tbuckley/cabot-search huggingface dataset:
Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy
Authors: Xin Lai, Florian S. Dreyer, Martina Cantone, Martin Eberhardt, Kerstin F. Gerer, Tanushree Jaitly, Steffen Uebe, Christopher Lischer, Arif Ekici, Jürgen Wittmann, Hans-Martin Jäck, Niels Schaft, Jan Dörrie, Julio Vera
Journal: Theranostics (2020)

Dendritic cells (DCs) are professional antigen-presenting cells that induce and regulate adaptive immunity by presenting antigens to T cells. Due to their coordinative role in adaptive immune responses, DCs have been used as cell-based therapeutic vaccination against cancer. The capacity of DCs to induce a therapeutic immune response can be enhanced by re-wiring of cellular signalling pathways with microRNAs (miRNAs). Methods: Since the activation and maturation of DCs is controlled by an interconnected signalling network, we deploy an approach that combines RNA sequencing data and systems biology methods to delineate miRNA-based strategies that enhance DC-elicited immune responses. Results: Through RNA sequencing of IKKβ-matured DCs that are currently being tested in a clinical trial on therapeutic anti-cancer vaccination, we identified 44 differentially expressed miRNAs. According to a network analysis, most of these miRNAs regulate targets that are linked to immune pathways, such as cytokine and interleukin signalling. We employed a network topology-oriented scoring model to rank the miRNAs, analysed their impact on immunogenic potency of DCs, and identified dozens of promising miRNA candidates, with miR-15a and miR-16 as the top ones. The results of our analysis are presented in a database that constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (https://www.synmirapy.net/dc-optimization). Conclusions: Our approach enables the systematic analysis and identification of functional miRNA-gene interactions that can be experimentally tested for improving DC immunogenic potency.
HGG-19. IDENTIFICATION OF NOVEL SUBGROUP-SPECIFIC miRNA EXOSOMAL BIOMARKERS IN PEDIATRIC HIGH-GRADE GLIOMAS
Authors: Lucia Lisa Petrilli, Alessandro Paolini, Angela Galardi, Giulia Pericoli, Marta Colletti, Roberta Ferretti, Virginia Di Paolo, Luisa Pascucci, Hector Peinado, Chris Jones, Antonella Cacchione, Luca De Palma, Marta Alonso, Andrew Moore, Angel Montero Carcaboso, Andrea Carai, Angela Mastronuzzi, Franco Locatelli, Andrea Masotti, Angela Di Giannatale, Maria Vinci
Journal: Neuro-Oncology (2020)

Abstract Pediatric high-grade gliomas (pHGG) are heterogeneous brain tumors for which new specific diagnostic/prognostic biomarkers are needed. In this study, we aimed to identify new pHGG subgroup specific biomarkers by exploiting exosomes, known vehicles of oncogenic signals. We used plasma from 23 patients (including 6 controls) and conditioned medium from 12 patient-derived cell-lines, representing all locational and molecular subgroups. Upon exosome isolation, total RNA was extracted and miRNAs were assessed using a PCR Panel. Analysis of plasma miRNome showed that tumor exosomal samples were largely clustered together, independently from their locational and/or molecular subgroup. We identified 20 significantly upregulated and 25 downregulated miRNAs compared to controls. Interestingly, 27 miRNAs were expressed only in tumors. Furthermore, the unsupervised clustering showed a clear separation based on locational (hemispheric vs pontine) and mutational (WT vs H3.3G34R or H3.3G34R vs H3K27M) subgroup comparisons, with the identification of distinct miRNomes underlying the key role of location and mutations in defining the pHGG exosomal miRNA profile. This was further confirmed analyzing the miRNOme from cell-line derived exosomes. Moreover, we identified a pool of significantly differentially regulated miRNAs in diagnose vs relapse and biopsy vs autopsy cell-lines. Most importantly, when comparing hemispheric vs pontine and H3.3G34R vs H3.3K27M, we identified respectively four and three miRNas equally dysregulated and in common between plasma and cell-lines. Those were strongly associated mainly to transcriptional regulation and targeting TTC9, linked to cancer invasion and metastasis. Based on this, we suggest exosomal miRNAs as a powerful new pHGG diagnostic/prognostic tool.
EXTH-05. NON-CYTOTOXIC RADIATION ENHANCES DELIVERY OF ANTISENSE OLIGONUCLEOTIDES AND IMPROVES CHEMO-RADIATION EFFICACY IN BRAIN TUMOR XENOGRAFTS
Authors: Jeffrey Wu, Samantha Holland, Leslie Muldoon, Edward Neuwelt, Prakash Ambady
Journal: Neuro-Oncology (2020)

Abstract Overexpression of O6-methylguanine DNA methyltransferase (MGMT) contributes to brain tumor chemo-resistance. Previously we found that non-cytotoxic radiation improved anti-MGMT Morpholino Oligonucleotides (AMONs) delivery to reduce MGMT levels in subcutaneous tumor xenografts. Here we evaluated if radiation enhanced the delivery of intravenous (IV) AMONs to rat brain and improved chemo-radiation therapy (CRT) efficacy using rat models of human brain tumors. Athymic nude rats bearing orthotopic cerebellar D283 medulloblastoma or intracerebral H460 non-small cell lung carcinoma (NSCLC) brain metastasis xenografts were used. The impact of cranial radiation on delivery of IV 3’-carboxyfluorescein labeled oligonucleotides across the neurovascular unit was evaluated using confocal microscopy. We found that high brain parencymal fluorescence in radiated compared to non-radiated rats. MGMT protein silencing was assessed by immunoblot in tumor-bearing rats 3 d after 2 Gy cranial radiation alone or followed in 1 d by IV AMONs (10.5 mg/kg). Radiation followed by AMONs reduced MGMT expression by 50% in both xenograft models. To evaluate efficacy, tumor-bearing rats received one dose of 2 Gy radiation plus oral temozolomide (20 mg/kg x 4d) with or without IV AMONs. AMONs concurrent with CRT reduced tumor volumes in the medulloblastoma model (p=0.012), and a similar trend was found in the NSCLC brain metastasis model. In conclusion, we demonstrate the use of a single clinically relevant radiation dose fraction to guide and enhance the delivery of oligonucleotides into brain tumor xenograft models to reduce MGMT levels and improve CRT efficacy.
Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of <i>in vitro</i>, <i>in vivo</i>, and clinical trials
Authors: Young Joo Han, Keum Hwa Lee, Sojung Yoon, Seoung Wan Nam, Seohyun Ryu, Dawon Seong, Jae Seok Kim, Jun Young Lee, Jae Won Yang, Jin Hee Lee, Ai Koyanagi, Sung Hwi Hong, Elena Dragioti, Joaquim Radua, Lee Smith, Hans Oh, Ramy Abou Ghayda, Andreas Kronbichler, Maria Effenberger, Daniela Kresse, Sara Denicolò, Woosun Kang, Louis Jacob, Hanwul Shin, Jae Il Shin
Journal: Theranostics (2020)

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity.However, no specific therapy has been established for this disease yet.We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19.Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020.Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study.Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated.There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19.Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461).Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), , and convalescent plasma therapy (n = 126).Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence.Further RCTs are required.
CTNI-34. INITIAL ANALYSIS OF PHASE-III TRIAL - STANDARD CHEMOTHERAPY VS. CHEMOTHERAPY GUIDED BY A CANCER STEM CELL TEST IN RECURRENT GLIOBLASTOMA (NCT03632135)
Authors: Tulika Ranjan, Ricky Chen, Dawit Aregawi, Rekha Chaudhary, Soma Sengupta, Christine Lu-Emerson, Hugh Moulding, Jon Glass, Jason Schroeder, Steven Jubelirer, Mark Anderson
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND ChemoID is a cancer stem cell (CSC) cytotoxicity assay for guiding personalized treatment in the clinical trial NCT03632135 using standard-of-care drugs for improving clinical outcomes. The ChemoID assay is a functional test that determines the response to chemotherapy treatments from a panel of FDA approved drugs or their combinations. The trial aims to determine the clinical utility of the ChemoID assay as a predictor of clinical response in recurrent glioblastoma (GBM). METHODS The study has been designed as a parallel group controlled clinical trial where participants with recurrent GBM amenable to surgery or biopsy are randomized at a ratio of 1:1 to either standard-of-care chemotherapy chosen by the physician or ChemoID-guided therapy. Response to therapy is measured by MRI imaging (RANO 1.1). The primary endpoint is median overall survival (OS) and secondary endpoints are OS at 6, 9, and 12 months, median progression-free survival (PFS), PFS at 4, 6, 9, and 12 months, objective tumor response, time to recurrence, and quality of life. RESULTS A total of 41 participants (29 males, 12 females) have been accrued to the trial thus far with a median age of 61yo. Data from 38 participants (27 males, 11 females) has reached maturity for analysis. 21 participants have been randomized to the assay-guided arm and 17 to the physician-choice arm. From an initial analysis, we observed that 71% (15/21) of the participants in the ChemoID-guided arm are alive and 29% (6/21) are deceased. We also observed that 41% (7/17) of the participants in the physician-choice arm are alive and 59% (10/17) are deceased. This gives the odds of death for the ChemoID-guided arm to be 72% lower than on the physician-guided arm (OR=0.28; (0.07–1.08); p=0.065). CONCLUSIONS Our preliminary results indicate that the ChemoID assay has the potential to improve survival of recurrent GBM patients.
SURG-30. SURGICAL RESECTION OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: IMPACT OF PATIENT SELECTION ON OVERALL SURVIVAL
Authors: Nadav Schellekes, Arianna Barbotti, Yael Abramov, Razi Sitt, Francesco Di Meco, Zvi Ram, Rachel Grossman
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE A possible prolonged survival after surgical resection for primary central nervous system lymphoma (PCNSL) lesions in selected patients has been suggested, but selection criteria for surgery, especially for solitary lesions, have never been established. METHODS We retrospectively searched our patient database for records of adult patients (≥18 years) who were diagnosed and treated for a solitary lesion of PCNSL between 2005 and 2019. Patients were divided into groups according to whether they underwent surgical resection or needle biopsy. Statistical analyses were performed in an attempt to identify variables affecting outcome and possible survival advantage and to characterize subgroups of patients who would benefit from resection of their tumor compared to undergoing biopsy only. RESULTS 113 patients with a solitary lesion of PCNSL were identified, 36 underwent surgical resection and 77 a diagnostic stereotaxic biopsy only. Pre-operative risk factors were found to include age &amp;gt; 70 years ([HR] 9.61, 95% [CI] 2.42-38.11, p=0.001) and deep seated lesions (adjusted HR 3.33, 95% CI 1.13-9.84, p=0.030). Having a postoperative Karnofsky Performance Scale (KPS) under 80 (adjusted HR 3.21, 95% CI 1.05-9.77, p=0.040) or surgical-site infections (adjusted HR 4.27, 95% CI 1.18-15.47, p=0.027) were significant postoperative risk factors. In a subgroup analysis, patients with a superficial tumor who underwent surgical resection had significantly longer survival times compared with those who underwent needle biopsy (median survival 34.3 months versus 8.9 months, p=0.014). Patients under 70 years who had a superficial tumor and underwent surgical resection had significantly prolonged survival, with a median survival of 35.0 months versus 8.9 months in patients from the same group who underwent needle biopsy (p=0.007). CONCLUSION Specific subgroups of patients with a solitary PCNSL lesion might gain a survival benefit from surgical resection compared to undergoing only a diagnostic biopsy.
MBCL-27. ASSOCIATION OF MEDULLOBLASTOMA WITH CHARCOT-MARIE-TOOTH DISEASE
Authors: Kenichiro Watanabe, Kazuyuki Komatsu, Koji Kawaguchi, Risa Makino, Takayuki Takachi, Taemi Ogura, Yasuo Horikoshi, Ryuji Ishizaki, Hideto Iwafuchi, Yuzuru Tashiro
Journal: Neuro-Oncology (2020)

Abstract Charcot-Marie-Tooth disease (CMT) is one of the most common hereditary neurological disorders and damages peripheral nerves that results in motor and sensory disturbance. Association of medulloblastoma (MBL) with CMT has been rarely reported. A one-year-old male was referred to our hospital because of cerebellar mass. He had partial resection of the tumor, and was pathologically diagnosed as having desmoplastic nodular medulloblastoma. He received chemotherapy according to the HIT protocol, however, developed severe peripheral neurotoxicity in the initial stage of the treatment. Reinvestigation of family history revealed his mother, grandmother, and aunt had muscle weakness. We suspected he had an inherited neurological disease including CMT, and discontinued administration of vincristine. Fluorescence in situ hybridization analysis detected duplication of PMP22 gene located on 17p11.2, confirming the diagnosis of CMT1A. He completed the rest of chemotherapy without vincristine, and remained in complete remission for four years from the end of treatment. In the literature, there are reports of patients with CMT who developed MBL and were complicated with severe peripheral neurotoxicity due to the use of vincristine. The present case, along with previous reports, suggests that medulloblastoma can develop in patients with CMT and reminds the importance of recalling the possibility of CMT when patients develop severe chemotherapy-induced peripheral neurotoxicity upon use of vincristine. Desmoplastic nodular medulloblastoma may be successfully treated by chemotherapy without vincristine.
RARE-30. A RARE CASE OF PRIMARY EWING’S SARCOMA OF THE CERVICAL SPINE
Authors: Amandeep Kalra, Jayson Neil, Sarah Mann, Pierre Giglio
Journal: Neuro-Oncology (2020)

Abstract Ewing sarcoma family of tumors predominantly affect the pediatric population in the long bones of the extremities or the pelvis, and only 8% of cases arise within the spine. Primary Ewing’s sarcoma of the cervical spine is extremely rare and less than 30 cases have been reported in the literature thus far. Here we present a case of primary Ewing’s sarcoma of the cervical spine in a 28-year-old female who presented with a three-month history of neck pain and right arm radiculopathy. MRI revealed a homogeneously contrast enhancing, eccentric mass with dural tail at C2-C7. After undergoing a hemilaminectomy, histopathology confirmed extraosseous Ewing’s sarcoma with CD99 positivity. A comprehensive systemic and neuraxis work-up ruled out overt metastasis. We extrapolated data from children’s cooperative group studies and IESS-II clinical trial to formulate a three phase treatment protocol as described below. To date, patient is in remission with no evidence of any residual disease in the cervical spine. In conclusion, although Primary Ewing’s sarcoma of the cervical spine is extremely rare it should be considered a differential diagnosis in patients with neck pain and a spinal mass under the age of thirty. Less than 25% of EFT’s present with overt metastasis and almost all have subclinical metastatic disease at the time of diagnosis, therefore, a comprehensive evaluation and systemic chemotherapy is recommended. We recommend a multidisciplinary approach of surgical decompression to preserve neurological functions, followed by compressed chemotherapy regimens, reevaluation for local treatment, and adjuvant chemotherapy.
The “New Normal” of Cancer Treatment Delays Is Nothing New
Authors: Laura Van Metre Baum, Kathryn Kline, Cardinale B. Smith
Journal: JAMA Network Open (2020)

Eugene B. Cone, MD; Maya Marchese, MS; Marco Paciotti, MD; David-Dan Nguyen, MPH; Junaid Nabi, MD; Alexander P. Cole, MD; George Molina, MD, MPH; Rose L. Molina, MD, MPH; Christina A. Minami, MD, MS; Lorelei A. Mucci, MPH, ScD; Adam S. Kibel, MD; Quoc-Dien Trinh, MD
LGG-44. PROGNOSTIC SIGNIFICANCE OF IMAGING CHARACTERISTICS IN PEDIATRIC LOW GRADE GLIOMAS
Authors: Muhammad Baig, Michael Chan, Jason Johnson, Sana Mohiuddin, Ruitao Lin, Michael Roth, Zsila Sadighi, John Slopis, Soumen Khatua, Wafik Zaky
Journal: Neuro-Oncology (2020)

Abstract Pediatric low-grade gliomas (pLGG) account for one third of all central nervous system (CNS) tumors. MRI is the preferred imaging modality for diagnosis and response evaluation. This study aims to evaluate if radiographic characteristics of pLGG at diagnosis are prognostic. Medical records of 700 pLGG patients were reviewed who were seen between 1998- 2019 at our institution. Summary statistics were provided to describe patient demographic and clinical characteristics. 603 patients were not eligible because incomplete records, 97 patients were identified and eligible for the review. There were 45 females and 52 males with the mean age of 6.5 years at diagnosis. Patients were categorized based on contrast enhancement to 2 groups; none/mild versus moderate/high with 65 and 32 patients respectively. 31 patients had infiltrative glioma (32.3%) with more than one lobe involved at diagnosis. Fifteen patients (15.46%) had hydrocephalous at initial diagnosis. 32 patients (32.9%) did not have any treatment and remained stable while 65(67.0%) had either surgery, chemotherapy or radiation or combination. 21 patients had neurofibromatosis type-1(NF-1) with better outcome comparing to non-NF1 as previously reported. No statistically significant difference in outcome was found based on the imaging characteristics at diagnosis including contrast enhancement, hydrocephalus, tumor size, presence of cyst or infiltrative tumors. The 5 years PFS rate for the entire cohort was 47%. Our study results are limited by low patient number, hence collaborative multi-institutional studies are warranted to delineate consensus and investigate prognostic factors to improve the outcome of pLGG.
Frailty Is Associated with Increased One-Year Mortality in Patients with Newly Diagnosed Diffuse Large-B-Cell Lymphoma: A Population-Based Study
Authors: Abi Vijenthira, Lee Mozessohn, Chenthila Nagamuthu, Ning Liu, Danielle Blunt, Shabbir Alibhai, Anca Prica, Matthew C. Cheung
Journal: Blood (2020)
Race, Power, and COVID-19: A Call for Advocacy within Bioethics
Authors: Zamina Mithani, Jane Cooper, J. Wesley Boyd
Journal: The American Journal of Bioethics (2020)

Events in 2020 have sparked a reimagination of how both individuals and institutions should consider race, power, health, and marginalization in society. In a response to these developments, we examine the current and past limitations of the ways in which bioethicists have considered race and, more generally, discourses of marginalization. We argue that the foundational principle of justice necessitates that bioethics, as an institution, maintain an active voice against systemic injustice. To carry out this charge, bioethics as a field should promote alternative narratives—"counter storytelling"—to the mainstream voices that have traditionally been heard and accepted, largely without opposition. Additionally, we engage with both Post-Colonial and Critical Race Theory, which we believe are important tools for bioethics in pursuit of equity. Ultimately, we advocate for a proactive form of bioethics that actively resists and denounces injustice and which considers a much wider variety of voices about justice than bioethics has historically considered.
A trilogy antimicrobial strategy for multiple infections of orthopedic implants throughout their life cycle
Authors: Yikai Wang, Wangsiyuan Teng, Zengjie Zhang, Xingzhi Zhou, Yuxiao Ye, Peng Lin, An Liu, Yan Wu, Binghao Li, Chongda Zhang, Xianyan Yang, Weixu Li, Xiaohua Yu, Zhongru Gou, Zhaoming Ye
Journal: Bioactive Materials (2020)

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles. However, ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc. As these incidents could easily introduce new microbial pathogens in/onto the implants. Herein, we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning, could effectively eradicate bacterial infection at various stages of implantation. Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating. Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating. Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo. Finally, the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc, which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating. Moreover, sustained release of Sr2+ and Zn2+ during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.
Cost-effectiveness of Statin Use Guidelines—Reply
Authors: Ankur Pandya, Jinyi Zhu, Aferdita Spahillari
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal