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https://www.readbyqxmd.com/read/27885740/asp5878-a-selective-fgfr-inhibitor-to-treat-fgfr3-dependent-urothelial-cancer-with-or-without-chemoresistance
#1
Aya Kikuchi, Tomoyuki Suzuki, Taisuke Nakazawa, Masateru Iizuka, Ayako Nakayama, Tohru Ozawa, Minoru Kameda, Nobuaki Shindoh, Tadashi Terasaka, Masaaki Hirano, Sadao Kuromitsu
FGF/FGFR gene aberrations such as amplification, mutation and fusion are associated with many types of human cancers including urothelial cancer. FGFR kinase inhibitors are expected to be a targeted therapy for urothelial cancer harboring FGFR3 gene alternations. ASP5878, a selective inhibitor of FGFR1, 2, 3 and 4 under clinical investigation, selectively inhibited cell proliferation of urothelial cancer cell lines harboring FGFR3 point mutation or fusion (UM-UC-14, RT-112, RT4 and SW 780) among 23 urothelial cancer cell lines...
November 25, 2016: Cancer Science
https://www.readbyqxmd.com/read/27873085/quantitative-analysis-of-supporting-cell-subtype-labeling-among-creer-lines-in-the-neonatal-mouse-cochlea
#2
Melissa M McGovern, Joseph Brancheck, Auston C Grant, Kaley A Graves, Brandon C Cox
Four CreER lines that are commonly used in the auditory field to label cochlear supporting cells (SCs) are expressed in multiple SC subtypes, with some lines also showing reporter expression in hair cells (HCs). We hypothesized that altering the tamoxifen dose would modify CreER expression and target subsets of SCs. We also used two different reporter lines, ROSA26 (tdTomato) and CAG-eGFP, to achieve the same goal. Our results confirm previous reports that Sox2 (CreERT2) and Fgfr3-iCreER (T2) are not only expressed in neonatal SCs but also in HCs...
November 21, 2016: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/27870574/evaluation-of-bgj398-a-fibroblast-growth-factor-receptor-1-3-kinase-inhibitor-in-patients-with-advanced-solid-tumors-harboring-genetic-alterations-in-fibroblast-growth-factor-receptors-results-of-a-global-phase-i-dose-escalation-and-dose-expansion-study
#3
Lucia Nogova, Lecia V Sequist, Jose Manuel Perez Garcia, Fabrice Andre, Jean-Pierre Delord, Manuel Hidalgo, Jan H M Schellens, Philippe A Cassier, D Ross Camidge, Martin Schuler, Ulka Vaishampayan, Howard Burris, G Gary Tian, Mario Campone, Zev A Wainberg, Wan-Teck Lim, Patricia LoRusso, Geoffrey I Shapiro, Katie Parker, Xueying Chen, Somesh Choudhury, Francois Ringeisen, Diana Graus-Porta, Dale Porter, Randi Isaacs, Reinhard Buettner, Jürgen Wolf
Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27865593/identification-of-novel-therapeutic-targets-in-anaplastic-thyroid-carcinoma-using-functional-genomic-mrna-profiling-paving-the-way-for-new-avenues
#4
Pascal K C Jonker, Gooitzen M van Dam, Sjoukje F Oosting, Schelto Kruijff, Rudolf S N Fehrmann
BACKGROUND: Currently, anaplastic thyroid carcinoma has a very poor prognosis and there is an unmet need for new therapeutic options. Therefore, this study aims to identify upregulated genes in anaplastic thyroid carcinoma with known drug interactions that could serve as new therapeutic targets. METHODS: Publicly available microarray expression profiles of anaplastic thyroid carcinoma and normal thyroid tissue were collected. FGmRNA-profiling was applied, which is a recently developed method that enhances the ability to capture the downstream effects of genomic alterations on gene expression levels...
November 16, 2016: Surgery
https://www.readbyqxmd.com/read/27852048/igfbp2-expression-predicts-idh-mutant-glioma-patient-survival
#5
L Eric Huang, Adam L Cohen, Howard Colman, Randy L Jensen, Daniel W Fults, William T Couldwell
Mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes occur in ~80% of lower-grade (WHO grade II and grade III) gliomas. Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. Interestingly, IDH mutations are associated with improved survival in glioma patients, but the underlying mechanism for the difference in survival remains unclear. Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846280/development-and-application-of-a-microfluidics-based-panel-in-the-basal-luminal-transcriptional-characterization-of-archival-bladder-cancers
#6
Doris Kim, YounJeong Choi, James Ireland, Oded Foreman, Rachel N Tam, Rajesh Patel, Erica B Schleifman, Maipelo Motlhabi, Dorothy French, Cheryl V Wong, Eric Peters, Luciana Molinero, Rajiv Raja, Lukas C Amler, Garret M Hampton, Mark R Lackner, Omar Kabbarah
In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes...
2016: PloS One
https://www.readbyqxmd.com/read/27845189/genome-analyses-identify-the-genetic-modification-of-lung-cancer-subtypes
#7
REVIEW
Yong Zhang, Diane C Wang, Lin Shi, Bijun Zhu, Zhihui Min, Jianjun Jin
Lung cancer is a highly intricate and heterogeneous disease with genomic diversity in each subtype. Global analyses of gene expression and sequencing provided us new understanding of the genetic variation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), including adenocarcinoma (ADC), and squamous cell carcinoma (SCC). The genetic variations of lung cancer subtypes in genomic studies were integrated and further analyzed using bioinformatics methods. The lung cancer subtypes share some genetic variations such as the dysfunction of tumor suppressor gene TP53, and also harbor specific variations of their own such as MET in ADC, FGFR1 and FGFR3 in SCC and MYC in SCLC...
November 11, 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27844328/molecular-profiling-of-thymoma-and-thymic-carcinoma-genetic-differences-and-potential-novel-therapeutic-targets
#8
Franz Enkner, Bettina Pichlhöfer, Alexandru Teodor Zaharie, Milica Krunic, Tina Maria Holper, Stefan Janik, Bernhard Moser, Karin Schlangen, Barbara Neudert, Karin Walter, Brigitte Migschitz, Leonhard Müllauer
Thymoma and thymic carcinoma are thymic epithelial tumors (TETs). We performed a molecular profiling to investigate the pathogenesis of TETs and identify novel targets for therapy. We analyzed 37 thymomas (18 type A, 19 type B3) and 35 thymic carcinomas. The sequencing of 50 genes detected nonsynonymous mutations in 16 carcinomas affecting ALK, ATM, CDKN2A, ERBB4, FGFR3, KIT, NRAS and TP53. Only two B3 thymomas had a mutation in noncoding regions of the SMARCB1 and STK11 gene respectively. Three type A thymomas harbored a nonsynonymous HRAS mutation...
November 14, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27836589/a-novel-non-invasive-detection-method-for-the-fgfr3-gene-mutation-in-maternal-plasma-for-a-fetal-achondroplasia-diagnosis-based-on-signal-amplification-by-hemin-mofs-ptnps
#9
Jun Chen, Chao Yu, Yilin Zhao, Yazhen Niu, Lei Zhang, Yujie Yu, Jing Wu, Junlin He
The small amount of cell-free fetal DNA (cffDNA) can be a useful biomarker for early non-invasive prenatal diagnosis (NIPD) of achondroplasia. In this study, a novel non-invasive electrochemical DNA sensor for ultrasensitive detecting FGFR3 mutation gene, a pathogenic gene of achondroplasia, based on biocatalytic signal materials and the biotin-streptavidin system are presented. Notably encapsulation of hemin in metal-organic frameworks-based materials (hemin-MOFs) and platinum nanoparticles (PtNPs) were used to prepare hemin-MOFs/PtNPs composites via a one-beaker-one-step reduction...
November 1, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27835695/reference-genes-for-addressing-gene-expression-of-bladder-cancer-cell-models-under-hypoxia-a-step-towards-transcriptomic-studies
#10
Luís Lima, Cristiana Gaiteiro, Andreia Peixoto, Janine Soares, Manuel Neves, Lúcio Lara Santos, José Alexandre Ferreira
Highly aggressive, rapidly growing tumors contain significant areas of hypoxia or anoxia as a consequence of inadequate and/or irregular blood supply. During oxygen deprivation, tumor cells withstand a panoply of adaptive responses, including a shift towards anaerobic metabolism and the reprogramming of the transcriptome. One of the major mediators of the transcriptional hypoxic response is the hypoxia-inducible factor 1 (HIF-1), whose stabilization under hypoxia acts as an oncogenic stimulus contributing to chemotherapy resistance, invasion and metastasis...
2016: PloS One
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#11
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27829236/fgfr3-as-a-receptor-tyrosine-kinase-is-associated-with-differentiated-biological-functions-and-improved-survival-of-glioma-patients
#12
Zheng Wang, Chuanbao Zhang, Lihua Sun, Jingshan Liang, Xing Liu, Guanzhang Li, Kun Yao, Wei Zhang, Tao Jiang
BACKGROUND: Activation of receptor tyrosine kinases is common in Malignancies. FGFR3 fusion with TACC3 has been reported to have transforming effects in primary glioblastoma and display oncogenic activity in vitro and in vivo. We set out to investigate the role of FGFR3 in glioma through transcriptomic analysis. RESULTS: FGFR3 increased in Classical subtype and Neural subtype consistently in CGGA and TCGA cohort. Similar patterns of FGFR3 distribution through subtypes were observed in CGGA and TCGA samples...
November 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27829009/the-morphogenesis-of-cranial-sutures-in-zebrafish
#13
Jolanta M Topczewska, Ramy A Shoela, Joanna P Tomaszewski, Rupa B Mirmira, Arun K Gosain
Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone...
2016: PloS One
https://www.readbyqxmd.com/read/27820126/identification-of-high-risk-cryptic-crlf2-rearrangements-in-b-cell-acute-lymphoblastic-leukemia-utilizing-an-fgfr3-igh-dual-color-dual-fusion-dna-probe-set
#14
Adam J Robin, Jess F Peterson, John W Grignon, Gabriela Gheorghe, Michael J Burke, Peter vanTuinen
B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy with gene rearrangements involving the IGH locus occurring in ∼5% of cases. Fluorescence in situ hybridization (FISH) probes targeting the IGH locus are not included in the standard children's oncology group (COG) fluorescence in situ hybridization panel. At our institute, we incorporated the use of FGFR3/IGH dual-color dual-fusion DNA probes for confirmation of aneuploidy 4 and 14 in diagnostic B-ALL specimens. Subsequently we have identified 4 B-ALL cases with cryptic CRLF2-IGH translocations that would otherwise have gone undetected...
November 4, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27812884/alofanib-an-allosteric-fgfr2-inhibitor-has-potent-effects-on-ovarian-cancer-growth-in-preclinical-studies
#15
Alexandra Tyulyandina, Daniel Harrison, Wei Yin, Evgenia Stepanova, Dmitry Kochenkov, Eliso Solomko, Nina Peretolchina, Frits Daeyaert, Jean-Baptiste Joos, Koen Van Aken, Mikhail Byakhov, Evgenia Gavrilova, Sergei Tjulandin, Ilya Tsimafeyeu
Purpose Early data suggest that combining FGFR2 inhibitors with platinum-containing cytotoxic agents for the treatment of epithelial ovarian cancer may yield increased antitumor activity. We investigated antitumor activity of alofanib (RPT835), a novel allosteric FGFR2 inhibitor, in ovarian cancer in vitro and in vivo. Methods Equal amounts of ovarian cancer cell (SKOV3) lysates were analyzed for FGFR1-3 protein expression using Wes. To assess the efficacy of alofanib on FGF-mediated cell proliferation, SKOV3 cells were incubated and were treated with serially diluted alofanib...
November 3, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27812792/polymorphous-low-grade-neuroepithelial-tumor-of-the-young-plnty-an-epileptogenic-neoplasm-with-oligodendroglioma-like-components-aberrant-cd34-expression-and-genetic-alterations-involving-the-map-kinase-pathway
#16
Jason T Huse, Matija Snuderl, David T W Jones, Carole D Brathwaite, Nolan Altman, Ehud Lavi, Richard Saffery, Alexandra Sexton-Oates, Ingmar Blumcke, David Capper, Matthias A Karajannis, Ryma Benayed, Lukas Chavez, Cheddhi Thomas, Jonathan Serrano, Laetitia Borsu, Marc Ladanyi, Marc K Rosenblum
Epileptogenic tumors affecting children and young adults are a morphologically diverse collection of neuroepithelial neoplasms that, as a group, exhibit varying levels of glial and/or neuronal differentiation. Recent advances in molecular profiling technology, including comprehensive DNA sequencing and methylation analysis, have enabled the application of more precise and biologically relevant classification schemes to these tumors. In this report, we describe a morphologically and molecularly distinct epileptogenic neoplasm, the polymorphous low-grade neuroepithelial tumor of the young (PLNTY), which likely accounts for a sizable portion of oligodendroglioma-like tumors affecting the pediatric population...
November 3, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27786351/fibroblast-growth-factor-receptor-3-epidermal-naevus-syndrome-with-urothelial-mosaicism-for-the-activating-p-ser249cys-fgfr3-mutation
#17
Didier Bessis, Julie Plaisancié, Véronique Gaston, Eric Bieth
is missing (Short communication).
October 27, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27785367/fgfr1-2-and-3-protein-overexpression-and-molecular-aberrations-of-fgfr3-in-early-stage-non-small-cell-lung-cancer
#18
Willemijn Sme Theelen, Lorenza Mittempergher, Stefan M Willems, Astrid J Bosma, Dennis Dgc Peters, Vincent van der Noort, Eva J Japenga, Ton Peeters, Koos Koole, Tonći Šuštić, J L Blaauwgeers, Carel J van Noesel, René Bernards, Michel M van den Heuvel
This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3-TACC3 translocation and FGFR3 amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC)) were analysed with immunohistochemistry (IHC) for expression of FGFR1, 2 and 3. Expression levels of FGFR1, 2 and 3 were correlated with clinicopathological features...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27771611/identification-of-a-fgfr3-tacc3-fusion-in-esophageal-cancer
#19
T Mizukami, K Sakai, S Naruki, T Taniyama, Y Horie, N Izawa, T Tsuda, T Fujino, N Boku, H Yasuda, T Fukunaga, T Eguchi Nakajima, K Nishio
No abstract text is available yet for this article.
October 22, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27767902/maternal-administration-of-meclozine-for-the-treatment-of-foramen-magnum-stenosis-in-transgenic-mice-with-achondroplasia
#20
Masaki Matsushita, Kenichi Mishima, Ryusaku Esaki, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh
OBJECTIVE Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum stenosis (FMS) is one of the serious neurological complications in ACH. Through comprehensive drug screening, the authors identified that meclozine, an over-the-counter drug for motion sickness, inhibited activation of FGFR3 signaling. Oral administration of meclozine to the growing ACH mice promoted longitudinal bone growth, but it did not prevent FMS...
October 21, 2016: Journal of Neurosurgery. Pediatrics
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