S Fulda

..Thus, inhibition of IAPs such as X chromosome-linked IAP may prove to be a successful strategy to overcome apoptosis resistance of human cancers that deserves further exploitation...

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..Therefore, caspase-8 presents a promising target to restore defective apoptosis programs in cancers in order to overcome resistance...

..Thus, mitochondrion-targeted agents such as BA hold great promise as a novel approach to bypass certain forms of drug resistance in human cancers...

..Thus, molecular targeted therapies that are specifically directed to the defects in apoptosis programs, open novel perspectives to restore apoptosis sensitivity in rhabdomyosarcoma...

..Hence, a better understanding of the molecular mechanisms underlying tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to develop molecular targeted therapies...

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..Therefore, insights into the mechanisms regulating drug-induced apoptosis provide rational targets for novel therapeutic interventions...

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..Thus, targeting IAPs, e.g. by antisense approaches or small molecule inhibitors, presents a promising novel approach for future drug development and may proof to be a successful strategy to overcome apoptosis resistance of human cancers...

..DISCUSSION: Further insights into the signaling network and interaction points modulated by resveratrol may provide the basis for novel drug discovery programs to exploit resveratrol for the prevention and treatment of human diseases...

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..Thus, our study provides novel insight into the biology of this tumor, which may have important clinical implications...

..Thus, Hif-1alpha and hypoxia-inducible genes represent attractive targets for the development of pharmacological inhibitors, which may offer new therapeutic options for a wide range of adult and also pediatric malignancies...

..This approach is expected to open new and more effective approaches for the treatment of childhood cancers...

..Therefore, a better understanding of the signaling pathways and molecules that govern apoptosis in neuroblastoma cells is expected to open new avenues for the design of molecular targeted therapies for neuroblastoma...

..Thus, IAPs present promising targets for the development of new biomarkers and cancer therapeutics in hematological malignancies...

..This review presents some examples of how apoptosis pathways are targeted by selected naturally occurring agents and how these events can be exploited for cancer therapy...

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..Eventually, PI3K/Akt/mTOR targeting agents may open novel perspectives to improve the poor prognosis of patients with neuroblastoma especially in advanced stages of the disease...

..Structure-based development of selective IAP inhibitors now provides, for the first time, evidence that simultaneous inhibition of the c-IAP proteins and XIAP is necessary for efficient induction of cancer cell death by IAP antagonists...

..Here we provide a brief review of the literature vis a vis the various mechanisms of defective apoptotic signaling in CSCs with potential for therapeutic intervention...

..How apoptosis pathways can be exploited for the treatment of pancreatic cancer will be discussed in this review...

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..Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers...

..Thus, mitochondrion-targeted agents such as BA hold great promise as a novel approach to overcome certain forms of drug resistance in human cancers...

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..Thus, targeting PI3K presents a novel and promising strategy to sensitize neuroblastoma cells for chemotherapy-induced apoptosis, which has important implications for the development of targeted therapies for neuroblastoma...

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..Thus, Smac agonists may be useful in cancer therapy, for example, for tumor control in minimal residual disease. Oncogene (2005) 24, 7190-7202. doi:10.1038/sj.onc.1208876; published online 8 August 2005...

..In conclusion, targeting XIAP, for example by small molecules, is a promising novel approach to enhance radiosensitivity of pancreatic cancer that warrants further investigation...

..These findings have important clinical implications for the design of experimental treatment protocols for medulloblastoma...

..In conclusion, our findings provide evidence that targeting IAPs (e.g., by Smac agonists) is a promising strategy to enhance radiosensitivity in human cancers...

..These results strongly indicate that oxidative damage-induced nuclear translocation of AIF and EndoG in 4-OOH-CY-treated T cells might represent an alternative death pathway in the absence of caspase activity...

..These findings indicate that using BetA as sensitizer in chemotherapy-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy, which warrants further investigation...

..TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFalpha signaling and therefore cell death...

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..Given the promising therapeutic potential of TRAIL as a novel anticancer drug, TRAIL-mediated survival or proliferation of target cells may restrict its use to apoptosis-sensitive tumors...

..Thus, XIAP inhibitors present a promising novel approach for apoptosis-based therapy of childhood ALL...

..Thus, hypoxia-inducible genes may represent novel targets for therapeutic intervention in some pediatric tumors, which warrants further investigation...

..Instead, proteasome inhibitors, which enhanced TRAIL-induced apoptosis in an NF-kappaB-independent manner, may open new perspectives to increase the efficacy of TRAIL-based regimens in glioblastoma, which warrants further investigation...

..Thus, resveratrol is a potent sensitiser for TRAIL in certain tumours. However, it may be ineffective in others, e.g. in tumours with enhanced Bcl-2 expression or defective death receptor signalling...

..By demonstrating that NF-kappaB promotes DNA damage formation and apoptosis upon pulse treatment with DNA intercalators, our findings provide novel insights into the control of the DNA damage response by NF-kappaB in glioblastoma...

..Thus, this combined sensitizer (resveratrol)/inducer (e.g., TRAIL) strategy may be a novel approach to enhance the efficacy of TRAIL-based therapies in a variety of human cancers...

..Since most human cancers represent type II cells, triggering the mitochondrial pathway by BetA may be a novel approach to enhance the efficacy of TRAIL-based therapies, which warrants further investigation...

..Further insights into the mechanisms regulating apoptosis in response to anticancer therapy and how cancer cells evade cell death may provide novel opportunities for drug development...

..Our results may stimulate the development of novel adoptive T cell transfer approaches for the management of BCP-ALL...

..These findings build the rationale for further (pre)clinical development of XIAP inhibitors and TRAIL against pancreatic cancer...

..Thus, Smac agonists are promising candidates for cancer therapy by potentiating cytotoxic therapies...

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..The findings presented may have immediate therapeutic impact for a subgroup of childhood AML-expressing c-KIT mutations...

..Repression of error-prone recombination subpathways could at least partially explain the chemopreventive effects of this natural plant constituent in animal cancer models...

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..Thus, agents designed to selectively activate death receptor pathways may enhance the efficacy of conventional therapies and may even overcome some forms of cancer resistance...

..The discovery of this novel activity of resveratrol significantly advances the knowledge of fat tissue regulation by resveratrol and has important implications for its use in metabolic and age-related diseases...

..Thus, the tools to overcome AMAR are already at our disposal and using them in this novel context of AMAR should lead to significant therapeutic benefit...

..Understanding the molecular events by which tumor cells evade apoptotic deletion and which induce apoptosis by cytotoxic therapies, have provided a paradigm to link normal growth control, malignant transformation and response to therapy...

..Thus, this study demonstrates for the first time that NF-?B exerts a pro-apoptotic role in TRAIL- and CD95-induced apoptosis in glioblastoma cells by facilitating DISC formation...

..Thus, our findings for the first time indicate that targeting XIAP represents a promising strategy to enhance the antitumor activity of TRAIL in pancreatic cancer, which has important clinical implications...

..Thus, small molecule XIAP inhibitors present a promising novel approach to enhance CD95-induced apoptosis in childhood acute leukemia...

..Because combined treatment also augmented the bystander cell kill, the addition of TRAIL may increase the efficacy of TK/GCV gene therapy of neuroblastoma...

..This effect of caloric restriction can be mimicked by resveratrol, a natural plant product present in grapes and red wine, which is known as a potent activator of sirtuin 1 [silent mating type information regulation 2 homolog 1 (Sirt1)]...

..Understanding the molecular mechanisms that regulate cell death programs including apoptosis, and how resistant forms of cancer evade apoptotic events, may provide novel opportunities for cancer drug development...

..By showing that PI3K inhibition broadly primes glioblastoma cells for apoptosis, our findings provide the rationale for using PI3K inhibitors in combination regimens to enhance TRAIL- or chemotherapy-induced apoptosis in glioblastoma...

..Thus, NF-kappaB inhibitors may open new perspectives to potentiate the efficacy of TRAIL-based protocols in the treatment of neuroblastoma...

..These data have important implications for developing apoptosis-targeted therapies in childhood leukemia...

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..Thus, novel strategies targeting tumor cell resistance will be based on insights into the molecular mechanisms of cell death...

..Thus, insights into the mechanisms regulating apoptosis in response to anticancer therapy and the ways in which cancer cells evade apoptosis might provide new opportunities for drug development...

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..Taken together, these analyses demonstrate that cyclin A1 exerts antiapoptotic functions by interacting with retinoblastoma and Ku proteins in leukemia cells...

..g. by Bcl-2 and by XIAP, these findings may have important clinical implication. Thus, strategies targeting the molecular basis of resistance towards TRAIL may be necessary in some tumors for cancer therapy with TRAIL...

..Thus, this combined sensitizer (resveratrol)/inducer (cytotoxic drugs) concept may be a novel strategy to enhance the efficacy of anticancer therapy in a variety of human cancers...

..Thus, novel strategies targeting tumor cell resistance will be based on further insights into the molecular mechanisms of cell death, e.g., triggered by TRAIL...

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..Thus, novel strategies targeting resistance of neuroblastoma cells will be based on insights into the molecular mechanisms of apoptosis as well as other forms of cell death...

..Here, we clarify the mechanism underlying cross-resistance of drug-resistant variants of the T-leukemia cell line CEM towards natural killer cells...

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