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https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#1
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#2
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29771639/hic-5-expression-is-a-major-indicator-of-cancer-cell-morphology-migration-and-plasticity-in-three-dimensional-matrices
#3
Anushree C Gulvady, Fatemeh Dubois, Nicholas O Deakin, Gregory J Goreczny, Christopher E Turner
The focal adhesion proteins, Hic-5 and Paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional extracellular matrices. However, their respective roles in other cancer cell types has not been evaluated. Herein, utilizing 3D cell-derived matrices and fibronectin-coated 1D substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity and in vitro invasiveness...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29769669/diverse-mechanisms-for-endogenous-regeneration-and-repair-in-mammalian-organs
#4
REVIEW
James M Wells, Fiona M Watt
Mammalian organs comprise an extraordinary diversity of cell and tissue types. Regenerative organs, such as the skin and gastrointestinal tract, use resident stem cells to maintain tissue function. Organs with a lower cellular turnover, such as the liver and lungs, mostly rely on proliferation of committed progenitor cells. In many organs, injury reveals the plasticity of both resident stem cells and differentiated cells. The ability of resident cells to maintain and repair organs diminishes with age, whereas, paradoxically, the risk of cancer increases...
May 2018: Nature
https://www.readbyqxmd.com/read/29769248/targeting-tumor-cell-plasticity-by-combined-inhibition-of-notch-and-mapk-signaling-in-colon-cancer
#5
Eva Marina Schmidt, Sebastian Lamprecht, Cristina Blaj, Christian Schaaf, Stefan Krebs, Helmut Blum, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
In colorectal cancer, signaling pathways driving tumor progression are promising targets for systemic therapy. Besides WNT and MAPK signaling, activation of NOTCH signaling is found in most tumors. Here, we demonstrate that high NOTCH activity marks a distinct colon cancer cell subpopulation with low levels of WNT and MAPK activity and with a pronounced epithelial phenotype. Therapeutic targeting of MAPK signaling had limited effects on tumor growth and caused expansion of tumor cells with high NOTCH activity, whereas upon targeting NOTCH signaling, tumor cells with high MAPK activity prevailed...
May 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29764565/cancer-stem-cell-metabolism-target-for-cancer-therapy
#6
Young Chan Chae, Jae Ho Kim
Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies...
May 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29759441/nuclear-organization-mediates-cancer-compromised-genetic-and-epigenetic-control
#7
REVIEW
Sayyed K Zaidi, Andrew Fritz, Kirsten Tracy, Jonathan Gordon, Coralee Tye, Joseph Boyd, Andre Van Wijnen, Jeffrey Nickerson, Anthony Imbalzano, Jane Lian, Janet Stein, Gary Stein
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2...
May 9, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29758330/human-liver-infiltrating-%C3%AE-%C3%AE-t-cells-are-composed-of-clonally-expanded-circulating-and-tissue-resident-populations
#8
Stuart Hunter, Carrie Willcox, Martin Davey, Sofya Kasatskaya, Hannah Jeffery, Dmitriy Chudakov, Ye Oo, Benjamin Willcox
BACKGROUND & AIM: γδ T-cells comprise a substantial proportion of tissue-associated lymphocytes. However, our current understanding of human γδ T-cells is primarily based on peripheral blood subsets, while the immunobiology of tissue-associated subsets remains largely unclear. METHODS: To address this, we characterised the TCR diversity, immunophenotype and function of human liver infiltrating γδ T-cells, focussing on the predominant tissue-associated Vδ2neg γδ subset, which is implicated in liver immunopathology...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29757267/assessment-of-the-effects-of-endocrine-disrupting-compounds-on-the-development-of-vertebrate-neural-network-function-using-multi-electrode-arrays
#9
Karla R Sanchez, Mahlet D Mersha, Harbinder S Dhillon, Murali K Temburni
Bis-phenols, such as bis-phenol A (BPA) and bis-phenol-S (BPS), are polymerizing agents widely used in the production of plastics and numerous everyday products. They are classified as endocrine disrupting compounds (EDC) with estradiol-like properties. Long-term exposure to EDCs, even at low doses, has been linked with various health defects including cancer, behavioral disorders, and infertility, with greater vulnerability during early developmental periods. To study the effects of BPA on the development of neuronal function, we used an in vitro neuronal network derived from the early chick embryonic brain as a model...
April 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29756093/lineage-plasticity-in-cancer-progression-and-treatment
#10
Clémentine Le Magnen, Michael M Shen, Cory Abate-Shen
Historically, it has been widely presumed that differentiated cells are determined during development and become irreversibly committed to their designated fates. In certain circumstances, however, differentiated cells can display plasticity by changing their identity, either by dedifferentiation to a progenitor-like state or by transdifferentiation to an alternative differentiated cell type. Such cellular plasticity can be triggered by physiological or oncogenic stress, or it can be experimentally induced through cellular reprogramming...
March 2018: Annual Review of Cancer Biology
https://www.readbyqxmd.com/read/29753523/testicular-transposition-in-children-undergoing-brachytherapy-for-bladder-and-or-prostate-rhabdomyosarcoma
#11
Guenolee de Lambert, Cyrus Chargari, Véronique Minard-Colin, Christine Haie-Meder, Florent Guérin, Hélène Martelli
BACKGROUND/PURPOSE: Fertility preservation is a major goal in treatment of children with cancer. We describe a new technique of testicular transposition (TT) in patients treated with pulse-dose-rate (PDR) brachytherapy as part of the multimodal conservative treatment of bladder neck and/or prostate rhabdomyosarcoma (BP RMS). METHODS: Medical records of consecutive patients treated between September 2016 and August 2017 were studied. These patients underwent a TT performed during BP RMS surgery by the same suprapubic incision...
April 13, 2018: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29748373/slan-monocytes-and-macrophages-mediate-cd20-dependent-b-cell-lymphoma-elimination-via-adcc-and-adcp
#12
William Vermi, Alessandra Micheletti, Giulia Finotti, Cristina Tecchio, Federica Calzetti, Sara Costa, Mattia Bugatti, Stefano Calza, Claudio Agostinelli, Stefano Pileri, Piera Balzarini, Alessandra Tucci, Giuseppe Rossi, Lara Furlani, Giuseppe Todeschini, Alberto Zamò, Fabio Facchetti, Luisa Lorenzi, Silvia Lonardi, Marco A Cassatella
Terminal tissue differentiation and function of slan+ monocytes in cancer is largely unexplored. Our recent studies demonstrated that slan+ monocytes differentiate into a distinct subset of dendritic cells (DC) in human tonsils and that slan+ cells colonize metastatic carcinoma-draining lymph nodes. Herein, we report by retrospective analysis of multi-institutional cohorts that slan+ cells infiltrate various types of non-Hodgkin lymphomas (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, including the most aggressive, nodal and extra-nodal, forms...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29747682/the-biology-and-role-of-cd44-in-cancer-progression-therapeutic-implications
#13
REVIEW
Chen Chen, Shujie Zhao, Anand Karnad, James W Freeman
CD44, a non-kinase transmembrane glycoprotein, is overexpressed in several cell types including cancer stem cells and frequently shows alternative spliced variants that are thought to play a role in cancer development and progression. Hyaluronan, the main ligand for CD44, binds to and activates CD44 resulting in activation of cell signaling pathways that induces cell proliferation, increases cell survival, modulates cytoskeletal changes, and enhances cellular motility. The different functional roles of CD44 standard (CD44s) and specific CD44 variant (CD44v) isoforms are not fully understood...
May 10, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29743249/cancer-stem-cells-cscs-metabolic-strategies-for-their-identification-and-eradication
#14
REVIEW
Ernestina M De Francesco, Federica Sotgia, Michael P Lisanti
Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full repertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies...
May 9, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29742179/demographic-and-tumor-characteristics-of-patients-younger-than-50-years-with-nonmelanoma-skin-cancer-referred-for-mohs-micrographic-surgery
#15
Nicola A Quatrano, Euphemia W Mu, David E Orbuch, Adele Haimovic, Roy G Geronemus, Jeremy A Brauer
BACKGROUND: An increase in nonmelanoma skin cancer (NMSC) in younger patients has been reported. Many are treated with Mohs micrographic surgery (MMS). OBJECTIVE: Investigate patient and tumor characteristics in patients less than 50 years undergoing MMS for NMSC at a large, referral-based practice. METHODS & MATERIALS: Retrospective chart review of 1,332 tumors occurring in 1,018 consecutive patients over a five-year period. RESULTS: 81...
May 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29736367/tissue-engineering-for-urinary-tract-reconstruction-and-repair-progress-and-prospect-in-china
#16
REVIEW
Qingsong Zou, Qiang Fu
Several urinary tract pathologic conditions, such as strictures, cancer, and obliterations, require reconstructive plastic surgery. Reconstruction of the urinary tract is an intractable task for urologists due to insufficient autologous tissue. Limitations of autologous tissue application prompted urologists to investigate ideal substitutes. Tissue engineering is a new direction in these cases. Advances in tissue engineering over the last 2 decades may offer alternative approaches for the urinary tract reconstruction...
April 2018: Asian Journal of Urology
https://www.readbyqxmd.com/read/29735981/grainyhead-like-2-grhl2-knockout-abolishes-oral-cancer-development-through-reciprocal-regulation-of-the-map-kinase-and-tgf-%C3%AE-signaling-pathways
#17
Wei Chen, Kyung L Kang, Abdullah Alshaikh, Saaket Varma, Yi-Ling Lin, Ki-Hyuk Shin, Reuben Kim, Cun-Yu Wang, No-Hee Park, Katharina Walentin, Kai M Schmidt-Ott, Mo K Kang
Grainyhead-Like 2 (GRHL2) is an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Prior studies suggested inverse regulation between GRHL2 and TGF-β in epithelial plasticity and potential carcinogenesis. Here, we report the role of GRHL2 in oral carcinogenesis in vivo using a novel Grhl2 knockout (KO) mouse model and the underlying mechanism involving its functional interaction with TGF-β signaling. We developed epithelial-specific Grhl2 conditional KO mice by crossing Grhl2 floxed mice with those expressing CreER driven by the K14 promoter...
May 8, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29734696/mammary-stem-cells-and-breast-cancer-stem-cells-molecular-connections-and-clinical-implications
#18
REVIEW
Toni Celià-Terrassa
Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy...
May 4, 2018: Biomedicines
https://www.readbyqxmd.com/read/29732370/microenvironmental-signals-and-biochemical-information-processing-cooperative-determinants-of-intratumoral-plasticity-and-heterogeneity
#19
REVIEW
Alexander E Davies, John G Albeck
Intra-tumor cellular heterogeneity is a major challenge in cancer therapy. Tumors are composed of multiple phenotypic subpopulations that vary in their ability to initiate metastatic tumors and in their sensitivity to chemotherapy. In many cases, cells can transition between these subpopulations, not by genetic mutation, but instead through reversible changes in signal transduction or gene expression programs. This plasticity begins at the level of the microenvironment where local autocrine and paracrine signals, exosomes, tumor-stroma interactions, and extracellular matrix (ECM) composition create a signaling landscape that varies over space and time...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29732000/loss-of-inter-cellular-cooperation-by-complete-epithelial-mesenchymal-transition-supports-favorable-outcomes-in-basal-breast-cancer-patients
#20
Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie MacIntosh, Aymeric Fouquier d'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang
According to the sequential metastasis model, aggressive mesenchymal (M) metastasis-initiating cells (MICs) are generated by an epithelial-mesenchymal transition (EMT) which eventually is reversed by a mesenchymal-epithelial transition (MET) and outgrowth of life-threatening epithelial (E) macrometastases. Paradoxically, in breast cancer M signatures are linked with more favorable outcomes than E signatures, and M cells are often dispensable for metastasis in mouse models. Here we present evidence at the cellular and patient level for the cooperation metastasis model, according to which E cells are MICs, while M cells merely support E cell persistence through cooperation...
April 13, 2018: Oncotarget
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