|Cancer Stem Cell News 5.49 December 14, 2016|
By comparing differentially expressed genes affected by non-CG methylation between tumor and corresponding non-tumor tissues in oesophageal squamous cell carcinoma, researchers found that Integrin α7 was characterized as a cancer stem cell marker. [Nat Commun]
Using both human and murine models of cancer stem cells (CSCs), scientists demonstrated that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate limiting enzyme in the NAD+ synthesis pathway nicotinamide phosphoribosyltransferase and the transcription factor POU5F1/OCT4. [Autophagy]
Investigators established libraries of glioma-initiating cell clones from patient samples and found extensive molecular and phenotypic variability among clones, including a range of responses to radiation and drugs. The widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-mesenchymal shift in the transcriptome. [Cell Rep]
Shp2/Ptpn11 is a proto-oncogene in hematopoietic cells and antagonizes the effect of tumor suppressor Pten in leukemogenesis. In contrast, the authors showed cooperative functions of Shp2 and Pten in suppressing hepatocarcinogenesis. [Cell Rep]
Basal mammalian target of rapamycin complex 1 (mTORC1) activity and its kinetics were investigated by scientists in brain tumor stem cell (BTSC) clones isolated from patients with glioblastoma and their differentiated progenies (DIFFs). BTSCs presented lower basal mTORC1 activity under each culture condition tested and a more rapid decline of mTORC1 activity after nutrient deprivation than observed in DIFFs. [Neuro Oncol]
Researchers examined the relationship between the presence of cancer stem cells at the invasive tumor front and prognosis in gastric cancer. CD44-positive cancer stem-like cells at the invasive tumor front indicated poor survival. [Br J Cancer]
Scientists reported that Oct4, Klf4, Sox2 and c-myc expression positively associated with AFP(+)/HBV(+) hepatocellular carcinoma (HCC) tissues, and the expression of the stemness markers CD44, CD133 and EpCAM was significantly higher in AFP(+)/HBV(+) HCC tissues compared to normal liver tissues or AFP(–)/HBV(–) HCC tissues. [Int J Cancer]
Researchers examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics. Their results showed that lung cancer stem cells (LCSCs) were more stem-like than differentiated LCSCs, and they displayed higher cell viability upon cisplatin treatment, confirming their drug resistance property. [Br J Pharmacol]
The authors demonstrated that BIX01294, an inhibitor of a G9a histone methyltransferase triggers autophagy in human glioma cells. BIX01294 treatment upregulates the expression of autophagy and differentiation-related genes in glioma stem-like cells. [Sci Rep]
Investigators developed a novel nondrug delivery system for the dual targeting of cancer stem cells (CSCs) by conjugating hyaluronic acid and grafting the doublecortin-like kinase 1 (DCLK1) monoclonal antibody to the surface of poly(ethylene glycol)–poly(d,l-lactide-co-glycolide) nanoparticles, which can specifically target CD44 receptors and the DCLK1 surface marker – the latter was shown to possess the capacity to distinguish between CSCs and normal stem cells. [Int J Nanomedicine]
Researchers simulated on cycle of environmental conditions to study reversibility by first generating floating tumorspheres from lung and breast cancer cells by culturing them in serum-free media without the addition of any external mitogenic stimulation, and subsequently re-incubating them back in serum-containing media to simulate routine culture conditions. [J Cell Physiol]
Scientists investigated neuroendocrine cells expressing somatostatin (SST) and somatostatin receptor type 1 (SSTR1) because SST inhibits intestinal proliferation. In colorectal cancer cell lines, the proportion of ALDH+ cells inversely correlates with proportion of SSTR1+ cells and with rate of proliferation and sphere-formation. [BMC Cancer]
The authors outline the role and function of aldehyde dehydrogenase (ALDH) activity in multiple cellular functions and in cancer stem cells (CSCs) and focus on the role of retinoic acid, one of the products of ALDH isozymes. They conclude with summary of the findings and potential impact of published studies on future use of RAs in the targeting of CSCs and drug resistance. [Cancer Chemother Pharmacol]
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Novartis announced additional analyses from the Phase III MONALEESA-2 study that show LEE011 plus letrozole significantly prolonged progression-free survival (PFS) across pre-planned patient subgroups with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2–) advanced or metastatic breast cancer, including post-menopausal women diagnosed de novo, those with visceral liver and lung metastases, and those with bone-only disease. [Press release from Novartis discussing research presented at 2016 San Antonio Breast Cancer Symposium, San Antonio]
The John Theurer Cancer Center at Hackensack University Medical Center is partnering with the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute as they launch a major collaboration focused on neoantigens, unique cancer markers that researchers believe may hold the key to developing targeted cancer immunotherapies. [The John Theurer Cancer Center]
AstraZeneca and its global biologics research and development arm, MedImmune, announced that the US Food and Drug Administration (FDA) has accepted the first Biologics License Application for durvalumab, a PD-L1 human monoclonal antibody, and granted priority review status with a Prescription Drug User Fee Act set for the second quarter of 2017. [AstraZeneca]
Scientists working for the Canadian government have successfully negotiated a clause in their new contract that guarantees their right to speak to the public and the media about science and their research, without needing approval from their managers. [ScienceInsider]
In early 2013, scientists working in a laboratory led by a prominent cancer researcher at the University of British Columbia (UBC) in Vancouver, Canada, were getting worried. They were unable to reproduce results from several of the researcher’s experiments, and suspected some of the original work was fraudulent. An investigation by UBC ultimately confirmed their fears: In 2014, investigators identified 29 instances of scholarly misconduct, 16 of them “serious,” including falsification and fabrication of data, according to university correspondence obtained by Retraction Watch. [ScienceInsider]
Around the world, individual researchers and representatives of scientific societies are signing letters of protest or advice, offering to counsel Trump’s transition team and ramping up efforts to communicate the value of science to the public. [Nature News]
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