The Microfluidic Environment Reveals a Hidden Role of Self-Organizing Extracellular Matrix in Hepatic Commitment and Organoid Formation of hiPSCs

Hepatic progenitor cells either derived in microfluidics or exposed to exogenous ECM stimuli showed a significantly higher potential of forming hepatic organoids that could be rapidly expanded for several passages and further differentiated into functional hepatocytes.
[Cell Reports]
Michielin, F., Giobbe, G. G., Luni, C., Hu, Q., Maroni, I., Orford, M. R., Manfredi, A., Filippo, L. D., David, A. L., Cacchiarelli, D., Coppi, P. D., Eaton, S., & Elvassore, N. (2020). The Microfluidic Environment Reveals a Hidden Role of Self-Organizing Extracellular Matrix in Hepatic Commitment and Organoid Formation of hiPSCs. Cell Reports, 33(9). https://doi.org/10.1016/j.celrep.2020.108453 Cite
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Hypoxia Induces Sorafenib Resistance Mediated by Autophagy via Activating FOXO3a in Hepatocellular Carcinoma

Investigators demonstrated here that hypoxia significantly attenuated sensitivity of hepatocellular carcinoma (HCC) cells to sorafenib treatment and reduced its proliferation. Autophagy was observed in sorafenib-treated HCC cells in hypoxia, and inhibition of autophagy by 3-MA eliminated hypoxia-induced sorafenib resistance.
[Cell Death & Disease]
Liang, C., Dong, Z., Cai, X., Shen, J., Xu, Y., Zhang, M., Li, H., Yu, W., & Chen, W. (2020). Hypoxia induces sorafenib resistance mediated by autophagy via activating FOXO3a in hepatocellular carcinoma. Cell Death & Disease, 11(11), 1–13. https://doi.org/10.1038/s41419-020-03233-y Cite
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Lkb1 Suppresses Amino Acid-Driven Gluconeogenesis in the Liver

Using genetic, proteomic and pharmacological approaches, the authors identified the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.
[Nature Communications]
Just, P.-A., Charawi, S., Denis, R. G. P., Savall, M., Traore, M., Foretz, M., Bastu, S., Magassa, S., Senni, N., Sohier, P., Wursmer, M., Vasseur-Cognet, M., Schmitt, A., Le Gall, M., Leduc, M., Guillonneau, F., De Bandt, J.-P., Mayeux, P., Romagnolo, B., … Perret, C. (2020). Lkb1 suppresses amino acid-driven gluconeogenesis in the liver. Nature Communications, 11(1), 6127. https://doi.org/10.1038/s41467-020-19490-6 Cite
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MicroRNA-9-5p Regulates the Mitochondrial Function of Hepatocellular Carcinoma Cells through Suppressing PDK4

Scientists attempted to investigate the potential role of miR-9-5p in the progression of hepatocellular carcinoma (HCC). Expression of pyruvate dehydrogenase kinase 4 and miR-9-5p was examined in HCC tissues collected from HCC patients and cell lines.
[Cancer Gene Therapy]
Si, T., Ning, X., Zhao, H., Zhang, M., Huang, P., Hu, Z., Yang, L., & Lin, L. (2020). microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4. Cancer Gene Therapy, 1–13. https://doi.org/10.1038/s41417-020-00253-w Cite
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Evidence for Liver and Peripheral Immune Cells Secreting Tumor-Suppressive Extracellular Vesicles in Melanoma Patients

The authors mimicked the interaction of tumor cells with liver cells and PBMC in vitro, and compared newly secreted extracellular vesicle (EV)-associated miRNAs and protein factors with those detected in melanoma patient`s plasma EV.
[Ebiomedicine]
Lee, J.-H., Eberhardt, M., Blume, K., Vera, J., & Baur, A. S. (2020). Evidence for liver and peripheral immune cells secreting tumor-suppressive extracellular vesicles in melanoma patients. EBioMedicine, 62. https://doi.org/10.1016/j.ebiom.2020.103119 Cite
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MCPIP1 Reduces HBV-RNA by Targeting Its Epsilon Structure

Overexpression of monocyte chemotactic protein-1-induced protein 1 (MCPIP1) decreased hepatitis B virus (HBV) RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction.
[Scientific Reports]
Li, Y., Que, L., Fukano, K., Koura, M., Kitamura, K., Zheng, X., Kato, T., Aly, H. H., Watashi, K., Tsukuda, S., Aizaki, H., Watanabe, N., Sato, Y., Suzuki, T., Suzuki, H. I., Hosomichi, K., Kurachi, M., Wakae, K., & Muramatsu, M. (2020). MCPIP1 reduces HBV-RNA by targeting its epsilon structure. Scientific Reports, 10(1), 20763. https://doi.org/10.1038/s41598-020-77166-z Cite
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In Vitro-Transcribed Antigen Receptor mRNA Nanocarriers for Transient Expression in Circulating T Cells In Vivo

In mouse models of human leukemia, prostate cancer and hepatitis B-induced hepatocellular carcinoma, repeated infusions of these polymer nanocarriers induced sufficient host T cells expressing tumor-specific CARs or virus-specific TCRs to cause disease regression at levels similar to bolus infusions of ex vivo engineered lymphocytes.
[Nature Communications]
Parayath, N. N., Stephan, S. B., Koehne, A. L., Nelson, P. S., & Stephan, M. T. (2020). In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo. Nature Communications, 11(1), 6080. https://doi.org/10.1038/s41467-020-19486-2 Cite
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iBiopsy®: Promising Results on a Preliminary Study to Identify the Severity of the Disease in Patients with Non-Alcoholic Steatohepatitis (NASH)

Median Technologies announced results of a preliminary retrospective study on the evaluation of the severity of hepatic fibrosis in NASH patients using a new imaging biomarker extracted from MRI/MRE images.
[Median Technologies]
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Exelixis Announces Partner Takeda Receives Approval in Japan for CABOMETYX® (Cabozantinib) for the Treatment of Unresectable Hepatocellular Carcinoma that has Progressed after Prior Systemic Therapy

Exelixis, Inc. announced that Takeda Pharmaceutical Company Ltd., its partner responsible for the clinical development and commercialization of CABOMETYX® in Japan, received approval from the Japanese Ministry of Health, Labor and Welfare to manufacture and market CABOMETYX as a treatment for patients with unresectable hepatocellular carcinoma that has progressed after prior systemic therapy.
[Exelixis, Inc.]
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Hepatocellular Carcinoma: Intratumoral EpCAM-Positive Cancer Stem Cell Heterogeneity Identifies High-Risk Tumor Subtype

Scientists investigated the spatial heterogeneity of cancer stem cell-features with the aim of identifying the unique hepatocellular carcinoma patient subgroups amenable to adjuvant treatment.
[BMC Cancer]
Krause, J., von Felden, J., Casar, C., Fründt, T. W., Galaski, J., Schmidt, C., Jung, C., Ittrich, H., Weidemann, S. A., Krech, T., Heumann, A., Li, J., Fischer, L., Sauter, G., Lohse, A. W., Wege, H., & Schulze, K. (2020). Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype. BMC Cancer, 20(1), 1130. https://doi.org/10.1186/s12885-020-07580-z Cite
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SIRT1 Alleviates Hepatic Ischemia-Reperfusion Injury Via the miR-182-Mediated XBP1/NLRP3 Pathway

In in vitro assays, NCTC1469 cells subjected to hypoxia/reoxygenation were transduced with siRNA/activator of SIRT1 or miR-182 agomir to confirm the effect of SIRT1 on NCTC1469 cell behaviors as well as the regulation of miR-182 and XBP1/NLRP3 signaling pathway.
[Molecular Therapy-Nucleic Acids]
SIRT1 Alleviates Hepatic Ischemia-Reperfusion Injury Via the miR-182-Mediated XBP1/NLRP3 Pathway: Molecular Therapy - Nucleic Acids. (n.d.). Retrieved November 26, 2020, from https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(20)30371-1 Cite
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