tbuckley/cabot-search huggingface dataset:
IMMU-44. INHIBITING IMMUNOSUPPRESSIVE IDO1 IN ADULTS WITH MALIGNANT GLIOMA – A MOVING TARGET THAT CHANGES WITH TREATMENT, CELL OF ORIGIN, AND AGING
Authors: Erik Ladomersky, Lijie Zhai, Kristen Lauing, Jun Qian, April Bell, Sebastian Otto-Meyer, Corey Dussold, Rimas Lukas, Derek Wainwright
Journal: Neuro-Oncology (2019)

Abstract We previously demonstrated that glioblastoma (GBM) cell IDO1 increases intratumoral immunosuppressive regulatory T cells (Tregs; CD4+CD25+FoxP3+) and decreases overall survival (OS) in the syngeneic GL261 model. IDO1 is characterized as an enzyme that converts the amino acid, tryptophan, into kynurenine. With the finding that IDO1 expression by GBM cells promotes intratumoral Treg accumulation, it was surprising to find that this process was unaffected by the pharmacological treatment with an IDO1 enzyme inhibitor (IDO1i). This led us to question the optimal therapeutic strategy for leveraging an IDO1i against GBM. Utilizing simultaneous whole brain radiation (RT), anti-PD-1 mAb, and an IDO1i, we discovered a long-term survival advantage in ~40% of young WT mice engrafted with either GL261 or CT-2A (n=9–10/group; p&lt; 0.01). Unexpectedly, dual treatment with RT and anti-PD-1 achieved a similar long-term survival advantage in IDO1KO-, but not in WT mice with GBM (n=14/group; p&lt; 0.01), confirming that the therapeutic target of IDO1i was in non-GBM cells. Notably, the triple immunotherapeutic treatment was less effective in elderly mice analogous to the median age of a GBM patient diagnosis (n=20–22/group; p&lt; 0.01) and coincident with increased IDO1 expression in the elderly human brain (n=1,152; p&lt; 0.01). Our working hypothesis is: (i) advanced aging increases IDO1 levels in the brain; (ii) RT elicits the release of GBM cell neoantigens; (iii) IDO1+ lymph node (LN) DCs process/present GBM cell neoantigens to cognate CD8+ T cells; (iv) IDO1i treatment decreases the suppression of IDO1+ DC:CD8+ T cell priming; (v) anti-PD1 treatment enhances LN priming initialized by RT + IDO1i; (vi) brain-resident IDO1+ DCs accumulate during advanced aging and suppress the newly-generated brain-infiltrating CD8+ GBM-specific T cells independent of IDO1i. Our work highlights the immunosuppressive role of advanced aging and the need to better understand gero-neuro-immuno-oncology interactions for enhancing future immunotherapeutic efficacy in adults with GBM.
Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial
Authors: Christoph Male, Anthonie W A Lensing, Joseph S Palumbo, Riten Kumar, Ildar Nurmeev, Kerry Hege, Damien Bonnet, Philip Connor, Hélène L Hooimeijer, Marcela Torres, Anthony K C Chan, Gili Kenet, Susanne Holzhauer, Amparo Santamaría, Pascal Amedro, Elizabeth Chalmers, Paolo Simioni, Rukhmi V Bhat, Donald L Yee, Olga Lvova, Jan Beyer-Westendorf, Tina T Biss, Ida Martinelli, Paola Saracco, Marjolein Peters, Krisztián Kállay, Cynthia A Gauger, M Patricia Massicotte, Guy Young, Akos F Pap, Madhurima Majumder, William T Smith, Jürgen F Heubach, Scott D Berkowitz, Kirstin Thelen, Dagmar Kubitza, Mark Crowther, Martin H Prins, Paul Monagle, Angelo C. Molinari, Ulrike Nowak Göttl, Juan Chain, Jeremy Robertson, Katharina Thom, Werner Streif, Rudolf Schwarz, Klaus Schmitt, Gernot Grangl, An Van Damme, Philip Maes, Veerle Labarque, Antonio Petrilli, Sandra Loggeto, Estela Azeka, Leonardo Brandao, Doan Le, Christine Sabapathy, Paola Giordano, Runhui Wu, Jie Ding, Wenyan Huang, Jianhua Mao, Päivi Lähteenmäki, Pascal Amedro, Stephane Decramer, Toralf Bernig, Martin Chada, Godfrey Chan, Krisztian Kally, Beatrice Nolan, Shoshana Revel-Vilk, Hannah Tamary, Carina Levin, Daniela Tormene, Maria Abbattista, Andrea Artoni, Takanari Ikeyama, Ryo Inuzuka, Satoshi Yasukochi, Michelle Morales Soto, Karina A Solis Labastida, Monique H Suijker, Marike Bartels, Rienk Y Tamminga, C Heleen Van Ommen, D. Maroeska Te Loo, Rui Anjos, Lyudmila Zubarovskaya, Natalia Popova, Elena Samochatova, Margarita Belogurova, Pavel Svirin, Tatiana Shutova, Vladimir Lebedev, Olga Barbarash, Pei L Koh, Joyce C Mei, Ludmila Podracka, Ruben Berrueco, Maria F Fernandez, Tony Frisk, Sebastian Grunt, Johannes Rischewski, Manuela Albisetti-Pedroni, Ali Antmen, Huseyin Tokgoz, Zeynep Karakas, Elizabeth Chalmers, Jayashree Motwani, Michael Williams, John Grainger, Jeanette Payne, Mike Richards, Susan Baird, Neha Bhatnagar, Angela Aramburo, Shelley Crary, Tung Wynn, Shannon Carpenter, Kerry Hege, Sanjay Ahuja, Neil Goldenberg, Gary Woods, Kamar Godder, Ajovi Scott-Emuakpor, Gavin Roach, Leslie Raffini, Nirmish Shah, Sanjay Shah, Courtney Thornburg, Ayesha Zia, Roger Berkow
Journal: The Lancet Haematology (2019)
ACTR-30. UPDATED EFFICACY AND SAFETY OF DABRAFENIB PLUS TRAMETINIB IN PATIENTS WITH RECURRENT/REFRACTORY BRAF V600E–MUTATED HIGH-GRADE GLIOMA (HGG) AND LOW-GRADE GLIOMA (LGG)
Authors: Patrick Wen, Alexander Stein, Martin van den Bent, Jacques De Greve, Sascha Dietrich, Filip De Vos, Nikolas von Bubnoff, Myra van Linde, Albert Lai, Gerald Prager, Mario Campone, Angelica Fasolo, Jose Lopez-Martin, Tae Min Kim, Warren Mason, Ralf-Dieter Hofheinz, Jean-Yves Blay, Daniel Cho, Anas Gazzah, Carlos Gomez-Roca, Jeffrey Yachnin, Aislyn Boran, Paul Burgess, Ilan Palanichamy, Eduard Gasal, Vivek Subbiah
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND There is a lack of treatment options for HGG and LGG patients. BRAFV600E mutations are uncommon in glioma, with a poor long-term prognosis. Combined BRAF/MEK inhibition extends progression-free survival (PFS) and overall survival (OS) in BRAF V600E–mutated melanoma, non small-cell lung cancer, and anaplastic thyroid cancer. METHODS This phase 2, open-label trial (NCT02034110) evaluated dabrafenib (BRAF inhibitor, 150mg BID) plus trametinib (MEK inhibitor, 2mg QD) in patients with BRAF V600E mutations in 9 rare tumor types, including HGG and LGG. Eligible patients had histologically-confirmed recurrent or progressive glioma (LGG:WHO grade 1 or 2; HGG:WHO grade 3 or 4), with HGG patients required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation. Treatment continued until unacceptable toxicity, disease progression, or death. Primary endpoint was investigator-assessed objective response rate (ORR) using RANO criteria. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. RESULTS Interim analysis (IA) #14 (data cutoff: April 2, 2018) reported additional 3 months follow-up, with 49 patients enrolled (HGG, n=39; LGG, n=10) and 3 patients not evaluable for response. In HGG patients, ORR was 27% (10/37; 95%CI: 13.8%-44.1%), including CR (n=1), PR (n=9), and SD (n=11), with 16 patients currently ongoing treatment. In LGG patients, ORR was 56% (5/9; 95%CI: 26.8%-79.3%), including PR (n=5) and SD (n=4), with 6 patients currently ongoing treatment. OS, PFS, and DOR will be presented (IA#15). In HGG patients, adverse events (AEs) included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%); grade 3/4 AEs included neutropenia (8%) and fatigue (5%). In LGG patients, AEs included headache (70%), fatigue, pyrexia (60% each), nausea, and arthralgia (50% each); grade 3/4 AEs included fatigue (20%). CONCLUSIONS Dabrafenib plus trametinib demonstrated promising efficacy in patients with recurrent or refractory BRAF V600E‒mutated HGG or LGG, with manageable AEs and no new safety signals.
Prediction for the Risk of Gvhd after Allogeneic HSCT in Patients with ATL Treated By Mogamulizumab
Authors: Yuhei Kamada, Ayako Kuroki, Naosuke Arima, Maiko Hayashida, Daisuke Nakamura, Makoto Yoshimitsu, Kenji Ishitsuka
Journal: Blood (2019)
HIV‐1 integrase inhibitors: 2003–2004 update
Authors: Raveendra Dayam, Jinxia Deng, Nouri Neamati
Journal: Medicinal Research Reviews (2006)

The integration of viral cDNA into the host genome is an essential step in the HIV-1-life cycle and is mediated by the virally encoded enzyme, integrase (IN). Inhibition of this process provides an attractive strategy for antiviral drug design. The discovery of beta-diketo acid inhibitors played a major role in validating IN as a legitimate antiretroviral drug target. Over a decade of research, a plethora of IN inhibitors have been discovered and some showed antiviral activity consistent with their effect on IN. To date, at least two compounds have been tested in human but none are close to the FDA approval. In this review, we provide a comprehensive report of all small-molecule IN inhibitors discovered during the years 2003 and 2004. Compilation of such data will prove beneficial in developing QSAR, virtual screening, pharmacophore hypothesis generation, and validation.
Letter: Oestrogens as a cause of endometrial carcinoma.
Authors: R Corcoran, R Howard
Journal: BMJ (1976)

The authors have become convinced that estrogen therapy for postmenopausal disturbances is often beneficial but they are perturbed by reports of such therapy causing endometrial cancer. The use of progestational compounds with the estrogen medication in hormone replacement regimens is noted as approved by others. Nevertheless, cases of endometrial cancer following use of an estrogen-progestogen oral contraceptive have been reported. It is suggested that such patients may have "islands" of endometrium refractory to the progestogen component and reactive only to estrogen. In such foci, endometrial cancer may develop.
Improvement in Survival of Multiple Myeloma Patients: A Long-Term Institutional Experience
Authors: Jordan Nunnelee, Qiuhong Zhao, Don M. Benson, Ashley E. Rosko, Maria Chaudhry, Naresh Bumma, Abdullah Mohammad Khan, Srinivas Devarakonda, Yvonne A. Efebera, Nidhi Sharma
Journal: Blood (2019)
PATH-52. ANAPLASTIC PILOMYXOID ASTROCYTOMA HARBORING BRAF FUSION, PTEN AND TERT MUTATIONS
Authors: Trisha Kissoon, Sridharan Gururangan, Jesse Kresak, Lance Governale
Journal: Neuro-Oncology (2019)

Abstract Pilomyxoid astrocytomas (PMA) are focal neoplasms that are often cured with total resection. We present a case of a progressive PMA with histologic and molecular features suggestive of malignant transformation. A 13-year old boy presented with headaches, diplopia, and seizures. He had previously been followed for 7 years by serial imaging for a cystic/solid enhancing mass in the right temporal lobe without biopsy that had remained stable up to 6 months prior to his current illness. MRI of brain demonstrated significant progression of the solid component with extension into the subependymal portions of the lateral ventricles, leptomeningeal spread in brain and spine, and hydrocephalus. Patient underwent a partial resection of tumor and VP shunt placement. Pathology demonstrated a prominent myxoid matrix with angiocentric arrangement of monomorphous bipolar cells. PHH3 and Ki-67 stains confirmed multiple mitoses and elevated proliferation rate. Next Generation sequencing of tumor confirmed the presence of a KIAA1549-BRAF duplication/fusion, CDKN2A deletion, along with PTEN and TERT promoter mutations without BRAF V600E or ATRX mutations. The histology and molecular features was suggestive of a pilomyxoid astrocytoma (PMA) with anaplastic transformation. Patient is currently receiving carboplatin + vincristine plus a MEK inhibitor (TrametinibTM, Novartis Corporation, Cambridge, MA) for tumor control. We believe that the tumor was initiated by the oncogenic BRAF fusion and the dramatic progression and spread of disease after a long period of stability was probably related to recent acquisition of additional deleterious mutations that have been previously reported in anaplastic pilocytic astrocytoma.
Protective Immunity against Severe Malaria in Children Is Associated with a Limited Repertoire of Antibodies to Conserved PfEMP1 Variants
Authors: Sofonias K. Tessema, Rie Nakajima, Algis Jasinskas, Stephanie L. Monk, Lea Lekieffre, Enmoore Lin, Benson Kiniboro, Carla Proietti, Peter Siba, Philip L. Felgner, Denise L. Doolan, Ivo Mueller, Alyssa E. Barry
Journal: Cell Host & Microbe (2019)
Annals Story Slam - Dirty Half Dozen
Authors: Shital Gandhi
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 November 2019Annals Story Slam - Dirty Half DozenFREEShital Gandhi, MDShital Gandhi, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0033 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Dirty Half Dozen "Dirty Half Dozen," by Shital Gandhi, MD (Duration 6:09)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 November 2019Volume 171, Issue 9Page: SS1 ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Vital Considerations for Aspirin in Prevention of Preeclampsia, a Multifaceted Pregnancy Disorder
Authors: Hooman Mirzakhani, Thomas F. McElrath, Scott T. Weiss
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Aortic Stenosis and Cardiac Amyloidosis
Authors: Julien Ternacle, Laura Krapf, Dania Mohty, Julien Magne, Annabelle Nguyen, Arnault Galat, Romain Gallet, Emmanuel Teiger, Nancy Côté, Marie-Annick Clavel, François Tournoux, Philippe Pibarot, Thibaud Damy
Journal: Journal of the American College of Cardiology (2019)
Somatic Mutation Profile Analyzed By Next-Generation Sequencing in Relapsed/Refractory Follicular Lymphoma Treated with Idelalisib
Authors: Philippine Robert, Cédric Rossi, Romain Aucagne, Caroline Chapusot, Selim Ramla, Robin Noel, Reda Bouabdallah, Morgan Avenin, Luc Xerri, Elise Toussaint, Marie-Pierre Chenard, Luc Mathieu Fornecker, Adrien Chauchet, Isabelle Bedgedjian, Anne Quinquenel, Saviz Nasri, Aude Marchal, Alain Jacques Delmer, Juliette Bouteloup, Jean-Noel Bastie, Laurent Martin, Mary Callanan, Olivier Casasnovas
Journal: Blood (2019)
Combining Clinical Features with Genetic Factors Improves Survival Prediction for Adults with Acute Myeloid Leukemia: Validation of a New Score System in 3 Cohorts
Authors: Douglas R. A. Silveira, Lynn Quek, Anna Corby, Juan L Coelho-Silva, Diego A Pereira-Martins, Grant Vallance, Benjamin Brown, Luciana Nardinelli, Wellington F Silva, Elvira DRP Velloso, Fabiola Traina, Andy Peniket, Paresh Vyas, Eduardo M Rego, Israel Bendit, Vanderson Rocha
Journal: Blood (2019)
A Unique Crosstalk between Tumor Cells and Hematopoietic Stem Cells Reveals a Myeloid Differentiation Pattern Signature Contributing to Metastasis
Authors: Ksenia Magidey, Ksenya Kveler, Rachelly Normand, Tongwu Zhang, Michael Timaner, Ziv Raviv, Brian James, Roi Gazit, Ze'ev Ronai, Shai Shen-Orr, Yuval Shaked
Journal: Blood (2019)
Hair Cortisol Is a Potential Indicator of Adrenal Insufficiency in Individuals with Sickle Cell Disease
Authors: Brittany Hollister, Mihail Zilbermint, Caterina P. Minniti, Ashley Buscetta, Khadijah Abdallah, Shuo You, Steven Soldin, Jerrold Meyer, Constantine Stratakis, Vence L. Bonham
Journal: Blood (2019)
The Proportion of CD52/GPI Negative T Cells Early Following Alemtuzumab Conditioned Haematopoetic Stem Cell Transplantation Is an Independent Risk Factor for Acute GvHD
Authors: Francesca Kinsella, Charlotte F Inman, Duncan Murray, Wayne Croft, Jianmin Zuo, Hayden Pearce, Sara Barbieri, Jane Nunnick, Sandeep Nagra, Charles Craddock, Ram K Malladi, Paul Moss
Journal: Blood (2019)
An RNA-Based Next Generation Sequencing (NGS) Strategy Detects More Cancer Gene Mutations Than a DNA-Based Approach for the Prediction and Assessment of Resistance in CML
Authors: Susan Branford, Carol Wadham, Naranie Shanmuganathan, Daniel Thomson, NUR Hezrin Shahrin, Jinghua Feng, Verity A Saunders, Wendy T Parker, Rob King, Paul Wang, Hamish S Scott, Andreas Schreiber, Timothy P. Hughes
Journal: Blood (2019)
Allogeneic Stem Cell Transplantation from Unmanipulated Haploidentical Donors Versus Unrelated Cord Blood in Patients with T-Cell Non-Hodgkin Lymphoma : A Retrospective Study from the Societe Francophone De Greffe De Moelle Et De Therapie Cellulaire (SFGMC-TC)
Authors: Jérôme Cornillon, Elisabeth Daguenet, Didier Blaise, Stephanie Nguyen, Gerard Socie, Hélène Labussière, Mohamad Mohty, Ibrahim Yakoub-Agha, Ali Bazarbachi, Claude-Eric Bulabois, Marie Robin, Jacques-Olivier Bay
Journal: Blood (2019)
Plasma Biomarker Predicts Lethal Acute Graft Versus Host Disease and Non-Relapse Mortality in Japanese Patients
Authors: Masaaki Hotta, Satake Atsushi, Yukie Tsubokura, Yoshiko Azuma, Hideaki Yoshimura, Takahisa Nakanishi, Shinya Fujita, Tomoki Ito, Kazuyoshi Ishii, Shosaku Nomura
Journal: Blood (2019)
Variation in blood pressure and long-term risk of dementia: A population-based cohort study
Authors: Yuan Ma, Frank J. Wolters, Lori B. Chibnik, Silvan Licher, M. Arfan Ikram, Albert Hofman, M. Kamran Ikram
Journal: PLoS Medicine (2019)

Background Variation in blood pressure may relate to dementia risk via autonomic disturbance or hemodynamic mechanisms, but the long-term associations are unclear. We aimed to determine whether blood pressure variation over a period of years, considering both magnitude and direction, is associated with the risk of dementia. Methods and findings In a prospective cohort study ongoing since 1989 in the Netherlands, 5,273 dementia-free participants (58.1% women; mean [SD] age, 67.6 [8.0] years) were included. As of 2016, 1,059 dementia cases occurred during a median follow-up of 14.6 years. Absolute variation in systolic blood pressure (SBP) was assessed as the absolute difference in SBP divided by the mean over two sequential visits every 4.2 (median) years, with the first quantile set as the reference level. The direction was the rise or fall in SBP, with the third quantile set as the reference level. We estimated the risk of dementia in relation to SBP variation measured at different time windows (i.e., at least 0, 5, 10, and 15 years) prior to dementia diagnosis, with adjustments for age, sex, education, apolipoprotein E (APOE) genotype, vascular risk factors, and history of cardiovascular disease. We repeated the above analysis for variation in diastolic blood pressure (DBP). A large SBP variation was associated with an increased dementia risk, which became more pronounced with longer intervals between the assessment of SBP variation and the diagnosis of dementia. The hazard ratio (HR) associated with large variation (the highest quintile) increased from 1.08 (95% confidence interval [CI] 0.88–1.34, P = 0.337) for risk within 5 years of SBP variation measurement to 3.13 (95% CI 2.05–4.77; P < 0.001) for risk after at least 15 years since the measurement of SBP variation. The increased long-term risk was associated with both large rises (HR for the highest quintile, 3.31 [95% CI 2.11–5.18], P < 0.001) and large falls in SBP (HR for the lowest quintile, 2.20 [95% CI 1.33–3.63], P = 0.002), whereas the higher short-term risk was only associated with large falls in SBP (HR, 1.21 [95% CI 1.00–1.48], P = 0.017). Similar findings were observed for variation in DBP. Despite our assessment of major confounders, potential residual confounding is possible, and the findings on blood pressure variability over periods of years may not be generalizable to variability over periods of days and other shorter periods. Conclusions Results of this study showed that a large blood pressure variation over a period of years was associated with an increased long-term risk of dementia. The association between blood pressure variation and dementia appears most pronounced when this variation occurred long before the diagnosis. An elevated long-term risk of dementia was observed with both a large rise and fall in blood pressure.
Survival Patterns in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma: Treatment Trajectories and Responses after the First Relapse
Authors: Ahmad S Halwani, Hsu-Chih Chien, Deborah Kay Morreall, Vikas Patil, Kelli M Rasmussen, Catherine Li, Zachary R Burningham, Anthony S Masaquel, Mary Halloran, Elisha Delong-Sieg, Mathias Schulz, Jia Li, Brian C Sauer
Journal: Blood (2019)
EXTH-12. RADIATION ENHANCES MELANOMA RESPONSE TO IMMUNOTHERAPY AND SYNERGIZES WITH BENZODIAZEPINES TO PROMOTE ANTI-TUMOR ACTIVITY
Authors: Daniel Pomeranz Krummel, Tahseen Nasti, Benjamin Izar, Maxwell Xu, Lindsey Lowder, Robert Press, Milota Kaluzova, Laura Kallay, Manali Rupji, Andre Burnham, Guanguan Li, Taukir Ahmed, Havi Rosen, Erin Connolly, Havva Keskin, Midhun Ben Thomas, Walter Curran, Ragini Kudchadkar, Brent Weinberg, Jeffrey Olson, Matthew Schniederjan, Stewart Neil, Jing Su, David Lawson, James Cook, Andrew Jenkins, Jeanne Kowalski, Mohammad Khan, Soma Sengupta
Journal: Neuro-Oncology (2019)

Abstract Melanoma brain metastases (MBM) occur in ~50% of advanced melanoma patients. It is unclear if systemic therapies synergize with radiotherapy (RT) and what the impact of RT timing has on efficacy. We find that RT followed by ICI (immune checkpoint inhibitors) (RTàICI) improves MBM patient survival compared to other combination strategies, also shown here in a murine melanoma model. RNA-seq of MBM tumors in the RTàICI group exhibit overrepresentation of genes implicated in NFKB signaling. There is also expression of GABAA receptor subunits across both treatment groups. We show that melanoma cells express functional GABAA receptors and that benzodiazepines impair tumor growth. Combination of sub-lethal RT doses with benzodiazepine results in significant ipsilateral and out of field abscopal anti-tumor activity, which is associated with enhanced tumor infiltration with poly-functional CD8 T-cells. This study provides evidence that RT enhances MBM response to ICI and synergizes with benzodiazepines to promote anti-tumor activity.
B2M Gene Expression Reflects an Immunologically Active Tumor Microenvironment in DLBCL
Authors: Clare Gould, Colm Keane, Valentine Murigneux, Harald Oey, Jonathan Ellis, Simone Birch, Jay Gunawardana, Dipti Talaulikar, Mark S. Hertzberg, Kimberley Jones, Maher K. Gandhi
Journal: Blood (2019)
Fyn Specifically Regulates the Activity of Red Cell Glucose-6-Phosphate-Dehydrogenase
Authors: Alessandro Mattè, Francesca Lupo, Elena Tibaldi, Maria Luisa Di Paolo, Carpentieri Andrea, Pietro Pucci, Anna Maria Brunati, Luca Cesaro, Francesco Turrini, Saúl Gómez Manzo, Soo Young Choi, Jaime Marcial Quino, Dae Won Kim, Antonella Pantaleo, Xiuli An, Enrica Federti, Iana Iatcenko, Maria Domenica Cappellini, Gian Luca Forni, Lucia De Franceschi
Journal: Blood (2019)