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P53 -apoptosis

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https://www.readbyqxmd.com/read/28651368/risk-of-recurrence-in-pituitary-neuroendocrine-tumors-a-prospective-study-using-a-five-tiered-classification
#1
Gérald Raverot, Emmanuelle Dantony, Julie Beauvy, Alexandre Vasiljevic, Sara Mikolasek, Françoise Borson-Chazot, Emmanuel Jouanneau, Pascal Roy, Jacqueline Trouillas
Background: Most pituitary neuroendocrine tumors (PitNET) show benign behavior, but a significant number are invasive, recur or resist to medical treatment. Based on a retrospective case-control study we recently proposed a classification of PitNETs of prognostic relevance. This prospective study aims to test the value of this classification in an independent patient cohort. Methods: The cohort included patients of a single center operated upon a PitNET. Using a grading system based on invasion on MRI, immunocytochemical profile (ICC), Ki-67, mitotic index, and p53 positivity, tumors were classified...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28649645/a-functionally-significant-snp-in-tp53-and-breast-cancer-risk-in-african-american-women
#2
Maureen E Murphy, Song Liu, Song Yao, Dezheng Huo, Qin Liu, Sonia C Dolfi, Kim M Hirshfield, Chi-Chen Hong, Qiang Hu, Andrew F Olshan, Temidayo O Ogundiran, Clement Adebamowo, Susan M Domchek, Katherine L Nathanson, Barbara Nemesure, Stefan Ambs, William J Blot, Ye Feng, Esther M John, Leslie Bernstein, Wei Zheng, Jennifer J Hu, Regina G Ziegler, Sarah Nyante, Sue A Ingles, Michael F Press, Sandra L Deming, Jorge L Rodriguez-Gil, Christopher A Haiman, Olufunmilayo I Olopade, Kathryn L Lunetta, Julie R Palmer, Christine B Ambrosone
A coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28648892/asciz-atmin-is-dispensable-for-atm-signaling-in-response-to-replication-stress
#3
Rui Liu, Ashleigh King, Nicolas C Hoch, Catherine Chang, Gemma L Kelly, Andrew J Deans, Jörg Heierhorst
The ATM kinase plays critical roles in the response to DNA double-strand breaks, and can also be activated by prolonged DNA replication blocks. It has recently been proposed that replication stress-dependent ATM activation is mediated by ASCIZ (also known as ATMIN, ZNF822), an essential developmental transcription factor. In contrast, we show here that ATM activation, and phosphorylation of its substrates KAP1, p53 and H2AX in response to the replication blocking agent aphidicolin was unaffected in both immortalized and primary ASCIZ/ATMIN-deficient murine embryonic fibroblasts compared to control cells...
June 17, 2017: DNA Repair
https://www.readbyqxmd.com/read/28647685/irtks-is-correlated-with-progression-and-survival-time-of-patients-with-gastric-cancer
#4
Li-Yu Huang, Xuefei Wang, Xiao-Fang Cui, He Li, Junjie Zhao, Chong-Chao Wu, Lingqiang Min, Zhicheng Zhou, Lixin Wan, Yu-Ping Wang, Chao Zhang, Wei-Qiang Gao, Yihong Sun, Ze-Guang Han
BACKGROUND AND OBJECTIVES: IRTKS functions as a novel regulator of tumour suppressor p53; however, the role of IRTKS in pathogenesis of gastric cancer is unclear. DESIGN: We used immunohistochemistry to detect IRTKS levels in 527 human gastric cancer specimens. We generated both IRTKS-deficient and p53-deficient mice to observe survival time of these mice and to isolate mouse embryonic fibroblasts (MEFs) for evaluating in vivo tumorigenicity. Co-immunoprecipitation was used to study the interaction among p53, MDM2 and IRTKS, as well as the ubiquitination of p53...
June 24, 2017: Gut
https://www.readbyqxmd.com/read/28647496/a-comprehensive-complex-systems-approach-to-the-study-and-analysis-of-mammalian-cell-cycle-control-system-in-the-presence-of-dna-damage-stress
#5
Ali Abroudi, Sandhya Samarasinghe, Don Kulasiri
Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other...
June 21, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28647401/human-papillomavirus-infection-increases-the-chemoradiation-response-of-esophageal-squamous-cell-carcinoma-based-on-p53-mutation
#6
Dakai Zhang, Wei Zhang, Wenzhi Liu, Yu Mao, Zhanzhao Fu, Jia Liu, Wei Huang, Zicheng Zhang, Dianzheng An, Baosheng Li
BACKGROUND AND PURPOSE: A retrospective study was carried out to analyze multiple prognostic predictors, including human papillomavirus (HPV) infection for chemoradiation treatment of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: DNA extracted from a total of 192 patients treated with chemoradiation for locally advanced ESCC was examined to determine HPV status by polymerase chain reaction (PCR) and P53 gene mutation by genetic sequencing. The relationships between the chemoradiation response (CRR) and overall survival (OS) rate with HPV status and P53 gene mutation were analyzed...
June 21, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28647100/assessment-of-dna-ploidy-in-the-promise-molecular-subgroups-of-endometrial-cancer
#7
L Proctor, M Pradhan, S Leung, A Cheng, C H Lee, R A Soslow, C B Gilks, A Talhouk, J M McAlpine, H E Danielsen, L N Hoang
OBJECTIVE: We sought to determine whether DNA ploidy correlates with the four molecular subgroups of endometrial carcinoma (EC) as determined using ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). METHODS: 90 cases of EC previously characterized by clinicopathological parameters, outcomes, and ProMisE molecular subgroup (POLE EDM, MMR-D, p53 wt or p53 abn) were assessed for DNA ploidy using image cytometry. Associations of ploidy with traditional clinicopathological parameters were also tested...
June 21, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28646407/associations-of-red-and-processed-meat-intake-with-major-molecular-pathological-features-of-colorectal-cancer
#8
Prudence R Carr, Lina Jansen, Stefanie Bienert, Wilfried Roth, Esther Herpel, Matthias Kloor, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister
Red and processed meat is an established risk factor for colorectal cancer (CRC). However, exact mechanisms to explain the associations remain unclear. Few studies have investigated the association with CRC by molecular tumor features, which could provide relevant information on associated molecular pathways. In this population-based case-control study from Germany (DACHS), 2449 cases and 2479 controls provided information on risk factors of CRC and completed a food frequency questionnaire. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between meat intake and risk of CRC by molecular pathologic features and specific subtypes...
June 23, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28646197/upregulate-kif4a-enhances-proliferation-invasion-of-hepatocellular-carcinoma-and-indicates-poor-prognosis-across-human-cancer-types
#9
Guojun Hou, Chuanpeng Dong, Zihui Dong, Gang Liu, Huilin Xu, Lei Chen, Lei Liu, Hongyang Wang, Weiping Zhou
Hepatocellular carcinoma (HCC) is one of the most aggressive and heterogeneous cancers worldwide. Herein, we demonstrate KIF4A (Chromosome-associated kinesin KIF4A) as a potential biomarker, is up-regulated in most samples of HCC. The expression level of KIF4A in tumor tissue is significantly associated with the survival time, and a significant correlation between KIF4A expression and clinical information stage, metastasis and tumor dimension was observed. We further measured the proliferation and migration ability of two HCC cell lines, HCC-LM3 and PLC/PRF/5, following KIF4A-siRNA transfection...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645738/human-germline-hedgehog-pathway-mutations-predispose-to-fatty-liver
#10
Maria J Guillen Sacoto, Ariel F Martinez, Yu Abe, Paul Kruszka, Karin Weiss, Joshua L Everson, Ramon Bataller, David E Kleiner, Jerrold M Ward, Kathleen K Sulik, Robert J Lipinski, Benjamin D Solomon, Maximilian Muenke
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations affecting this pathway. METHODS: Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD...
June 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#11
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644435/p53-amyloid-formation-leading-to-its-loss-of-function-implications-in-cancer-pathogenesis
#12
Saikat Ghosh, Shimul Salot, Shinjinee Sengupta, Ambuja Navalkar, Dhiman Ghosh, Reeba Jacob, Subhadeep Das, Rakesh Kumar, Narendra Nath Jha, Shruti Sahay, Surabhi Mehra, Ganesh M Mohite, Santanu K Ghosh, Mamata Kombrabail, Guruswamy Krishnamoorthy, Pradip Chaudhari, Samir K Maji
The transcriptional regulator p53 has an essential role in tumor suppression. Almost 50% of human cancers are associated with the loss of p53 functions, where p53 often accumulates in the nucleus as well as in cytoplasm. Although it has been previously suggested that amyloid formation could be a cause of p53 loss-of-function in subset of tumors, the characterization of these amyloids and its structure-function relationship is not yet established. In the current study, we provide several evidences for the presence of p53 amyloid formation (in human and animal cancer tissues); along with its isolation from human cancer tissues and the biophysical characterization of these tissue-derived fibrils...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644233/tyrosine-kinase-inhibitor-vatalanib-inhibits-proliferation-and-migration-of-human-pterygial-fibroblasts
#13
Hong Kyu Kim, Ji-Young Choi, Sang Min Park, Chang Rae Rho, Kyong Jin Cho, Sangmee Ahn Jo
PURPOSE: Vatalanib is a small-molecule tyrosine kinase inhibitor. We investigated the effects of vatalanib on the proliferation and migration of cultured human pterygial fibroblasts (HPFs). METHODS: Pterygium tissues were obtained after pterygium excision surgery and subjected to primary culture. HPFs were treated with vatalanib at various concentrations. Mitomycin C (MMC) was used as a positive control. Cell proliferation and migration assays were used to investigate the effects of vatalanib...
June 21, 2017: Cornea
https://www.readbyqxmd.com/read/28644145/colorectal-carcinoma-with-osseous-metaplasia
#14
Xibo Liu, Jinghong Xu, Lirong Chen
Osseous metaplasia (OM) is rarely observed in colorectal cancer (incidence < 0.4% in rectal cancer), where it has a non-specific clinical presentation and unknown pathogenesis. Here, we report three cases of colorectal carcinoma with OM and propose a new hypothesis. All three patients (two males and one female) were Chinese and had different sites of colorectal carcinoma with OM: rectum, sigmoid colon, and appendix. The pathologic diagnoses were serrated adenocarcinoma; moderately to poorly differentiated adenocarcinoma with micropapillary carcinoma and cribriform comedo-type adenocarcinoma; and mucinous adenocarcinoma, respectively...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644127/mpi-depletion-enhances-o-glcnacylation-of-p53-and-suppresses-the-warburg-effect
#15
Charles DeRossi, Nataly Shtraizent, Shikha Nayar, Ravi Sachidanandam, Liora S Katz, Adam Prince, Anna P Koh, Adam Vincek, Yoav Hadas, Yujin Hoshida, Donald K Scott, Efrat Eliyahu, Hudson H Freeze, Kirsten C Sadler, Jaime Chu
Rapid cellular proliferation in early development and cancer depends on glucose metabolism to fuel macromolecule biosynthesis. Metabolic enzymes are presumed regulators of this glycolysis-driven metabolic program, known as the Warburg effect, however few have been identified. We uncover a previously unappreciated role for Mannose phosphate isomerase (MPI) as a metabolic enzyme required to maintain Warburg metabolism in zebrafish embryos and in both primary and malignant mammalian cells. The functional consequences of MPI loss are striking: glycolysis is blocked and cells die...
June 23, 2017: ELife
https://www.readbyqxmd.com/read/28643424/mdm2-is-implicated-in-high-glucose-induced-podocyte-mitotic-catastrophe-via-notch1-signalling
#16
Hui Tang, Chun-Tao Lei, Chen Ye, Pan Gao, Cheng Wan, Shan Chen, Fang-Fang He, Yu-Mei Wang, Hua Su, Chun Zhang
Podocyte injury and depletion are essential events involved in the pathogenesis of diabetic nephropathy (DN). As a terminally differentiated cell, podocyte is restricted in 'post-mitosis' state and unable to regenerate. Re-entering mitotic phase will cause podocyte disastrous death which is defined as mitotic catastrophe (MC). Murine double minute 2 (MDM2), a cell cycle regulator, is widely expressed in renal resident cells including podocytes. Here, we explore whether MDM2 is involved in podocyte MC during hyperglycaemia...
June 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28643165/molecularly-targeted-therapies-for-p53-mutant-cancers
#17
REVIEW
Dekuang Zhao, William M Tahaney, Abhijit Mazumdar, Michelle I Savage, Powel H Brown
The tumor suppressor p53 is lost or mutated in approximately half of human cancers. Mutant p53 not only loses its anti-tumor transcriptional activity, but also often acquires oncogenic functions to promote tumor proliferation, invasion, and drug resistance. Traditional strategies have been taken to directly target p53 mutants through identifying small molecular compounds to deplete mutant p53, or to restore its tumor suppressive function. Accumulating evidence suggest that cancer cells with mutated p53 often exhibit specific functional dependencies on secondary genes or pathways to survive, providing alternative targets to indirectly treat p53-mutant cancers...
June 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28642877/the-effect-of-sodium-valproate-on-the-glioblastoma-u87-cell-line-tumor-development-on-the-chicken-embryo-chorioallantoic-membrane-and-on-ezh2-and-p53-expression
#18
Dovilė Kavaliauskaitė, Donatas Stakišaitis, Justė Martinkutė, Lina Šlekienė, Arūnas Kazlauskas, Ingrida Balnytė, Vaiva Lesauskaitė, Angelija Valančiūtė
Literature data support evidences that glioblastoma (GBM) patients experience prolonged survival due to sodium valproate (NaVP) treatment. The study assessed the human GBM cell U87 xenograft studied in the chicken embryo chorioallantoic membrane (CAM) model evaluating NaVP effect on tumor. Three groups of tumors (each n = 10) were studied: nontreated, treated with 4 mM, and treated with 8 mM of NaVP. The majority of tumors without NaVP treatment during tumor growth destroyed the chorionic epithelium, invaded the mesenchyme, and induced angiogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642860/ataxia-telangiectasia-mutated-atm-polymorphisms-and-risk-of-lung-cancer-in-a-chinese-population
#19
Ajay A Myneni, Shen-Chih Chang, Rungui Niu, Li Liu, Baoxing Zhao, Jianping Shi, Xiaoyou Han, Jiawei Li, Jia Su, Shunzhang Yu, Zuo-Feng Zhang, Lina Mu
BACKGROUND: The ataxia telangiectasia-mutated (ATM) gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs) with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer. METHODS: A population-based case-control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28641640/-application-of-cd138-immunomagnetic-sorting-myeloma-cells-combined-with-fluorescence-in-situ-hybridization-for-detecting-cytogenetic-abnormalities-of-multiple-myeloma
#20
Lu Gao, Qing Liu, Yan Shi, Hui Dang, Qi He, Zheng Wang, Lin Feng, Ye Li, Xiao-Yan Wang, Na Li, Wen-Jie Song, Yan-Lin Wang, Shu Kong, Jin Lu, Xiao-Jun Huang, Yue-Yun Lai
OBJECTIVE: To investigate the efficiency of direct fluorescence in situ hybridization (D-FISH) versus FISH on CD138 immunomagnetic sorting myeloma cells (MACS-FISH) to detect the cytogenetic abnormalities of multiple myeloma. METHODS: Thirty-one patients with multiple myeloma (MM) were detected by D-FISH and MACS-FISH, using 5 probes, including 1q21, D13S319, RB1, IgH, P53. The IgH rearrangement positive patients were further examined by 3 IgH rearrangement subtype FISH probes including IgH/FGFR3, IgH/MAF and IgH/CCND1...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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