tbuckley/cabot-search huggingface dataset:
The journey to CAR T cell therapy: the pediatric and young adult experience with relapsed or refractory B-ALL
Authors: George Hucks, Susan R. Rheingold
Journal: Blood Cancer Journal (2019)

Abstract Outcomes of pediatric and young adult patients diagnosed with acute lymphoblastic leukemia (ALL) have improved significantly in the past few decades. Treatment advances have provided 5-year survival rates ranging from 78 to 91% depending on the age at diagnosis. However, approximately 2–3% of patients will present with refractory disease that is unresponsive to chemotherapy, and 10–15% of patients will relapse. Outcomes post-relapse show significantly reduced 5-year survival rates that continue to decrease with each subsequent relapse. Despite our increased understanding of risk factors and disease predictors, treatment strategies for patients with relapsed or refractory (r/r) disease, including variations of chemotherapy and stem cell transplant, remain ineffective for many patients. To improve outcomes of patients with r/r disease, immunotherapies targeting specific B cell antigens are being developed. Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy recently approved by the US Food and Drug Administration for patients with refractory leukemia or those with second or later relapse. In this treatment strategy, a patient’s own T cells are transduced to express an anti-CD19 CAR that, when reintroduced into the patient, directs specific binding and killing of CD19+ B cells. In a phase 2, single-arm, multicenter, global study, tisagenlecleucel resulted in a remission rate of 81% in pediatric and adolescent patients with r/r B cell ALL. This review article summarizes four typical cases of pediatric and adolescent r/r B-cell ALL, focusing on the patient’s journey from initial diagnosis to treatment with CAR T cell therapy.
A Questionnaire Survey Study To Determine Association of Dental Hygiene Practices in Hereditary Angioedema Subjects with The Incidence of Post-Procedural Angioedema Attacks
Authors: Umesh Singh, Aleena Banerji, Paula J. Busse, Sandra C. Christiansen, Timothy J. Craig, Mark Davis-Lorton, Joshua S. Jacobs, H. Henry Li, William R. Lumry, Marc A. Riedl, Raffi Tachdjian, H. James Wedner, Bruce L. Zuraw, Jonathan A. Bernstein
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 16073: Long-Term Outcome of Medical Treatment for Chronic Functional Mitral Regurgitation Secondary to Left Ventricular Dysfunction
Authors: Ran Heo, Seung-Ah Lee, Sahmin Lee, Dae-Hee Kim, Kee-Joon Choi, Joo-Hee Zo, Jong-Min Song, Jae-Kwan Song, Duk-Hyun Kang
Journal: Circulation (2017)

Introduction: Severity of functional mitral regurgitation (MR) is associated with extent of left ventricular (LV) remodeling and dysfunction, but it is unclear whether medical treatment for LV dysf...
Anti–PD-L1 Treatment Results in Functional Remodeling of the Macrophage Compartment
Authors: Huizhong Xiong, Stephanie Mittman, Ryan Rodriguez, Marina Moskalenko, Patricia Pacheco-Sanchez, Yagai Yang, Dorothee Nickles, Rafael Cubas
Journal: Cancer Research (2019)

Checkpoint inhibitors like anti-PD1/PD-L1 have demonstrated significant therapeutic efficacy in a subset of patients partly through reinvigoration of CD8 T cells. However, their impact on myeloid cells remains largely unknown. Here, we report that anti-PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment toward a more proinflammatory phenotype. This phenotype was characterized by a decrease in Arginase-I (ARG1) expression and an increase in iNOS, MHCII, and CD40 expression. Whole-transcriptome profiling further confirmed extensive polarization of both tumor monocytes and macrophages from a suppressive to a proinflammatory, immunostimulatory phenotype. This polarization was driven mainly through IFNγ and was associated with enhanced T-cell activity. Transfer of monocytes into anti-PD-L1-treated tumor-bearing mice led to macrophage differentiation into a more proinflammatory phenotype, with an increase in CD8 T cells expressing granzyme-B and an increase in the CD8/Treg ratio compared with control-treated mice. Although in responsive tumor models, anti-PD-L1 treatment remodeled the macrophage compartment with beneficial effects on T cells, both macrophage reprogramming and depletion were needed to maximize anti-PD-L1 responses in a tumor immune contexture with high macrophage burden. Our results demonstrate that anti-PD-L1 treatment can favorably remodel the macrophage compartment in responsive tumor models toward a more proinflammatory phenotype, mainly through increased IFNγ levels. They also suggest that directly targeting these cells with reprogramming and depleting agents may further augment the breadth and depth of response to anti-PD-L1 treatment in less responsive or more macrophage-dense tumor microenvironments. SIGNIFICANCE: This work demonstrates that increased IFNγ signaling following anti-PD-L1 treatment can remodel the macrophage compartment to enhance T-cell responses.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/7/1493/F1.large.jpg.
Remarkable Response of Pulmonary Metastases Rather Than Remnant Thyroid in 131I Therapy of Follicular Thyroid Cancer
Authors: Tian Tian, Yu Chen, Yongzhao Xiang, Lina Liu, Bin Liu
Journal: Clinical Nuclear Medicine (2019)

A 66-year-old man with follicular thyroid cancer after total thyroidectomy was referred for I therapy. Thyroid function tests before I administration exhibited severe thyrotoxicosis although the patient did not take levothyroxine after thyroidectomy. A 185 MBq I whole-body scintigraphy and SPECT/CT revealed multiple iodine-avid pulmonary metastases with the largest tumor diameter of 1.4 cm and remnant thyroid. A diagnosis of thyrotoxicosis caused by hyperfunctioning pulmonary metastases was then made. The patient was administered 7.4 GBq of I. Six months after I therapy, a significant reduction of the pulmonary metastatic disease and thyroglobulin level was observed. However, the remnant thyroid was still visualized.
Artificial intelligence in cancer imaging: Clinical challenges and applications
Authors: Wenya Linda Bi, Ahmed Hosny, Matthew B. Schabath, Maryellen L. Giger, Nicolai J. Birkbak, Alireza Mehrtash, Tavis Allison, Omar Arnaout, Christopher Abbosh, Ian F. Dunn, Raymond H. Mak, Rulla M. Tamimi, Clare M. Tempany, Charles Swanton, Udo Hoffmann, Lawrence H. Schwartz, Robert J. Gillies, Raymond Y. Huang, Hugo J. W. L. Aerts
Journal: CA A Cancer Journal for Clinicians (2019)

Abstract Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.
Atypical Chronic Myeloid Leukemia Challenge in Russian Hematology Practice
Authors: Vasily Shuvaev, Karina Krutikova, Svetlana Menshakova, Natalya Kalinova, Irina Martynkevich, Lyubov Polushkina, Elena Belyakova, Yury Krivolapov, Sergei Voloshin
Journal: Blood (2018)
Incidence and trends of pancreatic cancer (PC) in Girona: A population-based study from the Girona Cancer Registry (1994-2015).
Authors: Adelaida Garcia-Velasco, Carmen Carmona, Antonia Bianca, Helena Teixidor, Marc Valero, Raquel Liñan, Walter Carbajal, Montserrat Puigdemont, Loreto Vilardell, Rafael Marcos
Journal: Journal of Clinical Oncology (2019)

225 Background: PC is the third leading-cause of cancer death in Spain. In this study we aim to investigate PC’s incidence and trends during 1994-2015 in Girona. Methods: Data were extracted from the population-based Girona Cancer Registry. Incident PC cases were classified using the ICD-O-3 Third Edition. Age-adjusted incidence rates (ASR E ) to the European standard population and world standard population (ASR W ) were obtained. Trends were assessed using the estimated annual percentage of change (EAPC) of the ASR E13. Results: We identified 1590 PC incident cases, 45.8% females and 54.2%. Patients &gt; 64 years old represented a 72.6% of cases. According to histology, epithelial tumors stand for a 44% of cases and neuroendocrine neoplasms represented only the 3% of all cases, being most of PC tumors’ histology non-specified. Cases detected only by death certificates (DCO) were 7.7% in males and 7.4% in females. For the whole study population, crude rate (CR) cancer incidence was 11.26 cases per 100,000 inhabitants/year (12.17 men; 10.34 women). Regarding the ASR, results show an ASR E13 of 12.99 (95% CI 12.36;13.65) and ASR W of 5.58 (95% CI 5.8;13.655.91). Age-specific rates reflected a drastic increase with age, having the population over 85 years the highest rate (74.5 cases per 100,000 inhabitants/year). We also found a significant increase in incidence of PC cases over the study period, with an EAPC of 1.41% per year, present in both men (EAPC = 1.30%) and women (EAPC = 1.37%). Conclusions: Incidence rates of PC in Girona are within the European average, and likewise they have been increasing for the last two decades. There is an increase of incidence in the elderly population reflected in age-specific rates, reason whereby we believe there are a high proportion of unspecific histologies. These results can be used as baseline for further research.
Metastatic Tumor-in-a-Dish, a Novel Multicellular Organoid to Study Lung Colonization and Predict Therapeutic Response
Authors: Prabhu Ramamoorthy, Sufi Mary Thomas, Gaurav Kaushik, Dharmalingam Subramaniam, Katherine M. Chastain, Animesh Dhar, Ossama Tawfik, Anup Kasi, Weijing Sun, Satish Ramalingam, Sumedha Gunewardena, Shahid Umar, Joshua M. Mammen, Subhash B. Padhye, Scott J. Weir, Roy A. Jensen, G. Sitta Sittampalam, Shrikant Anant
Journal: Cancer Research (2019)

Abstract Metastasis is a major cause of cancer-related deaths. A dearth of preclinical models that recapitulate the metastatic microenvironment has impeded the development of therapeutic agents that are effective against metastatic disease. Because the majority of solid tumors metastasize to the lung, we developed a multicellular lung organoid that mimics the lung microenvironment with air sac–like structures and production of lung surfactant protein. We used these cultures, called primitive lung-in-a-dish (PLiD), to recreate metastatic disease using primary and established cancer cells. The metastatic tumor-in-a-dish (mTiD) cultures resemble the architecture of metastatic tumors in the lung, including angiogenesis. Pretreating PLiD with tumor exosomes enhanced cancer cell colonization. We next tested the response of primary and established cancer cells to current chemotherapeutic agents and an anti-VEGF antibody in mTiD against cancer cells in two-dimensional (2D) or 3D cultures. The response of primary patient-derived colon and ovarian tumor cells to therapy in mTiD cultures matched the response of the patient in the clinic, but not in 2D or single-cell–type 3D cultures. The sensitive mTiD cultures also produced significantly lower circulating markers for cancer similar to that seen in patients who responded to therapy. Thus, we have developed a novel method for lung colonization in vitro, a final stage in tumor metastasis. Moreover, the technique has significant utility in precision/personalized medicine, wherein this phenotypic screen can be coupled with current DNA pharmacogenetics to identify the ideal therapeutic agent, thereby increasing the probability of response to treatment while reducing unnecessary side effects. Significance: A lung organoid that exhibits characteristics of a normal human lung is developed to study the biology of metastatic disease and therapeutic intervention.
Strength in numbers: A survival strategy that helps explain social bonding and commitment
Authors: Adam Lankford
Journal: Behavioral and Brain Sciences (2018)

We seek strength in numbers as a survival strategy, so it seems unlikely that social bonds would make us want to intentionally die. However, our deep desire to be protected may explain our attraction to exaggerated notions of intentional self-sacrifice - even though research on suicide terrorists, kamikaze pilots, and cult members suggests they were not actually dying for their group.
<scp>CD</scp>300a expression is modulated in atopic dermatitis and could influence the inflammatory response
Authors: Laila Karra, Roopesh Singh Gangwar, Pier Giorgio Puzzovio, Nanna Fyhrquist, Yael Minai‐Fleminger, Nadine Landolina, Hans‐Uwe Simon, Harri Alenius, Vera Leibovici, Dagmar Simon, Francesca Levi‐Schaffer
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 18643: The Quantitative Prediction of Hemodynamics Under Interatrial Shunting in Heart Failure Model Dogs
Authors: Keita Saku, Takuya Nishikawa, Kiyoshi Uike, Genya Sunagawa, Kazunori Uemura, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2017)

Backgrounds: Although interatrial shunting (IAS) has been reported to lower left atrial pressure (LAP) and improve exercise capacity in heart failure (HF) patients, hemodynamic benefits of IAS remain unpredictable. We used the framework of extended circulatory equilibrium (ECE) that we developed by generalizing Guyton’s circulatory equilibrium. Guyton’s framework defines circulatory equilibrium only at the systemic vein-right heart junction, whereas ECE defines circulatory equilibrium at the pulmonary vein-left heart junction as well. Pressures at these junctions approximate right atrial pressure (RAP) and LAP. Thus ECE could model IAS hemodynamics. We used Bernoulli’s principle to dictate IAS flow. Fundamental equations were provided in Fig. 1. Simultaneous solutions of these equations predict IAS hemodynamics. Methods: In 4 mongrel dogs, we connected the left and right atria with centrifugal pump to mimic IAS hemodynamics. After recording control hemodynamics, we changed shunt flow (Fshunt) stepwise at ...
PARP14 Is a Novel Therapeutic Target in STAT6 mutant Follicular Lymphoma
Authors: Verena Passerini, Michael Boesl, Elisabeth Silkenstedt, Elisa Osterode, Michael Heide, Robert Kridel, Christoph Ziegenhain, Annette M. Staiger, German Ott, Monika Szczepanowski, Julia Richter, Wolfram Klapper, Andreas Rosenwald, Wolfgang Enard, Wolfgang Hiddemann, Deepak Bararia, Zimber-Strobl Ursula, Oliver Weigert
Journal: Blood (2018)
Type I interferon induces CXCL13 to support ectopic germinal center formation
Authors: Alice E. Denton, Silvia Innocentin, Edward J. Carr, Barry M. Bradford, Fanny Lafouresse, Neil A. Mabbott, Urs Mörbe, Burkhard Ludewig, Joanna R. Groom, Kim L. Good-Jacobson, Michelle A. Linterman
Journal: The Journal of Experimental Medicine (2019)

Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation.
Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma
Authors: Isabelle Atkins, Ben Kinnersley, Quinn T. Ostrom, Karim Labreche, Dora Il'yasova, Georgina N. Armstrong, Jeanette E. Eckel-Passow, Minouk J. Schoemaker, Markus M. Nöthen, Jill S. Barnholtz-Sloan, Anthony J. Swerdlow, Matthias Simon, Preetha Rajaraman, Stephen J. Chanock, Joellen Shildkraut, Jonine L. Bernstein, Per Hoffmann, Karl-Heinz Jöckel, Rose K. Lai, Elizabeth B. Claus, Sara H. Olson, Christoffer Johansen, Margaret R. Wrensch, Beatrice Melin, Robert B. Jenkins, Marc Sanson, Melissa L. Bondy, Richard S. Houlston
Journal: Cancer Research (2019)

Abstract Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P &amp;lt; 5.69 × 10−6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 × 10−6). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis. Significance: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.
An Efficient Combination Immunotherapy for Primary Liver Cancer by Harmonized Activation of Innate and Adaptive Immunity in Mice
Authors: Liang Wen, Bing Xin, Panyisha Wu, Chia‐Hao Lin, Chuanhui Peng, Gaowei Wang, Jin Lee, Li‐Fan Lu, Gen‐Sheng Feng
Journal: Hepatology (2019)

Immunotherapy with checkpoint inhibitors for liver cancer, while active in many clinical trials worldwide, may have uncertain outcomes due to the unique immunotolerant microenvironment of the liver. In previous experiments, we unexpectedly identified a robust liver tumor‐preventive effect of a synthetic double‐stranded RNA, polyinosinic‐polycytidylic acid (polyIC), in mice. Herein we further demonstrate that polyIC given at the precancer stage effectively prevented liver tumorigenesis by activating natural killer cells, macrophages, and some T‐cell subsets; no inhibitory effect was observed on tumor progression if injected after tumor initiation. Nevertheless, polyIC administration potently induced programmed death ligand 1 (PD‐L1) expression in liver sinusoid endothelial cells, which prompted us to test a combined treatment of polyIC and PD‐L1 antibody (Ab). Although injecting PD‐L1 Ab alone did not show any therapeutic effect, injection of polyIC sensitized the hepatic response to PD‐L1 blockade. Combination of polyIC and PD‐L1 Ab resulted in sustained accumulation of active cluster of differentiation 8 cytotoxic T cells and robust liver tumor suppression and conferred a survival advantage in mice. These preclinical data in animal models suggest that, despite the low efficacy of PD‐L1/PD‐1 blockade alone, careful design of mechanism‐based combinatorial immunotherapeutic protocols may shift the paradigm in liver cancer treatment by coordinating maximal activation of multiple innate and adaptive immune functions. Conclusion: We provide proof of principle for the development of an efficient prevention strategy of liver tumorigenesis and a powerful combination immunotherapy for primary liver cancer.
Letter to Editor: The Synergistic Effect of Albumin on Terlipressin in Acute‐on‐Chronic Liver Failure With Acute Kidney Injury
Authors: Shengtao Lin, Da Dorothy Zhang, Yuan Gao, Yueke Zhu, Bing Hou
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the trial conducted by Arora et al.1 in which the authors reported superiority of terlipressin over noradrenaline in treating patients with acute‐on‐chronic liver failure (ACLF) and acute kidney injury (AKI). In this study, patients receiving terlipressin had better clinical response and survival compared with those receiving noradrenaline. We nevertheless suspect the reported treatment advantage of terlipressin is conditionally subject to the conjunctional use of high‐dose albumin (60 g/day). The dose of albumin used in this trial was much higher than that in previous studies,2 in which terlipressin failed to demonstrate any advantages over other vasoconstrictors. We therefore speculated that it is the high‐dose albumin that has potentiated the full therapeutic power of terlipressin by remedying its hemodynamic shortcomings. It is known that liver cirrhosis leads to decreased systemic vascular resistance. To compensate for it, the cardiac output (CO) would first increase. But in end stage of cirrhosis, the compensatory response of CO may become inadequate, which is an indication for poor prognosis.3 Both terlipressin and noradrenaline are vasoconstrictors used widely in patients with cirrhosis and hepatorenal syndrome to help restore the systemic vascular resistance. It is known that terlipressin can constrict splanchnic vasculature better than noradrenaline, but simultaneously reduces CO. In contrast, noradrenaline has no negative effect on CO.4 Therefore, isolated use of terlipressin is unfavorable in these patients.5 Albumin, as a volume expander, at high dose can increase CO in patients with cirrhosis3 and is thus capable of compensating for the negative impact of terlipressin on CO, although it had little hemodynamic benefit to noradrenaline. We suspect it is the synergistic effect of high‐dose albumin and terlipressin, which is not present with high‐dose albumin and noradrenalin, that resulted in better patient outcomes in the trial. We suggest that to conclude whether terlipressin with or without combinational use of high‐dose albumin is genuinely superior to noradrenaline in treating patients with ACLF with AKI, further evaluation may be required.