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Motoko Sasaki, Yasunori Sato, Yasuni Nakanuma
Dysregulated autophagy may be a central player in trehe pathogenesis of primary biliary cholangitis (PBC) by inducing autoimmune processes via abnormal expression of mitochondrial antigens such as pyruvate dehydrogenase complex, E2 component (PDC-E2) and also by inducing cellular senescence in biliary epithelial cells (BECs) in bile duct lesions in PBC. We examined the association of an impaired "biliary bicarbonate umbrella" due to dysfunction of anion exchanger 2 (AE2) with dysregulated autophagy and cellular senescence in PBC...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Huihui Wang, Qi Zhong, Tianshu Yang, Ying Qi, Mengchen Fu, Xi Yang, Lu Qiao, Qi Ling, Shangfeng Liu, Yumei Zhao
Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are types of human dental tissue‑derived mesenchymal stem cells (MSCs). These cells possess a capacity for self‑renewal, multilineage differentiation potential and immunomodulatory functions. Previous studies have reported that DPSCs and SHED may be beneficial in regenerative treatments and immunotherapy. The substantial expansion of cells in vitro is a prerequisite to obtaining adequate cell numbers required for cell‑based therapy...
March 9, 2018: Molecular Medicine Reports
Sugela Blancas, Rogelio Medina-Berlanga, Liliana Ortíz-García, Alfredo Loredo-Ramírez, Leticia Santos
Specific markers in lesions of the human uterine cervix cancer (UCC) are still needed for prognostic, diagnostic and/or therapeutic purposes. In this study we evaluated key molecules at protein level between normal epithelium, cervical intraepithelial neoplasia (CIN1-3) and invasive cancer of a group of molecules previously reported at mRNA level. For that purpose, human formalin-fixed paraffin embedded tissue microarrays (TMAs) were constructed containing 205 Mexican tissue core specimens. Immunohistochemistry and quantitative analysis of histological staining was performed against twenty-two distinct proteins for each core and the processing platform ImageJ...
March 12, 2018: Pathology Oncology Research: POR
Yasmine Ghantous, Sharon Akrish, Yoav Leiser, Imad Abu El-Naaj
BACKGROUND: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate. OBJECTIVES: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC. METHODS: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel...
March 2018: Israel Medical Association Journal: IMAJ
Adam D Hudgins, Cagdas Tazearslan, Archana Tare, Yizhou Zhu, Derek Huffman, Yousin Suh
Cellular senescence is a state of irreversible cellular growth arrest accompanied by distinct changes in gene expression and the acquisition of a complex proinflammatory secretory profile termed the senescence-associated secretory phenotype (SASP). Senescent cells accumulate in aged tissues and contribute to age-related disease in mice. Increasing evidence that selective removal of senescent cells can ameliorate diseases of late life and extend lifespan in mice has given rise to the development of senolytics that target senescent cells as anti-aging therapeutics...
2018: Frontiers in Genetics
Ali C M Johnson, Richard A Zager
Background: P21, a cyclin kinase inhibitor, is upregulated by renal 'ischemic preconditioning' (IPC), and induces a 'cytoresistant' state. However, P21-induced cell cycle inhibition can also contribute to cellular senescence, a potential adverse renal event. Hence, this study assessed whether: (i) IPC-induced P21 upregulation is associated with subsequent renal senescence; and (ii) preconditioning can be established 'independent' of P21 induction and avoid a post-ischemic senescent state? Methods: CD-1 mice were subjected to either IPC (5-15 min) or to a recently proposed 'oxidant-induced preconditioning' (OIP) strategy (tin protoporphyrin-induced heme oxygenase inhibition +/- parental iron administration)...
March 7, 2018: Nephrology, Dialysis, Transplantation
Emilie A C Dronkers, Senada Koljenovic, Gerda M Verduijn, Robert J Baatenburg de Jong, Jose A U Hardillo
OBJECTIVES/HYPOTHESIS: This study aimed to analyze the effect of human papillomavirus (HPV)-associated T1-2 node-positive oropharyngeal squamous cell carcinoma (OPSCC) on nodal response, recurrent disease, and survival in patients treated according to the Rotterdam protocol. STUDY DESIGN: Retrospective cohort study. METHODS: In total, 77 patients with T1-2 OPSCC with nodal disease, treated between 2000 and 2012, were included in this study...
March 9, 2018: Laryngoscope
Hailian Wang, Xia He, Tiantian Lei, Yilong Liu, Guoli Huai, Minghan Sun, Shaoping Deng, Hongji Yang, Rongsheng Tong, Yi Wang
Previous studies by our group on mangiferin demonstrated that it exerts an anti‑hyperglycemic effect through the regulation of cell cycle proteins in 3‑month‑old, partially pancreatectomized (PPx) mice. However, β‑cell proliferation is known to become severely restricted with advanced age. Therefore, it is unknown whether mangiferin is able to reverse the diabetic condition and retain β‑cell regeneration capability in aged mice. In the present study, 12‑month‑old C57BL/6J mice that had undergone PPx were subjected to mangiferin treatment (90 mg/kg) for 28 days...
March 1, 2018: International Journal of Molecular Medicine
Sheetal Chauhan, Seema Sen, Anjana Sharma, Seema Kashyap, Radhika Tandon, Mandeep S Bajaj, Neelam Pushker, Murugesan Vanathi, Shyam S Chauhan
AIMS: To evaluate the expression and methylation status of the p16INK4a gene in early and advanced American Joint Committee on Cancer (AJCC) stages of ocular surface squamous neoplasia (OSSN) and to correlate its association with clinicopathological features and survival. METHODS: Sixty-four (35 early and 29 advanced AJCC stage) patients with OSSN formed part of this study and were followed up for 36-58 (mean 48±3.6) months. Immunohistochemical expression of the p16INK4a protein and methylation status of the p16INK4a gene were determined by methylation-specific PCR...
March 6, 2018: British Journal of Ophthalmology
Mariëtte E C Waaijer, David A Gunn, Diana van Heemst, P Eline Slagboom, John M Sedivy, Roeland W Dirks, Hans J Tanke, Rudi G J Westendorp, Andrea B Maier
Little is known on how well senescence markers in vitro and in situ correlate within individual donors. We studied correlations between the same and different in vitro markers. Furthermore, we tested correlations between in vitro markers with in situ p16INK4a positivity.From 100 donors (20-91 years), cultured dermal fibroblasts were assessed for reactive oxygen species (ROS), telomere-associated foci (TAF), p16INK4a and senescence-associated β-gal (SAβ-gal), with/ without 0.6 µM rotenone for 3 days (short-term)...
February 28, 2018: Aging
Chung-Guei Huang, Li-Ang Lee, Tuan-Jen Fang, Hsueh-Yu Li, Chun-Ta Liao, Chung-Jan Kang, Tzu-Chen Yen, Kuo-Chien Tsao, Tse-Ching Chen, Shin-Ru Shih
BACKGROUND/PURPOSE: To examine whether the prevalence rate of human papillomavirus (HPV) infection in Taiwanese patients with primary laryngeal squamous cell carcinoma (LSCC) is different from that in those with a vocal polyp (VP) or vocal fold leukoplakia (VFL). METHODS: This prospective cohort study recruited 41 consecutive patients with primary LSCC and 27 and 20 patients with VP and VFL, respectively. The HPV L1 gene in surgical specimens was detected using polymerase chain reaction...
February 21, 2018: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Marisa Mena, Miren Taberna, Sara Tous, Sandra Marquez, Omar Clavero, Beatriz Quiros, Belen Lloveras, Maria Alejo, Xavier Leon, Miquel Quer, Silvia Bagué, Ricard Mesia, Julio Nogués, Montserrat Gomà, Anton Aguila, Teresa Bonfill, Carmen Blazquez, Marta Guix, Rafael Hijano, Montserrat Torres, Dana Holzinger, Michael Pawlita, Miguel Angel Pavon, Ignacio G Bravo, Silvia de Sanjosé, Francesc Xavier Bosch, Laia Alemany
BACKGROUND: The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. METHODS: We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16INK4a /pRb/p53/Cyclin-D1 immunohistochemistry...
March 2018: Oral Oncology
Jaskaren Kohli, Judith Campisi, Marco Demaria
p16Ink4a is a potent cell cycle inhibitor engaged to support cell cycle arrest during cellular senescence. However, in tumors carrying mutations in key downstream effectors, p16Ink4a is highly expressed but fails to block cell proliferation. p16Ink4a -overexpressing tumor cells are highly aggressive and no targeted interventions are available. To study the effect of specific therapies, we generated murine sarcomas by overexpressing RAS oncogene and disrupting p53 activity. We observed that p16Ink4a -overxpressing murine sarcoma cells were resistant to ABT-263 and ABT-737, anti-cancer small molecules previously shown to eliminate p16Ink4a+ senescent cells...
January 26, 2018: Oncotarget
Xiangrui Li, Zhijian Zhang, Yao Zhang, Yuxiang Cao, Huijun Wei, Zhihao Wu
BACKGROUND: The preferential use of aerobic glycolysis by tumor cells lead to high accumulation of lactate in tumor microenvironment. Clinical evidence has linked elevated lactate concentration with cancer outcomes. However, the role and molecular mechanisms of lactate in cellular senescence and tumor progression remain elusive. METHODS: The function of Snail in lactate-induced EMT in lung cancer cells was explored by wound healing assay and cell invasion assay...
February 26, 2018: Journal of Experimental & Clinical Cancer Research: CR
Roberson A Moron, Carlos Eduardo Jacob, Claudio José Caldas Bresciani, Kleber Simões, Venâncio Avancini Ferreira Alves, Kyoshi Irya, Joaquim Gama-Rodrigues, Ivan Cecconello, Adhemar Longatto-Filho, Bruno Zilberstein
The aim of the present study was to determine the clinical significance of p53 and p21ras p21wafl , p27kip1 and p16ink4a expression in cases of early gastric cancer. A total of 81 patients who had undergone gastrectomy with D2 lymphadenectomy between 1971 and 2004 were retrospectively investigated. The immunohistochemical expression of p21ras , p53, p21waf1/cip1 , p27kip1 and p16ink4a in the tissues was evaluated. In normal, metaplastic and tumoral mucosa, p53 was positive in 53, 87.3, and 87.1% of the cases, respectively...
March 2018: Molecular and Clinical Oncology
Yorihisa Orita, Yuka Gion, Tomoyasu Tachibana, Kana Ikegami, Hidenori Marunaka, Seiichiro Makihara, Yasuhiko Yamashita, Kentaro Miki, Takuma Makino, Naoki Akisada, Yusuke Akagi, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato
Objective: To delineate the association between characteristics of adult-onset laryngeal squamous cell papilloma and human papillomavirus (HPV) infection. Methods: Clinical records and paraffin-embedded specimens of 77 papilloma patients who had been treated between 1998 and 2014 were collected. Of the 77 cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC) staining for anti-p16INK4a antibody...
February 13, 2018: Japanese Journal of Clinical Oncology
Shi-Lung Lin, Shao-Yao Ying
Today's researchers generating induced pluripotent stem cells (iPS cells or iPSCs) usually consider their pluripotency rather than potential tumorigenicity. Oncogenic factors such as c-Myc and Klf4 are frequently used to boost the survival and proliferative rates of iPSCs, creating an inevitable problem of tumorigenicity that hinders the therapeutic usefulness of these iPSCs. To prevent stem cell tumorigenicity, we have examined mechanisms by which the cell cycle genes are regulated in embryonic stem cells (ESCs)...
2018: Methods in Molecular Biology
San-Chi Chen, Peter Mu-Hsin Chang, Hsiao-Jung Wang, Shyh-Kuan Tai, Pen-Yuan Chu, Muh-Hwa Yang
PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16 INK4A expression were determined using immunohistochemistry...
February 2018: Oncology Letters
Jasbir D Upadhyaya, Sarah G Fitzpatrick, Mohammed N Islam, Indraneel Bhattacharyya, Donald M Cohen
Proliferative verrucous leukoplakia (PVL) is defined as an aggressive, relentless and recalcitrant form of leukoplakia that has a high propensity for malignant transformation. The aim of this study was to evaluate the malignant potential of PVL and determine its possible association with high-risk human papillomavirus (HPV). Twenty cases with a clinical and biopsy proven diagnosis of PVL were collected from the University of Florida Oral Medicine clinic database. Immunohistochemistry was performed to evaluate the expression of p16INK4A and p53 genes in the PVL lesions...
February 9, 2018: Head and Neck Pathology
Tomoe Tsuboi, Morihiko Maeda, Toshio Hayashi
L-citrulline and L-arginine supplementation has been shown to have several beneficial effects on the cardiovascular system. Nitric oxide (NO) protects against the progression of atherosclerosis and is synthesized by nitric oxide synthase (NOS), which converts L-arginine (L-Arg) into L-citrulline (L-Cit). Our previous study revealed that chronic administration of a combination of L-Cit and L- Arg has a better therapeutic effect on high cholesterol-induced atherosclerosis in rabbits. We investigated how L-Arg and L-Cit affect endothelial function, aging and atherosclerosis...
2018: PloS One
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