tbuckley/cabot-search huggingface dataset:
RADT-10. SURVIVAL IN PATIENTS FULFILLING CCTG CE.7 ELIGIBILITY CRITERIA: EVALUATING INITIAL STEREOTACTIC RADIOSURGERY FOR 5-15 BRAIN METASTASES
Authors: Jason Gurewitz, Bernadine Donahue, Joshua S Silverman, Carolina Benjamin, Kenneth Bernstein, Douglas Kondziolka
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The suitability of stereotactic radiosurgery (SRS) in patients with 5-15 brain metastases (BM) is being evaluated in the ongoing CCTG CE.7 randomized trial testing SRS against HA-WBRT. Our study examines the survival of patients with 5-15 BM treated at initial SRS. METHODS Review of our Gamma Knife registry identified 163 patients who fulfilled CCTG CE.7 eligibility criteria. RESULTS 92 females (56%) and 71 males (44%) with median age of 51.6 years (23-98.9) and primary diagnoses of lung (n = 108, 28 EGFR/ALK mutations), breast (n =14, 1 Her2+), melanoma (n = 27, 9 BRAF+), and 14 other were identified. 145 had active extracranial disease (89%); median KPS was 90 (50-100). Median number of tumors at first SRS was 8.2; 114 patients (70%) had 5-9 and 49 (30%) had 10-15 tumors. 73 patients (45%) had subsequent SRS to a median of 19 (6-84) cumulative subsequent tumors at a median time to 2nd treatment of 3.9 months (0.7-30.3). 32 patients (20%) had a 3rd SRS and 24 patients (15%) had 4 or more treatments. 16 patients (10%) received WBRT after initial SRS. 73 patients (45%) were alive at time of data analysis. Median OS from initial SRS for all patients was 15.5 months and was 15, 17.6, 13.4, and 8.7 months, for breast, lung, melanoma, and other respectively. Median OS with 5-9 metastases vs 10-15 metastases was 17.5 vs. 13.3 months (p=.15). Median OS with vs without subsequent SRS was 21.8 vs 8 months (p=.0013). CONCLUSION Patients with 5-15 BM treated with initial SRS can achieve survivals that compare favorably with or better than those of WBRT. These findings potentially challenge the assumption that such patients may be better candidates for HA-WBRT than upfront SRS. Our experience supports the ongoing efforts to prospectively evaluate upfront SRS in these patients.
111In-Labeled White Blood Cell Uptake in the Urinary Bladder in Occult Urinary Tract Infection
Authors: Henrik Ullman, Karoly Viragh, Mariam Thomas, Chiayi Ni
Journal: Clinical Nuclear Medicine (2020)

A 55-year-old woman with multiple medical problems, including anuric, dialysis-dependent, end-stage renal disease, presented with persistent fever of unknown origin. Despite extensive workup with cross-sectional imaging and panculture, the etiology was not found. Eventually, an 111In-labeled WBC scan was performed to evaluate for occult infection, which revealed intense heterogeneous uptake in the urinary bladder. Subsequent bladder catheterization showed pus and blood, which grew Klebsiella pneumoniae. The fevers resolved with adjustment of the therapy. Although urinary analysis and culture are standard practice in the workup of fever of unknown origin, anuria may obscure this common source of infection.
CTIM-07. IDENTIFICATION OF A BASELINE BIOMARKER ASSOCIATED WITH TUMOR RESPONSES IN A PHASE I/IIa TRIAL OF A THERAPEUTIC CMV VACCINE AGAINST RECURRENT GLIOBLASTOMA (GBM)
Authors: Patrick Wen, David Reardon, Deborah Forst, Eudocia Lee, Fabio Iwamoto, Francisco Diaz-Mitoma, David Anderson, Andrew Lassman
Journal: Neuro-Oncology (2020)

Abstract Cytomegalovirus (CMV) antigens have been reported in over 90% of GBM tumors. CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens, respectively, and are immunogenic targets in a CMV-based GBM vaccine. We enrolled 10 patients (6 women, 4 men) with KPS at least 70 and first recurrence of GBM to a trial (Phase IIa extension) of gB/pp65 enveloped virus-like particles (eVLPs) with GM-CSF. Intradermal vaccination was administered every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Median age was 59 years (range 33–67). Among 8 response-evaluable patients, we observed 1 SD and 1 PR. Among all patients treated on phase I and II (n=26), a normal baseline ratio of CD4/CD8 T cells in peripheral blood predicted response (n=6). Other baseline peripheral blood markers did not correlate with efficacy, including total white blood cell, lymphocyte percentage, and absolute lymphocyte count. During treatment, the peripheral blood of responders demonstrated dynamic losses followed by subsequent reappearance and expansion of CMV-specific CD4+ effector memory T cells. Based on these encouraging results, a new arm is enrolling subjects combining gB/pp65 eVLPs (at the same dose) formulated with adjuvant intramuscular AS01B and results will be presented.
ETMR-13. NFI GENES IN ETMR TUMORIGENESIS AND NEURODEVELOPMENT
Authors: Jens Bunt, Sander Lambo, Jonathan Lim, Monika Mauermann, Stefan Pfister, Linda Richards, Marcel Kool
Journal: Neuro-Oncology (2020)

Abstract Embryonal tumors with multilayered rosettes (ETMRs) are aggressive pediatric embryonal brain tumors with a universally poor prognosis. These tumors are commonly characterized by amplification of C19MC, but other miRNA-related aberrations, such as DICER mutations or MIR17HG amplifications, are also observed. Nevertheless, it remains unknown how these aberrations are driving the tumorigenesis. We applied miRNA target prediction to investigate the downstream targets shared by these aberrations affecting normal brain development and tumorigenesis. The nuclear factor one (NFI) family of transcription factors were found to be top candidates shared by both miRNA clusters. These genes are expressed at very low levels in ETMRs, in contrast to other brain tumors. During normal brain development these genes are expressed in radial glial progenitors and are required for the transition of proliferation to differentiation. Since radial glial progenitors are the potential cell-of-origin of ETMRs, we hypothesize that downregulation of NFI is required for the proliferative, undifferentiated state of ETMRs. Indeed, mouse models with deletion of an Nfi family member display sustained proliferation and delayed differentiation of radial glial progenitors during development. This leads into brain overgrowth, which has also been observed in humans with intellectual disabilities caused by NFI haploinsufficiency. When multiple Nfi family members are simultaneously targeted in mice, the progenitors are retained and both neurogenesis and gliogenesis are inhibited, resulting in a neuropathology similar to that of human ETMR tumors. Hence, downregulation of NFI genes resulting from miRNA aberrations could contribute to the developmental state and possibly tumorigenesis of ETMRs.
Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Antitumor T-cell Immunity
Authors: Aayoung Hong, Marco Piva, Sixue Liu, Willy Hugo, Shirley H. Lomeli, Vincent Zoete, Christopher E. Randolph, Zhentao Yang, Yan Wang, Jordan J. Lee, Skylar J. Lo, Lu Sun, Agustin Vega-Crespo, Alejandro J. Garcia, David B. Shackelford, Steven M. Dubinett, Philip O. Scumpia, Stephanie D. Byrum, Alan J. Tackett, Timothy R. Donahue, Olivier Michielin, Sheri L. Holmen, Antoni Ribas, Gatien Moriceau, Roger S. Lo
Journal: Cancer Discovery (2020)

MAPK targeting in cancer often fails due to MAPK reactivation. MEK inhibitor (MEKi) monotherapy provides limited clinical benefits but may serve as a foundation for combination therapies. Here, we showed that combining a type II RAF inhibitor (RAFi) with an allosteric MEKi durably prevents and overcomes acquired resistance among cancers with KRAS, NRAS, NF1, BRAF non-V600, and BRAF V600 mutations. Tumor cell-intrinsically, type II RAFi plus MEKi sequester MEK in RAF complexes, reduce MEK/MEK dimerization, and uncouple MEK from ERK in acquired-resistant tumor subpopulations. Immunologically, this combination expands memory and activated/exhausted CD8+ T cells, and durable tumor regression elicited by this combination requires CD8+ T cells, which can be reinvigorated by anti-PD-L1 therapy. Whereas MEKi reduces dominant intratumoral T-cell clones, type II RAFi cotreatment reverses this effect and promotes T-cell clonotypic expansion. These findings rationalize the clinical development of type II RAFi plus MEKi and their further combination with PD-1/L1-targeted therapy. SIGNIFICANCE: Type I RAFi + MEKi are indicated only in certain BRAF V600MUT cancers. In contrast, type II RAFi + MEKi are durably active against acquired MEKi resistance across broad cancer indications, which reveals exquisite MAPK addiction. Allosteric modulation of MAPK protein/protein interactions and temporal preservation of intratumoral CD8+ T cells are mechanisms that may be further exploited.This article is highlighted in the In This Issue feature, p. 521.
Eastern Kentucky’s Lost Generation and the Echoes That Remain—The Aftermath of the Opioid Epidemic
Authors: Brian S. Barnett
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Improving Risk Stratification for Heart Failure: A Role for Serial Testing of B-Type Natriuretic Peptides?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Matthew G. Daly, Christopher M. Frampton, Richard W. Troughton
Journal: Journal of the American College of Cardiology (2010)
COVD-08. THE DIVIDED PRINCIPLE OF JUSTICE: ETHICAL DECISION-MAKING IN CANCER CARE DURING THE COVID-19 PANDEMIC
Authors: Connor Brenna, Sunit Das
Journal: Neuro-Oncology (2020)

Abstract The four-principle approach to medical ethics, balancing prima facie obligations to beneficence, nonmaleficence, autonomy, and justice, has supplied a common language for the application of ethical analysis to medical practice for the last four decades. The frayed edges of this edifice are made visible, however, by the ongoing COVID-19 pandemic (and other historical circumstances of severe resource limitation in the healthcare system). We interrogate ethical considerations involved in the state of medical care during the COVID-19 pandemic, as demonstrated by reconsiderations of cancer care, in which the pillar of justice is exposed as internally divided. Specifically, we identify both patient-oriented and system-oriented principles of justice constituting a broader collective, unique among the classical four principles. This leads us to suggest a formal recognition of justice as a divided category, and a reclassification of the term into two subcategories which serve fundamentally different interests. The result is a more cohesive four principle approach in which all principles favour the deontological relationships fostered between patients and providers, which exists in constant balance with the utilitarian interests of the broader medical system.
Preoperative Biopsy Diagnosis in Pulmonary Carcinoids, a Shot in the Dark
Authors: Laura Moonen, Jules L. Derks, Bregtje C.M. Hermans, Iris M. Bunnik, Lisa M. Hillen, Robert Jan van Suylen, Michael A. den Bakker, Jan H. von der Thüsen, Ronald A. Damhuis, Esther C. van den Broek, Wieneke A. Buikhuisen, Anne-Marie C. Dingemans, Ernst Jan M. Speel
Journal: Journal of Thoracic Oncology (2020)
NFB-11. WHITE MATTER DIFFERENCES IN CHILDREN WITH NF1 COMPARED TO CONTROLS
Authors: Lisa Bruckert, Katie Travis, Emily McKenna, Kristen Yeom, Cynthia Campen
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Neurofibromatosis type 1 (NF1) is a genetic condition in which children develop learning challenges and glioma. White matter tracts (WMT) are implicated in these cognitive functions, while oligodendroglial precursor cells are implicated in both gliomagenesis and white-matter development. Specific WMTs have not been well characterized in NF1. METHODS Twenty NF1 patients aged 1.4–17.6 years (M = 9.5 years, 24 male) and 20 age-and-sex-matched controls underwent dMRI at 3T (25 directions, b=1000 s/mm2). Automated segmentation of WMTs extracted fractional anisotropy (FA) and mean diffusivity (MD) of 18 major WMTs. Covariance analysis examined the effect of group (NF1/controls) on FA/MD after controlling for intracranial volume. Regression analyses for WMTs determined the interaction of FA/MD with age for NF1 patients compared to controls. Significance was set at p&amp;lt;0.05 after correcting for multiple comparisons using false discovery rate. RESULTS Compared to controls, children with NF1 had significantly decreased FA in 8 and increased MD in 12/18 tracts. Differences held after controlling for intracranial volume. The interaction between group and age accounted for a significant proportion of the variance in FA in 9 and in MD in 16/18 tracts. FA and MD differences between children with NF1 and controls were greater at younger than older ages. CONCLUSION Microstructural differences were observed in WMTs in children with NF1 compared to controls. These differences were not explained by intracranial volume and were most pronounced in younger children with NF1 compared to controls. These findings have implications for understanding neurocognitive deficits and gliomagenesis observed in children with NF1.
Which is Better for Nanomedicines: Nanocatalysts or Single‐Atom Catalysts?
Authors: Mengyang Zhao, Nan Zhang, Ruigeng Yang, Deliang Chen, Yongxing Zhao
Journal: Advanced Healthcare Materials (2020)

With the rapid advancements in nanotechnology and materials science, numerous nanomaterials have been used as catalysts for nanomedical applications. Their design and modification according to the microenvironment of diseases have been shown to achieve effective treatment. Chemists are in pursuit of nanocatalysts that are more efficient, controllable, and less toxic by developing innovative synthetic technologies and improving existing ones. Recently, single-atom catalysts (SACs) with excellent catalytic activity and high selectivity have attracted increasing attention because of their accurate design as nanomaterials at the atomic level, thereby highlighting their potential for nanomedical applications. In this review, the recent advances in nanocatalysts and SACs are briefly summarized according to their synthesis, characterizations, catalytic mechanisms, and nanomedical applications. The opportunities and future scope for their development and the issues and challenges for their application as nanomedicine are also discussed. As far as it is known, the review is the systematic comparison of nanocatalysts and SACs, especially in the field of nanomedicine, which has promoted the development of nanocatalytic medicine.
CTNI-43. ANLOTINIB COMBINED WITH STUPP REGIMEN IN TREATING PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME: A PHASE II PILOT STUDY
Authors: Shuzhen Lai, Yuanyuan Chen
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Anlotinib, an orally multi-target tyrosine kinase inhibitor, inhibits tumor angiogenic and proliferative signal pathways. We performed a phase II trial of anlotinib in combination with the STUPP regimen in patients with newly diagnosed glioblastoma multiforme（GBM）to determine whether the combination therapy would safely improve outcomes in this group of patients. An initial pilot study assessed interim safety and tolerability. METHODS AND MATERIALS Ten newly diagnosed GBM patients were included in this study. All patients received standard radiation of 60 Gy in 30 fractions starting within 4–6 weeks after surgery with concurrent TMZ (daily, 75 mg/m2) and anlotinib (8mg per day, from day 1 to 14, every 3 weeks). After a 4-week break, adjuvant therapy including 6 cycles of TMZ (150–200 mg/m², from day 1 to 5, every 4 weeks) and 8 cycles of anlotinib (8mg per day, from day 1 to 14, every 3 weeks) was given. For patients completing adjuvant therapy, anlotinib alone (8mg per day, from day 1 to 14, every 3 weeks) was administrated until disease progression. RESULTS All patients completed concurrent chemo-radiotherapy without interruption. One patient developed grade 3 weight loss at 56th week and grade 3 presumed radiation-induced cognitive disturbance at 60th week. Fatigue and hypertension were frequently observed during treatment, which potentially be related to the treatment. No severe toxicity was observed in other patients. Up to this writing, none of these patients developed disease progression. CONCLUSION Anlotinib combined with the STUPP regimen is a potential choice for newly diagnosed GBM patients. It is well tolerated and the toxicity is manageable. It’s acceptable to continue enrolling of this Phase II study.
Transplantation of autologous extracellular vesicles for cancer-specific targeting
Authors: Alessandro Villa, Mariangela Garofalo, Daniela Crescenti, Nicoletta Rizzi, Electra Brunialti, Andrea Vingiani, Paolo Belotti, Carlo Sposito, Silvia Franzè, Francesco Cilurzo, Giancarlo Pruneri, Camilla Recordati, Chiara Giudice, Alessia Giordano, Monica Tortoreto, Giangiacomo Beretta, Damiano Stefanello, Giacomo Manenti, Nadia Zaffaroni, Vincenzo Mazzaferro, Paolo Ciana
Journal: Theranostics (2020)

Nano-and microsized extracellular vesicles (EVs) are naturally occurring cargo-bearing packages of regulatory macromolecules, and recent studies are increasingly showing that EVs are responsible for physiological intercellular communication.Nanoparticles encapsulating anti-tumor theranostics represent an attractive "exosome-interfering" strategy for cancer therapy.Methods: Herein, by labeling plasma-derived EVs with indocyanine green (ICG) and following their biodistribution by in vivo and ex vivo imaging, we demonstrate the existence of nanoparticles with a highly selective cancer tropism in the blood of colorectal cancer (CRC) patients but not in that of healthy volunteers.Results: In CRC patient-derived xenograft (PDX) mouse models, we show that transplanted EVs recognize tumors from the cognate nanoparticle-generating individual, suggesting the theranostic potential of autologous EVs encapsulating tumor-interfering molecules.In large canine breeds bearing spontaneous malignant skin and breast tumors, the same autologous EV transplantation protocol shows comparable safety and efficacy profiles.Conclusions: Our data show the existence of an untapped resource of intercellular communication present in the blood of cancer patients, which represents an efficient and highly biocompatible way to deliver molecules directly to the tumor with great precision.The novel EV-interfering approach proposed by our study may become a new research direction in the complex interplay of modern personalized cancer therapy.
Current Clinical Applications of In Vivo Gene Therapy with AAVs
Authors: Jerry R. Mendell, Samiah A. Al-Zaidy, Louise R. Rodino-Klapac, Kimberly Goodspeed, Steven J. Gray, Christine N. Kay, Sanford L. Boye, Shannon E. Boye, Lindsey A. George, Stephanie Salabarria, Manuela Corti, Barry J. Byrne, Jacques P. Tremblay
Journal: Molecular Therapy (2020)

Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity. There are now five treatments approved for commercialization and currently available, i.e., Luxturna, Zolgensma, the two chimeric antigen receptor T cell (CAR-T) therapies (Yescarta and Kymriah), and Strimvelis (the gammaretrovirus approved for adenosine deaminase-severe combined immunodeficiency [ADA-SCID] in Europe). Dozens of other treatments are under clinical trials. The review article presents a broad overview of the field of therapy by in vivo gene transfer. We review gene therapy for neuromuscular disorders (spinal muscular atrophy [SMA]; Duchenne muscular dystrophy [DMD]; X-linked myotubular myopathy [XLMTM]; and diseases of the central nervous system, including Alzheimer's disease, Parkinson's disease, Canavan disease, aromatic l-amino acid decarboxylase [AADC] deficiency, and giant axonal neuropathy), ocular disorders (Leber congenital amaurosis, age-related macular degeneration [AMD], choroideremia, achromatopsia, retinitis pigmentosa, and X-linked retinoschisis), the bleeding disorder hemophilia, and lysosomal storage disorders.
Detection of Left Atrial Appendage Thrombus by Cardiac Computed Tomography: A Word of Caution⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Mario J. Garcia
Journal: JACC. Cardiovascular imaging (2009)