928 research outputs found
Small molecule tyrosine kinase inhibitors in pancreatic cancer
No full textSachin Gupta, Bassel F El-RayesDepartment of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, MI, USAAbstract: Pancreatic cancer has proven to be chemo-resistant, with gemcitabine being the only cytotoxic agent approved for advanced pancreatic cancer since 1996. Tyrosine kinase inhibitors represent a newer generation of chemotherapeutic agents targeting specific tumor pathways associated with carcinogenesis including cell cycle control, signal transduction, apoptosis and angiogenesis. These agents present a more selective way of treating pancreatic cancer. Erlotinib is the prototype of the tyrosine kinase inhibitors with proven efficacy in advanced pancreatic cancer and has been recently approved in that setting. Multiple other tyrosine kinase inhibitors targeting the VEGFR, PDGFR, and Src kinases are in various phases of clinical trials testing. The preliminary results of these trials have been disappointing. Current challenges in pancreatic cancer clinical trials testing include improving patient selection, identifying effective combinations, improving the predictive value of current preclinical models and better study designs. This review summarizes the present clinical development of tyrosine kinase inhibitors in pancreatic cancer and strategies for future drug development.Keywords: pancreatic cancer, erlotinib, tyrosine kinase inhibitor
La temporalité psychosomatique. Le cas Bassel
No full textInternational audienceA la suite du travail d’élaboration que nous avons fait pour la demi-journée du 29 mai 2021 sur la résonnance des croyances culturelles dans les psychothérapies, et après avoir exploré ma clinique convoquée à ce sujet, un de mes patients et mes investigations heuristiques organisent ma réflexion. Je pense à Bassel mon patient depuis 3 ans, qui me permettra d’élaborer, dans le contexte de la psychosomatique intégrative, la dimension temporelle inhérente à tous les phénomènes du corps, de la psyché et de la nature.Cette publication fait suite à un article déjà publié dans les Annales de psychologie Psycho-Echo de la Faculté des Lettres et des Sciences Humaines de l'Université Saint Joseph de Beyrouth, et intitulé "La temporalité psychosomatique : De la défaillance de la "loi rythmique" et du hors temps psychologique dans le fonctionnement opératoire
La temporalité psychosomatique. Le cas Bassel
No full textInternational audienceA la suite du travail d’élaboration que nous avons fait pour la demi-journée du 29 mai 2021 sur la résonnance des croyances culturelles dans les psychothérapies, et après avoir exploré ma clinique convoquée à ce sujet, un de mes patients et mes investigations heuristiques organisent ma réflexion. Je pense à Bassel mon patient depuis 3 ans, qui me permettra d’élaborer, dans le contexte de la psychosomatique intégrative, la dimension temporelle inhérente à tous les phénomènes du corps, de la psyché et de la nature.Cette publication fait suite à un article déjà publié dans les Annales de psychologie Psycho-Echo de la Faculté des Lettres et des Sciences Humaines de l'Université Saint Joseph de Beyrouth, et intitulé "La temporalité psychosomatique : De la défaillance de la "loi rythmique" et du hors temps psychologique dans le fonctionnement opératoire
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Abstract 1695: Paricalcitol plus hydroxychloroquine enhances gemcitabine activity and induces mesenchymal to epithelial transition in pancreatic ductal adenocarcinoma
No full textAbstract Epithelial mesenchymal transition (EMT) describes a process by which the epithelial cells acquire mesenchymal properties associated with increased migration, invasion, and resistance to therapy. Targeting the intercellular communications and molecular changes that enable EMT is a rational therapeutic approach in PDAC. Our group has previously reported on KPC-Luc PDAC orthotopic mouse models treated with 1. Sham, 2. paricalcitol plus hydroxychloroquine (PH), 3. gemcitabine (G), and 4. GPH. Single cell RNA sequence (scRNASeq) was performed and analyzed using hdWGCNA (high dimensional Weighted Gene Co-expression Network Analysis) and GSEA (Gene Set Enrichment Analysis) to plot and determine intracellular interactions as well as gene expression changes in various treatment conditions. GPH treatment reduces EMT, which is associated with the downregulation of the essential gene fibronectin (Fn1). Collagen and Fn1 pathways co-expression decreases in GPH-treated KPC-Luc tumors. Cancer-associated fibroblasts (CAFs) appear dominant in Collagen signaling, whereas macrophages mediate Fn1 signaling. GPH treatment reduces the expression interaction strength between ligands and receptors (Collagen-Integrin and Fn1-Cd44 or Fn1-Sdc4) compared to sham, PH, and G. This comprehensive study of cell-cell communication and molecular changes during therapy offers a deep understanding of the molecular underpinnings of PDAC-EMT and metastasis and identifies possible targets for GPH. Citation Format: Ganji Purnachandra Nagaraju, Madhu Sudhana Saddala, Sujith Sarvesh, Dhanasekhar Reddy Bandi, Ateeq Muhammed Khaliq, Ashiq Masood, Mehmet Akce, Bassel F. El-Rayes. Paricalcitol plus hydroxychloroquine enhances gemcitabine activity and induces mesenchymal to epithelial transition in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1695
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