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https://www.readbyqxmd.com/read/29053726/prevalence-of-deleterious-germline-variants-in-risk-genes-including-brca1-2-in-consecutive-ovarian-cancer-patients-ago-tr-1
#1
Philipp Harter, Jan Hauke, Florian Heitz, Alexander Reuss, Stefan Kommoss, Frederik Marmé, André Heimbach, Katharina Prieske, Lisa Richters, Alexander Burges, Guido Neidhardt, Nikolaus de Gregorio, Ahmed El-Balat, Felix Hilpert, Werner Meier, Rainer Kimmig, Karin Kast, Jalid Sehouli, Klaus Baumann, Christian Jackisch, Tjoung-Won Park-Simon, Lars Hanker, Sandra Kröber, Jacobus Pfisterer, Heidrun Gevensleben, Andreas Schnelzer, Dimo Dietrich, Tanja Neunhöffer, Mathias Krockenberger, Sara Y Brucker, Peter Nürnberg, Holger Thiele, Janine Altmüller, Josefin Lamla, Gabriele Elser, Andreas du Bois, Eric Hahnen, Rita Schmutzler
BACKGROUND: Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/29053175/distinct-pattern-of-tp53-mutations-in-human-immunodeficiency-virus-related-head-and-neck-squamous-cell-carcinoma
#2
Frederico O Gleber-Netto, Mei Zhao, Sanchit Trivedi, Jiping Wang, Samar Jasser, Christina McDowell, Humam Kadara, Jiexin Zhang, Jing Wang, William N William, J Jack Lee, Minh Ly Nguyen, Sara I Pai, Heather M Walline, Dong M Shin, Robert L Ferris, Thomas E Carey, Jeffrey N Myers, Curtis R Pickering
BACKGROUND: Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC...
October 20, 2017: Cancer
https://www.readbyqxmd.com/read/29050228/mutation-landscape-and-intra-tumor-heterogeneity-of-two-manecs-of-the-esophagus-revealed-by-multi-region-sequencing
#3
Wenqing Yuan, Zhen Liu, Wanjun Lei, Li Sun, Haijun Yang, Yu Wang, Shweta Ramdas, Xiao Dong, Ruiping Xu, Hong Cai, Jun Z Li, Yang Ke
Mixed adenoneuroendocrine carcinoma (MANEC) in the esophagus is an infrequent but highly malignant cancer with few known genomic alterations. We conducted whole-exome sequencing and whole-genome SNP genotyping for 4-6 tumor subregions and 5-6 adjacent normal tissue sites and 1-3 lymph node metastases in two esophageal MANECs to detect somatic mutations and copy number alterations, and to explore their spatial heterogeneity and underlying clonal structure. TP53 mutation, RB1 deletion or LOH, and PIK3CA, PTEN, KRAS, SOX2, DVL3, TP63 amplification appeared in all regions in both tumors...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049012/transcriptome-profiling-uncovers-potential-common-mechanisms-in-fetal-trisomies-18-and-21
#4
Marija Volk, Aleš Maver, Alenka Hodžić, Luca Lovrečić, Borut Peterlin
Human trisomies have recently been investigated using transcriptomics approaches to identify the gene expression (GE) signatures characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the activation of resilience mechanisms that are common to different trisomies and that are reflected by specific shared GE patterns. We report in this article our microarray GE analyses of amniocytes from fetuses with viable trisomy conditions, trisomy 21 or trisomy 18, to detect such common expression signatures...
October 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/29048679/enhanced-wild-type-p53-expression-by-small-activating-rna-dsp53-285-induces-cell-cycle-arrest-and-apoptosis-in-pheochromocytoma-cell-line-pc12
#5
Dengqiang Lin, Li Meng, Feifei Xu, Jianpo Lian, Yunze Xu, Xin Xie, Xiaojing Wang, Hongchao He, Chenghe Wang, Yu Zhu
Malignant pheochromocytoma (PHEO) is diagnosed only when metastasis has occurred, making it less likely for patients to obtain the benefits of traditional chemotherapy. Anti-oncogene TP53 mutation has been detected in PHEO and is possibly related to disease progression. However, whether the upregulation of wild-type TP53 has antitumoral effects on PHEO remains completely unknown. In the present study, we used RNA activation (RNAa) technique to upregulate the expression of wild-type TP53 by transfecting synthetic dsP53‑285 into PHEO cell line PC12...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048416/increased-frequency-of-kras-mutations-in-african-americans-compared-with-caucasians-in-sporadic-colorectal-cancer
#6
Jonas J Staudacher, Cemal Yazici, Vadim Bul, Joseph Zeidan, Ahmer Khalid, Yinglin Xia, Nancy Krett, Barbara Jung
OBJECTIVES: The basis for over-representation of colorectal cancer (CRC) in African-American (AA) populations compared with Caucasians are multifactorial and complex. Understanding the mechanisms for this racial disparity is critical for delivery of better care. Several studies have investigated sporadic CRC for differences in somatic mutations between AAs and Caucasians, but owing to small study sizes and conflicting results to date, no definitive conclusions have been reached. METHODS: Here, we present the first systematic literature review and meta-analysis investigating the mutational differences in sporadic CRC between AAs and Caucasians focused on frequent driver mutations (APC,TP53, KRAS,PI3CA, FBXW7,SMAD4, and BRAF)...
October 19, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/29048129/realgar-nanoparticles-versus-ato-arsenic-compounds-induce-in%C3%A2-vitro-and-in%C3%A2-vivo-activity-against-multiple-myeloma
#7
Danka Cholujova, Zdenka Bujnakova, Erika Dutkova, Teru Hideshima, Richard W Groen, Constantine S Mitsiades, Paul G Richardson, David M Dorfman, Peter Balaz, Kenneth C Anderson, Jana Jakubikova
Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow, remains incurable despite the use of novel and conventional therapies. In this study, we demonstrated MM cell cytotoxicity triggered by realgar (REA; As4 S4 ) nanoparticles (NREA) versus Arsenic trioxide (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo anti-MM activity, resulting in significantly decreased tumour burden. The anti-MM activity of NREA and ATO is associated with apoptosis, evidenced by DNA fragmentation, depletion of mitochondrial membrane potential, cleavage of caspases and anti-apoptotic proteins...
October 19, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29046940/gastric-cancer-immunohistochemical-classification-of-molecular-subtypes-and-their-association-with-clinicopathological-characteristics
#8
Eva-Maria Birkman, Naziha Mansuri, Samu Kurki, Annika Ålgars, Minnamaija Lintunen, Raija Ristamäki, Jari Sundström, Olli Carpén
Gastric cancer is traditionally divided into intestinal and diffuse histological subtypes, but recent molecular analyses have led to novel classification proposals based on genomic alterations. While the intestinal- and diffuse-type tumours are distinguishable from each other at the molecular level, intestinal-type tumours have more diverse molecular profile. The technology required for comprehensive molecular analysis is expensive and not applicable for routine clinical diagnostics. In this study, we have used immunohistochemistry and in situ hybridisation in molecular classification of gastric adenocarcinomas with an emphasis on the intestinal subtype...
October 19, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29046615/integrated-genomic-characterization-of-cancer-genes-in-glioma
#9
Aijun Liang, Bin Zhou, Wei Sun
BACKGROUND: Cancers are caused by the acquisition of somatic mutations. Numerous efforts have been made to characterize the key driver genes and pathways in glioma, however, the etiology of glioma is still not completely known. This study was implemented to characterize driver genes in glioma independently of somatic mutation frequencies. METHODS: Driver genes and pathways were predicted by OncodriveCLUST, OncodriveFM, Icages, Drgap and Dendrix in glioma using 31,958 somatic mutations from TCGA, followed by an integrative characterization of driver genes...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29046333/the-p53-inducible-long-noncoding-rna-trings-protects-cancer-cells-from-necrosis-under-glucose%C3%A2-starvation
#10
Muhammad Riaz Khan, Shaoxun Xiang, Zhiyin Song, Mian Wu
The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells...
October 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29044141/cdk2-strengthens-the-intra-s-checkpoint-and-counteracts-cell-cycle-exit-induced-by-dna-damage
#11
Katarina Bačević, Gérald Lossaint, Thiziri Nait Achour, Virginie Georget, Daniel Fisher, Vjekoslav Dulić
Although cyclin-dependent kinase 2 (Cdk2) controls the G1/S transition and promotes DNA replication, it is dispensable for cell cycle progression due to redundancy with Cdk1. Yet Cdk2 also has non-redundant functions that can be revealed in certain genetic backgrounds and it was reported to promote the G2/M DNA damage response checkpoint in TP53 (p53)-deficient cancer cells. However, in p53-proficient cells subjected to DNA damage, Cdk2 is inactivated by the CDK inhibitor p21. We therefore investigated whether Cdk2 differentially affects checkpoint responses in p53-proficient and deficient cell lines...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29043881/characterization-of-the-mutational-profile-of-11-diffuse-large-b-cell-lymphoma-cell-lines
#12
Darius Juskevicius, Anne Müller, Hind Hashwah, Pontus Lundberg, Alexandar Tzankov, Thomas Menter
Investigation of cancer cell lines is important for oncology research to characterize and understand mechanisms of cellular signaling and survival strategies in cancer. We analyzed the mutational profile of 11 diffuse large B-cell lymphoma (DLBCL) cell lines using a customized high throughput sequencing panel. We compared our data to previously published mutation data to better characterize these cell lines and establish consensus on the mutational status of some functionally relevant genes. With our targeted sequencing approach we detected 61 somatic mutations...
October 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29043595/stress-hormone-cortisol-enhances-bcl2-like-12-expression-to-inhibit-p53-in-hepatocellular-carcinoma-cells
#13
Weizhong Wu, Sanguang Liu, Yunfei Liang, Zegao Zhou, Wei Bian, Xueqing Liu
BACKGROUND AND AIMS: The pathogenesis of hepatocellular carcinoma (HC) is unclear. It is suggested that psychological stress associates with the pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53 protein. This study tests a hypothesis that the major stress hormone, cortisol, inhibits the expression of p53 in HC cells (HCC) via up regulating the expression of Bcl2L12. METHODS: Peripheral blood samples were collected from patients with HC to be analyzed for the levels of cortisol...
October 17, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29039494/internal-driving-factors-leading-to-extrahepatic-manifestation-of-the-hepatitis%C3%A2-c-virus-infection
#14
Zhou-Yi Wu, Jian-Rui Li, Meng-Hao Huang, Jun-Jun Cheng, Hu Li, Jin-Hua Chen, Xiao-Qin Lv, Zong-Gen Peng, Jian-Dong Jiang
The hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, which are correlated with poor outcomes, and thus increase the morbidity and mortality of chronic hepatitis C (CHC). Therefore, understanding the internal linkages between systemic manifestations and HCV infection is helpful for treatment of CHC. Yet, the mechanism by which the virus evokes the systemic diseases remains to be elucidated. In the present study, using gene set enrichment analysis (GSEA) and signaling pathway impact analysis (SPIA), a comprehensive analysis of microarray data of mRNAs was conducted in HCV-infected and -uninfected Huh7...
October 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29039119/clinical-implications-of-germline-mutations-in-breast-cancer-tp53
#15
REVIEW
Katherine Schon, Marc Tischkowitz
PURPOSE: This review describes the prevalence of germline TP53 mutations, the risk of breast cancer and other cancers in mutation carriers and management implications for women with breast cancer and unaffected women. METHODS: Literature review of English language papers available through PubMed. RESULTS: Women who carry germline mutations in the TP53 gene have a very high risk of breast cancer of up to 85% by age 60 years. Most of these breast cancers are early onset with a median age at diagnosis of 34 years...
October 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29036643/glass-assisted-and-standardized-assessment-of-gene-variations-from-sanger-sequence-trace-data
#16
Karol Pal, Vojtech Bystry, Tomas Reigl, Martin Demko, Adam Krejci, Tasoula Touloumenidou, Evangelia Stalika, Boris Tichy, Paolo Ghia, Kostas Stamatopoulos, Sarka Pospisilova, Jitka Malcikova, Nikos Darzentas
Motivation: Sanger sequencing is still being employed for sequence variant detection by many laboratories, especially in a clinical setting. However, chromatogram interpretation often requires manual inspection and in some cases, considerable expertise. Results: We present GLASS, a web-based Sanger sequence trace viewer, editor, aligner and variant caller, built to assist with the assessment of variations in 'curated' or user-provided genes. Critically, it produces a standardized variant output as recommended by the Human Genome Variation Society...
July 13, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29031505/-histological-and-molecular-classification-of-endometrial-carcinoma-and-therapeutical-implications
#17
REVIEW
Catherine Genestie, Alexandra Leary, Mojgan Devassoux-Shisheboran, Aurélie Auguste
Endometrial cancer is the fourth cause of cancer in women in France and is the second most common cancer of the gynecologic cancer after breast cancer with 7275 new cases in 2012. The incidence of this neoplasm tends to increase with population aging, diabetes and obesity's augmentation. In rare cases, a hereditary factor has been described: Lynch's syndrome. The therapeutic management of the patient depends on the endometrial biopsy which specifies the histological type and the histo-prognostic grade as well as the MRI which allow the tumor staging...
October 11, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29030491/autophagy-is-activated-in-the-ovarian-tissue-of-polycystic-ovary-syndrome
#18
Da Li, Yue You, Fang-Fang Bi, Tie-Ning Zhang, Jiao Jiao, Tian-Ren Wang, Yi-Ming Zhou, Zi-Qi Shen, Xiu-Xia Wang, Qing Yang
The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased...
October 13, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29029550/b-lymphoblastic-leukemia-lymphoma-new-insights-into-genetics-molecular-aberrations-subclassification-and-targeted-therapy
#19
REVIEW
Xiaohui Zhang, Prerna Rastogi, Bijal Shah, Ling Zhang
B lymphoblastic leukemia/lymphoma (B-ALL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mostly occurs in children and adolescents and is regarded as one of top leading causes of death related to malignancies in this population. Despite the majority of patients with B-ALL have fairly good response to conventional chemotherapeutic interventions followed by hematopoietic stem cell transplant for the last decades, a subpopulation of patients show chemo-resistance and a high relapse rate...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029407/molecular-profiling-of-colorectal-pulmonary-metastases-and-primary-tumours-implications-for-targeted-treatment
#20
Sing Y Moorcraft, Thomas Jones, Brian A Walker, George Ladas, Eleftheria Kalaitzaki, Lina Yuan, Ruwaida Begum, Zakaria Eltahir, Andrew Wotherspoon, Angeles Montero-Fernandez, Larissa S Teixeira Mendes, David Gonzalez de Castro, Sanna Hulkki Wilson, Paula Proszek, Ye M To, Eliza Hawkes, Amitesh Roy, David Cunningham, Sheela Rao, David Watkins, Naureen Starling, Anne M Bowcock, Ian Chau
This study aimed to molecularly characterise colorectal pulmonary metastases (PM) and investigate whether their molecular profiles were concordant with those of the primary tumour. Clinical data and archival formalin fixed paraffin embedded tissue samples were retrospectively collected from patients who underwent ≥ 1 pulmonary metastasectomies for colorectal cancer between 1997-2012. Primary tumour and metastatic samples were analysed using a targeted capture sequencing panel of 46 cancer-associated genes...
September 12, 2017: Oncotarget
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