system
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: Animals, Brain Neoplasms, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cyanoacrylates, Cytotoxicity, Immunologic, Dose-Response Relationship, Drug, Drug Synergism, Female, Immunoblotting, Immunologic Factors, Interferon-alpha, Kaplan-Meier Estimate, Killer Cells, Natural, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Neoplasm Metastasis, Pyridines, STAT3 Transcription Factor, T-Lymphocytes, Treatment Outcome.
user
Does inhibition of p-STAT3 enhance IFN-alpha efficacy against metastatic melanoma in a murine model? Context: Melanoma is a common and deadly tumor that upon metastasis to the central nervous system has a median survival duration of <6 months. Activation of the signal transducer and activator of transcription 3 (STAT3) has been identified as a key mediator that drives the fundamental components of melanoma malignancy, including immune suppression in melanoma patients. We hypothesized that WP1193, a novel inhibitor of STAT3 signaling, would enhance the antitumor activity of IFN-alpha against metastatic melanoma. Combinational therapy of STAT3 blockade agents with IFN-alpha was investigated in a metastatic and an established syngeneic intracerebral murine tumor model of melanoma. The immunologic in vivo mechanisms of efficacy were investigated by T-cell and natural killer (NK) cell cytotoxic assays. IFN-alpha immunotherapy was synergistic with WP1193 showing marked in vivo efficacy against metastatic and established intracerebral melanoma. At autopsy, it was noted that there was a decreased trend in mice with melanoma developing leptomeningeal disease treated with combinational therapy. The combinational approach enhanced both NK-mediated and T-cell-mediated antitumor cytotoxicity.
assistant
The immune modulatory effects of STAT3 blockade can enhance the therapeutic efficacy of IFN-alpha immunotherapy by enhancing both innate and adaptive cytotoxic T-cell activities. This combination therapy has the potential in the treatment of metastatic melanoma that is typically refractory to this type of immune therapeutic approach. Final Decision: yes