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https://www.readbyqxmd.com/read/28325277/reverse-expression-of-aging-associated-molecules-through-transfection-of-mirnas-to-aged-mice
#1
Jung-Hee Kim, Bo-Ram Lee, Eun-Sook Choi, Kyeong-Min Lee, Seong-Kyoon Choi, Jung Hoon Cho, Won Bae Jeon, Eunjoo Kim
Molecular changes during aging have been studied to understand the mechanism of aging progress. Herein, changes in microRNA (miRNA) expression in the whole blood of mice were studied to systemically reverse aging and propose them as non-invasive biomarkers. Through next-generation sequencing analysis, we selected 27 differentially expressed miRNAs during aging. The most recognized function involved was liver steatosis, a type of non-alcoholic fatty liver disease (NAFLD). Among 27 miRNAs, six were predicted to be involved in NAFLD, miR-16-5p, miR-17-5p, miR-21a-5p, miR-30c-5p, miR-103-3p, and miR-130a-3p; alterations in their blood and liver levels were confirmed by real-time qPCR...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28283584/clinical-benefit-in-response-to-palbociclib-treatment-in-refractory-uterine-leiomyosarcomas-with-a-common-cdkn2a-alteration
#2
Julia A Elvin, Laurie M Gay, Rita Ort, Joseph Shuluk, Jennifer Long, Lauren Shelley, Ronald Lee, Zachary R Chalmers, Garrett M Frampton, Siraj M Ali, Alexa B Schrock, Vincent A Miller, Philip J Stephens, Jeffrey S Ross, Richard Frank
BACKGROUND: Uterine leiomyosarcoma (uLMS) responds poorly to conventional chemotherapeutic agents, and personalized therapies have yet to be systematically explored. Comprehensive genomic profiling (CGP) can identify therapeutic targets and provide insight into the biology of this highly aggressive tumor. We report a case of uLMS treated with the CGP-matched therapy palbociclib, a CDK4/6 inhibitor, with sustained clinical benefit in this rare and deadly malignancy. MATERIALS AND METHODS: This study analyzed 279 clinically advanced/recurrent uLMS samples...
March 10, 2017: Oncologist
https://www.readbyqxmd.com/read/28278054/p16-loss-rescues-functional-decline-of-brca1-deficient-mammary-stem-cells
#3
Alexandria Scott, Feng Bai, Ho Lam Chan, Shiqin Liu, Joyce M Slingerland, David J Robbins, Anthony J Capobianco, Xin-Hai Pei
Recent evidence indicates that the accumulation of endogenous DNA damage can induce senescence and limit the function of adult stem cells. It remains elusive whether deficiency in DNA damage repair is associated with the functional alteration of mammary stem cells. In this article, we reported that senescence was induced in mammary epithelial cells during aging along with increased expression of p16Ink4a (p16), an inhibitor of CDK4 and CKD6. Loss of p16 abrogated the age-induced senescence in mammary epithelial cells and significantly increased mammary stem cell function...
February 22, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28276034/are-synchronous-and-metachronous-bilateral-breast-cancers-different-an-immunohistochemical-analysis-focused-on-cell-cycle-regulation
#4
Elżbieta Senkus, Jolanta Szade, Beata Pieczyńska, Michał Kunc, Agnieszka Pliszka, Jacek Jassem
INTRODUCTION: The biology and pathomechanisms of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous (sBBC) and metachronous bilateral breast cancers (mBBC), with special focus on cell cycle regulation and its correlation with markers determining intrinsic phenotype. METHODS: Immunohistochemical expression of p16Ink4A, p21(WAF1/CIP1), p27Kip1, p53, cyclin A, cyclin B, cyclin D1, cyclin D3 and cyclin E was assessed in tissue microarrays containing primary breast tumor cores from 113 mBBC and 61 sBBC...
March 9, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28245508/immunohistochemical-expression-of-the-tumor-suppressor-protein-p16ink4a-in-cervical-adenocarcinoma
#5
José Eleutério, Thiago Silva Lima, Maria do Perpétuo Socorro Cunha, Diane Isabelle Magno Cavalcante, Angélica Maria Holanda Silva
Objective To evaluate the diagnostic utility of the p16(ink4a) protein expression as a marker for adenocarcinoma of the cervix. Methods In a cross-sectional study, p16(ink4a) expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16(ink4a) was evaluated using a conventional contingency table, and the Kappa (κ) index was used to evaluate the agreement of the marker with the tissue diagnosis...
January 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28240601/foxp1-controls-mesenchymal-stem-cell-commitment-and-senescence-during-skeletal-aging
#6
Hanjun Li, Pei Liu, Shuqin Xu, Yinghua Li, Joseph D Dekker, Baojie Li, Ying Fan, Zhenlin Zhang, Yang Hong, Gong Yang, Tingting Tang, Yongxin Ren, Haley O Tucker, Zhengju Yao, Xizhi Guo
A hallmark of aged mesenchymal stem/progenitor cells (MSCs) in bone marrow is the pivot of differentiation potency from osteoblast to adipocyte coupled with a decrease in self-renewal capacity. However, how these cellular events are orchestrated in the aging progress is not fully understood. In this study, we have used molecular and genetic approaches to investigate the role of forkhead box P1 (FOXP1) in transcriptional control of MSC senescence. In bone marrow MSCs, FOXP1 expression levels declined with age in an inverse manner with those of the senescence marker p16INK4A...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28192409/melanocyte-transformation-requires-complete-loss-of-all-pocket-protein-function-via-a-mechanism-that-mitigates-the-need-for-mapk-pathway-activation
#7
I D Tonks, P Mukhopadhyay, W A Schroder, A Sorolla, A W Mould, H Y Handoko, B Ferguson, H K Muller, P Keith, N K Hayward, G J Walker, G F Kay
Deregulation of p16INK4A is a critical event in melanoma susceptibility and progression. It is generally assumed that the major effect of loss of p16 function is mediated through the CDK-cyclin pathway via its influence on the pocket protein (PP) pRb. However, there are also two other PPs, p107 and p130, which, when phosphorylated by CDK-cyclin complexes, play a role in permitting cell progression. Cohorts of mice carrying melanocyte-specific knockouts (KOs) of various combinations of the three PPs were generated...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28184004/ets-proto-oncogene-1-transcriptionally-up-regulates-the-cholangiocyte-senescence-associated-protein-cyclin-dependent-kinase-inhibitor-2a
#8
Steven P O'Hara, Patrick L Splinter, Christy E Trussoni, Maria J Lorenzo Pisarello, Lorena Loarca, Noah S Splinter, Bryce F Schutte, Nicholas F LaRusso
Primary sclerosing cholangitis (PSC) is a chronic, fibro-inflammatory cholangiopathy (disease of the bile ducts) of unknown pathogenesis. We reported that cholangiocyte senescence features prominently in PSC and neuroblastoma RAS viral oncogene homolog (NRAS) is activated in PSC cholangiocytes. Additionally, persistent microbial insult (e.g., lipopolysaccharides [LPS]) induces Cyclin Dependent Kinase Inhibitor 2A (CDKN2A/p16INK4a) expression and senescence in cultured cholangiocytes in an NRAS-dependent manner...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28124466/cellular-senescence-in-osteoarthritis-pathology
#9
REVIEW
Kendal McCulloch, Gary J Litherland, Taranjit Singh Rai
Cellular senescence is a state of stable proliferation arrest of cells. The senescence pathway has many beneficial effects and is seen to be activated in damaged/stressed cells, as well as during embryonic development and wound healing. However, the persistence and accumulation of senescent cells in various tissues can also impair function and have been implicated in the pathogenesis of many age-related diseases. Osteoarthritis (OA), a severely debilitating chronic condition characterized by progressive tissue remodeling and loss of joint function, is the most prevalent disease of the synovial joints, and increasing age is the primary OA risk factor...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/28073915/ube2e1-ubch6-is-a-critical-in-vivo-e2-for-the-prc1-catalyzed-ubiquitination-of-h2a-at-lys-119
#10
Keith Wheaton, Feroz Sarkari, Beena Stanly Johns, Hossein Davarinejad, Olga Egorova, Lilia Kaustov, Brian Raught, Vivian Saridakis, Yi Sheng
UbE2E1/UbcH6 is an E2 ubiquitin-conjugating enzyme that is regulated by USP7. We identified UbE2E1 as a novel component of Polycomb repressive complex 1 (PRC1), the E3 ligase complex responsible for histone H2A ubiquitination and gene silencing. We demonstrate that UbE2E1 is critical for the monoubiquitination of H2A at residue Lys-119 (uH2AK119) through its association with the PRC1 complex. UbE2E1 interacts with PRC1 subunits including Ring1A and Ring1B. Overexpression of UbE2E1 results in increased levels of uH2AK119, whereas overexpression of catalytically inactive UbE2E1_C131A or UbE2E1 knockdown results in decreased levels of uH2AK119...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28038969/corrigendum-to-an-association-of-dnmt3b-protein-expression-with-p16ink4a-promoter-hypermethylation-in-non-smoking-female-lung-cancer-with-human-papillomavirus-infection-cancer-lett-226-1-2005-aug-8-77-84
#11
Torng-Sen Lin, Huei Lee, Ruei-A Chen, Ming-Lin Ho, Chia-Yu Lin, Ya-Hui Chen, Yi-Yu Tsai, Ming-Chih Chou, Ya-Wen Cheng
No abstract text is available yet for this article.
December 27, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27997910/effects-of-cdkn2a-p16ink4a-p14arf-over-expression-on-proliferation-and-migration-of-human-melanoma-a375-cells
#12
Ming Bai, Nan-Ze Yu, Fei Long, Cheng Feng, Xiao-Jun Wang
OBJECTIVE: This study aims to investigate the effects of CDKN2A (p16INK4A/p14ARF) over-expression on the proliferation and migration of human melanoma A375 cells. METHODS: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16INK4A) and CDKN2A (p14ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16INK4A and p14ARF groups. The expression of CDKN2A (p16INK4A) and CDKN2A (p14ARF) mRNA and protein was detected by qRT-PCR and Western blotting...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27965321/suppressing-p16ink4a-and-p14arf-pathways-overcomes-apoptosis-in-individualized-human-embryonic-stem-cells
#13
Wenqian Wang, Yanling Zhu, Ke Huang, Yongli Shan, Juan Du, Xiaoya Dong, Ping Ma, Penafei Wu, Jian Zhang, Wenhao Huang, Tian Zhang, Baojian Liao, Deyang Yao, Guangjin Pan, Jiajun Liu
Dissociation-induced apoptosis is a striking phenomenon in human embryonic stem cells (hESCs), but not in naïve mouse ESCs. Rho-associated kinase-dependent actin-myosin hyperactivation is an underlying mechanism that triggers apoptosis in dissociated hESCs; however, in this study, we show that the Ink4A-ARF-mediated senescence pathway is another mechanism to cause apoptosis in individualized hESCs. We show that P16(INK4A) and P14(ARF) are immediately induced in hESCs upon dissociation, but not in mouse ESCs...
December 13, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27937072/altered-expression-of-g1-s-phase-cell-cycle-regulators-in-placental-mesenchymal-stromal-cells-derived-from-preeclamptic-pregnancies-with-fetal-placental-compromise
#14
Anna Maria Nuzzo, Domenica Giuffrida, Bianca Masturzo, Paolo Mele, Ettore Piccoli, Carola Eva, Tullia Todros, Alessandro Rolfo
Herein, we evaluated whether Placental Mesenchymal Stromal Cells (PDMSCs) derived from normal and Preeclamptic (PE) placentae presented differences in the expression of G1/S-phase regulators p16(INK4A), p18(INK4C), CDK4 and CDK6. Finally, we investigated normal and PE-PDMSCs paracrine effects on JunB, Cyclin D1, p16(INK4A), p18(INK4C), CDK4 and CDK6 expressions in physiological term villous explants. PDMSCs were isolated from physiological (n = 20) and PE (n = 24) placentae. Passage three normal and PE-PDMSC and conditioned media (CM) were collected after 48h...
January 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#15
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
February 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27902704/methylation-of-breast-cancer-predisposition-genes-in-early-onset-breast-cancer-australian-breast-cancer-family-registry
#16
Cameron M Scott, JiHoon Eric Joo, Neil O'Callaghan, Daniel D Buchanan, Mark Clendenning, Graham G Giles, John L Hopper, Ee Ming Wong, Melissa C Southey
DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development...
2016: PloS One
https://www.readbyqxmd.com/read/27902467/autocrine-il-6-mediates-pituitary-tumor-senescence
#17
Melanie Sapochnik, Mariana R Haedo, Mariana Fuertes, Pablo Ajler, Guillermo Carrizo, Andrés Cervio, Gustavo Sevlever, Günter K Stalla, Eduardo Arzt
Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899422/high-risk-hpv-biomarkers-and-outcome-in-matched-cohorts-of-head-and-neck-cancer-patients-positive-and-negative-for-hiv
#18
Heather M Walline, Thomas E Carey, Christine M Goudsmit, Emily L Bellile, Gypsyamber D'Souza, Lisa A Peterson, Jonathan B McHugh, Sara I Pai, J Jack Lee, Dong M Shin, Robert L Ferris
In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR, and in situ hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells...
February 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27893418/high-risk-hpv-genotypes-and-p16ink4a-expression-in-a-cohort-of-head-and-neck-squamous-cell-carcinoma-patients-in-singapore
#19
Louise Soo Yee Tan, Petersson Fredrik, Liang Ker, Feng Gang Yu, De Yun Wang, Boon Cher Goh, Kwok Seng Loh, Chwee Ming Lim
Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC)...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27861555/p16ink4a-expression-and-immunologic-aging-in-chronic-hiv-infection
#20
Susan Pereira Ribeiro, Jeffrey M Milush, Edecio Cunha-Neto, Esper G Kallas, Jorge Kalil, Luiz Felipe D Passero, Peter W Hunt, Steven G Deeks, Douglas F Nixon, Devi SenGupta
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls...
2016: PloS One
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