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https://www.readbyqxmd.com/read/29290803/glutathione-peroxidase-3-delivered-by-hipsc-mscs-ameliorated-hepatic-ir-injury-via-inhibition-of-hepatic-senescence
#1
Xiang Qi, Kevin Tak-Pan Ng, Qizhou Lian, Chang Xian Li, Wei Geng, Chang Chun Ling, Wai Ho Yeung, Yuen Yuen Ma, Xiao Bing Liu, Hui Liu, Jiang Liu, Xin Xiang Yang, Chung Mau Lo, Kwan Man
Background and Aims: Down-regulation of GPx3 accelerated hepatic senescence, which further caused overwhelming inflammation and severe liver graft injury. MSCs derived from human induced pluripotent stem cells (hiPSC-MSCs) have been developed as more efficient delivery vehicle with the property of injury tropism. Here, we aimed to explore the suppressive role of GPx3 in hepatic IR injury using novel delivery system of hiPSC-MSCs. Methods: The mice IR injury model with partial hepatectomy was established. The engineered hiPSC-MSCs delivering GPx3 was constructed...
2018: Theranostics
https://www.readbyqxmd.com/read/29234059/p16ink4a-and-p21cip1-waf1-promote-tumour-growth-by-enhancing-myeloid-derived-suppressor-cells-chemotaxis
#2
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/29161981/presenting-symptoms-and-clinical-findings-in-hpv-positive-and-hpv-negative-oropharyngeal-cancer-patients
#3
Timo Carpén, Anni Sjöblom, Marie Lundberg, Caj Haglund, Antti Markkola, Stina Syrjänen, Jussi Tarkkanen, Antti Mäkitie, Jaana Hagström, Petri Mattila
OBJECTIVES: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. METHODS: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody...
November 21, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/29159804/antibodies-against-human-papillomaviruses-as-diagnostic-and-prognostic-biomarker-in-patients-with-neck-squamous-cell-carcinoma-from-unknown-primary
#4
Lea Schroeder, Gunnar Wichmann, Maria Willner, Angelika Michel, Manuel Wiesenfarth, Christa Flechtenmacher, Tanja Gradistanac, Michael Pawlita, Andreas Dietz, Tim Waterboer, Dana Holzinger
Treatment of patients with neck lymph node metastasis of squamous cell carcinoma (SCC) from unknown primary tumor (NSCCUP) is challenging due to the risk of missing occult tumors or inducing toxicity to unaffected sites. Human papillomavirus (HPV) is a promising biomarker given its causal link to oropharyngeal SCC and superior survival of patients with HPV-driven oropharyngeal SCC and NSCCUP. Identification of HPV-driven NSCCUP could focus diagnostic work-up and treatment on the oropharynx. For the first time, we assessed HPV antibodies and their prognostic value in NSCCUP patients...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29150788/ck4-ck6-cyclin-d1-p16-ink4a-and-egfr-expression-in-glioblastoma-with-a-primitive-neuronal-component
#5
Guiyan Xu, Jian Yi Li
Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases...
November 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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 p16INK4a 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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