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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Apoptosis, Autocrine Communication, B-Lymphocytes, Brain-Derived Neurotrophic Factor, Carbazoles, Cell Division, Cell Line, Tumor, Culture Media, Conditioned, DNA Replication, Humans, Indole Alkaloids, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, NF-kappa B, Neoplasm Proteins, Nerve Growth Factor, Nerve Growth Factors, RNA, Messenger, RNA, Neoplasm, Receptors, Nerve Growth Factor, Signal Transduction, Tyrphostins.
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Does neurotrophin signaling through tropomyosin receptor kinases contribute to survival and proliferation of non-Hodgkin lymphoma? Context: Neurotrophin receptor signaling has been increasingly recognized as an important factor in the development and progression of a variety of malignancies. In order to analyze the potential contribution of neurotrophin signaling to lymphoma cell survival, we investigated the role of a neurotrophin axis in promoting survival and proliferation of non-Hodgkin lymphoma (NHL) cells. The role of neurotrophins in the survival and proliferation of NHL cells was determined by exposing cells to the Trk-specific inhibitor, K252a, and then performing (3)H-thymidine incorporation and Annexin-V/propidium iodide staining. The involvement of nuclear factor-kappaB (NF-kappaB) in this process was studied using Western blot, electrophoretic mobility shift assay, and immunofluorescence assays. Here we demonstrate that both primary NHL cells and diffuse large B-cell lymphoma cell lines express Trk receptors and their neurotrophin ligands. Furthermore, these cells are sensitive to the Trk-specific inhibitor, K252a, as evidenced by the inhibition of proliferation and/or induction of apoptosis. Analysis of the mechanism into the effects of K252a revealed that, in the OCI-LY3 cell line, K252a induced a subnuclear distribution of NF-kappaB resulting in the sequestration of RelA in the nucleolus, thereby inhibiting NF-kappaB-dependent gene transcription. This results in the loss of interleukin-6 production; a known survival-promoting signal for OCI-LY3, as well as many primary diffuse large B-cell lymphomas.
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Thus, Trk receptors represent a novel therapeutic target for the treatment of NHL. Final Decision: yes