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https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#1
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29137390/a-cocktail-of-p16-ink4a-and-ki-67-p16-ink4a-and-minichromosome-maintenance-protein-2-as-triage-tests-for-human-papillomavirus-primary-cervical-cancer-screening
#2
Hai-Rui Wang, Yu-Cong Li, Hui-Qin Guo, Lu-Lu Yu, Zeni Wu, Jian Yin, Guang-Dong Liao, Yi-Min Qu, Yu Jiang, Dong Wang, Wen Chen
Most human papillomavirus (HPV) infections are transient and additional triage approaches should be built after HPV-based primary cervical cancer screening. We evaluated the accuracy of p16/Ki-67 and p16/mcm2 dual staining as biomarkers for triaging HPV positive women in China. 4070 participants aged 35 to 64 years attending ongoing cervical cancer screening were enrolled in 2015-2016. Cervical exfoliated cells were collected for HPV DNA analysis and the residual positive specimens were tested for liquid-based cytology and biomarkers...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133977/5-aza-2-deoxycytidine-protects-against-emphysema-in-mice-via-suppressing-p16-ink4a-expression-in-lung-tissue
#3
Zhi-Hui He, Yan Chen, Ping Chen, Sheng-Dong He, Hui-Hui Zeng, Ji-Ru Ye, Da Liu, Jun Cao
Background: There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs) contribute to neovascularization and play an important role in the development of COPD. The gene for p16(Ink4a) is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16(Ink4a) in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE), and further to search for a potential candidate agent protecting against emphysema induced by CSE...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29123987/jun-dimerization-protein-2-controls-hypoxia-induced-replicative-senescence-via-both-the-p16-ink4a-prb-and-arf-p53-pathways
#4
Koji Nakade, Chang-Shen Lin, Xiao-Yu Chen, Ming-Ho Tsai, Kenly Wuputra, Zhi-Wei Zhu, Jian-Zhi Pan, Kazunari K Yokoyama
The main regulators of replicative senescence in mice are p16(Ink4a) and Arf, inhibitors of cell cycle progression. Jun dimerization protein 2 (JDP2)-deficient mouse embryonic fibroblasts are resistant to replicative senescence through recruitment of the Polycomb repressive complexes 1 and 2 to the promoter of the gene that encodes p16(Ink4a) and inhibits the methylation of lysine 27 of the histone H3 locus. However, whether or not JDP2 is able to regulate the chromatin signaling of either p16(Ink4a)-pRb or Arf-p53, or both, in response to oxidative stress remains elusive...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29116073/-differential-expression-of-an-ensemble-of-the-key-genes-involved-in-cell-cycle-regulation-in-lung-cancer
#5
G S Krasnov, G A Puzanov, A V Kudryavtseva, A A Dmitriev, A D Beniaminov, T T Kondratieva, V N Senchenko
Targeted cancer therapy directed at individual targets is often accompanied by the rapid development of drug resistance. The development of a new generation of antitumor drugs involves the search for many targets simultaneously to block or, conversely, restore their activity. In this regard, simultaneous analysis of gene expression in a complex network of interactions, primarily cell cycle control elements, is relevant for the search of specific molecular markers for the differential diagnosis of adenocarcinoma (ADC) and squamous cell lung cancer (SCC), as well as new targets for therapy...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29112861/long-fiber-carbon-nanotubes-replicate-asbestos-induced-mesothelioma-with-disruption-of-the-tumor-suppressor-gene-cdkn2a-ink4a-arf
#6
Tatyana Chernova, Fiona A Murphy, Sara Galavotti, Xiao-Ming Sun, Ian R Powley, Stefano Grosso, Anja Schinwald, Joaquin Zacarias-Cabeza, Kate M Dudek, David Dinsdale, John Le Quesne, Jonathan Bennett, Apostolos Nakas, Peter Greaves, Craig A Poland, Ken Donaldson, Martin Bushell, Anne E Willis, Marion MacFarlane
Mesothelioma is a fatal tumor of the pleura and is strongly associated with asbestos exposure. The molecular mechanisms underlying the long latency period of mesothelioma and driving carcinogenesis are unknown. Moreover, late diagnosis means that mesothelioma research is commonly focused on end-stage disease. Although disruption of the CDKN2A (INK4A/ARF) locus has been reported in end-stage disease, information is lacking on the status of this key tumor suppressor gene in pleural lesions preceding mesothelioma...
November 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29103737/synchronous-bilateral-tonsillar-carcinomas-patient-characteristics-and-human-papillomavirus-genotypes
#7
Camelia Nami Saber, Christian Grønhøj, David Hebbelstrup Jensen, Cecilie Nørregaard, Amanda Carlander, Emilie Garnæs, Katalin Kiss, Lena Specht, Christian von Buchwald
INTRODUCTION: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing, but data on the incidence of synchronous, bilateral tonsillar squamous cell carcinomas (BiTSCCs) is sparse. In this study, we report the incidence and tumour characteristics of BiTSCCs in a population-based, consecutive cohort of OPSCCs. METHODS: We identified all patients diagnosed with tonsillar squamous cell carcinoma (TSCC) in eastern Denmark during a 15-year period to detect the incidence of synchronous BiTSCCs...
November 2017: Oral Oncology
https://www.readbyqxmd.com/read/29100961/influence-of-hpv-status-on-survival-of-patients-with-tonsillar-carcinomas-tscc-treated-by-co2-laser-surgery-plus-risk-adapted-therapy-a-10-year-retrospective-single-centre-study
#8
Markus Hoffmann, Elgar Susanne Quabius, Silke Tribius, Stephan Gebhardt, Tibor Görögh, Jürgen Hedderich, Karen Huber, Jürgen Dunst, Petra Ambrosch
The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment...
November 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29074172/low-prevalence-of-hpv-driven-head-and-neck-squamous-cell-carcinoma-in-north-east-italy
#9
Lorena Baboci, Dana Holzinger, Paolo Boscolo-Rizzo, Giancarlo Tirelli, Roberto Spinato, Valentina Lupato, Roberto Fuson, Markus Schmitt, Angelika Michel, Gordana Halec, Maria Cristina Da Mosto, Michael Pawlita, Annarosa Del Mistro
OBJECTIVES: To investigate the frequency of Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) among patients living in North-East Italy, by assessing HPV-DNA positivity in all tumors and additional markers whenever possible. MATERIAL AND METHODS: HPV types, viral load, viral RNA, HPV16/18 E6 protein and p16(INK4a) and pRb expression were determined in primary tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was analyzed in 102 patients...
December 2016: Papillomavirus Research
https://www.readbyqxmd.com/read/29072058/p16ink4a-expression-in-cervical-lesions-correlates-with-histologic-grading-a-tertiary-level-medical-facility-based-retrospective-study
#10
Usha Sarma, Ira Biswas, Alakananda Das, Gokul Chandra Das, Chandan Saikia, Bidula Sarma
p16INK4a is a tumor-suppressor protein and cyclin-dependent kinase (cdk) inhibitor that blocks cdk4- and cdk6-mediated pRb phosphorylation to inhibit E2F-dependent transcription and cell-cycle progression. Because the E7 protein of high-risk HPVs inactivates pRB, the resulting overexpression of p16INK4a may be a good marker for infection with high risk HPV types. Immunostaining of p16INK4a allows precise identification of even small CIN or cervical cancer lesions in biopsy sections and can help reduce inter-observer variation in the histopathological interpretation of cervical biopsy specimens...
October 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29057301/uncovering-a-novel-pathway-for-p16-silencing-therapeutic-implications-for-lung-cancer
#11
C Gamell, T Gulati, B Solomon, S Haupt, Y Haupt
A key step during onset of most cases of non-small cell lung cancer (NSCLC) is the loss of the tumor suppressor p16(INK4a) (best known as p16), commonly due to promoter hypermethylation. We recently reported a novel regulatory pathway involving E6-associated protein and cell division control protein 6, which provides a methylation-independent mechanism for p16 silencing in patients with a particularly aggressive form of NSCLC.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29054535/adipose-tissue-inflammation-in-aging
#12
REVIEW
Theresa Mau, Raymond Yung
Adipose tissue has traditionally been viewed as an organ of interest within studies of obesity and diet-associated metabolic disorders. However, as studies reveal the role white adipose tissue plays as an energy storage, a lipid metabolism site, and an adipokine secretor, it has become recognized as an organ of importance for metabolic health in both the young obese and the old obese. Within the realms of aging research, the pursuit of senolytics has taken the field's spotlight, where the clearance of senescent cells has shown to attenuate aspects of age-related disorders...
October 18, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29050279/ssecks-akap12-scaffolding-functions-suppress-b16f10-induced-peritoneal-metastasis-by-attenuating-cxcl9-10-secretion-by-resident-fibroblasts
#13
Masashi Muramatsu, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Shin Akakura, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein known to suppress metastasis by attenuating tumor-intrinsic PKC- and Src-mediated signaling pathways [1]. In addition to downregulation in metastatic cells, in silico analyses identified SSeCKS downregulation in prostate or breast cancer-derived stroma, suggesting a microenvironmental cell role in controlling malignancy. Although orthotopic B16F10 and SM1WT1[Braf(V600E)] mouse melanoma tumors grew similarly in syngeneic WT or SSeCKS-null (KO) mice, KO hosts exhibited 5- to 10-fold higher levels of peritoneal metastasis, and this enhancement could be adoptively transferred by pre-injecting naïve WT mice with peritoneal fluid (PF), but not non-adherent peritoneal cells (PC), from naïve KO mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29042141/involvement-of-bmi-1-gene-in-the-development-of-gastrointestinal-stromal-tumor-by-regulating-p16-ink4a-p14-arf-gene-expressions-an-in-vivo-and-in-vitro-study
#14
Jiang-Li Wang, Jiang-Hong Wu, Cai Hong, Ya-Nong Wang, Ye Zhou, Zi-Wen Long, Ying Zhou, Hai-Shu Qin
OBJECTIVE: This study was conducted in order to explore the role that Bmi-1 plays during the development of a gastrointestinal stromal tumor (GIST) by regulation of the p16(Ink4A) and p14(ARF) expressions. METHODS: Eighty-six patients diagnosed with GIST were selected to take part in this experiment. The Bmi-1 protein expressions in GIST and adjacent normal tissues were detected using immunohistochemistry and further analyzed by using photodensitometry. To monitor and track the progression of the GIST, a 3-year follow-up was conducted for all affected patients...
September 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29034342/p16-ink4a-expression-in-invasive-laryngeal-cancer
#15
Brenda Y Hernandez, Mobeen Rahman, Charles F Lynch, Wendy Cozen, Elizabeth R Unger, Martin Steinau, Trevor Thompson, Maria Sibug Saber, Sean F Altekruse, Marc T Goodman, Amy Powers, Christopher Lyu, Mona Saraiya
We examined p16 expression in tumors from a population-based sample of laryngeal cancer cases diagnosed in the U.S. Samples had been previously genotyped for HPV DNA. Overall, p16 expression was observed in laryngeal tissue from 8 of 101 (7.9%) cases. p16 expression was observed in 2 of 16 (12.5%) cases previously determined to be HPV DNA positive. The two cases dually positive for p16 and HPV DNA were non-keratinizing SCC and papillary SCC tumors that were positive for genotypes 18 and 35/89, respectively...
December 2016: Papillomavirus Research
https://www.readbyqxmd.com/read/29021820/introduction-of-p16-ink4a-as-a-surrogate-biomarker-for-hpv-in-women-with-invasive-cervical-cancer-in-sudan
#16
Hina Sarwath, Devendra Bansal, Nazik Elmalaika Husain, Mahmoud Mohamed, Ali A Sultan, Shahinaz Bedri
BACKGROUND: Cervical cancer is the fourth most common cancer in women worldwide with highest incidence reported in Eastern Africa in 2012. The primary goal of this study was to study the expression of p16(INK4a) in squamous cell carcinoma (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with clinico-pathological parameters. This study further explored the correlation of p16(INK4a) immunostaining with another proliferation marker, Ki-67 and to study if human papillomavirus (HPV) IHC can be used as a marker for detection of virus in high-grade dysplasia...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29018245/transient-postnatal-overfeeding-causes-liver-stress-induced-premature-senescence-in-adult-mice
#17
Catherine Yzydorczyk, Na Li, Hassib Chehade, Dolores Mosig, Mickael Bidho, Basile Keshavjee, Jean Baptiste Armengaud, Katya Nardou, Benazir Siddeek, Mohamed Benahmed, Catherine Vergely, Umberto Simeoni
Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28982864/down-regulation-of-toll-like-receptor-tlr4-is-associated-with-hpv-dna-integration-in-penile-carcinoma
#18
Miklos Damasdi, Krisztina Kovacs, Nelli Farkas, Ferenc Jakab, Gyula Kovacs
BACKGROUND/AIM: Development of penile cancers is attributed to HPV-related carcinogenesis. Our aim was to analyze HPV positivity and TLR4, p16(ink4a) and p53 expression. MATERIALS AND METHODS: HPV presence was assessed with virus-specific TaqMan PCR and HPV Genotyping Test in 31 penile cancers. Immunohistochemistry was carried out on tissue microarray. RESULTS: TLR4 expression was detected in 4 of the 16 HPV positive and 13 of the 15 HPV negative tumors...
October 2017: Anticancer Research
https://www.readbyqxmd.com/read/28980705/empowering-human-cardiac-progenitor-cells-by-p2y14-nucleotide-receptor-overexpression
#19
Farid G Khalafalla, Waqas Kayani, Arwa Kassab, Kelli Ilves, Megan M Monsanto, Roberto Alvarez, Monica Chavarria, Benjamin Norman, Walter P Dembitsky, Mark A Sussman
Autologous cardiac progenitor cell (hCPC) therapy is a promising alternative approach to current inefficient therapies for heart failure (HF). However, ex vivo expansion and pharmacological/genetic modification of hCPCs are necessary interventions to rejuvenate aged/diseased cells and improve their regenerative capacities. This study was designed to assess the potential of improving hCPC functional capacity by targeting P2Y14 purinergic receptor (P2Y14 R), which has been previously reported to induce regenerative and anti-senescence responses in a variety of experimental models...
October 5, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28969078/clinical-significance-of-p16-ink4a-and-p14-arf-promoter-methylation-in-renal-cell-carcinoma-a-meta-analysis
#20
Yu Ren, Li Xiao, Guobin Weng, Bingyi Shi
The inactivation of p16(INK4A) and p14(ARF) via promoter methylation has been investigated in various cancers. However, the clinical effects of p16(INK4A) and p14(ARF) 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 p16(INK4A) and p14(ARF) were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2...
September 8, 2017: Oncotarget
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