,Hansen AB,Noes-Holt G,Jensen KL,Rathje M,Jensen DB,Erlendsson S,Bartling CR,Ammendrup-Johnsen I,Pedersen SE,Schönauer M,Nissen KB,Midtgaard SR,Teilum K,Arleth L,Sørensen AT

更新日期：2020-06-08 00:00:00

abstract：:The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the ...

journal_title：EMBO molecular medicine

authors： Xu Y,Wang Y,Yan S,Zhou Y,Yang Q,Pan Y,Zeng X,An X,Liu Z,Wang L,Xu J,Cao Y,Fulton DJ,Weintraub NL,Bagi Z,Hoda MN,Wang X,Li Q,Hong M,Jiang X,Boison D,Weber C,Wu C,Huo Y

更新日期：2017-09-01 00:00:00

abstract：:Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence va...

journal_title：EMBO molecular medicine

authors： Falik-Zaccai TC,Barsheshet Y,Mandel H,Segev M,Lorber A,Gelberg S,Kalfon L,Ben Haroush S,Shalata A,Gelernter-Yaniv L,Chaim S,Raviv Shay D,Khayat M,Werbner M,Levi I,Shoval Y,Tal G,Shalev S,Reuveni E,Avitan-Hersh E,V

更新日期：2017-03-01 00:00:00

abstract：:The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells w...

journal_title：EMBO molecular medicine

authors： Testoni E,Stephenson NL,Torres-Ayuso P,Marusiak AA,Trotter EW,Hudson A,Hodgkinson CL,Morrow CJ,Dive C,Brognard J

更新日期：2016-02-01 00:00:00

abstract：:Mitochondrial disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We in...

journal_title：EMBO molecular medicine

authors： Buzkova J,Nikkanen J,Ahola S,Hakonen AH,Sevastianova K,Hovinen T,Yki-Järvinen H,Pietiläinen KH,Lönnqvist T,Velagapudi V,Carroll CJ,Suomalainen A

更新日期：2018-12-01 00:00:00

abstract：:Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 muta...

journal_title：EMBO molecular medicine

authors： Inaguma Y,Hamada N,Tabata H,Iwamoto I,Mizuno M,Nishimura YV,Ito H,Morishita R,Suzuki M,Ohno K,Kumagai T,Nagata K

更新日期：2014-03-01 00:00:00

abstract：:Sterile inflammation underlies many diseases of the cornea including serious chemical burns and the common dry eye syndrome. In search for therapeutic targets for corneal inflammation, we defined the kinetics of neutrophil infiltration in a model of sterile injury to the cornea and identified molecular and cellular me...

journal_title：EMBO molecular medicine

authors： Oh JY,Choi H,Lee RH,Roddy GW,Ylöstalo JH,Wawrousek E,Prockop DJ

更新日期：2012-05-01 00:00:00

abstract：:The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body...

journal_title：EMBO molecular medicine

authors： Wang T,Liu J,McDonald C,Lupino K,Zhai X,Wilkins BJ,Hakonarson H,Pei L

更新日期：2017-08-01 00:00:00

abstract：:Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and prom...

journal_title：EMBO molecular medicine

authors： Lee SW,Jeong HK,Lee JY,Yang J,Lee EJ,Kim SY,Youn SW,Lee J,Kim WJ,Kim KW,Lim JM,Park JW,Park YB,Kim HS

更新日期：2012-09-01 00:00:00

abstract：:Genomic data sharing is becoming more important as scientists join forces across borders in biomedical research for the benefit of patients and society. The EU's General Data Protection Regulation (GDPR) helps simplify sharing of such data at the European and international level. However, initial optimism has dried up...

journal_title：EMBO molecular medicine

authors： Molnár-Gábor F,Korbel JO

更新日期：2020-03-06 00:00:00

abstract：:Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, gen...

journal_title：EMBO molecular medicine

authors： Dunbar LA,Patni P,Aguilar C,Mburu P,Corns L,Wells HR,Delmaghani S,Parker A,Johnson S,Williams D,Esapa CT,Simon MM,Chessum L,Newton S,Dorning J,Jeyarajan P,Morse S,Lelli A,Codner GF,Peineau T,Gopal SR,Alagramam K

更新日期：2019-09-01 00:00:00

abstract：:Diabetes mellitus (DM) is a growing international concern. Considerable mortality and morbidity associated with diabetes mellitus arise predominantly from thrombotic cardiovascular events. Oxidative stress-mediated mitochondrial damage contributes significantly to enhanced thrombosis in DM A basal autophagy process ha...

journal_title：EMBO molecular medicine

authors： Lee SH,Du J,Stitham J,Atteya G,Lee S,Xiang Y,Wang D,Jin Y,Leslie KL,Spollett G,Srivastava A,Mannam P,Ostriker A,Martin KA,Tang WH,Hwa J

更新日期：2016-07-01 00:00:00

abstract：:RAD51 recombinase activity plays a critical role for cancer cell proliferation and survival, and often contributes to drug-resistance. Abnormally elevated RAD51 function and hyperactive homologous recombination (HR) rates have been found in a panel of cancers, including breast cancer and chronic myeloid leukaemia (CML...

journal_title：EMBO molecular medicine

authors： Zhu J,Zhou L,Wu G,Konig H,Lin X,Li G,Qiu XL,Chen CF,Hu CM,Goldblatt E,Bhatia R,Chamberlin AR,Chen PL,Lee WH

更新日期：2013-03-01 00:00:00

abstract：:Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently ...

journal_title：EMBO molecular medicine

authors： Sahashi K,Ling KK,Hua Y,Wilkinson JE,Nomakuchi T,Rigo F,Hung G,Xu D,Jiang YP,Lin RZ,Ko CP,Bennett CF,Krainer AR

更新日期：2013-10-01 00:00:00

abstract：:Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a...

journal_title：EMBO molecular medicine

authors： Sprenger HG,Wani G,Hesseling A,König T,Patron M,MacVicar T,Ahola S,Wai T,Barth E,Rugarli EI,Bergami M,Langer T

更新日期：2019-01-01 00:00:00

abstract：:There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but have thus far been complex. Using real-time PCR analysis, we evaluated the expression profile...

journal_title：EMBO molecular medicine

authors： Maertzdorf J,McEwen G,Weiner J 3rd,Tian S,Lader E,Schriek U,Mayanja-Kizza H,Ota M,Kenneth J,Kaufmann SH

更新日期：2016-02-01 00:00:00

abstract：:In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. Here, we show that tumour growth triggers hepatic metabolic dysfunction as part of the cancer cachectic phenotype, particularly by reduced hepatic very-low-density-lipoprotein (VLDL) sec...

journal_title：EMBO molecular medicine

authors： Jones A,Friedrich K,Rohm M,Schäfer M,Algire C,Kulozik P,Seibert O,Müller-Decker K,Sijmonsma T,Strzoda D,Sticht C,Gretz N,Dallinga-Thie GM,Leuchs B,Kögl M,Stremmel W,Diaz MB,Herzig S

更新日期：2013-02-01 00:00:00

abstract：:The Plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. However, it has recently been demonstrated that priming also occurs in the skin. We wished to establish if sterile protection could be obtained in ...

journal_title：EMBO molecular medicine

authors： Obeid M,Franetich JF,Lorthiois A,Gego A,Grüner AC,Tefit M,Boucheix C,Snounou G,Mazier D

更新日期：2013-02-01 00:00:00

abstract：:Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neur...

journal_title：EMBO molecular medicine

authors： Ramos-Montoya A,Lamb AD,Russell R,Carroll T,Jurmeister S,Galeano-Dalmau N,Massie CE,Boren J,Bon H,Theodorou V,Vias M,Shaw GL,Sharma NL,Ross-Adams H,Scott HE,Vowler SL,Howat WJ,Warren AY,Wooster RF,Mills IG,Neal DE

更新日期：2014-05-01 00:00:00

abstract：:Patients affected by mitochondrial OXPHOS disorders are still faced with a grim lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent data by Giovanni Manfredi on PKA's functions in the mitochondria and now its modulation can improve respiration and ATP production in COX-defective cells. ...

journal_title：EMBO molecular medicine

authors： Moraes CT

更新日期：2009-11-01 00:00:00

abstract：:The transcription factors of the MYC family play pivotal roles in the initiation and progression of human cancers. High oncogenic level of MYC invades low-affinity sites and enhancer sequences, which subsequently alters the transcriptome, causes metabolic imbalance, and induces stress response. The endoplasmic reticul...

journal_title：EMBO molecular medicine

authors： Zhang T,Li N,Sun C,Jin Y,Sheng X

更新日期：2020-05-08 00:00:00

abstract：:The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has pro...

journal_title：EMBO molecular medicine

authors： Demminger DE,Walz L,Dietert K,Hoffmann H,Planz O,Gruber AD,von Messling V,Wolff T

更新日期：2020-05-08 00:00:00

abstract：:Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inact...

journal_title：EMBO molecular medicine

authors： Magnotti F,Lefeuvre L,Benezech S,Malsot T,Waeckel L,Martin A,Kerever S,Chirita D,Desjonqueres M,Duquesne A,Gerfaud-Valentin M,Laurent A,Sève P,Popoff MR,Walzer T,Belot A,Jamilloux Y,Henry T

更新日期：2019-11-07 00:00:00

abstract：:Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross-talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FG...

journal_title：EMBO molecular medicine

authors： Maddaluno L,Urwyler C,Rauschendorfer T,Meyer M,Stefanova D,Spörri R,Wietecha M,Ferrarese L,Stoycheva D,Bender D,Li N,Strittmatter G,Nasirujjaman K,Beer HD,Staeheli P,Hildt E,Oxenius A,Werner S

更新日期：2020-09-07 00:00:00

abstract：:Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-c...

journal_title：EMBO molecular medicine

authors： Patel R,Fleming J,Mui E,Loveridge C,Repiscak P,Blomme A,Harle V,Salji M,Ahmad I,Teo K,Hamdy FC,Hedley A,van den Broek N,Mackay G,Edwards J,Sansom OJ,Leung HY

更新日期：2018-04-01 00:00:00

abstract：:Over thousands of years microbes and mammals have co-evolved, resulting in extraordinarily sophisticated molecular mechanisms permitting the organisms to survive together. Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human populatio...

journal_title：EMBO molecular medicine

authors： Mortellaro A,Robinson L,Ricciardi-Castagnoli P

更新日期：2009-04-01 00:00:00

abstract：:Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combi...

journal_title：EMBO molecular medicine

authors： Benedetti S,Uno N,Hoshiya H,Ragazzi M,Ferrari G,Kazuki Y,Moyle LA,Tonlorenzi R,Lombardo A,Chaouch S,Mouly V,Moore M,Popplewell L,Kazuki K,Katoh M,Naldini L,Dickson G,Messina G,Oshimura M,Cossu G,Tedesco FS

更新日期：2018-02-01 00:00:00

abstract：:A homozygous mutation in the gene for sigma 1 receptor (Sig1R) is a cause of inherited juvenile amyotrophic lateral sclerosis (ALS16). Sig1R localizes to the mitochondria-associated membrane (MAM), which is an interface of mitochondria and endoplasmic reticulum. However, the role of the MAM in ALS is not fully elucida...

journal_title：EMBO molecular medicine

authors： Watanabe S,Ilieva H,Tamada H,Nomura H,Komine O,Endo F,Jin S,Mancias P,Kiyama H,Yamanaka K

更新日期：2016-12-01 00:00:00