US Food and Drug Administration Accepts for Priority Review Application for Opdivo® (Nivolumab) Combined with Chemotherapy as First-Line Treatment in Metastatic Gastric Cancer, Gastroesophageal Junction Cancer and Esophageal Adenocarcinoma

Bristol Myers Squibb announced that the FDA has accepted its supplemental Biologics License Application for Opdivo®, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, based on results from the CheckMate -649 trial.
[Bristol Myers Squibb]
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A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Non-Essential Modes of Oncogenic Transformation

CRISPR/Cas9-mediated ARID1A knockout in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity and mucinous differentiation.
[Cancer Discovery]
Lo, Y.-H., Kolahi, K. S., Du, Y., Chang, C.-Y., Krokhotin, A., Nair, A., Sobba, W. D., Karlsson, K., Jones, S. J., Longacre, T. A., Mah, A. T., Tercan, B., Sockell, A., Xu, H., Seoane, J. A., Chen, J., Shmulevich, I., Weissman, J. S., Curtis, C., … Kuo, C. J. (2021). A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and non-essential modes of oncogenic transformation. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-1109 Cite
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European Medicines Agency Validates Bristol Myers Squibb’s Application for Opdivo (Nivolumab) Combined with Chemotherapy as First-Line Treatment in Metastatic Gastric Cancer, Gastroesophageal Junction Cancer and Esophageal Adenocarcinoma

Bristol Myers Squibb announced that the European Medicines Agency validated its Type II Variation Marketing Authorization Application for Opdivo in combination with fluoropyrimidine- and platinum-based combination chemotherapy for the first-line treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma.
[Bristol Myers Squibb]
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E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling

E7386 demonstrated clear antitumor activity via modulation of the Wnt/β-catenin signal pathway and alteration of the tumor and immune microenvironments, and its antitumor activity could be enhanced in combination with anti-PD-1 antibody.
[Cancer Research]
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Zai Lab Partner MacroGenics Announces FDA Approval of MARGENZA for Patients with Pretreated Metastatic HER2-Positive Breast Cancer

Zai Lab Limited announced that the FDA has approved MARGENZA, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.
[Zai Lab Limited]
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HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation was significantly associated with time to rebound after treatment discontinuation across three independent cohorts.
[Cell Reports]
Offersen, R., Yu, W.-H., Scully, E. P., Julg, B., Euler, Z., Sadanand, S., Garcia-Dominguez, D., Zheng, L., Rasmussen, T. A., Jennewein, M. F., Linde, C., Sassic, J., Lofano, G., Vigano, S., Stephenson, K. E., Fischinger, S., Suscovich, T. J., Lichterfeld, M., Lauffenburger, D., … Alter, G. (2020). HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound. Cell Reports, 33(11). https://doi.org/10.1016/j.celrep.2020.108502 Cite
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Matrix Stiffness Epigenetically Regulates the Oncogenic Activation of the Yes-Associated Protein in Gastric Cancer

Scientists showed that in gastric cancer cells, the stiffness of the ECM reversibly regulates the DNA methylation of the promoter region of the mechanosensitive Yes-associated protein.
[Nature Biomedical Engineering]
Jang, M., An, J., Oh, S. W., Lim, J. Y., Kim, J., Choi, J. K., Cheong, J.-H., & Kim, P. (2020). Matrix stiffness epigenetically regulates the oncogenic activation of the Yes-associated protein in gastric cancer. Nature Biomedical Engineering, 1–10. https://doi.org/10.1038/s41551-020-00657-x Cite
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Lymphatic Metastasis-Related TBL1XR1 Enhances Stemness and Metastasis in Gastric Cancer Stem-Like Cells by Activating ERK1/2-SOX2 Signaling

The correlation of expression of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) and clinical features and gastric cancer patients’ outcomes was evaluated. Knockdown or exogenous expression of TBL1XR1 was combined with in vitro and in vivo assays to evaluate the function of TBL1XR1.
[Oncogene]
Lu, J., Bang, H., Kim, S. M., Cho, S.-J., Ashktorab, H., Smoot, D. T., Zheng, C., Ryeom, S. W., Yoon, S. S., Yoon, C., & Lee, J. H. (2020). Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01571-x Cite
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Gastric Organoids—an In Vitro Model System for the Study of Gastric Development and Road to Personalized Medicine

Investigators review different adult stem cell derived gastric organoid model systems and focus on their establishment, phenotypic and genotypic characterizations as well as their use in predicting therapy response.
[Cell Death & Differentiation]
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MiR-22, Regulated by MeCP2, Suppresses Gastric Cancer Cell Proliferation by Inducing a Deficiency in Endogenous S-Adenosylmethionine

Scientists revealed that the metabolic profiles in gastric cancer tissues were altered. S-adenosylmethionine, a universal methyl donor for histone and DNA methylation, which is specifically involved in the epigenetic maintenance of cancer cells, was found increased.
[Oncogenesis]
Tong, D., Zhang, J., Wang, X., Li, Q., Liu, L., Lu, A., Guo, B., Yang, J., Ni, L., Qin, H., Zhao, L., & Huang, C. (2020). MiR-22 , regulated by MeCP2, suppresses gastric cancer cell proliferation by inducing a deficiency in endogenous S-adenosylmethionine. Oncogenesis, 9(11), 1–16. https://doi.org/10.1038/s41389-020-00281-z Cite
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Molecular Biological Analysis of 5-FU-Resistant Gastric Cancer Organoids; KHDRBS3 Contributes to the Attainment of Features of Cancer Stem Cell

Scientists established GC organoids (GCOs) and gradually treated them with higher concentrations of 5-FU. They successfully harvested four 5-FU-resistant GCOs, which were supported by significant changes in the expression of molecules related to 5-FU metabolism. Microarray analysis was peformed using three normal gastric organoids and three pairs of 5-FU-resistant and parental GCOs.
[Oncogene]
Ukai, S., Honma, R., Sakamoto, N., Yamamoto, Y., Pham, Q. T., Harada, K., Takashima, T., Taniyama, D., Asai, R., Fukada, K., Naka, K., Tanabe, K., Ohdan, H., & Yasui, W. (2020). Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell. Oncogene, 1–14. https://doi.org/10.1038/s41388-020-01492-9 Cite
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