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https://www.readbyqxmd.com/read/28915557/loss-of-p16-ink4a-stimulates-aberrant-mitochondrial-biogenesis-through-a-cdk4-rb-independent-pathway
#1
Ethika Tyagi, Bin Liu, Chelsea Li, Tong Liu, Jared Rutter, Douglas Grossman
The tumor suppressor p16INK4A (p16) inhibits cell cycle progression through the CDK4/Rb pathway. We have previously shown that p16 regulates cellular oxidative stress, independent of its role in cell cycle control. We investigated whether loss of p16 had a direct impact on the mitochondria. We found that p16-null primary mouse fibroblasts (PMFs) displayed increased mitochondrial mass and expression of mitochondrial respiratory subunit proteins compared to wild-type (WT) PMFs. These findings in p16-null PMFs were associated with increased expression of the mitochondrial biogenesis transcription factors PRC and TFAM...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893373/peroxiredoxin-i-participates-in-the-protection-of-reactive-oxygen-species-mediated-cellular-senescence
#2
Young-Ho Park, Hyun-Sun Kim, Jong-Hee Lee, Seon-A Choi, Jin-Man Kim, Goo Taeg Oh, Sang Won Kang, Sun-Uk Kim, Dae-Yeul Yu
Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16INK4a expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I-/- MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I-/- mice showed an increased number of cells with senescence associated-β-galactosidase (SA-β-gal) activity in a variety of tissues...
September 12, 2017: BMB Reports
https://www.readbyqxmd.com/read/28861601/the-role-of-high-risk-human-papillomavirus-infections-in-laryngeal-squamous-cell-carcinoma
#3
REVIEW
Claus Wittekindt, Nora Wuerdemann, Stefan Gattenlöhner, Alexander Brobeil, Malgorzata Wierzbicka, Steffen Wagner, Jens Peter Klußmann
The contribution of human papillomavirus (HPV) to the development and clinical outcome of oropharyngeal cancers has been well documented. The association of HPV in laryngeal squamous cell carcinoma (LSCC) has been examined in several studies, but controversy exists regarding its role in carcinogenesis, the outcome of the patients and thus, clinical significance of HPV testing in LSCC. In this review, we give an update of known associations between HPV-positive testing and carcinogenesis in laryngeal cancer...
August 31, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28855649/dysfunction-of-the-circadian-transcriptional-factor-clock-in-mice-resists-chemical-carcinogen-induced-tumorigenesis
#4
Ken-Ichi Hashikawa, Chiharu Katamune, Naoki Kusunose, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo
The chronic disruption of circadian rhythms has been implicated in the risk of cancer development in humans and laboratory animals. The gene product CLOCK is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in various physiological processes. However, we demonstrated here that Clk/Clk mice resisted chemical carcinogen-induced tumorigenesis by suppressing epidermal growth factor (EGF) receptor-mediated proliferation signals. The repetitive application of 7,12-dimethylbenz[α]anthracene (DMBA) to skin on the back resulted in the significant development of tumors in wild-type mice, whereas chemically-induced tumorigenesis was alleviated in Clk/Clk mice...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28844647/unmasking-transcriptional-heterogeneity-in-senescent-cells
#5
Alejandra Hernandez-Segura, Tristan V de Jong, Simon Melov, Victor Guryev, Judith Campisi, Marco Demaria
Cellular senescence is a state of irreversibly arrested proliferation, often induced by genotoxic stress [1]. Senescent cells participate in a variety of physiological and pathological conditions, including tumor suppression [2], embryonic development [3, 4], tissue repair [5-8], and organismal aging [9]. The senescence program is variably characterized by several non-exclusive markers, including constitutive DNA damage response (DDR) signaling, senescence-associated β-galactosidase (SA-βgal) activity, increased expression of the cyclin-dependent kinase (CDK) inhibitors p16INK4A (CDKN2A) and p21CIP1 (CDKN1A), increased secretion of many bio-active factors (the senescence-associated secretory phenotype, or SASP), and reduced expression of the nuclear lamina protein LaminB1 (LMNB1) [1]...
September 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28830923/frequent-genetic-aberrations-in-the-cdk4-pathway-in-acral-melanoma-indicate-the-potential-for-cdk4-6-inhibitors-in-targeted-therapy
#6
Yan Kong, Xinan Sheng, Xiaowen Wu, Junya Yan, Meng Ma, Jiayi Yu, Lu Si, Zhihong Chi, Chuanliang Cui, Jie Dai, Yiqian Li, Huan Yu, Tianxiao Xu, Huan Tang, Bixia Tang, Lili Mao, Bin Lian, Xuan Wang, Xieqiao Yan, Siming Li, Jun Guo
PURPOSE: Effective therapies for the majority of metastatic acral melanoma (AM) patients has not been established. Thus, we investigated genetic aberrations of CDK4 pathway in AM and evaluate the efficacy of CDK4/6 inhibitors in targeted therapy of AM. EXPERIMENTAL DESIGN: A total of 514 primary AM samples were examined for the copy number variations (CNVs) of CDK4 pathway-related genes, including Cdk4, Ccnd1 and P16INK4a, by QuantiGenePlex DNA Assay. The sensitivity of established AM cell lines and patient-derived xenograft (PDX) containing typical CDK4 aberrations to CDK4/6 inhibitors was evaluated...
August 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28819445/dna-dependent-protein-kinase-catalytic-subunit-functions-in-metastasis-and-influences-survival-in-advanced-stage-laryngeal-squamous-cell-carcinoma
#7
Sha-Sha He, Yong Chen, Xiao-Ming Shen, Hong-Zhi Wang, Peng Sun, Jun Dong, Gui-Fang Guo, Ju-Gao Chen, Liang-Ping Xia, Pei-Li Hu, Hui-Juan Qiu, Shou-Sheng Liu, Yi-Xin Zhou, Wei Wang, Wei-Han Hu, Xiu-Yu Cai
Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818106/morphoproteomics-e6-e7-in-situ-hybridization-and-biomedical-analytics-define-the-etiopathogenesis-of-hpv-associated-oropharyngeal-carcinoma-and-provide-targeted-therapeutic-options
#8
Robert E Brown, Syed Naqvi, Mary F McGuire, Jamie Buryanek, Ron J Karni
BACKGROUND: Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation...
August 17, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28807346/application-of-a-time-resolved-fluoroimmunoassay-for-detection-of-p16ink4a-in-cervix
#9
Li Ding, Qiong Chen, Wanting Fan, Xianjin Zou
OBJECTIVE: To establish a time-resolved fluoroimmunoassay (TRFIA) method to detect p16INK4a. METHODS: 119 cases of exfoliative cells following Thinprep cytologic test (TCT) test were selected for TRFIA and biopsy tissues of these patients according to TCT results were collected for immunohistochemical (IHC) staining. RESULTS: There were 40 cases with cervicitis, 16 cases of cervical intraepithelial neoplasia grade 1 (CIN1), 15 cases of CIN2, 26 cases of CIN3, and 22 cases of squamous cell carcinoma (SCC)...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28777150/utility-of-stathmin-1-as-a-novel-marker-in-evaluating-anal-intraepithelial-neoplasia-ain
#10
Erika Hissong, Adela Cimic, Annemiek Leeman, Edyta C Pirog
The aim of this study is to determine whether immunohistochemistry for Stathmin-1 enhances diagnostic accuracy of anal dysplasia. The study included 40 biopsies with diagnosis of benign anal transitional zone (n=10), low-grade anal intraepithelial neoplasia (AIN) (AIN1, n=10), and high-grade AIN (AIN2, n=10, AIN3, n=10). The cases were selected to represent classic features. Immunohistochemistry for Stathmin-1, p16, and Ki-67 was performed and assessed for distribution within epithelial thickness. Stathmin-1 was expressed only in the basal layer of benign anal epithelium...
August 2, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28736821/testing-for-high-risk-hpv-in-cervical-and-tonsillar-paraffin-embedded-tissue-using-a-cartridge-based-assay
#11
Elina Virtanen, Pekka Laurila, Jaana Hagström, Pekka Nieminen, Eeva Auvinen
This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin-fixed paraffin-embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining...
July 24, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28711940/clinical-significance-of-p16ink4a-and-p14arf-promoter-methylation-in-renal-cell-carcinoma-a-meta-analysis
#12
Yu Ren, Li Xiao, Guobin Weng, Bingyi Shi
The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16INK4A and p14ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706164/clinicopathological-significance-of-the-p16-hypermethylation-in-multiple-myeloma-a-systematic-review-and-meta-analysis
#13
Huiqing Yu, Liejun Yang, Yunfeng Fu, Meng Gao, Ling Tian
It is well known that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of the p16 gene; however, whether or not the inactivation is associated with the clinical significance of multiple myeloma (MM) remains elusive. A meta-analysis was conducted to quantitatively determine the role of the p16 hypermethylation in the clinical significance of MM. We demonstrated that MM patients show much higher hypermethylation rates on the p16 gene in bone marrow compared to normal individuals, as well as monoclonal gammopathy of undetermined significance (MGUS)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701722/asxl1-deficiency-in-embryonic-fibroblasts-leads-to-cellular-senescence-via-impairment-of-the-akt-e2f-pathway-and-ezh2-inactivation
#14
Hye Sook Youn, Tae-Yoon Kim, Ui-Hyun Park, Seung-Tae Moon, So-Jung An, Yong-Kyu Lee, Jin-Taek Hwang, Eun-Joo Kim, Soo-Jong Um
Although ASXL1 mutations are frequently found in human diseases, including myeloid leukemia, the cell proliferation-associated function of ASXL1 is largely unknown. Here, we explored the molecular mechanism underlying the growth defect found in Asxl1-deficient mouse embryonic fibroblasts (MEFs). We found that Asxl1, through amino acids 371 to 655, interacts with the kinase domain of AKT1. In Asxl1-null MEFs, IGF-1 was unable to induce AKT1 phosphorylation and activation; p27Kip1, which forms a ternary complex with ASXL1 and AKT1, therefore remained unphosphorylated...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682291/cellular-senescence-what-why-and-how
#15
Matthew J Regulski
Cellular senescence is a process that results from a variety of stresses and leads to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age-related diseases. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis; however, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists...
June 2017: Wounds: a Compendium of Clinical Research and Practice
https://www.readbyqxmd.com/read/28658942/cellular-senescence-biomarker-p16ink4a-cell-burden-in-thigh-adipose-is-associated-with-poor-physical-function-in-older-women
#16
Jamie N Justice, Heather Gregory, Tamar Tchkonia, Nathan K LeBrasseur, James L Kirkland, Stephen B Kritchevsky, Barbara J Nicklas
Background: Ample evidence implicates cellular senescence as a contributor to frailty and functional decline in rodents, but considerable effort remains to translate these findings to human aging. Methods: We quantified senescence biomarker p16INK4a-expressing cells in thigh adipose tissue obtained from older women previously enrolled in a 5-month resistance training intervention, with or without caloric restriction (RT±CR, n=11 baseline, 8 pre-post-intervention pairs)...
June 27, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28658331/evaluation-of-telomerase-htert-ki67-and-p16ink4a-expressions-in-low-and-high-grade-cervical-intraepithelial-lesions
#17
Ana Paula Szezepaniak Goulart, Manoel Afonso Guimarães Gonçalves, Vinicius Duval DA-Silva
Objective : to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods : we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone...
March 2017: Revista do Colégio Brasileiro de Cirurgiões
https://www.readbyqxmd.com/read/28652169/oncogene-induced-senescence-and-its-evasion-in-a-mouse-model-of-thyroid-neoplasia
#18
Roberto Bellelli, Donata Vitagliano, Giorgia Federico, Pina Marotta, Anna Tamburrino, Paolo Salerno, Orlando Paciello, Serenella Papparella, Jeffrey A Knauf, James A Fagin, Samuel Refetoff, Giancarlo Troncone, Massimo Santoro
Here we describe a conditional doxycycline-dependent mouse model of RET/PTC3 (NCOA4-RET) oncogene-induced thyroid tumorigenesis. In these mice, after 10 days of doxycycline (dox) administration, RET/PTC3 expression induced mitogen activated protein kinase (MAPK) stimulation and a proliferative response which resulted in the formation of hyperplastic thyroid lesions. This was followed, after 2 months, by growth arrest accompanied by typical features of oncogene-induced senescence (OIS), including upregulation of p16INK4A and p21CIP, positivity at the Sudan black B, activation of the DNA damage response (DDR) markers γH2AX and pChk2 T68, and induction of p53 and p19ARF...
June 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28646455/human-nucleus-pulposus-intervertebral-disc-cells-becoming-senescent-using-different-treatments-exhibit-a-similar-transcriptional-profile-of-catabolic-and-inflammatory-genes
#19
Sotiris-Spyros Vamvakas, Eleni Mavrogonatou, Dimitris Kletsas
PURPOSE: Chronic low back pain has been associated with intervertebral disc (IVD) degeneration, which is characterized by the accumulation of extracellular matrix (ECM)-degrading proteases and inflammatory molecules in the degenerate tissue. IVD degeneration could be the outcome of natural organismal ageing and/or of the exposure of the disc to cumulative stressful environmental stimuli and is accompanied by an increased population of senescent cells in the tissue. On the other hand, senescent cells are known to secrete proteolytic enzymes and inflammatory molecules, which can contribute to ECM catabolism...
August 2017: European Spine Journal
https://www.readbyqxmd.com/read/28627675/distinctive-crypt-shape-in-a-sessile-serrated-adenoma-polyp-distribution-of-ki67-p16ink4a-wnt5a-positive-cells-and-intraepithelial-lymphocytes
#20
Kenji Hisamatsu, Kei Noguchi, Hiroyuki Tomita, Aoi Muto, Natsumi Yamada, Kazuhiro Kobayashi, Akihiro Hirata, Tomohiro Kanayama, Ayumi Niwa, Kazuhisa Ishida, Takayuki Nakashima, Yuichiro Hatano, Natsuko Suzui, Tatsuhiko Miyazaki, Akira Hara
Serrated lesions in the colorectum are currently predominantly classified as hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs) according to their morphology. However, the histological morphology and the molecular changes in the serrated lesions are still unclear. We performed immunohistochemistry for Ki67, p16INK4a, and WNT5A in human HPs (n=22), SSA/Ps (n=41), and TSAs (n=19). The distribution of Ki67 and p16INK4a positive cells in TSAs was different from that in HPs and SSA/Ps...
June 15, 2017: Oncology Reports
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