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https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#1
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28628306/lysine-deacetylation-by-hdac6-regulates-the-kinase-activity-of-akt-in-human-neural-progenitor-cells
#2
Jonathan Iaconelli, Jasmin Lalonde, Bradley Watmuff, Bangyan Liu, Ralph Mazitschek, Stephen J Haggarty, Rakesh Karmacharya
AKT family of serine-threonine kinases functions downstream of phosphatidylinositol 3-kinase (PI3K) to transmit signals by direct phosphorylation of a number of targets, including the mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β) and β-catenin. AKT binds to phosphatidylinositol (3,4,5)-triphosphate (PIP3) generated by PI3K activation, which results in its membrane localization and subsequent activation through phosphorylation by phosphoinositide-dependent protein kinase 1 (PDK1)...
June 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28627604/the-c-terminus-domain-of-the-hepatitis-b-virus-x-protein-stimulates-the-proliferation-of-mouse-foetal-hepatic-progenitor-cells-although-it-is-not-required-for-the-formation-of-spheroids
#3
Liming Yu, Shu Chen, Na Luo, Song He
The hepatitis B virus X (HBx) protein is an important factor in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). The C-terminal region of HBx plays a major role in the replication of HBV. Notably, HBx promotes the expansion and tumourigenesis of hepatic progenitor cells (HPCs) in mice. However, it remains unclear as to whether the C-terminal region of HBx is required for the stimulation fo the proliferation of mouse foetal HPCs (FHPCs). In our study, we used EpCAM+, CD133+ and CD49f+ FHPCs, which are bipotential clonogenic cells...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627468/a-novel-chalcone-derivative-lqfm064-induces-breast-cancer-cells-death-via-p53-p21-kit-and-pdgfra
#4
Bruna Lannuce Silva Cabral, Artur Christian Garcia da Silva, Renato Ivan de Ávila, Alane Pereira Cortez, Rangel Magalhães Luzin, Luciano Morais Lião, Eric de Souza Gil, Gérman Sanz, Boniek G Vaz, José R Sabino, Ricardo Menegatti, Marize Campos Valadares
This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28626726/cancer-stem-cells-in-oral-cavity-squamous-cell-carcinoma-a-review
#5
REVIEW
Ranui Baillie, Swee T Tan, Tinte Itinteang
Cancer stem cells (CSCs) have been identified in oral cavity squamous cell carcinoma (OCSCC). CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells and cancer cells that drive tumor growth. Studies of many cancer types including OCSCC have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple CSC subtypes within OCSCC, making investigation reliant on the use of multiple markers...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28619754/antitumor-effect-of-the-atypical-retinoid-st1926-in-acute-myeloid-leukemia-and-nanoparticle-formulation-prolongs-lifespan-and-reduces-tumor-burden-of-xenograft-mice
#6
Leeanna El-Houjeiri, Walid Saad, Berthe Hayar, Patrick Aouad, Nadim Tawil, Rana Abdel-Samad, Rita Hleihel, Maguy Hamie, Angelo Mancinelli, Claudio Pisano, Hiba El Hajj, Nadine Darwiche
Acute myeloid leukemia (AML) is one of the most frequent types of blood malignancies. It is a complex disorder of undifferentiated hematopoietic progenitor cells. The majority of patients generally respond to intensive therapy. Nevertheless, relapse is the major cause of death in AML, warranting the need for novel treatment strategies. Retinoids have demonstrated potent differentiation and growth regulatory effects in normal, transformed and hematopoietic progenitor cells. All-trans retinoic acid (ATRA) is the paradigm of treatment in acute promyelocytic leukemia, an AML subtype...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28618670/re-low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#7
https://www.readbyqxmd.com/read/28615219/zfp521-regulates-murine-hematopoietic-stem-cell-function-and-facilitates-mll-af9-leukemogenesis-in-mouse-and-human-cells
#8
Brian S Garrison, Adrian P Rybak, Isabel Beerman, Balthasar Heesters, Francois E Mercier, David T Scadden, David Bryder, Roland Baron, Derrick J Rossi
The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521/Zfp521 as a conserved hematopoietic stem cell (HSC)-enriched transcription factor in human and murine hematopoiesis, whose function in HSC biology remains elusive...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28603917/a-rare-castration-resistant-progenitor-cell-population-is-highly-enriched-in-pten-null-prostate-tumors
#9
Lucila Sackmann Sala, Florence Boutillon, Giulia Menara, Andréa De Goyon-Pélard, Mylène Leprévost, Julie Codzamanian, Natalie Lister, Jan Pencik, Ashlee Clark, Nicolas Cagnard, Christine Bole-Feysot, Richard Moriggl, Gail P Risbridger, Renea A Taylor, Lukas Kenner, Jacques-Emmanuel Guidotti, Vincent Goffin
Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen-deprivation remain poorly described despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild-type (WT) mouse prostates a rare population of luminal progenitor cells that we called LSC(med) according to their FACS profile (Lin(-) /Sca-1(+) /CD49f(med) ). Here we investigated the prevalence and castration-resistance of LSC(med) in various mouse models of prostate tumorigenesis (Pb-PRL, Pten(pc-/-) , Hi-Myc mice)...
June 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28599319/regulation-of-human-glioblastoma-cell-death-by-combined-treatment-of-cannabidiol-%C3%AE-radiation-and-small-molecule-inhibitors-of-cell-signaling-pathways
#10
Vladimir N Ivanov, Jinhua Wu, Tom K Hei
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The challenging problem in cancer treatment is to find a way to upregulate radiosensitivity of GBM while protecting neurons and neural stem/progenitor cells in the brain. The goal of the present study was upregulation of the cytotoxic effect of γ-irradiation in GBM by non-psychotropic and non-toxic cannabinoid, cannabidiol (CBD). We emphasized three main aspects of signaling mechanisms induced by CBD treatment (alone or in combination with γ-irradiation) in human GBM that govern cell death: 1) CBD significantly upregulated the active (phosphorylated) JNK1/2 and MAPK p38 levels with the subsequent downregulation of the active phospho-ERK1/2 and phospho-AKT1 levels...
May 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598999/lymphatic-endothelial-progenitors-originate-from-plastic-myeloid-cells-activated-by-toll-like-receptor-4
#11
Lisa D Volk-Draper, Kelly L Hall, Andrew C Wilber, Sophia Ran
BACKGROUND: Myeloid-derived lymphatic endothelial cells (M-LECP) are induced by inflammation and play an important role in adult lymphangiogenesis. However, the mechanisms driving M-LECP differentiation are currently unclear. We previously showed that activation of Toll-like receptor-4 (TLR4) induces myeloid-lymphatic transition (MLT) of immortalized mouse myeloid cells. Here the goals were to assess the potential of different TLR4 ligands to induce pro-lymphatic reprogramming in human and mouse primary myeloid cells and to identify transcriptional changes regulating this process...
2017: PloS One
https://www.readbyqxmd.com/read/28591745/disc1-overexpression-promotes-non-small-cell-lung-cancer-cell-proliferation
#12
Shuo Wang, Ying-Ying Chen, Yu-Peng Li, Jun Gu, Shu-Dong Gu, Hai Shi, Xue-Song Li, Xiao-Ning Lu, Xiang Li, Shuang-Long Zhang, Kang-Jun Yu, Kun Liu, Li-Li Ji
Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/β-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and may promote neural progenitor cell and pancreatic β-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3β, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589491/synthesis-and-characterization-of-novel-bmi1-inhibitors-targeting-cellular-self-renewal-in-hepatocellular-carcinoma
#13
Monica Bartucci, Mohamed S Hussein, Eric Huselid, Kathleen Flaherty, Michele Patrizii, Saurabh V Laddha, Cindy Kui, Rachel A Bigos, John A Gilleran, Mervat M S El Ansary, Mona A M Awad, S David Kimball, David J Augeri, Hatem E Sabaawy
BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types. OBJECTIVE: We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC...
June 6, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28588728/maternal-embryonic-leucine-zipper-kinase-inhibits-epithelial-mesenchymal-transition-by-regulating-transforming-growth-factor-%C3%AE-signaling
#14
Jianjian Cheng, Binyu Qin, Bao Liu, Taibo Huang, Yuguang Li, Lijun Ma
Maternal embryonic leucine zipper kinase (MELK) performs an important role in self-renewal and proliferation of progenitor cells or tumor stem cells, and is expressed in aggressive cancers, contributing to tumorigenesis. However, the function of MELK in metastasis is unknown. In the present study, the lung cancer A549 cell line was utilized in order to study the role of MELK in epithelial-mesenchymal transitions (EMTs), the initial step of tumor metastasis. It was identified that transforming growth factor-β (TGF-β) could downregulate the expression of MELK, and that MELK could inhibit EMT by regulating TGF-β signaling...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28588019/enasidenib-induces-acute-myeloid-leukemia-cell-differentiation-to-promote-clinical-response
#15
Michael D Amatangelo, Lynn Quek, Alan Shih, Eytan M Stein, Mikhail Roshal, Muriel D David, Benoit Marteyn, Noushin Rahnamay Farnoud, Stephane de Botton, Olivier A Bernard, Bin Wu, Katharine E Yen, Martin S Tallman, Elli Papaemmanuil, Virginie Penard-Lacronique, Anjan Thakurta, Paresh Vyas, Ross L Levine
Recurrent mutations at R140 and R172 in isocitrate dehydrogenase 2 (IDH2) occur in many cancers, including ~12% of acute myeloid leukemia (AML). In preclinical models these mutations cause accumulation of the oncogenic metabolite R-2-hydroxyglutarate (2-HG) and induce hematopoietic differentiation block. Single-agent enasidenib (AG-221/CC-90007), a selective mutant IDH2 (mIDH2) inhibitor, produced an overall response rate of 40.3% in relapsed/refractory AML patients with mIDH2 in a phase 1 trial. However, its mechanism of action and biomarkers associated with response remain unclear...
June 6, 2017: Blood
https://www.readbyqxmd.com/read/28579318/the-zebrafish-kidney-mutant-zeppelin-reveals-that-brca2-fancd1-is-essential-for-pronephros-development
#16
Paul T Kroeger, Bridgette E Drummond, Rachel Miceli, Michael McKernan, Gary F Gerlach, Amanda N Marra, Annemarie Fox, Kristen K McCampbell, Ignaty Leshchiner, Adriana Rodriguez-Mari, Ruth BreMiller, Ryan Thummel, Alan J Davidson, John Postlethwait, Wolfram Goessling, Rebecca A Wingert
The zebrafish kidney is conserved with other vertebrates, making it an excellent genetic model to study renal development. The kidney collects metabolic waste using a blood filter with specialized epithelial cells known as podocytes. Podocyte formation is poorly understood but relevant to many kidney diseases, as podocyte injury leads to progressive scarring and organ failure. zeppelin (zep) was isolated in a forward screen for kidney mutants and identified as a homozygous recessive lethal allele that causes reduced podocyte numbers, deficient filtration, and fluid imbalance...
June 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28576946/flt3-inhibitors-in-acute-myeloid-leukemia-current-status-and-future-directions
#17
REVIEW
Maria Larrosa-Garcia, Maria R Baer
The receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3), involved in regulating survival, proliferation, and differentiation of hematopoietic stem/progenitor cells, is expressed on acute myeloid leukemia (AML) cells in most patients. Mutations of FLT3 resulting in constitutive signaling are common in AML, including internal tandem duplication (ITD) in the juxtamembrane domain in 25% of patients and point mutations in the tyrosine kinase domain in 5%. Patients with AML with FLT3-ITD have a high relapse rate and short relapse-free and overall survival after chemotherapy and after transplant...
June 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28573141/c-kit-positive-adipose-tissue-derived-mesenchymal-stem-cells-promote-the-growth-and-angiogenesis-of-breast-cancer
#18
Wenjie Li, Haiqian Xu, Cheng Qian
BACKGROUND: Adipose tissue-derived mesenchymal stem cells (ASCs) improve the regenerative ability and retention of fat grafts for breast reconstruction in cancer patients following mastectomy. However, ASCs have also been shown to promote breast cancer cell growth and metastasis. For the safety of ASC application, we aimed to identify specific markers for the subpopulation of ASCs that enhance the growth of breast cancer. METHODS: ASCs and bone marrow-derived vascular endothelial progenitor cells (EPCs) were isolated from Balb/c mice...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28561650/higher-level-pathway-objectives-of-epigenetic-therapy-a-solution-to-the-p53-problem-in-cancer
#19
Vamsidhar Velcheti, Tomas Radivoyevitch, Yogen Saunthararajah
Searches for effective yet nontoxic oncotherapies are searches for exploitable differences between cancer and normal cells. In its core of cell division, cancer resembles normal life, coordinated by the master transcription factor MYC. Outside of this core, apoptosis and differentiation programs, which dominantly antagonize MYC to terminate cell division, necessarily differ between cancer and normal cells, as apoptosis is suppressed by biallelic inactivation of the master regulator of apoptosis, p53, or its cofactor p16/CDKN2A in approximately 80% of cancers...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28560292/metaplasia-in-the-stomach-arises-from-gastric-chief-cells
#20
Jason C Mills, James R Goldenring
The development of intestinal-type gastric cancer is preceded by loss of parietal cells (oxyntic atrophy) and the induction of metaplastic cell lineages in the gastric mucosa. For example, mouse models have shown that spasmolytic polypeptide-expressing metaplasia can develop following oxyntic atrophy through transdifferentiation of zymogen-secreting chief cells. Evolution of spasmolytic polypeptide-expressing metaplasia from chief cells occurs via a coordinated dismantling of their secretory apparatus and reprogramming of their transcriptome...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
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