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Ying-Hua Pan, Mei Yang, Li-Ping Liu, Dan-Chun Wu, Ming-Yue Li, Shu-Guang Su
Ubiquitin-conjugating enzyme E2S (UBE2S) plays pivotal roles in the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unknown. Here, we show that UBE2S is upregulated in HCC and exhibits oncogenic activities via enhancing the ubiquitination of p53. Increased expression of UBE2S was significantly correlated with higher serum AFP level, higher pathological grade, advanced TNM stage, larger tumor size, vascular invasion and unfavorable patient survivals in two independent cohorts containing a total of 845 patients with HCC...
June 18, 2018: Biochemical and Biophysical Research Communications
Satoshi Kaneko, Xue Li
Men are much more likely than women to develop bladder cancer (BCa), but the underlying cause of this gender disparity remains poorly defined. Using sex-reversed mice, we show that the sex chromosome complement is an independent cause and, moreover, amplifies the biasing effects of sex hormones. We also show that the X-linked lysine demethylase 6A ( KDM6A ) is a sexually dimorphic gene. Wild-type but not catalytically dead KDM6A confers sustained tumor suppressor activity in vitro. Knockout of mouse Kdm6a reduces expression of Cdkn1a and Perp , canonical gene targets of the tumor suppressor p53 ...
June 2018: Science Advances
Xia Chen, Hua Guan, Xiao-Dan Liu, Da-Fei Xie, Yu Wang, Teng Ma, Bo Huang, Ping-Kun Zhou
Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells...
July 2018: Oncology Letters
Jiukai Wan, Jun Zhang, Junqiang Zhang
The present study aimed to investigate the expression of tumor protein p53 (p53), and its mechanism of function, in prostate cancer (PC). Small interfering RNA (siRNA) was used to interfere with p53 expression in the PC cell line, DU145. Cell viability and p53 expression were analyzed using cell counting kit-8 (CCK-8) and western blotting. The effects of p53 expression on the proliferation, migration and adhesion abilities of PC cells were analyzed using Cell Counting kit-8, Transwell and adhesion assays. Changes in cell proliferation, migration and adhesion ability were observed following treatment with extracellular signal-regulated kinase (ERK) inhibitor, PD184352, and janus kinase (JNK) inhibitor, SP60012...
July 2018: Oncology Letters
Joanna Huszno, Ewa Grzybowska
Tumor protein 53 ( TP53 ) is a tumor suppressor gene that encodes tumor protein p53. Tumor protein p53 regulates the expression of target genes in response to cellular stress. Additionally, p53 participates in the regulation of cell cycle checkpoints, DNA repair and apoptosis. Mutations in the TP53 gene are associated with numerous types of human cancer, including breast cancer, sarcomas, brain tumors and adrenal cortical carcinomas. In breast cancer, TP53 mutations are a negative prognostic factor. Tumors with TP53 mutations are more likely to be aggressive (triple-negative or human epidermal growth factor receptor 2-positive breast cancer), and resistant to chemotherapy and radiotherapy...
July 2018: Oncology Letters
Parisa Zargar, Esmaeel Ghani, Farideh Jalali Mashayekhi, Amin Ramezani, Ebrahim Eftekhar
5-Fluorouracil (5-FU)-based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5-FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5-FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5-FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay...
June 2018: Oncology Letters
Wenzheng Xia, Meng Hou
Doxorubicin (DOXO) is a chemotherapeutic agent widely used in the treatment of various types of cancer. However, cardiotoxicity is a major side effect of DOXO therapy due to the ability of this compound to induce cardiac cellular senescence. It is well known that microRNA (miR)-34a serves a role in cardiac dysfunction and ageing, and that it is involved in several cellular processes associated with DOXO-induced cardiotoxicity. Furthermore, mesenchymal stem cell (MSC)-based therapies have been reported to modulate cellular senescence...
June 2018: Oncology Letters
Nariaki Tomiyama, Ryuji Ikeda, Yukihiko Nishizawa, Shogo Masuda, Yusuke Tajitsu, Yasuo Takeda
Cancer stem-like cells (CSCs), which possess the ability to self-renewal and are multipotent, are regarded as the cause of tumor formation, recurrence, metastasis and drug resistance. It is necessary to understand the properties of CSCs in order to treat them effectively. It has been previously reported that S100 family proteins, which carry calcium-binding EF-hand motifs and are associated with tumorigenic processes, serve crucial roles in maintaining cancer stem-like properties. S100A16 is upregulated in various types of cancer, including bladder, lung and pancreatic...
June 2018: Oncology Letters
Shuhui Hong, Xiaoyan Li, Ying Zhao, Qifeng Yang, Beihua Kong
The major problems faced during the treatment of ovarian cancer are metastasis and the development of intrinsic or acquired drug resistance. The present study assessed whether tumor protein p53 binding protein 1 (53BP1) regulated migration and modulated chemotherapy resistance in SKOV3 cells and identified proteins associated with the molecular mechanisms underlying this coordinate regulation. SKOV3 cells were transfected using a 53BP1-expressing vector, which induced 53BP1 overexpression. The migration of the transfected cells was observed using a Transwell assay...
June 2018: Oncology Letters
Lin Li, Rong-Li Qiu, Yu Lin, Ying Cai, Yong Bian, Yan Fan, Xiao-Jun Gao
Numerous studies have demonstrated the apoptotic and anti-proliferative effects of resveratrol, a natural polyphenolic phytoalexin, on various cancer cell lines. However, the effects of resveratrol on the regulation of human cervical carcinoma, and the mechanisms underlying these effects, remain to be elucidated. In the present study, the potential mechanisms underlying the effects of resveratrol in HeLa cervical carcinoma cells were investigated. The results revealed that resveratrol inhibited proliferation and induced apoptosis in HeLa human cervical cancer cells in a dose-dependent and time-dependent manner...
June 2018: Oncology Letters
Hong Gao, Hai Dong, Guijun Li, Hui Jin
The aim of the present study was to determine whether acetazolamide (Ace) treatment enhances the chemosensitivity of Hep-2 laryngeal cells to cisplatin (Cis). At the logarithmic growth phase, Hep-2 cells were treated with Ace, Cis or both, and cell viability was detected using an MTT assay. The degree of apoptosis was detected using flow cytometry. Expression levels of apoptosis-related proteins, including BCL2 apoptosis regulator (bcl-2), BCL2 associated X (bax) and caspase-3, and of proliferation-related proteins, including proliferating cell nuclear antigen (PCNA) and tumor protein p53 (P53), were detected using western blotting...
June 2018: Oncology Letters
Zhongcheng Zhu
The active ingredients of natural plants are important sources of antitumor agents. Miltirone is a major effective ingredient in traditional Chinese medicine and it is considered to have anti-infection and immunosuppressive activities. Clinically, it is often used for the treatment of arthritis and immune diseases. The effect of miltirone on cisplatin-resistant lung cancer cells has not been investigated to date. The present study aimed to examine the anticancer effect of miltirone in cisplatin-resistant lung cancer cells...
June 2018: Oncology Letters
Somaia M Abdelmegeed, Sulma Mohammed
Animal models for examining human breast cancer (HBC) carcinogenesis have been extensively studied and proposed. With the recent advent of immunotherapy, significant attention has been focused on the dog as a model for human cancer. Dogs develop mammary tumors and other cancer types spontaneously with an intact immune system, which exhibit a number of clinical and molecular similarities to HBC. In addition to the spontaneous tumor presentation, the clinical similarities between human and canine mammary tumors (CMT) include the age at onset, hormonal etiology and course of the diseases...
June 2018: Oncology Letters
Shahnawaz Ali, Md Zubbair Malik, Soibam Shyamchand Singh, Keilash Chirom, Romana Ishrat, R K Brojen Singh
The breast cancer network constructed from 70 experimentally verified genes is found to follow hierarchical scale free nature with heterogeneous modular organization and diverge leading hubs. The topological parameters (degree distributions, clustering co-efficient, connectivity and centralities) of this network obey fractal rules indicating absence of centrality lethality rule, and efficient communication among the components. From the network theoretical approach, we identified few key regulators out of large number of leading hubs, which are deeply rooted from top to down of the network, serve as backbone of the network, and possible target genes...
2018: PloS One
Stefanie Klenke, Sebastian Eul, Jürgen Peters, Till Neumann, Michael Adamzik, Ulrich H Frey
Ischemic cardiomyopathy (ICM) is characterized by accumulation of p53 causing apoptosis of cardiomyocytes and resulting in upregulation of miRNA (miR)-192, which plays an important role in the development of heart failure after acute myocardial infarction. However, for other cardiomyopathies, miR-192 seems to have minor relevance. We tested in a prospective, observational study comprising 91 patients with diagnosed heart failure (59.3% ICM and 40.7% non-ICM), the hypothesis that miR-192 expression predicts survival in patients with ICM...
June 21, 2018: Future Cardiology
Hailin Guo, Xufeng Peng, Chongrui Jin, Lin Wang, Fang Chen, Yinglong Sa
To evaluate the characteristics of lichen sclerosus (LS) accompanied by urethral squamous cell carcinoma (USCC) and to raise urologists' awareness about the early management of LS, a retrospective analysis was performed on the clinical features, diagnosis, treatment, and prognosis of 18 male genital LS accompanied by USCC patients who were referred to Shanghai Sixth People's Hospital between June 2000 and August 2014. All of the patients had a long-term history of LS, urethral strictures, and urethral dilatation...
June 1, 2018: American Journal of Men's Health
Soojin Jang, Se Min Ryu, Jooyeon Lee, Hanbyeol Lee, Seok Ho Hong, Kwon Soo Ha, Won Sun Park, Eun Taek Han, Se Ran Yang
BACKGROUND: Idiopathic pulmonary fibrosis involves irreversible alveolar destruction. Although alveolar epithelial type II cells are key functional participants within the lung parenchyma, how epithelial cells are affected upon bleomycin (BLM) exposure remains unknown. In this study, we determined whether BLM could induce cell cycle arrest via regulation of Schlafen (SLFN) family genes, a group of cell cycle regulators known to mediate growth-inhibitory responses and apoptosis in alveolar epithelial type II cells...
June 19, 2018: Tuberculosis and Respiratory Diseases
Ming-Yue Liu, Ming-Jia Zhang, Ming-Jie Xie
AMP-activated protein kinase (AMPK), an evolutionarily conserved serine/threonine protein kinase, is known as the "cellular energy regulator" and a key molecule to maintain the energy balance of cells and organism. Recent studies have shown that AMPK exerts anti-inflammatory effects mainly through activating SIRT1, PGC-1α, p53, FoxO3a and p300, and down-regulating the activity of various inflammatory related proteins such as NF-κB and AP-1. This article reviews the molecular mechanisms of the anti- inflammatory effects of AMPK, and provides some clues for the development of AMPK-targeted therapeutics to treat inflammation and related diseases...
June 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Jennifer Fraszczak, Charles Vadnais, Marissa Rashkovan, Julie Ross, Hugues Beauchemin, Riyan Chen, Damien Grapton, Cyrus Khandanpour, Tarik Möröy
Growth factor independent 1 (Gfi1) controls myeloid differentiation by regulating gene expression and limits the activation of p53 by facilitating its de-methylation at Lysine 372. In human myeloid leukemia, low GFI1 levels correlate with an inferior prognosis. Here, we show that knockdown (KD) of Gfi1 in mice causes a fatal myeloproliferative disease (MPN) that could progress to leukemia after additional mutations. Both KO and KD mice accumulate myeloid cells that show signs of metabolic stress and high levels of reactive oxygen species...
June 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Katherine A White, Vicki J Swier, Jacob T Cain, Jordan L Kohlmeyer, David K Meyerholz, Munir R Tanas, Johanna Uthoff, Emily Hammond, Hua Li, Frank A Rohret, Adam Goeken, Chun-Hung Chan, Mariah R Leidinger, Shaikamjad Umesalma, Margaret R Wallace, Rebecca D Dodd, Karin Panzer, Amy H Tang, Benjamin W Darbro, Aubin Moutal, Song Cai, Wennan Li, Shreya S Bellampalli, Rajesh Khanna, Christopher S Rogers, Jessica C Sieren, Dawn E Quelle, Jill M Weimer
Loss of the NF1 tumor suppressor gene causes the autosomal dominant condition, neurofibromatosis type 1 (NF1). Children and adults with NF1 suffer from pathologies including benign and malignant tumors to cognitive deficits, seizures, growth abnormalities, and peripheral neuropathies. NF1 encodes neurofibromin, a Ras-GTPase activating protein, and NF1 mutations result in hyperactivated Ras signaling in patients. Existing NF1 mutant mice mimic individual aspects of NF1, but none comprehensively models the disease...
June 21, 2018: JCI Insight
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