Project description:Cudrania tricuspidata extracts and 3 major compounds, including 4'-O-Methylalpinumisoflavone, Alpinumisoflavone and 6,8-diprenylgenistein
Project description:Andrographis paniculata Nees and its major compound andrographolide is known to exhibit a pleothera of activities. Active component enriched extracts are known to provide various beneficial effects, and therefore it was interesting to investigate whether increased amount of major compound alters gene expression. To acheive this, HePG2 cells treated with Andrographis paniculata extract (AP) and andrographolide enriched –extract (AP20) were subjected to microarray analysis to check their effect on global gene expression.
Project description:Use CEN quechers method to extract 2.5g honey and use PSA to clean up matrix. Using ACN-water-0.01%HCOOH for compound separation and HRMS analysis with Thermo Orbitrap Exploris 120. Data was acquired in Full scan-ddms2 mode. This included a full scan over the m/z range 100- 1000 at full width at half maximum (FWHM) resolution of 60,000, and a data-dependent-MS2 scan at FWHM resolution of 15,000 on the top 4 ions. The ionization was performed in positive ESI with an inlusion list collated from OPPIN website, and to gain more information about fragment ions in the QC sample, we use an Automated Exclusion List Generation workflow, so one QC sample finally gave 3 injections.
Project description:Apoptotic cells are immunosuppressive, creating a potential therapeutic barrier in cancer therapy. In this reportwe investigated responses to apoptotic tumor cell phagocytosis (i.e. efferocytosis) after therapy in the tumor draining lymph node (TDLN). Treatment with cisplatin or the BRAF inhibitor PLX4720 caused a significant increase in accumulation of apoptotic tumor material in the TDLN. We identified the primary phagocyte population responsible for clearing dying tumors in the TDLN was medullary sinus macrophages (MSMs). Tumor cell efferocytosis by MSMs induced an immune suppressive transcriptional program distinct from other macrophage or dendritic cell populations in the TDLN. One of the most differentially induced mRNAs in MSMs wasIl33,coding fora potent immune-regulatory cytokine. Administration of neutralizing anti-IL-33 receptor antibodies or deletion ofIl33in MSMs altered tumor responses to therapy with a significant enhancement of anti-tumor activity compared to controls. Mechanistically, IL-33 activated Treg cells in the TDLN with subsequent suppression of CD8+T cell responses. Importantly, combining IL-33 receptor blockade, BRAF inhibitor, and PD-1 blockade significantly improved tumor regression with enhanced, CD8+T cell dependent immunity. Finally, apoptotic tumor cells induced IL-33 expression in human macrophages, IL-33 expression in sentinel lymph nodes positively corresponded with disease stage and negatively correlated with survival in melanoma and breast cancer. Thus, the data identifies an immune response to therapy that abrogates nascent anti-tumor immunity, providing a previously undescribed functional interaction with broad implications for cancer therapy.
Project description:Apoptotic cells are immunosuppressive, creating a potential therapeutic barrier in cancer therapy. In this reportwe investigated responses to apoptotic tumor cell phagocytosis (i.e. efferocytosis) after therapy in the tumor draining lymph node (TDLN). Treatment with cisplatin or the BRAF inhibitor PLX4720 caused a significant increase in accumulation of apoptotic tumor material in the TDLN. We identified the primary phagocyte population responsible for clearing dying tumors in the TDLN was medullary sinus macrophages (MSMs). Tumor cell efferocytosis by MSMs induced an immune suppressive transcriptional program distinct from other macrophage or dendritic cell populations in the TDLN. One of the most differentially induced mRNAs in MSMs wasIl33,coding fora potent immune-regulatory cytokine. Administration of neutralizing anti-IL-33 receptor antibodies or deletion ofIl33in MSMs altered tumor responses to therapy with a significant enhancement of anti-tumor activity compared to controls. Mechanistically, IL-33 activated Treg cells in the TDLN with subsequent suppression of CD8+T cell responses. Importantly, combining IL-33 receptor blockade, BRAF inhibitor, and PD-1 blockade significantly improved tumor regression with enhanced, CD8+T cell dependent immunity. Finally, apoptotic tumor cells induced IL-33 expression in human macrophages, IL-33 expression in sentinel lymph nodes positively corresponded with disease stage and negatively correlated with survival in melanoma and breast cancer. Thus, the data identifies an immune response to therapy that abrogates nascent anti-tumor immunity, providing a previously undescribed functional interaction with broad implications for cancer therapy.