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https://www.readbyqxmd.com/read/27874062/systemic-perioperative-management-of-muscle-invasive-bladder-cancer-and-future-horizons
#1
REVIEW
Samuel A Funt, Jonathan E Rosenberg
Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop distant metastatic disease. Over the past three decades, perioperative cisplatin-based chemotherapy has been investigated for its ability to reduce the number of deaths from bladder cancer. Insufficient evidence is available to fully support the use of such chemotherapy in the adjuvant setting; however, neoadjuvant cisplatin-based combination chemotherapy has become a standard of care for eligible patients based on the improved disease-specific and overall survival demonstrated in two randomized phase III trials, compared with surgery alone...
November 22, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27865458/the-interaction-between-human-papillomaviruses-and-the-stromal-microenvironment
#2
B Woodby, M Scott, J Bodily
Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs, or progression of lesions to cancer is less understood...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27853865/adequately-defining-tumor-cell-proportion-in-tissue-samples-for-molecular-testing-improves-interobserver-reproducibility-of-its-assessment
#3
Benoît Lhermitte, Caroline Egele, Noëlle Weingertner, Damien Ambrosetti, Bérengère Dadone, Valérie Kubiniek, Fanny Burel-Vandenbos, John Coyne, Jean-François Michiels, Marie-Pierre Chenard, Etienne Rouleau, Jean-Christophe Sabourin, Jean-Pierre Bellocq
Gene mutation status assessment of tumors has become standard practice in diagnostic pathology. This is done using samples comprising tumor cells but also non-tumor cells, which may dramatically dilute the proportion of tumor DNA and induce false negative results. Increasing sensitivity of molecular tests presently allows detection of a targeted mutation in a sample with a small percentage of tumor cells, but assessment of tumor cellularity remains essential to adequately interpret the results of molecular tests...
November 16, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27826838/the-role-of-dna-methylation-in-cancer
#4
Ranjani Lakshminarasimhan, Gangning Liang
The malignant transformation of normal cells is driven by both genetic and epigenetic changes. With the advent of next-generation sequencing and large-scale multinational consortium studies, it has become possible to profile the genomes and epigenomes of thousands of primary tumors from nearly every cancer type. From these genome-wide studies, it became clear that the dynamic regulation of DNA methylation is a critical epigenetic mechanism of cancer initiation, maintenance, and progression. Proper control of DNA methylation is not only crucial for regulating gene transcription, but its broader consequences include maintaining the integrity of the genome and modulating immune response...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27813113/promoter-cpg-site-methylation-of-the-kai1-metastasis-suppressor-gene-contributes-to-its-epigenetic-repression-in-prostate-cancer
#5
Jaeseob Lee, Moon-Sung Lee, Doo-Il Jeoung, Young-Myeong Kim, Hansoo Lee
BACKGROUND: Repression of the KAI1 metastasis suppressor gene is closely associated with malignancy and poor prognosis in many human cancer types including prostate cancer. Since gene repression in human cancers frequently results from epigenetic alterations by DNA methylation and histone modifications, we examined whether the KAI1 gene becomes silenced through these epigenetic mechanisms in prostate cancer. METHODS: KAI1 mRNA and protein levels were determined by RT-PCR and immunoblotting analyses, respectively...
November 3, 2016: Prostate
https://www.readbyqxmd.com/read/27803929/advances-in-understanding-how-heavy-metal-pollution-triggers-gastric-cancer
#6
REVIEW
Wenzhen Yuan, Ning Yang, Xiangkai Li
With the development of industrialization and urbanization, heavy metals contamination has become a major environmental problem. Numerous investigations have revealed an association between heavy metal exposure and the incidence and mortality of gastric cancer. The mechanisms of heavy metals (lead, cadmium, mercury, chromium, and arsenic) contamination leading to gastric cancer are concluded in this review. There are four main potential mechanisms: (1) Heavy metals disrupt the gastric mucosal barrier by decreasing mucosal thickness, mucus content, and basal acid output, thereby affecting the function of E-cadherin and inducing reactive oxygen species (ROS) damage...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27791148/rna-polymerase-ii-senses-obstruction-in-the-dna-minor-groove-via-a-conserved-sensor-motif
#7
Liang Xu, Wei Wang, Deanna Gotte, Fei Yang, Alissa A Hare, Timothy R Welch, Benjamin C Li, Ji Hyun Shin, Jenny Chong, Jeffrey N Strathern, Peter B Dervan, Dong Wang
RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27771483/senataxin-genome-guardian-at-the-interface-of-transcription-and-neurodegeneration
#8
Matthias Groh, Laura Oana Albulescu, Agnese Cristini, Natalia Gromak
R-loops comprise an RNA/DNA hybrid and displaced single-stranded DNA. They play crucial biological functions and are implicated in neurological diseases, including ataxias, amyotrophic lateral sclerosis, nucleotide expansion disorders (Friedreich ataxia, Fragile X syndrome) and cancer. Currently it is unclear which mechanisms cause R-loops structures to become pathogenic. The RNA/DNA helicase Senataxin (SETX) is one of the best characterised R-loop-binding factors in vivo. Mutations in SETX are linked to two neurodegenerative disorders: ataxia with oculomotor apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4)...
October 19, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27730285/big-data-mining-powers-fungal-research-recent-advances-in-fission-yeast-systems-biology-approaches
#9
Zhe Wang
Biology research has entered into big data era. Systems biology approaches therefore become the powerful tools to obtain the whole landscape of how cell separate, grow, and resist the stresses. Fission yeast Schizosaccharomyces pombe is wonderful unicellular eukaryote model, especially studying its division and metabolism can facilitate to understanding the molecular mechanism of cancer and discovering anticancer agents. In this perspective, we discuss the recent advanced fission yeast systems biology tools, mainly focus on metabolomics profiling and metabolic modeling, protein-protein interactome and genetic interaction network, DNA sequencing and applications, and high-throughput phenotypic screening...
October 11, 2016: Current Genetics
https://www.readbyqxmd.com/read/27721191/structural-characterization-of-mammalian-bhlh-pas-transcription-factors
#10
Dalei Wu, Fraydoon Rastinejad
The mammalian basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) transcription factors share common architectural features that include a bHLH DNA-binding domain and tandemly positioned PAS domains. The sixteen members of this family include the hypoxia-inducible factors (HIF-1α and HIF-2α), ARNT (also known as HIF-1β), CLOCK and BMAL1. Most bHLH-PAS proteins have been genetically linked to variety of diseases in humans, including cancers, metabolic syndromes and psychiatric conditions. To function as transcription factors, the bHLH-PAS proteins must form heterodimeric complexes...
October 6, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27706596/detecting-the-potential-cancer-association-or-metastasis-by-multi-omics-data-analysis
#11
L Hua, W Y Zheng, H Xia, P Zhou
Comprehensive multi-omics data analyses have become an important means for understanding cancer incidence and progression largely driven by the availability of high-throughput sequencing technologies for genomes, proteomes, and transcriptomes. However, how tumor cells from the site of origin of the cancer begin to grow in other sites of the body is very poorly understood. In order to examine potential connections between different cancers and to gain an insight into the metastatic process, we conducted a multi-omics data analysis using data deposited in The Cancer Genome Atlas database...
August 19, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27679854/the-role-of-trex-in-gene-expression-and-disease
#12
REVIEW
Catherine G Heath, Nicolas Viphakone, Stuart A Wilson
TRanscription and EXport (TREX) is a conserved multisubunit complex essential for embryogenesis, organogenesis and cellular differentiation throughout life. By linking transcription, mRNA processing and export together, it exerts a physiologically vital role in the gene expression pathway. In addition, this complex prevents DNA damage and regulates the cell cycle by ensuring optimal gene expression. As the extent of TREX activity in viral infections, amyotrophic lateral sclerosis and cancer emerges, the need for a greater understanding of TREX function becomes evident...
October 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27588601/do-dna-double-strand-breaks-drive-aging
#13
REVIEW
Ryan R White, Jan Vijg
DNA double-strand breaks (DSBs) are rare, but highly toxic, lesions requiring orchestrated and conserved machinery to prevent adverse consequences, such as cell death and cancer-causing genome structural mutations. DSBs trigger the DNA damage response (DDR) that directs a cell to repair the break, undergo apoptosis, or become senescent. There is increasing evidence that the various endpoints of DSB processing by different cells and tissues are part of the aging phenotype, with each stage of the DDR associated with specific aging pathologies...
September 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27546618/addiction-to-the-igf2-id1-igf2-circuit-for-maintenance-of-the-breast-cancer-stem-like-cells
#14
K Tominaga, T Shimamura, N Kimura, T Murayama, D Matsubara, H Kanauchi, A Niida, S Shimizu, K Nishioka, E-I Tsuji, M Yano, S Sugano, Y Shimono, H Ishii, H Saya, M Mori, K Akashi, K-I Tada, T Ogawa, A Tojo, S Miyano, N Gotoh
The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself...
August 22, 2016: Oncogene
https://www.readbyqxmd.com/read/27503998/mechanisms-of-nucleosome-dynamics-in-vivo
#15
REVIEW
Steven Henikoff
Nucleosomes function to tightly package DNA into chromosomes, but the nucleosomal landscape becomes disrupted during active processes such as replication, transcription, and repair. The realization that many proteins responsible for chromatin regulation are frequently mutated in cancer has drawn attention to chromatin dynamics; however, the basic mechanisms whereby nucleosomes are disrupted and reassembled is incompletely understood. Here, I present an overview of chromatin dynamics as has been elucidated in model organisms, in which our understanding is most advanced...
2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27471558/gut-microbiota-imbalance-and-base-excision-repair-dynamics-in-colon-cancer
#16
REVIEW
Debolina Ray, Dawit Kidane
Gut microbiota are required for host nutrition, energy balance, and regulating immune homeostasis, however, in some cases, this mutually beneficial relationship becomes twisted (dysbiosis), and the gut flora can incite pathological disorders including colon cancer. Microbial dysbiosis promotes the release of bacterial genotoxins, metabolites, and causes chronic inflammation, which promote oxidative DNA damage. Oxidized DNA base lesions are removed by base excision repair (BER), however, the role of this altered function of BER, as well as microbiota-mediated genomic instability and colon cancer development, is still poorly understood...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27423864/synthesis-and-assay-of-sirt1-activating-compounds
#17
H Dai, J L Ellis, D A Sinclair, B P Hubbard
The NAD(+)-dependent deacetylase SIRT1 plays key roles in numerous cellular processes including DNA repair, gene transcription, cell differentiation, and metabolism. Overexpression of SIRT1 protects against a number of age-related diseases including diabetes, cancer, and Alzheimer's disease. Moreover, overexpression of SIRT1 in the murine brain extends lifespan. A number of small-molecule sirtuin-activating compounds (STACs) that increase SIRT1 activity in vitro and in cells have been developed. While the mechanism for how these compounds act on SIRT1 was once controversial, it is becoming increasingly clear that they directly interact with SIRT1 and enhance its activity through an allosteric mechanism...
2016: Methods in Enzymology
https://www.readbyqxmd.com/read/27308470/the-cancer-stem-cell-phenotype-you-can-t-win-until-you-learn-how-to-lose-it
#18
Hernando Lopez-Bertoni, John Laterra
Cancer stem cells and their relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. We recently showed that reprogramming transcription factors induce glioblastoma cells to become stem-like and tumor propagating via a mechanism involving changes in global DNA methylation and downregulation of miRNAs.
July 2015: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27270041/proliferation-of-double-strand-break-resistant-polyploid-cells-requires-drosophila-fancd2
#19
Heidi S Bretscher, Donald T Fox
Conserved DNA-damage responses (DDRs) sense genome damage and prevent mitosis of broken chromosomes. How cells lacking DDRs cope with broken chromosomes during mitosis is poorly understood. DDRs are frequently inactivated in cells with extra genomes (polyploidy), suggesting that study of polyploidy can reveal how cells with impaired DDRs/genome damage continue dividing. Here, we show that continued division and normal organ development occurs in polyploid, DDR-impaired Drosophila papillar cells. As papillar cells become polyploid, they naturally accumulate broken acentric chromosomes but do not apoptose/arrest the cell cycle...
June 6, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27235851/keeping-the-senescence-secretome-under-control-molecular-reins-on-the-senescence-associated-secretory-phenotype
#20
REVIEW
Nicolas Malaquin, Aurélie Martinez, Francis Rodier
Cellular senescence is historically associated with cancer suppression and aging. Recently, the reach of the senescence genetic program has been extended to include the ability of senescent cells to actively participate in tissue remodelling during many physiological processes, including placental biology, embryonic patterning, wound healing, and tissue stress responses caused by cancer therapy. Besides growth arrest, a significant feature of senescent cells is their ability to modify their immediate microenvironment using a senescence-associated (SA) secretome, commonly termed the SA secretory phenotype (SASP)...
September 2016: Experimental Gerontology
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