Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors.

abstract：:The angiopoietin (Ang)-Tie pathway has been intensely pursued as candidate second-generation anti-angiogenic target. While much of the translational work has focused on the ligand Ang2, the clinical efficacy of Ang2-targeting drugs is limited and failed to improve patient survival. In turn, the orphan receptor Tie1 re...

journal_title：EMBO molecular medicine

authors： Singhal M,Gengenbacher N,La Porta S,Gehrs S,Shi J,Kamiyama M,Bodenmiller DM,Fischl A,Schieb B,Besemfelder E,Chintharlapalli S,Augustin HG

更新日期：2020-06-08 00:00:00

abstract：:Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target-agnostic approach based...

journal_title：EMBO molecular medicine

authors： Lanzavecchia A

更新日期：2018-03-01 00:00:00

abstract：:The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF-induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which l...

journal_title：EMBO molecular medicine

authors： Souffriau J,Timmermans S,Vanderhaeghen T,Wallaeys C,Van Looveren K,Aelbrecht L,Dewaele S,Vandewalle J,Goossens E,Verbanck S,Boyen F,Eggermont M,De Commer L,De Rycke R,De Bruyne M,Tito R,Ballegeer M,Vandevyver S,Velho

更新日期：2020-10-07 00:00:00

abstract：:The six transmembrane protein of prostate 2 (STAMP2) is an androgen-regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also s...

journal_title：EMBO molecular medicine

authors： Jin Y,Wang L,Qu S,Sheng X,Kristian A,Mælandsmo GM,Pällmann N,Yuca E,Tekedereli I,Gorgulu K,Alpay N,Sood A,Lopez-Berestein G,Fazli L,Rennie P,Risberg B,Wæhre H,Danielsen HE,Ozpolat B,Saatcioglu F

更新日期：2015-03-01 00:00:00

abstract：:There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells be...

journal_title：EMBO molecular medicine

authors： Droz-Georget Lathion S,Rochat A,Knott G,Recchia A,Martinet D,Benmohammed S,Grasset N,Zaffalon A,Besuchet Schmutz N,Savioz-Dayer E,Beckmann JS,Rougemont J,Mavilio F,Barrandon Y

更新日期：2015-04-01 00:00:00

abstract：:The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplas...

journal_title：EMBO molecular medicine

authors： Ceder S,Eriksson SE,Cheteh EH,Dawar S,Corrales Benitez M,Bykov VJN,Fujihara KM,Grandin M,Li X,Ramm S,Behrenbruch C,Simpson KJ,Hollande F,Abrahmsen L,Clemons NJ,Wiman KG

更新日期：2020-12-14 00:00:00

abstract：:Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis a...

journal_title：EMBO molecular medicine

authors： Whidbey C,Vornhagen J,Gendrin C,Boldenow E,Samson JM,Doering K,Ngo L,Ezekwe EA Jr,Gundlach JH,Elovitz MA,Liggitt D,Duncan JA,Adams Waldorf KM,Rajagopal L

更新日期：2015-04-01 00:00:00

abstract：:Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regu...

journal_title：EMBO molecular medicine

authors： Cheng YY,Yan YT,Lundy DJ,Lo AH,Wang YP,Ruan SC,Lin PJ,Hsieh PC

更新日期：2017-02-01 00:00:00

abstract：:The molecular networks that control the progression of chronic kidney diseases (CKD) are poorly defined. We have recently shown that the susceptibility to development of renal lesions after nephron reduction is controlled by a locus on mouse chromosome 6 and requires epidermal growth factor receptor (EGFR) activation....

journal_title：EMBO molecular medicine

authors： Laouari D,Burtin M,Phelep A,Bienaime F,Noel LH,Lee DC,Legendre C,Friedlander G,Pontoglio M,Terzi F

更新日期：2012-08-01 00:00:00

abstract：:High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to ac...

journal_title：EMBO molecular medicine

authors： Germann M,Zangger N,Sauvain MO,Sempoux C,Bowler AD,Wirapati P,Kandalaft LE,Delorenzi M,Tejpar S,Coukos G,Radtke F

更新日期：2020-01-09 00:00:00

abstract：:Intellectual disability (ID) is a condition that affects approximately 1% of the population (Maulik et al, 2011). The numbers may differ across nations, owing to different systems and diagnosis entries or lack of such, but usually range between 0.6 and 3% (Stromme & Valvatne, 1998). Persons with ID are a heterogeneous...

journal_title：EMBO molecular medicine

authors： Kolset SO

更新日期：2020-10-07 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：: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：:Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview o...

journal_title：EMBO molecular medicine

authors： Hartmann J,Schüßler-Lenz M,Bondanza A,Buchholz CJ

更新日期：2017-09-01 00:00:00

abstract：:Highly active antiretroviral therapy (HAART) has improved the outlook for the HIV epidemic, but does not provide a cure. The proposed "shock-and-kill" strategy is directed at inducing latent HIV reservoirs, which may then be purged via boosted immune response or targeting infected cells. We describe five novel compoun...

journal_title：EMBO molecular medicine

authors： Hashemi P,Barreto K,Bernhard W,Lomness A,Honson N,Pfeifer TA,Harrigan PR,Sadowski I

更新日期：2018-02-01 00:00:00

abstract：:The combinations of genetic alterations that cooperate with von Hippel-Lindau (VHL) mutation to cause clear cell renal cell carcinoma (ccRCC) remain poorly understood. We show that the TP53 tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of Vhl and Trp53 in primary mouse embryo...

journal_title：EMBO molecular medicine

authors： Albers J,Rajski M,Schönenberger D,Harlander S,Schraml P,von Teichman A,Georgiev S,Wild PJ,Moch H,Krek W,Frew IJ

更新日期：2013-06-01 00:00:00

abstract：:Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests tha...

journal_title：EMBO molecular medicine

authors： Holmberg FE,Seidelin JB,Yin X,Mead BE,Tong Z,Li Y,Karp JM,Nielsen OH

更新日期：2017-05-01 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 cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cell...

journal_title：EMBO molecular medicine

authors： Tosoni D,Pambianco S,Ekalle Soppo B,Zecchini S,Bertalot G,Pruneri G,Viale G,Di Fiore PP,Pece S

更新日期：2017-05-01 00:00:00

abstract：:Diabetic nephropathy is the leading cause of end-stage renal disease. Although dysfunction of podocytes, also termed glomerular visceral epithelial cells, is critically associated with diabetic nephropathy, the mechanism underlying podocyte dysfunction still remains obscure. Here, we identify that KDM6A, a histone lys...

journal_title：EMBO molecular medicine

authors： Lin CL,Hsu YC,Huang YT,Shih YH,Wang CJ,Chiang WC,Chang PJ

更新日期：2019-05-01 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：:Prevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity. Native ...

journal_title：EMBO molecular medicine

authors： Jimenez V,Jambrina C,Casana E,Sacristan V,Muñoz S,Darriba S,Rodó J,Mallol C,Garcia M,León X,Marcó S,Ribera A,Elias I,Casellas A,Grass I,Elias G,Ferré T,Motas S,Franckhauser S,Mulero F,Navarro M,Haurigot V,Rube

更新日期：2018-08-01 00:00:00

abstract：:Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still n...

journal_title：EMBO molecular medicine

authors： Garcia AI,Buisson M,Bertrand P,Rimokh R,Rouleau E,Lopez BS,Lidereau R,Mikaélian I,Mazoyer S

更新日期：2011-05-01 00:00:00

abstract：:Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are co...

journal_title：EMBO molecular medicine

authors： Rustighi A,Zannini A,Tiberi L,Sommaggio R,Piazza S,Sorrentino G,Nuzzo S,Tuscano A,Eterno V,Benvenuti F,Santarpia L,Aifantis I,Rosato A,Bicciato S,Zambelli A,Del Sal G

更新日期：2014-01-01 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：:Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod deg...

journal_title：EMBO molecular medicine

authors： Zhao L,Zabel MK,Wang X,Ma W,Shah P,Fariss RN,Qian H,Parkhurst CN,Gan WB,Wong WT

更新日期：2015-09-01 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：:Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-t...

journal_title：EMBO molecular medicine

authors： Perli E,Giordano C,Pisano A,Montanari A,Campese AF,Reyes A,Ghezzi D,Nasca A,Tuppen HA,Orlandi M,Di Micco P,Poser E,Taylor RW,Colotti G,Francisci S,Morea V,Frontali L,Zeviani M,d'Amati G

更新日期：2014-02-01 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：: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