Guido Kroemer

..Similarly, alterations in the autophagic compartment are linked to carcinogenesis and resistance to chemotherapy. Targeting these pathways might constitute a novel approach to cancer therapy...

..These results underscore the role of p38 MAPK as a pro-apoptotic kinase in the p53-dependant pathway for the therapeutic elimination of polyploidy cells...

..Tetraploid cells were also more resistant against UVC and gamma-irradiation. These data indicate the existence of p53-dependent alterations in apoptosis regulation in tetraploid cells...

..In summary, we demonstrate that phosphorylation of p53S15 by mTOR/FRAP plays a critical role in syncytial apoptosis driven by HIV-1 Env...

..Thus, hyperosmotic stress kills cells by triggering different molecular pathways, which converge at mitochondria where pro- and anti-apoptotic members of the Bcl-2 family exert their control...

..Specifically, we discuss the alterations in signal transduction pathways and/or enzymatic machineries that account for metabolic reprogramming of transformed cells...

..So instead of an auto-apotheosis, this piece will simply translate what I could tell a friend during an after-dinner conversation, knowing that the plans for the future (optimistically) outnumber the experiences in the past...

..Another example concerns the so-called apoptosis-inducing factor (AIF), another mitochondrial intermembrane protein which can translocate to the nucleus where it induces chromatin condensation and DNA fragmentation...

..Such alternative strategies may either target catabolic hydrolases or be aimed at preventing mitochondrial membrane permeabilization and its upstream triggers...

..The detailed investigation of the mechanisms of MMP will hopefully lead to the discovery of suitable drug targets for therapeutic intervention on cell death control...

..All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways...

..This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including 'entosis', 'mitotic catastrophe', 'necrosis', 'necroptosis' and 'pyroptosis'...

..We also list the caveats that must be considered when deciding whether or not autophagy is an important effector mechanism of cell death...

..Our findings delineate a molecular pathway through which DNA damage, failure to arrest the cell cycle and inhibition of apoptosis can favor the occurrence of cytogenetic abnormalities that are likely to participate in oncogenesis...

..In synthesis, our data reveal the unexpected capacity of STS to induce DNA lesions and suggest qualitative differences in the cytoprotective and DNA repair-inducing potential of different apoptosis inhibitors...

..Hence, ATP release is a general correlate of apoptotic cell death induced by conventional anticancer therapies...

..Altogether, these results indicate that Chk2 (but not Chk1) participates in the DNA damage-elicited pro-apoptotic cascade that leads to the demise of Env-elicited syncytia...

..The data reported herein indicate that LMP does not suffice to trigger caspase activation and that Bax/Bak-dependent MMP is a critical step of LMP-induced cell death...

..Conversely, inhibition of caspases did not prevent MMP. These results indicate that Env-elicited syncytial apoptosis involves the intrinsic (mitochondrial) pathway...

..Inhibition of Chk2 thus can sensitize proliferating cells to chemotherapy-induced apoptosis...

..In the absence of p53, Mos knockdown prevents multipolar mitoses and exerts genome-stabilizing effects. These results elucidate the mechanisms through which asymmetric cell division drives chromosomal instability in tetraploid cells...

..These data identify CRT as a key feature determining anticancer immune responses and delineate a possible strategy for immunogenic chemotherapy...

..Contagious apoptosis could be induced in primary human T cells, as well as in vivo, in T cells exposed to dying Env-expressing cells. Altogether, these data point to a novel mechanism through which HIV-1 can induce bystander killing...

..Hence, Apaf-1 exerts two distinct, phylogenetically conserved roles in response to mitochondrial membrane permeabilization and DNA damage. These data point to a role for Apaf-1 as a bona fide tumor suppressor...

..We surmise that subtle and concerted alterations in the acetylproteome regulate autophagy at multiple levels...

..The response to chemotherapy and/or radiotherapy may thus combine both direct cytotoxic effects and the development of long-term antitumor immunity. We anticipate that these new results will have major impact on cancer management...

..These results suggest that the PP1/GADD34 complex plays a major role in the regulation of CRT exposure...

..vMIA neutralizes Bax by recruiting it to mitochondria and "freezing" its pro-apoptotic activity. These data unravel a novel strategy of subverting an intrinsic pathway of apoptotic signaling...

..We review these two molecular mechanisms that dictate the radio/chemotherapy-elicited antitumor immune response and discuss how this knowledge can be clinically exploited to predict and also ameliorate the success of chemo/radiotherapy...

..Altogether, these results identify miR-181a and miR-630 as novel modulators of the CDDP response in NSCLC...

..We conclude that the mitotic progression of p53(-/-) (but not p53(+/+)) tetraploids heavily relies on p38alpha, revealing a novel function for this protein in the context of aneuploidizing cell divisions...

..Thus, combination therapies with erlotinib and rapamycin might be beneficial for MDS and AML patients...

..Dominant-negative MKK3 or MKK6 inhibited syncytial activation of p38, p53S46P, and apoptosis. Altogether, these findings indicate that p38 MAPK-mediated p53 phosphorylation constitutes a critical step of Env-induced apoptosis...

..The challenge will be to determine whether the exposure of calreticulin translocation on the tumour cell surface is linked to chemotherapy-induced anti-tumour immune responses and therapeutic efficacy in human cancer...

..Depletion of PERK, caspase-8 or SNAREs had no effect on cell death induced by anthracyclines, yet abolished the immunogenicity of cell death, which could be restored by absorbing recombinant CRT to the cell surface...

..Moreover, QM31 can inhibit mitochondrial outer membrane permeabilization, an effect that is independent from its action on Apaf-1...

..Nonetheless, numerous details on the molecular events that define immunogenicity remain to be defined, both at the level of the dying cancer cells and at the level of the responding innate effectors...

..Altogether these results indicate that apoptosis induced by a fusogenic HIV-1 Env follows a pro-apoptotic pathway involving the sequential activation of ATM, p38MAPK and p53...

..Altogether, these data indicate that 4-HPR induces MMP through an ROS-mediated pathway that involves the obligatory contribution of the proapopotic Bcl-2 family members Bax and/or Bak...

..Thus, PK11195 potently sensitizes to apoptosis via a pathway that involves mitochondria, yet does not involve the PBR...

..These results indicate that micronuclei can be subjected to autophagic degradation. Moreover, it can be speculated that removal of micronuclei may contribute to the genome-stabilizing effects of autophagy...

..Thus, autophagy is essential for the immunogenic release of ATP from dying cells, and increased extracellular ATP concentrations improve the efficacy of antineoplastic chemotherapies when autophagy is disabled...

..These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53...

..BH3-only proteins and pharmacological BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2 or Bcl-X(L)...

..These results delineate a novel procedure for studying the intersection between cell cycle regulation and cell death mechanisms...

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..Altogether these results suggest that Chir-124-mediated radiosensitization is profoundly influenced by the p53 and cell cycle checkpoint system...

..Altogether, these data underscore the importance of an autophagy regulatory network of antagonistic deacetylases and acetylases that can be pharmacologically manipulated...

..The implications of these findings for the pathophysiology of HIV-1 infection is discussed...

..We speculate that human cancers that are incapable of activating the CRT exposure pathway are refractory to the immune-mediated component of anticancer therapies...

..Moreover, recombinant KARS protein was unable to stimulate macrophages in vitro. These results underscore the contribution of KARS to the emission of (one of) the principal signal(s) of immunogenic cell death, CRT exposure...

..Altogether, these results suggest that autophagy-incompetent tumor cells escape from chemotherapy-induced (and perhaps natural?) immunosurveillance because they are unable to release ATP...

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..Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers...

..Accordingly, we describe a strategy for discriminating cell death with autophagy from cell death through autophagy...

..Based on the recent clinical or experimental findings, several strategies have been suggested to improve the immunogenicity of cell death and augment antitumor immunity...

..These results suggest that erlotinib and gefitinib share a mechanistically related off-target effect that may be taken advantage of for the therapy of MDS and AML...

..In summary, we here provide novel evidence in vitro, ex vivo, and in vivo for the potential therapeutic efficacy of erlotinib in the treatment of high-risk MDS and AML...

..g., Puma, Bax, Bak, caspase-2, etc.) and DNA damage-related proteins (e.g., ERCC1, hTERT) exerted cytoprotective effects. BMS-690514 is a new pan-HER/VEGFR inhibitor that may become an alternative to erlotinib for the treatment of NSCLC...

..These data point to an intrinsic resistance of tetraploid cells against radiotherapy and DNA-targeted chemotherapy that may be linked to the status of the p53 system...

..Collectively, our data indicate that upon exposure to tumor cells, IKDC subserve DC-like functions...

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..Thus, p53 may constitute a novel therapeutic target for the treatment of AIDS...

..Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection...

..Altogether, these data support the contention that AZD1152 mediates radiosensitization in vivo by enhancing mitotic catastrophe, which can be used as a biomarker of treatment efficacy...

..Altogether, our data indicate that mitochondria are indispensable for cell death initiated by lysosomal destabilization...

..Thus, localized caspase activation is causal to proplatelet formation. We conclude that proplatelet formation is regulated by a caspase activation limited to only some cellular compartments...

..These data suggest that a multistep pathway, including DNA endoreduplication, polyploidy, then depolyploidization and generation of clonogenic escape cells can account for tumor relapse after initial efficient chemotherapy...

..Similarly, knockdown of the phosphate carrier reduced cell size. Our data suggest that the cytopathic effect of CMV can be explained by vMIA effects on mitochondrial bioenergetics...

..IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. These results imply a novel danger signal, ATP, and a novel receptor, P2RX7, in the chemotherapy-elicited anticancer immune response...

..Bcl-2-mediated regulation of mitochondrial membrane permeabilization may contribute to apoptosis control by preventing mitochondrial, pre-processed caspase-9 from interacting with its cytosolic activators...

..We speculate that combinations of these molecules determine the route by which dying cells are engulfed and the nature of the immune response that their death elicits...

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..In conclusion, tetraploid cells are particular vulnerable to undergo mitotic catastrophe after genetic or pharmacological inhibition of Eg5...

..Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies...

..These results delineate a procedure for the generation of cancer vaccines and the stimulation of anti-neoplastic immune responses in vivo...

..This delineates a molecular pathway through which failure to arrest the cell cycle and inhibition of apoptosis can favor the occurrence of cytogenetic abnormalities which are likely to participate in oncogenesis...

..Together, these results suggest that MK polyploidization per se does not regulate gene expression but is intrinsically included in the differentiation process...

..Thus, a stereotyped pattern of mitochondrial alterations accompanies differentiation-associated MK death in MDS...

..Here, we detail this methodology, which has been instrumental for investigating the functional link between ploidy status and oncogenesis...

..NF-kappaB inhibition may constitute a novel therapeutic strategy if apoptosis induction of MDS stem cells is the goal...

..In conclusion, BaxBH3 and Bcl2BH3 induce MMP and apoptosis through a mechanism which overcomes cytoprotection by Bcl-2 and Bcl-X(L)...

..As tetraploid cells represent a metastable intermediate between normal diploidy and cancer-associated aneuploidy, this novel route to tetraploidization may constitute (one of) the functional link(s) between aging and carcinogenesis...

..Thus, the subcellular location of Apaf-1 (but not that of p53 or Hsp70) constitutes an accurate prognostic factor for overall survival in NSCLC...

..Cdk1 inhibition prevents the death of syncytia elicited by HIV-1 infection of primary CD4 lymphoblasts. Thus, HIV-1 elicits a pro-apoptotic signal transduction pathway relying on the sequential action of cyclin B-Cdk1, mTOR and p53...

..This effect may involve a direct effect on the PTPC and/or indirect effects secondary to the NO-mediated inhibition of oxidative phosphorylation. This has far-reaching implications for the pathophysiology of NO...

..These results establish novel functional links between microtubules and autophagy, identify a new chemotherapy resistance-associated autophagic defect, and describe the existence of LC3 puncta outside from autophagosomes...

..The purpose of this review is to summarize recent insights into the immunogenicity of dying tumor cells as a function of the cell death modality...

..Our review recapitulates the results of these studies and proposes novel strategies of inhibiting post-mitochondrial apoptosis in neurons...

..We will summarize the immune adjuvants that can boost the immunogenicity of cell death to augment the efficacy of chemotherapy...

..These results point to a hitherto neglected crosstalk between autophagic vacuolization and cell cycle regulation...

..Thus, viral proteins can regulate apoptosis at the mitochondrial level by acting on a variety of different targets...

..In this review, we will discuss recent advances in the cooperation between ANT and Bax/Bcl-2 family members, the multiplicity of agents affecting ANT pore function and the putative role of ANT isoforms in apoptosis control...

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..In this review, we discuss several mechanisms by which mitochondria can contribute to malignant transformation and tumor progression...