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https://www.readbyqxmd.com/read/30103733/early-increase-in-blood-supply-eibs-is-associated-with-tumor-risk-in-the-azoxymethane-model-of-colon-cancer
#1
Sarah Ruderman, Adam Eshein, Vesta Valuckaite, Urszula Dougherty, Anas Almoghrabi, Andrew Gomes, Ajaypal Singh, Baldeep Pabla, Hemant K Roy, John Hart, Marc Bissonnette, Vani Konda, Vadim Backman
BACKGROUND: The present study aimed to investigate the role of blood supply in early tumorigenesis in colorectal cancer. We leveraged the renin angiotensin system (RAS) to alter colonic blood supply and determine the effect on tumor initiation and progression. METHODS: To test the effect of blood supply on tumorigenesis, 53 male A/J mice were randomly assigned to one of three RAS modulation groups and one of two AOM treatments. The RAS modulation groups were I) water (RAS-unmodulated) as a control group, II) angiotensin-II and III) the angiotensin receptor blocker, Losartan...
August 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30097457/flywch1-a-novel-suppressor-of-nuclear-%C3%AE-catenin-regulates-migration-and-morphology-in-colorectal-cancer
#2
Belal A Muhammad, Sheema Almozyan, Roya Babaei-Jadidi, Emenike K Onyido, Anas Saadeddin, Seyed Hossein Kashfi, Bradley Spencer-Dene, Mohammad Ilyas, Anbarasu Lourdusamy, Axel Behrens, Abdolrahman Shams Nateri
Wnt/β-catenin signaling plays a critical role during development of both normal and malignant colorectal cancer (CRC) tissues. Phosphorylation of β-catenin protein alters its trafficking and function. Such conventional allosteric regulation usually involves a highly specialized set of molecular interactions, which may specifically turn on a particular cell phenotype. This study identifies a novel transcription modulator with an FLYWCH/Zn-finger DNA-binding domain, called "FLYWCH1". Using a modified yeast-2-hybrid based Ras-Recruitment system, it is demonstrated that FLYWCH1 directly binds to unphosphorylated (nuclear) β-catenin efficiently suppressing the transcriptional activity of Wnt/β-catenin signaling that cannot be rescued by TCF4...
August 10, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/30096712/generation-of-a-human-juvenile-myelomonocytic-leukemia-ipsc-line-chopi001-a-with-a-mutation-in-cbl
#3
Alyssa L Gagne, Jean Ann Maguire, Shilpa Gandre-Babbe, Stella T Chou, Sarah K Tasian, Mignon L Loh, Mitchell J Weiss, Paul Gadue, Deborah L French
Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disorder of early childhood characterized by expansion of clonal myelomonocytic cells and hyperactive Ras/MAPK signaling. The disorder is caused by somatic and/or germline mutations in genes involved in the Ras/MAPK and JAK/STAT signaling pathways, including CBL. Here we describe the generation of an iPSC line with a homozygous CBL c.1111T->C (Y371H) mutation, designated CHOPJMML1854.
July 5, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/30091651/the-leucine-rich-region-of-flightless-i-interacts-with-r-ras-to-regulate-cell-extension-formation
#4
P D Arora, T He, K Ng, C A McCulloch
Flightless I (FliI) is a calcium-dependent, actin severing and capping protein that localizes to cell matrix adhesions, contributes to the generation of cell extensions and co-localizes with Ras. Currently the mechanism by which FliI interacts with Ras to enable assembly of actin-based cell protrusions is not defined. R-Ras but not K-ras, H-ras or N-ras, associated with the leucine-rich region (LRR) of FliI. Mutations of the proline-rich region of R-ras (P202A, P203A) prevented this association. Knockdown of Ras-GTPase-activating SH3 domain binding protein (G3BP1) or Rasgap120 by siRNA inhibited the formation of cell extensions and prevented interaction of R-ras and G3BP1 in FliI WT cells...
August 9, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/30088202/a-natural-flavonoid-lawsonaringenin-induces-cell-cycle-arrest-and-apoptosis-in-ht-29-colorectal-cancer-cells-by-targeting-multiple-signalling-pathways
#5
Areeba Anwar, Nizam Uddin, Bina Shaheen Siddiqui, Rafat Ali Siddiqui, Sabira Begum, Muhammad Iqbal Choudhary
Colorectal cancer is the third most common malignancy in the world having a high mortality rate. Flavonoids possess many biological activities including anti-cancer activity. lawsonaringenin (LSG) is a flavonoid isolated from leaves of Lawsonia alba Lam. The objective of this study was to demonstrate the anti-cancer potential of LSG in colorectal cancer for the first time. The HT-29 cells were treated with LSG or 5-fluoruracil, as a positive control, to determine its effect on cell cytotoxicity by a MTT cell proliferation assay, and cell cycle progression and apoptosis using flowcytometry...
August 7, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/30086092/role-of-18f-fdg-pet-ct-in-restrictive-allograft-syndrome-after-lung-transplantation
#6
Stijn E Verleden, Olivier Gheysens, Karolien E Goffin, Bart M Vanaudenaerde, Erik K Verbeken, Birgit Weynand, Dirk E Van Raemdonck, Geert M Verleden, Robin Vos
BACKGROUND: Differential diagnosis of phenotypes of chronic lung allograft dysfunction (CLAD) remains troublesome. We hypothesized that F-FDG PET/CT may help in differential diagnosis of CLAD phenotypes, as it showed promising results regarding diagnosis and prognosis in interstitial lung diseases. METHODS: A monocentric, retrospective study was performed including all lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) who underwent F-FDG PET/CT scan, in comparison with stable lung transplant recipients...
August 6, 2018: Transplantation
https://www.readbyqxmd.com/read/30085274/distinct-genomic-profile-and-specific-targeted-drug-responses-in-adult-cerebellar-glioblastoma
#7
Hee Jin Cho, Junfei Zhao, Sang Won Jung, Erik Ladewig, Doo-Sik Kong, Yeon-Lim Suh, Yeri Lee, Donggeon Kim, Sun Hee Ahn, Mykola Bordyuh, Hyun Ju Kang, Jason K Sa, Yun Jee Seo, Sung Tae Kim, Do Hoon Lim, Yun-Sik Dho, Jung-Il Lee, Ho Jun Seol, Jung Won Choi, Woong-Yang Park, Chul-Kee Park, Raul Rabadan, Do-Hyun Nam
Background: Despite extensive efforts on the genomic characterization of gliomas, very few studies have reported the genetic alterations of cerebellar glioblastomas (C-GBM), a rare and lethal disease. Here, we provide a systematic study of C-GBM to better understand the specific genomic features of C-GBM. Methods: We collected a cohort of C-GBM patients and compared patient demographics and tumor pathologies to supratentorial glioblastoma (S-GBM). To uncover the molecular characteristics, we performed DNA- and mRNA-sequencing, and DNA methylation arrays on 19, 6, and 4 C-GBM cases, respectively...
July 31, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/30084508/radical-anions-radical-anion-salts-and-anionic-complexes-of-2-1-3-benzochalcogenadiazoles-s-se-te
#8
Nikolay Pushkarevsky, Elena Chulanova, Leonid Shundrin, Anton Smolentsev, Georgy Salnikov, Elena Pritchina, Alexander Genaev, Irina Irtegova, Irina Bagryanskaya, Sergey Konchenko, Nina Gritsan, Jens Beckmann, Andrey Zibarev
With cyclic voltammetry (CV) and DFT calculations, it was found that electron acceptor ability of the 2,1,3-benzochalcogenadiazoles 1-3 (chalcogen: S, Se and Te, respectively) increases with the atomic number of chalcogen. This trend is nontrivial since it contradicts the electronegativity and atomic electron affinity of the chalcogens. In contrast to radical anions (RAs) [1]*- and [2]*-, RA [3]*- was not detected by EPR under the CV conditions. Chemical reduction of 1-3 was performed and new thermally-stable RA salts [K(THF)]+[2]*- (8) and [K(18-crown-6)]+[2]*- (9) were isolated in addition to known salt [K(THF)]+[1]*- (7)...
August 7, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/30083774/glucagon-like-peptide-1-receptor-agonists-and-fracture-risk-a-network-meta-analysis-of-randomized-clinical-trials
#9
Y S Zhang, W Y Weng, B C Xie, Y Meng, Y H Hao, Y M Liang, Z K Zhou
Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433). INTRODUCTION: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients...
August 6, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/30067506/biochemical-and-kinetic-properties-of-the-complex-roco-g-protein-cycle
#10
Lina Wauters, Susanne Terheyden, Bernd K Gilsbach, Margaux Leemans, Panagiotis S Athanasopoulos, Giambattista Guaitoli, Alfred Wittinghofer, Christian Johannes Gloeckner, Wim Versées, Arjan Kortholt
Roco proteins have come into focus after mutations in the gene coding for the human Roco protein Leucine-rich repeat kinase 2 (LRRK2) were discovered to be one of the most common genetic causes of late onset Parkinson's disease. Roco proteins are characterized by a Roc domain responsible for GTP binding and hydrolysis, followed by a COR dimerization device. The regulation and function of this RocCOR domain tandem is still not completely understood. To fully biochemically characterize Roco proteins, we performed a systematic survey of the kinetic properties of several Roco protein family members, including LRRK2...
July 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/30062471/association-between-fusobacterium-nucleatum-pathway-mutation-and-patient-prognosis-in-colorectal-cancer
#11
Dae-Won Lee, Sae-Won Han, Jun-Kyu Kang, Jeong Mo Bae, Hwang-Phill Kim, Jae-Kyung Won, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae-You Kim
BACKGROUND: There is a close link between Fusobacterium nucleatum and colorectal cancer (CRC) tumorigenesis and chemoresistance. However, the genetic characteristics and clinical significance of CRC related with F. nucleatum remains unclear. This study evaluated the relationship between F. nucleatum, pathway mutation, and patient prognosis. METHODS: Fusobacterium nucleatum amount in the tumor tissue and adjacent normal tissue were measured by quantitative polymerase chain reaction in adjuvant (N = 128) and metastatic (N = 118) cohorts...
July 30, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/30061153/mtor-complex-1-controls-the-nuclear-localization-and-function-of-glycogen-synthase-kinase-3%C3%AE
#12
Stephen J Bautista, Ivan Boras, Adriano Vissa, Noa Mecica, Christopher M Yip, Peter K Kim, Costin N Antonescu
Glycogen synthase kinase 3β (GSK3β) phosphorylates and thereby regulates a wide range of protein substrates involved in diverse cellular functions. Some GSK3β substrates, such as c-myc and snail, are nuclear transcription factors, suggesting the possibility that GSK3β function is controlled through its nuclear localization. Here, using ARPE-19 and MDA-MB-231 human cell lines, we found that inhibition of mTOR complex 1 (mTORC1) leads to partial redistribution of GSK3β from the cytosol to the nucleus and to a GSK3β-dependent reduction of the levels of both c-myc and snail...
July 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30059502/ras-erk-ets-inhibition-alleviates-neuronal-mitochondrial-dysfunction-by-reprogramming-mitochondrial-retrograde-signaling
#13
Olivia F Duncan, Lucy Granat, Ramya Ranganathan, Vandana K Singh, David Mazaud, Manolis Fanto, David Chambers, Clive G Ballard, Joseph M Bateman
Mitochondrial dysfunction activates the mitochondrial retrograde signaling pathway, resulting in large scale changes in gene expression. Mitochondrial retrograde signaling in neurons is poorly understood and whether retrograde signaling contributes to cellular dysfunction or is protective is unknown. We show that inhibition of Ras-ERK-ETS signaling partially reverses the retrograde transcriptional response to alleviate neuronal mitochondrial dysfunction. We have developed a novel genetic screen to identify genes that modify mitochondrial dysfunction in Drosophila...
July 30, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/30054333/mucosal-hpv-e6-e7-peptide-vaccination-in-combination-with-immune-checkpoint-modulation-induces-regression-of-hpv-oral-cancers
#14
Stephanie Dorta-Estremera, Renee L Chin, Gloria Sierra, Courtney Nicholas, Ananta V Yanamandra, Nookala Sita Mahalakshmi Krishna, Guojun Yang, Shailbala Singh, Michael A Curran, K Jagannadha Sastry
High-risk human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx (SCCOP) are among the fastest growing cancers. After standard of care treatment, however, patients with HPV+ SCCOP have better overall and disease-specific survival than HPV- SCCOP patients, suggesting the importance of HPV-specific immunity. We reasoned that therapeutic vaccination targeting the HPV-16 E6 and E7 oncogenes could elicit high-affinity, high-frequency tumor antigen-specific T cell responses, which could then be augmented and shielded from suppression in the tumor microenvironment by immune checkpoint modulation...
July 27, 2018: Cancer Research
https://www.readbyqxmd.com/read/30050996/deregulation-of-methionine-metabolism-as-determinant-of-progression-and-prognosis-of-hepatocellular-carcinoma
#15
REVIEW
Rosa M Pascale, Claudio F Feo, Diego F Calvisi, Francesco Feo
The under-regulation of liver-specific MAT1A gene codifying for S-adenosylmethionine (SAM) synthesizing isozymes MATI/III, and the up-regulation of widely expressed MAT2A , MATII isozyme occurs in hepatocellular carcinoma (HCC). MATα1:MATα2 switch strongly contributes to the fall in SAM liver content both in rodent and human liver carcinogenesis. SAM administration to carcinogen-treated animals inhibits hepatocarcinogenesis. The opposite occurs in Mat1a-KO mice, in which chronic SAM deficiency is followed by HCC development...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/30043672/small-gtpase-ras-in-multiple-sclerosis-exploring-the-role-of-ras-gtpase-in-the-etiology-of-multiple-sclerosis
#16
Samantha Messina
RAS signaling is involved in the development of autoimmunity in general. Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. It is widely recognized that a reduction of Foxp3+ regulatory T (Treg) cells is an immunological hallmark of MS, but the underlying mechanisms are unclear. In experimental autoimmune models, N-Ras and K-Ras inhibition triggers an anti-inflammatory effect up-regulating, via foxp3 elevation, the numbers and the functional suppressive properties of Tregs...
July 25, 2018: Small GTPases
https://www.readbyqxmd.com/read/30042874/in-silico-guided-sequence-modifications-of-k-ras-epitopes-improve-immunological-outcome-against-g12v-and-g13d-mutant-kras-antigens
#17
Allan Wee Ren Ng, Pei Jun Tan, Winfrey Pui Yee Hoo, Dek Shen Liew, Michelle Yee Mun Teo, Pui Yan Siak, Sze Man Ng, Ee Wern Tan, Raha Abdul Rahim, Renee Lay Hong Lim, Adelene Ai Lian Song, Lionel Lian Aun In
Background: Somatic point substitution mutations in the KRAS proto-oncogene primarily affect codons 12/13 where glycine is converted into other amino acids, and are highly prevalent in pancreatic, colorectal, and non-small cell lung cancers. These cohorts are non-responsive to anti-EGFR treatments, and are left with non-specific chemotherapy regimens as their sole treatment options. In the past, the development of peptide vaccines for cancer treatment was reported to have poor AT properties when inducing immune responses...
2018: PeerJ
https://www.readbyqxmd.com/read/30042150/phase-ib-results-of-the-rational-combination-of-selumetinib-and-cyclosporin-a-in-advanced-solid-tumors-with-an-expansion-cohort-in-metastatic-colorectal-cancer
#18
Anuradha Krishnamurthy, Arvind Dasari, Anne M Noonan, Janice M Mehnert, Albert Craig Lockhart, Stephen Leong, Anna Capasso, Mark N Stein, Hanna K Sanoff, James J Lee, Aaron Hansen, Usha Malhotra, Sarah Rippke, Daniel L Gustafson, Todd M Pitts, Kim Ellison, S Lindsey Davis, Wells A Messersmith, S Gail Eckhardt, Christopher H Lieu
MEK inhibition is of interest in cancer drug development, but clinical activity in metastatic colorectal cancer (mCRC) has been limited. Preclinical studies demonstrated Wnt pathway overexpression in KRAS mutant cell lines resistant to the MEK inhibitor, selumetinib. The combination of selumetinib and cyclosporin A (CsA), a non-canonical Wnt pathway modulator, demonstrated antitumor activity in mCRC patient-derived xenografts (PDX). To translate these results, we conducted a NCI CTEP-approved multicenter Phase I/IB trial (NCT02188264) of the combination of selumetinib and CsA...
July 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/30035358/fgf-2-antiproliferative-stimulation-induces-proteomic-dynamic-changes-and-high-expression-of-fosb-and-junb-in-k-ras-driven-mouse-tumor-cells
#19
Francisca Nathalia de Luna Vitorino, Fabio Montoni, Jaqueline Neves Moreno, Bruno Ferreira de Souza, Mariana de Camargo Lopes, Barbara Cordeiro, Cecilia Sella Fonseca, Joshua M Gilmore, Mihaela I Sardiu, Marcelo Silva Reis, Laurence A Florens, Michael P Washburn, Hugo Aguirre Armelin, Julia Pinheiro Chagas da Cunha
FGF-2 is a well-known cell proliferation promoter; however, it can also induce cell cycle arrest. To gain insight into the molecular mechanisms of this antiproliferative effect, we investigated, for the first time, the early systemic proteomic differences induced by this growth factor in a K-Ras-driven mouse tumor cell line using a quantitative proteomics approach. More than 2900 proteins were quantified, indicating that terms associated with metabolism, RNA processing, replication, and transcription were enriched among proteins differentially expressed upon FGF2 stimulation...
July 23, 2018: Proteomics
https://www.readbyqxmd.com/read/30035279/high-concentration-aqueous-magnetic-fluids-structure-colloidal-stability-magnetic-and-flow-properties
#20
Corina Vasilescu, M Latikka, K D Knudsen, V M Garamus, V Socoliuc, Rodica Turcu, Etelka Tombácz, Daniela Susan-Resiga, R H A Ras, L Vékás
This paper is an in-depth analysis devoted to two basic types of water based magnetic fluids (MFs), containing magnetite nanoparticles with electrostatic and with electro-steric stabilization, both obtained by chemical coprecipitation synthesis under atmospheric conditions. The two sets of magnetic fluid samples, one with citric acid (MF/CA) and the other with oleic acid (MF/OA) coated magnetic nanoparticles, respectively, achieved saturation magnetization values of 78.20 kA m-1 for the electrostatically and 48...
July 23, 2018: Soft Matter
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