|Cancer Stem Cell News 8.36 September 18, 2019|
Mechanistically, KLF4 repressed the Dyrk2 gene in leukemic stem/progenitor cells; thus, loss of KLF4 resulted in elevated levels of DYRK2 kinase, which were associated with inhibition of survival and self-renewal via depletion of c-Myc protein and p53 activation. In addition to transcriptional regulation, stabilization of DYRK2 protein by inhibiting ubiquitin E3 ligase SIAH2 with vitamin K3 promoted apoptosis and abrogated self-renewal in murine and human chronic myeloid leukemia stem/progenitor cells. [Blood]
By investigating public databases containing colorectal cancer (CRC) patient data, researchers explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts. [J Exp Clin Cancer Res]
Real-time PCR was used to examine the expression of circPTN in glioma tissues and normal brain tissues. Assays of dual- luciferase reporter system, biotin label RNA pull-down and FISH were used to determine that circPTN could sponge miR-145-5p and miR-330-5p. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell. [J Exp Clin Cancer Res]
Employing a comparative approach involving 21 cancers, investigators uncovered clinically-relevant, pan-cancer drivers of Notch and Hedgehog. GISTIC datasets were used to evaluate copy number alterations. Receiver operating characteristic and Cox regression were employed for survival analyses. [Br J Cancer]
Comparison of 2D versus 3D cancer cell cultures from different tissues of origin suggest that NUDT5 increases the aggressiveness of the disease via the modulation of several key driver genes, including ubiquitin specific peptidase 22, RAB35B, focadhesin and prostagladin E synthase. NUDT5 functioned as a master regulator of key oncogenic pathways and of genes involved in cell adhesion, cancer stem cell maintenance and epithelial to mesenchyme transition. [Cancers]
The stem cell marker CD44 was used to sort gastric (G) CSCs by fluorescence‐activated cell sorting. They found that CD44 (+) cells had higher invasiveness and formed more number of sphere colonies than CD44 (−) cells. Quantitative real-time PCR revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. [J Cell Physiol]
The authors showed that Os(II) complex 2 was capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its submicromolar potency to kill CSCs was considerably higher than that of its Ru analog, [Ru(η6-pcym)(bphen)(dca)]PF6, and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. [Sci Rep]
Researchers report that miR-133b was downregulated in colorectal spheroids, which were enriched with CSC and displayed stem cell-like characteristics, including upreulation of CSCs surface markers and elevated chemoresistance. Additionally, miR-133b overexpression reduced colorectal cancer (CRC) stemness and overrode chemoresistance to 5-Fluorouracil and oxaliplatin, indicating a negative role of miR-133b in regulating CRC stemness and chemoresistance. [Exp Cell Res]
Scientists report the miRNA expression characteristics of two cell lines, MIA PaCa-2 and PANC-1, and discovered three miRNAs that were involved in CSC suppression. After transfection of each miRNA’s mimic into PANC-1 cells which exhibited higher stemness feature than MIA-PaCa-2 cells, partial reduction of CSC surface markers and inhibition of tumor sphere formation were observed. [Int J Mol Sci]
The authors highlight the role of CSCs in every step of the metastatic cascade from cancer cell invasion into blood vessels, survival in the blood stream, attachment and extravasation as well as colonization of the host organ and subsequent establishment of distant macrometastasis. [Semin Cancer Biol]
Investigators survey the latest evidence concerning the role of genomic alteration in current triple-negative breast cancer (TNBC) treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. [Cancers]
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Bristol-Myers Squibb Company announced that the Phase III CheckMate -548 trial evaluating the addition of Opdivo to the current standard of care versus the standard of care alone did not meet one of its primary endpoints, progression-free survival, in patients with newly diagnosed glioblastoma multiforme that is O6-methylguanine-DNA methyltransferase (MGMT)-methylated. [Bristol-Myers Squibb Company]
Genmab A/S annoucned topline results from the Phase III CANDOR study, sponsored by Amgen, of daratumumab in combination with carfilzomib and dexamethasone (Kd) versus Kd alone in patients with multiple myeloma who have relapsed after one to three prior therapies. The study met the primary endpoint of improving progression free survival. [Genmab A/S]
Kura Oncology, Inc. announced that the first patient has been dosed in a Phase I clinical trial of KO-539, the company’s first-in-class inhibitor of the menin-mixed lineage leukemia (menin-MLL) interaction, in patients with relapsed or refractory acute myeloid leukemia. [Kura Oncology, Inc.]
GT Biopharma, Inc. announced that it notified the FDA that it was commencing enrollment in its first-in-human GTB-3550 Phase I/II clinical trial. [GT Biopharma, Inc.]
Celgene Corporation announced top-line results from the international Phase III, randomized, double-blind, placebo-controlled study, QUAZAR AML-001. The study evaluated the efficacy and safety of investigational therapy CC-486 as maintenance therapy in patients with newly diagnosed acute myeloid leukemia (AML) who achieved first complete response or complete response with incomplete blood count recovery with induction chemotherapy. [Celgene Corporation]
A Senate spending panel today released a draft 2020 spending bill containing a hefty $3 billion increase for the National Institutes of Health (NIH) that would bring the agency’s total budget to $42.1 billion. That 7.7% boost is $1 billion more than a House of Representatives committee approved in its version of the bill in April, and would amount to a 40% increase in NIH’s budget over the past 5 years. [ScienceMagazine]
A project that included funders backing Plan S, the European-led effort to speed the transition to open access, released a set of contract templates and tips meant to help small, independent publishers reach deals with libraries that would eventually eliminate subscriptions while protecting revenue. [ScienceInsider]
After months of outcry over whether the United States government is unfairly targeting foreign-born researchers over purported security breaches, President Donald Trump’s science adviser is launching an effort to strengthen national policies on research security. [Nature News]
NEW Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges
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