PTEN Status Determines Chemosensitivity to Proteasome Inhibition in Cholangiocarcinoma

Scientists determined that phosphate and tensin homology deleted on chromosome ten (PTEN) deficiency promoted protein synthesis and proteasome subunit expression and proteolytic activity, creating a dependency on the proteasome for cancer cell growth and survival.
[Science Translational Medicine]
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A Novel β2-AR/YB-1/β-Catenin Axis Mediates Chronic Stress-Associated Metastasis in Hepatocellular Carcinoma

Investigators performed immunoprecipitation-mass spectrometry analysis of hepatocellular carcinoma (HCC) tissues. A vital oncoprotein, Y-box binding protein 1 (YB-1), was shown to interact with β2-adrenergic receptor (β2-AR) in HCC cells.
[Oncogenesis]
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T. Gondii Infection Induces Il-1R Dependent Chronic Cachexia and Perivascular Fibrosis in the Liver and Skeletal Muscle

IL-1α was sufficient to activate cultured fibroblasts and primary hepatic stellate cells in vitro, and IL-1α was elevated in the sera and liver of cachectic, suggesting a mechanism by which chronic IL-1R signaling could be leading to cachexia-associated fibrosis.
[Scientific Reports]
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GENFIT Announces First Patient First Visit for ELATIVE Phase III Study Evaluating Elafibranor in PBC

GENFIT are a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and liver diseases. They have announced the first patient first visit for ELATIVE, the global, pivotal, Phase III study evaluating elafibranor in Primary Biliary Cholangitis (PBC).
[GENFIT]
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Agios Announces Final Overall Survival Data from Phase III ClarIDHy Study of TIBSOVO® (ivosidenib tablets) in Previously Treated IDH1-Mutant Cholangiocarcinoma Patients

Agios Pharmaceuticals, Inc.has announced the results of the final overall survival analysis from its global Phase III ClarIDHy trial of TIBSOVO® in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 mutation.
[Agios Pharmaceuticals, Inc.]
Press Release
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Extracellular Vesicles in Hepatology: Physiological Role, Involvement in Pathogenesis, and Therapeutic Opportunities

The authors summarize systematically and comprehensively the myriad of works that appeared in the last decade and lighted the discussion about the best opportunities for using extracellular vesicles in liver disease therapeutics.
[Pharmacology & Therapeutics]
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T-Plastin Reinforces Membrane Protrusions to Bridge Matrix Gaps during Cell Migration

Using micropatterned ECMs, researchers identified T-Plastin, one of the most ancient actin bundling proteins, as an actin stabilizer that promoted membrane protrusions and enabled bridging of ECM gaps.
[Nature Communications]
Garbett, D., Bisaria, A., Yang, C., McCarthy, D. G., Hayer, A., Moerner, W. E., Svitkina, T. M., & Meyer, T. (2020). T-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration. Nature Communications, 11(1), 4818. https://doi.org/10.1038/s41467-020-18586-3 Cite
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Hepatic Lipocalin 2 Promotes Liver Fibrosis and Portal Hypertension

Investigators found hepatic lipocalin 2 (LCN2) expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with alcoholic hepatitis.
[Scientific Reports]
Chen, J., Argemi, J., Odena, G., Xu, M.-J., Cai, Y., Massey, V., Parrish, A., Vadigepalli, R., Altamirano, J., Cabezas, J., Gines, P., Caballeria, J., Snider, N., Sancho-Bru, P., Akira, S., Rusyn, I., Gao, B., & Bataller, R. (2020). Hepatic lipocalin 2 promotes liver fibrosis and portal hypertension. Scientific Reports, 10(1), 15558. https://doi.org/10.1038/s41598-020-72172-7 Cite
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CPEB3-Mediated MTDH mRNA Translational Suppression Restrains Hepatocellular Carcinoma Progression

Researchers demonstrated that cytoplasmic polyadenylation element-binding protein 3 (CPEB3) played an important role in hepatocellular carcinoma progression and targeting CPEB3-mediated mRNA translation may be a favorable therapeutic approach.
[Cell Death & Disease]
Zhang, H., Zou, C., Qiu, Z., E, F., Li, Q., Chen, M., Wang, D., Tan, Q., Yin, W., Matunda, C., Wang, H., Zhang, Y., Zhan, C., Wang, C., Wu, Y., Xuan, X., Wang, Y., Zou, C., Lv, G., & Gao, X. (2020). CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression. Cell Death & Disease, 11(9), 1–17. https://doi.org/10.1038/s41419-020-02984-y Cite
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Efficacy of Anti-CD147 Chimeric Antigen Receptors Targeting Hepatocellular Carcinoma

The authors report that T and NK cells transduced with a chimeric antigen receptor that recognize the surface marker, CD147, also known as Basigin, can effectively kill various malignant hepatocellular carcinoma (HCC) cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models.
[Nature Communications]
Tseng, H., Xiong, W., Badeti, S., Yang, Y., Ma, M., Liu, T., Ramos, C. A., Dotti, G., Fritzky, L., Jiang, J., Yi, Q., Guarrera, J., Zong, W.-X., Liu, C., & Liu, D. (2020). Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma. Nature Communications, 11(1), 4810. https://doi.org/10.1038/s41467-020-18444-2 Cite
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(+)-Clausenamide Protects against Drug-Induced Liver Injury by Inhibiting Hepatocyte Ferroptosis

Scientists report a novel mechanism that contributed to acetaminophen-induced hepatotoxicity through the induction of ferroptosis, a distinctive form of programmed cell death.
[Cell Death & Disease]
Wang, M., Liu, C.-Y., Wang, T., Yu, H.-M., Ouyang, S.-H., Wu, Y.-P., Gong, H.-B., Ma, X.-H., Jiao, G.-L., Fu, L.-L., Wu, Q.-S., Kurihara, H., Li, Y.-F., Shen, T., & He, R.-R. (2020). (+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis. Cell Death & Disease, 11(9), 1–15. https://doi.org/10.1038/s41419-020-02961-5 Cite
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