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Genomic instability

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https://www.readbyqxmd.com/read/29774951/protein-kinase-c%C3%AE-pkc%C3%AE-involved-in-the-regulation-of-pakt1-ser473-on-the-release-of-mouse-oocytes-from-diplotene-arrest
#1
Lingling Liu, Sen Li, Hanwen Li, Dahai Yu, Chunyu Li, Gensong Li, Yu Cao, Chen Feng, Xin Deng
Defects in meiotic maturation may lead to chromosome segregation errors and genomic instability. Previous reports indicated that protein kinase C delta (PKCδ) may interact with microtubule organizing center-associated protein to play a role on meiotic spindle organization of mammalian oocytes. In this study, we explored the potential role of protein kinase B alpha (PKBα/Akt1), PKCδ, and their relationship on meiotic maturation of mouse oocytes. We examined the expression and localization of pAkt1 (Ser473) and/or pPKCδ (Thr505) under the treatment of SH-6 or Sotrastaurin...
May 18, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#2
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29770269/ten-years-of-progress-and-promise-of-induced-pluripotent-stem-cells-historical-origins-characteristics-mechanisms-limitations-and-potential-applications
#3
Adekunle Ebenezer Omole, Adegbenro Omotuyi John Fakoya
The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy...
2018: PeerJ
https://www.readbyqxmd.com/read/29770165/targeting-oxidatively-induced-dna-damage-response-in-cancer-opportunities-for-novel-cancer-therapies
#4
REVIEW
Pierpaola Davalli, Gaetano Marverti, Angela Lauriola, Domenico D'Arca
Cancer is a death cause in economically developed countries that results growing also in developing countries. Improved outcome through targeted interventions faces the scarce selectivity of the therapies and the development of resistance to them that compromise the therapeutic effects. Genomic instability is a typical cancer hallmark due to DNA damage by genetic mutations, reactive oxygen and nitrogen species, ionizing radiation, and chemotherapeutic agents. DNA lesions can induce and/or support various diseases, including cancer...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29769340/the-htlv-1-basic-leucine-zipper-factor-hbz-attenuates-repair-of-double-stranded-dna-breaks-via-non-homologous-end-joining-nhej
#5
A W Rushing, K Hoang, N Polakowski, I Lemasson
Adult T-cell leukemia (ATL) is a fatal malignancy of CD4+ T-cells infected with human T-cell leukemia virus type I (HTLV-1). ATL cells often exhibit random gross chromosomal rearrangements that are associated with the induction and improper repair of double-stranded DNA breaks (DSBs). The viral oncoprotein Tax has been reported to impair DSB repair, but is not shown to be consistently expressed throughout all phases of infection. The viral oncoprotein HTLV-1 basic leucine zipper factor (HBZ) is consistently expressed prior to and throughout disease progression, but it is unclear whether it also influences DSB repair...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769196/an-in-vivo-screen-identifies-pygo2-as-a-driver-for-metastatic-prostate-cancer
#6
Xin Lu, Xiaolu Pan, Chang-Jiun Wu, Di Zhao, Shan Feng, Yong Zang, Rumi Lee, Sunada Khadka, Samirkumar B Amin, Eun-Jung Jin, Xiaoying Shang, Pingna Deng, Yanting Luo, William R Morgenlander, Jacqueline Weinrich, Xuemin Lu, Shan Jiang, Qing Chang, Nora M Navone, Patricia Troncoso, Ronald A DePinho, Y Alan Wang
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29765774/how-shall-we-treat-early-triple-negative-breast-cancer-tnbc-from-the-current-standard-to-upcoming-immuno-molecular-strategies
#7
REVIEW
Ji Hyun Park, Jin-Hee Ahn, Sung-Bae Kim
Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the 'BRCAness' highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors...
2018: ESMO Open
https://www.readbyqxmd.com/read/29760781/understanding-aneuploidy-in-cancer-through-the-lens-of-system-inheritance-fuzzy-inheritance-and-emergence-of-new-genome-systems
#8
REVIEW
Christine J Ye, Sarah Regan, Guo Liu, Sarah Alemara, Henry H Heng
Background: In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29760601/tumor-cell-accelerated-senescence-is-associated-with-dna-pkcs-status-and-telomere-dysfunction-induced-by-radiation
#9
Miaomiao Zhang, Xiaopeng Guo, Yue Gao, Dong Lu, Wenjian Li
Whether telomere structure integrity is related to radiosensitivity is not well investigated thus far. In this study, we investigated the relation between telomere instability and radiation-induced accelerated senescence. Partial knockdown of DNA-dependent catalytic subunit of protein kinase (DNA-PKcs) in human breast cancer cell line MCF-7 was established by small interfering RNA. Radiosensitivity of control and DNA-PKcs knockdown MCF-7 cells was analyzed by clonogenetic assay. Cell growth was measured by real-time cell electronic sensing...
April 2018: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/29757397/uncovering-key-small-rnas-associated-with-gametocidal-action-in-wheat
#10
Dan Wang, Lei Ling, Wenrui Zhang, Yan Bai, Yongjun Shu, Changhong Guo
Gametocidal (Gc) chromosomes can kill gametes that lack them by causing chromosomal breakage to ensure their preferential transmission, and have been exploited in genetic breeding. The present study investigated the possible roles of small RNAs (sRNA) in Gc action. By sequencing two small RNA libraries from the anthers of Triticum aestivum cv. Chinese Spring (CS) and Chinese Spring-Gc 3C chromosome monosomic addition line (CS-3C), we identified 239 conserved and 72 putative novel microRNAs (miRNAs), including 135 differentially expressed miRNAs...
May 11, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29752549/promising-new-agents-for-colorectal-cancer
#11
REVIEW
Satya Das, Kristen K Ciombor, Sigurdis Haraldsdottir, Richard M Goldberg
Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility...
May 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29750959/a-btb-zf-protein-znf131-is-required-for-early-b-cell-development
#12
Tomohiro Iguchi, Emako Miyauchi, Sumiko Watanabe, Hisao Masai, Shoichiro Miyatake
Members of the BTB-ZF transcription factor family play important roles in lymphocyte development. During T cell development, ZNF131, a BTB-ZF protein, is critical for the double-negative (DN) to double-positive (DP) transition and is also involved in cell proliferation. Here, we report that knockout of Znf131 at the pre-pro-B cell stage in mb1-Cre knock-in mouse resulted in defect of pro-B to pre-B cell transition. ZNF131 was shown to be required for efficient pro-B cell proliferation as well as for immunoglobulin heavy chain gene rearrangement that occur in the proliferating pro-B cells...
May 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29750295/endogenous-leu332gln-mutation-in-p53-disrupts-the-tetramerization-ability-in-a-canine-mammary-gland-tumor-cell-line
#13
Kazuhiko Ochiai, Daigo Azakami, Masami Morimatsu, Hinako Hirama, Shota Kawakami, Takayuki Nakagawa, Masaki Michishita, Ai S Egusa, Takanori Sasaki, Masami Watanabe, Toshinori Omi
Mutations in the p53 gene are associated with more than half of all human cancers. These mutations often cause a disruption of the tumor-suppressor function of p53 and induce genomic instabilities. Wild‑type p53 requires tetramerization to function as an initiator of cell cycle arrest and apoptosis. Although alterations in p53 tetramerization caused by mutation have been well studied, there are few cell lines containing an endogenous mutation in the tetramerization domain of p53. Here, we report the discovery of a canine mammary gland tumor cell line CTB‑m2, which contains the Leu332Gln (L332Q) mutation corresponding to Leu344 in the tetramerization domain of human p53...
May 2, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29747151/role-of-pon1-sod2-ogg1-xrcc1-and-xrcc4-polymorphisms-on-modulation-of-dna-damage-in-workers-occupationally-exposed-to-pesticides
#14
Vivian F Silva Kahl, Fernanda Rabaioli da Silva, Jodel da Silva Alves, Gabrieli Flesch da Silva, Juliana Picinini, Varinderpal Singh Dhillon, Michael Fenech, Melissa Rosa de Souza, Johnny F Dias, Claudia Telles de Souza, Mirian Salvador, Cátia Dos Santos Branco, Flávia Valadão Thiesen, Daniel Simon, Juliana da Silva
Tobacco farming has been proving to induce poor health outcomes in agricultural workers, genomic instability being the triggering one. This study evaluated influence of PON1 (paraoxonase 1), SOD2 (superoxide dismutase), OGG1 (8-oxoguanine glycosylase), XRCC1 (X-ray repair cross-complementing protein 1), and XRCC4 (X-ray repair cross-complementing protein 4) genes polymorphisms on DNA damage in 121 subjects occupationally exposed to pesticides mixtures and nicotine at tobacco fields and 121 non-exposed individuals...
May 7, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29745724/radiosensitivity-and-transgenerational-effects-in-non-human-species
#15
C Adam-Guillermin, T Hertal-Aas, D Oughton, L Blanchard, F Alonzo, O Armant, N Horemans
The ALLIANCE working group on effects of ionising radiation on wildlife brings together European researchers to work on the topics of radiosensitivity and transgenerational effects in non-human biota. Differences in radiation sensitivity across species and phyla are poorly understood, but have important implications for understanding the overall effects of radiation and for radiation protection; for example, sensitive species may require special attention in monitoring and radiation protection, and differences in sensitivity between species also lead to overall effects at higher levels (community, ecosystem), since interactions between species can be altered...
January 1, 2018: Annals of the ICRP
https://www.readbyqxmd.com/read/29743854/microsatellite-instability-in-colorectal-cancer
#16
REVIEW
Jafar Nouri Nojadeh, Shahin Behrouz Sharif, Ebrahim Sakhinia
Colorectal cancer (CRC) is a heterogeneous disease that is caused by the interaction of genetic and environmental factors. Although it is one of the most common cancers worldwide, CRC would be one of the most curable cancers if it is detected in the early stages. Molecular changes that occur in colorectal cancer may be categorized into three main groups: 1) Chromosomal Instability (CIN), 2) Microsatellite Instability (MSI), and 3) CpG Island Methylator phenotype (CIMP). Microsatellites, also known as Short Tandem Repeats (STRs) are small (1-6 base pairs) repeating stretches of DNA scattered throughout the entire genome and account for approximately 3 % of the human genome...
2018: EXCLI Journal
https://www.readbyqxmd.com/read/29743566/going-going-gone-predicting-the-fate-of-genomic-insertions-in-plant-rna-viruses
#17
Anouk Willemsen, José L Carrasco, Santiago F Elena, Mark P Zwart
Horizontal gene transfer is common among viruses, while they also have highly compact genomes and tend to lose artificial genomic insertions rapidly. Understanding the stability of genomic insertions in viral genomes is therefore relevant for explaining and predicting their evolutionary patterns. Here, we revisit a large body of experimental research on a plant RNA virus, tobacco etch potyvirus (TEV), to identify the patterns underlying the stability of a range of homologous and heterologous insertions in the viral genome...
May 10, 2018: Heredity
https://www.readbyqxmd.com/read/29742286/study-of-promoter-hypomethylation-profiles-of-ras-oncogenes-in-hepatocellular-carcinoma-derived-from-hepatitis-c-virus-genotype-3a-in-pakistani-population
#18
Maria Maryam, Muhammad Idrees
Epigenetic modifications such as DNA methylation contribute to progression of Hepatitis C virus (HCV) infection to life-threatening hepatocellular carcinoma (HCC), by promoting the silencing of tumor suppressor genes due to DNA hypermethylation and by causing genomic instability due to global hypomethylation. However few studies addressed promoter region hypomethylation status of the oncogenes involved in HCV derived HCC. In this study, we analyzed the promoter region methylation pattern of RAS oncogenes (HRAS, KRAS, NRAS) using methylation-specific PCR (MSP) for 50 Chronic HCV patients infected with genotype 3a (27 HCC patients and 23 Control non-HCC patients)...
May 9, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29741737/genetic-and-epigenetic-features-of-rapidly-progressing-idh-mutant-astrocytomas
#19
Timothy E Richardson, Adwait Amod Sathe, Mohammed Kanchwala, Gaoxiang Jia, Amyn A Habib, Guanghua Xiao, Matija Snuderl, Chao Xing, Kimmo J Hatanpaa
IDH-mutant astrocytomas are significantly less aggressive than their IDH-wildtype counterparts. We analyzed The Cancer Genome Atlas dataset (TCGA) and identified a small group of IDH-mutant, WHO grade II-III astrocytomas (n = 14) with an unexpectedly poor prognosis characterized by a rapid progression to glioblastoma and death within 3 years of the initial diagnosis. Compared with IDH-mutant tumors with the typical, extended progression-free survival in a control group of age-similar patients, the tumors in the rapidly progressing group were characterized by a markedly increased level of overall copy number alterations ([CNA]; p = 0...
May 7, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29741650/flap-endonuclease-overexpression-drives-genome-instability-and-dna-damage-hypersensitivity-in-a-pcna-dependent-manner
#20
Jordan R Becker, David Gallo, Wendy Leung, Taylor Croissant, Yee Mon Thu, Hai Dang Nguyen, Timothy K Starr, Grant W Brown, Anja-Katrin Bielinsky
Overexpression of the flap endonuclease FEN1 has been observed in a variety of cancer types and is a marker for poor prognosis. To better understand the cellular consequences of FEN1 overexpression we utilized a model of its Saccharomyces cerevisiae homolog, RAD27. In this system, we discovered that flap endonuclease overexpression impedes replication fork progression and leads to an accumulation of cells in mid-S phase. This was accompanied by increased phosphorylation of the checkpoint kinase Rad53 and histone H2A-S129...
May 7, 2018: Nucleic Acids Research
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