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https://www.readbyqxmd.com/read/29678550/low-level-shear-stress-promotes-migration-of-liver-cancer-stem-cells-via-the-fak-erk1-2-signalling-pathway
#1
Jinghui Sun, Qing Luo, Lingling Liu, Guanbin Song
Cancer stem cells (CSCs) are a small subpopulation of tumour cells that have been proposed to be responsible for cancer initiation, chemotherapy resistance and cancer recurrence. Shear stress activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, little is known about the effects of shear stress on the migration of liver cancer stem cells (LCSCs). Here, we studied the effects of shear stress that are generated from a parallel plated flow chamber system, on LCSC migration and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2), using transwell assay and western blot, respectively...
April 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29674709/known-and-novel-roles-of-the-met-oncogene-in-cancer-a-coherent-approach-to-targeted-therapy
#2
REVIEW
Paolo M Comoglio, Livio Trusolino, Carla Boccaccio
The MET oncogene encodes an unconventional receptor tyrosine kinase with pleiotropic functions: it initiates and sustains neoplastic transformation when genetically altered ('oncogene addiction') and fosters cancer cell survival and tumour dissemination when transcriptionally activated in the context of an adaptive response to adverse microenvironmental conditions ('oncogene expedience'). Moreover, MET is an intrinsic modulator of the self-renewal and clonogenic ability of cancer stem cells ('oncogene inherence')...
April 19, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29672847/loss-of-n-wasp-drives-early-progression-in-an-apc-model-of-intestinal-tumourigenesis
#3
Hayley T Morris, Loic Fort, Heather J Spence, Rachana Patel, David F Vincent, James H Park, Scott B Snapper, Francis A Carey, Owen J Sansom, Laura M Machesky
N-WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N-WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N-WASP in the initiation and progression of colorectal cancer. While deletion of N-wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche and migration up the crypt-villus axis was enhanced...
April 19, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29671404/regulation-of-dual-specificity-phosphatases-in-breast-cancer-during-initial-treatment-with-herceptin-a-boolean-model-analysis
#4
Petronela Buiga, Ari Elson, Lydia Tabernero, Jean-Marc Schwartz
BACKGROUND: 25% of breast cancer patients suffer from aggressive HER2-positive tumours that are characterised by overexpression of the HER2 protein or by its increased tyrosine kinase activity. Herceptin is a major drug used to treat HER2 positive breast cancer. Understanding the molecular events that occur when breast cancer cells are exposed to Herceptin is therefore of significant importance. Dual specificity phosphatases (DUSPs) are central regulators of cell signalling that function downstream of HER2, but their role in the cellular response to Herceptin is mostly unknown...
April 11, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29670296/paracrine-roles-of-cellular-senescence-in-promoting-tumourigenesis
#5
REVIEW
Jose Mario Gonzalez-Meljem, John Richard Apps, Helen Christina Fraser, Juan Pedro Martinez-Barbera
Senescent cells activate genetic programmes that irreversibly inhibit cellular proliferation, but also endow these cells with distinctive metabolic and signalling phenotypes. Although senescence has historically been considered a protective mechanism against tumourigenesis, the activities of senescent cells are increasingly being associated with age-related diseases, including cancer. An important feature of senescent cells is the secretion of a vast array of pro-inflammatory cytokines, chemokines, and growth factors collectively known as the senescence-associated secretory phenotype (SASP)...
April 19, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29669735/ctgf-vegfa-activated-fibroblasts-promote-tumor-migration-through-micro-environmental-modulation
#6
Wei Wu, Esther A Zaal, Celia R Berkers, Simone Lemeer, Albert J R Heck
Fibroblast activation is associated with tumour progression and implicated in metastasis, but the initial triggering signals required to kick-start this process remain largely unknown. Since small cancerous lesions share limited physical contact with neighboring fibroblasts, we reasoned the first tumour-derived signal for fibroblast activation should be secreted and diffusible. By pulsed metabolic labeling and click-chemistry based affinity enrichment, we sieved through the ductal carcinoma secretome for potential fibroblast activators...
April 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29667772/tead4-exerts-pro-metastatic-effects-and-is-negatively-regulated-by-mir6839-3p-in-lung-adenocarcinoma-progression
#7
Qun Zhang, Hang Fan, Qian Zou, Hongda Liu, Bing Wan, Suhua Zhu, Yangbo Hu, Huijuan Li, ChenXi Zhang, Li Zhou, Qingqing Zhu, Kunhong Xiao, Jianya Zhang, Ping Zhan, Tangfeng Lv, Yong Song
Several studies have shown the tumorigenesis role of transcriptional enhancer associate domain (TEAD) proteins; here, we initially explored expression, function and signalling mechanisms of TEAD4 in lung adenocarcinoma (LAD). Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour-promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes...
April 18, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29666865/preparation-of-lactic-acid-and-glucose-responsive-poly-%C3%AE%C2%B5-caprolactone-b-poly-ethylene-oxide-block-copolymer-micelles-using-phenylboronic-ester-as-a-sensitive-block-linkage
#8
David Vrbata, Mariusz Uchman
The present study describes the synthesis, self-assembly and responsiveness to glucose and lactic acid of biocompatible and biodegradable block copolymer micelles using phenylboronic ester as the linkage between hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic poly(ethylene oxide) (PEO). The PCL block with pendant phenylboronic acid (PCLBA) was synthesized by combining ε-caprolactone (ε-CL) ring-opening polymerisation (ROP), using 4-hydroxymethyl(phenylboronic) acid pinacolate as the initiator, and pinacol deprotection...
April 18, 2018: Nanoscale
https://www.readbyqxmd.com/read/29666135/study-protocol-for-the-saron-trial-a-multicentre-randomised-controlled-phase-iii-trial-comparing-the-addition-of-stereotactic-ablative-radiotherapy-and-radical-radiotherapy-with-standard-chemotherapy-alone-for-oligometastatic-non-small-cell-lung-cancer
#9
John Conibear, Brendan Chia, Yenting Ngai, Andrew Tom Bates, Nicholas Counsell, Rushil Patel, David Eaton, Corinne Faivre-Finn, John Fenwick, Martin Forster, Gerard G Hanna, Susan Harden, Philip Mayles, Syed Moinuddin, David Landau
INTRODUCTION: Following growing evidence to support the safety, local control (LC) and potential improvement in overall survival (OS) in patients with oligometastatic non-small cell lung cancer (NSCLC) that have been treated with local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS), we initiate the SARON trial to investigate the impact and feasibility of adding SABR/SRS and radical radiotherapy (RRT) following standard chemotherapy on OS...
April 17, 2018: BMJ Open
https://www.readbyqxmd.com/read/29666124/generation-of-a-double-binary-transgenic-zebrafish-model-to-study-myeloid-gene-regulation-in-response-to-oncogene-activation-in-melanocytes
#10
Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Vanessa Chong-Morrison, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
A complex network of inflammatory genes is closely linked to somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. Here, we describe the development of a double binary zebrafish model that enables regulatory programming of the myeloid cells as they respond to oncogene-activated melanocytes to be explored, focussing on the initial phase when cells become the precursors of cancer...
April 6, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29662549/tumour-necrosis-factor-interferon-gamma-and-interleukins-as-predictive-markers-of-antiprogrammed-cell-death-protein-1-treatment-in-advanced-non-small-cell-lung-cancer-a-pragmatic-approach-in-clinical-practice
#11
Efimia Boutsikou, Kalliopi Domvri, Georgia Hardavella, Dora Tsiouda, Konstantinos Zarogoulidis, Theodoros Kontakiotis
Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29660158/cutaneous-presentation-preceding-acute-myeloid-leukemic-with-cd4-cd56-expression-misdiagnosed-as-a-blastic-plasmocytoid-dendritic-cell-neoplasm-a-case-report
#12
Vanessa Szablewski, Valérie Costes, Caroline Bret, Olivier Dereure, Hicheri Yosr, Melissa Alame, Valère Cacheux
Acute myeloid leukemia (AML) may initially present as cutaneous lesions corresponding to blasts involving the skin as the first clinical manifestation prior to blood and bone marrow (BM) infiltration. Such presentation is known as myeloid leukemia cutis (LC). Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is an aggressive tumour derived from the precursors of plasmocytoid dendritic cells with cutaneous and bone marrow (BM) involvement and leukemic dissemination. Myeloid LC and BPDCN may be difficult to distinguish as they share similar clinical and histopathological features, in particular AML with monocytic differentiation...
April 16, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29651130/targeting-the-tumour-stroma-to-improve-cancer-therapy
#13
REVIEW
Kenneth C Valkenburg, Amber E de Groot, Kenneth J Pienta
Cancers are not composed merely of cancer cells alone; instead, they are complex 'ecosystems' comprising many different cell types and noncellular factors. The tumour stroma is a critical component of the tumour microenvironment, where it has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote the resistance of cancer cells to such therapies, eventually resulting in fatal disease. Therefore, novel treatment strategies should combine anticancer and antistromal agents...
April 12, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29650681/dntp-metabolism-links-mechanical-cues-and-yap-taz-to-cell-growth-and-oncogene-induced-senescence
#14
Giulia Santinon, Irene Brian, Arianna Pocaterra, Patrizia Romani, Elisa Franzolin, Chiara Rampazzo, Silvio Bicciato, Sirio Dupont
YAP/TAZ, downstream transducers of the Hippo pathway, are powerful regulators of cancer growth. How these factors control proliferation remains poorly defined. Here, we found that YAP/TAZ directly regulate expression of key enzymes involved in deoxynucleotide biosynthesis and maintain dNTP precursor pools in human cancer cells. Regulation of deoxynucleotide metabolism is required for YAP-induced cell growth and underlies the resistance of YAP-addicted cells to chemotherapeutics targeting dNTP synthesis. During RAS-induced senescence, YAP/TAZ bypass RAS-mediated inhibition of nucleotide metabolism and control senescence...
April 12, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29644518/mathematical-modelling-of-the-interaction-between-cancer-cells-and-an-oncolytic-virus-insights-into-the-effects-of-treatment-protocols
#15
Adrianne L Jenner, Chae-Ok Yun, Peter S Kim, Adelle C F Coster
Oncolytic virotherapy is an experimental cancer treatment that uses genetically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity Kim et al. (Biomaterials 32(9):2314-2326, 2011) modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. Whilst PEG modification appeared to improve plasma retention and initial infectivity, it also increased the virus particle arrival time...
April 11, 2018: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29628793/challenging-tumour-immunological-techniques-that-help-to-track-cancer-stem-cells-in-malignant-melanomas-and-other-solid-tumours
#16
Beatrix Kotlan, Vanda Plotar, Klara Eles, Szabolcs Horvath, Timea Balatoni, Orsolya Csuka, Mihaly Újhelyi, Ákos Sávolt, Andras Szollar, Istvan Vamosi-Nagy, Laszlo Toth, Emil Farkas, Jozsef Toth, Miklos Kasler, Gabriella Liszkay
Aim of the study: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. Materials and methods: As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29628312/alt-803-an-il-15-superagonist-in-combination-with-nivolumab-in-patients-with-metastatic-non-small-cell-lung-cancer-a-non-randomised-open-label-phase-1b-trial
#17
John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein
BACKGROUND: Immunotherapy with PD-1 or PD-L1 blockade fails to induce a response in about 80% of patients with unselected non-small cell lung cancer (NSCLC), and many of those who do initially respond then develop resistance to treatment. Agonists that target the shared interleukin-2 (IL-2) and IL-15Rβγ pathway have induced complete and durable responses in some cancers, but no studies have been done to assess the safety or efficacy of these agonists in combination with anti-PD-1 immunotherapy...
April 5, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29626432/newcastle-disease-virus-strain-af2240-as-an-oncolytic-virus-a-review
#18
REVIEW
Jeevanathan Kalyanasundram, Aini Hamid, Khatijah Yusoff, Suet Lin Chia
The discovery of tumour selective virus-mediated apoptosis marked the birth of an alternative cancer treatment in the form of oncolytic viruses. Even though, its oncolytic efficiency was demonstrated more than 50 years ago, safety concerns which resulted from mild to lethal side effects hampered the progress of oncolytic virus research. Since the classical oncolytic virus studies rely heavily on its natural oncolytic ability, virus manipulation was limited, thereby, restricted efforts to improve its safety...
April 4, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29623208/a-rare-challenging-case-of-co-existent-craniopharyngioma-acromegaly-and-squamous-cell-lung-cancer
#19
Athanasios Fountas, Shu Teng Chai, John Ayuk, Neil Gittoes, Swarupsinh Chavda, Niki Karavitaki
Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29620223/resveratrol-decreases-rad51-expression-and-sensitizes-cisplatin%C3%A2-resistant-mcf%C3%A2-7-breast-cancer-cells
#20
I Leon-Galicia, J Diaz-Chavez, M E Albino-Sanchez, E Garcia-Villa, R Bermudez-Cruz, J Garcia-Mena, L A Herrera, A García-Carrancá, P Gariglio
Resveratrol (RES), a polyphenol compound with anti‑proliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the anti‑proliferative effects of cisplatin (CIS) on MCF‑7 cells, focusing on the inhibitory effects on DNA repair of double‑strand breaks (DSBs). Chemoresistant MCF‑7 cells (MCF‑7R) were generated by continuous exposure to low concentrations of CIS (10 µM CIS‑IC40) during 5 passages, with the IC50 value increasing ~3‑fold...
March 27, 2018: Oncology Reports
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