|Cancer Stem Cell News 6.15 April 19, 2017|
Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSCs). To validate this hypothesis in vivo, investigators developed a clinically relevant chemotherapeutic approach treating patient-derived xenograft with cytarabine. Cytarabine residual AML cells are enriched neither in immature, quiescent cells nor LSCs. [Cancer Discov]
The authors showed how breast cancer progression is facilitated by IL-4 secreted by adipose tissue and estrogen receptor-positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL-4 signaling with the IL-4Rα antagonist IL-4DM compromised breast cancer cell proliferation, invasion and tumor growth by downregulating MAPK pathway activity. [Cancer Res]
Researchers provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent in malignant glioma, increased NOTCH activity in brain tumor-initiating cells (BTICs) to promote their growth. They demonstrated the proximal localization of TNC and BTICs in human glioblastoma specimens, and in the brains of mice implanted with human BTIC intracranial xenografts. [Cancer Res]
To better understand the role of modified progesterone receptors (PRs) in breast cancer, scientists measured total and phospho-Ser294 PRs in 209 human breast tumors represented on 2754 individual tissue spots within a tissue microarray and assayed the regulation of this site in human tumor explants cultured ex vivo. They concluded that PR Ser294 phosphorylation is a common event in breast cancer progression that is required to maintain breast cancer stem cell fate. [J Hematol Oncol]
Head and neck squamous cell carcinoma (HNSCC) are resistant to standard treatments, partly due to cancer stem cells (CSCs) localized in hypoxic niches. Two HNSCC cell lines and their CSC sub-populations were studied in response to photons or carbon ion irradiation, in normoxia or hypoxia, after inhibition or not of hypoxia-inducible factor-1α (HIF-1α). Under hypoxia, compared to non-CSCs, HIF-1α was expressed earlier in CSCs. [Br J Cancer]
Investigators explored the specific role of PBX3 and its associated regulatory network in leukemia progression. They found that Pbx3 deletion significantly prolonged the survival of leukemic mice and decreased the leukemia burden by decreasing the capacity of leukemia stem cells (LSCs) and promoting LSC apoptosis. [Int J Cancer]
Researchers found that cisplatin, but not paclitaxel and doxorubicin, induced the enrichment of cancer stem cells (CSCs) and conferred multidrug resistance in non-small cell lung cancer cell lines. In vivo study confirmed that drug-resistant tumors displayed enhanced expressions of CSC transcription factors. [Cell Death Dis]
Scientists report the discovery of a molecular interaction between WDR79 and USP7 and showed its functional significance in linking the Mdm2-p53 pathway to the proliferation of non-small cell lung cancer (NSCLC) cells. They found that WDR79 colocalized and interacted with USP7 in the nucleus of NSCLC cells. [Cell Death Dis]
Oct4A is a well-established marker for cancer stem cell (CSC) in malignancies. In an effort to understand the regulatory role of Oct4A in tumor biology, the authors employed the use of an ovarian cancer shRNA Oct4A knockdown cell line (HEY) and a global mass spectrometry-based proteomic analysis to investigate novel biological targets of Oct4A in HEY samples. [Sci Rep]
Glioblastoma stem-like cells are a promising target for glioblastoma (GBM) treatment. Researchers identified the cellular prion protein and its partner, the co-chaperone Hsp70/90 organizing protein, as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance. They observed that, when GBM cells are cultured as neurospheres, they express specific stemness markers such as CD133, CD15, Oct4, and SOX2. [Stem Cell Res Ther]
Human colorectal tumors and human colon cancer cells express a novel short isoform of DCLK1 (DCLK1-S) from β-promoter of human DCLK1 gene, while normal colons express long isoform (DCLK1-L) from 5′(α)-promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells (CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino acids, scientists succeeded in generating a monospecific DCLK1-S-antibody, which did not cross-react with DCLK1-L, and specifically detected CSCs. [Lab Invest]
Metformin, a first-line drug for type 2 diabetes mellitus, was demonstrated to target breast cancer stem cells selectively. Investigators demonstrated that metformin decreased the percentage of triple-negative breast cancer (TNBC) stem cells partially through the downregulation of the expression of the stem cell transcription factor Krüppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines. [Cell Discov]
The authors discuss the role of malignant RNA processing in cancer stem cell (CSC) generation and maintenance, including mechanisms of RNA methylation, RNA editing and RNA splicing, and the functional consequences of their aberrant regulation in human malignancies. They highlight the potential of these events as novel CSC biomarkers as well as therapeutic targets. [Nat Rev Cancer]
Scientists consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. They discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them. [NPJ Breast Cancer]
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Zhou, principal investigator on a new $1.7 million grant from the National Cancer Institute, studies how in response to some powerful chemotherapy agents, the body can begin to produce myeloid-derived suppressor cells that typically help calm the immune response. [Augusta University]
OncoMed Pharmaceuticals, Inc. reported top-line results from the company’s randomized 145-patient Phase II PINNACLE clinical trial of tarextumab in combination with etoposide plus either cisplatin or carboplatin chemotherapy in previously untreated patients with extensive-stage small cell lung cancer. The trial did not meet its primary endpoint of progression-free survival or secondary endpoints of overall survival and biomarkers reflective of Notch pathway gene activation. [OncoMed Pharmaceuticals, Inc.]
Cellectar Biosciences, Inc. announced the Japanese Patent Office has granted a method of use patent for two of the company’s phospholipid drug conjugates, CLR 131, the company’s lead compound, and CLR 125, each in combination with radiation and/or other therapies to treat cancer stem cells. [Cellectar Biosciences, Inc.]
Regen BioPharma Inc., in conjunction with its medicinal chemistry partner, ChemDiv, Inc., has identified three new series of compounds that activate NR2F6. These compounds are small molecules and were identified using Regen’s patented screening methodology and unique chemical libraries. [Regen BioPharma Inc. (PR Newswire Association LLC.)]
Theresa May’s plan to hold a general election on the 8th of June raises implications for universities in terms of whether the Higher Education and Research Bill can continue, the vote’s status as the “Brexit election”, and the expected emergence of Labor’s plan to scrap tuition fees. [Times Higher Education]
Conservative academics face a growing tension between their politics and the liberal atmosphere on many US campuses. [Nature News]
For scientists in France, the presidential contest is often a chance to debate research and science-related issues. When Nicolas Sarkozy was elected a decade ago, for example, university reforms and environmental policy featured prominently in the campaigns. But this time, science has barely been mentioned — elbowed out by political scandals and the rise of Marine Le Pen’s far-right Front National party. [Nature News]
Almost every scientist agrees: Applying for research funding is a drag. Writing a good proposal can take months, and the chances of getting funded are often slim. Funding agencies, meanwhile, spend more and more time and money reviewing growing stacks of applications. That’s why two researchers are proposing a radically different system that would do away with applications and reviews; instead scientists would just give each other money. [ScienceInsider]
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