|Cancer Stem Cell News 7.41 October 17, 2018
Researchers interrogated compounds that targeted HK2 effectively and restricted tumor growth in cell lines, patient derived glioma stem cells, and mouse models of GBM. A screen identified the azole class of antifungals as inhibitors of tumor metabolism. Treatment of mice bearing GBM with Ketoconazole and Posaconazole increased their survival, reduced tumor cell proliferation, and decreased tumor metabolism. [Clin Cancer Res]
Genetic probes showed that mouse glioblastoma (GBM)-derived circulating tumor cells (CTC) exhibited Sox2/ETn transcriptional activation and expressed glioma CSC markers, consistent with robust expression of stemness-associated genes including SOX2, OCT4, and NANOG in human GBM patient-derived samples containing CTC. Wnt activation induced stemness and chemoresistance in CTC. [Cancer Res]
Phospholipase D2 (PLD2) was overexpressed in colon tumors and was secreted by cancer cells, inducing senescence in neighboring fibroblasts. Senescence induced by its product, phosphatidic acid, led to a senescence-associated secretory phenotype able to increase the stem properties of cancer cells. [Oncogene]
Knockdown of CD24 attenuated cancer stemness properties. High-CD24-expressing cells, isolated from patient-derived urothelial carcinoma of the bladder (UCB) xenograft tumors, exhibited enhanced stemness properties. CD24 was overexpressed not only in primary tumors, but also in urine from UCB subjects. [Br J Cancer]
Inhibitors of farnesyl diphosphate synthase (FDPS), such as alendronate and zoledronate, significantly reduced the formation of glioblastoma spheres, and alendronate was effective at a lower molar concentration than zoledronate. Knockdown of FDPS using short hairpin RNA completely inhibited the formation of secondary spheres. [Exp Mol Med]
When microglia-induced growth arrest specific 1 (Gas1)-expressing brain tumor-initiating cells (BTICs) were implanted intra-cranially in mice, tumor growth was markedly decreased; this was mirrored in the remarkable increase in survival of mGas1-BT025 and mGas1-BT048 implanted mice, compared to mice implanted with non-microglia-exposed BTICs. [Sci Rep]
Researchers identified transcriptional repressor GATA binding 1, an atypical GATA-type transcription factor, as a critical transcriptional regulator that repressed SRY-box 2 expression and thereby suppressed cancer stemness and tumorigenesis. [J Biol Chem]
Downregulation of glioma-associated oncogene homolog 1 (GLI1) by inhibitor treatment in colorectal adenocarcinoma cell lines resulted in reduced expression of CSC markers, cell clonogenicity, S-phase subpopulations, as well as the migration and invasion ability. Akt inhibitor, Perifosine, significantly inhibited the expression of pAkt and GLI1 in colorectal adenocarcinoma cells. [Exp Cell Res]
Scientists found that NFκB inhibition by specific inhibitor JSH23 or siRNA targeting subunit p65 dramatically impaired the induction of ovarian cancer stem cells by HER2, indicating that NFκB mediated HER2-induced ovarian cancer stem cells. [Biosci Rep]
The authors summarize recent advances in our understanding of the metabolic phenotypes of cancer cells and CSCs and how these processes are affected by the tumor microenvironment (TME). They also discuss how the evolving TME modulates tumor cells and CSCs in cancer progression. [Semin Cancer Biol]
Despite progress in the research of new therapeutic targets and compounds, resistant cells displaying stem-like properties seem to play a leading role in therapeutic failures and to be the culprit cells responsible for associated tumor recurrence. A whole new plethora of research studies suggest that drug-tolerant cancer stem cells may be induced by conventional cancer chemotherapeutics such as doxorubicin, cisplatinum and ionizing radiation. [Pharmacol Res]
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Six researchers at Washington University in St. Louis have received funding from the Longer Life Foundation — a cooperative effort between the School of Medicine and the Reinsurance Group of America — that helps junior investigators launch research projects and assists more established researchers as they extend their investigations into new areas. [Washington University School of Medicine in St. Louis]
AIVITA Biomedical announced the successful completion of the manufacturing quality consultation and clinical safety consultation for its patient-specific cancer immunotherapy with the Japanese regulatory agency, Pharmaceutical and Medical Devices Agency (PMDA). [AIVITA Biomedical]
Beset by economic woes and dissatisfied with the left-wing politicians in power for most of the past 15 years, Brazil appears poised to make a hard turn and elect a far-right candidate, Jair Bolsonaro, as its next president. His rapid ascent has unnerved local researchers, who worry about the future of Brazilian science, the protection of the country’s biodiversity, and its role in the global struggle against climate change. [ScienceInsider]
Shekhar Mande, a structural biologist, took over as director-general of India’s Council of Scientific and Industrial Research (CSIR), headquartered in New Delhi, which operates a network of 40 research labs around the country. Mande is the first outsider to take on the top job at CSIR since 1984. [ScienceInsider]
A proposal by the Chinese government to create a national blacklist of journals is creating much debate among the country’s scientists, who are still waiting for the list to be revealed, five months after the plan to create it was announced. [Nature News]
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