A5092034122- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Thyroid Cancer Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Viral Infections and Vectors
- Calpain Protease Function and Regulation
- S100 Proteins and Annexins
The Ohio State University
2023-2025
The Ohio State University Wexner Medical Center
2023-2025
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<div>Abstract<p>Colorectal cancer is the second leading cause of mortality in United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful treating a subset patients with colorectal cancer, response rates remain low. We found that riluzole, well-tolerated FDA-approved oral medicine for amyotrophic lateral sclerosis, increased intratumoral CD8<sup>+</sup> T cells and suppressed tumor growth colon syngeneic immune–competent...
Background: Medullary thyroid cancer (MTC) is a frequently metastatic tumor of the that develops from malignant transformation C-cells. These tumors most commonly have activating mutations within RET or RAS proto-oncogenes. Germline result in C-cell hyperplasia, and cause MTC pre-disposition disorder, multiple endocrine neoplasia, type 2A (MEN2A). Single-agent therapies for MTC, including vandetanib (VAN) cabozantinib all MTCs selpercatinib (SEL) RET-mutated lead to partial responses but are...
Abstract BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in US. 5-fluorouracil (5-FU)-based chemotherapies combination with targeted agents remain standard care patients metastatic or locally advanced disease. New treatment strategies are needed for CRC microsatellite stable Preclinical studies showed that riluzole, an oral medicine amyotrophic lateral sclerosis, inhibits glutamate release and synergizes 5-FU to reduce cell viability lines....
FOLFOX, composed of 5-FU, oxaliplatin and leucovorin, is a first line chemotherapy regimen for colorectal cancer (CRC) treatment. In this study, we show that 5-FU induce DNA damage activate cGAS/STING signaling leading to enhanced expression interferon (IFN) β, IFN-stimulated genes inflammatory cytokines in mouse human colon cells as well increased intratumoral CD8 + T mice. Crucially, increase PD-L1 at the mRNA protein levels, which has been shown inhibit cell function. Depletion cGAS,...
Abstract The cGAS/STING cytosolic DNA-sensing pathway plays a significant role in antitumor immunity. Expression of STING is tightly regulated and commonly reduced or defective many types cancer. We have identified SIX4 as regulator expression colon cancer cells. showed that knockout decreased at the mRNA protein levels while ectopic increased expression. Depletion led to attenuated activation downstream signaling. Reexpression cells reversed effect. Ectopic enhanced DMXAA cGAMP-induced...
Abstract Colorectal cancer is the second leading cause of mortality in United States. Although immune checkpoint blockade therapies including anti-PD-1/PD-L1 have been successful treating a subset patients with colorectal cancer, response rates remain low. We found that riluzole, well-tolerated FDA-approved oral medicine for amyotrophic lateral sclerosis, increased intratumoral CD8+ T cells and suppressed tumor growth colon syngeneic immune–competent mice. Riluzole-mediated suppression was...
<p>Supplemental Figure 3 shows the quantification of western blots shown in 2C.</p>
<p>Supplemental Figure 4 shows the quantification of western blots shown in 2D.</p>
<p>Supplemental Figure 2 shows the quantification of western blots shown in 2A and 2B.</p>
<p>Supplemental Figure 4 shows the quantification of western blots shown in 2D.</p>
<p>Supplemental Figure 3 shows the quantification of western blots shown in 2C.</p>
<p>Supplemental Figure 2 shows the quantification of western blots shown in 2A and 2B.</p>
<p>Supplemental Figure 1 shows the quantification of western blots shown in 1A and 1B.</p>
<div>Abstract<p>The cGAS/STING cytosolic DNA-sensing pathway plays a significant role in antitumor immunity. Expression of STING is tightly regulated and commonly reduced or defective many types cancer. We have identified SIX4 as regulator expression colon cancer cells. showed that knockout decreased at the mRNA protein levels while ectopic increased expression. Depletion led to attenuated activation downstream signaling. Reexpression cells reversed effect. Ectopic enhanced DMXAA...
<div>Abstract<p>The cGAS/STING cytosolic DNA-sensing pathway plays a significant role in antitumor immunity. Expression of STING is tightly regulated and commonly reduced or defective many types cancer. We have identified SIX4 as regulator expression colon cancer cells. showed that knockout decreased at the mRNA protein levels while ectopic increased expression. Depletion led to attenuated activation downstream signaling. Reexpression cells reversed effect. Ectopic enhanced DMXAA...
<p>SIX4 modulates STING activation in colon cancer cells. <b>A,</b> MC38 SIX4 knockout cells and those with SIX4- or STING-reexpressing were treated 10 µg/mL of DMXAA for 6 hours. Western blot analysis was performed to examine expression phosphorylation TBK1 ISG15 (left). IFNβ CXCL10 mRNA determined by Q-PCR (right). <b>B,</b> CT26 control SIX-overexpressing The SIX4-overexpressing HT29 (<b>C</b>) TENN (<b>D</b>) transfected cGAMP. Cells...
<p>SIX4 regulates expression of STING mRNA and protein. <b>A,</b> SIX4 was knocked out in MC38 cells by two gRNAs (gRNA2 gRNA3). An empty vector (V) or SIX4-expressing (SIX4) introduced into knockout cells. Depletion significantly reduced reexpression rescued at protein levels determined Western blot (top) Q-PCR (bottom) analysis, respectively. <b>B,</b> ectopically expressed CT26, HT29, TENN cells, which led to increased Results are shown as mean ± SD. *,...
<p>Knockout of SIX4 reduces the efficacy anti-PD-1 tumor suppression effect <i>in vivo</i>. <b>A,</b> Colony formation assays were performed in MC38 control and knockout cells (gRNA2 gRNA3) with representative images after MTT staining (left). After dissolving DMSO, relative cell numbers determined by spectrophotometry at 570 nm (right). <b>B,</b> SIX4-overexpressing <b>C,</b> Xenograft growth curves (KO) treated a IgG or an antibody are...
<p>SIX4 expression is positively associated with inflammatory response in colon cancer patient specimens. <b>A,</b> GSEA plots of enrichment the Inflammatory Response signatures from MsigDB samples TCGA stratified by SIX4 expression. <b>B,</b> Correlation between and STING or IFN marker gene TCGA. <b>C,</b> cytokine/chemokine <b>D,</b> CD8A TCGA.</p>