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https://www.readbyqxmd.com/read/28655075/-surgical-treatment-of-colorectal-liver-metastases
#1
J M Xu, D X Zhu, L Ren
Surgical resection of the metastases offers the only opportunity for long-term survival in colorectal liver metastases. However, only 10% to 20% of patients present with resectable disease, and so how to increase surgical patients has been a clinical hotspot. In addition to expanding surgical indications, two-stage hepatectomy and convertible therapy are optional. In convertible therapy, initial treatment regimen decides long-term benefit, and it is important to select appropriate patient population in addition to Ras status when anti-epithelial growth factor receptor monoclonal antibody is used...
July 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28654140/epidermal-growth-factor-receptor-egfr-inhibitors-for-metastatic-colorectal-cancer
#2
REVIEW
David Lok Hang Chan, Eva Segelov, Rachel Sh Wong, Annabel Smith, Rebecca A Herbertson, Bob T Li, Niall Tebbutt, Timothy Price, Nick Pavlakis
BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors prevent cell growth and have shown benefit in the treatment of metastatic colorectal cancer, whether used as single agents or in combination with chemotherapy. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). However, there is ongoing debate as to which patient populations gain maximum benefit from EGFR inhibition and where they should be used in the metastatic colorectal cancer treatment paradigm to maximise efficacy and minimise toxicity...
June 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28653888/dj-1-as-a-potential-biomarker-for-the-early-diagnosis-in-lung-cancer-patients
#3
Binbin Han, Jiwen Wang, Jia Gao, Shana Feng, Yu Zhu, Xuexiang Li, Ting Xiao, Jun Qi, Wei Cui
DJ-1 is a novel oncogene that can transform NIH3T3 cells in cooperation with the activated ras gene. DJ-1 appears to have its greatest effect on tumourigenesis, and it may have a greater impact on early-stage lung cancers. In this study, we proposed to investigate the clinical value of DJ-1 protein in the early diagnosis of lung cancer and compared its diagnostic value with other biomarkers. Preoperative serum DJ-1 levels were measured in 300 lung cancer patients and compared with benign pulmonary disease (n = 44) and healthy volunteers (n = 64)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28653397/acute-myeloid-leukaemia-genomics
#4
REVIEW
Michael Medinger, Jakob R Passweg
Acute myeloid leukaemia (AML) is a biologically complex, molecularly and clinically heterogeneous disease. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, standard treatment options have not significantly changed during the past three decades. AML is characterized by multiple somatically acquired mutations that affect genes of different functional categories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28653224/acquisition-of-anoikis-resistance-promotes-alterations-in-the-ras-erk-and-pi3k-akt-signaling-pathways-and-matrix-remodeling-in-endothelial-cells
#5
Ana Paula de Sousa Mesquita, Silvana de Araújo Lopes, Paulo Castanho A Pernambuco Filho, Helena B Nader, Carla Cristina Lopes
Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix. Anoikis resistance is a critical mechanism in tumor metastasis. Cancer cells deregulate and adapt their metabolism to survive in the absence of adhesion, spreading metastases to distant organs. These adaptations include abnormal regulation of growth factor receptors activating prosurvival signaling pathways, such as the Ras/ERK and PI3K/Akt pathways, and extracellular matrix remodeling, leading to metastasis by an increase of invasiveness and inhibiting anoikis...
June 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28653203/ras-screening-in-colorectal-cancer-a-comprehensive-analysis-of-the-results-from-the-uk-neqas-colorectal-cancer-external-quality-assurance-schemes-2009-2016
#6
Susan D Richman, Jennifer Fairley, Rachel Butler, Zandra C Deans
Evidence strongly indicates that extended RAS testing should be undertaken in mCRC patients, prior to prescribing anti-EGFR therapies. With more laboratories implementing testing, the requirement for External Quality Assurance schemes increases, thus ensuring high standards of molecular analysis. Data was analysed from 15 United Kingdom National External Quality Assessment Service (UK NEQAS) for Molecular Genetics Colorectal cancer external quality assurance (EQA) schemes, delivered between 2009 and 2016. Laboratories were provided annually with nine colorectal tumour samples for genotyping...
June 26, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28652417/k-ras-mutations-as-the-earliest-driving-force-in-a-subset-of-colorectal-carcinomas
#7
REVIEW
Nikolaos Margetis, Myrsini Kouloukoussa, Kyriaki Pavlou, Spyridon Vrakas, Theodoros Mariolis-Sapsakos
K-ras oncogene is a key factor in colorectal cancer. Based on published and our data we propose that K-ras could be the oncogene responsible for the inactivation of the tumor-suppressor gene APC, currently considered as the initial step in colorectal tumorigenesis. K-ras fulfills the criteria of the oncogene-induced DNA damage model, as it can provoke well-established causes for inactivating tumor-suppressors, i.e. DNA double-strand breaks (causing allele deletion) and ROS production (responsible for point mutation)...
July 2017: In Vivo
https://www.readbyqxmd.com/read/28652304/thymic-progenitors-of-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intestinal-intraepithelial-lymphocytes-require-rasgrp1-for-development
#8
Dominic P Golec, Romy E Hoeppli, Laura M Henao Caviedes, Jillian McCann, Megan K Levings, Troy A Baldwin
Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRαβ(+)CD8αα intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling...
June 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28651317/effects-of-multi-environmental-factors-on-physiological-and-biochemical-responses-of-large-yellow-croaker-larimichthys-crocea
#9
Qian-Feng Wang, Wei-Liang Shen, Cheng Liu, Dan-Li Mu, Xiong-Fei Wu, Nian-Gang Guo, Jun-Quan Zhu
Land-based recirculating aquaculture systems (RAS) and cage culture are important methods of Larimichthys crocea production. The effects of environmental factors on physiological and biochemical aspects of L. crocea require clarification. Temperature and salinity are controlled in RAS and directly affect L. crocea growth and survival. To explore optimal parameters, the oxygen consumption rate (RO), ammonium excretion rate (RN), and O/N ratio at different temperatures (8, 14, 20, 26, and 32 °C) and salinities (5, 15, 25, and 35‰) were determined...
June 13, 2017: Chemosphere
https://www.readbyqxmd.com/read/28651158/prospective-validation-of-a-lymphocyte-infiltration-prognostic-test-in-stage-iii-colon-cancer-patients-treated-with-adjuvant-folfox
#10
Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb
BACKGROUND: The prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use. PATIENTS AND METHODS: According to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study...
June 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28650844/long-term-persistence-of-hcv-ns5a-resistance-associated-substitutions-after-treatment-with-the-hcv-ns5a-inhibitor-ledipasvir-without-sofosbuvir
#11
David Wyles, Alessandra Mangia, Wendy Cheng, Stephen Shafran, Christian Schwabe, Wen Ouyang, Charlotte Hedskog, John McNally, Diana M Brainard, Brian P Doehle, Evguenia Svarovskaia, Michael D Miller, Hongmei Mo, Hadas Dvory-Sobol
BACKGROUND: Data on persistence of NS5A resistance associated substitutions (RASs) may have implications for resistance testing approaches and selection of initial and retreatment strategies. METHODS: Long-term persistence of NS5A RASs in HCV genotype (GT) 1 infected subjects (n=76) who did not achieve sustained virologic response after receiving ledipasvir (LDV) without sofosbuvir (SOF) and were subsequently enrolled in an ongoing 3-year follow-up registry study was investigated by population or deep sequencing...
June 26, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28650561/craniosynostosis-in-patients-with-rasopathies-accumulating-clinical-evidence-for-expanding-the-phenotype
#12
Kimiko Ueda, Masako Yaoita, Tetsuya Niihori, Yoko Aoki, Nobuhiko Okamoto
RASopathies are phenotypically overlapping genetic disorders caused by dysregulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome, Costello syndrome, Neurofibromatosis type 1, Legius syndrome, Noonan syndrome with multiple lentigines, Noonan-like syndrome, hereditary gingival fibromatosis, and capillary malformation/arteriovenous malformation syndrome. Recently, six patients with craniosynostosis and Noonan syndrome involving KRAS mutations were described in a review, and a patient with craniosynostosis and Noonan syndrome involving a SHOC2 mutation has also been reported...
June 26, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#13
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649886/epidermal-growth-factor-inhibitors-in-first-line-for-metastatic-colorectal-cancer-with-ras-wild-type-a-perspective-based-on-pharmacological-costs
#14
Jacopo Giuliani, Andrea Bonetti
In light of the relevant expenses of pharmacological interventions it might be interesting to make a balance between the cost of the new drugs administered, such as EGFRIs (cetuximab and panitunumab) and the added value represented by the improvement of the clinical parameters of interest such as progression free survival (PFS). Areas Covered: The analysis was conducted to assess the effect of front-line chemotherapy on the PFS, separately, on each arm of the evaluated trials. Only phase III randomized controlled trials (RCTs) were considered...
June 24, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28649228/ras-activity-tunes-the-period-and-modulates-the-entrainment-of-the-suprachiasmatic-clock
#15
REVIEW
Tsvetan Serchov, Rolf Heumann
The small GTPase Ras is a universal eukaryotic cytoplasmic membrane-anchored protein, which regulates diverse downstream signal transduction pathways that play an important role in the proper functioning of neurons. Ras activity is a central regulator of structural and functional synaptic plasticity in the adult nervous system, where it channels neuronal responses to various extracellular cues allowing the organism to adapt to complex environmental stimuli. The suprachiasmatic nucleus (SCN) is the principle pacemaker of the circadian clock, and the circadian and photic regulation of Ras activity in the SCN is an important modulator of the clockwork...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28648093/s-nitrosylation-of-ras-mediates-nitric-oxide-dependent-post-injury-neurogenesis-in-a-seizure-model
#16
Ana Isabel Santos, Bruno Pereira Carreira, Alicia Izquierdo-Álvarez, Elena Ramos, Ana Sofia Lourenço, Daniela Santos, Maria Inês Morte, Luís Filipe Ribeiro, Ana Marreiros, Nuria Sánchez-López, Anabel Marina, Caetana Monteiro Carvalho, Antonio Martínez-Ruiz, Inês M Araújo
AIMS: Nitric oxide (NO) is involved in the upregulation of endogenous neurogenesis in the subventricular zone and in the hippocampus after injury. One of the main neurogenic pathways activated by NO is the ERK/MAPK pathway, downstream of the EGF receptor. However, the mechanism by which NO stimulates cell proliferation through activation of the ERK/MAPK pathway remains unknown, although p21Ras seems to be one of the earliest targets of NO. Here, we aimed to study the possible neurogenic action of NO by post-translational modification of p21Ras as a relevant target for early neurogenic events promoted by NO in neural stem cells (NSC)...
June 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28647697/analysis-of-k-ras-interactions-by-biotin-ligase-tagging
#17
Christopher Ritchie, Andrew Mack, Logan Harper, Ayna Alfadhli, Philip J S Stork, Xiaolin Nan, Eric Barklis
BACKGROUND: Mutations of the human K-Ras 4B (K-Ras) G protein are associated with a significant proportion of all human cancers. Despite this fact, a comprehensive analysis of K-Ras interactions is lacking. Our investigations focus on characterization of the K-Ras interaction network. MATERIALS AND METHODS: We employed a biotin ligase-tagging approach, in which tagged K-Ras proteins biotinylate neighbor proteins in a proximity-dependent fashion, and proteins are identified via mass spectrometry (MS) sequencing...
July 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28646021/eif1ax-and-nras-mutations-co-occur-and-cooperate-in-low-grade-serous-ovarian-carcinomas
#18
Dariush Etemadmoghadam, Walid J Azar, Ying Lei, Tania Moujaber, Dale W Garsed, Catherine Kennedy, Sian Fereday, Chris Mitchell, Yoke-Eng Chiew, Joy Hendley, Australian Ovarian Cancer Study Group, Raghwa Sharma, Paul Harnett, Jason Li, Elizabeth L Christie, Ann-Marie Patch, Joshy George, George Au-Yeung, Gisela Mir Arnau, Timothy P Holloway, Timothy Semple, John V Pearson, Nicola Waddell, Sean Grimmond, Martin Köbel, Helen Rizos, Ivan Lomakin, David D L Bowtell, Anna DeFazio
Low-grade serous ovarian carcinomas (LGSC) are associated with a poor response to chemotherapy and are molecularly characterized by RAS pathway activation. Using exome and whole genome sequencing we identified recurrent mutations in the protein translational regulator EIF1AX and in NF1, USP9X, KRAS, BRAF and NRAS. RAS pathway mutations were mutually exclusive, however we found significant co-occurrence of mutations in NRAS and EIF1AX Missense EIF1AX mutations were clustered at the N-terminus of the protein in a region associated with its role in ensuring translational initiation fidelity...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645859/discovery-of-a-novel-pan-raf-inhibitor-with-potent-anti-tumor-activity-in-preclinical-models-of-braf-v600e-mutant-cancer
#19
Sung Pyo Hong, Soon Kil Ahn
AIMS: BRAF mutations, especially BRAF V600E, are a frequent occurrence in malignant melanomas. The BRAF inhibitors are used as the care standard for BRAF-mutant metastatic melanomas. However, melanomas rapidly develop resistance to BRAF inhibitors after a median response duration of 6months, and the subsequent rapid development of cutaneous toxicity is enhanced by the paradoxical activation of CRAF. In this study, we discovered a potent and selective pan-RAF inhibitor: INU-152. The goal of this study was to investigate whether the inhibition of pan-RAF with INU-152 completely disrupts the MAPK pathway in cancer cells bearing BRAF or RAS mutations...
June 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28644741/ras-signaling-regulates-stem-cells-and-amelogenesis-in-the-mouse-incisor
#20
X Zheng, A F Goodwin, H Tian, A H Jheon, O D Klein
The role of Ras signaling during tooth development is poorly understood. Ras proteins-which are activated by many upstream pathways, including receptor tyrosine kinase cascades-signal through multiple effectors, such as the mitogen-activated protein kinase (MAPK) and PI3K pathways. Here, we utilized the mouse incisor as a model to study how the MAPK and PI3K pathways regulate dental epithelial stem cells and amelogenesis. The rodent incisor-which grows continuously throughout the life of the animal due to the presence of epithelial and mesenchymal stem cells-provides a model for the study of ectodermal organ renewal and regeneration...
June 1, 2017: Journal of Dental Research
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