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Documents  92C40 | enregistrements trouvés : 11

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Multi angle  RNA secondary structures
Hofacker, Ivo (Auteur de la Conférence) | CIRM (Editeur )

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Cancer patients often respond differently to the same treatment. Precision oncology aims at predicting which treatments will be effective on a given patient. Such predictive biomarkers of drug response typically take the form of a particular somatic mutation. However, lessons from the past indicate that these single gene-drug response associations are rare and/or often fail to achieve a significant impact in clinic. In this context, Machine Learning (ML) is emerging as a particularly promising complementary approach to precision oncology. Our results show that combining multiple gene alterations of the tumours via ML often results in better discrimination than that provided by the corresponding single-gene marker. This approach also permits assessing which type of molecular profile is most predictive of tumour response depending on treatment and cancer type. Moreover, ML multi-gene predictors generally retrieve a much higher proportion of treatment-sensitive tumours (i.e. they have a higher recall) than the corresponding single-gene marker. The latter suggest that a higher proportion of patients could benefit from precision oncology by applying this ML methodology to existing clinical pharmacogenomics data sets.
Cancer patients often respond differently to the same treatment. Precision oncology aims at predicting which treatments will be effective on a given patient. Such predictive biomarkers of drug response typically take the form of a particular somatic mutation. However, lessons from the past indicate that these single gene-drug response associations are rare and/or often fail to achieve a significant impact in clinic. In this context, Machine ...

92C40 ; 68Uxx

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Multi angle  RNA design in theory and practice
Findeiss, Sven (Auteur de la Conférence) | CIRM (Editeur )

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The emergence of drug-resistance is a major challenge in chemotherapy. In this talk we will present our recent mathematical models for describing the dynamics of drug-resistance in solid tumors. Our models follow the dynamics of the tumor, assuming that the cancer cell population depends on a phenotype variable that corresponds to the resistance level to a cytotoxic drug. We incorporate the dynamics of nutrients and two different types of drugs: a cytotoxic drug, which directly impacts the death rate of the cancer cells, and a cytostatic drug that reduces the proliferation rate. Through analysis and simulations, we study the impact of spatial and phenotypic heterogeneity on the tumor growth under chemotherapy. We demonstrate that heterogeneous cancer cells may emerge due to the selection dynamics of the environment. Our models predict that under certain conditions, multiple resistant traits emerge at different locations within the tumor. We show that a higher dosage of the cytotoxic drug may delay a relapse, yet, when this happens, a more resistant trait emerges. Moreover, we estimate the expansion rate of the tumor boundary as well as the time of relapse, in terms of the resistance trait, the level of the nutrient, and the drug concentration. Finally, we propose an efficient drug schedule aiming at minimizing the growth rate of the most resistant trait. By combining the cytotoxic and cytostatic drugs, we demonstrate that the resistant cells can be eliminated.
The emergence of drug-resistance is a major challenge in chemotherapy. In this talk we will present our recent mathematical models for describing the dynamics of drug-resistance in solid tumors. Our models follow the dynamics of the tumor, assuming that the cancer cell population depends on a phenotype variable that corresponds to the resistance level to a cytotoxic drug. We incorporate the dynamics of nutrients and two different types of drugs: ...

92C50 ; 92C37 ; 92C40

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Multi angle  Non-genetic cancer cell plasticity
Pisco, Angela (Auteur de la Conférence) | CIRM (Editeur )

Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. However, the ubiquitous nongenetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. Cancer therapy inevitably spares some cancer cells, even in the absence of resistant mutants. Accumulating observations suggest that the non-killed, residual tumour cells actively acquire a new phenotype simply by exploiting their developmental potential. These surviving cells are stressed by the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of responses. By entering such stem-like, stress-response states, the surviving cells strengthen their capacity to cope with future noxious agents. Considering nongenetic cell state dynamics and the relative ease with which surviving but stressed cells can be tipped into latent attractors of the gene regulatory network provides a foundation for exploring new therapeutic approaches that seek not only to kill cancer cells but also to avoid promoting resistance and relapse that are inherently linked to the attempts to kill them.

Keywords: cancer attractor, epigenetic landscape, multi-drug resistance
Therapy resistance and tumour relapse after drug therapy are commonly explained by Darwinian selection of pre-existing drug-resistant, often stem-like cancer cells resulting from random mutations. However, the ubiquitous nongenetic heterogeneity and plasticity of tumour cell phenotype raises the question: are mutations really necessary and sufficient to promote cell phenotype changes during tumour progression? Tumorigenesis is a dynamic ...

92C50 ; 92C37 ; 92C40

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Multi angle  New hints from the reward system
Apicella, Paul (Auteur de la Conférence) ; Loewenstein, Yonatan (Auteur de la Conférence) | CIRM (Editeur )

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- Talk 1: Paul Apicella - Striatal dopamine and acetylcholine mechanisms involved in reward-related learning

The midbrain dopamine system has been identified as a major component of motivation and reward processing. One of its main targets is the striatum which plays an important role in motor control and learning functions. Other subcortical neurons work in parallel with dopamine neurons. In particular, striatal cholinergic interneurons participate in signaling the reward-related significance of stimuli and they may act in concert with dopamine to encode prediction error signals and control the learning of stimulus-response associations. Recent studies have revealed functional cooperativity between these two neuromodulatory systems of a complexity far greater than previously appreciated. In this talk I will review the difference and similarities between dopamine and acetylcholine reward-signaling systems, the possible nature of reward representation in each system, and discuss the involvement of striatal dopamine-acetylcholine interactions during leaning and behavior.

- Talk 2: Yonatan Loewenstein - Modeling operant learning: from synaptic plasticity to behavior

- Discussion with Paul Apicella and Yonatan Loewenstein
Start the video and click on the track button in the timeline to move to talk 1, 2 and to the discussion.

- Talk 1: Paul Apicella - Striatal dopamine and acetylcholine mechanisms involved in reward-related learning

The midbrain dopamine system has been identified as a major component of motivation and reward processing. One of its main targets is the striatum which plays an important role in motor control and learning functions. Other ...

68T05 ; 68Uxx ; 92B20 ; 92C20 ; 92C40

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Dans une première partie, je présenterai différentes problématiques liées à des statistiques d'occurrences de mots dans des génomes et décortiquerai plus en détail la question de savoir comment détecter si un mot a une fréquence d'apparition significativement anormale dans une séquence. Dans une deuxième partie, je présenterai différentes extensions pour tenir compte du fait qu'un motif d'ADN fonctionnel n'est pas toujours un " mot ", mais qu'il peut avoir une structure plus complexe qui nécessite le développement de nouvelles méthodes statistiques.
Dans une première partie, je présenterai différentes problématiques liées à des statistiques d'occurrences de mots dans des génomes et décortiquerai plus en détail la question de savoir comment détecter si un mot a une fréquence d'apparition significativement anormale dans une séquence. Dans une deuxième partie, je présenterai différentes extensions pour tenir compte du fait qu'un motif d'ADN fonctionnel n'est pas toujours un " mot ", mais qu'il ...

92C40 ; 62P10 ; 60J20 ; 92C42

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