tbuckley/cabot-search huggingface dataset:
Aberrant Ras Activation Associated with Functional Loss of Tnk1/Kos1 In Human B-Cell Lymphoma
Authors: Kishalay Hoare, Sarasija Hoare, Bernadette Zamora, Tammy Flagg, Ann Dongtao Fu, Steve McClellan, Margaret A. Shipp, Mary Reinhard, W. Stratford May
Journal: Blood (2010)
Can Assessment of Patient Monoclonal Immunoglobulins By Heavy/Light Analysis be Used to Assign Patient Responses Analogous to IMWG Response Criteria?
Authors: Eileen Boyle, Guillemette Fouquet, Julie Lejeune, Salomon Manier, Lucile Musset, Claire Bories, Remy Dulery, Stéphanie Guidez, Sarah Bonnet, Brigitte Onraed, Jean-Luc Faucompre, Sabine Tricot, Stephanie Poulain, Veronique Leblond, Kym Snell, Xavier Leleu
Journal: Blood (2015)
NIMG-42. PENETRATION OF RADIOLABELED TEMOZOLOMIDE CORRELATES WITH CONTRAST ENHANCEMENT IN PATIENTS WITH RECURRENT GBM TREATED WITH BEVACIZUMAB
Authors: Yi-Fen Yen, Xiao Da, Ciprian Catana, Yangming Ou, Jacob Hooker, Jayashree Kalpathy-Cramer, Bruce Rosen, Tracy Batchelor, Elizabeth Gerstner
Journal: Neuro-Oncology (2016)

Anti-angiogenic agents can decrease vascular permeability raising concern that these agents may also decrease blood brain barrier (BBB) penetration of concomitantly administered chemotherapy. We evaluated if the volume of contrast enhancement in recurrent glioblastoma (GBM) patients correlated with the volume of temozolomide penetration using MR-PET. After labeling temozolomide with the positron emitter [11C], we performed MR-PET scans in patients receiving bevacizumab 10mg/kg Q2weeks and temozolomide 50mg/m2 daily. Patients were scanned prior to bevacizumab (but after achieving steady state for oral temozolomide to minimize nonspecific binding), 1 day post first bevazicumab infusion, and prior to the third bevacizumab infusion. Tumor regions of interest were outlined on the T1-post contrast and FLAIR images. Volume of temozolomide delivery within the FLAIR hyperintensity (greatest potential extent of visible tumor) was determined by selecting all voxels above a threshold by using 3D Slicer software on the SUV map. This SUV volume was correlated to the volume of contrast enhancement and also correlated to the volume of FLAIR hyperintensity using Pearson correlation coefficient (PCC). Each visit was considered a separate data point even if it was from the same patient. Eight patients have been accrued to the study. A total of 9 MR-PET visits have been analyzed. The preliminary analysis showed the volume of contrast enhancement correlated with volume of PET uptake (PCC = 0.74) and the volume of FLAIR hyperintensity also correlated with volume of PET update (PCC = 0.86). These indicate that smaller volumes of radiolabeled temozolomide uptake corresponded to smaller contrast enhancing volumes and smaller FLAIR hyperintensity volumes. Volume of penetration of radiolabeled temozolomide correlates with contrast enhancement in patients with recurrent GBM treated with bevacizumab. Contrast enhancement may be a surrogate marker for concomitant drug delivery even with drugs such as temozolomide which penetrate an intact BBB.
Bone Marrow Specific Scatter Pattern on Multiple Myeloma and the M:E Ratio and Cellularity Analysed by the CELL-DYN 4000® Methodology
Authors: Ana Teresa Simoes, Rogerio FC Barreira, Alexandra Alves Pereira, Sara Cardeira, Raquel Sanches, Carla Silva Costa, Ana Paula Gonsalves, Adilia Marques, Susana Santos, Ramon Salvado, Marta Duarte, Maria Leticia Ribeiro
Journal: Blood (2008)
Pharmacogenomic evaluation of single nucleotide polymorphisms associated with oxaliplatin-induced peripheral neuropathy: a preliminary study
Authors: F. Nichetti, G. Infante, R. Miceli, R. Berenato, M. Caporale, F. Morano, F.S. Falvella, M. Niger, I. Bossi, G. Fucà, A. Mennitto, M. Di Bartolomeo, F. Prof de Braud, F. Pietrantonio
Journal: Annals of Oncology (2016)
In Vitro Analyses of Umbilical Cord Blood (UCB) Derived Monocytes Support Adjunct Topical Application to Augment Platelet Rich Plasma (PRP) in Wound Healing.
Authors: Graham C. Chapman, Nicholas Greco, Richard Patrick Weitzel, Phil Paul, Peter Haviernik, Mathew L. Lesniewski, Aaron R. Victor, Gordon Preston, Mary J. Laughlin
Journal: Blood (2008)
EXTH-38. A TRIPLET BIOLUMINESCENCE IMAGING SYSTEM REAL-TIME REVEALS VIRAL INFECTION, REPLICATION AND TUMOR VIABILITY IN VIVO
Authors: Yuhui Zhang, E. Antonio Chiocca
Journal: Neuro-Oncology (2016)

Oncolytic HSV-1 (hereinafter referred to as oHSV1) is one of the promising bioagents for cancer virotherapy. However, variability exists in oHSV1 mediated cytotoxicity and replication towards panels of patient-derived and mouse glioblastoma multiforme (GBM) cells. We hypothesized that cell-specific differences may exist in oHSV1 infection/replication kinetics accounting for the observed variability. To study this, we have engineered a novel oHSV1 that expresses different luciferase cDNAs for bioluminescence imaging (BLI) in vitro and in vivo. This new oHSV1 (NG34-duLuc) expresses both firefly luciferase (Fluc) and Renilla luciferase (Rluc) genes under the viral late gene and immediate early gene promoters respectively, to monitor different phases of the viral replicative cycle. Cypridina luciferase (Cluc) gene is expressed under the PGK promoter of tumor cell to monitor tumor viability. The NG34-duLuc vector DNA was generated in E.coli with the fHsvQuik system (Gene Ther. 2006;13(8):705-14), based on the NG34 virus backbone (H Nakashima, EA Chiocca et al., in preparation). Gli36, U87 human glioma cells and CT2A, Gl261 mouse glioma cells were used in the project. Firstly, we successfully transfected Cluc gene into tumor cells and confirmed its expression. Then cells were infected by isolated viral clones that expressed both Rluc and Fluc luciferases. We further validated the bioluminescence of each luciferase in vitro. Viral infection, replication and brain tumor viability were assayed by Rluc, Fluc and Cluc imaging in mouse models in vivo. Magnetic Resonance Imaging of animals brains and immunofluorescence of brain were used to validate the in vivo fluorescence images. We were able to show that oncolytic virus expression of genes inversely correlated with tumor viability in vivo. This triplet bioluminescence imaging system can thus be used in glioblastoma mouse models in real-time to measure viral infection, replication and tumor viability in vivo.
Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone
Authors: Dana E. Rathkopf, Emmanuel S. Antonarakis, Neal D. Shore, Ronald F. Tutrone, Joshi J. Alumkal, Charles J. Ryan, Mansoor Saleh, Ralph J. Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla J. de Boer, Margaret K. Yu, Howard I. Scher
Journal: Clinical Cancer Research (2017)

Purpose: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC).Experimental Design: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day. Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and time on treatment.Results: Forty-six patients enrolled in the AAP-naïve (n = 25) and post-AAP (n = 21) cohorts. The 12-week PSA response rate was 88% (22/25) and 22% (4/18), median time to PSA progression was 18.2 months [95% confidence interval (CI), 8.3 months-not reached) and 3.7 months (95% CI, 2.8-5.6 months), and median time on treatment 21 months (range, 2.6-37.5) and 4.9 months (range, 1.3-23.2), for the AAP-naïve and post-AAP cohorts, respectively. Eighty percent (95% CI, 59-93) and 64% (95% CI, 43-82) of AAP-naïve and 43% (95% CI, 22-66) and 10% (95% CI, 1-30) of post-AAP patients remained on treatment for 6+ and 12+ months, respectively. Common treatment-emergent adverse events in both cohorts were grade 1 or 2 fatigue, diarrhea, nausea, and abdominal pain.Conclusions: Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC, with 80% of AAP-naïve and 43% of post-AAP patients, remaining on treatment for 6 months or longer. Clin Cancer Res; 23(14); 3544-51. ©2017 AACR.
Expansion of Inhibitory NK Receptor (CD94/NKG2A)-Expressing Cytolytic CD8 T Cells and CD4+CD25+ Regulatory T Cells from the Same Cord Blood.
Authors: Junji Tanaka, Junichi Sugita, Naoko Kato, Tomomi Toubai, Jun Ibata, Yusuke Shono, Shuichi Ota, Masahiro Asaka, Masahiro Imamura
Journal: Blood (2006)
MPTH-57. GENOTYPING OF GLIOMA INCLUDING 1p19q CODELETION BY TARGETED SEQUENCING
Authors: Hiroshi Nishihara, Shigeki Tanishima, Sayaka Yuzawa, Lei Wang, Shigeru Yamaguchi, Hiroyuki Kobayashi, Shunsuke Terasaka, Shinya Tanaka
Journal: Neuro-Oncology (2016)

Gliomas are the most common primary brain tumors, accounting for about 25% of all intracranial tumors. To date, detailed genotyping for glioma detecting the mutation in IDH1/2, ATRX, p53, TERT promoter region in addition to 1p19q codeletion is mandatory for final diagnosis especially for selecting the treatment after surgery. Currently, the practical genotyping methods for glioma are still discordant i.e., Sanger sequence for each genes and FISH for codeletion, nevertheless of recent development of next generation sequencer. Here we established rapid and valuable targeted sequence pipeline for glioma genotyping for not only SNV detection but also 1p19q codeleiton. Surgically resected glioma samples were fixed with PAXgene Tissue System (QIAGEN) and embedded in paraffin (PFPE). Capture sequencing panel targeted 16 genes including ATRX,IDH1,IDH2, TP53,TERT were designed by SeqCap EZ target enrichment system (Roche). Genomic DNA was extracted from PFPE tissues and the libraries were sequenced by the MiSeq (Illumina). The raw read data obtained from amplicon sequencing were processed by originally designed, dedicated analysis pipeline by Genome Jack (Mitsubishi Space Software Inc.) We detected IDH1 R132H mutation in 3 out of 7 high grade gliomas. In addition, 1p19q codeletion was identified in these 3 cases by out sequence pipeline and also FISH. Moreover, we successfully detected LOH of PTEN and amplification of EGFR and MET. Here we established the rapid clinical sequence system for glioma by targeted sequencing using a desktop sequencer Miseq. Our workflow can be finished within 7 working days with reasonable cost, offering a practical laboratory developed test for glioma genotyping.
Microvesicle Mediated Genetic Phenotype Modulation.
Authors: Jason M Aliotta, Mandy Pereira, Mark Dooner, Gerri Dooner, Bharat Ramratnam, David Lee, Kevin Johnson, Douglas Hixson, Nicole DePaz, David Berz, Djuro Josic, Kate Brilliant, Peter J. Quesenberry
Journal: Blood (2009)
Clinical time courses, characteristics, and prognosis of the patients suspected with carcinoma of unknown primary
Authors: Yoshikazu Utsu, Ayako Nakamura, Shunichirou Inagaki, Hironori Arai, Hiromi Yuasa, Shinichi Masuda, Yasuhiro Matsuura, Nobuyuki Aotsuka, Hisashi Wakita
Journal: Annals of Oncology (2016)
Efficacy and Safety of Deferasirox in Chinese Patients with Non-Transfusion-Dependent Thalassemia: 1-Year Results from the Thetis Study
Authors: Yong-Rong Lai, Rong Rong Liu, M Domenica Cappellini, Yesim Aydinok, John B Porter, Zewen Zhu, Candace Wang, Xue Qi, Ali T Taher
Journal: Blood (2015)
A New Clinically-Based Subclassification Proposal in CMML with Significant Prognostic Implications to Overcome the MDS/MPN Categorizing Dilemma
Authors: Francesco Onida, Simona Iacobelli, Guillermo Garcia-Manero, Mrinal M Patnaik, Raphaël Itzykson, Terra L. Lasho, Aziz Nazha, Raajit K. Rampal, Matias Eugenio Sanchez, Elias J. Jabbour, Najla H Al Ali, Zachary Thompson, Simona Colla, Pierre Fenaux, Hagop M. Kantarjian, Sally Killick, Sekeres A Mikkael, Alan F. List, Rami S. Komrokji, Ayalew Tefferi, Eric Solary, Eric Padron
Journal: Blood (2016)
OSU-HDAC42, a Novel Histone Deacetylase Inhibitor, Induces Apoptosis in a Caspase-Dependent Manner and Induces p21WAF1/CIP1 and p16 Expression in Multiple Myeloma Cell Lines.
Authors: Valerie L. White, Shuhong Zhang, David Lucas, Ching-Shih Chen, Sherif S. Farag
Journal: Blood (2006)
Could we see a prescription opioid epidemic in the UK?
Authors: Michael H Basler
Journal: BMJ (2017)

The World Health Organization lists opioids and benzodiazepines as essential medicines.1 A recent UK report from the charity Drugwise has highlighted the misuse of these prescribed substances.2

But this problem is not new. Many historical remedies (mainly based on opium) have been used to calm nerves and treat tantrums as well as relieve pain.

The report says prescriptions for opioids increased 400% in the past decade and those for antidepressants by 500% since 1992.2 But the degree of our misuse problem is unclear because we lack adequate data, particularly about diagnoses.

Prescription rates cannot differentiate patients with musculoskeletal pain who rely on a mid-range analgesic to function at work from the “Hartlepool housewives” who the report says are using codeine just to “get through the day.” When …
Daratumumab Is Effective in the Treatment of Refractory Post-Transplant Autoimmune Hemolytic Anemia: A Pediatric Case Report
Authors: Vanessa P. Tolbert, Robert Goldsby, James Huang, Kristin Shimano, Alexis Melton, Jennifer Willert, Biljana N. Horn, Christopher C. Dvorak, Justin T. Wahlstrom
Journal: Blood (2016)
Tumor Site and Metastases as Predictors of Venous Thromboembolism Recurrence among Active Cancer Patients with Incident Deep Vein Thrombosis or Pulmonary Embolism: A Population-Based Cohort Study.
Authors: Cheng E. Chee, John A. Heit, Aneel A. Ashrani, Tanya M. Petterson, Sara A. Farmer, Kent R. Bailey, L. Joseph Melton
Journal: Blood (2006)
Tumor mutation load assessed by FoundationOne (FM1) is associated with improved efficacy of atezolizumab (atezo) in patients with advanced NSCLC
Authors: M. Kowanetz, W. Zou, D.S. Shames, C. Cummings, N. Rizvi, A.I. Spira, G.M. Frampton, V. Leveque, S. Flynn, S. Mocci, G. Shankar, R. Funke, M. Ballinger, D. Waterkamp, A. Sandler, G. Hampton, L. Amler, P.S. Hegde, M. Hellmann
Journal: Annals of Oncology (2016)
MPTH-12. TERT PROMOTER MUTATION IS A POOR PROGNOSTIC MARKER FOR GBMS AND INTERACTS WITH MGMT METHYLATION STATUS
Authors: Hideyuki Arita, Kai Yamasaki, Taishi Nakamura, Mitsuaki Shirahata, Keiichi Kobayashi, Kaoru Tamura, Junya Fukai, Yuzo Terakawa, Kanji Mori, Hideo Nakamura, Koji Yoshimoto, Yonehiro Kanemura, Akitake Mukasa, Motoo Nagane, Keisuke Ueki, Takashi Komori, Ryo Nishikawa, Yoshitaka Narita, Koichi Ichimura
Journal: Neuro-Oncology (2016)

The prognostic impact of TERT promoter mutation in glioblastomas (GBMs) has been controversial in literatures although TERT is considered as a positive marker for GBM in IDH-wt gliomas. We analyzed a homogeneous cohort consisting of 453 IDH-wt GBM cases treated with concurrent radiation and temozolomide in order to evaluate the impact of TERT on the outcome. TERT promoter mutation was present in 58% of all cases. Both TERT mutation and MGMT un-methylation were associated with poor prognosis in univariate analysis (Hazard ratio (HR) for overall survival (OS), 0.73 and 0.43, each; p<0.01, both). However, median OS did not differ according to the TERT status in the MGMT methylated groups (30.0 months for TERT mutated cases vs. 26.5 months for TERT wild cases, p>0.05). A multivariate Cox proportional hazard model incorporating clinical backgrounds showed a significant interaction between TERT and MGMT status on survival. When incorporating the interaction, the HR for OS against TERT-mut/MGMT methylated tumor was 0.27 for TERT-mut/ MGMT-unmethylated, 0.32 for TERT-wt/ MGMT methylated and 0.54 for TERT-wt/ MGMT-unmethylated cases. Our results indicate that TERT promoter mutation is a poor prognostic factor for GBMs and interacts with the MGMT methylation status. The TERT-mut/ MGMT-unmethylated type has the poorest prognosis, thus clinical trials targeting this subtype would be warranted.
Final results of NAPOLI-1: A phase 3 study of nal-IRI (MM-398) ± 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy
Authors: L.-T. Chen, A. Wang-Gillam, C.-P. Li, G. Bodoky, A. Dean, Y.-S. Shan, G.S. Jameson, T. Macarulla, K.-H. Lee, D. Cunningham, J.-F. Blanc, R. Hubner, C.-F. Chiu, G. Schwartsmann, F. Braiteh, B. Belanger, E. Bayever, F. de Jong, D.D. von Hoff, J.T. Siveke
Journal: Annals of Oncology (2016)
NCOG-02. PREDICTORS OF SEIZURE IN GLIOMA AT INITIAL TUMOR PRESENTATION
Authors: Sandra Johnston, Sara Ranjbar, Andrea Hawkins-Daarud, Robert Rostomily, Daniel Silbergeld, Maciej Mrugala, James Chandler, Priya Kumthekar, Bernard Bendok, Ross Mitchell, Kristin Swanson
Journal: Neuro-Oncology (2016)

Seizures are frequent presenting symptoms of gliomas, particularly low-grade gliomas. Predictive factors for seizure at presentation are not clearly understood, therefore complicating when to treat with antiepileptic agents (AED). We hypothesized that smaller, diffuse, and multifocal tumors would predict seizure at initial tumor presentation (SP). From our database we identified 187 patients with contrast enhancing gliomas (WHO grade II (n=35), III (n=35), and IV (n=135)) with known seizure status. Patients were divided into two groups: SP, (n=91) and no seizure at tumor presentation (n=96). Mathematical model of tumor kinetics was used to calculate an invasiveness ratio (D/r) of migration (D, mm2/yr) and proliferation (r, 1/yr). Including pathology grade, tumor size, D/r, tumor multifocality, and age, random forest (RF) in conjunction with cross validation methods was conducted on 133 patients with complete datasets (SP n=57) looking for predictive characteristics. In all grades, RF predicted SP with 75.9% accuracy where smaller, more diffuse tumors and younger age were the primary predictive features. In GBM, RF predicted SP with 77.75% accuracy where smaller, more diffuse tumors and fewer lobes (<3) with tumor were the primary features. SP had T1gd radial size significantly smaller (11.28 vs. 18.22, p<0.0005), tumors were more diffuse (p=0.07), were younger (46.78 vs. 51.45, p=0.03), had prolonged time to progression (TTP, 888.56 days vs. 584.56 days, p=0.156), and significantly greater overall survival (OS, 1479.23 vs. 982.96, p= 0.011). Low-grade gliomas had greatest occurrence of SP (grade II (68.6%), grade III (48.6%)) versus grade IV (36.3%). Extent of resection was similar between groups (p=0.73). SP can be accurately predicted by tumor size, tumor multifocality and age. SP were younger, had smaller and more diffuse tumors, longer TTP, and greater OS. Identifying predictive factors for seizure presentation may improve patient-specific AED use determination and overall prognostication.
Hypersegmented Neutrophil Percentage Using Automated Digital Cell Morphology: A Simple Laboratory Parameter to Monitor Hydroxyurea Therapy in Sickle Cell Disease Patients
Authors: Kleber Yotsumoto Fertrin, Elza Miyuki Kimura, Fernanda Madureira de Oliveira Araujo, Maria de Fatima Pereira Gilberti, Sara T.O. Saad, Fernando F Costa
Journal: Blood (2015)
Correlation of circulating tumor cells with myeloid-derived suppressive cells in the peripheral blood of patients with advanced small cell lung cancer
Authors: I. Messaritakis, A. Koutoulaki, D. Aggouraki, E.K. Vetsika, E. Politaki, S. Apostolaki, V. Georgoulias, A. Kotsakis
Journal: Annals of Oncology (2016)
A Markov Decision Analysis of Post-Remission Strategies in 2029 Patients with AML in First Remission (CR1): Should We Perform Allogeneic Hematopoietic Cell Transplantation in CR1?.
Authors: Saiko Kurosawa, Takuhiro Yamaguchi, Naoyuki Uchida, Shuichi Miyawaki, Heiwa Kanamori, Kensuke Usuki, Takuya Yamashita, Masato Watanabe, Kazuaki Yakushiji, Shingo Yano, Yuichiro Nawa, Jun Taguchi, Jin Takeuchi, Yuko Nakamura, Yasuhito Nannya, Yasushi Okoshi, Yoshinobu Kanda, Ikuo Miura, Yoichi Takaue, Takahiro Fukuda
Journal: Blood (2009)
A phase 1b study of abemaciclib, an inhibitor of CDK4 and CDK6, in combination with endocrine and HER2-targeted therapies for patients with metastatic breast cancer
Authors: M. Beeram, S.M. Tolaney, J.T. Beck, M.N. Dickler, A.K. Conlin, C. Dees, T.L. Helsten, P.R. Conkling, W.J. Edenfield, D.A. Richards, S.R.P. Kambhampati, T.M. Costigan, E. Chan, S. Pant, K. Kalinsky, H.A. Burris, C.H. Becerra, B.N. Rexer, S.L. Puhalla, M.P. Goetz
Journal: Annals of Oncology (2016)
Low dose CT scan screening versus empiric surveillance in asbestos exposed subjects: Update of ATOM 002 study
Authors: G. Fasola, A. Follador, F. Barbiero, V. Rosolen, O. Belvedere, F. Grossi, C. Rossetto, S. Rizzato, M. Giavarra, L. Gerratana, F. Barbone
Journal: Annals of Oncology (2016)
Transcriptional Mechanisms of Resistance to Anti–PD-1 Therapy
Authors: Maria L. Ascierto, Alvin Makohon-Moore, Evan J. Lipson, Janis M. Taube, Tracee L. McMiller, Alan E. Berger, Jinshui Fan, Genevieve J. Kaunitz, Tricia R. Cottrell, Zachary A. Kohutek, Alexander Favorov, Vladimir Makarov, Nadeem Riaz, Timothy A. Chan, Leslie Cope, Ralph H. Hruban, Drew M. Pardoll, Barry S. Taylor, David B. Solit, Christine A. Iacobuzio-Donahue, Suzanne L. Topalian
Journal: Clinical Cancer Research (2017)

To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response.
PDTB-22. THE ROLE OF THE CHROMOSOME 19 microRNA CLUSTER (C19MC) IN EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES (ETMR)
Authors: Myra Joy Chen, Rajiv Dixit, Patrick Sin-Chan, Annie Huang, Jennifer A. Chan
Journal: Neuro-Oncology (2016)

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive primitive neuroectodermal brain tumor that affects infants and children under the age of four. Histologically, the tumor is characterized by a growth pattern that includes sheets of primitive cells punctuated by zones of neuropil and multilayered rosettes that are reminiscent of embryonic neuroepithelium. Genetically, ETMR is characterized by a focal amplification of chromosome 19q13.42, encoding the chromosome 19 microRNA cluster (C19MC). Previous studies have suggested that overexpression of the microRNAs within this cluster, including miR-517a, miR-517c and miR-520g, can increase malignancy of cell lines derived from non-ETMR primitive neuroectodermal tumours. Here, we ask whether overexpression of selected miRNAs in the cluster is sufficient to alter the cell fate of normal embryonic neural stem cells in the developing cortex. Using in utero electroporation to overexpress selected C19MC microRNAs in embryonic ventricular zone progenitors during the neurogenic period, we found that transient overexpression of miR-520g or a construct containing miR-517,-519, and -520 resulted in focal lesions containing both stem-like cells and a collection of heterochronic differentiating neurons ectopically arrested in the intermediate zone. The ectopic cells showed increasing maturation with time. Similar overexpression at postnatal ages did not yield analogous lesions. Our results suggest that the embryonic neuroepithelial cells are the substrate for transformation in ETMR, and that miRNAs in the C19MC cluster can regulate the temporal identity of immature/embyonic neural progenitors. Additional studies are required to determine the effects of stable overexpression of C19MC miRNAs, and to discern the effects on cell fate upon C19MC miRNA overexpression.
Neoadjuvant therapy with FEC followed by weekly paclitaxel and concurrent trastuzumab in Her2 positive non operable breast cancer: a phase II study
Authors: A. Levaggi, F. Poggio, M. Lambertini, A. D'Alonzo, S. Giraudi, C. Bighin, E. Blondeaux, S. Pastorino, A. Abate, G. Iacono, M. Vaglica, B. Conte, P. Pronzato, L. Del Mastro
Journal: Annals of Oncology (2016)