Background: The aim of this study was to explore the expression levels and biological significance of TDO2 in colorectal cancer (CRC).
Methods: First, we explored the potential oncogenic roles of TDO2 across 33 tumors based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Second, we evaluated TDO2 protein expression in 55 CRC tissue samples and 30 cDNA samples by immunohistochemistry and qPCR. Third, we investigated the effect of TDO2 on CRC cells by cell proliferation, wound healing, invasion, and colony formation assays. Finally, we determined the protein that is most closely associated with TDO2 via bioinformatics analysis, enriched the key pathways, and verified them.
Results: The expression level of TDO2 was found to be associated with the tumor clinical stage in CRC. A high expression of TDO2 was associated with a poor outcome in CRC patients. Inhibition of TDO2 expression by RNAi in LoVo and HCT116 cell lines significantly reduced the proliferation, migration, and invasion abilities as well as colony formation abilities of cells. Further, knockdown of TDO2 expression induced inactivation of the TDO2-KYNU-AhR signaling pathway.
Conclusion: The results suggest that TDO2 plays an important role in the progression of CRC. Accordingly, TDO2 is a potential therapeutic target in CRC.
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http://dx.doi.org/10.1016/j.gene.2021.145736 | DOI Listing |
Int J Mol Sci
December 2024
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 561113, China.
Astragalus membranaceus (AM) herb is a component of traditional Chinese medicine used to treat various cancers. Herein, we demonstrate a strong anti-leukemic effect of AM injected (Ai) into the mouse model of erythroleukemia induced by Friend virus. Chemical analysis combined with mass spectrometry of AM/Ai identified the compounds Betulinic acid, Kaempferol, Hederagenin, and formononetin, all major mediators of leukemia inhibition in culture and in vivo.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, originating from the malignant proliferation of squamous epithelial cells. However, its pathogenesis remains unclear. To further explore the mechanisms underlying cSCC, we analyzed the data from one single-cell RNA sequencing study and discovered a significant upregulation of tryptophan 2,3-dioxygenase (TDO2) in the cancer-associated fibroblasts (CAFs).
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Background: Glioblastoma (GB) is the stage IV of glioma and mesenchymal GB represents the most common and malignant subtype characterized with elevated expression of a mesenchymal marker YKL-40 and resistance to immune drug therapy. Here, we determined if YKL-40 regulates kynurenine (Kyn) pathway (KP) metabolism that contributes to establishing an immune suppressive microenvironment in GB.
Methods: Tumor cells expressing YKL-40 from GB patients were isolated and activated cellular metabolisms were identified via gene microarray analysis.
Genomics
January 2025
Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Laboratory Medicine, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University; Shenzhen 518020, Guangdong China.. Electronic address:
Skin wound repair involves myofibroblasts crucial for tissue integrity. This study utilized single-cell RNA sequencing to explore myofibroblast diversity in various wound healing scenarios. Analysis of 89,148 cells from skin ulcers, keloids, and normal scars identified 13 cell clusters.
View Article and Find Full Text PDFClin Cancer Res
December 2024
Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), UVic-UCC, IOB-Quirón, Barcelona, Spain.
Purpose: To evaluate linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies.
Patients And Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1).
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