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https://www.readbyqxmd.com/read/29345338/miat-lncrna-is-overexpressed-in-breast-cancer-and-its-inhibition-triggers-senescence-and-g1-arrest-in-mcf7-cell-line
#1
Firooz Jannat Alipoor, Malek Hossein Asadi, Masoud Torkzadeh-Mahani
Long non-coding RNAs are known as key regulators in the progression and metastasis of breast cancer. Miat originally has been considered as an lncRNA to be associated with a susceptibility to myocardial infarction. Here, we have detected the expression of Miat in different cancer cells and a series of breast tumor tissue. Miat expression was much higher in high-grade tumors compared to low-grade ones. Unlike P53 positive tumors, Miat expression was upregulated in ER, PR, Her2 positive tumor tissues. Knockdown Miat suppressed breast cancer cell proliferation and caused G1 arrest in cell cycle...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29331666/age-related-oxidative-changes-in-pancreatic-islets-are-predominantly-located-in-the-vascular-system
#2
Richard Kehm, Jeannette König, Kerstin Nowotny, Tobias Jung, Stephanie Deubel, Sabrina Gohlke, Tim Julius Schulz, Annika Höhn
Aged tissues usually show a decreased regenerative capacity accompanied by a decline in functionality. During aging pancreatic islets also undergo several morphological and metabolic changes. Besides proliferative and regenerative limitations, endocrine cells lose their secretory capacity, contributing to a decline in functional islet mass and a deregulated glucose homeostasis. This is linked to several features of aging, such as induction of cellular senescence or the formation of modified proteins, such as advanced glycation end products (AGEs) - the latter mainly examined in relation to hyperglycemia and in disease models...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29321040/automated-image-analysis-detects-aging-in-clinical-grade-mesenchymal-stromal-cell-cultures
#3
S Oja, P Komulainen, A Penttilä, J Nystedt, M Korhonen
BACKGROUND: Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Indeed, cell morphology is routinely evaluated during MSC production using subjective methods. We have therefore explored the possibility of utilizing automated imaging-based analysis of cell morphology in clinical cell manufacturing...
January 10, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29312762/ciliated-muconodular-papillary-tumor-of-the-lung-harboring-braf-v600e-mutation-and-p16ink4a-overexpression-without-proliferative-activity-may-represent-an-example-of-oncogene-induced-senescence
#4
Lucia Kim, Young Sam Kim, Jin Soo Lee, Suk Jin Choi, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu
Ciliated muconodular papillary tumor (CMPT) is a rare peripheral lung tumor that shows puzzling histologic features encompassing metaplastic and neoplastic nature. This type of tumor is occasionally misdiagnosed as lung adenocarcinoma clinically and pathologically, and its pathogenic mechanism has not been well characterized. We experienced a case of CMPT in a 73-year-old male and performed targeted deep sequencing to characterize its molecular features. The tumor was an ill-defined, subpleural, and non-endobronchial nodule showing glandular and papillary proliferation of mucous cells, ciliated columnar cells, and basal cells without any cytologic atypia...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29289557/salidroside-attenuates-endothelial-cellular-senescence-via-decreasing-the-expression-of-inflammatory-cytokines-and-increasing-the-expression-of-sirt3
#5
Sha-Sha Xing, Jian Li, Lin Chen, Ya-Fei Yang, Ping-Lin He, Jun Li, Jin Yang
OBJECTIVE: Endothelial cellular senescence is an important contributor to the endothelial dysfunction and atherosclerosis. Our previous studies suggested that salidroside (SAL) can alleviate atherosclerosis and protect endothelial cells against oxidative stress induced damage. However, the effect and mechanism of SAL on endothelial cellular senescence is still unclear. Here, we investigated the underlying mechanisms of SAL on preventing endothelial cellular premature senescence. METHODS AND RESULTS: We established a hyperhomocysteinemia (HHcy)mouse model via high methionine diet (HMD) to explore the protective effect of SAL...
December 28, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29284773/phenotypic-features-of-endometrial-tumors-in-patients-with-family-history-of-cancer
#6
L G Buchynska, N P Iurchenko, N M Glushchenko, I P Nesina
AIM: To determine the peculiarities of expression of a number of proteins-regulators of the cell cycle in endometrial cancer (EC) cells in patients with a family history of oncological pathologies. PATIENTS AND METHODS: 95 EC patients (stage І-ІІ) were included into the study. Clinical-genealogical analysis was performed. 54 patients (group I) had healthy relatives, and in families of 41 patients (group II) an aggregation of malignant tumors of different genesis (mainly tumors of the gastrointestinal tract and the female reproductive system) was recorded...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29280266/senescence-promotes-in%C3%A2-vivo-reprogramming-through-p16ink4a-and-il-6
#7
Lluc Mosteiro, Cristina Pantoja, Alba de Martino, Manuel Serrano
Cellular senescence is a damage response aimed to orchestrate tissue repair. We have recently reported that cellular senescence, through the paracrine release of interleukin-6 (IL6) and other soluble factors, strongly favors cellular reprogramming by Oct4, Sox2, Klf4, and c-Myc (OSKM) in nonsenescent cells. Indeed, activation of OSKM in mouse tissues triggers senescence in some cells and reprogramming in other cells, both processes occurring concomitantly and in close proximity. In this system, Ink4a/Arf-null tissues cannot undergo senescence, fail to produce IL6, and cannot reprogram efficiently; whereas p53-null tissues undergo extensive damage and senescence, produce high levels of IL6, and reprogram efficiently...
December 27, 2017: Aging Cell
https://www.readbyqxmd.com/read/29275400/tubular-cell-senescence-in-the-donated-kidney-predicts-allograft-function-but-not-donor-remnant-kidney-function-in-living-donor-kidney-transplantation
#8
Tadashi Sofue, Yoshio Kushida, Taro Ozaki, Masahiro Moritoki, Yoko Nishijima, Hiroyuki Ohsaki, Nobufumi Ueda, Yoshiyuki Kakehi, Akira Nishiyama, Tetsuo Minamino
BACKGROUND: It is uncertain whether kidneys from marginal donors are suitable for live kidney transplantation. In deceased donor kidneys, tubular cell senescence affects allograft function. However, the degree of cell senescence in a living donor kidney with marginal factors has not been reported. In this study, we assessed the association of tubular cell senescence with allograft and remnant kidney function by a prospective observational clinical study. METHODS: Thirty-eight living donor kidney transplantations were analyzed prospectively...
December 22, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29258294/senescence-associated-reprogramming-promotes-cancer-stemness
#9
Maja Milanovic, Dorothy N Y Fan, Dimitri Belenki, J Henry M Däbritz, Zhen Zhao, Yong Yu, Jan R Dörr, Lora Dimitrova, Dido Lenze, Ines A Monteiro Barbosa, Marco A Mendoza-Parra, Tamara Kanashova, Marlen Metzner, Katharina Pardon, Maurice Reimann, Andreas Trumpp, Bernd Dörken, Johannes Zuber, Hinrich Gronemeyer, Michael Hummel, Gunnar Dittmar, Soyoung Lee, Clemens A Schmitt
Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16INK4a, p21CIP1 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells...
December 20, 2017: Nature
https://www.readbyqxmd.com/read/29248196/a-systematic-review-and-meta-analysis-on-the-attribution-of-human-papillomavirus-hpv-in-neuroendocrine-cancers-of-the-cervix
#10
REVIEW
Philip E Castle, Amanda Pierz, Mark H Stoler
BACKGROUND: There remains uncertainty about the role of human papillomavirus (HPV) infection in causing small-cell neuroendocrine carcinoma (SCNC) and large-cell neuroendocrine carcinoma (LCNC) of the cervix. To clarify the role of HPV in the development of SCNC and LCNC, we conducted a systematic review and meta-analyses. METHODS: PubMed and Embase were searched to initially identify 143 articles published on or before June 1, 2017. Studies were limited to methods that tested for HPV in the cancer tissue directly to minimize misattribution...
December 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29245970/calcitriol-induces-cell-senescence-of-kidney-cancer-through-jmjd3-mediated-histone-demethylation
#11
Yongqing Shen, Dan Yu, Pan Qi, Xuliang Wang, Xiaoqiang Guo, Aili Zhang
Calcitriol, also known as 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3), is a biologically active form of vitamin D and has a wide range of anticancer activity against various cancer cell lines. However, the mechanism of calcitriol remains to be further studied. In this study, the biological effect and epigenetic regulation of calcitriol on kidney cancer cells were investigated. Calcitriol can significantly inhibit cell proliferation of kidney cancer cell lines 786-O (P<0.05). Calcitriol also induced cell apoptosis and senescence of 786-O and ACHN (P<0...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29240242/the-9p21-locus-a-potential-therapeutic-target-and-prognostic-marker-in-breast-cancer
#12
REVIEW
Mahdi Rivand, Mohammad-Sadegh Khorrami, Hamid Fiuji, Soodabeh Shahidsales, Malihe Hasanzadeh, Mir Hadi Jazayeri, Seyed Mahdi Hassanian, Gordon A Ferns, Nafiseh Saghafi, Amir Avan
Breast cancer is an important cause of cancer related mortality in women. Despite extensive efforts to identify valid biomarkers for risk stratification, there are relatively few with proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to breast cancer. Recent genome-wide-association-studies and gene expression analysis have demonstrated that a locus on chromosome 9p21, which contains three genes; CDKN2B (encoding p15ink4b), CDKN2A (encoding p16ink4a and p14ARF) and the 3' end of CDKN2BAS [an antisense noncoding RNA in the INK4 locus (ANRIL)] are associated with an increased risk of this malignancy...
December 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29234059/p16ink4a-and-p21cip1-waf1-promote-tumour-growth-by-enhancing-myeloid-derived-suppressor-cells-chemotaxis
#13
Atsushi Okuma, Aki Hanyu, Sugiko Watanabe, Eiji Hara
p16Ink4a and p21Cip1/Waf1 act as tumour suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not well understood. Here, we report an unexpected function of p16Ink4 and p21Cip1/Waf1, namely, tumour promotion through chemotaxis. In monocytic myeloid-derived suppressor cells (Mo-MDSCs), p16Ink4 and p21Cip1/Waf1 are highly expressed and stimulate CX3CR1 chemokine receptor expression by preventing CDK-mediated phosphorylation and inactivation of SMAD3...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29220669/modulation-of-dietary-folate-with-age-confers-selective-hepatocellular-epigenetic-imprints-through-dna-methylation
#14
Rauf Ahmad Najar, Nissar Ahmad Wani, Javeed Ahmad Bhat, Nawab John Dar, Beenish Rahat, Ajai Prakash Gupta, Jaspreet Kaur, Jyotdeep Kaur, Abid Hamid
The present study has been designed to determine the effect of folate modulation (deficiency/supplementation) with aging on the promoter methylation of tumor suppressor and proto-oncogenes to understand the underlying mechanism of epigenetic alterations. Folate deficiency was induced for 3 and 5 months in weanling, young and adult groups, and after 3 months of folate deficiency, they were repleted with physiological folate (2 mg/kg diet) and folate oversupplementation (8 mg/kg diet) for another 2 months. The methylation facet in the present study revealed that the combined effect of folate deficiency and aging decreased the methylation index...
November 2, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29216274/functional-analysis-of-a-cdkn2a-5-utr-germline-variant-associated-with-pancreatic-cancer-development
#15
William Bruno, Virginia Andreotti, Alessandra Bisio, Lorenza Pastorino, Giuseppe Fornarini, Stefania Sciallero, Giovanna Bianchi-Scarrà, Alberto Inga, Paola Ghiorzo
CDKN2A coding region germline variants are associated with pancreatic adenocarcinoma (PC) susceptibility. Recently, we described functional germline 5'UTR CDKN2A variants from melanoma patients affecting the post-transcriptional regulation of p16INK4a mRNA that is dependent, at least in part, on an Internal Ribosome Entry Site (IRES) in the 5'UTR region. Here we describe a 5'UTR c.-201_-198delinsCTTT CDKN2A variant (frequency 0.0028 based on 350 PC patients), which seems to be private to PC, since it has never been found in public databases nor in thousands of melanoma patients tested...
2017: PloS One
https://www.readbyqxmd.com/read/29212231/zbp-89-function-in-colonic-stem-cells-and-during-butyrate-induced-senescence
#16
Ramon Ocadiz-Ruiz, Amanda L Photenhauer, Michael M Hayes, Lin Ding, Eric R Fearon, Juanita L Merchant
ZBP-89 (Zfp148, ZNF148) is a Kruppel-type zinc-finger family transcription factor that binds to GC-rich DNA elements. Earlier studies in cell lines demonstrated that ZBP-89 cooperates with Wnt β-catenin signaling by inducing β-catenin gene expression. Since β-catenin levels are normally highest at the crypt base, we examined whether ZBP-89 is required for stem cell maintenance. Lineage-tracing using a Zfp148CreERT2 transgenic line demonstrated expression in both intestine and colonic stem cells. Deleting the Zfp148 locus in the colon using the Cdx2NLSCreERT2 transgene, reduced the size and number of polyps formed in the Apc-deleted mice...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207716/expression-of-p16ink4a-protein-in-cervical-intraepithelial-neoplasia-and-invasive-carcinoma-of-uterine-cervix
#17
Vatsala Kishore, Anuradha G Patil
Introduction: Cervical cancer still ranks as the most frequent cancer among women in India. Infection with Human Papilloma Virus (HPV) results in precancerous lesions and invasive cervical cancer. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to upregulation of p16INK4A, a cyclin dependent kinase inhibitor. Therefore, p16INK4A overexpression is a surrogate biomarker of HPV infection making it useful in evaluating HPV associated premalignant and malignant lesions of gynaecological tract...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29207089/overexpression-of-p16ink4a-regulates-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway-in-pancreatic-cancer-cells
#18
Hui Zhang, Xun Li, Wenbo Meng, Lei Zhang, Xiaoliang Zhu, Zhongtian Bai, Jun Yan, Wence Zhou
The pathogenesis and etiology of pancreatic cancer remain to be fully elucidated; therefore, associated investigations are required to improve the outcome and prognosis of patients. In the present study, the effects of the overexpression of p16ink4a on the Wnt/β‑catenin signaling pathway were investigated in pancreatic cancer cell lines. Two pancreatic cancer cell lines, Bxpc‑3 and Miapaca‑2, characterized by low expression of p16ink4a, were transfected with the pc‑DNA3.0‑p16ink4a plasmid. After 24 h, Reverse transcription‑polymerase chain reaction and western blot analyses were performed to evaluate the expression of p16ink4a, β‑catenin, which is a key molecule in the Wnt/β‑catenin signaling pathway, c‑myc and cyclin D1, which are molecules downstream of β‑catenin...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29205871/pharmacogenetic-analysis-of-the-model-based-pharmacokinetics-of-five-anti-hiv-drugs-how-does-this-influence-the-effect-of-aging
#19
Jingxian Chen, Farida S Akhtari, Michael J Wagner, Oscar Suzuki, Tim Wiltshire, Alison A Motsinger-Reif, Julie B Dumond
Analysis of aging and pharmacogenetics (PGx) on antiretroviral pharmacokinetics (PKs) could inform precision dosing for older human HIV-infected patients. Seventy-four participants receiving either atazanavir/ritonavir (ATV/RTV) or efavirenz (EFV) with tenofovir/emtricitabine (TFV/FTC) provided PK and PGx information. Aging-PGx-PK association and interaction analyses were conducted using one-way analysis of variance (ANOVA), multiple linear regression, and Random Forest ensemble methods. Our analyses associated unbound ATV disposition with multidrug resistance protein (MRP)4, RTV with P-glycoprotein (P-gp), and EFV with cytochrome P450 (CYP)2B6 and MRP4 genetic variants...
December 3, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/29179500/hysk1-promotes-cancer-cell-proliferation-and-migration-through-negative-regulation-of-p16ink4a-under-hypoxic-conditions
#20
Mee-Hyun Lee, Zigang Dong, Young-Joon Surh, Bu Young Choi
The alteration of expression of p16INK4a, a well-known cyclin-dependent kinase inhibitor involved in cell cycle control, in tumors is unclear, especially under hypoxic conditions. To evaluate p16INK4a regulation, we performed a protein microarray analysis. Among 1,800 proteins in the array, we identified hYSK1 as a novel protein that interacts with the tumor suppressor p16INK4a. hYSK1, a member of the Ste20 family of serine/threonine protein kinases, promotes cell migration and tumorigenesis and is activated by oxidative stress...
October 24, 2017: Oncotarget
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