By using a high-throughput CRISPR/Cas9-based genetic screen in HepG2 hepatocellular carcinoma cells to search for metabolic proteins inhibiting ferroptosis, researchers identified a branched-chain amino acid aminotransferase 2 as a novel suppressor of ferroptosis.
[Cell Death & Differentiation]
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Wang, K., Zhang, Z., Tsai, H., Liu, Y., Gao, J., Wang, M., Song, L., Cao, X., Xu, Z., Chen, H., Gong, A., Wang, D., Cheng, F., & Zhu, H. (2020). Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells. Cell Death & Differentiation, 1–15. https://doi.org/10.1038/s41418-020-00644-4 Cite
Investigators showed interlukine-17 receptor B (IL-17RB) expression was positively correlated with mucin 1 (MUC1) and MUC4 expression in pancreatic cancer cells and tumor tissue.
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Tsai, L.-H., Hsu, K.-W., Chiang, C.-M., Yang, H.-J., Liu, Y.-H., Yang, S.-F., Peng, P.-H., Cheng, W.-C., & Wu, H.-H. (2020). Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer. Scientific Reports, 10(1), 17817. https://doi.org/10.1038/s41598-020-73659-z Cite
In CFPAC-I and HPAF-II pancreatic cancer cell lines, the combined in vitro effect of tumor treating fields and radiotherapy was evaluated by measuring cell counts, markers of apoptosis, and clonogenic cell survival.
[International Journal of Radiation Biology]
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miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability, apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. The roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice.
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Investigators used sublines to screen molecular targets for the treatment of pancreatic cancer. Among the genes with increased expression levels in the sublines, they focused on those encoding cell surface receptors that may be involved in the interactions between cancer cells and the tumor microenvironment.
The authors analyze the role of cancer associated fibroblasts (CAFs) in therapeutic resistance of pancreatic cancer and discuss potential CAFs-targeting strategies basing on the diverse biological functions of CAFs, thus to improve the outcome of pancreatic cancer treatment.
[Biochimica et Biophysica Acta-Reviews On Cancer]
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Han, X., Zhang, W.-H., Wang, W.-Q., Yu, X.-J., & Liu, L. (2020). Cancer-associated fibroblasts in therapeutic resistance of pancreatic cancer: Present situation, predicaments, and perspectives. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1874(2), 188444. https://doi.org/10.1016/j.bbcan.2020.188444 Cite
The cytotoxic effect of diltiazem, gemcitabine, and 5-fluorouracil in single and combined forms against PANC-1 and AsPC-1 cells were assayed by MTT. Flow cytometric analysis was used for the determination of cell cycle, apoptosis, and stemness markers in pancreatic cancer cells.
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El-Mahdy, H. A., El-Husseiny, A. A., Kandil, Y. I., & Gamal El-Din, A. M. (2020). Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells through inhibition of P-glycoprotein. Life Sciences, 118518. https://doi.org/10.1016/j.lfs.2020.118518 Cite
This study displayed histological and immunohistochemical analyses of a malignant tumor model developed from cancer stem cells converted from human iPSCs in a cancer microenvironment prepared from the conditioned medium of a pancreatic cancer cell line.
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Researchers determined that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibited preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions.
[Journal of Biological Chemistry]
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Scientists demonstrated that TSPAN1 was upregulated in pancreatic cancer and that TSPAN1 depletion decreased pancreatic cancer cell proliferation in vitro and in vivo. TSPAN1 expression was correlated with poor overall survival of pancreatic cancer patients.
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Zhou, C., Liang, Y., Zhou, L., Yan, Y., Liu, N., Zhang, R., Huang, Y., Wang, M., Tang, Y., Ali, D. W., Wang, Y., Michalak, M., Chen, X.-Z., & Tang, J. (2020). TSPAN1 promotes autophagy flux and mediates cooperation between WNT-CTNNB1 signaling and autophagy via the MIR454-FAM83A-TSPAN1 axis in pancreatic cancer. Autophagy, 0(ja), null. https://doi.org/10.1080/15548627.2020.1826689 Cite
Functional experiments demonstrated that tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) promoted pancreatic cancer (PC) cells’ proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo.