tbuckley/cabot-search huggingface dataset:
Halo 110-101: Early safety results of pegvorhyaluronidase alfa (PEGPH20; PVHA) + cisplatin (C) + gemcitabine (G) ± atezolizumab (ATZ) in patients (pts) with locally advanced or metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GBC).
Authors: Do-Youn Oh, Mann Muhsin, Andrea J. Bullock, Ghassan K. Abou-Alfa, Rachna T. Shroff, Darren Sigal, Vincent Chung, J. Randolph Hecht, Wilson Wu, Mitesh J. Borad
Journal: Journal of Clinical Oncology (2019)

408 Background: Standard of care for CCA/GBC is C-G therapy. MAbs (ATZ, pembrolizumab) targeting PD-L1 show promise in treating CCA/GBC. Hyaluronan (HA), which may impede drug and immune cell access, is high (67%) in CCA/GBC tumors. PEGPH20 enzymatically degrades HA. HALO 110-101 (NCT03267940) evaluates safety and activity of PEG-C-G-ATZ or PEG-C-G versus C-G in CCA/GBC pts. Methods: This study comprises two parts. In Run-In (RI) six pts were enrolled in PEG-C-G arm, then six pts in PEG-C-G-ATZ arm. Eight additional pts may be enrolled for tolerability. In Expansion (EX), up to 50 pts will be enrolled for efficacy. Treatment (Tx) cycle is 21 days (d). PEGPH20 dose is 3 μg/kg on d1, eight and 15 and ATZ dose is 1200 mg (one–three hours after PEGPH20) on d1 (PEG-C-G-ATZ only). C-G is dosed at 25 mg/m 2 C and 1000 mg/m 2 G on d2 and nine. In C-G arm (EX only), C-G is dosed on d1 and 8. Primary endpoints are ORR (RECIST v1.1), AEs (NCI CTCAE v4.03), laboratory/safety (RI only); secondary endpoints are PK; DOR, DCR, PFS; OS, OS by PD-L1 expression; ORR and DOR (imRECIST). Results: Eighteen pts have been enrolled (nine in each arm). The mean (SD) age is 57 (12.2) yrs in PEG-C-G and 69 (8.8) yrs in PEG-C-G-ATZ. 56% were men. All pts experienced ≥ 1 AE. The most common AEs are nausea, fatigue (50% each); decreased appetite (44%); anemia, constipation (39% each); thrombocytopenia, oedema peripheral, AST increased, myalgia (33% each). To date, there has been one dose-limiting toxicity (febrile neutropenia) in the PEG-C-G arm. There have been no deaths due to AEs. Conclusions: The overall safety profile of PEGPH20 + C + G ± ATZ is acceptable and consistent with safety observed for the individual components. There were no DLTs resulting in a dose reduction of PEGPH20, which is being dosed at 3 μg/kg in the EX phase. Clinical trial information: NCT03267940. [Table: see text]
Abstract 1440: Platelet Response to Aspirin is Under Polygenic Control of Variants in the VAV3 and Phospholipase C Gamma 2 (PLCG2) Genes
Authors: J. E Herrera, Rehan Qayyum, Nauder Faraday, Lisa R Yanek, Dhananjay Vaidya, Diane M Becker, Lewis C Becker
Journal: Circulation (2008)

Background: VAV3 (a guanine nucleotide exchange factor) and PLCG2 (phospholipase Cγ2) participate in platelet activation via outside-in signaling mediated by integrin receptor αIIbβ3. VAV3 plays a ...
Abstract 9419: Clinical Impact of Incidental Findings Detected on Computed Tomography in Patients Evaluated for Transcatheter Aortic Valve Replacement
Authors: Nicholas M Orme, Thomas C Wright, Gil E Harmon, Vuyisile T Nkomo, Eric E Williamson, Paul Sorajja, Thomas A Foley, Kevin L Greason, Rakesh M Suri, Charanjit S Rihal, Phillip M Young
Journal: Circulation (2013)

Background: Patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR) undergo aortoiliac computed tomographic angiography (CTA) of the chest/abdomen/pelvis. Despite the increasing number of TAVR procedures worldwide, little is known regarding the clinical significance of non-cardiovascular incidental findings (IFs) on TAVR-CTA scans. Objective: To determine the frequency, clinical significance and impact on survival of non-cardiovascular IFs detected on TAVR-CTA scans. Methods: CTA studies for 424 consecutive patients being evaluated for TAVR were reviewed for non-cardiovascular IFs (62% male, median age 82±8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival. Results: An IF was present in nearly all patients (99%). The mean number of IFs per patient was 5.3 (±2.8; range 0-14). After excluding obviously benign IFs, 67% had at least one potentially pathologic IF (mean 1.1±1.0). Factors associated with higher numbers of IFs were age (p&lt;0.0001) and use of IV contrast (p=0.03). IFs prompted clinical work-up in 39 patients (9.2%) and delayed or cancelled procedures in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of IFs was predictive of poor overall survival before (HR 1.09; 95% CI (1.02 to 1.70), p=0.02) and after adjustment for baseline clinical variables (HR 1.07; (1.0 to 1.15); p=0.04). Conclusions: This investigation demonstrates that IFs are present in nearly all TAVR-CTA scans, commonly require further clinical evaluation, and are associated with poorer survival. TAVR institutions should have mechanisms in place to ensure communication and follow-up of IFs.
Minimal Residual Disease (MRD) Analysis Using Multiparametric Flow Cytometry (MFC) and Identification of Differences in Subpopulations Using Next Generation Sequencing (NGS) in the Bone Marrow (BM) of Multiple Myeloma (MM) Patients (pts)
Authors: Sandra M. Dold, Veronika Riebl, Dagmar Wider, Marie Follo, Stefan J. Mueller, Ingrid Bartsch, Milena Pantic, Cornelius Miething, Chrissoula Kiote-Schmidt, K. Martin Kortüm, Mihaela Zlei, Abdel Kareem Azab, Mascha Binder, Justyna Rawluk, Justus Duyster, Robert Zeiser, Ralph Wäsch, Monika Engelhardt
Journal: Blood (2018)
Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk Five Study
Authors: Kwee Yong, Samantha Hinsley, Debbie Sherratt, Jessica Kendall, Sarah R Brown, Louise Flanagan, Catherine Williams, Jamie Cavenagh, Martin Kaiser, Neil K Rabin, Karthik Ramasamy, Mamta Garg, Holger W. Auner, Stephen F. Hawkins, Ceri Bygrave, Ruth M De Tute, Gareth Morgan, Faith E. Davies, Roger G. Owen
Journal: Blood (2018)
Rapidly Evolving Extensive Fluorodeoxyglucose-Positive Soft-Tissue Activity During Nivolumab Therapy
Authors: Joanna Mangana, Caroline S. Buset, Reinhard Dummer
Journal: JAMA Oncology (2019)

A 41-year-old woman with stage IIa melanoma of the upper thigh presented with diffuse erythematous induration of the upper thigh expanding to the lower left abdominal area and palpable subcutaneous nodules on the ipsilateral gluteal region and leg during nivolumab therapy. What is your diagnosis?
Recent strategies on targeted delivery of thrombolytics
Authors: Ting Huang, Ni Li, Jianqing Gao
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Thrombus formed in blood vessel is a progressive process, which would lead to life-threatening thrombotic diseases such as ischemic stroke. Unlike other diseases, the recognition of thrombus is usually in the late stage where blood vessels are largely blocked. So acute thrombotic diseases have a narrow therapeutic window, and remain leading causes of morbidity and mortality, whereas current thrombolysis therapy has limited therapeutic effects and bleeding complications. Thrombolytic agents in unwanted sites would cause hemorrhage due to the activation of plasminogen. Moreover, untargeted thrombolysis therapy require large amounts of thrombolytic agents, which in return would enhance hemorrhage risk. To improve the efficiency while minimizing the adverse effects of traditional thrombolysis therapy, novel drug delivery systems have been investigated. Various targeting strategies including ultrasound and magnetic field directed targeting, and specific binding, have been designed to deliver thrombolytic drugs to the thrombotic sites. These strategies demonstrate promising results in reducing bleeding risk as well as allowing less dosage of thrombolytic drugs with lowered clot lysis time. In this review, we discuss recent progress on targeted delivery of thrombolytics, and summarize treatment advantages and shortcomings, potentially helping to further promote the development of targeted thrombolysis.
Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization
Authors: Jinxuan Zhao, Xueling Li, Jiaxin Hu, Fu Chen, Shuaihua Qiao, Xuan Sun, Ling Gao, Jun Xie, Biao Xu
Journal: Cardiovascular Research (2019)

Mesenchymal stromal cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischaemia/reperfusion (I/R) and its implications in cardiac injury repair. Exosomes were isolated from the supernatant of MSCs using gradient centrifugation method. Administration of MSC-Exo to mice through intramyocardial injection after myocardial I/R reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and toll-like receptor 4 (TLR4) as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial I/R. Our data indicate that MSC-Exo attenuates myocardial I/R injury in mice via shuttling miR-182 that modifies the polarization status of macrophages. This study sheds new light on the application of MSC-Exo as a potential therapeutic tool for myocardial I/R injury.
Abstract 17835: Femoral Artery Temperatures Are Associated With the Extent of Coronary Artery Disease
Authors: Georgios Benetos, Konstantinos Toutouzas, Georgios Oikonomou, Rafail Kotronias, Iosif Koutagiar, Spyros Galanakos, Fotini Mitropoulou, Eleftherios Tsiamis, Elias Siores, Dimitris Tousoulis
Journal: Circulation (2017)

Introduction: Femoral and carotid atherosclerotic plaques can both accurately predict the presence of coronary artery disease. The correlation, however, of femoral artery inflammation with coronary...
Abstract 18100: Altered Placental Bold Signal is Associated With Reduced Fetal Brain Functional Connectivity in Congenital Heart Disease
Authors: Vidya Rajagopalan, Vincent K Lee, William Reynolds, Alex El-Ali, Jenna Schabdach, Julia Wallace, Alexandria Zahner, Rafael Ceschin, Jodie Votava-Smith, Jacqueline Weinberg, Vincent J Schmithorst, Ashok Panigrahy
Journal: Circulation (2017)

Introduction: Fetal brain dysmaturation in congenital heart disease (CHD) has been linked to reduced oxygenation. Placental blood oxygen level dependent (BOLD) MRI measures placental oxygenation and vascularity in utero. Hypothesis: We tested the hypothesis that altered intrinsic placental BOLD signal would be predictive of reduced resting state brain networks (RSN) in fetuses with CHD compared to healthy controls. Methods: Dedicated placental and fetal BOLD MR imaging on 23 CHD and 52 healthy control maternal participants were obtained. Temporal variance in BOLD signal between CHD and Controls were compared, including histogram-based distribution difference analyses were conducted using Kolmogorov-Smirnov (KS) test. Parametric mapping was used to characterize placental spatial variance. Fetal brain BOLD was corrected for motion artifact and analyzed using ICA for RSN. Results: Placental BOLD demonstrated higher temporal variance, increased kurtosis (p<0.010) in fetuses with CHD compared to controls. CHD ...
Phase I/II Study of Escalating Doses of Thalidomide in Conjunction with Bortezomib and High Dose Melphalan As a Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma
Authors: Noa Biran, Shijia Zhang, Scott D. Rowley, David H. Vesole, Michele L. Donato, Alan P Skarbnik, Joshua R Richter, Andrew L. Pecora, David S Siegel
Journal: Blood (2018)
Effect of FOLFIRINOX with PEG-G-CSF for unresectable/recurrent pancreatic cancer.
Authors: Ichiro Moriyama, Hiroki Sonoyama, Yasunari Kawabata, Fumiyoshi Ikejiri, Masaya Inoue, Fumimasa Takahashi, Shinichiro Matsuda, Norimi Ugata, Yasumasa Shimasaki, Ayumi Fujimoto, Yusuke Okada, Shunsuke Ito, Takahiro Okada, Yumi Jo, Tsutomu Takahashi, Takaaki Miyake, Tatsuo Kodama, Ritsuro Suzuki, Yoshitsugu Tajima, Junji Suzumiya
Journal: Journal of Clinical Oncology (2019)

411 Background: FOLFIRINOX (FFX) is a standard therapy for unresectable/recurrent pancreatic cancer, but it is associated with a high frequency of severe adverse events, especially blood toxicity. Human pegylated granulocyte colony-stimulating factor (PEG-G-CSF) can reduce the outpatient frequency during outpatient chemotherapy. However, there are few reports on the effectiveness of PEG-G-CSF in preventing febrile neutropenia during FFX. We retrospectively investigated the usefulness of PEG-G-CSF in reducing the incidence of FN during FFX. Methods: From June 2014 to January 2017, 40 patients with unresectable pancreatic cancer received FFX (including modified FFX) at our hospital. Twenty-three patients were administered PEG-G-CSF as primary/secondary preventive therapy (G group) and 17 were not administered any G-CSF (NG group). Results: The median patient ages in the G and NG groups were 65 (range, 48-78) and 63 (range, 42-81) years, respectively, and the male to female ratios were 13:10 and 11:6, respectively. There were 13 and 10 patients, respectively, in the G group with performance statuses of 0 and 1 and 8 and 9 such patients, respectively, in the NG group. Seventeen and five patients in the G and NG groups, respectively, had metastatic disease and six and two patients, respectively, had locally advanced disease. The respective response rates (RRs) in the G and NG groups were 30% and 6% (p = 0.0608), and the respective disease control rates (DCRs) were 30% and 41% (p = 0.0407). The median progression-free survivals in the G and NG groups were 7.3 (95% confidence interval [CI], 3–9.4) and 4.5 (95% CI, 1.9–8.5) months, respectively (p = 0.173), and the respective overall survivals were 16.9 (95% CI, 10.2–NA) and 14.2 (95% CI, 7.8–20.5) months (p = 0.302). Conclusions: The DCR was significantly greater in the G group than in the NG group, and the RR tended to be greater in the G group than in the NG group. A high tumor shrinking effect of FFX with PEG-G-CSF indicated that it might be useful as a neoadjuvant chemotherapy. A prospective study is needed to examine first-line chemotherapy in unresectable/recurrent pancreatic cancer and neoadjuvant chemotherapy in borderline/locally advanced pancreatic cancer.
Variable 131I Activity in Multiple Hepatic Cysts in a Patient With Thyroid Cancer
Authors: Fuqiang Shao, Jiali Tang, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2019)

Abstract Various etiologies could cause focal 131 I accumulation. Hepatic cyst is one of these etiologies. Here we present a 59-year-old man with a history of papillary thyroid cancer resection who received radioiodine therapy for three times. The images after the 131 I therapy of the second and third time showed variable activity uptake in the same hepatic cysts.
Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5
Authors: Sandy Giuliano, Maeva Dufies, Papa Diogop Ndiaye, Julien Viotti, Delphine Borchiellini, Julien Parola, Valérie Vial, Yann Cormerais, Mickaël Ohanna, Véronique Imbert, Emmanuel Chamorey, Nathalie Rioux-Leclercq, Ariel Savina, Jean-Marc Ferrero, Baharia Mograbi, Gilles Pagès
Journal: Theranostics (2019)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Resistance to lysosomotropic drugs used to treat kidney and breast cancers involves autophagy and inflammation and converges in inducing CXCL5
Characterization Of Allergen Sensitization Patterns In Canadian Preschool Children With Severe Wheezing
Authors: Jennifer A. Hoang, Pouria Mashouri, Vera Dai, May Brydges, Aimée Dubeau, Claire Lépine, Xiaojun Yin, Krzysztof Kowalik, Stephanie DeLorenzo, Theo Moraes, Reshma Amin, Indra Narang, Kathy Boutis, Suzanne Schuh, Geoffrey N. Maksym, Arun Ramani, Padmaja Subbarao, Thomas Eiwegger
Journal: Journal of Allergy and Clinical Immunology (2019)
Increased Methamphetamine, Injection Drug, and Heroin Use Among Women and Heterosexual Men with Primary and Secondary Syphilis — United States, 2013–2017
Authors: Sarah E. Kidd, Jeremy A. Grey, Elizabeth A. Torrone, Hillard S. Weinstock
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During 2013-2017, the national annual rate of reported primary and secondary (P&S) syphilis cases in the United States increased 72.7%, from 5.5 to 9.5 cases per 100,000 population (1). The highest rates of P&S syphilis are seen among gay, bisexual, and other men who have sex with men (collectively referred to as MSM) (2), and MSM continued to account for the majority of cases in 2017 (1). However, during 2013-2017, the P&S syphilis rate among women increased 155.6% (from 0.9 to 2.3 cases per 100,000 women), and the rate among all men increased 65.7% (from 10.2 to 16.9 cases per 100,000 men), indicating increasing transmission between men and women in addition to increasing transmission between men (1). To further understand these trends, CDC analyzed national P&S syphilis surveillance data for 2013-2017 and assessed the percentage of cases among women, men who have sex with women only (MSW), and MSM who reported drug-related risk behaviors during the past 12 months. Among women and MSW with P&S syphilis, reported use of methamphetamine, injection drugs, and heroin more than doubled during 2013-2017. In 2017, 16.6% of women with P&S syphilis used methamphetamine, 10.5% used injection drugs, and 5.8% used heroin during the preceding 12 months. Similar trends were seen among MSW, but not among MSM. These findings indicate that a substantial percentage of heterosexual syphilis transmission is occurring among persons who use these drugs, particularly methamphetamine. Collaboration between sexually transmitted disease (STD) control programs and partners that provide substance use disorder services will be important to address recent increases in heterosexual syphilis.
Abstract #2701: Effects of paeoniflorin, baicalein, hesperidin and oleanolic acid on human breast and prostate cancer cells
Authors: Choong Jae Lee, Mary Ann Jordan, Leslie Wilson, Su Yel Lee, Mi Nam Lee
Journal: Cancer Research (2009)

Several herbal medicines were used as folk medicines for controlling breast and prostate cancer in traditional oriental medicine. To elucidate the pharmacological actions and mechanisms of action of those herbal medicines and their major components, in the present study, we investigated whether natural products including paeoniflorin, bacalein, hesperidin and oleanolic acid affect proliferations of MCF-7 human breast cancer cells transfected with green fluorescent protein (GFP)/\#945;-tubulin (MCF7-GT), and LNCaP, PC-3 and DU-145 prostate cancer cells. The results were as follows: (1) Oleanolic acid inhibited proliferations of MCF7-GT, LNCaP, PC-3 and DU-145 cells; (2) Baicalein and hesperidin inhibited proliferations of MCF7-GT and LNCaP cells; (3) Paeoniflorin did not affect proliferations of MCF7-GT, LNCaP, PC-3 and DU-145 cells, even at 100 microM; (4) All the four natural compounds did not affect mitotic division of MCF7-GT cells. We conclude that oleanolic acid, hesperidin and baicalein do not show anti-mitotic mechanism in inhibiting proliferation of breast cancer cells and they should be investigated for the potential interaction with androgenic receptors and involvement in signaling pathway after receptor binding in prostate cancer cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2701.
Abstract 17164: The Pentameric Form of Phospholamban is Important for the Regulation of Phospholamban Phosphorylation and Function
Authors: Tanja Wittmann, Martin J. Lohse, Joachim P. Schmitt
Journal: Circulation (2013)

Phospholamban (PLN) regulates myocyte calcium cycling by inhibiting the Ca2+ATPase SERCA2a. Protein kinase A (PKA) mediated phosphorylation attenuates PLN activity leading to enhanced calcium uptake rates and accelerated cardiac relaxation. In vivo, PLN is present in monomeric and pentameric form. It is believed that PKA primarily targets the PLN monomer. However, we found that a R9C mutant of PLN dominantly inhibits PLN phosphorylation only within the pentamer suggesting a significant role of the pentamer in determining phosphorylation and, thus, PLN activity. To investigate the role of the pentamer in PLN phosphorylation and function, the sensitivity, kinetics and stoichiometry of phosphorylation were analyzed in monomeric and pentameric PLN mutants expressed in a human cell line (HEK293AD). We found an independent increase of phosphorylation for monomer and pentamer upon forskolin stimulation, both in a concentration and time-dependent manner. Intriguingly, phosphorylation signals of PLN pentamers incr...
Patients believe that cosmetic procedures affect their quality of life: An interview study of patient-reported motivations
Authors: Abigail Waldman, Amanda Maisel, Alexandra Weil, Sanjana Iyengar, Kaitlyn Sacotte, Jake M. Lazaroff, Sasha Kurumety, Sara L. Shaunfield, Kelly A. Reynolds, Emily Poon, June K. Robinson, Murad Alam
Journal: Journal of the American Academy of Dermatology (2019)
Isavuconazole in Hematological Patients: Results of a Real-Life Multicenter Seifem Study
Authors: Chiara Cattaneo, Doriana Gramegna, Alessandro Busca, Valentina Mancini, Chiara Pagani, Katia Perruccio, Rosa Fanci, Monica Piedimonte, Stelvio Ballanti, Angelica Spolzino, Marianna Criscuolo, Anna Candoni, Gianpaolo Nadali, Nicola Fracchiolla, Francesco Marchesi, Margherita Sciumé, Mario Tumbarello, Franco Aversa, Giuseppe Rossi, Livio Pagano
Journal: Blood (2018)
Characteristics, Social Factors, and Trends in HIV and AIDS-Related Lymphoma: A 23-Year Analysis Since the Implementation of c ART, a County Hospital AIDS Malignancy Project (CHAMP) Study
Authors: Camille E. Demarco, Pei Lu, David F. Peace, Sunny Singh, Dennis F. Angelov, Kelly A. Benante, Ahmed T. Ahmed, Paul G. Rubinstein
Journal: Blood (2018)
Macrophage cell tracking PET imaging using mesoporous silica nanoparticles via in vivo bioorthogonal F-18 labeling
Authors: Hyeon Jin Jeong, Ran Ji Yoo, Jin Kwan Kim, Min Hwan Kim, Su Hong Park, Haebin Kim, Jae Wook Lim, Sun Hee Do, Kyo Chul Lee, Yong Jin Lee, Dong Wook Kim
Journal: Biomaterials (2019)