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Oncogenesis

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https://www.readbyqxmd.com/read/29334356/p53-suppresses-mutagenic-rad52-and-pol%C3%AE-pathways-by-orchestrating-dna-replication-restart-homeostasis
#1
Sunetra Roy, Karl-Heinz Tomaszowski, Jessica W Luzwick, Soyoung Park, Jun Li, Maureen Murphy, Katharina Schlacher
Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks driving genomic instability genetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease...
January 15, 2018: ELife
https://www.readbyqxmd.com/read/29332977/the-role-of-wnt-signalling-in-angiogenesis
#2
REVIEW
Jun Jun Olsen, Sebastian Öther-Gee Pohl, Abhijeet Deshmukh, Malini Visweswaran, Natalie C Ward, Frank Arfuso, Mark Agostino, Arun Dharmarajan
Angiogenesis is a normal biological process wherein new blood vessels form from the growth of pre-existing blood vessels. Preventing angiogenesis in solid tumours by targeting pro-angiogenic factors including vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), basic fibroblast growth factor (bFGF), hepatocyte growth factor, and platelet-derived growth factor (PDGF) is currently under investigation for cancer treatment. Concurrently targeting the cell signalling pathways involved in the transcriptional and post-translational regulation of these factors may provide positive therapeutic results...
November 2017: Clinical Biochemist. Reviews
https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#3
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29330094/p21-activated-kinase-signaling-in-cancer
#4
REVIEW
Chetan K Rane, Audrey Minden
The p21 Activated Kinases (PAKs) are a family of serine threonine kinases, that consist of 6 members, PAKs 1-6, which are positioned at an intersection of multiple signaling pathways implicated in oncogenesis. The PAKs were originally identified as protein kinases that function downstream of the Ras related Rho GTPases Cdc42 and Rac. PAK1 and PAK4, which belong to Group I and Group II PAKs, respectively, are most often associated with tumorigenesis. On account of their well characterized roles in cancer, several small molecule inhibitors are being developed to inhibit the PAKs, and there is interest in investigating their efficacy as either first line or adjuvant treatments for cancer...
January 9, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29329590/frequent-overexpression-of-amap1-an-arf6-effector-in-cell-invasion-is-characteristic-of-the-mmtv-pymt-rather-than-the-mmtv-neu-human-breast-cancer-model
#5
Yutaro Otsuka, Tsukasa Oikawa, Hinako Yoshino, Shigeru Hashimoto, Haruka Handa, Hiroki Yamamoto, Ari Hashimoto, Hisataka Sabe
BACKGROUND: The small GTPase Arf6 and its downstream effector AMAP1 (also called ASAP1/DDEF1) constitute a signaling pathway promoting cell invasion, in which AMAP1 interacts with several different proteins, including PRKD2, EPB41L5, paxillin, and cortactin. Components of this pathway are often overexpressed in human breast cancer cells, to be correlated with poor prognosis of the patients, whereas overexpression of the Arf6 pathway did not correlate with the four main molecular classes of human breast tumors...
January 5, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29328417/microrna-129-5p-suppresses-cell-proliferation-migration-and-invasion-via-targeting-rock1-in-osteosarcoma
#6
Chaofan Han, Wenbo Wang
Osteosarcoma (OS) is the most common primary malignancy of the bone in teenagers and accounts for 20‑35% of all malignant primary bone tumors. Increasing evidence shows that microRNAs (miRNAs) are abnormally expressed in several types of human cancer. miRNAs are necessary to maintain the malignant phenotype of cancer cells and can function as either tumor suppressors or oncogenes. The present study aimed to measure the expression of miRNA‑129‑5p (miR‑129‑5p) in OS, determine the effects of miR‑129‑5p on the malignant behaviors of OS cells, and elucidate the molecular mechanism underlying the oncogenesis and progression of OS...
January 4, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29326437/insertional-mutagenesis-in-a-her2-positive-breast-cancer-model-reveals-eras-as-a-driver-of-cancer-and-therapy-resistance
#7
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, Annabel Vendel-Zwaagstra, Chris Klijn, Jelle Ten Hoeve, Jos Jonkers, Lodewyk F Wessels, John Hilkens
Personalized medicine for cancer patients requires a deep understanding of the underlying genetics that drive cancer and the subsequent identification of predictive biomarkers. To discover new genes and pathways contributing to oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu-transgenic mouse models. The screens revealed 34 common integration sites (CIS) in mammary tumors of MMTV-infected mice, highlighting loci with multiple independent MMTV integrations in which potential oncogenes are activated, most of which had never been reported as MMTV CIS...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29322421/immuno-detection-of-immature-and-bioactive-forms-of-the-inflammatory-cytokine-il-18
#8
Brendan J Jenkins, Virginie Deswaerte
Gastric cancer (GC) is the third most lethal cancer worldwide, and like many other types of cancers, it is associated with precursory chronic inflammatory responses. In the context of many inflammation-associated cancers such as GC, activation of the innate immune response by infectious microbes and/or host-derived molecules is often characterized by production of the cytokines interleukin (IL)-1β and IL-18, which can often have divergent and opposing (i.e., pro or anti) roles in inflammation and oncogenesis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321660/activated-alk-signals-through-the-erk-etv5-ret-pathway-to-drive-neuroblastoma-oncogenesis
#9
Lucille Lopez-Delisle, Cécile Pierre-Eugène, Caroline Louis-Brennetot, Didier Surdez, Virginie Raynal, Sylvain Baulande, Valentina Boeva, Sandrine Grossetête-Lalami, Valérie Combaret, Michel Peuchmaur, Olivier Delattre, Isabelle Janoueix-Lerosey
Activating mutations of the ALK receptor occur in a subset of neuroblastoma tumors. We previously demonstrated that Alk mutations cooperate with MYCN overexpression to induce neuroblastoma in mice and identified Ret as being strongly upregulated in MYCN/Alkmut tumors. By a genetic approach in vivo, we now document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We show that MYCN/RetM919T tumors exhibit histological features and expression profiles close to MYCN/Alkmut tumors...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29320577/genome-wide-profiling-of-the-piwi-interacting-rna-mrna-regulatory-networks-in-epithelial-ovarian-cancers
#10
Garima Singh, Jyoti Roy, Pratiti Rout, Bibekanand Mallick
PIWI-interacting (piRNAs), ~23-36 nucleotide-long small non-coding RNAs (sncRNAs), earlier believed to be germline-specific, have now been identified in somatic cells, including cancer cells. These sncRNAs impact critical biological processes by fine-tuning gene expression at post-transcriptional and epigenetic levels. The expression of piRNAs in ovarian cancer, the most lethal gynecologic cancer is largely uncharted. In this study, we investigated the expression of PIWILs by qRT-PCR and western blotting and then identified piRNA transcriptomes in tissues of normal ovary and two most prevalent epithelial ovarian cancer subtypes, serous and endometrioid by small RNA sequencing...
2018: PloS One
https://www.readbyqxmd.com/read/29319182/long-noncoding-rna-casc2-regulates-hepatocellular-carcinoma-cell-oncogenesis-through-mir-362-5p-nf-%C3%AE%C2%BAb-axis
#11
Liang Zhao, Yongjian Zhang, Yubao Zhang
The long non-coding RNA segment cancer susceptibility candidate 2 (CASC2) has been shown to suppress tumor growth in a variety of cancers, including hepatocellular carcinoma (HCC). However, the mechanism by which CASC2 exerts control over HCC has yet to be established. In the present study, we first demonstrated that CASC2 is downregulated in human HCC tissues and HCC cell lines as compared to adjacent non-tumor tissues and a liver cell line, respectively. After finding that CASC2 knockdown significantly promotes HCC cells migration and invasion as well as that CASC2 overexpression inhibits cell migration and invasion, we identified the microRNA miR-362-5p as an endogenous target of CASC2...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29318605/leukocyte-telomere-length-in-relation-to-risk-of-lung-adenocarcinoma-incidence-findings-from-the-singapore-chinese-health-study
#12
Jian-Min Yuan, Kenneth B Beckman, Renwei Wang, Caroline Bull, Jennifer Adams-Haduch, Joyce Y Huang, Aizhen Jin, Patricia Opresko, Anne B Newman, Yun-Ling Zheng, Michael Fenech, Woon-Puay Koh
Telomeres are crucial in the maintenance of chromosome integrity and genomic stability. Critically short telomeres can trigger programmed cell death while cells with longer telomeres may have increased likelihood of replicative errors, resulting in genetic mutations and chromosomal alterations, and ultimately promoting oncogenesis. Data on telomere length and lung cancer risk from large prospective cohort studies are spare. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction (qPCR) method in 26,540 participants of the Singapore Chinese Health Study...
January 10, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29315288/the-promise-of-immunotherapy-in-anal-squamous-cell-carcinoma-a-novel-approach-for-an-orphan-disease
#13
Benny Johnson, Cathy Eng
An estimated 8200 men and women in the United States will receive a diagnosis of squamous cell carcinoma of the anal canal (SCCA) in 2017. Although SCCA is rare, accounting for 2.6% of gastrointestinal cancers, its incidence rate has been steadily increasing over the last few decades in the United States and around the world. More than 90% of cases of SCCA occur in the context of prior human papillomavirus (HPV) infection. To date, preventive vaccinations against HPV remain markedly underutilized. Most patients who have SCCA present with locoregional disease that is cured with chemoradiation...
December 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29311715/the-bone-marrow-niche-in-mds-and-mgus-implications-for-aml-and-mm
#14
REVIEW
Irene M Ghobrial, Alexandre Detappe, Kenneth C Anderson, David P Steensma
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis...
January 9, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29311131/posttranslational-modifications-of-ras-proteins
#15
Ian Ahearn, Mo Zhou, Mark R Philips
The three human RAS genes encode four proteins that play central roles in oncogenesis by acting as binary molecular switches that regulate signaling pathways for growth and differentiation. Each is subject to a set of posttranslational modifications (PTMs) that modify their activity or are required for membrane targeting. The enzymes that catalyze the various PTMs are potential targets for anti-RAS drug discovery. The PTMs of RAS proteins are the focus of this review.
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29296886/constitutive-ras-signaling-and-ink4a-arf-inactivation-cooperate-during-the-development-of-b-all-in-mice
#16
Tomasz Sewastianik, Meng Jiang, Kumar Sukhdeo, Sanjay S Patel, Kathryn Roberts, Yue Kang, Ahmad Alduaij, Peter S Dennis, Brian Lawney, Ruiyang Liu, Zeyuan Song, Jessie Xiong, Yunyu Zhang, Madeleine E Lemieux, Geraldine S Pinkus, Jeremy N Rich, David M Weinstock, Charles G Mullighan, Norman E Sharpless, Ruben D Carrasco
Despite recent advances in treatment, human precursor B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging clinical entity. Recent genome-wide studies have uncovered frequent genetic alterations involving RAS pathway mutations and loss of the INK4A/ARF locus, suggesting their important role in the pathogenesis, relapse, and chemotherapy resistance of B-ALL. To better understand the oncogenic mechanisms by which these alterations might promote B-ALL and to develop an in vivo preclinical model of relapsed B-ALL, we engineered mouse strains with induced somatic KrasG12D pathway activation and/or loss of Ink4a/Arf during early stages of B-cell development...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288986/expression-profile-of-three-splicing-factors-in-pleural-cells-based-on-the-underlying-etiology-and-its-clinical-values-in-patients-with-pleural-effusion
#17
A-Lum Han, Hak-Ryul Kim, Keum-Ha Choi, Jae-Won Ryu, Ki-Eun Hwang, Hong-Seob So, Min-Cheol Park, Mengyu Zhu, Yuya Huang, Young-Jin Lee, Do-Sim Park
Splicing factors (SFs) are involved in oncogenesis or immune modulation, the common underlying processes giving rise to pleural effusion (PE). The expression profiles of three SFs (HNRNPA1, SRSF1, and SRSF3) and their clinical values have never been assessed in PE. The three SFs (in pellets of PE) and conventional tumor markers were analyzed using PE samples in patients with PE (N = 336). The sum of higher-molecular weight (Mw) forms of HNRNPA1 (Sum-HMws-HNRNPA1) and SRSF1 (Sum-HMws-SRSF1) and SRSF3 levels were upregulated in malignant PE (MPE) compared to benign PE (BPE); they were highest in cytology-positive MPE, followed by tuberculous PE and parapneumonic PE...
December 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29279606/nuclear-receptors-in-cancer-uncovering-new-and-evolving-roles-through-genomic-analysis
#18
REVIEW
Vineet K Dhiman, Michael J Bolt, Kevin P White
Nuclear receptors (NRs) have historically been at the forefront of cancer research, where they are known to act as critical regulators of disease. They also serve as biomarkers for tumour subclassification and targets for hormone therapy. However, most tumour types express extensive repertoires of NRs, whose interactions provide multiple paths for disease progression and offer potentially untapped mechanisms for therapeutic interventions. Recently, next-generation sequencing technologies have provided genome-wide insights into the complex interplay of NR transcriptional networks and their contribution to the development and progression of cancer...
December 27, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29279355/gadd45%C3%AE-loss-ablates-innate-immunosuppression-in-cancer
#19
Daniela Verzella, Jason Bennett, Mariafausta Fischietti, Anil Kumar Thotakura, Camilla Recordati, Fabio Pasqualini, Daria Capece, Davide Vecchiotti, Daniel D'Andrea, Barbara Di Francesco, Marcella De Maglie, Federica Begalli, Laura Tornatore, Salvatore Papa, Toby Lawrence, Stuart Forbes, Antonio Sica, Edoardo Alesse, Francesca Zazzeroni, Guido Franzoso
T cell exclusion from the tumour microenvironment (TME) is a major barrier to overcoming immune escape. Here we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumour-associated inflammation and T cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma (HCC) and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of pro-inflammatory tumour-associated macrophages (TAM) and intratumoural immune infiltration, thereby diminishing oncogenesis...
December 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29275043/signatures-of-protein-expression-revealed-by-secretome-analyses-of-cancer-associated-fibroblasts-and-melanoma-cell-lines
#20
Tarcísio Liberato, Dayelle S Pessotti, Isabella Fukushima, Eduardo S Kitano, Solange M T Serrano, André Zelanis
The imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Hence, the study of tumoral secretomes provides insights for understanding the cross-talk between cells within the tumor microenvironment as well as the key effectors for the establishment of the pre-metastatic niche in distant tumor sites. In this context, we performed a proteomic analysis of the secretomes derived from four cell lines: a paired set of fibroblasts - Hs 895...
December 21, 2017: Journal of Proteomics
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