In syngeneic mouse colorectal cancer (CRC) models and human patient-derived CRC organoid models, atractylenolide I treatment promoted the cytotoxicity of CD8+ T cells and thus profoundly enhanced the efficacy of immune checkpoint blockade therapy.
[Journal of Clinical Investigation]
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Xu, H., Jeught, K. V. der, Zhou, Z., Zhang, L., Yu, T., Sun, Y., Li, Y., Wan, C., So, K., Liu, D., Frieden, M., Fang, Y., Mosley, A. L., He, X., Zhang, X., Sandusky, G. E., Liu, Y., Meroueh, S. O., Zhang, C., … Lu, X. (2021). Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI146832 Cite
Mutationally activated KRAS in tumor cells reprograms macrophages to a tumor-associated macrophage-like phenotype via a combination effect of tumor-derived CSF2 and lactate.
[Signal Transduction and Targeted Therapy]
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Liu, H., Liang, Z., Zhou, C., Zeng, Z., Wang, F., Hu, T., He, X., Wu, X., Wu, X., & Lan, P. (2021). Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer. Signal Transduction and Targeted Therapy, 6(1), 1–13. https://doi.org/10.1038/s41392-021-00534-2 Cite
Daiichi Sankyo Company, Limited AstraZeneca announced that the first patient was dosed in DESTINY-CRC02, a global Phase II trial evaluating the efficacy and safety of ENHERTU® in patients with HER2 overexpressing locally advanced, unresectable or metastatic colorectal cancer with progression following treatment with standard of care chemotherapy.
[Daiichi Sankyo Company]
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Researchers addressed the role of typhoid toxin in modulation of the host-microbial interaction in health and disease.
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Martin, O. C. B., Bergonzini, A., Chiloeches, M. L., Paparouna, E., Butter, D., Theodorou, S. D. P., Haykal, M. M., Boutet-Robinet, E., Tebaldi, T., Wakeham, A., Rhen, M., Gorgoulis, V. G., Mak, T., Pateras, I. S., & Frisan, T. (2021). Influence of the microenvironment on modulation of the host response by typhoid toxin. Cell Reports, 35(1). https://doi.org/10.1016/j.celrep.2021.108931 Cite
A dual-luciferase reporter system and RIP assays showed that UCC specifically bound to miR-143-3p and acted as a sponge of miR-143-3p in NSCLC cells.
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Scientists demonstrated the enhanced anti-cancer activity between two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. They validated these findings in subcutaneous xenograft models and in patient derived primary epithelial 3D organoids.
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Shimura, T., Sharma, P., Sharma, G. G., Banwait, J. K., & Goel, A. (2021). Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer. Scientific Reports, 11(1), 7548. https://doi.org/10.1038/s41598-021-87283-y Cite
Utidelone (UTD1) dramatically inhibited colorectal cancer cell proliferation in vitro. Immunofluorescence staining showed that UTD1 induced the formation of microtubule bundling and asters in RKO cells.
[Cell Death & Disease]
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To elucidate the interplay between epidermal growth factor signaling and extracellular-regulated kinase activation in tumors, scientists used patient-derived organoids from KRAS and BRAF mutant colorectal cancer.
[Nature Cell Biology]
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Ponsioen, B., Post, J. B., Buissant des Amorie, J. R., Laskaris, D., van Ineveld, R. L., Kersten, S., Bertotti, A., Sassi, F., Sipieter, F., Cappe, B., Mertens, S., Verlaan-Klink, I., Boj, S. F., Vries, R. G. J., Rehmann, H., Vandenabeele, P., Riquet, F. B., Trusolino, L., Bos, J. L., & Snippert, H. J. G. (2021). Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00654-5 Cite
The authors generated two iPSC lines ZNHi001-A and ZNHi001-B from a prostate cancer patient carrying germline mutation in CHEK2 which might increase the risk of prostate cancer. Pluripotency and multi-lineage differentiation capacity of the two iPSC lines were confirmed by gene expression and teratoma assay.
[Stem Cell Research]
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Functional experiments showed that MCF2L‐AS1 knockdown suppressed the cancer stem cell‐like traits of non-small cell lung cancer cells through qRT‐PCR, western blot, tumor‐sphere formation, and ALDH activity detection.
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The characteristic surface markers of cancer stem cells and the related mechanism of drug resistance are discussed in detail by the authors.