|Cancer Stem Cell News 8.24 June 26, 2019|
The effects of SHP099 on cell survival of neural progenitor cells, glioblastoma cell lines, and patient-derived glioma stem-like cells were evaluated. Brain and plasma pharmacokinetics of SHP099 and its ability to inhibit SHP-2 signaling were assessed. [Neuro Oncol]
To gain insight into the unique biology of CSCs, scientists developed patient-derived xenograft tumors (PDXs) from ER– breast cancers from which they isolated mammospheres that were enriched for CSCs. Comparative global proteomic analysis was performed on patient tumor tissues and corresponding PDXs and mammospheres. [Cell Rep]
The CUL4B complex epigenetically repressed IL-6 transcription in myeloid cells. The IL-6 produced by myeloid-derived suppressor cells (MDSCs) rendered cancer cells stem cell-like properties by activating the IL-6/STAT3 signaling. This crosstalk was effectively blocked either by blocking IL-6 in MDSCs or by inhibition of STAT3 activation in tumor cells. [Oncogene]
Bcl-2/Bcl-xL inhibition exerted synergistic anti-proliferative effects across established, primary cultured and stem-like glioblastoma cells when combined with CUSP9 which had been reduced to only one tenth of its proposed original concentration. The combination treatment also led to enhanced apoptosis with loss of mitochondrial membrane potential and activation of caspases. [Br J Pharmacol]
Investigators revealed that ISO could inhibit stem cell-like phenotype and invasivity of human bladder cancer by specific attenuation of expression of CD44 but not SOX-2, at both the protein transcription and degradation levels. ISO also down-regulated USP28 expression, which in turn reduced CD44 protein stability. [Cell Mol Life Sci]
Researchers analyzed the effect of afatinib and temozolomide combination on gioblastoma (GBM) cells U87MG and U251 engineered to express wild type epidermal growth factor receptor (EGFR), EGFRvIII or EGFRvIII dead kinase, CSCs isolated from U87 and U87EGFRvIII in vitro. The therapeutic utility of the drug combination was investigated on tumor growth and progression using intracranially injected U87EGFRvIII GBM xenografts. [J Exp Clin Cancer Res]
Activation of either XBP1 or ATF6 resulted in reduced cellular proliferation and reduced expression of markers of intestinal epithelial stemness. XBP1-mediated loss of stemness and proliferation resulted from crossactivation of PERK-eIF2α signaling and could be rescued by constitutive expression of eIF2α phosphatase GADD34. [Cell Death Dis]
The authors sought to examine KRAS activation in epithelial-to-mesenchymal transition (EMT) and generation of CSCs. Transduction of nontransformed HFE-145 gastric epithelial cells with oncogenic KRASG12V significantly decreased expression of the epithelial marker E-cadherin, increased expression of the mesenchymal marker vimentin and the EMT transcription factor Slug, and increased migration and invasion of by 15- to 17-fold. [Mol Cancer Res]
Silencing endogenous XB130 regulated the cancer stem cell-like properties of breast cancer, including the formation of self-renewing spheres and the proportion of breast cancer SP+ cells. Mechanistically, scientists indicated that downregulation of XB130 restrained the epithelial-mesenchymal transition and Wnt/β-catenin signaling, so as to weaken the tumor-initiating cell-like phenotype of breast cancer cells. [Mol Carcinog]
Patient-derived glioblastoma (GBM) spheroids were co-cultured with brain endothelial cells (ECs) in microfabricated collagen gels. Integrating these systems with 3D imaging and biochemical assays revealed that ECs increased GBM invasiveness and growth through interleukin-8 (IL-8)-mediated enrichment of CSCs. Blockade of IL-8 inhibited these effects in GBM-EC co-cultures, while IL-8 supplementation increased CSC-mediated growth and invasion in GBM-monocultures. [Sci Rep]
Researchers explored whether or not miR-448 and melanoma-associated antigen 6 (MAGEA6) were involved in the self-renewal and stemness maintenance of hepatocellular carcinoma stem cells. The interaction among miR-448, MAGEA6, and the AMPK signaling pathway was evaluated. [J Cell Physiol]
The authors focus on the two dominant trends in glioma science: the characterization of diagnostic and prognostic tumor markers and the identification of genetic and other risk factors. An overview of the many challenges still facing glioma researchers is also included. [Nat Rev Neurol]
Investigators highlight progress made in the understanding of MET signaling in glioma and advances in therapies targeting hepatocyte growth factor/MET molecules for glioma patients in recent years, in addition to studies on the expression and mutation status of MET. [J Exp Clin Cancer Res]
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Ono Pharmaceutical Co., Ltd. announced that it entered into an exclusive license agreement with Rafael Pharmaceuticals, Inc. for the development and commercialization of CPI-613, its first-in-class clinical lead compound, which targets cancer metabolism enzymes, as well as its other related compounds. [Ono Pharmaceutical Co., Ltd.]
Ziopharm Oncology, Inc. announced completion of enrollment of the third cohort of a Phase I clinical trial evaluating controlled IL-12, in combination with the PD-1 inhibitor OPDIVO® for the treatment of recurrent or progressive glioblastoma multiforme in adults. [Ziopharm Oncology, Inc.]
Daiichi Sankyo Company, Limited announced that the company received a Complete Response Letter from the FDA for the New Drug Application of quizartinib for the treatment of adults with relapsed/ refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Limited]
Bioasis Technologies Inc. announced it had received feedback to its pre-Investigational New Drug (IND) submission to the FDA regarding the planned development of xB3-001, the company’s lead investigational candidate to treat brain cancer. [Bioasis Technologies Inc.]
Leaders and senior scientists at a national mouse-genetics center in the United Kingdom have written an open letter decrying a recommendation to close the facility’s on-site academic research unit. The closure of the MRC Harwell Institute’s Mammalian Genetics Unit – where scientists study disease using animal models – would be “a major threat to mouse genetics in the UK”, says the letter, organized by 14 senior Harwell scientists. [Nature News]
The US Court of Appeals for the Federal Circuit ruled last September that patents held by the Broad Institute of MIT and Harvard University were not in conflict with previously submitted patents from the University of California (UC), Berkeley. But the US Patent and Trademark Office (USPTO) has now posted documents declaring interference between them- meaning they may cover overlapping IP. [The Scientist]
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