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Hallmarks, cancer

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https://www.readbyqxmd.com/read/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#1
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28089890/single-chromosome-gains-commonly-function-as-tumor-suppressors
#2
Jason M Sheltzer, Julie H Ko, John M Replogle, Nicole C Habibe Burgos, Erica S Chung, Colleen M Meehl, Nicole M Sayles, Verena Passerini, Zuzana Storchova, Angelika Amon
Aneuploidy is a hallmark of cancer, although its effects on tumorigenesis are unclear. Here, we investigated the relationship between aneuploidy and cancer development using cells engineered to harbor single extra chromosomes. We found that nearly all trisomic cell lines grew poorly in vitro and as xenografts, relative to genetically matched euploid cells. Moreover, the activation of several oncogenic pathways failed to alleviate the fitness defect induced by aneuploidy. However, following prolonged growth, trisomic cells acquired additional chromosomal alterations that were largely absent from their euploid counterparts and that correlated with improved fitness...
December 29, 2016: Cancer Cell
https://www.readbyqxmd.com/read/28089831/monomethyltransferase-setd8-regulates-breast-cancer-metabolism-via-stabilizing-hypoxia-inducible-factor-1%C3%AE
#3
Run Huang, Yang Yu, Xiangyun Zong, Xiaolin Li, Lisi Ma, Qi Zheng
SETD8 is a methyltransferase that specifically catalyzes the monomethylation of lysine 20 on histone H4. Previous studies have demonstrated that SETD8 is associated with proper cell cycle progression, DNA damage response, and transcriptional regulation. A recent study revealed that SETD8 played an important role in epithelial-mesenchymal transition (EMT) in association with TWIST and enhanced metastatic potential of breast cancer cells. However, the contribution of SETD8 to metabolism reprogramming, one hallmark of cancer, has never been reported...
January 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#4
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
January 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28088687/whole-genome-dna-methylation-profiling-identifies-epigenetic-signatures-of-uterine-carcinosarcoma
#5
Jing Li, Xiaoyun Xing, Daofeng Li, Bo Zhang, David G Mutch, Ian S Hagemann, Ting Wang
Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma...
January 12, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28088583/environmental-carcinogenesis-and-ph-homeostasis-not-only-a-matter-of-dysregulated-metabolism
#6
REVIEW
Kévin Hardonniere, Laurence Huc, Odile Sergent, Jørn A Holme, Dominique Lagadic-Gossmann
According to the World Health Organization, around 20% of all cancers would be due to environmental factors. Among these factors, several chemicals are indeed well recognized carcinogens. The widespread contaminant benzo[a]pyrene (B[a]P), an often used model carcinogen of the polycyclic aromatic hydrocarbons' family, has been suggested to target most, if not all, cancer hallmarks described by Hanahan and Weinberg. It is classified as a group I carcinogen by the International Agency for Research on Cancer; however, the precise intracellular mechanisms underlying its carcinogenic properties remain yet to be thoroughly defined...
January 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28088463/stress-induced-egf-receptor-signaling-through-stat3-and-tumor-progression-in-triple-negative-breast-cancer
#7
Nikolas Balanis, Cathleen R Carlin
Elevated STAT3 activity is a hallmark of many epithelial carcinomas particularly in breast cancers where it is known to contribute to tumor progression through a variety of context-dependent biological responses. However, its role downstream of stress-exposed EGF receptors (EGFR) that are transactivated in endosomes independent of exogenous ligand has not been studied. This review discusses how STAT3 signaling induced by therapeutic stress in EGFR-driven triple-negative breast cancers (TNBC) might override normal epithelial homeostatic mechanisms and provide a survival advantage for tumor cells before they leave the primary tumor and spread to distant sites...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28088074/anti-angiogenic-treatment-in-breast-cancer-facts-successes-failures-and-future-perspectives
#8
REVIEW
Kim C Aalders, Konstantinos Tryfonidis, Elżbieta Senkus, Fatima Cardoso
Angiogenesis is one of the hallmarks of cancer and a crucial requisite in the development of tumors. Interrupting this process by blocking the vascular endothelial growth factor (VEGF) with the monoclonal antibody bevacizumab has been considered a possible breakthrough in the treatment of various types of cancer, especially for advanced disease. However in breast cancer, studies have shown ambivalent results causing debate about the value of this drug. In this article, we review the evidence for anti-angiogenic treatment options for breast cancer, as well as discuss the possible factors limiting the effectiveness of anti-angiogenic agents and offer a recommendation regarding the future research on these therapies for the treatment of breast cancer...
January 3, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28087780/oncogenes-without-a-neighboring-tumor-suppressor-gene-are-more-prone-to-amplification
#9
William K K Wu, Xiangchun Li, Xiansong Wang, Rudin Z W Dai, Alfred S L Cheng, Maggie H T Wang, Thomas Kwong, Tai C Chow, Jun Yu, Matthew T V Chan, Sunny H Wong
Focal copy number gains or losses are important genomic hallmarks of cancer. The genomic distribution of oncogenes and tumor-suppressor genes (TSG) in relation to focal copy number aberrations is unclear. Our analysis revealed that the mean distance of TSGs from oncogenes was significantly shorter than that of non-cancer genes, suggesting that oncogenes and TSGs tend to be in close physical proximity in the human genome. Such relationship was conserved in mouse and drosophila. Pan-cancer analysis using data from The Cancer Genome Atlas indicated that oncogenes without a nearby TSG are more prone to amplification...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087343/calcium-remodeling-in-colorectal-cancer
#10
REVIEW
Carlos Villalobos, Diego Sobradillo, Miriam Hernández-Morales, Lucía Núñez
: Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087320/poly-adp-ribose-polymerase-activity-and-inhibition-in-cancer
#11
REVIEW
Caleb Dulaney, Samuel Marcrom, Jennifer Stanley, Eddy S Yang
Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination...
January 10, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28086949/nek2-promotes-aerobic-glycolysis-in-multiple-myeloma-through-regulating-splicing-of-pyruvate-kinase
#12
Zhimin Gu, Jiliang Xia, Hongwei Xu, Ivana Frech, Guido Tricot, Fenghuang Zhan
BACKGROUND: Aerobic glycolysis, a hallmark of cancer, is characterized by increased metabolism of glucose and production of lactate in normaxia. Recently, pyruvate kinase M2 (PKM2) has been identified as a key player for regulating aerobic glycolysis and promoting tumor cell proliferation and survival. METHODS: Tandem affinity purification followed up by mass spectrometry (TAP-MS) and co-immunoprecipitation (Co-IP) were used to study the interaction between NIMA (never in mitosis gene A)-related kinase 2 (NEK2) and heterogeneous nuclear ribonucleoproteins (hnRNP) A1/2...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28081468/role-of-mir-15a-in-intervertebral-disc-degeneration-through-targeting-map3k9
#13
Ping Cai, Ting Yang, Xingjie Jiang, Minghui Zheng, Gang Xu, Jianlong Xia
BACKGROUND: Accumulating evidence indicates that microRNAs are involved in various cellular processes, including cell proliferation, differentiation, apoptosis and metastasis. miR-15a is an important regulator of immune responses and angiogenesis, endogenous controls as well as potential targets and hallmarks of cancer. However, the role of miR-15a in intervertebral disc degeneration (IDD) has not been elucidated. METHODS: Total RNA was extracted from degenerative nucleus pulposus (NP) tissues of 20 patients with IDD and NP cells, respectively...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28079891/crb3-regulates-contact-inhibition-by-activating-the-hippo-pathway-in-mammary-epithelial-cells
#14
Xiaona Mao, Pingping Li, Yaochun Wang, Zheyong Liang, Jie Liu, Juan Li, Yina Jiang, Gang Bao, Lei Li, Bofeng Zhu, Yu Ren, Xinhan Zhao, Jianmin Zhang, Yu Liu, Jin Yang, Peijun Liu
The loss of contact inhibition is a hallmark of cancer cells. The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo signalling. However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28076304/the-use-of-liquid-chromatography-tandem-mass-spectrometry-for-therapeutic-drug-monitoring-of-antibiotics-in-cancer-patients
#15
Nahed El-Najjar, Jonathan Jantsch, André Gessner
Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28073359/whole-transcriptome-analysis-of-pre-invasive-and-invasive-early-squamous-lung-carcinoma-in-archival-laser-microdissected-samples
#16
Andre Koper, Leo A H Zeef, Leena Joseph, Keith Kerr, John Gosney, Mark A Lindsay, Richard Booton
BACKGROUND: Preinvasive squamous cell cancer (PSCC) are local transformations of bronchial epithelia that are frequently observed in current or former smokers. Their different grades and sizes suggest a continuum of dysplastic change with increasing severity, which may culminate in invasive squamous cell carcinoma (ISCC). As a consequence of the difficulty in isolating cancerous cells from biopsies, the molecular pathology that underlies their histological variability remains largely unknown...
January 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28072763/epithelial-to-mesenchymal-transition-and-hpv-infection-in-squamous-cell-oropharyngeal-carcinomas-the-papillophar-study
#17
Marine Lefevre, Alexandra Rousseau, Thomas Rayon, Véronique Dalstein, Christine Clavel, Agnès Beby-Defaux, Jean-Luc Pretet, Patrick Soussan, Myriam Polette, Jean Lacau Saint Guily, Philippe Birembaut
BACKGROUND: Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas. METHODS: We have studied the relationship of EMT markers (E-cadherin, β-catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16(INK4a) expression and survival outcomes in a cohort of 296 patients with OPC...
January 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28068672/genomic-hallmarks-of-localized-non-indolent-prostate-cancer
#18
Michael Fraser, Veronica Y Sabelnykova, Takafumi N Yamaguchi, Lawrence E Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Fouad Yousif, Xihui Lin, Andre P Masella, Natalie S Fox, Michael Xie, Stephenie D Prokopec, Alejandro Berlin, Emilie Lalonde, Musaddeque Ahmed, Dominique Trudel, Xuemei Luo, Timothy A Beck, Alice Meng, Junyan Zhang, Alister D'Costa, Robert E Denroche, Haiying Kong, Shadrielle Melijah G Espiritu, Melvin L K Chua, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas B Buchner, Michèle Orain, Valérie Picard, Helène Hovington, Alexander Murison, Ken Kron, Nicholas J Harding, Christine P'ng, Kathleen E Houlahan, Kenneth C Chu, Bryan Lo, Francis Nguyen, Constance H Li, Ren X Sun, Richard de Borja, Christopher I Cooper, Julia F Hopkins, Shaylan K Govind, Clement Fung, Daryl Waggott, Jeffrey Green, Syed Haider, Michelle A Chan-Seng-Yue, Esther Jung, Zhiyuan Wang, Alain Bergeron, Alan Dal Pra, Louis Lacombe, Colin C Collins, Cenk Sahinalp, Mathieu Lupien, Neil E Fleshner, Housheng H He, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D McPherson, Robert G Bristow, Paul C Boutros
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries...
January 9, 2017: Nature
https://www.readbyqxmd.com/read/28063379/oxidative-stress-mitochondrial-abnormalities-and-antioxidant-defense-in-ataxia-telangiectasia-bloom-syndrome-and-nijmegen-breakage-syndrome
#19
REVIEW
Mateusz Maciejczyk, Bozena Mikoluc, Barbara Pietrucha, Edyta Heropolitanska-Pliszka, Malgorzata Pac, Radosław Motkowski, Halina Car
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis...
December 28, 2016: Redox Biology
https://www.readbyqxmd.com/read/28062977/angiopoietin-pathway-gene-expression-associated-with-poor-breast-cancer-survival
#20
Rajesh Ramanathan, Amy L Olex, Mikhail Dozmorov, Harry D Bear, Leopoldo Jose Fernandez, Kazuaki Takabe
PURPOSE: Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a "big data" approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA)...
January 6, 2017: Breast Cancer Research and Treatment
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