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TP53 disruption

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https://www.readbyqxmd.com/read/29228154/comparative-transcriptomic-analysis-of-human-placentae-at-term-and-preterm-delivery
#1
Alison G Paquette, Heather M Brockway, Nathan D Price, Louis J Muglia
Purpose: Preterm birth affects 1 out of every 10 infants in the United States, resulting in substantial neonatal morbidity and mortality. Currently, there are few predictive markers and few treatment options to prevent preterm birth. A healthy, functioning placenta is essential to positive pregnancy outcomes. Previous studies have suggested that placental pathology may play a role in preterm birth etiology. Therefore, we tested the hypothesis that preterm placentae may exhibit unique transcriptomic signatures compared to term samples reflective of their abnormal biology leading to this adverse outcome...
December 4, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29222275/the-mutational-landscape-of-chronic-lymphocytic-leukemia-and-its-impact-on-prognosis-and-treatment
#2
REVIEW
Gianluca Gaidano, Davide Rossi
The typical genome of chronic lymphocytic leukemia (CLL) carries ∼2000 molecular lesions. Few mutations recur across patients at a frequency >5%, whereas a large number of biologically and clinically uncharacterized genes are mutated at lower frequency. Approximately 80% of CLL patients carry at least 1 of 4 common chromosomal alterations, namely deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Knowledge of the CLL genome has translated into the availability of molecular biomarkers for prognosis and treatment prediction...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29192272/ribosomal-stress-and-tp53-mediated-neuronal-apoptosis-in-response-to-capsid-protein-of-the-zika-virus
#3
Lukasz P Slomnicki, Dong-Hoon Chung, Austin Parker, Taylor Hermann, Nolan L Boyd, Michal Hetman
We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29143255/pcb-exposure-and-potential-future-cancer-incidence-in-slovak-children-an-assessment-from-molecular-finger-printing-by-ingenuity-pathway-analysis-ipa%C3%A2-derived-from-experimental-and-epidemiological-investigations
#4
Somiranjan Ghosh, Christopher A Loffredo, Partha S Mitra, Tomas Trnovec, Lubica Palkovicova Murinova, Eva Sovcikova, Eric P Hoffman, Kepher H Makambi, Sisir K Dutta
The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and disorder pathways, viz., endocrine disruption, metabolic disorder & diabetes, and cancer, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention...
November 15, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29100379/gambogic-acid-inhibits-thioredoxin-activity-and-induces-ros-mediated-cell-death-in-castration-resistant-prostate-cancer
#5
Hong Pan, Keith H Jansson, Michael L Beshiri, JuanJuan Yin, Lei Fang, Supreet Agarwal, Holly Nguyen, Eva Corey, Ying Zhang, Jie Liu, HuiTing Fan, HongSheng Lin, Kathleen Kelly
Advanced prostate cancer (PrCa) is treated with androgen deprivation therapy, and although there is usually a significant initial response, recurrence arises as castrate resistant prostate cancer (CRPC). New approaches are needed to treat this genetically heterogeneous, phenotypically plastic disease. CRPC with combined homozygous alterations to PTEN and TP53 comprise about 30% of clinical samples. We screened eleven traditional Chinese medicines against a panel of androgen-independent Pten/Tp53 null PrCa-derived cell lines and identified gambogic acid (GA) as a highly potent growth inhibitor...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29077690/small-cell-lung-cancer-what-we-know-what-we-need-to-know-and-the-path-forward
#6
REVIEW
Adi F Gazdar, Paul A Bunn, John D Minna
Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling...
October 27, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29063177/approach-to-richter-transformation-of-chronic-lymphocytic-leukemia-in-the-era-of-novel-therapies
#7
REVIEW
Maliha Khan, Rabbia Siddiqi, Philip A Thompson
Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. About 2-10% of CLL patients develop aggressive histological transformation, most commonly to diffuse large B cell lymphoma (DLBCL), historically called Richter transformation (RT). Clinical features suggestive of RT include elevated LDH and non-specific symptoms such as fever, weight loss, and lymphadenopathy. 18-fluorodeoxyglucose (18-FDG) uptake is increased on PET scan (standardized uptake value max most commonly ≥ 10). PET/CT study can identify optimal site for excisional biopsy, which is the gold standard for RT diagnosis, as well as aid in disease staging and prognostication...
October 23, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29025288/-state-of-the-art-molecular-diagnostics-and-therapy-of-chronic-lymphocytic-leukaemia-in-the-era-of-new-targeted-therapies
#8
Tímea Gurbity Pálfi, Viktória Fésüs, Csaba Bödör, Zita Borbényi
Chronic lymphoid leukaemia (CLL) has a heterogeneous clinical course depending on many clinical and molecular prognostic markers, which play an important role in the selection of the best treatment option. So far, TP53 disruption is the key prognostic and predictive factor assisting treatment decisions, especially in the era of novel therapies. Asymptomatic patients in early stages of the disease will still benefit from watchful waiting. In the frontline setting, chemoimmunotherapy is still the standard care in the majority of standard risk CLL patients...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28994094/novel-prognostic-molecular-factors-a-quantum-leap-in-the-field-of-chronic-lymphocytic-leukemia
#9
Ewelina Zakrzewska, Marta Pirog, Joanna Purkot, Krzysztof Giannopoulos
Cytogenetic lesions do not completely explain clinical heterogeneity of chronic lymphocytic leukemia (CLL). The 2016 revision of the World Health Organization classification 2008 introduced that molecular lesions of TP53, NOTCH1, SF3B1 and BIRC3 have potential clinical relevance and could be integrated into an updated risk profile. The negative clinical implications of TP53 disruptions are well constituted and patients with these mutations should be considered for novel, small molecule signal transduction inhibitors therapies...
October 10, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28973975/identification-of-linkages-between-edcs-in-personal-care-products-and-breast-cancer-through-data-integration-combined-with-gene-network-analysis
#10
Hyeri Jeong, Jongwoon Kim, Youngjun Kim
Approximately 1000 chemicals have been reported to possibly have endocrine disrupting effects, some of which are used in consumer products, such as personal care products (PCPs) and cosmetics. We conducted data integration combined with gene network analysis to: (i) identify causal molecular mechanisms between endocrine disrupting chemicals (EDCs) used in PCPs and breast cancer; and (ii) screen candidate EDCs associated with breast cancer. Among EDCs used in PCPs, four EDCs having correlation with breast cancer were selected, and we curated 27 common interacting genes between those EDCs and breast cancer to perform the gene network analysis...
September 30, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28911001/whole-exome-analysis-of-a-li-fraumeni-family-trio-with-a-novel-tp53-prd-mutation-and-anticipation-profile
#11
Sara Franceschi, Laura Spugnesi, Paolo Aretini, Francesca Lessi, Rosa Scarpitta, Alvaro Galli, Caterina Congregati, Maria Adelaide Caligo, Chiara Maria Mazzanti
Li-Fraumeni syndrome is a clinically heterogeneous familial cancer predisposition syndrome with autosomal-dominant inheritance caused by heterozygous germline mutations in the TP53 gene. We here analyze the genetic background of a family with a 4-year-proband presented with a Li-Fraumeni tumor. The mother developed breast cancer at age 37 and the proband died at age 8. We performed Sanger sequencing and whole-exome sequencing on peripheral blood DNA from proband and relatives. Data analysis selected only high-quality score and depth reads, rare variants and protein impact involving missense, non-sense, frameshift and splice disrupt mutations...
September 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#12
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28790111/amiloride-an-old-diuretic-drug-is-a-potential-therapeutic-agent-for-multiple-myeloma
#13
Elizabeta A Rojas, Luis Antonio Corchete, Laura San-Segundo, Juan F Martínez-Blanch, Francisco M Codoñer, Teresa Paíno, Noemí Puig, Ramón García-Sanz, María Victoria Mateos, Enrique M Ocio, Irena Misiewicz-Krzeminska, Norma C Gutiérrez
Purpose: The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent antimyeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.Experimental Design: Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq experiments, qRT-PCR, immunoblotting, and immunofluorescence assays...
November 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28776759/melatonin-ameliorates-hypoglycemic-stress-induced-brain-endothelial-tight-junction-injury-by-inhibiting-protein-nitration-of-tp53-induced-glycolysis-and-apoptosis-regulator
#14
Cheng-Kun Wang, Muhammad Masood Ahmed, Quan Jiang, Nan-Nan Lu, Chao Tan, Yin-Ping Gao, Qaisar Mahmood, Dan-Yang Chen, Kohji Fukunaga, Mei Li, Zhong Chen, Christopher S Wilcox, Ying-Mei Lu, Zheng-Hong Qin, Feng Han
Severe hypoglycemia has a detrimental impact on the cerebrovasculature, but the molecular events that lead to the disruption of the integrity of the tight junctions remain unclear. Here, we report that the microvessel integrity was dramatically compromised (59.41% of wild-type mice) in TP53-induced glycolysis and apoptosis regulator (TIGAR) transgenic mice stressed by hypoglycemia. Melatonin, a potent antioxidant, protects against hypoglycemic stress-induced brain endothelial tight junction injury in the dosage of 400 nmol/L in vitro...
November 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28760909/circulating-tumor-dna-reveals-clinically-actionable-somatic-genome-of-metastatic-bladder-cancer
#15
Gillian Vandekerkhove, Tilman Todenhöfer, Matti Annala, Werner J Struss, Amanda Wong, Kevin Beja, Elie Ritch, Sonal Brahmbhatt, Stanislav V Volik, Jörg Hennenlotter, Matti Nykter, Kim N Chi, Scott North, Arnulf Stenzl, Colin C Collins, Bernhard J Eigl, Peter C Black, Alexander W Wyatt
Purpose: Targeted agents and immunotherapies promise to transform the treatment of metastatic bladder cancer, but therapy selection will depend on practical tumor molecular stratification. Circulating tumor DNA (ctDNA) is established in several solid malignancies as a minimally invasive tool to profile the tumor genome in real-time, but is critically underexplored in bladder cancer.Experimental Design: We applied a combination of whole-exome sequencing and targeted sequencing across 50 bladder cancer driver genes to plasma cell-free DNA (cfDNA) from 51 patients with aggressive bladder cancer, including 37 with metastatic disease...
July 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28718729/the-novel-autophagy-inhibitor-elaiophylin-exerts-antitumor-activity-against-multiple-myeloma-with-mutant-tp53-in-part-through-endoplasmic-reticulum-stress-induced-apoptosis
#16
Gaoxiang Wang, Pan Zhou, Xing Chen, Lei Zhao, Jiaqi Tan, Yang Yang, Yong Fang, Jianfeng Zhou
Elaiophylin is a natural compound and a novel and potent inhibitor of late stage autophagy with outstanding antitumor activity in human ovarian cancer cells. However, the possible biologic effects and functional linkage between elaiophylin and multiple myeloma (MM) have not been explored. This study aimed to assess the effect of elaiophylin on MM cells with mutant TP53 and the possible molecular mechanism. The results suggested that elaiophylin exerted anti-myeloma activity by inducing apoptosis and proliferation arrest...
August 3, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28664506/prevalence-and-spectrum-of-germline-rare-variants-in-brca1-2-and-palb2-among-breast-cancer-cases-in-sarawak-malaysia
#17
Xiaohong R Yang, Beena C R Devi, Hyuna Sung, Jennifer Guida, Eliseos J Mucaki, Yanzi Xiao, Ana Best, Lisa Garland, Yi Xie, Nan Hu, Maria Rodriguez-Herrera, Chaoyu Wang, Kristine Jones, Wen Luo, Belynda Hicks, Tieng Swee Tang, Karobi Moitra, Peter K Rogan, Michael Dean
PURPOSE: To characterize the spectrum of germline mutations in BRCA1, BRCA2, and PALB2 in population-based unselected breast cancer cases in an Asian population. METHODS: Germline DNA from 467 breast cancer patients in Sarawak General Hospital, Malaysia, where 93% of the breast cancer patients in Sarawak are treated, was sequenced for the entire coding region of BRCA1; BRCA2; PALB2; Exons 6, 7, and 8 of TP53; and Exons 7 and 8 of PTEN. Pathogenic variants included known pathogenic variants in ClinVar, loss of function variants, and variants that disrupt splice site...
June 29, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28620865/involvement-of-atm-and-trp53-in-neural-cell-loss-due-to-terf2-inactivation-during-mouse-brain-development
#18
Jusik Kim, Inseo Choi, Youngsoo Lee
Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure...
November 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28537240/-point-mutations-in-the-dna-binding-domain-of-p53-contribute-to-glioma-progression-and-poor-prognosis
#19
P P Sarma, D Dutta, Z Mirza, K Kr Saikia, B Kr Baishya
TP53 mutations play a significant role in glioma tumorigenesis. When located in in the DNA binding domain, these mutations can perturb p53 protein conformation and its function, often culminating in altered downstream signaling. Here we describe prevalent pattern of TP53 point mutations in a cohort of 40 glioma patients and show their relevance to gliomagenesis. Point mutations in exon 5-9 of TP53 gene were detected by DNA sequencing. Possible influence of identified mutations at the function of p53 was studied computationally and correlated with the survival...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#20
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
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