tbuckley/cabot-search huggingface dataset:
Uterine Cancer: Adjuvant Therapy and Management of Metastatic Disease
Authors: Carien L. Creutzberg, Karen H. Lu, Gini F. Fleming
Journal: Journal of Clinical Oncology (2019)

Article Tools REVIEW ARTICLES Gynecologic Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.19.00037 Journal of Clinical Oncology - published online before print August 12, 2019 PMID: 31403860 Uterine Cancer: Adjuvant Therapy and Management of Metastatic Disease Carien L. Creutzberg, MD, PhD1xCarien L. CreutzbergSearch for articles by this author; Karen H. Lu, MD2xKaren H. LuSearch for articles by this author; and Gini F. Fleming, MD3xGini F. FlemingSearch for articles by this author Show More 1Leiden University Medical Center, Leiden, the Netherlands2University of Texas MD Anderson Cancer Center, Houston, TX3University of Chicago Medical Center, Chicago, IL https://doi.org/10.1200/JCO.19.00037 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology
Immunodepletion of MDSC By AMV564, a Novel Tetravalent Bispecific CD33/CD3 T Cell Engager Restores Immune Homeostasis in MDS in Vitro
Authors: Pingyan Cheng, Erika Eksioglu, Xianghong Chen, Max Wei, Jeanmarie Guenot, Judy Fox, Alan F List, Sheng Wei
Journal: Blood (2017)
Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution
Authors: Vaia Florou, Andrew E. Rosenberg, Eric Wieder, Krishna V. Komanduri, Despina Kolonias, Mohamed Uduman, John C. Castle, Jennifer S. Buell, Jonathan C. Trent, Breelyn A. Wilky
Journal: Journal for ImmunoTherapy of Cancer (2019)

Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas.We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue.We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities.This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.
Improving the estimation of the global burden of antimicrobial resistant infections
Authors: Direk Limmathurotsakul, Susanna Dunachie, Keiji Fukuda, Nicholas A Feasey, Iruka N Okeke, Alison H Holmes, Catrin E Moore, Christiane Dolecek, H Rogier van Doorn, Nandini Shetty, Alan D Lopez, Sharon J Peacock
Journal: The Lancet Infectious Diseases (2019)
Role of Asparagine Endopeptidase in Mediating Wild-Type p53 Inactivation of Glioblastoma
Authors: Yingying Lin, Keman Liao, Yifeng Miao, Zhongrun Qian, Zhaoyuan Fang, Xi Yang, Quanmin Nie, Gan Jiang, Jianhua Liu, Yiyi Yu, Jieqing Wan, Xiaohua Zhang, Yaomin Hu, Jiyao Jiang, Yongming Qiu
Journal: JNCI Journal of the National Cancer Institute (2019)

Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood.We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients' specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6-8 per group). The statistical significance between groups was determined using two-tailed Student t tests.We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery.Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM.
Variability in Opioid-Prescribing Patterns in Endocrine Surgery and Discordance With Patient Use
Authors: Elizabeth Lancaster, Christina Inglis-Arkell, Kenzo Hirose, Carolyn D. Seib, Elizabeth Wick, Julie A. Sosa, Quan-Yang Duh
Journal: JAMA Surgery (2019)

Variability in Opioid-Prescribing Patterns in Endocrine Surgery and Discordance With Patient UsePrescription opioid abuse has become a considerable problem in the United States, with prevalence increasing over the last 2 decades. 1 Overprescription of opioid medications contributes to the epidemic of prescription opioid abuse, with less than 40% of prescribed pills actually being used by patients. 2ecent studies have found that the quantity of opioids prescribed varied significantly by clinician for the same operation within the same institution. 1,3Factors contributing to overprescription of opioids include a deficiency of standardized prescribing guidelines for patients after surgery and a lack of prescriber education around options for nonopioid pain medications.The goal of this study was to develop patient-centered analgesia-prescribing practices for patients who had undergone endocrine surgery.We hypothesized that current prescribing practices at the study institution were variable and poorly reflected actual patient needs.
Abstract 19637: Two Decades of Cardiovascular Trials With Primary Surrogate Endpoints: 1990- 2011
Authors: Behnood Bikdeli, Natdanai Punnanithinont, Yasir Akram, Ike Lee, Nihar R Desai, Joseph S Ross, Harlan M Krumholz
Journal: Circulation (2015)

Background: Surrogate endpoint trials can test strategies more efficiently, but are accompanied by uncertainty about the relationship between changes in surrogate markers and clinical outcomes. We sought to determine recent trends in the publication of cardiovascular trials with surrogate outcomes. Methods: We identified cardiovascular trials with primary surrogate endpoints published in NEJM, Lancet, and JAMA from January 1990 to December 2011. Trends in publication of surrogate endpoint trials, and the success of the trials in meeting their primary endpoint were evaluated. We also tracked the above three journals for publication of clinical outcome trials on the interventions tested in surrogate trials. Results: We screened 3016 articles and identified 848 primary hypothesis cardiovascular trials, which included 220 surrogate endpoint trials. There was an increase over time in the number of surrogate endpoint trials (P=0.01). From the total of 220 surrogate trials, 157 (71.4 %) were positive for their primary endpoint. Sixty (27.5%) surrogate trials were followed by at least one clinical outcome trial. Among these 60 surrogate trials, in 24 cases the outcomes trial results validated the positive surrogates; whereas in 21 subsequent outcome trials were negative following positive results on a surrogate. However, we identified only 3 examples in which the surrogate trial was negative but a subsequent outcomes trial was conducted and showed benefit (Figure). Conclusions: Cardiovascular surrogate outcomes trials are common, frequently show superiority of the tested intervention and are infrequently followed by a prominent outcomes trial. However, when there was a high profile clinical outcomes study, half of the positive surrogate trials were not validated. Cardiovascular surrogate outcome trials may be more appropriate for excluding benefit from the patient perspective than for identifying it.
Conservative and functional surgery in the treatment of salivary gland tumours
Authors: Guangyan Yu, Xin Peng
Journal: International Journal of Oral Science (2019)

The principle of modern oncological surgery is to conserve the functional organs or tissues as much as possible based on eradication of the tumour. For salivary gland tumours, conservative and functional salivary surgery, including partial sialoadenectomy as well as anatomical and functional preservation of the facial nerve, great auricular nerve, superficial musculo-aponeurotic system (SMAS), and Stensen’s duct, has become increasingly popular. In the present review, we discuss the following aspects of conservative and functional surgery in the treatment of salivary gland tumours: (i) partial superficial parotidectomy (PP) to treat benign parotid gland tumours, (ii) modification of surgical incisions to improve cosmetic results, (iii) modification of the surgical approach to decrease complications, (iv) extracardial dissection to treat benign superficial parotid tumours, (v) partial sialoadenectomy to treat benign submandibular gland tumours, and (vi) 125I brachytherapy to preserve facial nerves. The majority of the operated parotid or submandibular glands are preserved, and surgical complications are also decreased. Conservative and functional surgery plays a significant role in maintaining normal salivary gland function and in improving patients’ quality of life during the treatment of salivary gland tumours and thus should be further promoted.
The time to relapse correlates with the histopathological growth pattern in nodular lymphocyte predominant Hodgkin lymphoma
Authors: Sylvia Hartmann, Annette Plütschow, Anja Mottok, Heinz‐Wolfram Bernd, Alfred C. Feller, German Ott, Sergio Cogliatti, Falko Fend, Leticia Quintanilla‐Martinez, Harald Stein, Wolfram Klapper, Peter Möller, Andreas Rosenwald, Andreas Engert, Martin‐Leo Hansmann, Dennis A. Eichenauer
Journal: American Journal of Hematology (2019)

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first-line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies. Among the 33 GHSG patients, 21 patients presented with a typical growth pattern at initial diagnosis, whereas 12 patients had a variant histology. The histopathological growth patterns at initial diagnosis and at relapse were consistent in 67% of cases. A variant histology at initial diagnosis was associated with a shorter median time to lymphoma recurrence (2.8 vs 5.2 years; P = .0219). A similar tendency towards a shorter median time to lymphoma recurrence was observed for patients presenting with a variant histology at relapse, irrespective of the growth pattern at initial diagnosis. Results obtained from the 41 NLPHL patients who had been treated outside GHSG studies were comparable (median time to lymphoma recurrence for variant histology vs typical growth pattern at initial diagnosis: 1.5 vs 7.0 years). In conclusion, the histopathological growth pattern remains consistent at relapse in the majority of NLPHL cases, and has major impact on the time of relapse.
BCL3 and NSCLC: Are they related?
Authors: Fotinos-Ioannis D Dimitrakopoulos, Anastasia E Kottorou, Anna G Antonacopoulou, Stella Marousi, Ioulia Koukourikou, Chrisoula D Scopa, Dimitrios Dougenis, Helen Papadaki, Haralabos Kalofonos
Journal: Journal of Clinical Oncology (2013)

e18507 Background: NFkB pathways have become objects of detailed research in the last years, although, little is known of the possible role of BCL3 in lung carcinogenesis. The aim of this study was to define the relation of the BCL3 single nucleotide polymorphism rs8100239 with NSCLC and its association with BCL3 protein expression. Methods: Using Tagger and Sysnps programs, we chose the rs8100239 polymorphism of BCL3.We used 294 blood and FFPE normal tissue specimens from patients with NSCLC and 280 blood specimens from healthy donors. DNA isolation was performed using the Qiagen DNA blood and the QIAamp DNΑ FFPE Tissue kits. Samples were genotyped using real-time PCR. Immunohistochemical analysis for BCL3 was performed on 90 FFPE specimens (80 tumors and 10 tumor-adjacent normal tissues) from NSCLC patients. Results: Approximately half of the healthy donors (45.5%) were AT heterozygotes, 36.6% were TT and 17.9% were AA homozygotes. The respective frequencies in patients were 43.8%, 33.1% and 23.1%. There was no statistically significant difference in allele frequencies between healthy controls and patients (p=0.297). However, patients of stage II carrying a T allele displayed two and five-year survival benefit compared to patients with AA genotype (p&lt;0.001). Immunohistochemical analysis for BCL3 protein revealed a statistically significant difference between malignant and normal lung tissue (p&lt;0.001). More specifically, BCL3 was detected in both the cytoplasm and nucleus in neoplastic tissues with strong intensity, whereas in non neoplastic tissue no immunostaining was noticed. BCL3 protein levels were not associated with the polymorphism. However, cytoplasmic expression of BCL3 was correlated with age (p=0.009), histological subtype (p=0.031) and disease stage (0.038). Furthermore, tumors with smaller diameter had higher BCL3 nuclear expression levels than larger tumors (p=0.009). Conclusions: Patients of stage II carrying a T allele had improved two and five-year survival. BCL3 expression is not correlated with rs8100239 status. However, it is related to histological subtype, stage and maximum diameter while it differs between malignant and normal lung tissue. This research has been co-financed by the EU and Greek national funds (Heracleitus II Program).
Ultrasonographic damages of major salivary glands are associated with cryoglobulinemic vasculitis and lymphoma in primary Sjogren’s syndrome: are the ultrasonographic features of the salivary glands new prognostic markers in Sjogren's syndrome?
Authors: Guillaume Coiffier, Amélie Martel, Jean-David Albert, Alain Lescoat, Aurore Bleuzen, Aleth Perdriger, Michel De Bandt, François Maillot
Journal: Annals of the Rheumatic Diseases (2019)

We read with great interest the new ultrasound scoring system of salivary glands for primary Sjogren’s syndrome (pSS) developed by Outcome Measures in Rheumatology (OMERACT) and recently reported by Jousse-Joulin et al .1 The salivary gland ultrasound (SGUS) is a simple, non-irradiating, non-expensive and accessible assessment tool. Several previous SGUS scoring systems have been proposed so far, but not all of them take into account every pathological features, especially in the parotid gland (such as hyperechoic bands) for the diagnosis of pSS. The lack of consensus between each of these SGUS scoring systems also had a negative impact on the reproducibility of the examination so far. By offering an updated consensual classification, the OMERACT initiative therefore constitutes an undeniable progress for the diagnosis of pSS.

Recently, in a multicentre prospective study of 97 patients referred for clinical sicca syndrome (39 pSS and 22 secondary Sjogren’s syndrome (sSS) according to American-European Consensus Group (AECG) criteria in comparison with 36 controls), we …
Antagonists of IAP proteins based on an azabicyclooctane scaffold
Authors: Frederick Cohen, Karl Doerner, Linda Elliot, Wayne Fairbrother, John Flygare, Matthew Franklin, Stacy Frankovitz, Stephen Keteltas, Lesley Murray, Jeane Philippe Stephan, Vickie Tsui, Domagoj Vucic, Harvey Wong
Journal: Cancer Research (2007)

4736  Starting from a co-crystal structure of the peptide AVPW with ML-IAP, the program CAVEAT was used to design potential proline mimetics. The synthesis of an azabicyclooctane core, and incorporation of this core into elaborated antagonists is described. The binding of these compounds to IAP proteins was assessed by fluorescence polarization competition assay, and several compounds with Kis of
SAT0697-HPR COMMON COMORBIDITIES IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A UNICENTRIC BIG COHORT
Authors: Anggie Aza, Michael Cabrera, Fernando Rodriguez, Pedro Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized chronic joint inflammation. RA and ageing are associated with comorbidities such as cardiovascular disease, malignancies and osteoporosis, these conditions have an important effect on the management of RA. These comorbidities can be associated with higher mortality, poor life quality, and the increasing of costs for the health system. <h3>Objectives:</h3> To describe the prevalence of comorbidities and characteristics of a Colombian unicentric big cohort that assist to a RA specialized center. <h3>Methods:</h3> We performed a descriptive analysis; our main goal was to provide real-life data regarding characteristics of patients with RA. We collected sociodemographic information, DAS28, and prevalence of comorbidities regarding hypertension, cerebrovascular disease, diabetes mellitus, osteoporosis, renal chronic disease, or Sjogren's syndrome. We calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. We estimated the prevalence of comorbidities and performed a bivariate analysis. <h3>Results:</h3> We reviewed the medical charts of 6541 patients, 82% were female and 18% male; median age was 60 years RIQ (50-67), regarding disease activity, mean DAS28 was 3.34 ± 1.28. The prevalence of comorbidities was 36%, the most common disease was high blood pressure followed by osteoporosis, see table 1. When we compared DAS28 and comorbidities 11% of patients who were in moderate or severe disease activity had one or more comorbidities. The relationship between disease activity and comorbidities was not associated and it was not statistically significant (P&gt;0.05) <h3>Conclusion:</h3> As other studies have shown high blood pressure is the most common disease among patients with RA followed by osteoporosis(1, 3). s. According to these results it is important to consider the patient's context, medical conditions, and the number of comorbidities in order to understand the complexity of the management of patient with RA. Additionally, it is important to explore barrier and health care services in order to plan a realistic plan where a patient is managed with all comorbidities. <h3> Disclosure of Interests:</h3> Anggie Aza: None declared, Michael Cabrera: None declared, Fernando Rodriguez: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB
PB2057 PRE-CLINICAL BLOCKING OF PD-L1 MOLECULE, WHICH EXPRESSION IS DOWN REGULATED BY NF-κB, JAK1/JAK2 AND BTK INHIBITORS, INDUCES REGRESSION OF ACTIVATED B-CELL LYMPHOMA
Authors: C. Vincent-Fabert, L. Roland, U. Zimber-Strobl, J. Feuillard, N. Faumont
Journal: HemaSphere (2019)

Background: Escape from immune control must be important in the natural course of B-cell lymphomas, especially for those with activation of NF-kB. Aims: To search for PD-L1 expression in mouse model L.CD40 that could explain the tumor B cells escape of immune surveillance. Methods The pre-clinical L.CD40 transgenic mouse model is characterized by B-cell specific CD40 signaling responsible for NF-kB continuous activation with a spleen monoclonal B-cell tumor after one year in 60% of cases. L.CD40 mice were injected with anti-PD-L1 antibody. Results: L.CD40 tumors B-cells expressed high levels of PD-L1. This expression was dependent on activation of either NF-kB, JAK1/JAK2 or BTK pathways since ex vivo treatment with the inhibitory molecules PHA-408, ruxolitinib and ibrutinib led to decrease of its expression. Treatment of L.CD40 lymphomatous mice with an anti-PD-L1 monoclonal antibody induced tumor regression with decreased spleen content, activation and proliferation rate of B-cells as well as a marked increase in T cell activation, as assessed by CD62L and CD44 expression. Summary/Conclusion: These results highlight the interest of therapies targeting the PD-1/PD-L1 axis in activated lymphomas with PD-L1 expression, with possible synergies with tyrosine kinase inhibitors.