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Oncogenesis

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https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#1
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28811834/high-risk-human-papilloma-viruses-hpvs-are-present-in-benign-prostate-tissues-before-development-of-hpv-associated-prostate-cancer
#2
Wendy K Glenn, Christopher C Ngan, Timothy G Amos, Richard J Edwards, Joshua Swift, Louise Lutze-Mann, Fei Shang, Noel J Whitaker, James S Lawson
BACKGROUND: Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28808254/ikk2-regulates-cytokinesis-during-vertebrate-development
#3
Hongyuan Shen, Eun Myoung Shin, Serene Lee, Sinnakaruppan Mathavan, Hiromi Koh, Motomi Osato, Hyungwon Choi, Vinay Tergaonkar, Vladimir Korzh
NFκB signaling has a pivotal role in regulation of development, innate immunity, and inflammation. Ikk2 is one of the two critical kinases that regulate the NFκB signaling pathway. While the role of Ikk2 in immunity, inflammation and oncogenesis has received attention, an understanding of the role of Ikk2 in vertebrate development has been compounded by the embryonic lethality seen in mice lacking Ikk2. We find that despite abnormal angiogenesis in IKK2 zygotic mutants of zebrafish, the maternal activity of Ikk2 supports embryogenesis and maturation of fertile animals and allows to study the role of IKK2 in development...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808044/germline-mutation-contribution-to-chromosomal-instability
#4
REVIEW
Sock Hoai Chan, Joanne Ngeow
Genomic instability is a feature of cancer that fuels oncogenesis through increased frequency of genetic disruption, leading to loss of genomic integrity and promoting clonal evolution as well as tumor transformation. A form of genomic instability prevalent across cancer types is chromosomal instability, which involves karyotypic changes including chromosome copy number alterations as well as gross structural abnormalities such as transversions and translocations. Defects in cellular mechanisms that are in place to govern fidelity of chromosomal segregation, DNA repair and ultimately genomic integrity are known to contribute to chromosomal instability...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28807562/targeting-signal-transducers-and-activators-of-transcription-stat-in-human-cancer-by-dietary-polyphenolic-antioxidants
#5
REVIEW
Hamed Amani, Marjan Ajami, Solmaz Nasseri Maleki, Hamidreza Pazoki-Toroudi, Maria Daglia, Arold Jorel Tsetegho Sokeng, Arianna Di Lorenzo, Seyed Fazel Nabavi, Kasi Pandima Devi, Seyed Mohammad Nabavi
Over the course of the last three decades, a large body of evidence has shown that polyphenols, the secondary metabolites occurring in plant foods and beverages, exert protective effects due to their antioxidant activity mediated through different mechanisms ranging from direct radical scavenging and metal chelating activities, to the capacity to inhibit pro-oxidant enzymes and to target specific cell-signalling pathways. In the last decade, dietary components, and polyphenols in particular have gained considerable attention as chemopreventive agents against different types of cancer...
August 11, 2017: Biochimie
https://www.readbyqxmd.com/read/28806393/craf-gene-fusions-in-pediatric-low-grade-gliomas-define-a-distinct-drug-response-based-on-dimerization-profiles
#6
P Jain, T M Fierst, H J Han, T E Smith, A Vakil, P J Storm, A C Resnick, A J Waanders
Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28801478/phosphatases-and-solid-tumors-focus-on-glioblastoma-initiation-progression-and-recurrences
#7
REVIEW
Matthias Dedobbeleer, Estelle Willems, Stephen Freeman, Arnaud Lombard, Nicolas Goffart, Bernard Rogister
Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or mutations affecting these enzymes have been demonstrated to be key factors for oncogenesis. The aim of this review is to shed light on the role of four different phosphatases (PTEN, PP2A, CDC25 and DUSP1) in five different solid tumors (breast cancer, lung cancer, pancreatic cancer, prostate cancer and ovarian cancer), in order to better understand the most frequent and aggressive primary cancer of the central nervous system, glioblastoma...
August 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28801369/hepatitis-b-virus-upregulates-the-expression-of-c-reactive-protein-both-in-vivo-and-in-vitro
#8
Shiyong Hao, Yan Wang, Guosheng Gao, Zhishan Li
Hepatitis B virus (HBV) infection induces immune-mediated inflammatory responses. The C-reactive protein (CRP) is an inflammatory marker that is synthesized by the liver. The aim of the present study was to investigate the effect of HBV infection on the expression of CRP and its clinical significance. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was employed to examine the expression of CRP mRNA in the human hepatocellular carcinoma (HCC) cell lines HepG2 and HepG2.2.15. A fully automatic biochemical analyzer was used to examine the serum levels of CRP in patients with chronic HBV infections and in healthy controls...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28801101/calcium-signaling-and-cell-cycle-progression-or-death
#9
REVIEW
Juliette Humeau, José Manuel Bravo-San Pedro, Ilio Vitale, Lucia Nuñez, Carlos Villalobos, Guido Kroemer, Laura Senovilla
Cytosolic Ca(2+) concentration levels fluctuate in an ordered manner along the cell cycle, in line with the fact that Ca(2+) is involved in the regulation of cell proliferation. Cell proliferation should be an error-free process, yet is endangered by mistakes. In fact, a complex network of proteins ensures that cell cycle does not progress until the previous phase has been successfully completed. Occasionally, errors occur during the cell cycle leading to cell cycle arrest. If the error is severe, and the cell cycle checkpoints work perfectly, this results into cellular demise by activation of apoptotic or non-apoptotic cell death programs...
July 25, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28800127/mnt-modulates-myc-driven-lymphomagenesis
#10
Kirsteen J Campbell, Cassandra J Vandenberg, Natasha S Anstee, Peter J Hurlin, Suzanne Cory
The transcriptional represser Mnt is a functional antagonist of the proto-oncoprotein Myc. Both Mnt and Myc utilise Max as an obligate partner for DNA binding, and Myc/Max and Mnt/Max complexes compete for occupancy at E-box DNA sequences in promoter regions. We have previously shown in transgenic mouse models that the phenotype and kinetics of onset of haemopoietic tumours varies with the level of Myc expression. We reasoned that a decrease in the level of Mnt would increase the functional level of Myc and accelerate Myc-driven tumorigenesis...
August 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28796927/epithelial-to-mesenchymal-transition-contributes-to-invasion-in-squamous-cell-carcinomas-originated-from-actinic-keratosis-through-the-differentiated-pathway-whereas-proliferation-plays-a-more-significant-role-in-the-classical-pathway
#11
X Saenz-Sardà, C Carrato, L Pérez-Roca, L Puig, C Ferrándiz, A Ariza, M T Fernández-Figueras
BACKGROUND: Every actinic keratosis (AK) starts with atypia at the basal layers of the epidermis (AK I). Progression into invasive squamous cell carcinoma (iSCC) may occur following two main pathways, classical and differentiated. In the former, iSCC only occurs after involvement of the upper epidermal layers by atypical cells (AK III), while in the latter iSCC develops directly from AK I. In the anogenital mucosa, these two pathways are associated with differential expression of p53 and p16...
August 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28789596/circular-rna-hsa_circ_0001564-facilitates-tumorigenesis-of-osteosarcoma-via-sponging-mir-29c-3p
#12
Ji-Feng Li, Yu-Ze Song
Circular RNAs are a novel type of non-coding RNAs generated from back splicing, which has been verified to mediate multiple tumorigenesis. However, the role of circular RNA in osteosarcoma is still unclear. In this study, we preliminarily screened the circular RNAs expression profiles in osteosarcoma and investigated the potential regulation mechanism. The circular RNAs expression profiles in osteosarcoma were screened using circular RNA microarray analysis, and results showed that there were 1152 circular RNAs upregulated and 915 circular RNAs downregulated in tumor tissue compared to adjacent tissue...
August 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28783725/a-braf-kinase-inactive-mutant-induces-lung-adenocarcinoma
#13
Patricia Nieto, Chiara Ambrogio, Laura Esteban-Burgos, Gonzalo Gómez-López, María Teresa Blasco, Zhan Yao, Richard Marais, Neal Rosen, Roberto Chiarle, David G Pisano, Mariano Barbacid, David Santamaría
The initiating oncogenic event in almost half of human lung adenocarcinomas is still unknown, a fact that complicates the development of selective targeted therapies. Yet these tumours harbour a number of alterations without obvious oncogenic function including BRAF-inactivating mutations. Inactivating BRAF mutants in lung predominate over the activating V600E mutant that is frequently observed in other tumour types. Here we demonstrate that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice (corresponding to the human BRAF(D594A) mutation) triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis...
August 10, 2017: Nature
https://www.readbyqxmd.com/read/28782268/reprogramming-antagonizes-the-oncogenicity-of-hoxa13-long-noncoding-rna-hottip-axis-in-gastric-cancer-cells
#14
Deng-Chyang Wu, Sophie S W Wang, Chung-Jung Liu, Kenly Wuputra, Kohsuke Kato, Yen-Liang Lee, Ying-Chu Lin, Ming-Ho Tsai, Chia-Chen Ku, Wen-Hsin Lin, Shin-Wei Wang, Shotaro Kishikawa, Michiya Noguchi, Chu-Chieh Wu, Yi-Ting Chen, Chee-Yin Chai, Chen-Lung Steve Lin, Kung-Kai Kuo, Ya-Han Yang, Hiroyuki Miyoshi, Yukio Nakamura, Shigeo Saito, Kyosuke Nagata, Chang-Shen Lin, Kazunari K Yokoyama
Reprogramming of cancer cells into induced pluripotent stem (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase (MLL1), WD repeat-containing protein 5 (WDR5), and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells...
August 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28781888/a-gwas-in-uveal-melanoma-identifies-risk-polymorphisms-in-the-clptm1l-locus
#15
Lenha Mobuchon, Aude Battistella, Claire Bardel, Ghislaine Scelo, Alexia Renoud, Alexandre Houy, Nathalie Cassoux, Maud Milder, Géraldine Cancel-Tassin, Olivier Cussenot, Olivier Delattre, Céline Besse, Anne Boland, Jean-François Deleuze, David G Cox, Marc-Henri Stern
Uveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43-2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28780541/associations-between-highly-active-antiretroviral-therapy-and-the-presence-of-hpv-premalignant-and-malignant-cervical-lesions-in-sub-saharan-africa-a-systematic-review-current-evidence-and-directions-for-future-research
#16
Sonia Menon, Rodolfo Rossi, Natasha Zdraveska, Mbabazi Kariisa, Sushama D Acharya, Davy Vanden Broeck, Steven Callens
OBJECTIVES: In sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions...
August 4, 2017: BMJ Open
https://www.readbyqxmd.com/read/28780319/cdk1-mediated-mitotic-phosphorylation-of-pbk-is-involved-in-cytokinesis-and-inhibits-its-oncogenic-activity
#17
Seth Stauffer, Yongji Zeng, Jiuli Zhou, Xingcheng Chen, Yuanhong Chen, Jixin Dong
PDZ-binding kinase (PBK) plays a major role in proliferation and in safeguarding mitotic fidelity in cancer cells. Frequently upregulated in many cancers, PBK drives tumorigenesis and metastasis. PBK has been shown to be phosphorylated in mitosis by cyclin-dependent kinase 1 (CDK1)/cyclin B, however, no studies have been done examining PBK mitotic phosphorylation in oncogenesis. Additionally to the previously identified Threonine-9 phosphorylation, we found that Threonine-24, Serine-32, and Serine-59 of PBK are also phosphorylated...
August 3, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28768863/hras-egfr-met-and-ron-are-recurrently-activated-by-provirus-insertion-in-mav-2-retrovirus-induced-liver-tumors
#18
Vladimir Pecenka, Petr Pajer, Vít Karafiat, Petra Kasparova, Jana Dudlova, Michal Dvorak
Myeloblastosis-associated virus-2 (MAV-2) is a highly tumorigenic simple avian retrovirus. Chickens infected in ovo with MAV-2 develop tumors in kidneys, lungs, and liver with a short latency of less then 8 weeks. Here we report the results of molecular analyses of MAV-2-induced liver tumors that fall into three classes: hepatic hemangiosarcomas (HHS), intrahepatic cholangiocarcinomas (ICC), and hepatocellular carcinomas (HCC). Comprehensive inverse PCR-based screening of 92 chicken liver tumors revealed that in ca 86 % of these tumors, MAV-2 provirus had integrated into one of four gene loci: HRAS, EGFR, MET, and RON Insertionally mutated genes correlated with tumor type - HRAS was hit in HHSs, MET in ICCs, RON mostly in ICCs and EGFR mostly in HCC...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768491/succinate-dehydrogenase-deficiency-in-a-pdgfra-mutated-gist
#19
Martin G Belinsky, Kathy Q Cai, Yan Zhou, Biao Luo, Jianming Pei, Lori Rink, Margaret von Mehren
BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor mutually exclusive gain of function mutations in the receptor tyrosine kinase (RTK) KIT (70-80%) or in the related receptor PDGFRA (~10%). These GISTs generally respond well to therapy with the RTK inhibitor imatinib mesylate (IM), although initial response is genotype-dependent. An alternate mechanism leading to GIST oncogenesis is deficiency in the succinate dehydrogenase (SDH) enzyme complex resulting from genetic or epigenetic inactivation of one of the four SDH subunit genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHX)...
August 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28765949/identification-of-mirna-mrna-crosstalk-in-laryngeal-squamous-cell-carcinoma
#20
Yonghua Fei, Ping Guo, Fuling Wang, Hu Li, Yanhua Lei, Wei Li, Xuehong Xun, Fengxiang Lu
The aim of the present study was to elaborate the underlying pathogenesis of laryngeal squamous cell carcinoma (LSCC). Micro (mi) RNA and messenger (m) RNA expression profiling of patients with LSCC were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) were identified in LSCC compared to normal control tissues. The DEMs targeted by DEMIs were identified and the negative correlation between DEMs and DEMIs was subjected to visualization...
July 31, 2017: Molecular Medicine Reports
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