tbuckley/cabot-search huggingface dataset:
P19.02 Clinical and radiological long term outcome of acoustic neuromas (Koos grade I - IV) after stereotactic radiosurgery
Authors: D. Rueß, L. Poehlmann, H. Treuer, M. Kocher, M. Ruge
Journal: Neuro-Oncology (2016)

AbstractIntroduction:In the management of acoustic neuroma (AN) stereotactic radiosurgery (SRS) has evolved as widely accepted treatment option for small-sized tumors (Koos I and II). For larger AN (Koos III and IV) microsurgery is treatment of choice. However, for patients not suitable for microsurgery SRS might also be an alternative that balances tumor control, hearing preservation and adverse effects. The purpose of this analysis was to evaluate the efficacy and toxicity of SRS for different Koos grades including AN Koos III and IV.Methods:In this single center retrospective analysis (1991 - 2015) we included all patients with previously untreated AN who underwent single session LINAC or Cyberknife® based SRS with a minimum follow-up of 3 months. Patient data were analyzed and correlated (Pearson`s coefficient) with the different Koos grades in terms of radiological tumor control, preservation of serviceable hearing, course of median pure tone averages (PTA) and adverse events rated by Common Terminology Criteria for Adverse Events (CTCAE; v4.03).Results:301 patients (f:m = 151:150, median age 59 years ±13.6, range 17–84) were identified with a mean follow-up of 50.9 months (range 3–265). Mean tumor volume was 1.85 ml ±2.4 (range 0.1–23.7, the mean marginal dose was 12.4 Gy ± 0.8 (range 11–20) and the prescription isodose was 69.3 % ± 12.5 (range 32.9–86.2). With regard to the Koos classification 52 patients were considered as grade I, 162 as grade II, 42 and 45 as grade III and IV, respectively.At last follow-up after SRS 94% of the patients showed radiological tumor control. There was no significant correlation (p < 0.113) between Koos grades I/II vs III/IV and radiological tumor control.Median PTA of Koos I/II tumors increased about 49% (37,2 dB prior to SRS up to 55,6 dB at last follow-up). In case of Koos III/IV tumors the increase of median PTA was similar (47%; 46,2 dB up to 68,2 dB).The rate of transient facial nerve dysfunction CTCAE grade 1 or 2 in Koos I/II tumors was 2.3% and 4.6% in Koos III/IV. Permanent facial nerve dysfunction CTCAE grade 1 was observed in one patient with Koos grade I and III, respectively. Transient trigeminal nerve impairment CTCAE grade 1/2 occurred with 3.7% in Koos I/II and with 6.9% in Koos III/IV. Four patients (4.6%) with Koos III/IV tumors had permanent trigeminal nerve impairment CTCAE grade 1/2.Conclusion:SRS for AN shows reliable long term tumor control and a high rate of hearing preservation and without considerable permanent side effects. Therefore, SRS can be proposed as safe and effective treatment option for AN, even with higher Koos grades.
What caused the spike in mortality in England and Wales in January 2015?
Authors: Lucinda Hiam, Danny Dorling, Dominic Harrison, Martin McKee
Journal: Journal of the Royal Society of Medicine (2017)

In the accompanying paper, we described the exceptionally large increase in mortality in England and Wales in 2015, showing how it was driven by deaths among older people, and pointed to a need to look at the functioning of the health and social care system. While that paper examined the overall increase in deaths in 2015, it also noted a very large spike in deaths in January. So far, consensus is lacking on its causes, with some suggesting influenza and cold weather, and others, the cuts to health and social care.1,2 In this essay, we examine the January spike in more detail.
Phase II Study of an AKT Inhibitor MK2206 in Patients with Relapsed or Refractory Lymphoma
Authors: Yasuhiro Oki, Michelle A. Fanale, Jorge E. Romaguera, Luis Fayad, Nathan Fowler, Amanda R. M. Copeland, Felipe Samaniego, Larry W. Kwak, Sattva S Neelapu, Michael Wang, Lei Feng, Anas Younes
Journal: Blood (2014)
Resistance Profiling of BCR-ABL Compound Mutations Linked to Tyrosine Kinase Inhibitor Therapy Failure in Chronic Myeloid Leukemia
Authors: Christopher A. Eide, Matthew S. Zabriskie, Lauren T. Adrian, Thoralf Lange, Michael W. Deininger, Brian J. Druker, Thomas O'Hare
Journal: Blood (2011)
Thrombin Generation Assay Is Not Able to Predict Hemostatic Efficacy of by-Passing Agents in Patients with Hemophilia and Inhibitors: Results From in Vivo Studies
Authors: Maria Elisa Mancuso, Elena Santagostino, Veena Chantarangkul, Marigrazia Clerici, Armando Tripodi
Journal: Blood (2012)
Imatinib at Weekly Dosage May Induce and Maintain Haematologic and Molecular Remission in Chronic Eosinophilic Leukemia Harbouring FIP1L1-PDGFRA Fusion Gene- An Extended Follow-up Study.
Authors: Grzegorz Helbig, Malgorzata Calbecka, Justyna Gajkowska, Andrzej Moskwa, Alina Urbanowicz, Alina Swiderska, Jacek Najda, Slawomira Krzemien
Journal: Blood (2008)
STMC-02. TUMOR RECURRENCE FROM CANCER STEM-LIKE CELLS POST-RADIATION IS REGULATED BY THE Shh-YAP-YB1-IGF2 AXIS IN MEDULLOBLASTOMA
Authors: Abhinav Dey, Anshu Malhotra
Journal: Neuro-Oncology (2016)

Sonic hedgehog (Shh)-mediated medulloblastoma growth requires IGF2 (Insulin-like Growth Factor 2) and we have shown that over-expression of Yes Associated Protein (YAP1) induces IGF2 expression as a part of YAP’s radiation resistance mechanism in mouse Shh-medulloblastoma cells and Shh-induced cerebellar granule neural precursors (CGNPs), proposed cells-of-origin for the SHH molecular subclass of medulloblastoma (1). The peri-vascular niche, a microenvironmental niche proposed to house so-called tumor re-populating cells that survive radiation and contribute to medulloblastoma recurrence, showed high levels of YAP and IGF2. The mechanism of IGF2 induction downstream of YAP is not understood. Using chromatin-IP and promoter binding-protein analyses, we have found that Y-box protein-1 (YB1) is a major regulator IGF2 expression downstream of YAP and Sonic Hedgehog signaling (2), and YB1 also localizes to the peri-vascular niche. To better comprehend how YAP, YB1, and IGF2 regulate peri-vascular niche cell survival, we have developed an ex vivo approach using organotypic brain tumor slice cultures. We observed that the stem-like population of perivascular niche increases markedly following exposure to radiation, and that targeting any component of the YAP1-YB1-IGF2 axis increases the level of cell death within the tumor microenvironment and reduces expansion of stem-like cell population. Our findings strongly suggest that therapeutic targeting of this pathway could be employed in combination with tumor resection and chemotherapy, to cut-down the use of cranio-spinal radiation of medulloblastoma patients, which causes life-long side effects that drastically impair quality of life. We are optimizing in vivo mouse models to further understand radiation resistance and identify additional functions for YB1 and YAP in tumor repopulating stem-like cells. REFERENCE: 1. Fernandez et al. Oncogenic YAP promotes radioresistance and genomic instability in medulloblastoma through IGF2-mediated Akt activation. Oncogene. (2012). 2. Dey et al. YB-1 is elevated in medulloblastoma and drives proliferation in Sonic hedgehog-dependent cerebellar granule neuron progenitor cells and medulloblastoma cells. Oncogene 01/2016; DOI:10.1038/onc.2015.491.
Breast-GPA and type of treatment predictors of survival in brain metastasis patients
Authors: J.L. Linares, A. Stradella, S. Pernas, A. Ortega, M. Galdeano, A. Lucas, M. Macia, N. Vidal, I. Morilla, R. Sabela, C. Falo, R. Velasco, M. Gil-Gil
Journal: Annals of Oncology (2016)
Clinical outcome of docetaxel plus cisplatin and fluorouracil (DCF) therapy for metastatic esophageal cancer
Authors: Yasuyoshi Sato, Masato Nishida, Koichi Yagi, Susumu Aikou, Yoshiharu Takenaka, Hiroharu Yamashita, Sachiyo Nomura, Yasuyuki Seto
Journal: Annals of Oncology (2016)
Proteomics profiling predicts poor prognosis in patients with muscle invasive urothelial carcinoma
Authors: G. De Velasco, A. Gámez-Pozo, M. Urbanowicz, G. Ruiz-Ares, J.M. Sepulveda, R. Manneh, B. Homet, L. Trilla-Fuertes, I. Otero, P. Celiz, F. Villacampa, L. Paz-Ares, J. Fresno Vara, D. Castellano
Journal: Annals of Oncology (2016)
The link between obesity and advanced breast cancer is a matter of much interest
Authors: L. Bastianelli, M. De Lisa, M. Pistelli, Z. Ballatore, M. Santoni, L. Cantini, A. Pagliacci, N. Battelli, E. Maccaroni, R. Bracci, A. Santinelli, H. Tahani, R. Berardi
Journal: Annals of Oncology (2016)
Treament options in advanced castration-resistant, prostate cancer (acrpc). preliminary results of a network meta-analysis
Authors: E. Bianchi, C. Cherubini, S.L.V. Nicoletti, M. Fantini, F. Drudi, V. Arcangeli, C. Santelmo, F. Montanari, A. Venturi, S.L.V. Nicoletti, L. Stocchi, D. Tassinari
Journal: Annals of Oncology (2016)
tk;4Is There an Impact of HLA Mismatch Direction on Outcomes After Umbilical Cord Blood Transplantantion?
Authors: Renato Cunha, Pascale Loiseau, Guillermo F Sanz, Gerard Michel, Anna Paola Iori, Gérard Socié, William Arcese, Annalisa Ruggeri, Karim Boudjedir, Eliane Gluckman, Vanderson Rocha
Journal: Blood (2011)
Serum IL-10 and IL-8 Among Variable Cytokines Derived From Helper T Cells Might Be Associated with Prognoses for Malignant Lymphoma Patients
Authors: Junichi Kitagawa, Hisashi Tsurumi, Naoe Goto, Katsuyoshi Takata, Nobuhiko Nakamura, Nobuhiro Kanemura, Takeshi Hara, Senji Kasahara, Takeshi Takahashi, Tadashi Yoshino, Hisataka Moriwaki
Journal: Blood (2012)
Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the phase 3b CONSIGN trial who had progression-free survival (PFS) &gt;4 months (m)
Authors: R. Garcia-Carbonero, E. Van Cutsem, F. Ciardiello, M. Ychou, J.-F. Seitz, R.D. Hofheinz, Y. Arriaga, U. Verma, A. Grothey, A. Miriyala, J. Kalmus, C. Kappeler, A. Falcone, A. Zaniboni
Journal: Annals of Oncology (2016)
Bortezomib-Based Triplets Are Associated with a High Probability of Dialysis Independence and Rapid Renal Recovery in Newly Diagnosed Myeloma Patients with Severe Renal Failure or Those Requiring Dialysis
Authors: Meletios A. Dimopoulos, Efstathios Kastritis, Maria Roussou, Erasmia Psimenou, Maria Gavriatopoulou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Dimitrios Ziogas, Ioannis Panagiotidis, Despoina Fotiou, Eftychia Kafantari, Stavroula Giannouli, Sofoklis Kontogiannis, Evangelos Terpos
Journal: Blood (2015)
Secondary efficacy results from a phase 3 study comparing efficacy and safety of biosimilar candidate ABP 215 with bevacizumab in patients with non-squamous non-small cell lung cancer (NSCLC)
Authors: N. Thatcher, M. Thomas, G. Ostoros, J. Pan, J. Goldschmidt, V. Hanes
Journal: Annals of Oncology (2016)
Therapeutic targeting of the pathological triad of extrasynaptic NMDA receptor signaling in neurodegenerations
Authors: Hilmar Bading
Journal: The Journal of Experimental Medicine (2017)

Activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors causes neurodegeneration and cell death. The disease mechanism involves a pathological triad consisting of mitochondrial dysfunction, loss of integrity of neuronal structures and connectivity, and disruption of excitation–transcription coupling caused by CREB (cyclic adenosine monophosphate–responsive element-binding protein) shut-off and nuclear accumulation of class IIa histone deacetylases. Interdependency within the triad fuels an accelerating disease progression that culminates in failure of mitochondrial energy production and cell loss. Both acute and slowly progressive neurodegenerative conditions, including stroke, Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, share increased death signaling by extrasynaptic NMDA receptors caused by elevated extracellular glutamate concentrations or relocalization of NMDA receptors to extrasynaptic sites. Six areas of therapeutic objectives are defined, based on which a broadly applicable combination therapy is proposed to combat the pathological triad of extrasynaptic NMDA receptor signaling that is common to many neurodegenerative diseases.
Survival and Neurodevelopmental Outcomes among Periviable Infants
Authors: Noelle Younge, Ricki F. Goldstein, Carla M. Bann, Susan R. Hintz, Ravi M. Patel, P. Brian Smith, Edward F. Bell, Matthew A. Rysavy, Andrea F. Duncan, Betty R. Vohr, Abhik Das, Ronald N. Goldberg, Rosemary D. Higgins, C. Michael Cotten
Journal: New England Journal of Medicine (2017)

Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among these infants relate to early childhood neurodevelopmental outcomes. We compared survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as assessed at 18 to 22 months of corrected age, across three consecutive birth-year epochs (2000-2003 [epoch 1], 2004-2007 [epoch 2], and 2008-2011 [epoch 3]). The infants were born at 11 centers that participated in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome measure was a three-level outcome - survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, or death. After accounting for differences in infant characteristics, including birth center, we used multinomial generalized logit models to compare the relative risk of survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, and death. Data on the primary outcome were available for 4274 of 4458 infants (96%) born at the 11 centers. The percentage of infants who survived increased from 30% (424 of 1391 infants) in epoch 1 to 36% (487 of 1348 infants) in epoch 3 (P<0.001). The percentage of infants who survived without neurodevelopmental impairment increased from 16% (217 of 1391) in epoch 1 to 20% (276 of 1348) in epoch 3 (P=0.001), whereas the percentage of infants who survived with neurodevelopmental impairment did not change significantly (15% [207 of 1391] in epoch 1 and 16% [211 of 1348] in epoch 3, P=0.29). After adjustment for changes in the baseline characteristics of the infants over time, both the rate of survival with neurodevelopmental impairment (as compared with death) and the rate of survival without neurodevelopmental impairment (as compared with death) increased over time (adjusted relative risks, 1.27 [95% confidence interval {CI}, 1.01 to 1.59] and 1.59 [95% CI, 1.28 to 1.99], respectively). The rate of survival without neurodevelopmental impairment increased between 2000 and 2011 in this large cohort of periviable infants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT00063063 and NCT00009633 .).
Treatment of Severe Acute Graft-Versus-Host Disease with Mesenchymal Stromal Cells.
Authors: Igor B Resnick, Polina Stepensky, Michael Y. Shapira, Claudine Barkatz, Gregory Elkin, Olga Gurevich, Avichai Shimoni, Nira Varda-Bloom, Moshe Yeshurun, Amos Toren, Tsila Zukerman, Michael Weintraub, Arnon Nagler, Reuven Or
Journal: Blood (2009)
A multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer (mCRC)
Authors: A. Antonio, M.C. Piccirillo, G. Nasti, G. Rosati, C. Chiara, C. Romano, D. Bilancia, A. De Stefano, A. Ottaiano, A. Cassata, F. Bianco, P. Delrio, F. Izzo, E. Di Gennaro, C. Caracò, R.V. Iaffaioli, S. Lastoria, C. Gallo, A. Budillon, F. Perrone
Journal: Annals of Oncology (2016)
HBVcircle: A novel tool to investigate hepatitis B virus covalently closed circular DNA
Authors: Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A.T. Young, Lu Gao
Journal: Journal of Hepatology (2017)
HER2 V659 and G660 transmembrane mutations that stabilize homo- and hetero-dimerization are rare oncogenic drivers in lung adenocarcinoma that are clinically responsive to afatinib
Authors: S.-H.I. Ou, A.B. Schrock, E.V. Bocharov, S.J. Klempner, C.K. Haddad, G. Steinecker, M. Johnson, B. Gitlitz, J. Chung, P. Campregher, J.S. Ross, P.J. Stephens, V.A. Miller, J. Suh, S.M. Ali, V. Velcheti
Journal: Annals of Oncology (2016)
EXTH-49. INTRAVENOUS INJECTION OF ONCOLYTIC PICORNAVIRUS SVV-001 PROLONGS ANIMAL SURVIVAL IN A NOVELPANEL OF PATIENT-DERIVED ORTHOTOPIC XENOGRAFT MOUSE MODELS OF ADULT GLIOBLASTOMA
Authors: Huiyuan Zhang, Yuchen Du, Lin Qi, Frank Braun, Mari Kogiso, Holly Lindsay, Sibo Zhao, Akash Patel, Nabil Ahmed, Sarah Injac, Patricia Baxter, Jack Su, Xiao-Nan Li
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is the most malignant and aggressive brain tumor. GBM is only minimally responsive to aggressive standard therapies. Seneca Valley virus (SVV-001) is a non-pathogenic oncolytic virus that can pass through the blood–brain barrier. In this study, we developed a new panel of patient derived orthotopic xenograft (PDOX) models to examine the efficacy of SVV-001 combined with irradiation. We also explored the mechanism of tumor cell infection with SVV-001 in malignant gliomas. Surgical GBM tumor samples were obtained from 17 patients and directly implanted into the right cerebrum of NOD/SCID mice (1x105 cells suspended in 2 uL growth medium). In vitro antitumor activities of SVV-001 were examined in primary cultures, pre-formed neurospheres, and monolayer cells derived from PDOX models. In vivo therapeutic efficacy was examined by single I.V. injection of SVV-001 alone or administered in combination with radiation treatment of pre-formed xenograft tumors in permissive models. 8 out from 17 samples had confirmed tumor formation in mouse brains; 4 of these samples have since been serially sub-transplanted for a total of 5 generations, while 7 intracerebral xenografts are in generation 2. These xenograft models precisely replicated histopathologic characteristics of their parental human tumors. SVV-001 at a multiplicity of infection of 0.5 to 25 replicated in and effectively killed primary cultures, pre-formed neurospheres, and monolayer glioma cells derived from adult glioma xenograft models in vitro. A single I.V. injection of SVV-001 (1 × 1011 viral particles/kg) administered immediately after radiation or 1 week after radiation led to the infection of orthotopic xenografts without harming normal mouse brain cells and resulted in significantly prolonged survival in permissive models. Our results demonstrated that SVV-001 possesses potent anti-tumor activity against adult malignant high-grade gliomas. This study provides a pre-clinical rationale that supports the consideration of SVV-001 for clinical trials against adult gliomas.
BRCA mutations and IGF-R1 expression in modulating sensitivity to trastuzumab in HER2-positive breast cancer
Authors: M. Pistelli, A. Santinelli, M. Santoni, F. Piva, F. Bianchi, L. Belvederesi, T. Biscotti, M. De Lisa, Z. Ballatore, G. Occhipinti, A. Pagliacci, E. Maccaroni, R. Bracci, N. Battelli, L. Cantini, L. Bastianelli, R. Berardi, S. Cascinu
Journal: Annals of Oncology (2016)
Two-Year Follow-up of a Randomized Clinical Trial of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care for Chronic Low Back Pain
Authors: Daniel C. Cherkin, Melissa L. Anderson, Karen J. Sherman, Benjamin H. Balderson, Andrea J. Cook, Kelly E. Hansen, Judith A. Turner
Journal: JAMA (2017)

This study describes the 2-year outcomes for participants of a randomized trial of mindfulness-based stress reduction vs cognitive behavioral therapy or usual care for adult participants with chronic low back pain.
The Stress-Induced PAI-1 Expression Is Enhanced in Obese Mice: A Possible Mechanism of Stress-Associated Thrombosis in Obese Subjects.
Authors: Koji Yamamoto, Tetsuhito Kojima, Tatsuya Adachi, Mutsuharu Hayashi, Tadashi Matsushita, Junki Takamatsu, David J. Loskutoff, Hidehiko Saito
Journal: Blood (2004)
PISARRO: A EUTROC phase 1b study of APR-246 with carboplatin (C) and pegylated liposomal doxorubicin (PLD) in relapsed platinum-sensitive high grade serous ovarian cancer (HGSOC)
Authors: B. Basu, C. Gourley, H. Gabra, I.B. Vergote, J.D. Brenton, L. Abrahmsen, A. Smith, M. Von Euler, J.A. Green
Journal: Annals of Oncology (2016)
PDTB-24. TARGETED THERAPY FOR LEPTOMENINGEAL METASTASIS OF MEDULLOBLASTOMA
Authors: Katie Grausam, Samuel Dooyema, Erliang Zeng, Haotian Zhao
Journal: Neuro-Oncology (2016)

Medulloblastoma (MB) is the most common malignant pediatric brain tumor that arises from the cerebellum. MB can disseminate through the cerebrospinal fluid to the leptomeninges covering the brain and spinal cord. Leptomeningeal metastasis, a frequent finding at diagnosis and recurrence, is associated with poor prognosis. Transcription factor Atonal Homolog 1 (ATOH1) plays a crucial role in cerebellum morphogenesis and the development of MB driven by aberrant Sonic Hedgehog/Patched (SHH/PTCH) signaling. Dysregulated ATOH1 expression is also associated with primary and recurrent SHH MBs. We generated several transgenic mouse lines with conditional Atoh1 expression, which were subsequently bred to Ptch1+/- mice that exhibit increased SHH signaling. Approximately 30% of Ptch1+/- mice develop MBs; however, Ptch1+/- animals with Atoh1 transgene expression all develop highly penetrant MBs with extensive leptomeningeal metastasis, a pattern identical to a xenograft model of human SHH MB. Non-invasive detection methods using bioluminescence assays and magnetic resonance imaging revealed primary tumors and metastatic tumors in the spinal cord of these animals. Comparative lineage studies also indicate metastatic tumor arises from primary tumor in the cerebellum. Similar to human MBs which maintain the SHH signature during metastasis and recurrence, metastatic tumors retain abnormal SHH signaling and Atoh1 expression. Gene expression profiling of metastatic tumors revealed significant enrichment for cytoskeletal and extracellular matrix networks, consistent with adaptation of metastatic tumor cells to an active migration and new microenvironment. Treatment with bone morphogenetic protein (BMP) or cyclopamine, a SHH antagonist, significantly suppressed the proliferation of tumor cells. Moreover, a 2-week treatment with vismodegib, a clinically approved SHH pathway inhibitor, is sufficient to almost completely wipe out metastatic MBs. Our studies reveal an important role for Atoh1 in MB metastasis. The efficacy of targeted therapy for metastatic MBs demonstrates the utility of this animal model for understanding mechanisms of metastasis and evaluating potential therapeutics.
Metaphase Cytogenetic Abnormalities (M-CA) and Interphase FISH for Deletion 13 (FISH 13) in Total Therapy 2 (TT 2): Follow up Observation among? 380 Patients with Newly Diagnosed Multiple Myeloma (MM).
Authors: John Shaughnessy, Frank Zhan, Bart Barlogie, Erik Rasmussen, Teresa Milner, Lisa Jackson, Athanasios Fassas, Maurizio Zangari, Choon-Kee Lee, Giampaolo Talamo, Raymond Thertulien, John Crowley, Guido Tricot
Journal: Blood (2004)