tbuckley/cabot-search huggingface dataset:
NIMG-67. DISAPPEARING DOTS – TRANSIENT LATE ENHANCING LESIONS YEARS AFTER BRAIN RADIOTHERAPY
Authors: Peter Pan, Oscar Padilla, Elizabeth Buss, Carl Elliston, Tony Wang, Adela Joanta-Gomez, Angela Lignelli-Dipple, Fabio Iwamoto, Teri Kreisl, Mary Welch, Aya Haggiagi, Laura Donovan, Marissa Barbaro, Jeffrey Bruce, Peter Canoll, Andrew Lassman
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Late-delayed radiation effects appear 6 months to years following radiotherapy. We characterize a species of small enhancing lesions in the late-delayed phase of post-radiotherapy that are distinct from the classic descriptions of radiation necrosis or pseudoprogression associated with mass effect and edema. These “disappearing dots” are small, do not exert mass effect nor edema, and spontaneously resolve. METHOD We retrospectively describe a series of cases with “disappearing dots” following brain radiotherapy. RESULTS There were 10 cases (4 men), median age 42 years (range 29-63). Diagnoses were glioblastoma (3); low grade astrocytoma, anaplastic astrocytoma, and anaplastic oligodendroglioma (2 each); and solitary fibrous tumor (1). All patients received 54-60 Gy (Gray) of external beam radiotherapy, except one (proton beam therapy to 60 cobalt Gray equivalent). Disappearing dots appeared at a median of 27 months (range 5-197) post-radiotherapy. Lesions were relatively small (~&amp;lt; 1 cm3), peri-ventricular, and within the radiotherapy field. Most enlarged before resolving. Advanced MR imaging and fluorodeoxyglucose (FGD)-PET results were inconsistent. Lesions persisted a median of 8.5 months (range 1-49) before spontaneous resolution. All were asymptomatic. Biopsy in one case revealed treatment effects rather than recurrent tumor. CONCLUSIONS Asymptomatic small periventricular enhancing lesions can develop and remit spontaneously, years following brain radiotherapy. Such disappearing dots should be part of the differential diagnosis along with tumor recurrence. of new enhancing lesions in the late-delayed phase post-radiotherapy.
NIMG-07. LONG-TERM FOLLOW-UP OF SCHWANNOMA GROWTH BEHAVIOR IN ADULT NEUROFIBROMATOSIS TYPE 2 AND SCHWANNOMATOSIS PATIENTS USING WHOLE-BODY MRI
Authors: Ina Ly, Raquel Thalheimer, Wenli Cai, Miriam Bredella, Alona Muzikansky, Vanessa Merker, Hamilton Herr, Jennifer Da, Gordon Harris, Scott Plotkin, Justin Jordan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are related genetic tumor predisposition syndromes caused by distinct germline pathogenic variants on chromosome 22. Both conditions are characterized by the presence of cranial, peripheral, and/or spinal nerve schwannomas. The long-term growth behavior of schwannomas is unknown but knowledge thereof would help guide patient surveillance and selection for treatment and improvement of clinical trial design. Whole-body MRI (WBMRI) can detect whole-body schwannoma burden in a single image acquisition session. METHODS 12 NF2 and 10 SWN patients who underwent a WBMRI between 2007-2010 underwent a repeat WBMRI between 2018-2019. Schwannomas were segmented on short tau inversion recovery (STIR) sequences. Tumor volume was calculated using a three-dimensional tumor quantification software (3DQI). Tumor growth and shrinkage were defined as a volume change ≥ 20% over the entire study period. RESULTS Median time between scans was 10 years. A total of 103 schwannomas (46 NF2-associated, 57 SWN-associated) were analyzed. In both NF2 and SWN, 50% of tumors grew. Median growth was 88.3% in NF2 and 100.4% in SWN. All growing NF2-associated schwannomas grew in the setting of exposure to systemic therapy whereas only one growing SWN-associated tumor had been treated systemically. Excluding resected tumors, 19.4% of schwannomas shrank. Median shrinkage was 48.5% in NF2 and 37.4% in SWN. All shrinking NF2-associated tumors had been treated with systemic therapy whereas none of the shrinking SWN-associated tumors had been. 19 new tumors (7 NF2-associated, 12 SWN-associated) developed in 8 patients. CONCLUSIONS Half of NF2- and SWN-associated schwannomas grow significantly over a decade. In NF2 patients, growth occurs despite systemic treatment whereas, in SWN patients, schwannomas may shrink spontaneously without treatment. These findings may suggest a more aggressive tumor phenotype in NF2. Continued patient enrollment and correlation of MRI findings with functional outcomes and hormone exposure history are ongoing.
GCT-70. INTRACRANIAL GROWING TERATOMA SYNDROME IN CHILDREN
Authors: Maria Carter Febres, Carol S Bruggers, Holly Zhou, Arie Perry, John Kestle, Nicholas Whipple
Journal: Neuro-Oncology (2020)

Abstract Germ cell tumors account for less than 5% of all intracranial malignancies in children. Intracranial growing teratoma syndrome (GTS) is a rare pathophysiologic process characterized by growth of mature teratoma elements of a non-germinomatous germ cell tumor (NGGCT) during or following treatment with chemotherapy, in addition to normalization of or declining AFP/βHCG of the cerebral spinal fluid (CSF)/serum. A 13-year-old male presented with headache, emesis, and diplopia. MRI of the brain/spine revealed a localized 3.1 x 3.1 x 3.2 cm pineal tumor. Biopsy confirmed NGGCT (germinoma, immature and mature teratoma). Serum AFP (227ng/ul) and βHCG (12 IU/L) and CSF AFP (21ng/ul) and βHCG (31 IU/L) were elevated. Prior to cycle two of chemotherapy, he developed unstable gait and moderate hearing loss. Repeat MRI brain demonstrated tumor enlargement (4.4 x 5.2 x 5.1 cm) and obstructive hydrocephalus, although serum AFP/βHCG had normalized. Gross total resection of tumor confirmed GTS, without residual immature/malignant elements. Following six cycles of multiagent chemotherapy (carboplatin, etoposide, ifosfamide) and proton beam craniospinal irradiation (36 Gy with 18 Gy boost), he remains free of disease at eleven months since diagnosis. The pathogenesis of GTS remains unclear. Care must be taken to avoid misdiagnosing GTS as progressive NGGCT, as treatment and prognosis differ significantly. Second-look surgery, with a goal of complete resection, should be considered in cases of NGGCT when residual tumor grows during or following therapy, as this may represent GTS. Although histologically benign, GTS can be fatal. In patients with GTS, complete resection is usually curative.
SURG-19. EVALUATION OF SERUM NEURON SPECIFIC ENOLASE, INTERFERON-ALPHA, AND INTERFERON-GAMMA IN RESPONSE TO LASER ABLATION OF HIGH GRADE GLIOMAS
Authors: Seamus Bartlett, Tavarekere Nagaraja, Lonni Schultz, James Ewing, Stephen Brown, Robert Knight, Ian Lee
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The blood-brain barrier (BBB) is a formidable obstacle in the treatment of gliomas. It has been speculated that the BBB may be temporarily disrupted in laser ablation, a relatively new treatment used for newly diagnosed and recurrent high grade gliomas (HGG). BBB disruption can be measured non-invasively through serum neuron specific enolase (NSE) levels. In addition to disrupting the BBB, laser ablation could trigger an immune response in brain that has yet to be studied. Interferon-alpha (IFN-α) and interferon-gamma (IFN-ɣ) are cytokines used as serum markers for an immune response. OBJECTIVE To measure NSE and IFN-α and IFN-ɣ as serum markers for BBB disruption and brain immune response activation, respectively, in patients undergoing laser ablation for recurrent high grade gliomas. METHODS Sixteen patients with recurrent HGG underwent laser ablation from 2/2017 to 12/2019. All 16 patients had gross total ablation of the contrast enhancing mass. Serum levels of NSE, IFN-α, IFN-ɣ were measured pre-operatively and at 24 hours, 2 weeks, and 8-16 weeks post-operatively, depending on adjuvant treatment received post-operatively. RESULTS Levels of NSE consistently increased 24 hours post-operatively (2.28±0.37 ng/ml) compared to pre-operative levels (1.62±0.29 ng/ml), p=0.032. Afterwards, NSE decreased and reached baseline by 2 weeks postoperatively (2 weeks- 1.67±0.29 ng/ml, 8 weeks- 1.85±0.91 ng/ml, 12 weeks- 0.81±0.33 ng/ml, 16 weeks- 1.23±0.93 ng/ml). Compared to their pre-operative levels, IFN-α and IFN-ɣ (85.46±35.29 and 1.62±0.47 pg/ml, respectively) did not display a significant difference in their serum levels (p=0.26-0.72 and 0.14-0.60, respectively, for IFN-α and IFN-ɣ) at any post-operative measurement time. Conclusions: Elevated NSE levels following laser ablation in HGG indicate a temporary disruption of the BBB that persists for approximately 2 weeks without eliciting an accompanying immune reaction in brain. Correlation studies with DCE-MRI are on-going.
QOLP-13. COMPARISON OF SYMPTOM BURDEN AND ASSOCIATED IMPACT ON DAILY LIFE IN GLIOBLASTOMA PATIENTS TREATED WITH AND WITHOUT TUMOR TREATING FIELDS
Authors: Megan Tipps, Meghan Tierney, Caitlin Monson, Kelsey Jackson, Nilanjana Banerji, Patricia Bruns, John Trusheim
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Clinical trials have demonstrated that the use of low intensity alternating electric fields, known as Tumor Treating Fields (TTFields), via the Optune™ device extends overall survival times in patients with glioblastoma when combined with standard chemotherapy. In addition to survival time, quality of life (QOL) is an important factor in treatment decisions for life-limiting diagnoses. Examinations of the impact of TTFields on QOL have yielded mixed RESULTS: Here, we describe patient-reported symptoms in patients with glioblastoma undergoing treatment with TTFields and compare symptom burden and associated interference with daily life to that of a historic non-TTFields cohort. METHODS Patients with primary glioblastoma who chose treatment with the Optune™ device were prospectively enrolled and asked to complete the brain tumor-specific MD Anderson Symptom Inventory (MDASI-BT) approximately every 8 weeks through cessation of active disease treatment. MDASI-BT assessments were examined for symptom frequency, severity, and relationships between symptom severity and interference with daily life. These results were also compared with a matched cohort of patients who did not chose TTFields treatment and completed MDASI-BT assessments as part of a previous study. RESULTS The most commonly reported symptoms for Optune™ users were fatigue, sleep disturbance and speaking/word finding. Fatigue and sleep disturbance were also among the symptoms rated as most severe, along with feeling drowsy/sleepy. Interference with general activities and overall enjoyment of life as both were reported as both the most common and most severe impacts on daily life. When compared with historic data from non-Optune™ users at the same point in treatment, we found no difference in either symptom burden (p=0.48) or interference scores (p=0.72). CONCLUSION Attention to both survival benefit and symptom experience related to treatment options can inform patient decisions and direct approaches to symptom management as well as improved QOL.
MBCL-12. MOLECULAR SIGNATURES AND TUMOR INFILTRATING IMMUNOLOGICAL CELLS ASSOCIATED WITH ASIAN MEDULLOBLASTOMA PATIENT SURVIVAL
Authors: Kung-Hao Liang, Kuo-Sheng Wu, Yi-Yen Lee, Muh-Lii Liang, Jun-Jeng Fen, Tai-Tong Wong
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Medulloblastoma is an aggressive pediatric brain tumor with surgery and post-resection radiotherapy plus chemotherapy as the major type of treatment currently. METHODS A cohort of 52 medulloblastoma patients were treated in Taipei Medical University Hospital and Taipei Veterans General Hospital. Among them, 28 (53.85%) are male. The average age at presentation is 7.21 ± 4.15. Genome-wide RNA profiling were performed on fresh-frozen surgical samples. Tumor infiltrating immune cell percentages were inferred by the cibersort immune deconvolution algorithm. RESULTS A total of 13 leading genes, including DLL1, ASIC2, SLC22A17, TRPM3, RPS2P5 and KCNC3, were found to be significantly associated with overall survival (All P &amp;lt; 0.001). A risk score was constructed, which is indicative of overall survival (Hazard Ratio [HR] = 2.720, 95% confidence interval [CI] = 1.798 ~ 4.112, P &amp;lt; 0.001) and recurrence-free survival (HR = 1.645, CI = 1.337 ~ 2.025, P &amp;lt; 0.001). After adjustment of clinical factors, the score remained significantly associated with overall survival (HR = 2.781, CI = 1.762 ~ 4.390, P &amp;lt; 0.001) and recurrence-free survival (HR = 1.604, CI = 1.292 ~ 1.992, P &amp;lt; 0.001). The percentage of Natural Killer and T follicular helper (Tfh) cells were higher in patients with better overall survival (P = 0.046 and 0.001, respectively). Furthermore, the Tfh percentage is also positively associated with mutation burdens in the expressed exonic regions (P &amp;lt; 0.001). CONCLUSION Higher mutation burdens are correlated with higher levels of tumor infiltrating Tfh cells, which is indicative of better post-surgery prognosis.
EXTH-10. COMBINATION OF EPIGENETIC ENZYME INHIBITORS, GSK-J4 AND BELINOSTAT, REVEALS HIGH EFFICACY IN IDH1 MUTANT GLIOMAS
Authors: Alisan Kayabolen, Gizem Nur Sahin, Fidan Seker, Ahmet Cingoz, Bekir Isik, Simge Acar, Hiroaki Wakimoto, Daniel Cahill, Ihsan Solaroglu, Adam Cribbs, Udo Oppermann, Tugba Bagci-Onder
Journal: Neuro-Oncology (2020)

Abstract Mutations in IDH1 and IDH2 genes are common in low grade gliomas and secondary GBM and are known to cause a distinct epigenetic landscape in these tumors. To interrogate the epigenetic vulnerabilities of IDH-mutant gliomas, we performed a chemical screen with inhibitors of chromatin modifiers and identified 5-azacytidine, Chaetocin, GSK-J4 and Belinostat as potent agents against primary IDH1-mutant cell lines. Testing the combinatorial efficacy of these agents, we demonstrated GSK-J4 and Belinostat combination as a very effective treatment for the IDH1-mutant glioma cells. Engineering established cell lines to ectopically express IDH1R132H, we showed that IDH1R132H cells adopted a different transcriptome with changes in stress-related pathways that were reversible with the mutant IDH1 inhibitor, GSK864. The combination of GSK-J4 and Belinostat was highly effective on IDH1R132H cells, but not on wt glioma cells or nonmalignant fibroblasts and astrocytes. The cell death induced by GSK-J4 and Belinostat combination involved the induction of cell cycle arrest and apoptosis. RNA sequencing analyses revealed activation of inflammatory and unfolded protein response pathways in IDH1-mutant cells upon treatment with GSK-J4 and Belinostat conferring increased stress to glioma cells. Specifically, GSK-J4 induced ATF4-mediated integrated stress response and Belinostat induced cell cycle arrest in primary IDH1-mutant glioma cells; which were accompanied by DDIT3/CHOP-dependent upregulation of apoptosis. Moreover, to dissect out the responsible target histone demethylase, we undertook genetic approach and demonstrated that CRISPR/Cas9 mediated ablation of both KDM6A and KDM6B genes phenocopied the effects of GSK-J4 in IDH1-mutant cells. Finally, GSK-J4 and Belinostat combination significantly decreased tumor growth and increased survival in an orthotopic model in mice. Together, these results suggest a potential combination epigenetic therapy against IDH1-mutant gliomas.
Cardiac Resynchronization for Asymptomatic or Mildly Symptomatic Heart Failure: A Bridge Too Far?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Christophe Leclercq, Philippe Mabo, Jean Noel Trochu
Journal: Journal of the American College of Cardiology (2008)
EPCO-16. LACTIC ACID IS AN EPIGENETIC METABOLITE THAT DRIVES GLIOBLASTOMA SURVIVAL AND GROWTH
Authors: Consuelo Torrini, Trang Nguyen, Chang Shu, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Georg Karpel-Massler, Jeffrey Bruce, Peter Canoll, Markus Siegelin
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is the most common primary malignant brain tumor with an unfavorable prognosis and a reprogrammed metabolism. While tumors utilize glucose, there are other carbon sources at their disposal. Originally considered as a waste product of glucose catabolism, lactate accumulates to a significant amount in tumor tissue. We launched our studies with the central hypothesis that lactate is metabolized by GBM cells to promote their survival via modulation of the epigenome. We showed that lactate rescued patient-derived xenograft (PDX) GBM cells from nutrient deprivation mediated cell death and inhibition of growth. Transcriptome analysis, Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), and CHIP-seq. showed that lactic acid exposure entertained a signature of cell cycle progression, oxidative phosphorylation (OXPHOS) and MYC target expression. LC/MS analysis demonstrated that U-13C-Lactate elicited substantial labeling of TCA-cycle metabolites, acetyl-CoA and histone protein acetyl-residues in PDX derived GBM cells. Given that acetyl-CoA is pivotal for histone acetylation we observed a dose-dependent elevation of histone marks (e.g. H3K27ac), which was rescued by genetic and pharmacological inhibition of lactic acid-uptake, ATP-citrate lyase, p300 histone-acetyl-transferase and OXPHOS, resulting in reversal of lactate mediated protection from cell death or facilitation of GBM growth. CHIP-seq. analysis demonstrated that lactic acid facilitated enhanced binding of H3K27ac to gene promoters and cis-regulatory elements (e.g. super-enhancers). Consistently, ATAC-seq. analysis highlighted enhanced accessibility of the chromatin by lactic acid. Finally, we assessed whether lactic acid is actively metabolized in vivo, utilizing an orthotopic PDX model of GBM. In a combined tracer experiment (U-13C-glucose and 3-C13-lactate), we made the fundamental observation that lactic acid carbons were predominantly labeling the TCA cycle metabolites over glucose, implying a critical role of lactic acid in GBMs and establishing lactic acid metabolism as a novel drug target for GBM that may be targeted with epigenetic drugs.
RARE-29. PRIMARY CENTRAL NERVOUS SYSTEM NON-HODGKIN LYMPHOMA IN AN 11-YEAR-OLD BOY: A CASE REPORT
Authors: Jorge Luis Ramírez-Melo, Regina M Navarro-Martin del Campo, Manuel D Martinez-Albarran, Fernando Sánchez-Zubieta, Ana L Orozco-Alvarado, Luis A Arredondo-Navarro, Lorelai Gutierrez-Oliva
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) are very rare in children. CLINICAL CASE: An 11-year-old male presented with a 2 months history with myoclonic movements in the upper right limb, and a sudden frontal headache, gait disturbance due to right hemiparesis and an ipsilateral convulsive episode. Upon admission he had critical condition, with hypertensive skull syndrome, Glasgow of 12, Karnofsky 40%, right hemiparesis, swallowing disorder, facial paralysis, and loss of photo motor reflex and unilateral amaurosis. A CT and MRI showed a huge tumor mass in the left tempo-parietal region, infiltrating the white matter and shifting the midline. A Tumor biopsy was done, and reported diffuse small cell non-Hodgkin lymphoma of high-grade, Burkitt type. Systemic lymphoma workup was negative. He received six cycles of chemotherapy based on high dose methotrexate, rituximab and triple intrathecal.After the second cycle an ophthalmologic evaluation was done, and found infiltration to the right retina, for which 6 cycles of intra vitreous chemotherapy with methotrexate were applied, he showed an excellent response, and recovered all his neurological functions except that right hemianopia persist. Control MRI showed partial response at 2nd cycle and complete response after the 4th cycle. No Radiation was performed. CONCLUSION This report highlights the fact that pediatric PCNSL may be effectively treated by a combination of HDMTX and rituximab-based chemoimmunotherapy without irradiation. Lack of awareness of this rare entity may lead to extense resections of brain, and potential permanent secuelae that were avoided in this illustrative case.
IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression
Authors: Lin Zhang, Yicong Wan, Zihan Zhang, Yi Jiang, Zhiyue Gu, Xiaoling Ma, Sipei Nie, Jing Yang, Jinghe Lang, Wenjun Cheng, Lan Zhu
Journal: Theranostics (2020)

N6-methyladenosine (m
Left Atrial Emptying Reserve: A Mirror of LV Diastolic Function That Predicts Prognosis?⁎⁎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: William C. Little, Takahiro Ohara
Journal: JACC. Cardiovascular imaging (2011)
Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy
Authors: Zheng‐Rong Lu, Victoria E. A. Laney, Ryan Hall, Nadia Ayat
Journal: Advanced Healthcare Materials (2020)

RNA interference (RNAi) is a promising technology to regulate oncogenes for treating cancer. The primary limitation of siRNA for clinical application is the safe and efficacious delivery of therapeutic siRNA into target cells. Lipid-based delivery systems are developed to protect siRNA during the delivery process and to facilitate intracellular uptake. There is a significant progress in lipid nanoparticle systems that utilize cationic and protonatable amino lipid systems to deliver siRNA to tumors. Among these lipids, environment-responsive lipids are a class of novel lipid delivery systems that are capable of responding to the environment changes during the delivery process and demonstrate great promise for clinical translation for siRNA therapeutics. Protonatable or ionizable amino lipids and switchable lipids as well as pH-sensitive multifunctional amino lipids are the presentative environment-responsive lipids for siRNA delivery. These lipids are able to respond to environmental changes during the delivery process to facilitate efficient cytosolic siRNA delivery. Environment-responsive lipid/siRNA nanoparticles (ERLNP) are developed with the lipids and are tested for efficient delivery of therapeutic siRNA into the cytoplasm of cancer cells to silence target genes for cancer treatment in preclinical development. This review summarizes the recent developments in environment-response lipids and nanoparticles for siRNA delivery in cancer therapy.