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L'histoire du développement de l'imatinib illustre parfaitement le processus par lequel la recherche scientifique combinée à l'expérimentation clinique peut mener à une approche ciblée du traitement du cancer.
L'efficacité spectaculaire de ce médicament a pourtant été contrecarrée par l'émergence de résistances imputables aux variétés génétiques de l'hôte.
Grâce à l'acquisition de données fondamentales concernant le mode d'action des tyrosine kinases et les bases moléculaires de cette résistance, une nouvelle génération d'ITK plus puissants que l'lM a pu être mise au point. Mis à part la mutation T31SI, le dasatinib et le nilotinib parviennent à surmonter la plupart des mutations insensibles à l'imatinib.
Cependant, bien qu'ils ciblent l'anomalie génétique à l'origine de la maladie, les ITK ne permettent pas dans la majorité des cas de « guérir» de la LMC.
Vaincre cette maladie résiduelle constitue par conséquent le défi futur de la recherche pharmaceutique. Les premiers résultats des essais thérapeutiques menés dans le but d'identifier des composés capables d'éradiquer les cellules souches leucémiques quiescentes fournissent d'ores et déjà des résultats très encourageants pour les patients.

Leukemia, Myeloid --- imatinib --- Drug Resistance

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Chronic myeloid leukemia is a well known disease. The must targeted treatments are the tyrosine kinas inhibitors. The inhibitory action on the anarchic proliferation of cells seems to be the best method to delay or stop the evolution of disease. The Glivec® is the paradigm in CML treatment. The discovery of this compound has considerably elevated the life level of patients suffering from chronic myeloid leukemia. Other tki showed their effectiveness, including nilotinib and dasatinib. Nevertheless, such patients develop resistance mechanism against tki. The bypass of these resistance mechanisms raises a lot of interest office of scientists La leucémie myéloïde chronique est une maladie relativement bien connue. Les traitements les plus ciblés actuellement sont les inhibiteurs des tyrosines kinases. En effet, l’action inhibitrice sur la prolifération anarchique des cellules s’avère être la méthode la plus efficace pour retarder ou stopper l’évolution de la maladie. Le paradigme du traitement de la LMC est le Glivec®. La découverte de ce médicament a considérablement augmenté le niveau de vie des patients souffrant de leucémie myéloïde chronique. D’autres inhibiteurs de tyrosine kinase (tki) ont montré leur efficacité, c’est le cas par exemple du nilotinib et du dasatinib. Cependant, chez certains patients, on voit apparaître des mécanismes de résistance aux inhibiteurs de tyrosine kinase. Le détournement de ces mécanismes de résistance suscite beaucoup d’intérêt auprès des chercheurs

Leukemia, Myelogenous, Chronic, BCR-ABL Positive --- antagonists and inhibitors --- imatinib

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The increased understanding of the molecular characteristics, these last years, is impressive. Identification of the essential factors for the development of some cancers, such as BCR-ABL and HER2, has aided pharmaceutical firms in the development of novel molecules, which could target oncogenes, oncoproteins and receptors. Thus, imatinib, trastuzumab and bevacizumab were developed. Three molecules, which have demonstrated the potential of molecularly targeted cancer therapeutics. However these molecules are confronted with various mechanisms of resistance. These mechanisms as well as some novel strategies to over-ride resistance will develop in this report Les progrès dans la compréhension de la biologie cellulaire effectués ces dernières années sont impressionnants. L’identification de facteurs essentiels pour le développement de certains cancers, tels que BCR-ABL et HER2, a encouragé les firmes pharmaceutiques à se focaliser sur le développement de molécules capables de cibler ces oncogènes, oncoprotéines ou récepteurs. Ainsi, fut développés l’imatinib, le trastuzumab et le bevacizumab ; trois molécules qui ont démontré le potentiel des thérapies du cancer à cible moléculaire. Cependant, ces molécules sont confrontées à divers mécanismes de résistance. Ces mécanismes de résistance ainsi que quelques nouvelles stratégies de traitement pour y faire face seront développés dans ce mémoire

imatinib --- Antineoplastic Agents --- trastuzumab --- bevacizumab --- Protein-Tyrosine Kinases --- Leukemia, Myelomonocytic, Chronic --- Breast Neoplasms

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Recent decades have seen remarkable advances in the treatment of upper gastrointestinal malignancies, i.e., adenocarcinoma and squamous cell carcinoma as well as gastrointestinal stromal and other rare tumors of the esophagus and stomach. While, historically, surgical resection has been the sole treatment for these tumors, multimodal therapies have meanwhile proven their efficacy. At present, pre- and postoperative chemotherapy and radiotherapy, targeted drug therapy, and stage-specific surgical approaches are all indispensable cornerstones of an individualized treatment for upper gastrointestinal malignancies. With such multimodal treatment, better outcomes comprising improved quality of life and prolonged survival have been achieved for patients. However, for many tumor entities and stages, the ideal combination and sequence of treatments is still being evaluated in clinical trials. Moreover, the value of novel approaches such as immunotherapy or robotic surgery remains a matter of research. In this Special Issue of Cancers, up-to-date original research, short communications, and comprehensive review articles on all modalities playing a role in the treatment of upper gastrointestinal malignancies have been published.

Public health & preventive medicine --- gastric cancer --- gastrectomy --- complications --- outcome --- survival --- lymph node ratio --- neoadjuvant chemotherapy --- conversion surgery --- cancer dormancy --- nuclear receptor NR2F1 --- clinical pathways --- gastric surgery --- oncological gastrectomy --- quality of care --- outcomes --- standardization --- adjuvant therapy --- gastrointestinal tract --- genetic diagnosis --- radiosensitivity --- mortality --- failure to rescue --- immunotherapy --- genetics --- esophageal cancer --- multidisciplinary --- gastric/gastroesophageal cancer --- perioperative chemotherapy --- overall survival --- relapse-free survival --- skeletal muscle index --- esophagectomy --- nutritional status --- sarcopenia --- esophageal anastomosis --- minimally invasive surgery --- induction chemotherapy --- chemo-radiotherapy --- neoadjuvant treatment --- esophageal squamous cell carcinoma --- multimodal treatment --- neoadjuvant chemoradiotherapy --- definitive chemoradiotherapy --- Lauren histotype --- gastrointestinal stromal tumor --- neuroendocrine tumor --- MALT lymphoma --- mucosal resection --- submucosal dissection --- GIST --- stomach --- neoadjuvant therapy --- imatinib --- organ preservation --- squamous cell esophageal cancer --- gastro-esophageal reflux disease --- Barrett’s esophagus --- early adenocarcinoma of esophagus --- endoscopic submucosal dissection --- endoscopic mucosal resection --- n/a --- Barrett's esophagus

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The development of paediatric medicines can be challenging since this is a different patient population with specific needs. A medicine designed for use in paediatric patients must consider the following aspects: patient population variability; the need for dose flexibility; route of administration; patient compliance; excipient tolerability. For example, the toxicity of excipients may differ in children compared to adults and children have different taste preferences. Globally, about 75% of drugs do not carry regulatory approval for use in children; worldwide, many medications prescribed for the treatment of paediatric diseases are used off-label, and less than 20% of package inserts have sufficient information for treating children. This book provides an update on both state-of-the-art methodology and operational challenges in paediatric formulation design and development. It aims at re-evaluating what is needed for more progress in the design and development of age-appropriate treatments for paediatric diseases, focusing on: formulation development; drug delivery design; efficacy, safety, and tolerability of drugs and excipients.

dasatinib --- Duchenne muscular dystrophy --- cyclodextrin inclusion complex --- phase solubility studies --- paediatric age --- liquid formulation --- tumorspheres --- retinoblastoma --- topotecan --- penetration --- confocal microscopy --- poorly water soluble drug --- solubility enhancement --- grinding --- spray congealing --- neglected tropical diseases --- polymorph --- Norvir® --- ritonavir --- poorly soluble compound --- pediatric --- palatability assessment --- bioavailability --- flavor profile --- Interleukin-1 --- anakinra --- canakinumab --- innovative biotechnologies --- autoinflammatory disease --- Kawasaki disease --- systemic juvenile idiopathic arthritis --- personalized medicine --- child --- pediatrics --- neonates --- formulation --- product development --- formulation development --- oral --- parenteral --- topical --- inhaled --- intra nasal --- biopharmaceutics --- administration --- excipient --- NICU --- device --- medication error --- dosage form --- modified release --- drug delivery --- paediatric formulation development --- paediatric dosage forms --- chronic myeloid leukemia --- tyrosine kinase inhibitors --- pediatric age --- imatinib --- nilotinb --- ponatinib --- Orodispersible formulation --- pyrazinamide --- pediatric drug delivery --- tuberculosis --- design of experiments --- children --- edible films --- development --- design --- paediatric --- age-related --- palatable --- taste-masking --- acceptable