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https://www.readbyqxmd.com/read/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#1
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445939/epigenetic-therapy-with-inhibitors-of-histone-methylation-suppresses-dna-damage-signaling-and-increases-glioma-cell-radiosensitivity
#2
Ozge Gursoy-Yuzugullu, Chelsea Carman, Rodolfo Bortolozo Serafim, Marios Myronakis, Valeria Valente, Brendan D Price
Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445830/overexpression-of-heme-oxygenase-1-in-bone-marrow-stromal-cells-promotes-microenvironment-mediated-imatinib-resistance-in-chronic-myeloid-leukemia
#3
Ping Liu, Dan Ma, Zhengyu Yu, Nana Zhe, Mei Ren, Ping Wang, Meisheng Yu, Jun Huang, Qin Fang, Jishi Wang
Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with stromal cells of the surrounding microenvironment. Bone marrow stromal cells (BMSCs) represent the main population in CML marrow stroma, which may play a key role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that is associated with cell proliferation and resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and evaluated whether BMSCs influenced K562 cells survival...
April 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#4
Anup Sharma, Rajita Vatapalli, Eihab Abdelfatah, K Wyatt McMahon, Zachary Kerner, Angela A Guzzetta, Jasvinder Singh, Cynthia Zahnow, Stephen B Baylin, Sashidhar Yerram, Yue Hu, Nilofer Azad, Nita Ahuja
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28445469/phylogenetic-ctdna-analysis-depicts-early-stage-lung-cancer-evolution
#5
Christopher Abbosh, Nicolai J Birkbak, Gareth A Wilson, Mariam Jamal-Hanjani, Tudor Constantin, Raheleh Salari, John Le Quesne, David A Moore, Selvaraju Veeriah, Rachel Rosenthal, Teresa Marafioti, Eser Kirkizlar, Thomas B K Watkins, Nicholas McGranahan, Sophia Ward, Luke Martinson, Joan Riley, Francesco Fraioli, Maise Al Bakir, Eva GrÖnroos, Francisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M Fennessy, Nicole Sponer, Diana Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin Hiley, Siow Ming Lee, Martin D Forster, Tanya Ahmad, Mary Falzon, Elaine Borg, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Dina Hafez, Ashwini Naik, Apratim Ganguly, Stephanie Kareht, Rajesh Shah, Leena Joseph, Anne Marie Quinn, Phil Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Dahmane Oukrif, Ayse U Akarca, John A Hartley, Helen L Lowe, Sara Lock, Natasha Iles, Harriet Bell, Yenting Ngai, Greg Elgar, Zoltan Szallasi, Roland F Schwarz, Javier Herrero, Aengus Stewart, Sergio A Quezada, Peter Van Loo, Caroline Dive, C Jimmy Lin, Matthew Rabinowitz, Hugo Jwl Aerts, Allan Hackshaw, Jacqui A Shaw, Bernhard G Zimmermann, Charles Swanton
The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#6
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445420/vitamin-d-and-calcium-are-required-during-denosumab-treatment-in-osteoporosis-with-rheumatoid-arthritis
#7
Yukio Nakamura, Takako Suzuki, Tomohiko Yoshida, Hideshi Yamazaki, Hiroyuki Kato
The aim of this 12-month retrospective study was to evaluate differences in the outcomes of denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients having osteoporosis (OP) with rheumatoid arthritis (RA). Patients were divided into the denosumab monotherapy group (denosumab group, 22 cases) or denosumab plus vitamin D supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), N-terminal propeptide of type 1 collagen (P1NP), tartrate-resistant acid phosphatase (TRACP)-5b, and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, and 1, 2, 4, 6, 8, and 12 months...
April 26, 2017: Nutrients
https://www.readbyqxmd.com/read/28445403/detection-of-hepatitis-b-virus-m204i-mutation-by-quantum-dot-labeled-dna-probe
#8
Cheng Zhang, Yiping Chen, Xinmiao Liang, Guanhua Zhang, Hong Ma, Leng Nie, Yu Wang
Quantum dots (QDs) are semiconductor nanoparticles with a diameter of less than 10 nm, which have been widely used as fluorescent probes in biochemical analysis and vivo imaging because of their excellent optical properties. Sensitive and convenient detection of hepatitis B virus (HBV) gene mutations is important in clinical diagnosis. Therefore, we developed a sensitive, low-cost and convenient QDs-mediated fluorescent method for the detection of HBV gene mutations in real serum samples from chronic hepatitis B (CHB) patients who had received lamivudine or telbivudine antiviral therapy...
April 26, 2017: Sensors
https://www.readbyqxmd.com/read/28445154/role-of-delta-like-4-in-jagged1-induced-tumour-angiogenesis-and-tumour-growth
#9
Chern Ein Oon, Esther Bridges, Helen Sheldon, Richard C A Sainson, Adrian Jubb, Helen Turley, Russell Leek, Francesca Buffa, Adrian L Harris, Ji-Liang Li
Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#10
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445101/second-line-hormonal-therapy-for-men-with-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-american-society-of-clinical-oncology-provisional-clinical-opinion-summary
#11
Katherine S Virgo, R Bryan Rumble, Eric A Singer
No abstract text is available yet for this article.
April 26, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28445002/glucose-metabolism-targeting-therapy-and-withaferin-a-are-effective-for-egfr-tki-induced-drug-tolerant-persisters
#12
Kei Kunimasa, Tatsuya Nagano, Yohei Shimono, Ryota Dokuni, Tatsunori Kiriu, Shuntaro Tokunaga, Daisuke Tamura, Masatsugu Yamamoto, Motoko Tachihara, Kazuyuki Kobayashi, Miyako Satouchi, Yoshihiro Nishimura
In pathway-targeted cancer drug therapies, the relatively rapid emergence of drug-tolerant persisters (DTPs) substantially limits the overall therapeutic benefit. However, little is known about the roles of DTPs in drug resistance. In this study, we investigated the features of EGFR-TKI induced DTPs and explored a new treatment strategy to overcome the emergence of these DTPs. We used two EGFR mutated lung adenocarcinoma cell lines, PC9 and II-18. They were treated with 2 μM gefitinib for 6, 12, or 24 days or 6 month...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28444829/disparities-in-hiv-1-transmitted-drug-resistance-detected-by-ultradeep-sequencing-between-men-who-have-sex-with-men-and-heterosexual-populations
#13
E Todesco, C Charpentier, M Bertine, M Wirden, A Storto, N Desire, M Grude, T Nguyen, S Sayon, Y Yazdanpanah, C Katlama, D Descamps, V Calvez, A G Marcelin
OBJECTIVES: Transmitted drug resistance (TDR) can impair the response to first-line antiretroviral therapy. In treatment-naïve patients chronically infected with HIV type 1 (HIV-1), it was previously shown through Sanger sequencing that TDR was more common in men who have sex with men (MSM) than in other transmission risk groups. We aimed to compare two HIV-1 transmission groups in terms of the presence of TDR mutations. METHODS: We investigated, through Sanger sequencing and ultradeep sequencing (UDS), the presence of resistance mutations, both in majority (> 20%) and in minority (1-20%) proportions, in 70 treatment-naïve MSM and 70 treatment-naïve heterosexual patients who recently screened positive for HIV-1...
April 26, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28444760/vancomycin-levels-are-frequently-subtherapeutic-in-critically-ill-patients-a-prospective-observational-study
#14
V Bakke, H Sporsem, E Von der Lippe, I Nordøy, Y Lao, H C Nyrerød, L Sandvik, K R Hårvig, J F Bugge, E Helset
BACKGROUND: Appropriate utilization of vancomycin is important to attain therapeutic targets while avoiding clinical failure and the development of antimicrobial resistance. Our aim was to observe the use of vancomycin in an intensive care population, with the main focus on achievement of therapeutic serum concentrations (15-20 mg/l) and to evaluate how this was influenced by dose regimens, use of guidelines and therapeutic drug monitoring. METHODS: A prospective observational study was carried out in the intensive care units at two tertiary hospitals in Norway...
April 25, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28444728/circulating-cell-free-braf-v600e-as-a-biomarker-in-children-with-langerhans-cell-histiocytosis
#15
Sébastien Héritier, Zofia Hélias-Rodzewicz, Hélène Lapillonne, Nathalie Terrones, Sonia Garrigou, Corinne Normand, Mohamed-Aziz Barkaoui, Jean Miron, Geneviève Plat, Nathalie Aladjidi, Anne Pagnier, Anne Deville, Marion Gillibert-Yvert, Despina Moshous, Alain Lefèvre-Utile, Anne Lutun, Catherine Paillard, Caroline Thomas, Eric Jeziorski, Philippe Nizard, Valérie Taly, Jean-François Emile, Jean Donadieu
The BRAF(V600E) mutation is reported in half of patients with Langerhans cell histiocytosis (LCH). This study investigated the detection of the BRAF(V600E) allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAF(V600E) -mutated LCH were investigated to detect ccf BRAF(V600E) at diagnosis (n = 48) and during follow-up (n = 17) using a picolitre-droplet digital PCR assay. At diagnosis, ccf BRAF(V600E) was positive in 15/15 (100%) patients with risk-organ positive multisystem (RO+ MS) LCH, 5/12 (42%) of patients with RO- MS LCH and 3/21 (14%) patients with single-system (SS) LCH (P < 0·001, Fisher's exact test)...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28444708/can-we-create-a-valid-treatment-algorithm-for-patients-with-drug-resistant-overactive-bladder-oab-syndrome-or-detrusor-overactivity-do-results-from-a-think-tank-ici-rs-2015
#16
REVIEW
Apostolos Apostolidis, Marcio Augusto Averbeck, Arun Sahai, Sajjad Rahmana'i, Ralf Anding, Dudley Robinson, Stavros Gravas, Roger Dmochowski
AIMS: To review and assess the definitions of drug resistance and the evidence supporting treatment for drug resistant overactive bladder/detrusor overactivity (OAB/DO). METHODS: Evidence review of the extant literature and consensus of opinion was used to derive the summary recommendations. RESULTS: Drug resistance or drug refractory status has been inconsistently defined and reported in current evident sources. Recent publications use some correlation of lack of efficacy and or experienced side effects to define drug resistance...
April 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28444622/a-brief-review-of-the-management-of-platinum-resistant-platinum-refractory-ovarian-cancer
#17
REVIEW
Bryan Oronsky, Carolyn M Ray, Alexander I Spira, Jane B Trepel, Corey A Carter, Hope M Cottrill
Ovarian cancer, which ranks fifth in cancer deaths among women, is the most lethal gynecologic malignancy. Epithelial ovarian cancer (EOC) is the most common histologic type, with the 5-year survival for all stages estimated at 45.6%. This rate increases to more than 70% in the minority of patients who are diagnosed at an early stage, but declines to 35% in the vast majority of patients diagnosed at advanced stage. Recurrent EOC is incurable. Platinum sensitivity (or lack thereof) is a major determinant of prognosis...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28444219/dna-methylation-of-a-novel-pak4-locus-influences-ototoxicity-susceptibility-following-cisplatin-and-radiation-therapy-for-pediatric-embryonal-tumors
#18
Austin L Brown, Kayla L Foster, Philip J Lupo, Erin C Peckham-Gregory, Jeffrey C Murray, M Fatih Okcu, Ching C Lau, Surya P Rednam, Murali Chintagumpala, Michael E Scheurer
Background: Ototoxicity is a common adverse side effect of platinum chemotherapy and cranial radiation therapy; however, individual susceptibility is highly variable. Therefore, the objective of this study was to conduct an epigenome-wide association study to identify differentially methylated CpG sites associated with ototoxicity susceptibility among cisplatin-treated pediatric patients with embryonal tumors. Methods: Samples were collected for a discovery (n=62) and a replication cohort (n=18) of medulloblastoma and primitive neuroectodermal tumor patients...
April 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28444174/catheter-ablation-for-ventricular-tachycardia-in-patients-with-cardiac-sarcoidosis-a-systematic-review
#19
Nikolaos Papageorgiou, Rui Providência, Konstantinos Bronis, Dirk G Dechering, Neil Srinivasan, Lars Eckardt, Pier D Lambiase
Aims: Cardiac sarcoidosis (CS) is associated with a poor prognosis. Important features of CS include heart failure, conduction abnormalities, and ventricular arrhythmias. Ventricular tachycardia (VT) is often refractory to antiarrhythmic drugs (AAD) and immunosuppression. Catheter ablation has emerged as a treatment option for recurrent VT. However, data on the efficacy and outcomes of VT ablation in this context are sparse. Methods and results: A systematic search was performed on PubMed, EMBASE, and Cochrane database (from inception to September 2016) with included studies providing a minimum of information on CS patients undergoing VT ablation: age, gender, VT cycle length, CS diagnosis criteria, and baseline medications...
April 21, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28444169/androgen-receptor-regulation-of-local-growth-hormone-in-prostate-cancer-cells
#20
M V Recouvreux, B Wu, A C Gao, S Zonis, V Chesnokova, N Bhowmick, L W Chung, S Melmed
Prostate cancer (PCa) growth is mainly driven by androgen receptor (AR), and tumors that initially respond to androgen deprivation therapy (ADT) or AR inhibition usually relapse into a more aggressive, castration resistant stage (CRPC). Circulating growth hormone (GH) has a permissive role in PCa development in animal models and in human PCa xenograft growth. As GH and GH receptor (GHR) are both expressed in PCa cells, we assessed whether prostatic GH production is linked to AR activity and whether GH contributes to the castration resistant phenotype...
April 21, 2017: Endocrinology
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