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https://www.readbyqxmd.com/read/28903422/cdk4-6-inhibition-is-more-active-against-the-glioblastoma-proneural-subtype
#1
Ming Li, Aizhen Xiao, Desiree Floyd, Inan Olmez, Jeongwu Lee, Jakub Godlewski, Agnieszka Bronisz, Krishna P L Bhat, Erik P Sulman, Ichiro Nakano, Benjamin Purow
Glioblastoma (GBM) is the most common and lethal brain tumor. Gene expression profiling has classified GBM into distinct subtypes, including proneural, mesenchymal, and classical, and identifying therapeutic vulnerabilities of these subtypes is an extremely high priority. We leveraged The Cancer Genome Atlas (TCGA) data, in particular for microRNA expression, to seek druggable core pathways in GBM. The E2F1-regulated miR-17˜92 cluster and its analogs are shown to be highly expressed in proneural GBM and in GSC lines, suggesting the E2F cell cycle pathway might be a key driver in proneural GBM...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28890889/a-novel-missense-mutation-in-the-aldh13-gene-causes-anophthalmia-in-two-unrelated-iranian-consanguineous-families
#2
Mohammadreza Dehghani, Masoud Dehghan Tezerjani, Zahra Metanat, Mohammad Yahya Vahidi Mehrjardi
Anophthalmia or microphthalmia (A/M) is a rare group of congenital/developmental ocular malformations, characterized by absent or small eye within the orbit affecting one or both eyes. It has complex etiology with chromosomal, monogenic with high heterogeneity, and environmental causes. We performed genome SNP-array analysis followed by autozygosity mapping and sequencing in the members of two families in which three individuals are suffering from severe bilateral anophthalmia. The genetic analysis revealed a novel missense c...
2017: International Journal of Molecular and Cellular Medicine
https://www.readbyqxmd.com/read/28871147/breast-cancer-spheroids-reveal-a-differential-cancer-stem-cell-response-to-chemotherapeutic-treatment
#3
Daniel S Reynolds, Kristie M Tevis, William A Blessing, Yolonda L Colson, Muhammad H Zaman, Mark W Grinstaff
An abnormal multicellular architecture is a defining characteristic of breast cancer and, yet, most in vitro tumor models fail to recapitulate this architecture or accurately predict in vivo cellular responses to therapeutics. The efficacy of two front-line chemotherapeutic agents (paclitaxel and cisplatin) are described within three distinct in vitro models employing the triple-negative basal breast cancer cell line MDA-MB-231 and the luminal breast cancer cell line MCF7: a) a 3D collagen embedded multicellular spheroid tumor model, which reflects the architecture and cellular heterogeneity of tumors in vivo; b) a 3D collagen model with a single cell-type diffusely embedded; and c) a 2D monolayer...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28751617/cdk4-6-inhibition-is-more-active-against-the-glioblastoma-proneural-subtype
#4
Ming Li, Aizhen Xiao, Desiree Floyd, Inan Olmez, Jeongwu Lee, Jakub Godlewski, Agnieszka Bronisz, Krishna P L Bhat, Erik P Sulman, Ichiro Nakano, Benjamin Purow
Glioblastoma (GBM) is the most common and lethal brain tumor. Gene expression profiling has classified GBM into distinct subtypes, including proneural, mesenchymal, and classical, and identifying therapeutic vulnerabilities of these subtypes is an extremely high priority. We leveraged The Cancer Genome Atlas (TCGA) data, in particular for microRNA expression, to seek druggable core pathways in GBM. The E2F1-regulated miR-17~92 cluster and its analogs are shown to be highly expressed in proneural GBM and in GSC lines, suggesting the E2F cell cycle pathway might be a key driver in proneural GBM...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732729/crystal-structures-of-an-atypical-aldehyde-dehydrogenase-having-bidirectional-oxidizing-and-reducing-activities
#5
Kyoungho Jung, Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Thien-Hoang Ho, Yeh-Jin Ahn, Deok-Kun Oh, Lin-Woo Kang
Aldehyde dehydrogenases (ALDHs) are NAD(P)(+)-dependent oxidoreductases that catalyze the oxidation of a variety of aldehydes to their acid forms. In this study, we determined the crystal structures of ALDH from Bacillus cereus (BcALDH), alone, and in complex with NAD(+) and NADP(+). This enzyme can oxidize all-trans-retinal to all-trans-retinoic acid using either NAD(+) or NADP(+) with equal efficiency, and atypically, as a minor activity, can reduce all-trans-retinal to all-trans-retinol using NADPH. BcALDH accommodated the additional 2'-phosphate of NADP(+) by expanding the cofactor-binding pocket and upshifting the AMP moiety in NADP(+)...
July 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28677722/regulation-of-retinoic-acid-synthetic-enzymes-by-wt1-and-hdac-inhibitors-in-293-cells
#6
Yifan Li, Lei Wang, Weipeng Ai, Nianhui He, Lin Zhang, Jihui Du, Yong Wang, Xingjian Mao, Junqi Ren, Dan Xu, Bei Zhou, Rong Li, Liwen Mai
All-trans retinoic acid (atRA), which is mainly generated endogenously via two steps of oxidation from vitamin A (retinol), plays an indispensible role in the development of the kidney and many other organs. Enzymes that catalyze the oxidation of retinol to generate atRA, including aldehyde dehydrogenase 1 family (ALDH1)A1, ALDH1A2 and ALDH1A3, exhibit complex expression patterns at different stages of renal development. However, molecular triggers that control these differential expression levels are poorly understood...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28648642/hpi-amf-inhibition-halts-the-development-of-the-aggressive-phenotype-of-breast-cancer-stem-cells
#7
Juan Carlos Gallardo-Pérez, Alhelí Adán-Ladrón de Guevara, Alvaro Marín-Hernández, Rafael Moreno-Sánchez, Sara Rodríguez-Enríquez
Cancer stem cells are responsible for tumor recurrence and metastasis. A new highly reproducible procedure for human breast cancer MCF-7 stem cells (BCSC) isolation and selection was developed by using a combination of hypoxia/hypoglycemia plus taxol and adriamycin for 24h. The BCSC enriched fraction (i) expressed (2-15 times) the typical stemness protein markers CD44+, ALDH1A3 and Oct 3/4; (ii) increased its clonogenicity index (20-times), invasiveness profile (>70%), migration capacity (100%) and ability to form mammospheres, compared to its non-metastatic MCF-7 counterpart...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28590501/novel-compound-heterozygous-mutations-of-aldh1a3-contribute-to-anophthalmia-in-a-non-consanguineous-chinese-family
#8
Yunqiang Liu, Yongjie Lu, Shasha Liu, Shunyao Liao
Anophthalmia is a rare eye development anomaly resulting in absent ocular globes or tissue in the orbit since birth. Here, we investigated a newborn with bilateral anophthalmia in a Chinese family. Exome sequencing revealed that compound heterozygous mutations c.287G > A (p.(Arg96His)) and c.709G > A (p.(Gly237Arg)) of the ALDH1A3 gene were present in the affected newborn. Both mutations were absent in all of the searched databases, including 10,000 in-house Chinese exome sequences, and these mutations were confirmed as having been transmitted from the parents...
April 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28581514/aldh1a3-is-epigenetically-regulated-during-melanocyte-transformation-and-is-a-target-for-melanoma-treatment
#9
M Pérez-Alea, K McGrail, S Sánchez-Redondo, B Ferrer, G Fournet, J Cortés, E Muñoz, J Hernandez-Losa, S Tenbaum, G Martin, R Costello, I Ceylan, V Garcia-Patos, J A Recio
Despite the promising targeted and immune-based interventions in melanoma treatment, long-lasting responses are limited. Melanoma cells present an aberrant redox state that leads to the production of toxic aldehydes that must be converted into less reactive molecules. Targeting the detoxification machinery constitutes a novel therapeutic avenue for melanoma. Here, using 56 cell lines representing nine different tumor types, we demonstrate that melanoma cells exhibit a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28576690/complement-component-c3ar-constitutes-a-novel-regulator-for-chick-eye-morphogenesis
#10
Erika Grajales-Esquivel, Agustin Luz-Madrigal, Jeffrey Bierly, Tracy Haynes, Edimara S Reis, Zeyu Han, Christian Gutierrez, Zachary McKinney, Apostolia Tzekou, John D Lambris, Panagiotis A Tsonis, Katia Del Rio-Tsonis
Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we analyzed its role in chick eye morphogenesis. During eye development, the optic vesicle (OV) invaginates to generate a bilayer optic cup (OC) that gives rise to the retinal pigmented epithelium (RPE) and neural retina...
August 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28550109/chronic-%C3%AE-cell-depolarization-impairs-%C3%AE-cell-identity-by-disrupting-a-network-of-ca-2-regulated-genes
#11
Jennifer S Stancill, Jean-Philippe Cartailler, Hannah W Clayton, James T O'Connor, Matthew T Dickerson, Prasanna K Dadi, Anna B Osipovich, David A Jacobson, Mark A Magnuson
We used mice lacking Abcc8, a key component of the β-cell KATP-channel, to analyze the effects of a sustained elevation in the intracellular Ca(2+) concentration ([Ca(2+)]i) on β-cell identity and gene expression. Lineage tracing analysis revealed the conversion of β-cells lacking Abcc8 into pancreatic polypeptide cells but not to α- or δ-cells. RNA-sequencing analysis of FACS-purified Abcc8(-/-) β-cells confirmed an increase in Ppy gene expression and revealed altered expression of more than 4,200 genes, many of which are involved in Ca(2+) signaling, the maintenance of β-cell identity, and cell adhesion...
August 2017: Diabetes
https://www.readbyqxmd.com/read/28506962/pair-feeding-but-not-insulin-phloridzin-or-rosiglitazone-treatment-curtails-markers-of-%C3%AE-cell-dedifferentiation-in-db-db-mice
#12
Emi Ishida, Ja Young Kim-Muller, Domenico Accili
β-Cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of β-cells can explain the slowly progressive onset and partial reversibility of β-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether β-cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes...
August 2017: Diabetes
https://www.readbyqxmd.com/read/28493069/comparison-of-molecular-marker-expression-in-early-zebrafish-brain-development-following-chronic-ethanol-or-morpholino-treatment
#13
Chengjin Zhang, Oswald Boa-Amponsem, Gregory J Cole
This study was undertaken to ascertain whether defined markers of early zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early brain development...
August 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28476022/aldh1a3-in-cscs
#14
Kelly E Sullivan, Richard A Cerione, Kristin F Wilson
No abstract text is available yet for this article.
May 3, 2017: Aging
https://www.readbyqxmd.com/read/28465496/the-hunt-for-elusive-cancer-stem-cells
#15
Salvatore Condello, Nkechiyere G Nwani, Daniela Matei
No abstract text is available yet for this article.
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443495/aldh1a3-correlates-with-luminal-phenotype-in-prostate-cancer
#16
Shangqian Wang, Chao Liang, Meiling Bao, Xiao Li, Lei Zhang, Shuang Li, Chao Qin, Pengfei Shao, Jie Li, Lixin Hua, Zengjun Wang
Prostate cancer is the most common male malignancies in the United States. The specific characteristics of different disease stages have been deeply investigated. We present our data on ALDH1A3 as a potential therapeutic target for the prostate cancer based on several functional investigations. Also, we used The Cancer Genome Atlas datasets for primary prostate cancer to detect the relevance of ALDH1A3 and prostate cancer luminal phenotype. We found that ALDH1A3 correlated with androgen receptor signaling pathway in primary prostate cancer, which is consistent with its luminal layer localization...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28423611/the-stem-cell-cancer-stem-cell-marker-aldh1a3-regulates-the-expression-of-the-survival-factor-tissue-transglutaminase-in-mesenchymal-glioma-stem-cells
#17
Kelly E Sullivan, Kathy Rojas, Richard A Cerione, Ichiro Nakano, Kristin F Wilson
Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and acyltransferase activities, has been implicated in the survival and chemotherapy resistance of aggressive cancer cells and cancer stem cells, including glioma stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs referred to as proneural (PN) and mesenchymal (MES), we find that the phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and survival of these cells was sensitive to treatment with tTG inhibitors, with a benefit being observed when combined with the standard of care for high grade gliomas (i...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28364347/cyp1a1-based-on-metabolism-of-xenobiotics-by-cytochrome-p450-regulates-chicken-male-germ-cell-differentiation
#18
Dong Li, Man Wang, Shaoze Cheng, Chen Zhang, Yilin Wang, Wenhui Zhang, Ruifeng Zhao, Changhua Sun, Yani Zhang, Bichun Li
This study aimed to explore the regulatory mechanism of metabolism of xenobiotics by cytochrome P450 during the differentiation process of chicken embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs) and consummate the induction differentiation system of chicken embryonic stem cells (cESCs) into SSCs in vitro. We performed RNA-Seq in highly purified male ESCs, male primordial germ cells (PGCs), and SSCs that are associated with the male germ cell differentiation. Thereinto, the metabolism of xenobiotics by cytochrome P450 was selected and analyzed with Venny among male ESC vs male PGC, male PGC vs SSC, and male ESC vs SSC groups and several candidates differentially expressed genes (DEGs) were excavated...
March 31, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28280900/paracrine-gaba-and-insulin-regulate-pancreatic-alpha-cell-proliferation-in-a-mouse-model-of-type-1-diabetes
#19
Allen L Feng, Yun-Yan Xiang, Le Gui, Gesthika Kaltsidis, Qingping Feng, Wei-Yang Lu
AIMS/HYPOTHESIS: This study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in conditions corresponding to type 1 diabetes in a mouse model and in vitro. METHODS: Type 1 diabetes was induced by injecting the mice with streptozotocin (STZ)...
June 2017: Diabetologia
https://www.readbyqxmd.com/read/28257834/anxa1ac2-26-peptide-a-possible-therapeutic-approach-in-inflammatory-ocular-diseases
#20
Laila Toniol Cardin, Nathália Martins Sonehara, Kallyne Kioko Oliveira Mimura, Anemari Ramos Dinarte Dos Santos, Wilson Araújo da Silva, Lays Martin Sobral, Andréia Machado Leopoldino, Bianca Rodrigues da Cunha, Eloiza H Tajara, Sonia Maria Oliani, Flávia Cristina Rodrigues-Lisoni
The eye is immunologically privileged when inflammatory responses are suppressed. One component responsible for the suppression of inflammatory responses is the blood retinal barrier, which comprises the retinal pigment epithelium. The destruction of this barrier initiates inflammation, which can affect any part of the eye. Therefore, inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1) protein acts as a modulator of inflammation. In this study we aimed to improve the knowledge of this area by investigating how a peptide of the ANXA1 protein (ANXA1Ac2-26) modulates the morphology, proliferation, migration and expression of genes and proteins in human retinal pigment epithelium cells (ARPE-19)...
May 30, 2017: Gene
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