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Huabo Wang, Jay Chauhan, Angela Hu, Kelsey Pendleton, Jeremy L Yap, Philip E Sabato, Jace W Jones, Mariarita Perri, Jianshi Yu, Erika Cione, Maureen A Kane, Steven Fletcher, Edward V Prochownik
[This corrects the article DOI: 10.18632/oncotarget.1108.].
October 12, 2018: Oncotarget
Caterina Chiappetta, Chiara Puggioni, Raffaella Carletti, Vincenzo Petrozza, Carlo Della Rocca, Claudio Di Cristofano
[This corrects the article DOI: 10.18632/oncotarget.25755.].
October 12, 2018: Oncotarget
Frank Griesinger, Julia Roeper, Christoph Pöttgen, Kay C Willborn, Wilfried E E Eberhardt
The progress in molecular biology has revolutionized systemic treatment of advanced non-small-cell lung cancer (NSCLC) from conventional chemotherapy to a treatment stratified by histology and genetic aberrations. Tumors harboring a translocation of the anaplastic-lymphoma-kinase (ALK) gene constitute a distinct genetic and clinico-pathologic NSCLC subtype with patients with ALK-positive disease being at a higher risk for developing brain metastases. Due to the introduction of effective targeted therapy with ALK-inhibitors, today, patients with advanced ALK-positive NSCLC achieve high overall response rates and remain progression-free for long time intervals...
October 12, 2018: Oncotarget
Hanna Engqvist, Toshima Z Parris, Elisabeth Werner Rönnerman, Elin M V Söderberg, Jana Biermann, Claudia Mateoiu, Karin Sundfeldt, Anikó Kovács, Per Karlsson, Khalil Helou
Ovarian cancer is the most lethal gynecological malignancy in the western world. Despite recent efforts to characterize ovarian cancer using molecular profiling, few targeted treatment options are currently available. Here, we examined genetic variants, fusion transcripts, SNP genotyping, and gene expression patterns for early-stage (I and II) ovarian carcinomas (n=96) in relation to clinicopathological characteristics and clinical outcome, thereby identifying novel genetic features of ovarian carcinomas. Furthermore, mutation frequencies of specific genetic variants and/or their gene expression patterns were associated with histotype and overall survival, e...
October 12, 2018: Oncotarget
Nachi Namatame, Naomi Tamaki, Yuya Yoshizawa, Mutsumi Okamura, Yumiko Nishimura, Kanami Yamazaki, Miwa Tanaka, Takuro Nakamura, Kentaro Semba, Takao Yamori, Shin-Ichi Yaguchi, Shingo Dan
Treatment of patients with advanced sarcoma remains challenging due to lack of effective medicine, with the development of novel drugs being of keen interest. A pan-PI3K inhibitor, ZSTK474, has been evaluated in clinical trials against a range of advanced solid tumors, with clinical benefit shown in sarcoma patients. In the present study, we developed a panel of 14 human sarcoma cell lines and investigated the antitumor effect of 24 anticancer agents including ZSTK474, other PI3K inhibitors, and those clinically used for sarcoma treatment...
October 12, 2018: Oncotarget
Alessio Montresor, Lara Toffali, Antonella Rigo, Isacco Ferrarini, Fabrizio Vinante, Carlo Laudanna
Bruton's tyrosine kinase (BTK) regulates the B-cell receptor (BCR) signaling pathway, which, in turn, plays a critical role in B-cell chronic lymphocytic leukemia (B-CLL) pathogenesis. The BTK-specific inhibitor Ibrutinib blocks BCR signaling and is now approved as effective B-CLL therapy. Chemokines, such as the homeostatic chemokine CXCL12, play a central role in B-CLL pathogenesis and progression, by regulating CLL cell interaction with the stromal microenvironment, leading to cells survival and proliferation...
October 12, 2018: Oncotarget
Donato Lacedonia, Giulia Scioscia, Grazia Pia Palladino, Crescenzio Gallo, Giovanna Elisiana Carpagnano, Roberto Sabato, Maria Pia Foschino Barbaro
Introduction: MicroRNAs (miRNAs) are small non coding RNAs which play a role in several cellular processes. MiRNA expression is influenced by oxidative stress, inflammatory cascade and hypoxia. Effects of different types of hypoxia (intermittent and chronic) have been poorly investigated. The aim of this study was to evaluate how intermittent and chronic hypoxia influence the expression of a pool of miRNAs. Results: Subjects with HI presented higher levels of miR-21, miR-23b, miR-145 and miR-210 compared to the other groups, while higher levels of miR-26 was observed in the HC group...
October 12, 2018: Oncotarget
Patricia D B Tiburcio, Bing Xiao, Yi Chai, Sydney Asper, Sheryl R Tripp, David L Gillespie, Randy L Jensen, L Eric Huang
Recurrent heterozygous mutation of isocitrate dehydrogenase 1 gene ( IDH1 ), predominantly resulting in histidine substitution at arginine 132, was first identified in glioma. The biological significance of IDH1R132H , however, has been controversial, and its prevalent association with glioma remains enigmatic. Although recent studies indicate that IDH1R132H is nonessential to tumor growth or even anti-tumor growth, whether IDH1R132H initiates gliomagenesis remains obscure. In this study, we report that IDH1R132H is intrinsically tumor-suppressive but the activity can be attenuated by glutamate-the cerebral neurotransmitter...
October 12, 2018: Oncotarget
Laura Gramantieri, Michele Baglioni, Francesca Fornari, Maria Antonella Laginestra, Manuela Ferracin, Valentina Indio, Matteo Ravaioli, Matteo Cescon, Vanessa De Pace, Simona Leoni, Camelia Alexandra Coadă, Massimo Negrini, Luigi Bolondi, Catia Giovannini
Long non-coding RNAs (lncRNAs) are ncRNAs more than 200 nucleotides long that participate to a wide range of biological functions. However, their role in cancer is poorly known. By using an NGS-based approach we analyzed the intragenic and poliA-lncRNAs in hepatocellular carcinoma (HCC) and we assayed the relationships between their deregulated expression and clinical-pathological characteristics. The expression profile of lncRNAs was studied in a discovery series of 28 HCC and matched cirrhosis and was validated in an independent cohort of 32 HCC patients both in tissue and serum...
October 12, 2018: Oncotarget
Estefanía Burgos-Morón, José Manuel Calderón-Montaño, Nuria Pastor, Andreas Höglund, Ángel Ruiz-Castizo, Inmaculada Domínguez, Miguel López-Lázaro, Nabil Hajji, Thomas Helleday, Santiago Mateos, Manuel Luis Orta
The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-2'-deoxycytidine (5-azadC) is a nucleoside analogue that covalently traps DNA methyltransferases (DNMTs) onto DNA. This anticancer drug has a double mechanism of action: it reverts aberrant hypermethylation in tumour-suppressor genes, and it induces DNA damage...
October 12, 2018: Oncotarget
Chiara Russo, Chiara Giannotti, Alessio Signori, Michele Cea, Roberto Murialdo, Alberto Ballestrero, Stefano Scabini, Emanuele Romairone, Patrizio Odetti, Alessio Nencioni, Fiammetta Monacelli
Objectives: Comprehensive Geriatric Assessment (CGA), the gold standard for detecting frailty in elderly cancer patients, is time-consuming and hard to apply in routine clinical practice. Here we compared the performance of two screening tools for frailty, G8 and SAOP2 for their accuracy in identifying vulnerable patients. Material and Methods: We tested G8 and SAOP2 in 282 patients aged 65 or older with a diagnosis of solid cancer and candidate to undergo surgical, medical and/or radiotherapy treatment...
October 12, 2018: Oncotarget
Martin Rupp, Zhor Senhaji Mouhri, Christopher Williams, Bertrand J Jean-Claude
Disordered expression of the epidermal growth factor receptor (EGFR) has been associated with induction of DNA repair genes (e.g. XRCC1, ERCC1) and resistance to radiation and genotoxic drugs. However, our previous work showed that EGFR inhibition did not affect O6 -methylguanine-DNA methyltransferase (MGMT)-mediated resistance. In order to block uncoupled events associated with EGFR and MGMT, we designed MR30, a single molecule termed "combi-molecule" that contains a quinazoline arm targeted to EGFR and an O6 -benzylguanine (O6 -BG) moiety to block MGMT...
October 12, 2018: Oncotarget
Roberta Coluccia, Salvatore Raffa, Danilo Ranieri, Andrea Micaloni, Sabatino Valente, Gerardo Salerno, Cristina Scrofani, Marco Testa, Giovanna Gallo, Erika Pagannone, Maria Rosaria Torrisi, Massimo Volpe, Speranza Rubattu
Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects...
October 12, 2018: Oncotarget
Madhawa Neranjan Gunathilake, Jeonghee Lee, Young Ae Cho, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
[This corrects the article DOI: 10.18632/oncotarget.24136.].
October 9, 2018: Oncotarget
Tzu-An Liu, Yee-Jee Jan, Bor-Sheng Ko, Yi-Ju Wu, Yi-Jhu Lu, Shu-Man Liang, Chia-Chia Liu, Shyh-Chang Chen, John Wang, Song-Kun Shyue, Jun-Yang Liou
[This corrects the article DOI: 10.18632/oncotarget.5734.].
October 9, 2018: Oncotarget
Ganiou Assani, Yudi Xiong, Fuxiang Zhou, Yunfeng Zhou
Cancer is one of the leading causes of death in the world. Many strategies of cancer treatment such as radiotherapy which plays a key role in cancer treatment are developed and used nowadays. However, the side effects post-cancer radiotherapy and cancer radioresistance are two major causes of the limitation of cancer radiotherapy effectiveness in the cancer patients. Moreover, reduction of the limitation of cancer radiotherapy effectiveness by reducing the side effects post-cancer radiotherapy and cancer radioresistance is the aim of several radiotherapy-oncologic teams...
October 9, 2018: Oncotarget
Xuran Yang, Wei Xia, Lin Chen, Chuan Xing Wu, Cathy C Zhang, Peter Olson, Xiao Qi Wang
As a multi-kinase inhibitor, sorafenib is beneficial in around 30% of hepatocellular carcinoma (HCC) patients; however, HCC patients develop acquired drug resistance quickly. Clinical benefits of sorafenib, in combination with transarterial chemoembolization (TACE), radiotherapy, and other chemodrugs are limited. We investigated the efficacy and mechanisms of Notch signaling inhibition as adjuvant to sorafenib in HCC spheroid-derived in vitro and in vivo tumor models, using the γ-secretase inhibitor (GSI), PF-03084014...
October 9, 2018: Oncotarget
Christian Posch, Martina Sanlorenzo, Jeffrey Ma, Sarasa T Kim, Mitchell Zekhtser, Susana Ortiz-Urda
Targeted therapy has become a cornerstone for the treatment of melanoma patients. Targeting NRAS function is particularly challenging. To date, only single MEK inhibitor treatment was able to show minimal clinical efficacy. The discovery that co-targeting of MEK and CDK4,6 has antitumor activity created excitement for patients and clinicians; however, it is largely unknown if only NRAS mutant patients might benefit from MEK/CDK4,6 blockade. In this study we investigate response patterns of NRAS, BRAF mutant and 'wild type' melanoma cells in vitro and in vivo when challenged with inhibitors of MEK, CDK4,6 and the combination of both...
October 9, 2018: Oncotarget
Claudia Duranti, Laura Carraresi, Angelica Sette, Matteo Stefanini, Tiziano Lottini, Silvia Crescioli, Olivia Crociani, Luisa Iamele, Hugo De Jonge, Ermanno Gherardi, Annarosa Arcangeli
Modern molecular imaging techniques have greatly improved tumor detection and post-treatment follow-up of cancer patients. In this context, antibody-based imaging is rapidly becoming the gold standard, since it combines the unique specificity of antibodies with the sensitivity of the different imaging technologies. The aim of this study was to generate and characterize antibodies in single chain Fragment variable (scFv) format directed to an emerging cancer biomarker, the human ether-à-go-go-related gene-1 (hERG1) potassium channel, and to obtain a proof of concept for their potential use for in vivo molecular imaging...
October 9, 2018: Oncotarget
Anthony Arlia-Ciommo, Anna Leonov, Karamat Mohammad, Adam Beach, Vincent R Richard, Simon D Bourque, Michelle T Burstein, Alexander A Goldberg, Pavlo Kyryakov, Alejandra Gomez-Perez, Olivia Koupaki, Vladimir I Titorenko
All presently known geroprotective chemical compounds of plant and microbial origin are caloric restriction mimetics because they can mimic the beneficial lifespan- and healthspan-extending effects of caloric restriction diets without the need to limit calorie supply. We have discovered a geroprotective chemical compound of mammalian origin, a bile acid called lithocholic acid, which can delay chronological aging of the budding yeast Saccharomyces cerevisiae under caloric restriction conditions. Here, we investigated mechanisms through which lithocholic acid can delay chronological aging of yeast limited in calorie supply...
October 9, 2018: Oncotarget
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