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Enforcement of stem-cell dormancy by nucleophosmin mutation is a critical determinant of unrestricted self-renewal during myeloid leukemogenesis.
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Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milan, Milan.
Mutations in the NPM1 gene (NPMc+) and in the FLT3 gene (FLT3-ITD) represent the most frequent co-occurring mutations in Acute Myeloid Leukemia (AML), yet the cellular and molecular mechanisms of their cooperation remain largely unexplored. Using mouse models that faithfully recapitulate human AML, we investigated the impact of these oncogenes on pre-leukemic and leukemic hematopoietic stem cells (HSCs), both separately and in combination. While both NPMc+ and Flt3-ITD promote the proliferation of pre-leukemia HSCs, only NPMc+ drives extended selfrenewal by preventing the depletion of the quiescent HSC pool.
View Article and Find Full Text PDFPanduratin A from Effectively Inhibits EGFR/STAT3/Akt Signaling Pathways, Inducing Apoptosis in NSCLC Cells with Wild-Type and T790M Mutations in EGFR.
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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok 26120, Thailand.
Non-small cell lung cancer (NSCLC) is a challenging disease, with the epidermal growth factor receptor (EGFR) being a key target for new, effective treatments crucial for the signaling pathways regulating cancer cell survival. Targeting EGFR-mediated signaling offers promising strategies to improve NSCLC therapies, particularly in overcoming resistance in EGFR-mutant lung cancer. In this study, we investigated the anticancer effects of panduratin A, a naturally occurring flavonoid from , on human NSCLC cell lines expressing both wild-type EGFR (A549) and mutant EGFR (H1975) using in vitro experiments and molecular docking approaches.
View Article and Find Full Text PDFCharacterization of Exhausted T Cell Signatures in Pan-Cancer Settings.
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Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
T cells play diverse roles in cancer immunology, acting as tumor suppressors, cytotoxic effectors, enhancers of cytotoxic T lymphocyte responses and immune suppressors; providing memory and surveillance; modulating the tumor microenvironment (TME); or activating innate immune cells. However, cancer cells can disrupt T cell function, leading to T cell exhaustion and a weakened immune response against the tumor. The expression of exhausted T cell (Tex) markers plays a pivotal role in shaping the immune landscape of multiple cancers.
View Article and Find Full Text PDFPro-Apoptotic Effects of Anandamide in Human Gastric Cancer Cells Are Mediated by AKT and ERK Signaling Pathways.
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Gastric cancer is one of the most common forms of cancer worldwide. A growing number of studies have addressed the anti-proliferative effects of cannabinoids on several tumor cells. The molecular mechanisms underlying the anti-proliferative effects of the endogenous cannabinoid anandamide (AEA) on gastric tumor cell lines have yet to be characterized.
View Article and Find Full Text PDFEstablishment of a Novel In Vitro and In Vivo Model to Understand Molecular Carcinogenesis of Endometriosis-Related Ovarian Neoplasms.
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Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan.
The molecular mechanisms through which endometriosis-related ovarian neoplasms (ERONs) develop from benign endometrioma remain unclear. It is especially a long-standing mystery why ovarian endometrioma has the potential to develop into two representative histological subtypes: endometrioid ovarian carcinoma or clear cell ovarian carcinoma. This study aimed to investigate the molecular carcinogenesis of ERONs using newly developed in vitro and in vivo carcinogenesis models.
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