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JOURNAL ARTICLE
Mathew Lozinski, Eugenie R Lumbers, Nikola A Bowden, Jennifer H Martin, Michael F Fay, Kirsty G Pringle, Paul A Tooney
Glioblastoma is a highly aggressive disease with poor survival outcomes. An emerging body of literature links the role of the renin-angiotensin system (RAS), well-known for its function in the cardiovascular system, to the progression of cancers. We studied the expression of RAS-related genes ( ATP6AP2 , AGTR1 , AGTR2 , ACE , AGT , and REN ) in The Cancer Genome Atlas (TCGA) glioblastoma cohort, their relationship to patient survival, and association with tumour microenvironment pathways. The expression of RAS genes was then examined in 12 patient-derived glioblastoma cell lines treated with chemoradiation...
April 5, 2024: Cells
#2
REVIEW
Iphigenia Gintoni, Michael Mastrogeorgiou, Veronica Papakosta, Stavros Vassiliou, Christos Yapijakis
Basal cell carcinoma (BCC) is the most prevalent human neoplasm, with constantly increasing annual incidence. Despite its slow growth, BCC is locally invasive and, if left untreated, can cause severe complications, including metastasis and death. The renin-angiotensin system (RAS) plays a key role in electrolyte balance, atrial pressure, tissue development, homeostasis, and inflammation, but also in cancer development. After binding to its type 1 receptor (AT1R), angiotensin II (ANGII), the system's principal hormonal effector, regulates cancer pathways spanning from the formation of the initial cancer cell to the construction and nutrition of the tumor microenvironment, angiogenesis, proliferation, and metastasis...
March 28, 2024: Biochemical Genetics
#3
JOURNAL ARTICLE
Kalina R Atanasova, Corey M Perkins, Ranjala Ratnayake, Jinmai Jiang, Qi-Yin Chen, Thomas D Schmittgen, Hendrik Luesch
Background: Acinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development. Methods: We developed a novel morphology-based screen using organoids from wildtype and p48Cre/+ (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA). Results: Of the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis...
2024: Frontiers in Pharmacology
#4
REVIEW
Michael Bader, U Muscha Steckelings, Natalia Alenina, Robson A S Santos, Carlos M Ferrario
The renin-angiotensin system is the most important peptide hormone system in the regulation of cardiovascular homeostasis. Its classical arm consists of the enzymes, renin, and angiotensin-converting enzyme, generating angiotensin II from angiotensinogen, which activates its AT1 receptor, thereby increasing blood pressure, retaining salt and water, and inducing cardiovascular hypertrophy and fibrosis. However, angiotensin II can also activate a second receptor, the AT2 receptor. Moreover, the removal of the C-terminal phenylalanine from angiotensin II by ACE2 (angiotensin-converting enzyme 2) yields angiotensin-(1-7), and this peptide interacts with its receptor Mas...
February 16, 2024: Hypertension
#5
JOURNAL ARTICLE
Mingchuan Yang, Ximing Wu, Yufeng He, Xiuli Li, Lumin Yang, Tingting Song, Fuming Wang, Chung S Yang, Jinsong Zhang
Green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) has been well studied for its biological activities in the prevention of chronic diseases. However, the biological activities of EGCG oxidation-derived polymers remain unclear. Previously, we found that these polymers accumulated in intraperitoneal tissues after intraperitoneal injection and gained an advantage over native EGCG in increasing insulin sensitivity via regulating the renin-angiotensin system (RAS) in type 2 diabetic mice. The present study determined the pro-apoptosis activities and anticancer mechanisms of the EGCG oxidation-derived polymer preparation (the >10 kDa EGCG polymers) in digestive tract cancer cells...
January 31, 2024: Food & Function
#6
JOURNAL ARTICLE
Zhuna Wu, Qiuya Lin, Liying Sheng, Weihong Chen, Meili Liang, Danni Wu, Yumin Ke
Objective: The tumor microenvironment plays a critical role in the radiotherapy and immunotherapy response of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Radioresistance is a key factor in treatment failure among patients who receive radical radiotherapy. Thus, new immune-related biomarkers associated with radiotherapy response in CESC are needed. Methods: In this study, the CIBERSORT and ESTIMATE methods were applied to determine the percentage of tumor-infiltrating cells and the number of immune components in 103 CESCs treated with radiotherapy from The Cancer Genome Atlas (TCGA) database...
2023: Frontiers in Molecular Biosciences
#7
JOURNAL ARTICLE
Yoshitaka Murota, Mariko Nagane, Mei Wu, Mithun Santra, Seshasailam Venkateswaran, Shinji Tanaka, Mark Bradley, Tetsuya Taga, Kouichi Tabu
BACKGROUND: Pancreatic adenocarcinoma (PAAD) is one of the most fatal human cancers, but effective therapies remain to be established. Cancer stem cells (CSCs) are highly resistant to anti-cancer drugs and a deeper understanding of their microenvironmental niche has been considered important to provide understanding and solutions to cancer eradication. However, as the CSC niche is composed of a wide variety of biological and physicochemical factors, the development of multidisciplinary tools that recapitulate their complex features is indispensable...
September 27, 2023: Inflammation and Regeneration
#8
JOURNAL ARTICLE
Christos Yapijakis, Iphigenia Gintoni, Sevastiana Charalampidou, Antonia Angelopoulou, Veronica Papakosta, Stavros Vassiliou, George P Chrousos
INTRODUCTION: The intake of angiotensin-converting enzyme (ACE) inhibitors and specific antagonists of angiotensin II receptors, widely used as antihypertensive drugs, significantly reduces the risk of developing basal cell carcinoma (BCC), highlighting the possible tumorigenic role of angiotensin II (AngII). We present here the investigated genetic association between the development of BCC and functional DNA polymorphisms M235T, I/D, and A1903G in the genes of angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and chymase (CMA1), which mediate AngII production levels...
2023: Advances in Experimental Medicine and Biology
#9
JOURNAL ARTICLE
Yubo Su, Jingwen Ai, Min Jia, Genquan Yue, Lingyan Zhao, Hailing Li, Qi Liu, Dongyang Liu, Yuqi Wang, Wenjing Zhang, Yumin Gao, Haisheng Wang
BACKGROUND: We aimed to examine the relationships between the angiotensinogen ( AGT ) and vascular endothelial growth factor ( VEGF ) gene single nucleotide polymorphisms and susceptibility to bladder and kidney cancers. METHODS: A 1:1 paired case-control study was conducted, which included 143 newly diagnosed kidney cancer cases, 182 newly diagnosed bladder cancer cases, and healthy subjects in the same period collected from two hospitals. Medical records and a questionnaire were used to obtain relevant information...
June 2023: Archivos Españoles de Urología
#10
REVIEW
Aditi D Kunvariya, Shivani A Dave, Zeal J Modi, Paresh K Patel, Sneha R Sagar
Angiotensin converting enzyme 2 (ACE2) is a homolog of ACE (a transmembrane bound dipeptidyl peptidase enzyme). ACE2 converts angiotensinogen to the heptapeptide angiotensin-(1-7). ACE2 and its product, angiotensin-(1-7), have counteracting effects against the adverse actions of other members of renin-angiotensin system (RAS). ACE2 and its principal product, angiotensin-(1-7), were considered an under recognized arm of the RAS. The COVID-19 pandemic brought to light this arm of RAS with special focus on ACE2...
May 2023: Heliyon
#11
MULTICENTER STUDY
Sarah L Kerns, Ashley Amidon Morlang, Sharon M Lee, Derick R Peterson, Brian Marples, Hong Zhang, Kevin Bylund, Doug Rosenzweig, William Hall, Kim De Ruyck, Barry S Rosenstein, Richard G Stock, Antonio Gómez-Caamaño, Ana Vega, Paloma Sosa-Fajardo, Begoña Taboada-Valladares, Miguel E Aguado-Barrera, Chris Parker, Liv Veldeman, Valérie Fonteyne, Renée Bultijnck, Christopher J Talbot, R Paul Symonds, Kerstie Johnson, Tim Rattay, Adam Webb, Maarten Lambrecht, Dirk de Ruysscher, Ben Vanneste, Ananya Choudhury, Rebecca M Elliott, Elena Sperk, Carsten Herskind, Marlon R Veldwijk, Tiziana Rancati, Barbara Avuzzi, Riccardo Valdagni, David Azria, Marie-Pierre Farcy Jacquet, Jenny Chang-Claude, Petra Seibold, Catharine West, Michelle Janelsins, Yuhchyau Chen, Edward Messing, Gary Morrow
BACKGROUND AND PURPOSE: Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension. MATERIALS AND METHODS: Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437)...
March 2022: Radiotherapy and Oncology
#12
JOURNAL ARTICLE
Maria Samara, Maria Papathanassiou, Ioanna Farmakioti, Maria Anagnostou, Maria Satra, Lampros Mitrakas, Dimitrios Anastasiou, Georgios Chasiotis, Agamemnon Christopoulos, Athanasios Anagnostou, Anastasios Christodoulou, Alexandros Daponte, Maria Ioannou, George Koukoulis, Vassilios Tzortzis, Panagiotis J Vlachostergios
The renin-angiotensin system (RAS), besides being a major regulator of blood pressure, is also involved in tumor angiogenesis. Emerging evidence suggests a correlation between the use of pharmacologic RAS inhibitors and a delay in urothelial bladder cancer (BC) progression. However, it is unknown whether RAS gene variants may predispose to the development of BC. This study examined the association of RAS single nucleotide polymorphisms (SNPs) including AT1R rs5186, AT2R rs11091046, REN rs12750834, ANG rs4762, and ANG rs699 with the risk of developing non-invasive BC...
November 15, 2021: Current Oncology
#13
JOURNAL ARTICLE
Jia-Wei Cai, Xiao-Ming Huang, Xiao-Lan Li, Si Qin, Yu-Ming Rong, Xi Chen, Jing-Rong Weng, Yi-Feng Zou, Xu-Tao Lin
BACKGROUND: Prognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD. METHODS: Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database ( n = 332) and The Cancer Genome Atlas database ( n = 431)...
October 2021: Gastroenterology Report
#14
JOURNAL ARTICLE
S L Kerns, A Morlang, S M Lee, W A Hall, D Peterson, B Marples, H Zhang, K C Bylund, D Rosenzweig, K de Ruyck, B S Rosenstein, A Gomez CaamaNo, A Vega, C Parker, C M L West, M Janelsins, Y Chen, E Messing, G Morrow
PURPOSE/OBJECTIVE(S): Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) near AGT associated with late hematuria following radiotherapy (RT) for prostate cancer. AGT encodes angiotensinogen and, in pre-clinical models, angiotensin pathway inhibition protects against late radiation toxicity in some tissues. Effects on the bladder have not been investigated. We tested the hypothesis that angiotensin converting enzyme inhibitors (ACEi) reduce risk of late hematuria following RT...
November 1, 2021: International Journal of Radiation Oncology, Biology, Physics
#15
JOURNAL ARTICLE
Wei Chen, Yihuan Chen, Kai Zhang, Wanjing Yang, Xiang Li, Jun Zhao, Kangdong Liu, Ziming Dong, Jing Lu
BACKGROUND: Colorectal carcinoma (CRC) is one of the most common aggressive tumors worldwide, and it is necessary to identify candidate biomarkers and therapeutic targets in CRC to improve patient outcomes. METHODS: The differentially expressed genes (DEGs) were obtained from CRC microarray. Functional enrichment was performed to explore the function of DEGs, and core genes were identified by Cytoscape. Then, the diagnosis and prognosis markers were identified by ROC curve and survival analyses...
December 2021: International Immunopharmacology
#16
JOURNAL ARTICLE
Jian Zhang, Huali Jiang, Kunpeng Du, Tao Xie, Baiyao Wang, Chengcong Chen, Bohong Cen, Yawei Yuan, Jiacai Ye
Background: Cancer patients are alleged to have poor coronavirus disease 2019 (COVID-19) outcomes. However, no systematic or comprehensive analyses of the role and mechanisms of COVID-19 receptor-related regulators in cancer are available. Methods: We comprehensively evaluated the genomic alterations and their clinical relevance of six COVID-19 receptor-related regulators [transmembrane serine protease 2 (TMPRSS2), angiotensinogen (AGT), angiotensin-converting enzyme 1 (ACE1), solute carrier family 6 member 19 (SLC6A19), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor type 2 (AGTR2)] across a broad spectrum of solid tumors...
2021: Frontiers in Medicine
#17
JOURNAL ARTICLE
Danial Mehranfard, Gabriela Perez, Andres Rodriguez, Julia M Ladna, Christopher T Neagra, Benjamin Goldstein, Timothy Carroll, Alice Tran, Malav Trivedi, Robert C Speth
MATERIALS AND METHODS: Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically. RESULTS: Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens...
2021: Journal of the Renin-angiotensin-aldosterone System: JRAAS
#18
JOURNAL ARTICLE
Sam Siljee, Olivia Buchanan, Helen D Brasch, Nicholas Bockett, Josie Patel, Erin Paterson, Gordon L Purdie, Paul F Davis, Tinte Itinteang, Swee T Tan
We investigated the expression of components of the renin-angiotensin system (RAS) by cancer stem cell (CSC) subpopulations in metastatic head and neck cutaneous squamous cell carcinoma (mHNcSCC). Immunohistochemical staining demonstrated expression of prorenin receptor (PRR), angiotensin-converting enzyme (ACE), and angiotensin II receptor 2 (AT2 R) in all cases and angiotensinogen in 14 cases; however, renin and ACE2 were not detected in any of the 20 mHNcSCC tissue samples. Western blotting showed protein expression of angiotensinogen in all six mHNcSCC tissue samples, but in none of the four mHNcSCC-derived primary cell lines, while PRR was detected in the four cell lines only...
January 27, 2021: Cells
#19
JOURNAL ARTICLE
Sheng Li, Chao Yu, Yuanguang Cheng, Fangchao Du, Gang Wen
Gastric cancer (GC) is one of the most common malignancies of the digestive system. In diffuse‑type GC, differentiation is relatively poor, and the probability of distant metastasis and lymph node metastasis is high, resulting in poor clinical prognosis. The purpose of this study was to identify specific genes that can predict the prognosis of different types of GC. Differentially expressed genes (DEGs) were screened in the GSE62254 dataset obtained from the Gene Expression Omnibus using the 'limma' and 'survival' R packages...
March 2021: Molecular Medicine Reports
#20
JOURNAL ARTICLE
Daniela Volonte, Morgan Sedorovitz, Victoria E Cespedes, Maria L Beecher, Ferruccio Galbiati
Oncogenic K-Ras (K-RasG12V ) promotes senescence in normal cells but fuels transformation of cancer cells after the senescence barrier is bypassed. The mechanisms regulating this pleiotropic function of K-Ras remain to be fully established and bear high pathological significance. We find that K-RasG12V activates the angiotensinogen (AGT) gene promoter and promotes AGT protein expression in a Kruppel Like Factor 6 (KLF6)-dependent manner in normal cells. We show that AGT is then converted to angiotensin II (Ang II) in a cell-autonomous manner by cellular proteases...
January 8, 2021: Journal of Biological Chemistry
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