tbuckley/cabot-search huggingface dataset:
Tumor regression grade in gastric cancer after preoperative therapy.
Authors: Naruhiko Ikoma, Jeannelyn Estrella, Prajnan Das, Bruce D. Minsky, Keith F. Fournier, Paul F. Mansfield, Mariela A. Blum, Jaffer A. Ajani, Brian D. Badgwell
Journal: Journal of Clinical Oncology (2019)

168 Background: The AJCC 8 th edition updated ypStage TNM grouping for patients with gastric cancer due to the increasing use of preoperative therapy. We previously reported that nodal status after preoperative therapy (ypN) was most predictive for overall survival (OS). We intended to investigate if tumor regression grade (TRG) of the primary tumor scored by pathologists is helpful to predict survival of gastric cancer patients treated with preoperative therapy. Methods: We reviewed an institutional database to identify patients with clinically non-metastatic gastric adenocarcinoma who underwent gastrectomy after preoperative chemo- or chemoradiation therapy. Pathology reports were reviewed, and TRG was classified into following categories: 0 (complete response), 1 (few clusters of viable tumor cells, £1-2%), 2 (significant response, viable cells £ 50%), 3 (minor or no treatment response, viable cells &gt; 50%). Associations between TRG and clinicopathological factors were examined. Univariable and multivariable Cox regressions were performed to determine associations with OS. Results: We identified 356 patients who met study criteria, including 80 (23%) patients with GEJ tumors; 56% were white and 60% were male. Preoperative chemoradiation therapy was given to 268 (75%). Fifty-six (16%) had TRG 0, 57 (16%) had TRG 1, 128 (36%) had TRG 2, and 115 (32%) had TRG 3. There were no associations between TRG and pretreatment factors. TRG 2 or 3 was associated with advanced ypT and ypN categories (both p &lt; 0.001), ypM1 (p = 0.004), and R1 resection (0.052). Of all patients, median OS was 6.6 y, and 5-year OS was 54.1%. TRG 3 was associated with worse OS than other groups ( p = 0.015), while there was no significant OS difference among TRG 0-2 groups ( p = 0.803) in univariate analyses. On multivariable analysis, TRG was not associated with OS after adjustment for ypN status. Conclusions: In patients with gastric cancer who underwent preoperative therapy, TRG 3 was associated with advanced ypStage and R1 resection. Patients with TRG 3 had worse OS, due to associated advanced ypStage, particularly ypN+ status. Further studies are warranted to identify better definitions of treatment response and to identify the optimal modality for obtaining ypN0 status.
Relapse and Mortality Prediction of Acute Myeloid Leukemia Patients Using Deep Bidirectional Long Short-Term Memory-Deep Neural Network Architecture
Authors: Bor-Sheng Ko, Yu-Fen Wang, Chih-Chuan Lu, Jeng-Lin Li, Chi-Chun Lee, Jih-Luh Tang, Hwei-Fang Tien
Journal: Blood (2018)
Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model
Authors: Mario Merlini, Victoria A. Rafalski, Pamela E. Rios Coronado, T. Michael Gill, Maya Ellisman, Gayathri Muthukumar, Keshav S. Subramanian, Jae Kyu Ryu, Catriona A. Syme, Dimitrios Davalos, William W. Seeley, Lennart Mucke, Robert B. Nelson, Katerina Akassoglou
Journal: Neuron (2019)
Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade
Authors: Chien-Chun Steven Pai, John T. Huang, Xiaoqing Lu, Donald M. Simons, Chanhyuk Park, Anthony Chang, Whitney Tamaki, Eric Liu, Kole T. Roybal, Jane Seagal, Mingyi Chen, Katsunobu Hagihara, Xiao X. Wei, Michel DuPage, Serena S. Kwek, David Y. Oh, Adil Daud, Katy K. Tsai, Clint Wu, Li Zhang, Marcella Fasso, Ravi Sachidanandam, Anitha Jayaprakash, Ingrid Lin, Amy-Jo Casbon, Gillian A. Kinsbury, Lawrence Fong
Journal: Immunity (2019)
In Situ Hybridization of HBZ and Tax in FFPE Samples from ATLL Patients and Its Association with Clinicopathological Characteristics
Authors: Kyohei Yamada, Hiroaki Miyoshi, Mai Takeuchi, Naoko Asano, Joji Shimono, Fumiko Arakawa, Kazutaka Nakashima, Kensaku Sato, Masao Seto, Koichi Ohshima
Journal: Blood (2018)
Peripheral Blood Blast Clearance As an Independent Predictor of Clinical Response and Outcomes in Acute Myeloid Leukemia
Authors: Noa G. Holtzman, Firas El Chaer, Omer Ali, Ameet Patel, Maria R. Baer, Vu H. Duong, Edward A. Sausville, Arash Etemadi, Ashkan Emadi
Journal: Blood (2018)
Vernal Kerataconjunctivitis Treated With Omalizumab: a serie of cases
Authors: Pamela Pittelkow Silva, Pâmela Pittelkow, Dirceu Sole, Marcia C. Mallozi, Carolina S. Aranda, Jessica Luna Junqueira Vasconcelos, Myrna Serapião dos Santos, Denise de Freitas
Journal: Journal of Allergy and Clinical Immunology (2019)
Long-Term Remission of CLL Sustained By Pauciclonal Anti-CD19 Chimeric Antigen Receptor T (CTL019) Cell Clones
Authors: J. Joseph Melenhorst, David L. Porter, Lifeng Tian, Simon F Lacey, Christopher L Nobles, Joseph A Fraietta, Noelle V. Frey, Irina Kulikovskaya, Minnal Gupta, Regina M Young, David E Ambrose, Don L. Siegel, Frederic D Bushman, Carl H June
Journal: Blood (2018)
Nanogold Flower‐Inspired Nanoarchitectonics Enables Enhanced Light‐to‐Heat Conversion Ability for Rapid and Targeted Chemo‐Photothermal Therapy of a Tumor
Authors: Jing Liu, Fenfen Zhai, Hong Zhou, Wenrong Yang, Shusheng Zhang
Journal: Advanced Healthcare Materials (2019)

Abstract Chemo‐photothermal therapy has become a promising tool for clinical noninvasive tumor therapy, which is able to efficiently avoid drug resistance and other side effects from chemical anticarcinogenic drugs. The ability to selectively fast‐heat tumor tissues over surrounding compartments is of fundamental importance and makes effective treatment of tumor margins and complex tumor geometries. Currently existing chemo‐photothermal methods mainly show slow light‐to‐heat conversion with increased temperature up to around 45–57 °C for 5–20 min or a longer time in vitro under regular near‐infrared laser irradiation, and during tumor therapy, worse performance in temperature changes are obtained due to the much longer penetration distance in vivo. Herein, nanoarchitectonics with excellent chemo‐photothermal performance are first proposed for tumors via in situ decoration of nanogold flowers on graphene oxide surface with further modification of the aptamer molecule. Even with simple synthesis processes, these nanoarchitectonics demonstrate impressive increased temperatures up to 85 °C in just 2 min under 808 nm laser irradiation with regular power density. Due to the fast light‐to‐heat conversion ability and specific binding effect between the aptamer and tumor cells, the designed nanocarrier shows a rapid and target therapy system with a targeted chemo‐photothermal tumor treatment.
A phase II study of GVAX colon vaccine with cyclophosphamide and pembrolizumab in patients with mismatch repair–proficient (MMR-p) advanced colorectal cancer.
Authors: Mark Yarchoan, Anna K. Ferguson, Jennifer N. Durham, Noah Rozich, Christina Rodriguez, Chiung-Yu Huang, Ilene S. Browner, Ana De Jesus-Acosta, Dung T. Le, Dan Laheru, Ross C. Donehower, Elizabeth M. Jaffee, Lei Zheng, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2019)

563 Background: Mismatch repair proficient (MMRp) colorectal cancer (CRC) is refractory to single-agent programmed cell death protein 1 (PD1) inhibitors. Cancer vaccines may prime the tumor microenvironment for anti-PD1 therapy. Colon GVAX is an allogeneic, whole-cell, GM-CSF-secreting vaccine that induces T-cell immunity against tumor-associated antigens. GVAX has previously been studied in combination with low-dose cyclophosphamide (Cy) to inhibit regulatory T cells. Methods: We conducted an open label, single-arm, phase 2 study of GVAX/Cy in combination with the PD1 inhibitor pembrolizumab in patients with MMRp CRC who had received at least two prior lines of therapy in the metastatic setting. Patients received pembrolizumab plus Cy on day 1, GVAX on day 2, of a 21 day cycle through 4 cycles, and were then continued on a maintenance regimen of pembolizumab every 3 weeks with cy/GVAX given every 12 weeks. Results: Seventeen patients were enrolled. There were no objective responses, and the disease control rate was 18% by RECIST and 29% by irRC. The median progression free survival was 2.7 months and the median overall survival was 7.0 months. Biochemical responses (≥30% decline in CEA) were observed in 7/17 (41%) of patients. Two patients (12%) had grade 3/4 adverse events that were attributed to study therapy. To test the hypothesis that the induction of a humoral response against CEA protein had resulted in the observed biochemical responses, we measured patient titers of anti-CEA antibodies. Anti-CEA antibody titers increased 13 of 13 patients (100%) with available paired pre- and on-treatment research blood samples, but the change in anti-CEA antibody titers were similar among CEA responders and non-responders. Multiplex immunohistochemistry performed on pre- and post- biopsy specimens will be reported at the conference. Conclusions: GVAX/Cy plus pembrolizumab is well tolerated in advanced MMRp CRC and resulted in CEA responses but not radiographic responses. PFS and OS compare favorably to historical controls in this small cohort. CEA responses were not observed with PD1 monotherapy in MMRp CRC, suggesting GVAX can modulate the antitumor immune response. Clinical trial information: NCT02981524.
MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans
Authors: Alexander W. Koch, Nikolaus Schiering, Samu Melkko, Stefan Ewert, Janeen Salter, Yiming Zhang, Peter McCormack, Jianying Yu, Xueming Huang, Yu-Hsin Chiu, Zhiping Chen, Simone Schleeger, Geraldine Horny, Keith DiPetrillo, Lionel Muller, Andreas Hein, Frederic Villard, Meike Scharenberg, Paul Ramage, Ulrich Hassiepen, Serge Côté, Julie DeGagne, Carsten Krantz, Jörg Eder, Brian Stoll, Kenneth Kulmatycki, David L. Feldman, Peter Hoffmann, Craig T. Basson, Robert J. A. Frost, Yasser Khder
Journal: Blood (2019)
TSPO-PET and diffusion-weighted MRI for imaging a mouse model of infiltrative human glioma
Authors: Hayet Pigeon, Elodie A Pérès, Charles Truillet, Benoit Jego, Fawzi Boumezbeur, Fabien Caillé, Bastian Zinnhardt, Andreas H Jacobs, Denis Le Bihan, Alexandra Winkeler
Journal: Neuro-Oncology (2019)

Glioblastoma (GBM) is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced PET and MRI techniques for visualizing biological activity and infiltration of the tumor.Using multimodality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18 kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (apparent diffusion coefficient, kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. In vivo imaging findings were confirmed by autoradiography and immunofluorescence.Increased tumor-to-contralateral [18F]DPA-714 uptake ratios (1.49 ± 0.11) were found starting 7 weeks after glioma cell implantation. TSPO-PET allowed visualization of glioma infiltration into the contralateral hemisphere 2 weeks earlier compared with the clinically relevant biomarker for biological glioma activity [18F]FET. Diffusion-weighted imaging (DWI), in particular kurtosis, was more sensitive than standard T2-weighted MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect in vivo findings. Interestingly, labeling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells.These results suggest that advanced PET and MRI methods, such as [18F]DPA-714 and DWI, may be superior to standard imaging methods to visualize glioma growth and infiltration at an early stage.
Abstract 15833: LRP1 is a Novel Receptor of Bmper and Required for Pathological Angiogenesis
Authors: Xi Li, Xinchun Pi
Journal: Circulation (2014)

Low density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional member of the LDL receptor family, impacting a variety of biological processes such as lipid metabolism, endocytosis and signal transduction. However, the role of LRP1 in endothelium was almost unknown. Until recently we discovered that LRP1 is a novel regulator of bone morphogenetic protein (Bmp) signaling through its association with the extracellular modulator-Bmper (Bmp-binding endothelial cell precursor-derived regulator) and regulates zebrafish vascular development. Here we studied the functional roles of LRP1 in mammalian system by performing cell culture studies with endothelial cells (ECs) and analyzing angiogenic defects in oxygen-induced retinopathy model with LRP1flox/flox;Tie2-Cre+/- mice (EC-LRP1 KO). In MECs, we observed that the activation of Src, ERK and tyrosine phosphorylation of multiple proteins were induced by Bmper and this activation was LRP1-dependent since LRP1 knockdown inhibited their activation. However, this Bmper-induced activation was not blocked by Bmp4 neutralized antibody, which suggests that LRP1 is required for Bmp4-independent signaling for Bmper. These data also indicate that Bmper and LRP1 is a novel ligand receptor pair. Moreover, we observed that LRP1 protein was induced in response to 1% hypoxia in both mouse ECs (MECs) and human retinal microvascular endothelial cells, suggesting that LRP1 is required for hypoxia induced endothelial function. In hypoxia condition, EC-LRP1 KO mice resulted in accelerated angiogenesis in retinal endothelial cells, similar to the pattern of Bmper deleted mice. Therefore, we identify that the Bmper/LRP1 signaling is a novel signaling pathway in endothelial cells and their activity regulates angiogenic responses during oxygen-induced retinopathy. This study provides mechanistic insights for angiogenesis-related pathophysiologic conditions.
Avenger 500, a phase III open-label randomized trial of the combination of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas.
Authors: Philip Agop Philip, Marc E. Buyse, Angela Tatiana Alistar, Caio Max Sao Pedro Rocha Lima, Sanjeev Luther, Timothy S. Pardee, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2019)

TPS479 Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Current treatments using FOLFIRINOX and gemcitabine plus nab-paclitaxel, provide median survivals of 11.1 and 8.5 months, respectively. PDAC cells have altered metabolism. CPI-613 is a novel TCA cycle inhibitor that targets cancer cells. In a phase I study mFFX plus CPI-613 resulted in a 61% objective response rate with 3 of 18 patients achieving a complete response. Methods: Avenger 500 (NCT03504423) is an open-label randomized trial of CPI-613 plus mFFX versus FFX in untreated patients with metastatic PDAC. 500 patients will be randomized 1:1 between arms. The experimental arm comprises CPI-613 500 mg/m 2 on day 1 and 3 of a 14-day cycle. The mFFX regimen is the standard dose and schedule of 5-Fluorouracil but reduced doses of oxaliplatin (65 mg/m²) and irinotecan (140 mg/m²). The control arm is standard dose FFX. There are two co-primary endpoints: Overall Response Rate (ORR, Complete Response + Partial Response). Best response within the first 12 cycles will be used for this determination, to be confirmed by independent, blinded, central review. Progression-Free Survival (PFS), is the second co-primary endpoint. Secondary endpoints are overall survival, duration of response and safety. Patient reported outcomes will be compared using the NCCN-FACT FHSI-18. An interim analysis will be done after 167 patients are evaluable for response. The difference in ORR will be tested using a Lan-DeMets Pocock type boundary for futility and efficacy. Futility will be declared if the difference in ORR between the arms is smaller than 5%, while efficacy will be declared if it is larger than 20%. The PFS hazard ratio will be tested using a Lan-DeMets O’Brien-Fleming type boundary. Efficacy will be declared if the hazard ratio is less than 0.48. The final analysis will be done with 500 patients randomized, when ~375 PFS events are available. Significance will be reached if the PFS hazard ratio is less than 0.80, or the difference in ORR is at least 11%. If the trial reaches significance for either primary endpoint, overall survival will be tested. Clinical trial information: NCT03504423.
Questioning Lay Health Worker Influence on Goals-of-Care Documentation and Patient Satisfaction
Authors: Nicholas Yew Wei Heng, Thineskrishna Anbarasan
Journal: JAMA Oncology (2019)

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Dose escalation and expansion cohort study for DS-8895a in patients with advanced solid tumors.
Authors: Taroh Satoh, Kohei Shitara, Satoru Iwasa, Kensei Yamaguchi, Kei Muro, Yoshito Komatsu, Tomohiro Nishina, Taito Esaki, Jun Hasegawa, Yasuyuki Kakurai, Emi Kamiyama, Tomoko Nakata, Kota Nakamura, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2019)

99 Background: Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface of many tumors and is associated with poor prognosis, suggesting EPHA2 as a target for cancer therapy. DS-8895a is an afucosylated, humanized anti-EPHA2 IgG1 monoclonal antibody with potent cytotoxicity. We report results from a phase I clinical trial to determine safety, tolerability, and pharmacokinetics (PK) of DS-8895a in Japanese patients with advanced solid tumors (NCT02004717). Methods: Step 1 (dose escalation cohort) had patients with advanced solid tumors and comprised of six dose levels (0.1–20 mg/mL, intravenous infusion, every 2 weeks [Q2W]) with a 28-day dose limiting toxicity (DLT) evaluation period. Step 2 (expansion cohort) patients had gastric or esophageal cancer confirmed to be EPHA2 positive by immunohistochemistry. Dose level in Step 2 was determined based on results obtained in Step 1. We evaluated safety, PK, potential biomarkers including circulating NK cells and cytokines, and tumor response. Results: Maximum tolerated dose was not reached in Step 1 (n = 22). DS-8895a was administered at 20 mg/kg Q2W in Step 2 (n = 15). Among 37 patients in the safety analysis set, adverse events (AEs) were reported in 97.3% (64.9% drug-related); 35.1% presented grade ≥ 3 AEs (8.1% drug-related). Dose delay and study discontinuation due to AEs (treatment related: grade 4 platelet decrease, hypoesthesia, hypotension, peripheral coldness, nausea, and vomiting) were observed in one and four patients (20 mg/kg), respectively. Infusion-related reactions occurred in 51.4% of patients resulting in 10 dose interruptions with one discontinuation. Serum inflammatory cytokines were transiently increased 4 h from the end of infusion drug administration. Serum DS-8895a maximum and trough concentrations increased dose-dependently. Biomarkers had no apparent relationship to best overall response. Seven patients in Step 1 achieved stable disease; in Step 2, six patients achieved stable disease and one patient achieved partial response. Conclusions: DS-8895a was safe and well tolerated up to 20 mg/kg. The PK of DS-8895a was dose-dependent as expected. Clinical trial information: NCT02004717.
Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes
Authors: Yue J. Wang, Daniel Traum, Jonathan Schug, Long Gao, Chengyang Liu, Mark A. Atkinson, Alvin C. Powers, Michael D. Feldman, Ali Naji, Kyong-Mi Chang, Klaus H. Kaestner
Journal: Cell Metabolism (2019)
PRC2 Inactivation Induces Resistance to Chemotherapy-Induced Apoptosis By Upregulating the TRAP1 Mitochondrial Chaperone in T-ALL
Authors: Kimberly Bodaar, Ingrid M. Aries, Salmaan Karim, Triona Ni Chonghaile, Melissa A. Burns, Laura Hinze, Maren Pfirrmann, James Degar, Jack Landrigan, Sebastian Balbach, Sofie Peirs, Bjorn Menten, Kristen E. Stevenson, Donna S Neuberg, Meenakshi Devidas, Mignon L. Loh, Stephen P. Hunger, David T Teachey, Karen R. Rabin, Stuart S. Winter, Kimberly P. Dunsmore, Brent Wood, Lewis B. Silverman, Stephen E. Sallan, Pieter Van Vlierberghe, Stuart H. Orkin, Birgit Knoechel, Anthony Letai, Alejandro Gutierrez
Journal: Blood (2018)
Nasal polypectomy is associated with decreased aspirin sensitivity and related eicosanoid changes in AERD patients
Authors: Elina Jerschow, Matthew Edin, Yuling Chi, Beth Hurst, Waleed Abuzeid, Nadeem Akbar, Marc Gibber, Weiguo Han, Marvin Fried, Teresa Pelletier, Zhen Ren, Taha Keskin, Gigia Roizen, Fred B. Lih, Artiom Gruzdev, J Alyce Bradbury, Victor Schuster, Simon Spivack, David L. Rosenstreich, Darryl C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2019)
Preclinical Characterization of AFM26, a Novel B Cell Maturation Antigen (BCMA)-Directed Tetravalent Bispecific Antibody for High Affinity Retargeting of NK Cells Against Myeloma
Authors: Thorsten Ross, Uwe Reusch, Susanne Wingert, Torsten Haneke, Katja Klausz, Anna-Kathrin Otte, Natalie Schub, Stefan Knackmuss, Thomas Müller, Kristina Ellwanger, Ivica Fucek, Ute Schniegler-Mattox, Joachim Koch, Thomas Valerius, Martin Gramatzki, Matthias Peipp, Michael Tesar, Erich Rajkovic, Martin Treder
Journal: Blood (2018)
The Effect of Asparaginase on Serum Triglycerides during Therapy for Acute Lymphoblastic Leukemia
Authors: Emily R Finch, Colton A Smith, Wenjian Yang, Nancy M Kornegay, John C Panetta, Kristine R Crews, Alejandro R Molinelli, Cheng Cheng, Deqing Pei, Laura B. Ramsey, Seth E Karol, Hiroto Inaba, John T. Sandlund, Monika Metzger, William E. Evans, Sima Jeha, Ching-Hon Pui, Mary V Relling
Journal: Blood (2018)