tbuckley/cabot-search huggingface dataset:
RADT-28. RADIATION DOSE-DEPENDENT LONG-TERM NEUROCOGNITIVE DECLINE IN LOW GRADE GLIOMA PATIENTS: RESULTS OF A CROSS-SECTIONAL STUDY
Authors: Peter Sinnige, Hiske van der Weide, Miranda Kramer, Roelien Enting, Ingeborg Bosma, Sandra Rakers, Rients Huitema, Anne Buunk, Jacoba Spikman, Johannes Langendijk
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Radiotherapy is a well-known risk factor for neurocognitive decline in glioma patients. Advanced radiotherapy techniques enable more selective brain irradiation. However, limited data exists on which brain regions are most relevant to avoid. The aim of this study was to explore the dose-effect relationship between brain subvolumes and neurocognitive performance. METHODS In this cross-sectional study, patients with grade II or III glioma treated with radiotherapy who were free of progression for at least one year were eligible. Patients underwent a neurocognitive test battery, including Rey Auditory Verbal Learning Test; (RAVLT), Trail Making Test (TMT), Copy of Rey’s Complex Figure Test (RCFT), Single Digit Modalities Test (SDMT) and Verbal Fluency tests (letters and categories). Test scores were correlated to radiation dose distributions in brain subvolumes using non-parametric tests. RESULTS The study was composed of 17 right-handed patients with grade II (n= 14) and grade III (n= 3) gliomas. The mean follow up after radiotherapy was 42 months, and the mean age 47 years. Performance on all tests was significantly worse for patients compared to healthy matched controls. Correlations were found between: 1) dose to the left hippocampus and performance on the RAVLT (Delayed Recall) (r= -0.60; p= 0.011); 2) dose to the supratentorial brain and performance on the TMT-A (r= 0.54; p= 0.025) and 3) dose to the left hemisphere and SDMT (r= -0.64; p= 0.006) and verbal fluency tests (for letters score: r= -0.73; p= 0.001). CONCLUSIONS We found significant correlations between radiation dose to the left hippocampus and hemisphere and neurocognitive performance. In this small sample we could not account for the effect of tumor location as a confounder. Reducing radiation dose to the left hippocampus and hemisphere by using advanced radiotherapy techniques may give superior neurocognitive outcomes.
Trump administration writes dozens of “midnight regulations” undermining health and environmental protections
Authors: Owen Dyer
Journal: BMJ (2020)

A last minute flurry of regulations by the Trump administration includes dozens of hard-to-undo rules that experts say would increase pollution, raise health costs, lower nutritional standards, and restrict the use of scientific evidence in government decision making.

The latest rule, finalised on 9 December, will bar the Environmental Protection Agency from considering illnesses and deaths avoided as benefits to be set against the financial cost of curbing air pollutants when writing regulations under the Clean Air Act.1

Earlier this week, another rule froze current restrictions on fine particulate pollution for at least five years to come, disregarding expert advice which said that continuing to tighten limits would save thousands of lives a year.

Passing what …
EPEN-35. PERITONEAL CARCINOMATOSIS OF ANAPLASTIC EPENDYMOMA: FIRST REPORTED CASE
Authors: Jonathan Schwartz, Dena Weinmann, Julia Guerin, Laurence Eckel, Keating Gesina, David Daniels
Journal: Neuro-Oncology (2020)

Abstract Peritoneal Carcinomatosis of anaplastic ependymoma is not a previously reported entity. The authors report on a child with multiple successfully treated brain and spine disease occurrences who subsequently develops carcinomatosis of the abdomen and no evidence of CNS recurrence. Ependymoma accounts for up to 10% of childhood CNS tumors diagnosed in the United States with a median age of 51–71 months. Typical locations are based on age. Disease is typically treated with surgical resection followed by radiation. The role of chemotherapy has not been proven but currently being examined with open clinical trials. We will describe patient’s presentations, clinical treatment and recurrence with subsequent treatment and outcome at time of meeting.
Effects of shear stress and flow pulsatility on endothelial function: Insights gleaned from external counterpulsation therapy**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: Joseph A Vita, Gary F Mitchell
Journal: Journal of the American College of Cardiology (2003)
MBRS-62. CURAXIN CBL0137 INHIBITS THE VIABILITY OF CANCEROUS CELLS IN PRE-CLINIC MODELS OF MYC-AMPLIFIED MEDULLOBLASTOMA
Authors: Jiajia Wang, Baocheng Wang, Yang Zhao, Jie Ma
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma is a malignant brain tumour that mostly occurs in children, and MYC-amplified medulloblastoma is characterized by pronounced invasiveness and dismal prognosis. There is no effective treatment for Medulloblastoma and its precise pathological mechanism remains obscure. Previous studies indicated that the altered epigenetic machinery manifested in the neoplastic transformation of MYC-amplified MB has become increasingly evident. It is hypothesized that epigenetic genes dependencies associated with small molecule inhibitors that have been approved or are in advanced development may help identify the potential therapeutic targets. By integrating mRNA expression profiles and the corresponding clinic-pathologic information of patients suffering from medulloblastoma, and analysing prior CRISPR screening results, we demonstrated that SSRP1 is a negative prognostic factor that functions to stimulate the viability of MB cells. SSRP1 is a subunit of the FACT complex, an important histone chaperone required for transcriptional regulation, DNA replication and damage repair. Its biological effect on tumour proliferation was assessed by using RNA interference and administering CBL0137, a small molecular inhibitor of FACT. Gene expression analysis also demonstrated that CBL0137 selectively downregulated the expression of MYC and NEUROD1. Furthermore, the administration of CBL0137 suppressed tumour growth in mouse xenograft models. This pharmacological method to selectively target MYC transcription was demonstrated in our study, and therefore can be applied as a promising treatment strategy for MYC-amplified medulloblastoma. In Conclusion, we identified an attractive strategy of selectively downregulating MYC transcription by applying inhibitor CBL0137, thereby revealing the potential clinical utility of CBL0137 to improve the prognosis of MYC-amplified medulloblastoma patients.
LINC-28. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH MEDULLOBLASTOMA TREATED AT THE NATIONAL CANCER INSTITUTE (INCA) IN RIO DE JANEIRO, BRAZIL
Authors: Gabriela Oigman, Diana Osorio, Joseph Stanek, Jonathan Finlay, Denizar Vianna, Sima Ferman
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. Brazil is an upper-middle income country according to World Bank, with features of LMIC and HIC. METHODS We conducted a retrospective review of 126 children (0–18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively; overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS The male/female ratio was 1.42 and the median age at diagnosis was 7.9 years. Headache (79%) and nausea/vomiting (75%) were the most common presenting symptoms. The median time from onset of symptoms to surgery was 50 days. The OS for standard-risk patients was 69% and 53% for high-risk patients. Patients initiating radiation therapy within 42 days after surgery (70.6% versus 59.6% p=0.016) experienced better OS. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.025). Patients who lived &amp;gt;40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS These findings suggest that socioeconomic factors, education, early diagnosis and continuous data collection, besides oncological treatment must be adressed to improve the survival of children with MB.
QOL-59. CEREBELLAR MUTISM SYNDROME AND THE SURGICAL RISK FACTORS: A PROSPECTIVE MULTICENTRE STUDY OF 500 PATIENTS UNDERGOING TUMOUR SURGERY IN THE POSTERIOR FOSSA
Authors: Jonathan Kjær Grønbæk, Morten Wibroe, Sebastian Toescu, Pernilla Grillner, Conor Mallucci, Emanuela Molinari, Kristin Solem, Mia Westerholm-Ormio, Rosita Kiudeliene, Katalin Mudra, Peter Hauser, Kirsten van Baarsen, Eelco Hoving, Julian Zipfel, Karsten Nysom, Kjeld Schmiegelow, Astrid Sehested, Marianne Juhler, René Mathiasen
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Cerebellar mutism syndrome (CMS) is a severe neurological complication of tumour surgery in the posterior fossa in childhood. The incidence is reported between 8 and 39%, where CMS sets in within days of surgery and resolves within months, yet long-term sequelae are seen in most patients. This prospective cohort study investigates the course of CMS and the surgical cause of the syndrome. POPULATION AND METHODS We included 500 children with a tumour in the posterior fossa with planned surgery or open biopsy. Enrolment was conducted between 2014 and 2020 in 26 centres in ten European countries. Speech, neurological symptoms and surgical procedure were registered in predefined standardized forms pre-operatively and at three post-operative follow-ups within one year. PRELIMINARY RESULTS A total of 426 children underwent primary surgery and were eligible for analyses. CMS occurred in 56 patients (13.1%) one day (median; IQR: 0–2 days) after surgery and resolved within 38 days (median; IQR: 4–52 days). Another 58 patients (13.6%) had less severe speech impairment. Mutism was associated with lower age (OR: 0.91 [95%CI: 0.85;0.98, p=0.014]), medulloblastoma (OR: 2.5 [95%CI: 1.4;4.7, p=0.0036]) and ATRT (OR: 12.9 [95%CI: 3.4;51.9, p=0.00018]) and tumour location in the fourth ventricle (OR: 4.0 [95%CI: 2.3;7.2, p&amp;lt;0.0001]). Preliminary multivariate analyses revealed no significant association between mutism and surgical access. CONCLUSION CMS is a common complication predominantly seen in younger children after tumour surgery for a medulloblastoma or ATRT in the fourth ventricle. The incidence is not related to the surgical access in this study population.
NHS England proposes new indicators to replace four hour target in emergency departments
Authors: Adrian O’Dowd
Journal: BMJ (2020)

New indicators could replace the existing four hour emergency department target in England, including patients being seen and assessed within 15 minutes in a hospital, under an official consultation launched on 15 December. NHS England’s consultation on transforming urgent and emergency care1 proposes that the current four hour target—which says that 95% of people arriving at emergency departments should be treated and then be discharged, admitted, or transferred within four hours—should be replaced with 10 indicators or a “bundle of standards.” Other indicators, which the consultation describes as a “more sophisticated and patient centred set of metrics,” include:
65MO A phase I clinical trial on intratumoural (IT) administration of ipilimumab (IPI) plus nivolumab (NIVO) followed by intracavitary (IC) administration of nivolumab in patients with recurrent glioblastoma
Authors: J.K. Schwarze, C. Bertels, G. Awada, J. Tijtgat, S. Tuyaerts, L. Cras, F. Vaeyens, A-M. Vanbinst, H. Everaert, A. Michotte, B. Caljon, C. Olsen, T. Janssen, S. Van Dooren, R. Forsyth, J. Duerinck, B. Neyns
Journal: Annals of Oncology (2020)
Early assessment of the impact of mitigation measures to control COVID-19 in 22 French metropolitan areas, October to November 2020
Authors: Guillaume Spaccaferri, Sophie Larrieu, Jérôme Pouey, Clémentine Calba, Thomas Benet, Cécile Sommen, Daniel Lévy-Bruhl, Sabira Smaili, Didier Che, Laurent Filleul, Céline Caserio-Schönemann, Fatima Ait-El-Belghiti, Sylvie Haeghebaert, Jean-Claude Desenclos, Laëtitia Huiart, Anne Laporte, Patrick Rolland
Journal: Eurosurveillance (2020)

In France, measures including curfew and lockdown were implemented to control the COVID-19 pandemic second wave in 2020. This study descriptively assesses their possible effects, also relative to their timing. A considerable decrease in incidence of COVID-19 cases and hospital admissions was observed 7 to 10 days after mitigation measures were put in place, occurring earlier in metropolitan areas which had implemented these first. This temporal coincidence suggests the measures’ positive impact, consistent with international experiences.
CCL16 maintains stem cell-like properties in breast cancer by activating CCR2/GSK3β/β-catenin/OCT4 axis
Authors: Wenzhi Shen, Xiaoyuan Zhang, Jiaping Tang, Zhixin Zhang, Renle Du, Dehong Luo, Xiaoran Liu, Yong Xia, Yanping Li, Shanshan Wang, Siyuan Yan, Wancai Yang, Rong Xiang, Na Luo, Yunping Luo, Jianjun Li
Journal: Theranostics (2020)

Rationale: Considerable evidence suggests that breast cancer metastasis and recurrence occur due to emergence of cancer stem cells (CSCs). In our previous study, we designed a high-throughput siRNA screening platform that identifies inflammation genes involved in the regulation of cancer cell stemness. We reported that CCL16 protein decreases OCT4 expression and reduces the ALDH+ subpopulation. However, the mechanism by which CCL16 maintains stem cell-like properties remains unclear. Methods: Tissue microarrays were used to evaluate CCL16 expression. Cancer stemness assays were performed in CCL16 knockdown and overexpressing cells in vitro and in a xenograft model in vivo. Human phosphokinase array, immunofluorescence and chromatin immunoprecipitation assays were performed to explore the underlying mechanism. Results: We report that CCL16 was overexpressed in breast tumors and significantly correlated with clinical progression. We found that silencing CCL16 in MDA-MB-231 and BT549 cells diminished CSC properties including ALDH+ subpopulation, side population, chemo-resistance, and sphere formation. Furthermore, mice bearing CCL16-silenced MDA-MB-231 xenografts had lower tumorigenic frequency and developed smaller tumors. Exploration of the underlying mechanism found that CCL16 selects CCR2 to activate p-AKT/GSK3β signaling and facilitate β-catenin nuclear translocation. Further, CCL16 binds to the OCT4 promoter and promotes OCT4 expression. In addition, shRNAs targeting CCR2 and XAV939 targeting β-catenin abolished CCL16-mediated cancer stemness. Upstream, IL10 mediates STAT3 activation, which binds to the CCL16 promoter and enhances its expression. The STAT3-targeted inhibitor Stattic suppressed CCL16 expression in vitro and restrained tumor progression in vivo. Conclusions: We identified a potential CSC regulator and suggest a novel mechanism for how CCL16 governs cancer cell stemness. We propose that CCL16 could be an effective target for breast cancer therapy.
Effects of Dietary Patterns on Serum Urate: Results From a Randomized Trial of the Effects of Diet on Hypertension
Authors: Stephen P. Juraschek, Chio Yokose, Natalie McCormick, Edgar R. Miller, Lawrence J. Appel, Hyon K. Choi
Journal: Arthritis & Rheumatology (2020)

Objective To determine whether the Dietary Approaches to Stop Hypertension (DASH) diet or an alternative, simplified diet, emphasizing high‐fiber fruits and vegetables (the FV diet), lowers serum urate levels. Methods We conducted a secondary study of the DASH feeding study, a 3‐arm, parallel‐design, randomized trial of 459 adults with systolic blood pressure (BP) of &lt;160 mm Hg and diastolic BP of 80–95 mm Hg, who were not receiving BP medications. Participants were randomized to receive 8 weeks of monitored feeding and ate 1 of 3 diets: 1) a typical American diet (control), 2) the FV diet, a diet rich in fruits and vegetables but otherwise similar to the control diet, or 3) the DASH diet, which was rich in fruits, vegetables, and low‐fat dairy products, and reduced in fat, saturated fat, and cholesterol. Body weight was kept constant throughout the study. Serum urate levels were measured at baseline and after 8 weeks of feeding. Results For the 327 participants with available specimens (mean ± SD age 45.4 ± 11.0 years, 47% women, 50% African American), the mean ± SD baseline serum urate level was 5.7 ± 1.5 mg/dl. Compared to the control diet, the FV diet reduced the mean serum urate level by 0.17 mg/dl (95% confidence interval [95% CI] −0.34, 0.00; P = 0.051) and the DASH diet reduced the mean serum urate level by 0.25 mg/dl (95% CI −0.43, −0.08; P = 0.004). These effects increased with increasing baseline serum urate levels (&lt;5, 5–5.9, 6–6.9, 7–7.9, and ≥8 mg/dl) for those receiving the DASH diet (a reduction of 0.08, 0.12, 0.42, 0.44, and 0.73 mg/dl, respectively; P for trend = 0.04), but not for those receiving the FV diet. Conclusion Our findings indicate that the DASH diet reduces serum urate levels, particularly among those with hyperuricemia. These findings support the growing need for a dedicated trial to test the DASH diet among patients with hyperuricemia and gout.
NIMG-17. VALIDATION OF DIFFUSION MRI AS AN IMAGING BIOMARKER FOR BEVACIZUMAB THERAPY IN RECURRENT GLIOBLASTOMA IN A RANDOMIZED PHASE III TRIAL OF BEVACIZUMAB WITH OR WITHOUT VB-111 (GLOBE)
Authors: Benjamin Ellingson, Timothy Cloughesy, Chencai Wang, Kunal Patel, Catalina Raymond, Andrew Brenner, John de Groot, Nicholas Butowski, Leor Zach, Jian Campian, Jacob Schlossman, Shan Rizvi, Yael Cohen, Noa Lowenton-Spier, Tamar Rachmilewitz Minei, Shifra Fain-Shmueli, Patrick Wen
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Evidence from independent single center as well as multicenter phase II trials have suggested diffusion MRI is a strong predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF monotherapy, but not systemic chemotherapies or combination therapies with anti-VEGF agents. The current study builds on this body of evidence by evaluating these diffusion MR phenotypes in a large randomized phase III clinical trial. METHODS Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus bevacizumab in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pre-treatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as having high (&amp;gt;1.24 um2/ms) or low (&amp;lt; 1.24 um2/ms) ADCL, the mean value of the lower peak in a double Gaussian model of the ADC histogram within the contrast enhancing tumor. RESULTS Baseline tumor volume (P=0.3460) and ADCL (P=0.2143) did not differ between treatment arms. Univariate analysis showed that patients with high ADCL had a significant survival advantage when pooling all patients (P=0.0006), as well as when examining the BV (P=0.0159) and BV+VB-111 individually (P=0.0262). Multivariable Cox regression accounting for treatment arm, age, baseline tumor volume and ADCL identified continuous measures of tumor volume (P&amp;lt; 0.0001; HR=1.0212) and ADCL phenotypes (P=0.0012; HR=0.5574) as independent predictors of OS. CONCLUSION Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111. Since ADCL was predictive of OS in combination BV+VB-111, results support the working hypothesis that co-administration of VB-111 with BV may block any VB-111 anti-tumor effect, whereas VB-111 monotherapy or priming may result in higher efficacy of VB-111.
Combining inhibition of galectin-3 with and before a therapeutic vaccination is critical for the prostate-tumor-free outcome
Authors: Carolina Tiraboschi, Lucas Gentilini, Carla Velazquez, Enrique Corapi, Felipe Martín Jaworski, José Daniel Garcia Garcia, Yorfer Rondón, Anne Chauchereau, Diego José Laderach, Daniel Compagno
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Prostate cancer (PCa) is a major health problem worldwide. Taxol derivatives-based chemotherapies or immunotherapies are usually proposed depending on the symptomatic status of the patient. In the case of immunotherapy, tumors develop robust immune escape mechanisms that abolish any protective response, and to date why prostate cancer is one of the most resistant diseases remains unresolved. Methods By using a combination of clinical data to study the transcriptome of metastasis samples from patients with castration-refractory prostate cancer, and state of the art cellular and molecular biology assays in samples from tumor-bearing mice that have been submitted to surgical resection of the tumor before receiving a vaccination, we answered several essential questions in the field of immunotherapy for prostate cancer. We also used two different methods to inhibit the expression of galectin-3 (Gal-3) in tumor cells: a stable RNA interference method to control the expression of this galectin efficiently only in tumor cells, and low and non-cytotoxic doses of docetaxel to easily transfer our findings to clinical settings. Results Herein, we show for the first time that Gal-3 expressed by prostate tumor cells is the main immune checkpoint responsible for the failure of vaccine-based immunotherapy. Our results show that low and non-cytotoxic doses of docetaxel lead to the inhibition of Gal-3 expression in PCa cells as well as in clinical samples of patients with metastatic and castration-resistant PCa promoting a Th1 response. We thus optimized a prostate cancer animal model that undergoes surgical resection of the tumor to mimic prostatectomy usually performed in patients. Importantly, using Gal-3-knocked down-PCa cells or low and non-cytotoxic doses of taxane before vaccination, we were able to highly control tumor recurrence through a direct impact on the proliferation and infiltration of CD8+ cytotoxic T. Conclusions Thus, Gal-3 expression by PCa cells is a crucial inhibitor for the success of immunotherapy, and low doses of docetaxel with non-cytotoxic effect on leukocyte survival could be used before immunotherapy for all patients with PCa to reduce the expression of this critical negative immune checkpoint, pre-conditioning the tumor-microenvironment to activate an antitumor immune response and promote tumor-free outcome.