|Cancer Stem Cell News 8.35 September 11, 2019|
The authors found that the oncofetal HMGA2 gene was aberrantly re-expressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 was abundantly present in the cytoplasm, where it interacted with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. [Nat Commun]
Scientists performed a cell proliferation/death-based drug screening using 10,560 independent compounds. They identified DHODH as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays. [Neuro Oncol]
Researchers report that Slug promotes leukemogenesis and its loss impaired leukemia stem cell (LSC) self-renewal and delayed leukemia progression. Mechanistically, Slc13a3, a direct target of Slug in LSCs, restricted the self-renewal of LSCs and markedly prolonged recipient survival. [Leukemia]
Cancer genomic analysis identified frequent amplification of biquitin-specific proteas (USP)21 in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlated with human PDAC progression, and enforced expression of USP21 accelerated murine PDAC tumor growth and drove PanIN to PDAC progression in immortalized human pancreatic ductal cells. [Genes Dev]
Heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) modulated imatinib response of K562 cells and HNRPDL silencing sensitized CML CD34+ cells to imatinib treatment. Mechanistically, investigators found that the stability of pre-B-cell leukemia homeobox 1 (PBX1) mRNA was sustained by HNRPDL through its binding to a specific motif (ACUAGC) in 3′-untranslated region of PBX1. [Oncogene]
Scientists demonstrated that correlation expression of TRIM29 and ISG15 in pancreatic ductal adenocarcinomas. They demonstrated that TRIM29 knockdown destabilized ISG15 protein via promoting its processing by calpain 3. [Oncogene]
Researchers found that PN-1 was up-regulated in breast cancer, which promoted cell invasion, migration and stemness. Furthermore, by using specific inhibitors, they discovered that epidermal growth factor (EGF) up-regulated PN-1 in breast cancer cells through cascade activation of epidermal growth factor receptor to the activation of protein kinase Cδ, mitogen-activated protein kinase and extracellular signal-related kinase, which finally led to the up-regulation of early growth response protein 1. [Cell Death Dis]
Primary cultures from early-stage non-small cell lung cancer patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. [Cell Death Dis]
Investigators performed studies aimed to enhance the anti-medulloblastoma effects of alpelisib by simultaneous catalytic targeting of the mTOR kinase. Pharmacological mTOR inhibition potently enhanced the suppressive effects of alpelisib on cancer cell proliferation, colony formation and apoptosis and additionally blocked sphere-forming ability of medulloblastoma stem-like cancer cells in vitro. [Sci Rep]
miR-29a expression levels in glioblastoma cells, stem cells and human tumors as well as normal astrocytes and normal brain were measured by quantitative PCR. miR-29a targets were uncovered by target prediction algorithms, and verified by immunoblotting and 3′ UTR reporter assays. [J Neurooncol]
The authors review the current state of the literature regarding mechanisms of prostate (P)CSC radioresistance, promising PCSC markers and novel PCSC-specific therapeutic approaches and their implications in prostate cancer treatment and prognosis. [Cancer Lett]
Investigators provide an overview of the immunologically relevant molecular targets expressed on leukemic stem cells in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition, they discuss the current status of antibody-based therapies in these malignancies, their mode of action, and successful examples from the field. [Int J Mol Sci]
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Celyad announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 of the Phase I DEPLETHINK trial. [Celyad]
VBI Vaccines Inc. announced a collaboration with GlaxoSmithKline (GSK) to clinically evaluate the combination of VBI-1901, VBI’s cancer vaccine immunotherapeutic, with GSK’s proprietary AS01B adjuvant system. [VBI Vaccines Inc.]
Selvita announced that the first patient enrolled in the Phase Ib study of company’s selective CDK8 inhibitor, SEL120, has received the first dose. SEL120 is being initially investigated in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. [Selvita]
Fate Therapeutics, Inc. announced that the FDA has cleared the company’s Investigational New Drug (IND) application for FT596, the company’s first off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell cancer immunotherapy which targets multiple tumor-associated antigens. [Fate Therapeutics, Inc.]
Omeros Corporation announced that the FDA agreed with the company’s proposed schedule for the rolling review of the Biologics License Application (BLA) for narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy. [Omeros Corporation]
Mariya Gabriel, a conservative politician from Bulgaria, is slated to become the next European research chief- although her job title, unlike that of her predecessors, doesn’t include the words “research” or “science.” Some researchers and science policy experts worry the new job title could signal a reduced standing for science within von der Leyen’s proposed executive branch for the European Union, made up of 26 commissioners. [ScienceMagazine]
The US Environmental Protection Agency (EPA) in Washington, DC, announced September 10th that it will stop conducting or funding studies on mammals by 2035. The move, which is already eliciting strong reactions from groups supporting or opposing experiments on animals, makes EPA the first federal agency to put a hard deadline on phasing out animal research. [Science Magazine]
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