Targovax ASA announced that the colorectal cancer cohort in part 1 of the ONCOS-102 and durvalumab trial in colorectal and platinum-resistant ovarian cancer that has spread to the peritoneum has met the pre-defined efficacy threshold of patients without progression at the end of week 24. The second part of the colorectal expansion cohort is now open for recruitment.
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FT282, JHOS2 and OVCAR4 cells were transiently transfected with either single or pooled TIMP-2 siRNAs. The expression of different genes after TIMP-2 knock down or in response to chemotherapy was determined at the mRNA level by quantitative real time PCR and at the protein level by immunofluorescence.
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Escalona, R. M., Bilandzic, M., Western, P., Kadife, E., Kannourakis, G., Findlay, J. K., & Ahmed, N. (2020). TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells. BMC Cancer, 20(1), 960. https://doi.org/10.1186/s12885-020-07274-6 Cite
Researchers used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor microenvironment. They included specific epitopes, PA nanofibers, and ECM macromolecules for the 3D culture of human ovarian cancer, endothelial, and mesenchymal stem cells.
Scientists used aspirin, a nonselective COX inhibitor, with cisplatin for several hours in cells and days in vivo, and studied the inhibition against human cisplatin‐resistant H460 cells.
Researchers collected the gene expression profiles of ovarian (O)CSCs were from five public cohorts and employed R software and Bioconductor packages to establish differently expressed genes between OCSCs and parental cells.
[Journal of Ovarian Research]
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Zhang, X., Su, Y., Wu, X., Xiao, R., Wu, Y., Yang, B., Wang, Z., Guo, L., Kang, X., & Wang, C. (2020). Integrative analysis of the common genetic characteristics in ovarian cancer stem cells sorted by multiple approaches. Journal of Ovarian Research, 13(1), 116. https://doi.org/10.1186/s13048-020-00715-7 Cite
Investigators report that omental macrophages promoted the migration and colonization of ovarian cancer cells to the omentum through the secretion of chemokine ligands that interacted with chemokine receptor 1.
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Krishnan, V., Tallapragada, S., Schaar, B., Kamat, K., Chanana, A. M., Zhang, Y., Patel, S., Parkash, V., Rinker-Schaeffer, C., Folkins, A. K., Rankin, E. B., & Dorigo, O. (2020). Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1. Communications Biology, 3(1), 1–13. https://doi.org/10.1038/s42003-020-01246-z Cite
Despite strong tumor rejection, IL-2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL-2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes.
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Drerup, J. M., Deng, Y., Pandeswara, S. L., Padrón, Á. S., Reyes, R. M., Zhang, X., Mendez, J., Liu, A., Clark, C. A., Chen, W., Conejo-Garcia, J. R., Hurez, V., Gupta, H., & Curiel, T. J. (2020). CD122-selective IL-2 complexes reduce immunosuppression, promote Treg fragility, and sensitize tumor response to PD-L1 blockade. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0002 Cite
Researchers investigated changes in expression levels of the cancer stem cell (CSC) biomarker, cluster of differentiation 133 (CD133), from primary ovarian cancer (OC) cell lines to induction of CSC-spheres in an attempt to explore the mechanisms related to modulation of stemness, drug resistance, and tumorigenesis in CSCs, thus facilitating the search for new therapeutics for OC.
[International Journal of Molecular Sciences]
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Scientists characterized tumor associated neutrophils (TANs) using flow cytometric analysis and immunofluorescence analysis. The prognostic merit of TANs in epithelial ovarian cancer was evaluated using cox regression analysis.
[British Journal of Cancer]
Researchers showed that relatively large anionic nanoparticles administered intraperitoneally selectively accumulated in tumor-associated macrophages.
[Proceedings of the National Academy of Sciences of the United States of America]
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Haber, T., Cornejo, Y. R., Aramburo, S., Flores, L., Cao, P., Liu, A., Mooney, R., Gilchrist, M., Tirughana, R., Nwokafor, U., Abidi, W., Han, E., Dellinger, T., Wakabayashi, M. T., Aboody, K. S., & Berlin, J. M. (2020). Specific targeting of ovarian tumor-associated macrophages by large, anionic nanoparticles. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1917424117 Cite
Scientists developed expandable ovarian cancer organoids in less than three weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumors.
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Nanki, Y., Chiyoda, T., Hirasawa, A., Ookubo, A., Itoh, M., Ueno, M., Akahane, T., Kameyama, K., Yamagami, W., Kataoka, F., & Aoki, D. (2020). Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing. Scientific Reports, 10(1), 12581. https://doi.org/10.1038/s41598-020-69488-9 Cite