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Oncotarget

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https://www.readbyqxmd.com/read/29774135/vemurafenib-in-langerhans-cell-histiocytosis-report-of-a-pediatric-patient-and-review-of-the-literature
#1
Anne Heisig, Jan Sörensen, Stefanie-Yvonne Zimmermann, Stefan Schöning, Dirk Schwabe, Hans-Michael Kvasnicka, Raphaela Schwentner, Caroline Hutter, Thomas Lehrnbecher
Selective BRAF inhibitors such as vemurafenib have become a treatment option in patients with Langerhans cell Histiocytosis (LCH). To date, only 14 patients receiving vemurafenib for LCH have been reported. Although vemurafenib can stabilize the clinical condition of these patients, it does not seem to cure the patients, and it is unknown, when and how to stop vemurafenib treatment. We present a girl with severe multisystem LCH who responded only to vemurafenib. After 8 months of treatment, vemurafenib was tapered and replaced by prednisone and vinblastine, a strategy which has not been described to date...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774134/an-undifferentiated-carcinoma-at-klatskin-position-with-long-term-complete-remission-after-chemotherapy
#2
Bruno Christian Köhler, Benjamin Goeppert, Nina Waldburger, Kai Schlamp, Peter Sauer, Dirk Jäger, Karl Heinz Weiss, Stephan Macher-Göppinger, Henning Schulze-Bergkamen, Peter Schirmacher, Christoph Springfeld
Background: Neoplasms anatomically adjacent to the bile duct usually derive from malignantly transformed cholangiocytes forming cholangiocarcinoma (CCA). CCAs are divided in extrahepatic (eCCA) and intrahepatic (iCCA) tumors. Patients with irresectable CCAs are treated with systemic chemotherapy and have an unfavorable prognosis with a median survival of about one year. Here, we report a case of an undifferentiated carcinoma in Klatskin-position with long-term remission after systemic chemotherapy...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774133/sporadic-renal-angiomyolipoma-in-a-patient-with-birt-hogg-dub%C3%A3-chaperones-in-pathogenesis
#3
Rebecca A Sager, Mark R Woodford, Oleg Shapiro, Mehdi Mollapour, Gennady Bratslavsky
Birt-Hogg-Dubé (BHD) is an autosomal dominant genetic syndrome caused by germline mutations in the FLCN gene that predisposes patients to develop renal tumors. Renal angiomyolipoma (AML) is not a renal tumor sub-type associated with BHD. AML is, however, a common phenotypic manifestation of Tuberous Sclerosis Complex (TSC) syndrome caused by mutations in either the TSC1 or TSC2 tumor suppressor genes. Previous case reports of renal AML in patients with BHD have speculated on the molecular and clinical overlap of these two syndromes as a result of described involvement of the gene products in the mTOR pathway...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774132/natural-products-a-hope-for-glioblastoma-patients
#4
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774131/methylation-of-dna-and-chromatin-as-a-mechanism-of-oncogenesis-and-therapeutic-target-in-neuroblastoma
#5
REVIEW
Ram Mohan Ram Kumar, Nina Felice Schor
Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774130/targeting-invadopodia-mediated-breast-cancer-metastasis-by-using-abl-kinase-inhibitors
#6
Tomer Meirson, Alessandro Genna, Nikola Lukic, Tetiana Makhnii, Joel Alter, Ved P Sharma, Yarong Wang, Abraham O Samson, John S Condeelis, Hava Gil-Henn
Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774129/combined-abiraterone-acetate-plus-prednisone-salvage-prostate-bed-radiotherapy-and-lh-rh-agonists-carlha-gep12-in-biochemically-relapsing-prostate-cancer-patients-following-prostatectomy-a-phase-i-study-of-the-getug-gep
#7
Stéphane Supiot, Loic Campion, Pascal Pommier, Mélanie Dore, Clément Palpacuer, Séverine Racadot, Emmanuel Rio, Gérard A Milano, Céline Mahier-Ait Oukhatar, Christian Carrie
Background: To establish the maximum tolerated dose of abiraterone acetate plus prednisone (AA) combined with salvage radiotherapy (SRT) and goserelin in a phase 1 study in men with rising PSA following radical prostatectomy. Methods: AA was given during one month before SRT at 1000 mg PO once daily, then 750 mg (Dose Level 1, DL1) or 1000 mg (DL2) during 5 months combined with 6-months goserelin by injection on the first day of irradiation (scheme NEO) or one month before starting SRT (scheme CONCO)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774128/systematic-review-and-meta-analysis-of-selected-toxicities-of-approved-alk-inhibitors-in-metastatic-non-small-cell-lung-cancer
#8
Rubens Barros Costa, Ricardo L B Costa, Sarah M Talamantes, Jason B Kaplan, Manali A Bhave, Alfred Rademaker, Corinne Miller, Benedito A Carneiro, Devalingam Mahalingam, Young Kwang Chae
Introduction: Anaplastic lymphoma kinase ( ALK ) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Materials and Methods: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#9
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774126/autophagy-deficient-breast-cancer-shows-early-tumor-recurrence-and-escape-from-dormancy
#10
Hussein F Aqbi, Liliya Tyutyunyk-Massey, Rebecca C Keim, Savannah E Butler, Theresa Thekkudan, Supriya Joshi, Timothy M Smith, Dipankar Bandyopadhyay, Michael O Idowu, Harry D Bear, Kyle K Payne, David A Gewirtz, Masoud H Manjili
Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774125/the-critical-role-that-stat3-plays-in-glioma-initiating-cells-stat3-addiction-in-glioma
#11
Debolina Ganguly, Meiyun Fan, Chuan He Yang, Blazej Zbytek, David Finkelstein, Martine F Roussel, Lawrence M Pfeffer
Glioma-Initiating Cells (GICs) are thought to be responsible for tumor initiation, progression and recurrence in glioblastoma (GBM). In previous studies, we reported the constitutive phosphorylation of the STAT3 transcription factor in GICs derived from GBM patient-derived xenografts, and that STAT3 played a critical role in GBM tumorigenesis. In this study, we show that CRISPR/Cas9-mediated deletion of STAT3 in an established GBM cell line markedly inhibited tumorigenesis by intracranial injection but had little effect on cell proliferation in vitro ...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#12
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774123/the-association-of-human-endogenous-retrovirus-h-long-terminal-repeat-associating-protein-2-hhla2-expression-with-gastric-cancer-prognosis
#13
Masataka Shimonosono, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matsushita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774122/the-down-regulation-of-the-cyp2c19-gene-is-associated-with-aggressive-tumor-potential-and-the-poorer-recurrence-free-survival-of-hepatocellular-carcinoma
#14
Ryo Ashida, Yukiyasu Okamura, Keiichi Ohshima, Yuko Kakuda, Katsuhiko Uesaka, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Takashi Sugino, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774121/mir-33-promotes-myocardial-fibrosis-by-inhibiting-mmp16-and-stimulating-p38-mapk-signaling
#15
Zhen Chen, Hua-Sheng Ding, Xin Guo, Jing-Jing Shen, Di Fan, Yan Huang, Cong-Xin Huang
Myocardial fibrosis occurs in the late stages of many cardiovascular diseases, and appears to be stimulated by various microRNAs (miRNAs). We previously found that miR-33 may stimulate cardiac remodeling. Here, we examined the involvement of miR-33 in myocardial fibrosis. Proximal left coronary descending artery occlusion was performed in rat, and antagomiR-33a was injected. Primary cardiac fibroblasts were cultured and transfected with miR-33a mimics and inhibitors. miR-33a levels were increased in the rat after surgery, and collagen deposition and heart fibrosis were observed in vivo ...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774120/carboplatin-in-combination-with-weekly-paclitaxel-as-first-line-therapy-in-patients-with-recurrent-metastatic-head-and-neck-squamous-cell-carcinoma-unfit-to-extreme-schedule
#16
Adeline Pêtre, Cécile Dalban, Andy Karabajakian, Eve-Marie Neidhardt, Pierre Eric Roux, Marc Poupart, Sophie Deneuve, Philippe Zrounba, Jérome Fayette
The standard first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma combines Cisplatin, 5 Fluorouracil and Cetuximab, but many patients aren't eligible. We retrospectively evaluated the efficacy and the tolerability of Carboplatin and Paclitaxel in this indication, mostly in patients unfit to Cisplatin. Paclitaxel (80mg/m2) was administered at day 1, 8 and 15 and Carboplatin area under the curve 5 at day 1, repeated every 28 days, for 6 cycles. Carboplatin could be administered at area under the curve 2 at day 1, 8 and 15...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774119/periostin-a-signal-transduction-intermediate-in-tgf-%C3%AE-induced-emt-in-u-87mg-human-glioblastoma-cells-and-its-inhibition-by-anthocyanidins
#17
Amira Ouanouki, Sylvie Lamy, Borhane Annabi
Periostin is a secreted protein that is highly expressed in glioblastoma cells as compared to normal brain tissue, and is therefore considered as a potential biomarker in therapeutic modalities. Its contribution in the cancer cells invasive phenotype is, however, poorly understood. This work investigates the role of periostin in U-87 MG glioblastoma cell invasion, cell migration and in Transforming Growth Factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT). Periostin gene silencing, using small interfering RNA, decreased TGF-β-induced mesenchymal marker expression of fibronectin and vimentin, partly through reduced Smad2, Akt and Fak phosphorylation as well as U-87 MG cell invasion and migration...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774118/proteomic-profiling-of-skeletal-and-cardiac-muscle-in-cancer-cachexia-alterations-in-sarcomeric-and-mitochondrial-protein-expression
#18
Angie M Y Shum, Anne Poljak, Nicholas L Bentley, Nigel Turner, Timothy C Tan, Patsie Polly
Background: Cancer cachexia is observed in more than 50% of advanced cancer patients, and impairs quality of life and prognosis. A variety of pathways are likely to be dysregulated. Hence, a broad-spectrum understanding of the disease process is best achieved by a discovery based approach such as proteomics. Results: More than 300 proteins were identified with > 95% confidence in correct sequence identification, of which 5-10% were significantly differentially expressed in cachectic tissues ( p -value of 0...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774117/investigation-of-tumor-tumor-interactions-in-a-double-human-cervical-carcinoma-xenograft-model-in-nude-mice
#19
Barbara Mertens, Tatiane Cristina de Araujo Nogueira, Dimitrios Topalis, Ruzena Stranska, Robert Snoeck, Graciela Andrei
Tumor-tumor distant interactions within one organism are of major clinical relevance determining clinical outcome. To investigate this poorly understood phenomenon, a double human cervical xenograft model in nude mice was developed. A first tumor was induced subcutaneously by injection of human papillomavirus positive cervical carcinoma cells into the mouse lower right flank and 3 weeks later, animals were challenged with the same tumor cell line injected subcutaneously into the upper left flank. These tumors had no direct physical contact and we found no systemic changes induced by the primary tumor affecting the growth of a secondary tumor...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774116/human-papilloma-virus-global-research-architecture-assessed-by-density-equalizing-mapping
#20
Dörthe Brüggmann, Luise Kayser, Jenny Jaque, Matthias Bundschuh, Doris Klingelhöfer, David A Groneberg
Human papilloma virus (HPV) infection is linked to cervical cancer, which represents the world's fourth most common cancer in women. So far, no detailed map of the worldwide HPV research architecture has been constructed. Hence, this study focuses on the chronological development and geographical distribution of the global HPV-specific publications and evaluates citation-based parameters as well as socioeconomic features of the publishing countries. In total, 29,330 HPV-related publications were identified...
April 24, 2018: Oncotarget
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