tbuckley/cabot-search huggingface dataset:
PDCT-17 (LTBK-11). PNOC007: H3.3K27M SPECIFIC PEPTIDE VACCINE COMBINED WITH POLY-ICLC FOR THE TREATMENT OF NEWLY DIAGNOSED HLA-A2+ H3.3K27M MIDLINE GLIOMAS
Authors: Sabine Mueller, Rishi Lulla, Stewart Goldman, Anu Banerjee, Susan Chi, Nicholas Whipple, John Crawford, Karen Gauvain, Kellie Nazemi, Javad Nazarian, Jared Taitt, Payal Watchmaker, Takahide Nejo, Kaori Okada, Lisa Butterfield, Annette Molinaro, Michael Prados, Hideho Okada
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To assess within a multi-center trial the safety of H3.3K27M specific peptide vaccine in combination with poly-ICLC in HLA-A02.01+ patients diagnosed with H3.3K27M+ diffuse midline gliomas. METHODS Subjects 3–21 years of age with CLIA confirmed H3.3K27 mutation status were eligible. Patients were enrolled after completion of focal radiation therapy. The trial enrolled two strata: Stratum A included newly diagnosed patients with diffuse intrinsic pontine glioma (DIPG) (n=19); Stratum B included non-DIPG midline glioma patients including spinal cord tumors as an exploratory strata (n=10). The H3.3K27M vaccine was administered in combination with poly-ICLC every 3 weeks for a total of 8 doses followed by every 6 weeks for a maximum of 96 weeks of therapy. Immuno-monitoring and imaging occurred every 3 months. Modified iRANO criteria are used for ongoing assessment of disease status. Patients’ peripheral blood mononuclear cell (PBMC) samples were evaluated by mass cytometry. RESULTS From November 2016 until March 2019, 19 eligible patients (median age 11, range 5–17 yrs; 53 % female) were enrolled in Stratum A and 10 eligible patients (median age 13, range 7–18 yrs; 60 % female) in Stratum B. Treatment was well tolerated with 7 grade 3 and 0 grade 4 treatment related toxicities. The most common related side effect included injection site reaction. Median number of vaccine administrations per patient was 6 (range 1–11). Overall survival at 12 months was 40% (95% CI 22–73%) for Stratum A and 39% (95% CI 16–93%) for Stratum B. A mass cytometry-based analysis of patient PBMCs (n = 16) revealed a trend towards an inverse correlation between polymorphonuclear myeloid-derived suppressor cells and the expansion of H3.3K27M-specific CD8+ T-cells (p-value = 0.154). CONCLUSION H3.3K27M specific vaccine in combination with poly-ICLC is well tolerated. Further evaluation will include a combination with checkpoint inhibitor nivolumab.
A multicenter, randomized, controlled, phase II trial exploring adjuvant combined therapy of apatinib and SHR-1210 (anti-PD-1), in patients with hepatocellular carcinoma at high risk of recurrence after radical resection
Authors: S. Yan, Y. Zhang, X. Bi, J. Zhao, S. Du, Z. Huang, Y. Zhang, D. Liu, Z. Li, J. Zhou, J. Cai, H. Zhao
Journal: Annals of Oncology (2019)
ATIM-49 (LTBK-01). AMG 596, A NOVEL ANTI-EGFRVIII BISPECIFIC T CELL ENGAGER (BITE®) MOLECULE FOR THE TREATMENT OF GLIOBLASTOMA (GBM): PLANNED INTERIM ANALYSIS IN RECURRENT GBM (RGBM)
Authors: Mark A Rosenthal, Carmen Balana, Myra E van Linde, Cyrus Sayehli, Walter M Fiedler, Martin Wermke, Christophe Massard, Ingo K Mellinghoff, Mustafa Khasraw, Agnes Ang, Erik Rasmussen, Johannes Kast, Sabine Stienen, Timothy F Cloughesy
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES The class III variant of the epidermal growth factor receptor (EGFRvIII) represents the most common EGFR mutation in GBM. AMG 596 is a bispecific T cell engager (BiTE®) molecule designed to engage a patient’s own CD3-positive T cells to EGFRvIII-positive tumor antigens. This is the first clinical data readout for AMG 596. METHODS This phase 1, first-in-human, open-label, sequential dose-escalation/expansion study evaluates continuous intravenous AMG 596 in patients with EGFRvIII-positive GBM or malignant glioma in recurrent (Group 1) or newly diagnosed in maintenance treatment (Group 2) settings. Eligible patients: adults with EGFRvIII-positive GBM or malignant glioma; ≤2 mg/day dexamethasone, ECOG performance status ≤1; life expectancy ≥3 months; and acceptable renal, hematological, and hepatic function. The primary objective evaluates safety and tolerability. Additional assessments include objective response rate per modified Response Assessment in Neuro-Oncology (RANO) Criteria. RESULTS As of June 2019, 15 rGBM patients (Group 1) were enrolled; 14 patients received ≥1 dose AMG 596. 14/15 (93.3%) patients were evaluable at time of analysis (safety analysis set). Median age was 54.5 years (range, 44–68); 50% were male. Seven patients discontinued for progressive disease (PD). AEs occurred in all patients and were serious in 7/14 (50%). None resulted in discontinuation; two (14.3%) fatal AEs were related to PD. Headache and depressed consciousness (both n=2, 14.3%) were the most common grade ≥3 treatment emergent AEs. In patients with sufficient follow-up to assess response (n=8), 1 (12.5%) achieved partial response, 2 (25%) had stable disease, 4 (50%) had PD at initial scan, and 1 (12.5%) discontinued treatment for PD. Semi-quantitative EGFRvIII expression analysis revealed a median H-score of 115 (range, 8–280). CONCLUSION This interim analysis suggests a first indication that AMG 596 may be well-tolerated and offer anti-tumor activity in patients with rGBM. Enrollment is ongoing and additional data will be presented. NCT03296696.
FRI0091 Angiogenesis in systemic lupus erythematosus (sle) and primary antiphospholipid syndrome (paps)
Authors: C Navarro, L Candia-Zúñiga, LH Silveira, V Ruiz, MC Amigo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Angiogenesis is an essential process of the body´s physiology and plays a role in several diseases such as rheumatoid arthritis, neoplasias or atherosclerosis. Vascular endothelial growth factor (VEGF) and angiogenin (Ang) are factors that promote angiogenesis <i>in vitro</i> and <i>in vivo</i>. However, new vessels formation seems limited to tissues with some degree of inflammation or with hypoxia. SLE and PAPS are characterised by endothelial damage and the mechanisms of angiogenesis have not been explored in these diseases. <h3>Objectives</h3> In this study we determine the possible role of VEGF and Ang in the pathogenesis of SLE and PAPS. <h3>Methods</h3> We included 28 SLE patients, 10 PAPS patients and 24 matched controls. VEGF and Ang plasma levels were measured by ELISA. <h3>Results</h3> The VEGF plasma levels were significantly increased in SLE patients compared with PAPS patients and controls, p &lt; 0.01. The Ang levels were similar in the three groups. No correlation between VEGF levels and clinical manifestations was found. <h3>Conclusion</h3> The raised levels of VEGF in SLE might be related to the process of endothelial repair present in different organs of lupus patients.
Image Gallery: Pemphigus vulgaris mimicking acrodermatitis continua of Hallopeau
Authors: Q. Chen, J. Du, J. Jin, J. Zhang
Journal: British Journal of Dermatology (2019)

Dear Editor, A 38-year-old man presented with a 2-month history of pruritic and painful erosions, blisters and pustules on all fingers and toes (a, b), clinically consistent with a diagnosis of acrodermatitis continua of Hallopeau. Pustules on his limbs and trunk, and oral erosions were also noted. Histopathology (c) showed intraepidermal acantholytic blisters, eosinophilic abscesses above the basal layer and infiltration of lymphocytes and eosinophils in the superficial dermis. Direct immunofluorescence (d) revealed intercellular C3 deposition in the lower epidermis. Indirect immunofluorescence was positive for anti-desmoglein (Dsg)1, 155 U mL−1 (normal 0–14 U mL−1) and anti-Dsg3, 112 U mL−1 (normal 0–7 U mL−1). Pemphigus vulgaris was diagnosed, which responded well to systemic corticosteroids.
Baseline Characteristics, Treatment Patterns, and Outcomes in Patients with HER2-Positive Metastatic Breast Cancer by Hormone Receptor Status from SystHERs
Authors: Melody Cobleigh, Denise A. Yardley, Adam M. Brufsky, Hope S. Rugo, Sandra M. Swain, Peter A. Kaufman, Debu Tripathy, Sara A. Hurvitz, Joyce O'Shaughnessy, Ginny Mason, Vincent Antao, Haocheng Li, Laura Chu, Mohammad Jahanzeb
Journal: Clinical Cancer Research (2019)

We report treatments and outcomes in a contemporary patient population with HER2-positive metastatic breast cancer (MBC) by hormone receptor (HR) status from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs).SystHERs (NCT01615068) was an observational, prospective registry study of U.S.-based patients with newly diagnosed HER2-positive MBC. Endpoints included treatment patterns and clinical outcomes.Of 977 eligible patients (enrolled from 2012 to 2016), 70.1% (n = 685) had HR-positive and 29.9% (n = 292) had HR-negative disease. Overall, 59.1% (405/685) of patients with HR-positive disease received any first-line endocrine therapy (with or without HER2-targeted therapy or chemotherapy); 34.9% (239/685) received HER2-targeted therapy + chemotherapy + sequential endocrine therapy. Patients with HR-positive versus HR-negative disease had longer median overall survival (OS; 53.0 vs 43.4 months; hazard ratio, 0.70; 95% confidence interval, 0.56-0.87). Compared with patients with high HR-positive staining (10%-100%, n = 550), those with low HR-positive staining (1%-9%, n = 60) received endocrine therapy less commonly (64.2% vs 33.3%) and had shorter median OS (53.8 vs 40.1 months). Similar median OS (43.4 vs 40.1 months) was observed in patients with HR-negative versus low HR-positive tumors (1%-9%).Despite evidence that first-line HER2-targeted therapy, chemotherapy, and sequential endocrine therapy improves survival in patients with HR-positive, HER2-positive disease, only 34.9% of patients in this real-world setting received such treatment. Patients with low tumor HR positivity (1%-9%) had lower endocrine therapy use and worse survival than those with high tumor HR positivity (10%-100%).
Methylation of the IGFBP-3 gene and prognosis of epithelial ovarian cancer
Authors: Andrew Wiley, Stefano Fracchioli, Dionyssios Katsaros, Herbert Yu
Journal: Cancer Research (2004)

1059  Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGF binding protein family (IGFBP) which regulates the mitogenic and anti-apoptotic effects of insulin-like growth factors (IGFs). IGFBP-3 is the most abundant IGFBP in the circulation and hypermethylation of the IGFBP-3 promoter has been found to suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer progression, we examined the survival of ovarian cancer patients in relation to IGFBP-3 promoter methylation and IGFBP-3 protein levels in ovarian tumor tissue. Two hundred forty-nine consecutive epithelial ovarian cancer patients were selected for the study from the Department of Gynecology and Obstetric at University of Turin and were followed for a median of 31 months after surgery. Genomic DNA was extracted from fresh frozen tumor tissue and treated with sodium bisulfite. IGFBP-3 promoter methylation was analyzed using methylation-specific PCR (MSP). Tissue cytosol was prepared with the use of a protein extraction kit and IGFBP-3 protein levels in the cytosol were determined using a commercial ELISA. Cox regression survival analysis was performed to examine the association of IGFBP-3 methylation with disease-free and overall survivals. The majority of patients in the study had advanced disease (69%, Stage III and IV) and aggressive tumors (66%, Grade 3). Promoter methylation of the IGFBP-3 gene was detected in 43% (107/248) of the patients. IGFBP-3 promoter methylation was not associated with disease progression (p=0.3972) or death (p=0.2983) in univariate analyssis, but the associations became statistically significant when clinical and pathological variables, including age at diagnosis, disease stage, histologic grade, debulking results, residual tumor size, and IGFBP-3 levels in tumor tissue, were adjusted in the analysis. The relative risk was 1.62 (95% CI: 1.06-2.47) for disease progression and 1.59 (95% CI: 1.04-2.43) for death. Tissue levels of IGFBP-3 protein were not significantly different by methylation status (p=0.30), and were not associated with disease progression (p=0.33) or death (p=0.18). In conclusion, the study did not find strong evidence to support the notion that IGFBP-3 promoter methylation suppresses IGFBP-3 expression in ovarian cancer and can be used as a molecular marker for ovarian cancer prognosis.
Correlation between exercise, personal income level and health-related quality of life in patients with newly diagnosed stable angina
Authors: Yi Wang, Lei Huang, Lai-Xin Zhou
Journal: Military Medical Research (2019)

Abstract Background Stable angina is one of the most common clinical types of coronary artery disease (CAD) and associated with poor health-related quality of life (HRQL). However, few studies have evaluated the risk factors associated with HRQL in patients with newly diagnosed stable angina. Methods A cross-sectional survey was conducted with 342 consecutive outpatients with newly diagnosed stable angina from October 2017 to January 2018 at the Second Affiliated Hospital of Army Medical University, Chongqing, China. Eight dimensions of HRQL were evaluated via the 36-item Short-Form Health Survey, including physical functioning, role limitation due to physical problems, bodily pain, general health, vitality, social functioning, role limitation due to emotional problems, and mental health. Physical and mental component summaries were calculated. Multiple stepwise regression was performed to determine the factors associated with HRQL. Results Patients who were older, were females, did not exercise, had lower educational levels, had lower monthly incomes, had smoking/drinking habits, and had diabetes, hypertension, or hyperlipemia showed lower physical HRQL scores, while those who were older with lower educational levels and lower monthly incomes showed lower mental HRQL scores. The results of the multiple stepwise regression analyses showed that physical and mental HRQL were positively correlated with exercise and monthly income and negatively associated with age. Patients with monthly income ≥5000 Yuan showed higher HRQL scores than those with monthly income &lt; 5000 Yuan. Sleep quality and drinking were negatively associated with physical, but not mental HRQL. Conclusions Our findings indicated that exercise and personal income level, both modifiable factors, were positively associated with physical and mental HRQL. These findings could have implications for clinical suggestions and strategies to improve HRQL in patients with stable angina.
Safety and Anti-Tumor Activity of CD5 CAR T-Cells in Patients with Relapsed/Refractory T-Cell Malignancies
Authors: LaQuisa C. Hill, Rayne H. Rouce, Tyler S. Smith, Lina Yang, Madhuwanti Srinivasan, Huimin Zhang, Silvana Perconti, Birju Mehta, Olga Dakhova, Josalind Randall, Bambi J. Grilley, Helen E. Heslop, Malcolm K. Brenner, Maksim Mamonkin
Journal: Blood (2019)
A multicenter study of NRG1 fusions in Chinese non-small cell lung cancer patients and response to afatinib using next generation sequencing
Authors: X. Li, W. Wang, C. Xu, X. Pu, S. Fang, X. Cai, Y. Fang, Y. Zhu, H. Wang, X. Liang, W. Zhuang, Y. Zhang, L. Wang, X. Cai, J. Li, H. Feng, M. Fang, G. Chen, T. Lv, Y. Song
Journal: Annals of Oncology (2019)
Are allergens more abundant and/or more stable than other proteins in pollens and dust?
Authors: Aurora Cabrera, Thomas A. Randall, Ryenne N. Ogburn, Betelihem Mebrahtu, Julia H. R. Johnson, Alexander C. Y. Foo, Michael C. Fitzgerald, Geoffrey A. Mueller
Journal: Allergy (2019)

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Development of Novel Second Generation DC/Tumor Fusion Vaccine in Lymphoma
Authors: Shira Orr, Marzia Capelletti, Haider Ghiasuddin, Dina Stroopinsky, Jessica Liegel, Myrna Nahas, Matthew Weinstock, Adam Morin, Robin M. Joyce, Salvia Jain, Jon E. Arnason, Maryam Rahimian, Lina Bisharat, Shufen Meng, Donald Kufe, Jacalyn Rosenblatt, David E. Avigan
Journal: Blood (2019)
Ketogenic Diets for Diabetes and Obesity
Authors: Frederick M. Hecht
Journal: JAMA Internal Medicine (2019)

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Author Correction: Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers
Authors: Aparna R. Parikh, Ignaty Leshchiner, Liudmila Elagina, Lipika Goyal, Chaya Levovitz, Giulia Siravegna, Dimitri Livitz, Kahn Rhrissorrakrai, Elizabeth E. Martin, Emily E. Van Seventer, Megan Hanna, Kara Slowik, Filippo Utro, Christopher J. Pinto, Alicia Wong, Brian P. Danysh, Ferran Fece de la Cruz, Isobel J. Fetter, Brandon Nadres, Heather A. Shahzade, Jill N. Allen, Lawrence S. Blaszkowsky, Jeffrey W. Clark, Bruce Giantonio, Janet E. Murphy, Ryan D. Nipp, Eric Roeland, David P. Ryan, Colin D. Weekes, Eunice L. Kwak, Jason E. Faris, Jennifer Y. Wo, François Aguet, Ipsita Dey-Guha, Mehlika Hazar-Rethinam, Dora Dias-Santagata, David T. Ting, Andrew X. Zhu, Theodore S. Hong, Todd R. Golub, A. John Iafrate, Viktor A. Adalsteinsson, Alberto Bardelli, Laxmi Parida, Dejan Juric, Gad Getz, Ryan B. Corcoran
Journal: Nature Medicine (2019)
Is allergy immunotherapy with birch sufficient to treat patients allergic to pollen of tree species of the birch homologous group?
Authors: Jörg Kleine‐Tebbe, Torsten Zuberbier, Thomas Werfel, Matthias Krüll, Martin Wagenmann, Niels Johansen, Peter Adler Würtzen, Hendrik Wolf, Victoria Mücke, Eike Wüstenberg, Tilo Biedermann
Journal: Allergy (2019)

Pollen from various Fagales tree species prolongs the season and makes tree pollen allergy a major health problem. Despite involving the same causative allergens, allergy immunotherapy (AIT) treatment habits differ significantly across different geographical regions. Diagnosis and treatment with AIT in patients allergic to tree pollen were discussed by a group of German medical experts who give practical recommendations based on the available data. Regulatory perspective: According to current guidelines on allergen products, birch pollen are the representative allergen source of the birch homologous group including several Fagales trees based on sequence and structural similarity of their allergen proteins. Immunological perspective: A high level of IgE cross-reactivity towards allergens from the birch homologous group has been observed in basic research and clinical trials. Clinical perspective: Clinical trial data show that the efficacy of birch pollen AIT is not only related to birch pollen allergy but extends to pollen from other trees, especially alder, hazel and oak. In order to optimize diagnosis and treatment of tree pollen allergy, the experts recommend to focus diagnosis and respective treatment with AIT primarily to birch as the representative allergen of the Fagales tree homologous group, but further diagnostics may be needed for some patients to determine adequate treatment.
Non-causal association of gut microbiome on the risk of rheumatoid arthritis: a Mendelian randomisation study
Authors: Jun Inamo
Journal: Annals of the Rheumatic Diseases (2019)

I read with great interest the article by Alpizar-Rodriguez et al regarding the risk of intestinal dysbiosis, particularly Prevotella spp enrichment, in preclinical rheumatoid arthritis (RA).1 Immune response in gut is assumed to be one of the triggers of development of RA.2 However, it is hard to assess causal association by case–control study due to limitations such as latent confounding factors; dysbiosis first or RA first . Therefore, to investigate causal effect of gut microbiome on the development of RA, I conducted Mendelian randomisation (MR) analysis.3 MR is useful to investigate causal association among phenotypes and/or biomarkers because it is based on genetic variation to mimic the design of randomised controlled trials. In MR, single nucleotide polymorphisms (SNP) are expected to be random and causally upstream of the exposure; thus, SNP are used as instrumental variables (IVs) in MR.

I used the publicly available two data sets of genome-wide association studies (GWASs) for gut microbiome (totally 3326 individuals) of European ancestry as the exposure4 5 and one data set …
Charles Jencks: architectural historian, landscape architect, and co-founder of Maggie’s Centres
Authors: Rebecca Wallersteiner
Journal: BMJ (2019)

Photo credit: Maggie Cancer Care Centres

Charles Jencks, landscape architect, critic, and author of 30 books on architectural history, who co-founded Maggie’s Centres to offer support to people with cancer, has died at his home in London at the age of 80.

Born in Baltimore, Maryland, USA, Charles Jencks was the son of composer Gardner Platt Jencks and his wife, Ruth (nee DeWitt Pearl). His family had made its fortune from safety deposit boxes. The studious young Jencks was educated at Brooks School in North Andover, Massachusetts, and read English at Harvard, staying on to do a masters in architecture at the Harvard Graduate School of Design, in 1965. That year, he came to London on a Fulbright scholarship and took a doctorate in architectural history at University College London under the radical modernist historian Reyner Banham, from whom he said he “learnt much.”

After the news of Jencks’s death, his friend and collaborator, architect Norman Foster, paid tribute, describing him as “a doyen of architectural criticism,” and said that he would always remember him for his “incisive focus and infectious humour” in co-founding the Maggie Cancer Care Centres and for “turning a personal tragedy into an institution that brings so much hope to so many people.”

Maggie’s chief executive, Laura Lee, said, “It’s hard to come to terms with Charles not being here as he has played a pivotal part in developing Maggie’s vision to offer support for people with cancer and turning that vision into a reality. Over the past 23 years, his passion, drive, and imagination meant that leading architects from across the world came to build these extraordinary centres, places that have benefited thousands of people with cancer, both in the UK and abroad. I know Charles will be remembered for his many talents, but for me, …
Results of PAC203: A Randomized Phase 2 Dose-Finding Study and Determination of the Recommended Dose of Pacritinib
Authors: Aaron T. Gerds, Michael R. Savona, Bart L. Scott, Moshe Talpaz, Miklos Egyed, Claire N Harrison, Abdulraheem Yacoub, Alessandro M. Vannucchi, Adam J. Mead, Jennifer O'Sullivan, Sarah A Buckley, Diane R. Mould, Shanthakumar Tyavanagimatt, Jennifer A. Smith, John Mascarenhas
Journal: Blood (2019)