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https://www.readbyqxmd.com/read/28454449/bioinformatics-analysis-of-the-prognostic-value-of-tripartite-motif-28-in-breast-cancer
#1
Ling Hao, Jun Leng, Ruijing Xiao, Tembo Kingsley, Xinran Li, Zhenbo Tu, Xiangyong Yang, Xinzhou Deng, Meng Xiong, Jie Xiong, Qiuping Zhang
Tripartite motif containing 28 (TRIM28) is a transcriptional regulator acting as an essential corepressor for Krüppel-associated box zinc finger domain-containing proteins in multiple tissue and cell types. An increasing number of studies have investigated the function of TRIM28; however, its prognostic value in breast cancer (BC) remains unclear. In the present study, the expression of TRIM28 was identified to be significantly higher in cancerous compared with healthy tissue samples. Furthermore, it was demonstrated that TRIM28 expression was significantly correlated with several clinicopathological characteristics of patients with BC, such as p53 mutation, tumor recurrence and Elston grade of the tumor...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454404/correlation-between-epidermal-growth-factor-receptor-mutations-and-the-expression-of-estrogen-receptor-%C3%AE-in-advanced-non-small-cell-lung-cancer
#2
Fang Deng, Ming Li, Wu-Lin Shan, Li-Ting Qian, Shui-Ping Meng, Xiao-Lei Zhang, Bao-Long Wang
Epidermal growth factor receptor (EGFR) mutations are more common in non-small cell lung cancer (NSCLC) and in female patients of East Asian origin. Therefore, the present study investigated the presence of EGFR mutations in advanced NSCLC, and assessed its correlation with clinicopathologic factors, including the expression of estrogen receptor-β (ER-β) and patient prognosis. The present study performed a retrospective analysis of 83 patients with stage IIIB-IV NSCLC. The expression of ER-β and p53 were examined using immunohistochemical methods...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454347/effect-of-cigarette-smoke-exposure-and-mutant-kras-overexpression-on-pancreatic-cell-proliferation
#3
Howard P Glauert, R Scott Elliott, Sung Gu Han, Mark Athey, Eun Y Lee, C Gary Gairola
Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRas(G12D)) in the pancreas as well as wild-type mice were exposed to environmental tobacco smoke for 2 weeks...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454325/mir-600-inhibits-cell-proliferation-migration-and-invasion-by-targeting-p53-in-mutant-p53-expressing-human-colorectal-cancer-cell-lines
#4
Peili Zhang, Zhigui Zuo, Aihua Wu, Wenjing Shang, Ruichun Bi, Qike Jin, Jianbo Wu, Lei Jiang
Mutations of the tumor protein p53 gene, a tumor suppressor, are one of the most frequent genetic alterations observed in cancer. It has been reported that mutations in p53 result in the loss of wild-type p53 activity, and the gain of novel oncogenic properties that promote tumor growth and progression. Recent studies have demonstrated that a number of microRNAs (miRs) are involved in the post-transcriptional regulation of p53. The present study demonstrates that miR-600 is a direct negative regulator of p53 through binding a site in the 3' untranslated region of p53 mRNA in human colorectal cancer (CRC) cells...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453558/tumor-targeted-sn38-inhibits-growth-of-early-stage-non-small-cell-lung-cancer-nsclc-in-a-kras-p53-transgenic-mouse-model
#5
Alexander Y Deneka, Leora Haber, Meghan C Kopp, Anna V Gaponova, Anna S Nikonova, Erica A Golemis
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities...
2017: PloS One
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#6
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
April 24, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28446533/prognostic-evaluation-of-epidermal-growth-factor-receptor-egfr-genotype-and-phenotype-parameters-in-triple-negative-breast-cancers
#7
Sofia Levva, Vassiliki Kotoula, Ioannis Kostopoulos, Kyriaki Manousou, Christos Papadimitriou, Kyriaki Papadopoulou, Sotiris Lakis, Kyriakos Koukoulias, Vasilios Karavasilis, George Pentheroudakis, Eufemia Balassi, Flora Zagouri, Ioannis G Kaklamanos, Dimitrios Pectasides, Evangelia Razis, Gerasimos Aravantinos, Pavlos Papakostas, Dimitrios Bafaloukos, Grigorios Rallis, Helen Gogas, George Fountzilas
BACKGROUND: Epidermal growth factor receptor (EGFR) aberrations have been implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their impact on prognosis and, therefore, druggability, remain controversial. Herein, we studied EGFR aberrations at different molecular levels and assessed their prognostic impact in patients with operable TNBC treated with adjuvant anthracycline-based chemotherapy. MATERIALS AND METHODS: We evaluated the prognostic impact of EGFR gene status by fluorescent in situ hybridization (FISH), EGFR coding mutations by Sanger and next-generation sequencing, relative EGFR messenger RNA (mRNA) levels by qPCR (upper quartile) and EGFR and p53 protein expression by immunohistochemistry (IHC), in 352 centrally-assessed tumors from an equal number of TNBC patients...
May 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28446506/analytic-pre-analytic-and-clinical-validation-of-p53-immunohistochemistry-for-detection-of-tp53-missense-mutation-in-prostate-cancer
#8
Liana Guedes, Fawaz Almutairi, Michael C Haffner, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Kasra Yousefi, Rajni Sharma, Angelo M De Marzo, George Netto, William B Isaacs, Ashley E Ross, Edward M Schaeffer, Tamara L Lotan
PURPOSE:TP53 missense mutations may help to identify prostate cancer (PCa) with lethal potential. Here, we pre-analytically, analytically and clinically validated a robust immunohistochemistry (IHC) assay to detect subclonal and focal TP53 missense mutations in PCa. <p>EXPERIMENTAL DESIGN: The p53 IHC assay was performed in a CLIA-accredited laboratory on the Ventana Benchmark immunostaining system. p53 protein nuclear accumulation was defined as any p53 nuclear labeling in >10% of tumor cells. 54 formalin fixed paraffin embedded (FFPE) cell lines from the NCI-60 panel and 103 FFPE PCa tissues (88 primary adenocarcinomas, 15 metastases) with known TP53 mutation status were studied...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28445531/antagomir-451-inhibits-oxygen-glucose-deprivation-ogd-induced-huvec-necrosis-via-activating-ampk-signaling
#9
Xi Yang, Xiao-Qing He, Guo-Dong Li, Yong-Qing Xu
Oxygen glucose deprivation (OGD) application in cultured human umbilical vein endothelial cells (HUVECs) mimics ischemic injuries. AntagomiR-451, the miroRNA-451 ("miR-451") inhibitor, could activate pro-survival AMP-activated protein kinase (AMPK) signaling. In the current study, we showed that forced-expression of antagomiR-451 depleted miRNA-451 and significantly attenuated OGD-induced necrosis of HUVECs. Activation of AMPK was required for antagomiR-451-mediated pro-survival actions. AMPK inhibition, by AMPKα shRNA or dominant negative mutation, almost completely abolishedantagomiR-451-mediated HUVEC protection again OGD...
2017: PloS One
https://www.readbyqxmd.com/read/28445466/human-pluripotent-stem-cells-recurrently-acquire-and-expand-dominant-negative-p53-mutations
#10
Florian T Merkle, Sulagna Ghosh, Nolan Kamitaki, Jana Mitchell, Yishai Avior, Curtis Mello, Seva Kashin, Shila Mekhoubad, Dusko Ilic, Maura Charlton, Genevieve Saphier, Robert E Handsaker, Giulio Genovese, Shiran Bar, Nissim Benvenisty, Steven A McCarroll, Kevin Eggan
Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28444994/induction-of-micronuclei-and-cell-cycle-arrest-by-some-tri-and-tetrachlorobiphenyls-in-mammalian-cells-deficient-in-xenobiotic-metabolizing-enzymes
#11
Haiyan Wang, Liwen Wei, Yifan Wu, Hansi Jia, Hao Jiang, Yungang Liu
Polychlorinated biphenyls (PCBs) are persistent organic pollutants with continued public health concerns. The lower chlorinated biphenyls are supposed to be mutagenic following metabolic activation. However, in a preliminary study, we recently observed induction of micronuclei by several PCBs in a subclone of Chinese hamster V79 cell line, V79-Mz, which is deficient in xenobiotic-metabolizing enzyme activities. In this study, metabolism-free genotoxicity of PCBs was investigated, using 10 tri- and tetrachlorobiphenyls, in V79, V79-Mz, and human hepatoma (HepG2) cell lines...
May 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28443149/inverted-urothelial-papilloma-a-review-of-diagnostic-pitfalls-and-clinical-management
#12
REVIEW
Mary K Sweeney, Soroush Rais-Bahrami, Jennifer Gordetsky
Inverted urothelial papilloma (IUP) is a rare, non-invasive endophytic lesion that accounts for 1-2% of urothelial tumours. On cystoscopy, IUP appears as a pedunculated/papillary mass with a smooth surface. On microscopy, IUP has an endophytic growth pattern with the bulk of the tumour covered by a superficial layer of urothelium, which can be hyperplastic or attenuated. The cytology should be bland, with uniform, spindled cells arranged in anastomosing trabeculae and cords with peripheral palisading of basaloid cells...
January 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28442631/p53-dynamics-in-response-to-dna-damage-vary-across-cell-lines-and-are-shaped-by-efficiency-of-dna-repair-and-activity-of-the-kinase-atm
#13
Jacob Stewart-Ornstein, Galit Lahav
Cellular systems show a wide range of signaling dynamics. Many of these dynamics are highly stereotyped, such as oscillations at a fixed frequency. However, most studies looking at the role of signaling dynamics focus on one or a few cell lines, leaving the diversity of dynamics across tissues or cell lines a largely unexplored question. We focused on the dynamics of the tumor suppressor protein p53, which regulates cell cycle arrest and apoptosis in response to DNA damage. We established live-cell reporters for 12 cancer cell lines expressing wild-type p53 and quantified p53 dynamics in response to double-strand break-inducing DNA damage...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28440661/morphological-features-and-prognostic-significance-of-arid1a-deficient-esophageal-adenocarcinomas
#14
Michael G Drage, Mingkhwan Tippayawong, Agoston T Agoston, Yifan Zheng, Raphael Bueno, Jason L Hornick, Robert D Odze, Amitabh Srivastava
CONTEXT: - The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. OBJECTIVE: - To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. DESIGN: - One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus-associated dysplasia, when feasible...
April 25, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28440416/fuca1-is-induced-by-wild-type-p53-and-expressed-at-different-levels-in-thyroid-cancers-depending-on-p53-status
#15
Nobuo Tsuchida, Masa-Aki Ikeda, Υoshizumu Ιshino, Michele Grieco, Giancarlo Vecchio
Fucose residues of cell surface glycans, which play important roles in growth, invasion and metastasis, are added by fucosyltransferases (FUTs) and removed by α-L-fucosidases (FUCAs). By the differential display method, we isolated a 3' non-coding region of α-L-fucosidase-1 (FUCA1) (a gene coding for the lysosomal fucosidase-1 enzyme) as a wild-type p53-inducible gene: 18S and 20S FUCA1 mRNA species were induced in Saos-2 cells transfected with a temperature-sensitive p53 mutant at the permissive temperature...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439615/wip1-phosphatase-as-pharmacological-target-in-cancer-therapy
#16
REVIEW
Soňa Pecháčková, Kamila Burdová, Libor Macurek
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target...
April 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28438622/p53-alteration-in-morphologically-normal-benign-breast-luminal-cells-in-brca-carriers-with-or-without-history-of-breast-cancer
#17
Xi Wang, Amber A El-Halaby, Hengwei Zhang, Qi Yang, Todd S Laughlin, Paul G Rothberg, Kristin Skinner, David G Hicks
Germ-line mutations in BRCA genes have been shown to predispose patients to breast cancer. Studies have suggested that p53 alteration is a necessary step in tumorigenesis in BRCA carriers. Our previous study showed p53 alteration in morphologically normal/benign breast luminal cells in sporadic breast cancer patients, the so-called "breast p53 signature". Here, we studied p53 status in 66 BRCA1/2 carriers' breasts; 29 patients with breast carcinoma (2 patients with bilateral breast carcinomas) and 37 without...
April 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28436392/the-dna-damage-response-in-neurons-die-by-apoptosis-or-survive-in-a-senescence-like-state
#18
Edward Fielder, Thomas von Zglinicki, Diana Jurk
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435450/exome-sequencing-of-oral-squamous-cell-carcinoma-reveals-molecular-subgroups-and-novel-therapeutic-opportunities
#19
Shih-Chi Su, Chiao-Wen Lin, Yu-Fan Liu, Wen-Lang Fan, Mu-Kuan Chen, Chun-Ping Yu, Wei-En Yang, Chun-Wen Su, Chun-Yi Chuang, Wen-Hsiung Li, Wen-Hung Chung, Shun-Fa Yang
Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features...
2017: Theranostics
https://www.readbyqxmd.com/read/28435405/establishment-and-characterization-of-6-novel-patient-derived-primary-pancreatic-ductal-adenocarcinoma-cell-lines-from-korean-pancreatic-cancer-patients
#20
Mi-Ju Kim, Min-Sun Kim, Sung Joo Kim, Soyeon An, Jin Park, Hosub Park, Jae Hoon Lee, Ki-Byung Song, Dae Wook Hwang, Suhwan Chang, Kyu-Pyo Kim, Seong-Yun Jeong, Song Cheol Kim, Seung-Mo Hong
BACKGROUND: Pancreatic ductal adenocarcinomas are among the most malignant neoplasms and have very poor prognosis. Our understanding of various cancers has recently improved the survival of patients with cancer, except for pancreatic cancers. Establishment of primary cancer cell lines of pancreatic ductal adenocarcinomas will be useful for understanding the molecular mechanisms of this disease. METHODS: Eighty-one surgically resected pancreatic ductal adenocarcinomas were collected...
2017: Cancer Cell International
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