Researchers showed that an iPSC-based cancer vaccine, comprised of autologous iPSCs and CpG, stimulated cytotoxic antitumor CD8+ T cell effector and memory responses, induced cancer-specific humoral immune responses, reduced immunosuppressive CD4+ T regulatory cells, and prevented tumor formation in 75% of pancreatic ductal adenocarcinoma mice.
[Stem Cell Reports]
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Ouyang, X., Liu, Y., Zhou, Y., Guo, J., Wei, T.-T., Liu, C., Lee, B., Chen, B., Zhang, A., Casey, K. M., Wang, L., Kooreman, N. G., Habtezion, A., Engleman, E. G., & Wu, J. C. (2021). Antitumor effects of iPSC-based cancer vaccine in pancreatic cancer. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2021.04.004 Cite
Fzd7/Wnt7b knockdown can reduce PDAC cell stemness and chemoresistance by reducing the percentage of cancer stem cells.
Scientists found that genetic deficiency for protease‐activated receptor 1(PAR1) increases acinar gene expression programs in the healthy pancreas and that PAR1 deficiency limits ductal transdifferentiation in experimental systems for acinar‐to‐ductal metaplasia.
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Tekin, C., Scicluna, B. P., Lodestijn, S. C., Shi, K., Bijlsma, M. F., & Spek, C. A. (n.d.). Protease-activated receptor-1 drives and maintains ductal cell-fates in the premalignant pancreas and ductal adenocarcinoma. Molecular Oncology, n/a(n/a). https://doi.org/https://doi.org/10.1002/1878-0261.12971 Cite
Scientists identified preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC.
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Rittmann, M.-C., Hussung, S., Braun, L. M., Klar, R. F. U., Biesel, E. A., Fichtner-Feigl, S., Fritsch, R., Wittel, U. A., & Ruess, D. A. (2021). Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma. Scientific Reports, 11(1), 7499. https://doi.org/10.1038/s41598-021-86779-x Cite
Most PDAC cells showed similar pleomorphic morphologies in 2D culture. Under 3D culture, PDAC cells with high E-cadherin and low vimentin expression levels formed small round spheres encircled with flat lining cells, whereas those with high vimentin and low E-cadherin expression levels formed large grape-like spheres without lining cells and were highly proliferative.
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The authors investigated the potential role and mechanisms of activating transcription factor 4 (ATF4) in cancer-associated fibroblasts-induced malignancy and gemcitabine resistance. They demonstrated that ATF4 was overexpressed in PDAC and associated with a poor prognosis.
[Cell Death & Disease]
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Wei, L., Lin, Q., Lu, Y., Li, G., Huang, L., Fu, Z., Chen, R., & Zhou, Q. (2021). Cancer-associated fibroblasts-mediated ATF4 expression promotes malignancy and gemcitabine resistance in pancreatic cancer via the TGF-β1/SMAD2/3 pathway and ABCC1 transactivation. Cell Death & Disease, 12(4), 1–14. https://doi.org/10.1038/s41419-021-03574-2 Cite
Scientists examined the differences in the morphological and functional characteristics of eight PDAC cell lines in 2D and 3D cultures.
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Minami, F., Sasaki, N., Shichi, Y., Gomi, F., Michishita, M., Ohkusu-Tsukada, K., Toyoda, M., Takahashi, K., & Ishiwata, T. (2021). Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures. Scientific Reports, 11(1), 6775. https://doi.org/10.1038/s41598-021-86028-1 Cite
Collection of an adequate number of PDAC cells is difficult due to the surrounding fibroblasts. The authors discovered novel biomarkers to predict chemosensitivity based on the collagen gel droplet-embedded drug sensitivity test results.
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Mitachi, K., Ariake, K., Shima, H., Sato, S., Miura, T., Maeda, S., Ishida, M., Mizuma, M., Ohtsuka, H., Kamei, T., Igarashi, K., & Unno, M. (2021). Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer. Scientific Reports, 11(1), 6541. https://doi.org/10.1038/s41598-021-86099-0 Cite
Scientists review the metabolic pathways that PDAC use to support their growth in the setting of an austere tumor microenvironment.
[Nature Reviews Gastroenterology & Hepatology]
Investigators provided evidence that macropinocytosis was operational in the pancreatic tumor stroma. They found that glutamine deficiency triggered macropinocytic uptake in pancreatic cancer-associated fibroblasts.
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Zhang, Y., Recouvreux, M. V., Jung, M., Galenkamp, K. M. O., Li, Y., Zagnitko, O., Scott, D. A., Lowy, A. M., & Commisso, C. (2021). Macropinocytosis in Cancer-Associated Fibroblasts is Dependent on CaMKK2/ARHGEF2 Signaling and Functions to Support Tumor and Stromal Cell Fitness. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-0119 Cite
Scientists investigated the expression of non-SMAD-transforming growth factor-beta (TGF-β) signaling proteins patient-derived tissues, cell lines and an immunocompetent mouse model.
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Hussain, S. M., Kansal, R. G., Alvarez, M. A., Hollingsworth, T. J., Elahi, A., Miranda-Carboni, G., Hendrick, L. E., Pingili, A. K., Albritton, L. M., Dickson, P. V., Deneve, J. L., Yakoub, D., Hayes, D. N., Kurosu, M., Shibata, D., Makowski, L., & Glazer, E. S. (2021). Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression. Cellular Oncology. https://doi.org/10.1007/s13402-021-00594-0 Cite