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https://www.readbyqxmd.com/read/29761897/chronic-ethanol-exposure-of-human-pancreatic-normal-ductal-epithelial-cells-induces-cancer-stem-cell-phenotype-through-satb2
#1
Wei Yu, Yuming Ma, Sharmila Shankar, Rakesh K Srivastava
The incidence of pancreatic cancer is on the rise. Risk factors for pancreatic cancer include alcohol toxicity and metabolic conditions such as obesity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes. However, the molecular mechanism by which chronic alcohol consumption contributes to pancreatic cancer is not well understood. The purpose of the study was to demonstrate the effects of long-term chronic ethanol exposure on the transformation of human pancreatic normal ductal epithelial (HPNE) cells...
May 15, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29716922/meis1-and-meis2-expression-and-prostate-cancer-progression-a-role-for-hoxb13-binding-partners-in-metastatic-disease
#2
Raj R Bhanvadia, Calvin VanOpstall, Hannah Brechka, Nimrod S Barashi, Marc Gillard, Erin M McAuley, Juan Apiz, Gladell P Paner, Wen-Ching Chan, Jorge Andrade, Angelo Demarzo, Misop Han, Russell Z Szmulewitz, Donald J Vander Griend
PURPOSE: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS-HOX interactions in prostate cancer etiology and progression.  The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. EXPERIMENTAL DESIGN: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691253/the-inhibitory-nkr-p1b-clr-b-recognition-axis-facilitates-detection-of-oncogenic-transformation-and-cancer-immunosurveillance
#3
Miho Tanaka, Jason H Fine, Christina L Kirkham, Oscar A Aguilar, Antoaneta Belcheva, Alberto Martin, Troy Ketela, Jason Moffat, David Sj Allan, James R Carlyle
Natural killer (NK) cells express receptors specific for MHC class I (MHC-I) molecules involved in "missing-self" recognition of cancer and virus-infected cells. Here we elucidate the role of MHC-I-independent NKR-P1B:Clr-b interactions in the detection of oncogenic transformation by NK cells. Ras oncogene overexpression was found to promote a real-time loss of Clr-b on mouse fibroblasts and leukemia cells, mediated in part via the Raf/MEK/ERK and PI3K pathways. Ras-driven Clr-b downregulation occurred at the level of the Clrb (Clec2d) promoter, nascent Clr-b transcripts, and cell surface Clr-b protein, in turn promoting missing-self recognition via the NKR-P1B inhibitory receptor...
April 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/29684900/generation-of-the-human-induced-pluripotent-stem-cell-hipsc-line-psmi003-a-from-a-patient-affected-by-an-autosomal-recessive-form-of-long-qt-syndrome-type-1
#4
Manuela Mura, Monia Ginevrino, Rita Zappatore, Federica Pisano, Marina Boni, Silvia Castelletti, Lia Crotti, Enza Maria Valente, Peter J Schwartz, Massimiliano Gnecchi
We generated human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a 51years old female patient homozygous for the mutation c.535 G>A p.G179S on the KCNQ1 gene, causing a severe form of autosomal recessive Long QT Syndrome type 1 (AR-LQT1), not associated with deafness. The hiPSCs, generated using four retroviruses each encoding for a reprogramming factor OCT4, SOX2, KLF4, cMYC, are pluripotent and can differentiate into spontaneously beating cardiomyocytes (hiPSC-CMs).
April 6, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29677589/generation-of-the-human-induced-pluripotent-stem-cell-hipsc-line-psmi002-a-from-a-patient-affected-by-the-jervell-and-lange-nielsen-syndrome-and-carrier-of-two-compound-heterozygous-mutations-on-the-kcnq1-gene
#5
Manuela Mura, Yee-Ki Lee, Monia Ginevrino, Rita Zappatore, Federica Pisano, Marina Boni, Federica Dagradi, Lia Crotti, Enza Maria Valente, Peter J Schwartz, Hung-Fat Tse, Massimiliano Gnecchi
We report the generation of human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a female patient carrier of the two compound heterozygous mutations c.568 C>T p.R190W (maternal allele), and c.1781 G>A p.R594Q (paternal allele) on the KCNQ1 gene, causing Jervell and Lange-Nielsen Syndrome (JLNS). To obtain hiPSCs, we used the classical approach of the four retroviruses each encoding for a reprogramming factor OCT4, SOX2, KLF4, cMYC. The obtained hiPSC clones display pluripotent stem cell characteristics, and differentiate into spontaneously beating cardiomyocytes (hiPSC-CMs)...
April 7, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29668843/effects-of-catecholamines-on-secretion-of-interferon-tau-and-expression-of-genes-for-synthesis-of-polyamines-and-apoptosis-by-ovine-trophectoderm
#6
Mohammed A Elmetwally, Yasser Lenis, Wanjin Tang, Guoyao Wu, Fuller W Bazer
Ovine trophectoderm (oTr1) cells were used to investigate effects of epinephrine (EP), norepinephrine (NE) and dopamine (DA) on their proliferation, migration and adhesion, secretion of interferon tau (IFNT), and expression of genes for synthesis of polyamines and apoptosis. Expression of mRNAs for agmatinase (AGMAT), arginine decarboxylase (ADC), ornithine decarboxylase (ODC1) and solute carrier family 7 (SLC7A1) cationic amino acid transporter, Y + system), member 1 increased (P < 0.05) in oTr1 cells in response to EP and DA...
April 12, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29664669/primary-nonsecretory-plasma-cell-leukemia-with-multiple-chromosomal-abnormalities-a-case-report
#7
Satoshi Nakayama, Tomohiro Oda, Shinya Minabe, Yukiharu Bamba, Haruko Ukawa, Rika Sato, Masaki Kawabata, Toshikatsu Horiuchi, Junichi Watanabe, Fumihiko Kimura, Hideyuki Shimazaki, Sho Ogata, Kuniaki Nakanishi
Primary nonsecretory plasma cell leukemia (PCL) is an extremely rare type of multiple myeloma. Here, we report a case of nonsecretory PCL with no previous history of multiple myeloma. The case exhibited extremely low levels of serum immunoglobulin and light chain, no detectable serum M-protein or free light chain restriction, no urine BJP, and no cytoplasmic light chain expression in flow cytometry. In fluorescence in situ hybridization, tumor cells exhibited fusion genes for IgH/BCL1 and IgH/cMyc, disappearance of the p53 signal, and a split signal for IgK(2p11), but no split signal for IgL (22q11)...
January 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/29644074/acquisition-of-pluripotency-in-the-chick-embryo-occurs-during-intrauterine-embryonic-development-via-a-unique-transcriptional-network
#8
Jae Yong Han, Hyo Gun Lee, Young Hyun Park, Young Sun Hwang, Sang Kyung Kim, Deivendran Rengaraj, Byung Wook Cho, Jeong Mook Lim
Background: Acquisition of pluripotency by transcriptional regulatory factors is an initial developmental event that is required for regulation of cell fate and lineage specification during early embryonic development. The evolutionarily conserved core transcriptional factors regulating the pluripotency network in fishes, amphibians, and mammals have been elucidated. There are also species-specific maternally inherited transcriptional factors and their intricate transcriptional networks important in the acquisition of pluripotency...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29568390/characterization-of-brain-tumor-initiating-cells-isolated-from-an-animal-model-of-cns-primitive-neuroectodermal-tumors
#9
Sergey Malchenko, Simone T Sredni, Jerusha Boyineni, Yingtao Bi, Naira V Margaryan, Maheedhara R Guda, Yulia Kostenko, Tadanori Tomita, Ramana V Davuluri, Kiran Velpula, Mary J C Hendrix, Marcelo B Soares
CNS Primitive Neuroectodermal tumors (CNS-PNETs) are members of the embryonal family of malignant childhood brain tumors, which remain refractory to current therapeutic treatments. Current paradigm of brain tumorigenesis implicates brain tumor-initiating cells (BTIC) in the onset of tumorigenesis and tumor maintenance. However, despite their significance, there is currently no comprehensive characterization of CNS-PNETs BTICs. Recently, we described an animal model of CNS-PNET generated by orthotopic transplantation of human Radial Glial (RG) cells - the progenitor cells for adult neural stem cells (NSC) - into NOD-SCID mice brain and proposed that BTICs may play a role in the maintenance of these tumors...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29562912/gas5-is-an-essential-lncrna-regulator-for-self-renewal-and-pluripotency-of-mouse-embryonic-stem-cells-and-induced-pluripotent-stem-cells
#10
Jiajie Tu, Geng Tian, Hoi-Hung Cheung, Wei Wei, Tin-Lap Lee
BACKGROUND: The regulatory role of long noncoding RNAs (lncRNAs) have been partially proved in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). METHODS: In the current study, we investigated mouse ESC (mESC) self-renewal, differentiation, and proliferation in vitro by knocking down a lncRNA, growth arrest specific 5 (Gas5). A series of related indicators were examined by cell counting kit-8 (CCK-8) assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, alkaline phosphatase staining, propidium iodide (PI) staining, Annexin V staining, competition growth assay, immunofluorescence, and chromatin immunoprecipitation (ChIP)-qPCR...
March 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29555554/timeless-is-a-novel-estrogen-receptor-co-activator-involved-in-multiple-signalling-pathways-in-mcf-7-cells
#11
Chantal Beatrice Magne Nde, Gloria Casas Gimeno, Maria Docanto, Kevin C Knower, Morag J Young, Jakob Buehn, Edris Sayed, Colin D Clyne
Activation of oestrogen receptor α (ERα) stimulates cell division and tumour growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homologue of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator...
March 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29545399/specificity-protein-transcription-factors-and-cancer-opportunities-for-drug-development
#12
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29527004/microrna-155-positively-regulates-glucose-metabolism-via-pik3r1-foxo3a-cmyc-axis-in-breast-cancer
#13
Sinae Kim, Eunji Lee, Jaeyun Jung, Jong Won Lee, Hee Jung Kim, Jisun Kim, Hyun Ju Yoo, Hee Jin Lee, Sun Young Chae, Sang Min Jeon, Byung Ho Son, Gyungyup Gong, Shyam K Sharan, Suhwan Chang
MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway...
March 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29506416/precise-nanoinjection-delivery-of-plasmid-dna-into-a-single-fibroblast-for-direct-conversion-of-astrocyte
#14
Hang-Soo Park, Hyosung Kwon, Jewon Yu, Yeonju Bae, Jae-Yong Park, Kyung-Ah Choi, Yeonho Choi, Sunghoi Hong
Direct conversion is a powerful approach to safely generate mature neural lineages with potential for treatment of neurological disorders. Astrocytes play a crucial role in neuronal homeostasis and their dysfunctions contribute to several neurodegenerative diseases. Using a single-cell approach for precision, we describe here a robust method using optimized DNA amounts for the direct conversion of mouse fibroblasts to astrocytes. Controlled amount of the reprogramming factors Oct4, Sox2, Klf4 and cMyc was directly delivered into a single fibroblast cell...
March 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29471262/generation-of-a-human-ipsc-line-iishdoi002-a-with-a-46-xy-47-xyy-mosaicism-and-belonging-to-an-african-mitochondrial-haplogroup
#15
María Del Carmen Ortuño-Costela, Ana Moreno-Izquierdo, Rafael Garesse, M Esther Gallardo
We have generated a human iPSC line, IISHDOi002-A, from commercial primary normal human dermal fibroblasts belonging to an African mitochondrial haplogroup (L3), and with a 46, XY/47, XYY mosaicism. For this purpose, reprogramming factors Oct3/4, Sox2, Klf4 and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus.
April 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29466855/nano-assembly-of-pamitoyl-bioconjugated-coenzyme-a-for-combinatorial-chemo-biologics-in-transcriptional-therapy
#16
Santosh K Misra, Taylor L Kampert, Dipanjan Pan
Pathogenesis, the biological mechanism that leads to the diseased state, of many cancers is driven by interruptions to the role of Myc oncoprotein, a regulator protein that codes for a transcription factor. One of the most significant biological interruptions to Myc protein is noted as its dimerization with Max protein, another important factor of family of transcription factors. Binding of this heterodimer to E-Boxes, enhancer boxes as DNA response element found in some eukaryotes that act as a protein-binding site and have been found to regulate gene expression, are interrupted to regulate cancer pathogenesis...
April 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29453128/generation-of-a-human-ipsc-line-from-a-patient-with-congenital-glaucoma-caused-by-mutation-in-cyp1b1-gene
#17
Arantxa Bolinches-Amorós, Dunja Lukovic, Ana Artero Castro, Marian León, Kunka Kamenarova, Radka Kaneva, Pavla Jendelova, Fiona Blanco-Kelly, Carmen Ayuso, Marta Cortón, Slaven Erceg
The human iPSC cell line, GLC-FiPS4F1 (ESi047-A), derived from dermal fibroblast from the patient with congenital glaucoma caused by the mutation of the gene CYP1B1, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors.
April 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29444438/commonly-occurring-cell-subsets-in-high-grade-serous-ovarian-tumors-identified-by-single-cell-mass-cytometry
#18
Veronica D Gonzalez, Nikolay Samusik, Tiffany J Chen, Erica S Savig, Nima Aghaeepour, David A Quigley, Ying-Wen Huang, Valeria Giangarrà, Alexander D Borowsky, Neil E Hubbard, Shih-Yu Chen, Guojun Han, Alan Ashworth, Thomas J Kipps, Jonathan S Berek, Garry P Nolan, Wendy J Fantl
We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29422234/an-overview-of-type-2-diabetes-and-importance-of-vitamin-d3-vitamin-d-receptor-interaction-in-pancreatic-%C3%AE-cells
#19
REVIEW
Abraham Neelankal John, Fang-Xu Jiang
One significant health issue that plagues contemporary society is that of Type 2 diabetes (T2D). This disease is characterised by higher-than-average blood glucose levels as a result of a combination of insulin resistance and insufficient insulin secretions from the β-cells of pancreatic islets of Langerhans. Previous developmental research into the pancreas has identified how early precursor genes of pancreatic β-cells, such as Cpal, Ngn3, NeuroD, Ptf1a, and cMyc, play an essential role in the differentiation of these cells...
April 2018: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29281720/reversible-dual-inhibitor-against-g9a-and-dnmt1-improves-human-ipsc-derivation-enhancing-met-and-facilitating-transcription-factor-engagement-to-the-genome
#20
Juan Roberto Rodriguez-Madoz, Edurne San Jose-Eneriz, Obdulia Rabal, Natalia Zapata-Linares, Estibaliz Miranda, Saray Rodriguez, Angelo Porciuncula, Amaia Vilas-Zornoza, Leire Garate, Victor Segura, Elizabeth Guruceaga, Xabier Agirre, Julen Oyarzabal, Felipe Prosper
The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods...
2017: PloS One
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