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https://www.readbyqxmd.com/read/28647401/human-papillomavirus-infection-increases-the-chemoradiation-response-of-esophageal-squamous-cell-carcinoma-based-on-p53-mutation
#1
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/28646407/associations-of-red-and-processed-meat-intake-with-major-molecular-pathological-features-of-colorectal-cancer
#2
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/28645738/human-germline-hedgehog-pathway-mutations-predispose-to-fatty-liver
#3
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/28644435/p53-amyloid-formation-leading-to-its-loss-of-function-implications-in-cancer-pathogenesis
#4
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/28644145/colorectal-carcinoma-with-osseous-metaplasia
#5
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/28643165/molecularly-targeted-therapies-for-p53-mutant-cancers
#6
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/28642860/ataxia-telangiectasia-mutated-atm-polymorphisms-and-risk-of-lung-cancer-in-a-chinese-population
#7
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/28640835/bilateral-blockade-of-mek-and-pi3k-mediated-pathways-downstream-of-mutant-kras-as-a-treatment-approach-for-peritoneal-mucinous-malignancies
#8
Murali R Kuracha, Peter Thomas, Brian W Loggie, Venkatesh Govindarajan
Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28638459/towards-prognostic-profiling-of-non-small-cell-lung-cancer-new-perspectives-on-the-relevance-of-polo-like-kinase-1-expression-the-tp53-mutation-status-and-hypoxia
#9
Jolien Van den Bossche, Christophe Deben, Ken Op de Beeck, Vanessa Deschoolmeester, Christophe Hermans, Ines De Pauw, Julie Jacobs, Paul Van Schil, Jan Baptist Vermorken, Patrick Pauwels, Marc Peeters, Filip Lardon, An Wouters
Background: Currently, prognosis of non-small cell lung cancer (NSCLC) patients is based on clinicopathological factors, including TNM stage. However, there are considerable differences in patient outcome within a similar staging group, even when patients received identical treatments. In order to improve prognostic predictions and to guide treatment options, additional parameters influencing outcome are required. Polo-like kinase 1 (Plk1), a master regulator of mitotic cell division and the DNA damage response, is considered as a new potential biomarker in this research area...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28636549/p53-independent-p21-induction-by-melk-inhibition
#10
Tatsuo Matsuda, Taigo Kato, Kazuma Kiyotani, Yunus Emre Tarhan, Vassiliki Saloura, Suyoun Chung, Koji Ueda, Yusuke Nakamura, Jae-Hyun Park
MELK play critical roles in human carcinogenesis through activation of cell proliferation, inhibition of apoptosis and maintenance of stemness. Therefore, MELK is a promising therapeutic target for a wide range of cancers. Although p21 is a well-known p53-downstream gene, we found that treatment with a potent MELK inhibitor, OTS167, could induce p21 protein expression in cancer cell lines harboring loss-of-function TP53 mutations. We also confirmed that MELK knockdown by siRNA induced the p21 expression in p53-deficient cancer cell lines and caused the cell cycle arrest at G1 phase...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633336/a278c-mutation-of-dihydropteridine-reductase-decreases-autophagy-via-mtor-signaling
#11
Qin Si, Sifan Sun, Yanting Gu
Dihydropteridine reductase (QDPR) plays an important role in the recycling of BH4 and is closely related to oxidative stress. We have previously reported that the overexpression of QDPR in human kidney HEK293T cells significantly protected against oxidative stress, and these beneficial effects were abolished by A278C mutation. To evaluate the effect of wild-type and mutant QDPR on autophagy and its mechanism in HEK293T cells, we constructed the wild-type and mutant QDPR expression plasmids and transfected them into HEK293T cells...
June 15, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28631713/-braf-positive-paucicellular-variant-of-anaplastic-carcinoma-in-the-presence-of-tall-cell-variant-papillary-thyroid-cancer
#12
O V Dolzhansky, E M Paltseva, D N Khmelkova, F A Konovalov, I V Kanivets, A V Lavrov, D V Pyankov, S A Korostelev, O A Levendyuk, V M Pominalnaya, D N Fedorov
To paper describes a case of paucicellular anaplastic cancer in the presence of tall cell variant papillary thyroid carcinoma. Microscopic examination showed that the differentiated component of the tumor was composed of papillary structures with tall cells, the height of which exceeded 3-4 times the width. Its anaplastic component consisted of fibrous tissue with occasional spindle-shaped cells and focal lymphocytic infiltration to the extent of 70%. The spindle-shaped cells expressed cytokeratins, β-catenin, p53, and vimentin...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28630281/evidence-of-a-prion-like-transmission-of-p53-amyloid-in-saccharomyces-cerevisiae
#13
Shinjinee Sengupta, Samir K Maji, Santanu K Ghosh
Loss of p53 function is largely responsible for the occurrence of cancer in human. Aggregation of mutant p53 has been found in multiple cancer cell types suggesting a role of aggregation for loss of p53 function and cancer development. The p53 protein has recently been hypothesized to possess a prion-like conformation although experimental evidence is lacking. Here, we report that human p53 can be inactivated upon exposure to preformed fibrils containing an aggregation prone sequence specific peptide PILTIITL derived from p53 and the inactive state was found to be stable for many generations...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28629288/p53-mutation-and-epigenetic-imprinted-igf2-h19-gene-analysis-in-mesenchymal-stem-cells-derived-from-amniotic-fluid-amnion-endometrium-and-wharton-s-jelly
#14
Tatsanee Phermthai, Puttachart Pokathikorn, Suparat Wichitwiengrat, Sasiprapa Thongbopit, Kittima Tungprasertpol, Suphakde Julavijitphong
Mesenchymal stem cells (MSC) are promising cells for medical therapy. In in vitro expansion, MSC can give rise to progeny with genomic and epigenomic alterations, resulting in senescence, loss terminal differentiation and transformation to cancer. However, MSC genome protects its genetic instability via a guardian function of the P53 tumor suppressor gene and epigenetic balance system during MSC culture. Mutations of P53 and epigenetic alterations have been reported to disrupt the quality and quantity of MSC and initiate tumorigenesis...
June 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28628120/intestinal-cancer-progression-by-mutant-p53-through-the-acquisition-of-invasiveness-associated-with-complex-glandular-formation
#15
M Nakayama, E Sakai, K Echizen, Y Yamada, H Oshima, T-S Han, R Ohki, S Fujii, A Ochiai, S Robine, D C Voon, T Tanaka, M M Taketo, M Oshima
Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated Apc(Δ716) Trp53(LSL•R270H) villin-CreER compound mice, in which mutant p53(R270H) was expressed in the intestinal epithelia upon tamoxifen treatment, and examined the intestinal tumor phenotypes and tumor-derived organoids...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28626092/-p53-gene-mutations-of-familial-breast-cancer-and-early-onset-breast-cancer-in-part-population-of-southern-china
#16
Xueli Hu, Huiying Ouyang, Hao Wang, Hui Li, Feiyu Chen, Xu Dai, Weibing Zhou, Yuanping Hu, Qian Xue
To investigate the site and characteristic of p53 gene mutations in familial or early-onset breast cancer patients in part population of southern China.
 Methods: A total of 150 patients with familial and early-onset breast cancer in parts population of southern China were enrolled. Genomic DNA was isolated from each peripheral blood sample, and the entire coding sequence and exon and intron splicing region of p53 gene were amplificated by PCR in the 150 patients. The mutation analysis were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by DNA sequence analysis...
May 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28625654/line-1-hypomethylation-is-associated-to-specific-clinico-pathological-features-in-stage-i-non-small-cell-lung-cancer
#17
Andrea Imperatori, Nora Sahnane, Nicola Rotolo, Francesca Franzi, Elisa Nardecchia, Laura Libera, Chiara Romualdi, Maria Cattoni, Fausto Sessa, Lorenzo Dominioni, Daniela Furlan
OBJECTIVES: We hypothesize that selected genetic and/or epigenetic changes associated with advanced tumours may help identifying early non-small cell lung cancers (NSCLCs) that recur after resection. Among epigenetic changes, long interspersed nuclear element-1 (LINE-1) hypomethylation is seen early during carcinogenesis and may act in concert with genetic alterations to cancer progression. LINE-1 hypomethylation and gene mutations frequently involved in lung cancer, were analysed to evaluate their prognostic role in resected stage I NSCLC...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28623607/presenilin-1-targeted-morpholino-induces-cognitive-deficits-increased-brain-a%C3%AE-1-42-and-decreased-synaptic-marker-psd-95-in-zebrafish-larvae
#18
Laura Roesler Nery, Natalia Eltz Silva, Raphaela Fonseca, Monica Ryff Moreira Vianna
Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also act as the catalytic core of the γ-secretase complex, which is responsible for the final cleavage of the amyloid precursor protein into Amyloid-β (Aβ) peptides of varying lengths. Presenilin-1 gene (psen1) mutations are the main cause of early-onset autosomal-dominant Familial Alzheimer Disease. Elucidating the roles of Presenilin-1 and other hallmark proteins involved in Alzheimer's disease is crucial for understanding the disease etiology and underlying molecular mechanisms...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28622687/identification-of-a-novel-p53-target-col17a1-that-inhibits-breast-cancer-cell-migration-and-invasion
#19
Varalee Yodsurang, Chizu Tanikawa, Takafumi Miyamoto, Paulisally Hau Yi Lo, Makoto Hirata, Koichi Matsuda
p53 mutation is a marker of poor prognosis in breast cancers. To identify downstream targets of p53, we screened two transcriptome datasets, including cDNA microarrays of MCF10A breast epithelial cells with wild-type p53 or p53-null background, and RNA sequence analysis of breast invasive carcinoma. Here, we unveil ten novel p53 target candidates that are up-regulated after the induction of p53 in wild-type cells. Their expressions are also high in breast invasive carcinoma tissues with wild-type p53. The GO analysis identified epidermis development and ectoderm development, which COL17A1 participates, as significantly up-regulated by wild-type p53...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#20
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
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