Bio-Path Holdings Announces Successful Completion of Safety Cohort of Triple Combination of Prexigebersen, Decitabine and Venetoclax in Stage II of Phase II Clinical Trial in Acute Myeloid Leukemia

Bio-Path Holdings, Inc. announced the successful completion of the safety run-in of the Stage II of the Phase II clinical study of prexigebersen, a liposomal Grb2 antisense, for the treatment of acute myeloid leukemia (AML), in combination with frontline therapies, decitabine and venetoclax, in AML patients.
[Bio-Path Holdings, Inc.]
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Low-Dose Decitabine Priming Endows CAR T Cells with Enhanced and Persistent Antitumor Potential via Epigenetic Reprogramming

Anti-tumor activities, cytokine production, and proliferation were enhanced in decitabine-treated chimeric antigen receptor T cells both in vitro and in vivo.
[Nature Communications]
Low-dose decitabine priming endows CAR T cells with enhanced and persistent antitumour potential via epigenetic reprogramming | Nature Communications. (n.d.). Retrieved January 18, 2021, from https://www.nature.com/articles/s41467-020-20696-x Cite
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Decitabine Induces Gene Derepression on Monosomic Chromosomes: In Vitro and In Vivo Effects in Adverse-Risk Cytogenetics AML

An unbiased RNA-seq approach was developed to interrogate DAC-induced transcriptome changes in AML cell lines with or without a deletion of chromosomes 7q, 5q or 17p. Hypomethylating agent treatment preferentially upregulated several hemizygous tumor suppressor genes in this genomic region, significantly derepressing endogenous retrovirus (ERV)3-1 with promoter demethylation, enhanced chromatin accessibility, and increased H3K4me3 levels.
[Cancer Research]
Greve, G., Schüler, J., Grüning, B. A., Berberich, B., Stomper, J., Zimmer, D., Gutenkunst, L., Bönisch, U., Meier, R., Blagitko-Dorfs, N., Grishina, O., Pfeifer, D., Weichenhan, D., Plass, C., & Lübbert, M. (2020). Decitabine induces gene derepression on monosomic chromosomes: in vitro and in vivo effects in adverse-risk cytogenetics AML. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-1430 Cite
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Astex Pharmaceuticals Expands Clinical Evaluation of Oral Decitabine and Cedazuridine Tablets through New Cooperative Research and Development Agreement (CRADA) with the US National Cancer Institute

Astex Pharmaceuticals, Inc. announced it has entered into a Cooperative Research and Development Agreement with the US National Cancer Institute, part of National Institutes of Health. The agreement calls for a range of new clinical and translational studies of oral decitabine and cedazuridine tablets as an anticancer agent to be conducted in collaboration with Astex.
[Astex Pharmaceuticals, Inc.]
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Sumitomo Dainippon Pharma Oncology Announces First Patient Dosed in the Dubermatinib Arm of The Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial in Patients with Acute Myeloid Leukemia

Sumitomo Dainippon Pharma Oncology, Inc. announced the first patient has been dosed in a Phase Ib/II study evaluating the oral investigational agent, dubermatinib, an AXL kinase inhibitor, in combination with decitabine, in patients 60 years or older with newly diagnosed acute myeloid leukemia who have TP53 mutations and/or complex karyotype.
[Sumitomo Dainippon Pharma Oncology, Inc.]
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Xeno- and Transgene-Free Reprogramming of Mesenchymal Stem Cells Toward the Cells Expressing Neural Markers Using Exosome Treatments

Scientists demonstrated that treatment with exosomes derived from neural stem cells makes MSCs capable of expressing neural cell markers bypassing the generation of iPSCs.
[PLoS One]
Valerio, L. S. A., & Sugaya, K. (2020). Xeno- and transgene-free reprogramming of mesenchymal stem cells toward the cells expressing neural markers using exosome treatments. PLOS ONE, 15(10), e0240469. https://doi.org/10.1371/journal.pone.0240469 Cite
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Inhibition of DNMT1 and ERRα Crosstalk Suppresses Breast Cancer via Derepression of IRF4

Genetic or pharmacological studies uncovered a hitherto unknown feedforward molecular link between DNA methyltransferase (DNMT1) and the estrogen related receptor α (ERRα), a key transcriptional regulator of cellular metabolism.
[Oncogene]
Vernier, M., McGuirk, S., Dufour, C. R., Wan, L., Audet-Walsh, E., St-Pierre, J., & Giguère, V. (2020). Inhibition of DNMT1 and ERRα crosstalk suppresses breast cancer via derepression of IRF4. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01438-1 Cite
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Epigenetic Silencing of the Ubiquitin Ligase Subunit FBXL7 Impairs C-SRC Degradation and Promotes Epithelial-to-Mesenchymal Transition and Metastasis

Researchers showed that the promoter of the gene that encoded the ubiquitin ligase subunit FBXL7 was hypermethylated in advanced prostate and pancreatic cancers, correlating with decreased FBXL7 mRNA and protein levels.
[Nature Cell Biology]
Moro, L., Simoneschi, D., Kurz, E., Arbini, A. A., Jang, S., Guaragnella, N., Giannattasio, S., Wang, W., Chen, Y.-A., Pires, G., Dang, A., Hernandez, E., Kapur, P., Mishra, A., Tsirigos, A., Miller, G., Hsieh, J.-T., & Pagano, M. (2020). Epigenetic silencing of the ubiquitin ligase subunit FBXL7 impairs c-SRC degradation and promotes epithelial-to-mesenchymal transition and metastasis. Nature Cell Biology, 1–13. https://doi.org/10.1038/s41556-020-0560-6 Cite
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S‐Adenosylmethionine in Combination with Decitabine Shows Enhanced Anti‐Cancer Effects in Repressing Breast Cancer Growth and Metastasis

Scientists investigated the combined therapeutic effects of an approved nutraceutical agent S‐adenosylmethionine and FDA‐approved hypomethylating agent decitabine using the MDA‐MB‐231 xenograft model of breast cancer and found a pronounced reduction in mammary tumour volume and lung metastasis compared to the animals in the control and monotherapy treatment arms.
[Journal of Cellular and Molecular Medicine]
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