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https://www.readbyqxmd.com/read/28214655/identification-of-microrna-biomarkers-for-response-of-advanced-soft-tissue-sarcomas-to-eribulin-translational-results-of-the-eortc-62052-trial
#1
Erik A C Wiemer, Agnieszka Wozniak, Herman Burger, Marcel Smid, Giuseppe Floris, Axelle Nzokirantevye, Raf Sciot, Stefan Sleijfer, Patrick Schöffski
BACKGROUND: Recent phase II and III clinical trials demonstrated anti-tumour activity of eribulin, a tubulin-interacting cytotoxic agent, in patients with metastatic soft tissue sarcoma (STS). In this exploratory study, we aimed to identify putative microRNA biomarkers that associate with eribulin sensitivity or resistance in STS. MATERIALS AND METHODS: Archival tumour tissue from primary tumours or metastatic lesions was collected prior to eribulin treatment, from 65 consenting patients involved in the EORTC trial 62052...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28212576/galectin-1-knockdown-improves-drug-sensitivity-of-breast-cancer-by-reducing-p-glycoprotein-expression-through-inhibiting-the-raf-1-ap-1-signaling-pathway
#2
Fang Wang, Pengwei Lv, Yuanting Gu, Lin Li, Xin Ge, Guangcheng Guo
Galectin-1 (Gal-1), a member of the galectin family of carbohydrate binding proteins, plays a pivotal role in various cellular processes of tumorigenesis. The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines. MTT assay and flow cytometry revealed that Gal-1 knockdown improved sensitivity to paclitaxel (PTX) and adriamycin (ADR) in MCF-7/PTX and MCF-7/ADR cells via inhibition of cell viability and promotion of cell apoptosis, while MDR1 overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28204974/lipid-peroxidation-dependent-cell-death-regulated-by-gpx4-and-ferroptosis
#3
Hirotaka Imai, Masaki Matsuoka, Takeshi Kumagai, Taro Sakamoto, Tomoko Koumura
Glutathione peroxidase 4 (Phospholipid hydroperoxide glutathione peroxidase, PHGPx) can directly reduce phospholipid hydroperoxide. Depletion of GPx4 induces lipid peroxidation-dependent cell death in embryo, testis, brain, liver, heart, and photoreceptor cells of mice. Administration of vitamin E in tissue specific GPx4 KO mice restored tissue damage in testis, liver, and heart. These results indicate that suppression of phospholipid peroxidation is essential for cell survival in normal tissues in mice. Ferroptosis is an iron-dependent non-apoptotic cell death that can elicited by pharmacological inhibiting the cystine/glutamate antiporter, system Xc(-) (type I) or directly binding and loss of activity of GPx4 (Type II) in cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression, but not in normal cells...
February 16, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28204731/hf10-therapy-for-chronic-back-pain-in-patients-with-nonoperated-kyphoscoliosis-the-importance-of-preoperative-assessment
#4
Maarten Moens, Ann De Smedt, Lisa Goudman, Peter Mariën, Jo Nijs, Patrick Herregodts, Raf Brouns
No abstract text is available yet for this article.
February 1, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28194438/a-role-for-muscarinic-receptors-in-neutrophil-extracellular-trap-formation-and-levamisole-induced-autoimmunity
#5
Carmelo Carmona-Rivera, Monica M Purmalek, Erica Moore, Meryl Waldman, Peter J Walter, H Martin Garraffo, Karran A Phillips, Kenzie L Preston, Jonathan Graf, Mariana J Kaplan, Peter C Grayson
Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28188628/histopathological-aspects-of-cutaneous-erythematous-papular-eruptions-induced-by-immune-checkpoint-inhibitors-for-the-treatment-of-metastatic-melanoma
#6
Raul E Perret, Nicolas Josselin, Anne-Chantal Knol, Amir Khammari, Julie Cassecuel, Lucie Peuvrel, Brigitte Dreno
BACKGROUND: Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized. METHODS: We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists...
February 10, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28188228/time-resolved-phosphoproteome-analysis-of-paradoxical-raf-activation-reveals-novel-targets-of-erk
#7
Peter Kubiniok, Hugo Lavoie, Marc Therrien, Pierre Thibault
Small molecules targeting aberrant RAF activity, like Vemurafenib (PLX4032), are highly effective against cancers harboring the V600E BRAF mutation, and are now approved for clinical use against metastatic melanoma. However, in tissues showing elevated RAS activity and in RAS-mutant tumors, these inhibitors stimulate RAF dimerization, resulting in inhibitor resistance and downstream paradoxical ERK activation. To understand the global signaling response of cancer cells to RAF inhibitors, we profiled the temporal changes of the phosphoproteome of two colon cancer cell lines (Colo205 and HCT116) that respond differently to Vemurafenib...
February 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28187824/expression-of-bacillus-thuringiensis-cytolytic-toxin-cyt2ca1-in-citrus-roots-to-control-diaprepes-abbreviatus-larvae
#8
Sulley Ben Mahmoud, John E Ramos, Robert G Shatters, David G Hall, Stephen L Lapointe, Randall P Niedz, Pierre Rougé, Ronald D Cave, Dov Borovsky
Diaprepes abbreviatus (L.) is an important pest of citrus in the USA. Currently, no effective management strategies of D. abbreviatus exist in citriculture, and new methods of control are desperately sought. To protect citrus against D. abbreviatus a transgenic citrus rootstock expressing Bacillus thuringiensis Cyt2Ca1, an insect toxin protein, was developed using Agrobacterium-mediated transformation of 'Carrizo' citrange [Citrus sinensis (L) Osbeck Poncirus trifoliate (L) Raf]. The transgenic citrus root stock expressed the cytolytic toxin Cyt2Ca1 constitutively under the control of a 35S promoter in the transgenic Carrizo citrange trifoliate hybrid including the roots that are the food source of larval D...
March 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28187004/didymin-an-orally-active-citrus-flavonoid-for-targeting-neuroblastoma
#9
REVIEW
Sharad S Singhal, Sulabh Singhal, Preeti Singhal, Jyotsana Singhal, David Horne, Sanjay Awasthi
Neuroblastoma, a rapidly growing yet treatment responsive cancer, is the third most common cancer of children and the most common solid tumor in infants. Unfortunately, neuroblastoma that has lost p53 function often has a highly treatment-resistant phenotype leading to tragic outcomes. In the context of neuroblastoma, the functions of p53 and MYCN (which is amplified in ~25% of neuroblastomas) are integrally linked because they are mutually transcriptionally regulated, and because they together regulate the catalytic activity of RNA polymerases...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186126/molecular-dissection-of-colorectal-cancer-in-pre-clinical-models-identifies-biomarkers-predicting-sensitivity-to-egfr-inhibitors
#10
Moritz Schütte, Thomas Risch, Nilofar Abdavi-Azar, Karsten Boehnke, Dirk Schumacher, Marlen Keil, Reha Yildiriman, Christine Jandrasits, Tatiana Borodina, Vyacheslav Amstislavskiy, Catherine L Worth, Caroline Schweiger, Sandra Liebs, Martin Lange, Hans-Jörg Warnatz, Lee M Butcher, James E Barrett, Marc Sultan, Christoph Wierling, Nicole Golob-Schwarzl, Sigurd Lax, Stefan Uranitsch, Michael Becker, Yvonne Welte, Joseph Lewis Regan, Maxine Silvestrov, Inge Kehler, Alberto Fusi, Thomas Kessler, Ralf Herwig, Ulf Landegren, Dirk Wienke, Mats Nilsson, Juan A Velasco, Pilar Garin-Chesa, Christoph Reinhard, Stephan Beck, Reinhold Schäfer, Christian R A Regenbrecht, David Henderson, Bodo Lange, Johannes Haybaeck, Ulrich Keilholz, Jens Hoffmann, Hans Lehrach, Marie-Laure Yaspo
Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28185929/chitosan-oligosaccharide-inhibits-egf-induced-cell-growth-possibly-through-blockade-of-epidermal-growth-factor-receptor-mitogen-activated-protein-kinase-pathway
#11
Qingsong Xu, Wenjing Wang, Wen Yang, Yuguang Du, Linsheng Song
Chitosan oligosaccharide (COS) has been shown to regulate various cellular and biological functions. Epidermal growth factor (EGF) plays a significant role in tumorigenesis and invasiveness of some cancers. The aim of this study was to evaluate the effects of COS on EGF-induced cell growth and the further mechanisms. The results demonstrated that COS could inhibit EGF-induced epithelial GE11 cells proliferation in a dose dependent manner. In addition, EGF stimulated the epithelial cells to undergo morphological alteration, exhibiting mesenchymal cells higher metastatic and invasive potential, however, COS could partly suppress aforementioned morphological change...
February 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28185819/expression-of-polysialic-acid-in-primary-laryngeal-squamous-cell-carcinoma
#12
Marko Klobučar, Sarah Visentin, Antonija Jakovčević, Mario Bilić, Lana Kovač-Bilić, Davorin Đanić, Krešimir Pavelić, Sandra Kraljević Pavelić
AIMS: Expression of polySia is associated with metastatic dissemination and progression of various malignant diseases. In particular, it may contribute to tumorigenesis by a negative modulatory effect on cellular signaling cascades responsible for cellular migration, differentiation and proliferation. In this study, we investigated the expression of polySia in primary metastatic and non-metastatic laryngeal squamous cell carcinoma (LSCC) tumor tissues and its potential impact on the LSCC progression...
February 6, 2017: Life Sciences
https://www.readbyqxmd.com/read/28184012/chromosome-20q-amplification-defines-a-subtype-of-microsatellite-stable-left-sided-colon-cancers-with-wild-type-ras-raf-and-better-overall-survival
#13
Ryan N Ptashkin, Carlos Pagan, Rona Yaeger, Sumit Middha, Jinru Shia, Kevin P O'Rourke, Michael F Berger, Lu Wang, Robert Cimera, Jiajing Wang, David S Klimstra, Leonard Saltz, Marc Ladanyi, Ahmet Zehir, Jaclyn F Hechtman
: Here comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma (CRC) harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced CRC underwent next generation sequencing (NGS) via MSK-IMPACT and a subset of case samples were subjected to high resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) CRC data. Of the CRC patients sequenced (n=401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28183255/melanoma-adjuvant-treatment-current-insight-and-clinical-features
#14
Carmine D Aniello, Francesco Perri, Giuseppina Della Vittoria Scarpati, Chiara Della Pepa, Salvatore Pisconti, Vincenzo Montesarchio, Nicolas Wernert, Mayra Rachele Zarone, Michele Caraglia, Gaetano Facchini, Massimiliano Berretta, Carla Cavaliere
Melanoma represents 2-3% of all cancers, 95% of them arise from skin, while only 5% are non-cutaneous melanoma. Despite an optimal surgery management, the risk of a local and systemic relapse remains high, particularly in high-risk patients (node-positive or node-negative T3b, T4 a/b). We conducted a systematic review of the main published and ongoing phase I/II/III trials between 2000 and June 2015 on the adjuvant treatment of cutaneous melanoma. The IFN remains the only option currently available for this aim...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183235/cactus-cladodes-opuntia-humifusa-extract-minimizes-the-effects-of-uv-irradiation-on-keratinocytes-and-hairless-mice
#15
Kyungmi Park, Hyeon-Son Choi, Yang Hee Hong, Eun Young Jung, Hyung Joo Suh
CONTEXT: Cactus cladodes [Opuntia humifusa (Raf.) Raf. (Cactaceae)] is one of the cactus genera, which has long been used as a folk medicine for skin disorders. OBJECTIVE: This study investigated the skincare potential of cactus cladodes extract (OHE), including its ability to regulate ultraviolet B (UVB)-induced hyaluronic acid (HA) production. MATERIALS AND METHODS: Gene expression levels of hyaluronic acid synthases (HASs) and hyaluronidase (HYAL) were measured in UVB-irradiated HaCaT cells with OHE treatment (10, 25, 50, 100 μg/mL) by real-time polymerase chain reaction (PCR)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28180061/kinase-suppressor-of-ras-2-ksr2-expression-in-the-brain-regulates-energy-balance-and-glucose-homeostasis
#16
Lili Guo, Diane L Costanzo-Garvey, Deandra R Smith, Beth K Neilsen, Richard G MacDonald, Robert E Lewis
OBJECTIVE: Kinase Suppressor of Ras 2 (KSR2) is a molecular scaffold coordinating Raf/MEK/ERK signaling that is expressed at high levels in the brain. KSR2 disruption in humans and mice causes obesity and insulin resistance. Understanding the anatomical location and mechanism of KSR2 function should lead to a better understanding of physiological regulation over energy balance. METHODS: Mice bearing floxed alleles of KSR2 (KSR2(fl/fl)) were crossed with mice expressing the Cre recombinase expressed by the Nestin promoter (Nes-Cre) to produce Nes-CreKSR2(fl/fl) mice...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28179375/quantitative-prediction-of-human-renal-clearance-and-drug-drug-interactions-of-organic-anion-transporter-substrates-using-in-vitro-transport-data
#17
Sumathy Mathialagan, Mary A Piotrowski, David A Tess, Bo Feng, John Litchfiled, Manthena V Varma
Organic anion transporters (OATs) play an important role in the renal secretion of drugs, and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir) and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance to in vivo secretory clearance...
February 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28179313/comparative-study-of-mutations-in-single-nucleotide-polymorphism-loci-of-kras-and-braf-genes-in-patients-who-underwent-screening-colonoscopy-with-and-without-premalignant-intestinal-polyps
#18
Michail Galanopoulos, Ioannis S Papanikolaou, Eleni Zografos, Nikos Viazis, George Papatheodoridis, Dimitrios Karamanolis, Evangelos Marinos, Gerassimos J Mantzaris, Maria Gazouli
AIM: Our aim was to perform a comparison study of the mutation rate of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-Raf murine sarcoma viral oncogene homolog-B (BRAF) genes between blood-based cell-free DNA (cfDNA), and tissue sample biopsies in individuals undergoing screening colonoscopy. MATERIALS AND METHODS: All specimens were collected from January 2015 to January 2016. A total of 92 blood samples and colonic biopsy specimens were collected from healthy individuals with no polyps undergoing screening colonoscopy (group A, n=35), patients with colorectal cancer (group B, n=27), and patients with neoplastic intestinal polyps (group C, n=30)...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28179093/sorafenib-and-fh535-in-combination-act-synergistically-on-hepatocellular-carcinoma-by-targeting-cell-bioenergetics-and-mitochondrial-function
#19
Lilia Turcios, Valery Vilchez, Luis F Acosta, Pratheeshkumar Poyil, David Allan Butterfield, Mihail Mitov, Francesc Marti, Roberto Gedaly
Treatment of advanced hepatocellular carcinoma (HCC) remains a challenge due to the high tumor heterogeneity. In the present study, we aim to evaluate the impact of the β-catenin inhibitor, FH535, alone or in combination with the Ras/Raf/MAPK inhibitor Sorafenib, on the bioenergetics profiles of the HCC cell lines Huh7 and PLC/PRF/5. Single low-dose treatments with FH535 or Sorafenib promoted different effects on mitochondrial respiration and glycolysis in a cell type specific manner. However, the combination of these drugs significantly reduced both mitochondrial respiration and glycolytic rates regardless of the HCC cells...
January 19, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#20
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
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