tbuckley/cabot-search huggingface dataset:
EPID-09. CMMRD (CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY) ASSOCIATED-BRAIN TUMORS: REPORT FROM THE EUROPEAN C4CMMRD CONSORTIUM
Authors: Léa Guerrini-Rousseau, Chrystelle Colas, Katharina Wimmer, Christine Devalck, Enrico Opocher, Franck Bourdeaut, Felipe Andreiuolo, Karin Dahan, Maurizio Genuardi, Yael Goldberg, Michaela Kuhlen, Vanesa Pérez Alonso, Astrid-Marie Sehested, Irene Slavc, Sheila Unger, Pascale Varlet, Jacques Grill, Laurence Brugières
Journal: Neuro-Oncology (2018)

Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome (OMIM#276300) due to biallelic germline mutations in MMR genes, leading to a broad spectrum of childhood malignancies including brain, hematologic and colorectal cancers associated with café-au-lait macules (CALM). Malignant brain tumors (BT) were reported in 48/78 patients (10 countries), registered in the C4MMRD database. Overall, 55 BT (47 high-grade gliomas (HGG) and 8 embryonal tumors) were diagnosed in 48 patients between 1988-2017. Median age at the first BT was 9.1y (1.1-40.6) with 8 patients over 18y. Twenty-eight patients developed multiple malignancies (including 17 before the BT). Twenty/37 families were consanguineous. All patients had biallelic germline mutations in MMR genes: PMS2 (26pts), MSH6 (10pts), MSH2 (7pts) and MLH1 (5pts). All patients with available cutaneous data but one had CALM. In addition several patients presented developmental brain anomalies. Most patients received standard treatment before immunotherapy era, without unusual treatment-related toxicity. Median survival after the first BT was 2y. Five-year overall-survival was 23% (95%-CI, 12-41) and 45% (95%-CI, 17-76) for HGG and embryonal tumors respectively. Ten patients are alive (7 HGG and 3 medulloblastomas) at last follow-up. Among the 38 deaths, 33 patients died because of their BT (first BT=28, second BT=5) and 5 of other cancers. Despite a high risk of multiple malignancies, this series suggests that some patients may be long-term survivors. Prognosis could be improved by early recognition of this rare condition leading to more specific treatments including immunotherapy and screening for second malignancies.
Comparing efficacy of 1-L Peg-Asc with prucalopride versus 2-L Peg-Asc for bowel preparation
Authors: S. Jang, Y. Jeen, S. Choi, J. Lee, S. Kim, J. Lee, H. Choi, E. Kim, B. Keum, H. Lee, H. Chun, C. Kim
Journal: Annals of Oncology (2018)

Introduction: Though numerous researches enabled decrease of the bowel preparation solution volume, it is still a major complaint of patients preparing colonoscopy. There have been studied that additional administration of laxatives could lessen the amount of aqueous formula with prokinetic effect. Prucalopride is a serotonin (5-HT4) receptor agonist which stimulate colonic mass movements and provide main propulsive force for defecation. The aim of this study is to compare 2-L PEG-Asc and 1-L PEG-Asc plus prucalopride for quality of bowel cleansing while preparing for colonoscopy and patient compliance. Methods: Two hundred patients were prospectively enrolled. Patients referred for colonoscopy were divided into group A (the split-dose 2-L PEG-Asc) and group B (1-L PEG-Asc + prucalopride) randomly. During colonoscopy, each patient's bowel preparation quality was evaluated with The Boston Bowel Preparation Scale (BBPS) and Aronchick Preparation Scale (APS). The tolerability and satisfaction of patients was determined based on a questionnaire-based survey. Results: One hundred patients received either 2-L PEG-Asc or 1-L PEG-Asc with prucalopride. Regarding colon cleansing outcome (BPPS and APS), the 1-L PEG-Asc with prucalopride group showed similar, but non-inferior results compared to the 2-L PEG-Asc group on both BBPS (7.65±1.27 vs 7.52±1.40, p = 0.586) and APS scales (93.3% vs 95%, p = 0.717). Tolerability was similar for both 1-L PEG-Asc with prucalopride and 2-L PEG-Asc. Conclusion: 1-L PEG-Asc plus prucalopride preparation showed comparable result to traditional 2-L PEG-Asc preparation. 1-L PEG-Asc plus prucalopride preparation method could be an alternative method for bowel preparation which can relieve patient's discomfort.
NSRG-19. CSF DISTURBANCES AFTER TRANSCALLOSAL RESECTION: ARE THERE PREDICTING FACTORS?
Authors: Christian Dorfer, Julia Vendl, Gregor Kasprian, Andreas Peyrl, Christine Haberler, Irene Slavc, Thomas Czech
Journal: Neuro-Oncology (2018)

To evaluate the frequency and potential predicting factors for CSF disturbances in a series of patients operated through a transcallosal approach. We retrospectively reviewed the medical charts of all patients operated at our institution via a transcallosal approach between January 2002 and December 2016. The following radiological parameters were assessed on pre- and multiple postoperative MR/CT images: ventricular size, as well as subdural space and interhemispheric fissure width. Statistical analyses were performed to identify clinical and radiological predicting factors for shunt dependent hydrocephalus within three months after surgery. We identified 74 patients (female n=40, male n=34; median age 17.6yrs, range from 6 mos - 76 yrs). An EVD was placed preoperatively in 18 patients (24.3%). Histology revealed a colloid cyst in 15 (20.3%), pilocytic astrocytoma in 14 (18.9%), diffuse astrocytoma WHO II in 5 (6.8%), diffuse astrocytoma WHO III+IV in 7 (9.5%), subependymal giant cell astrocytoma in 5 (6.8%), craniopharyngioma in 5 (6.8%) and other in 23 (31.0%). After a median time of 24 days (range from 10 days - 3 mos) since transcallosal resection implantation of a VP-shunt was necessary in 9 patients (12.2%) and a subduro-peritoneal shunt in 5 (6.6%). The mean age at shunt implantation was 14.3 yrs. The necessity for postoperative shunt implantation was significantly associated with younger age. The incidence of early shunt dependent hydrocephalus after transcallosal resection is high (18.8%), especially in younger children. The reason for shunt dependency is multifactorial.
Poly(GR) impairs protein translation and stress granule dynamics in C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis
Authors: Yong-Jie Zhang, Tania F. Gendron, Mark T. W. Ebbert, Aliesha D. O’Raw, Mei Yue, Karen Jansen-West, Xu Zhang, Mercedes Prudencio, Jeannie Chew, Casey N. Cook, Lillian M. Daughrity, Jimei Tong, Yuping Song, Sarah R. Pickles, Monica Castanedes-Casey, Aishe Kurti, Rosa Rademakers, Bjorn Oskarsson, Dennis W. Dickson, Wenqian Hu, Aaron D. Gitler, John D. Fryer, Leonard Petrucelli
Journal: Nature Medicine (2018)
DEV-01. QUANTITATIVE NEEDS ASSESSMENT DIFFERENCES IN THE MANAGEMENT OF CHILDREN WITH CENTRAL NERVOUS SYSTEM (CNS) CANCER IN A MIDDLE-INCOME COUNTRY AND A HIGH-INCOME COUNTRY
Authors: Allison Fischer, Roberto Roecker, Jonathan Finlay, Andrea Capellano, Diana Osorio
Journal: Neuro-Oncology (2018)

Pediatric cancer cure rates differ among high-income countries (HIC) and low-to-middle income (LMIC) countries. The World Health Organization reports 20% of LMIC have the necessary data and resources to significantly decrease the rate of mortality in their patients. We compared individual capacities of two major pediatric institutions from a HIC and LMIC caring for children with CNS cancer, the second most common type of cancer of childhood. A quantitative-needs assessment questionnaire and key informant interviews were used to evaluate the treatment of children with CNS cancer at IOP/GRAACC/UNIFESP children’s cancer center in São Paulo, Brazil and Nationwide Children’s Hospital/The Ohio State University (NCH/OSU) in Columbus, OH; United States. Both hospitals have 24-hour pediatric oncology, nursing and pediatric intensivist coverage. Supportive care including social workers, psychologists, child life specialists, and physical/occupational/speech therapists are available at both centers. Differences included 2 part-time neuro-radiologists and 2 pathologists at IOP/GRAACC/UNIFESP, whereas 8 full-time neuro-radiologists and 12 pathologists (with 2 specially trained in neuro-pathology) at NCH/OSU. There are 4 pediatric neurosurgeons on staff at each hospital, however, 2 surgical days at IOP/GRAACC/UNIFESP, compared to 7 days/week at NCH/OSU. Additionally, delays in initiation of radiation treatment at IOP/GRAACC/UNIFESP extended 2–4 weeks compared to less than 1 week at NCH/OSU. Center-specific differences in resources exist in highly-specialized hospitals caring for children with CNS cancer in LMIC and HIC. This quantitative-needs assessment can develop targeted strategies for effective interventions to improve on the management of children with CNS cancers.
QOL-07. INVESTMENT IN TRAINING TEACHERS OF PAEDIATRIC ONCOLOGY PATIENTS INFLUENCES SUPPORT PROVIDED IN THE SCHOOL ENVIRONMENT
Authors: Sarah Jane Watts, Katherine Cox
Journal: Neuro-Oncology (2018)

Every year approximately 2000 children in the UK are diagnosed with cancer, the majority of which are of school age. Literature suggests a strong positive correlation between school attendance and psychological wellbeing, both during and after active treatment. Teachers can provide a supportive professional link between hospital and school, and impact on the extent to which re-entry to school is successful. The extent to which teachers understand issues related to cancer diagnosis and treatment has been shown to affect the level of school support that paediatric oncology patients receive. This suggests that the provision of medical and psychological education to teachers is a key investment in the long term wellbeing of paediatric oncology patients. Will the provision of a full-day training course to teaching staff increase the understanding of cancer diagnosis and treatment, and the implications of these factors on pupil support needs at school? 76 teaching staff attended an Oncology Teacher’s Day full-day training held in December 2016 at Newcastle University, UK. A thematic analysis was conducted on the data collated from post-training questionnaires. Respondent data demonstrated a greater understanding of the issues affecting the education of pupils with cancer and their siblings. Additionally, respondents felt that they gained a number of useful strategies and resources from the day to implement in their own practice. Investment of time in providing training to teaching staff is likely to indirectly influence paediatric oncology patient support in the school environment.
EPEN-16. PATIENT-DERIVED PFA EPENDYMOMA XENOGRAFT MODEL
Authors: Andrea Griesinger, Angela Pierce, Davis Witt, Patrick Flannery, Andrew Donson, Katherine Gowan, Todd Hankinson, Michael Handler, Kenneth Jones, Adam Green, Rajeev Vibhakar, Nicholas Foreman
Journal: Neuro-Oncology (2018)

Advances in ependymoma (EPN) treatment have been hampered due to lack of relevant in vitro and in vivo models. Our lab successfully generated patient derived posterior fossa group A (PFA) EPN cell lines. Our present goal is to establish patient derived xenograft (PDX) mouse models. Disaggregated cells from a primary PFA tumor (811) were injected subcutaneously into NSG mice flanks forming tumors 8 months post injection. Tumors were confirmed as EPN by typical histologic features by a neuropathologist. This flank tumor was successfully used to establish monolayer cell lines. 850K methylation array on flank tumor showed the same chromosome abnormalities as the primary tumor, including gain of 1q. Transcriptomic clustering analysis showed that flank tumor grouped with PFA EPN primary tumors. Flank tumor cells were disaggregated into single cell suspension and serially injected both subcutaneous and intracranial. Serial flank tumors formed within 2 months of injection. MRI imaging of one intracranial injected mouse showed a large mass in the cerebellum. Additionally, before MRI scans could be performed, a second symptomatic mouse with intra-ventricle injection was euthanized. Necropsy revealed an encapsulated mass between the midbrain and cerebellum and histology confirmed classic EPN features. This mass was serially transplanted into lateral ventricle of several additional mice. In addition to MAF811_5, we have preliminary evidence, that needs to be confirmed, that 2 further EPN tumors have established flank xenografts and cell lines. These PDXs are promising in showing the feasibility of establishing PFA xenograft models together with matching cell lines.
CRAN-25. METASTATIC CHOROID PLEXUS CARCINOMA WITHOUT ADJUVANT TREATMENT WITH GOOD SURVIVAL: A CASE REPORT
Authors: Lacey Carter, Naina Gross
Journal: Neuro-Oncology (2018)

Three-year-old previously healthy female presented with drowsiness and vomiting found to have a 3.6x5.1x6.1cm enhancing solid, partially cystic mass centered within the atrium of the right ventricle and an enhancing intradural mass at S1/S2 with enhancement of nerve roots concerning for leptomeningeal carcinomatosis. Patient underwent subtotal resection of the ventricular mass determined to be choroid plexus carcinoma with associated p53 mutation. Family elected palliative care. Patient had an Ommaya reservoir placed for intermittent removal of CSF for headaches. After developing elevated intracranial pressure not relieved by drainage, patient underwent repeat subtotal resection thirty-one months after initial resection. Microscopic examination in the original tumor was difficult due to crush artifact which obscured any mitoses, but demonstrated severe pleomorphism and was invasive into surrounding neural tissue. The tumor was positive for p53, Kir7.1, synaptophysin, and CAM5.2 and negative for PLAP, glypican-3 and EMA. Frequency of Ki67/Mib-1 immunolabeling was variable, but focally high. Despite the lack of obvious mitotic activity, given p53 and Ki67/Mib-1 immunolabeling, patient was diagnosed with choroid plexus carcinoma. Specimen from second resection showed the same results. Patient presented with multiple poor prognostic factors including p53 mutation, metastasis at presentation, subtotal resection, and no adjuvant treatment. Meta-analysis indicates subtotal resection without adjuvant treatment leads to estimated median survival of less than five months. Patient has not only survived, but has done very well. This case illustrates a clinical course that does not match the predicted disease course for the pathologic diagnosis. Further delineation of these tumors is needed.
Epithelial–Mesenchymal Transition in Human Prostate Cancer Demonstrates Enhanced Immune Evasion Marked by IDO1 Expression
Authors: Kimberley Kolijn, Esther I. Verhoef, Marcel Smid, René Böttcher, Guido W. Jenster, Reno Debets, Geert J.L.H. van Leenders
Journal: Cancer Research (2018)

Cancer invasion and metastasis are driven by epithelial-mesenchymal transition (EMT), yet the exact mechanisms that account for EMT in clinical prostate cancer are not fully understood. Expression of N-cadherin is considered a hallmark of EMT in clinical prostate cancer. In this study, we determined the molecular mechanisms associated with N-cadherin expression in patients with prostate cancer. We performed laser capture microdissection of matched N-cadherin-positive and -negative prostate cancer areas from patient samples (n = 8), followed by RNA sequencing. N-cadherin expression was significantly associated with an immune-regulatory signature including profound upregulation of indoleamine 2,3-dioxygenase (IDO1; log2-fold change = 5.1; P = 2.98E-04). Fluorescent immunostainings of patient samples confirmed expression of IDO1 protein and also its metabolite kynurenine in primarily N-cadherin-positive areas. N-cadherin-positive areas also exhibited a local decrease of intraepithelial cytotoxic (CD8+) T cells and an increase of immunosuppressive regulatory T cells (CD4+/FOXP3+). In conclusion, EMT in clinical prostate cancer is accompanied by upregulated expression of IDO1 and an increased number of regulatory T cells. These data indicate that EMT, which is an important step in tumor progression, can be protected from effective immune control in patients with prostate cancer.Significance: These findings demonstrate EMT is linked to an immunosuppressive environment in clinical prostate cancer, suggesting that patients with prostate cancer can potentially benefit from combinatorial drug therapy. Cancer Res; 78(16); 4671-9. ©2018 AACR.
PCLN-07. A 3D HYDROGEL CULTURE SYSTEM FACILITATES STUDY OF PRIMARY PEDIATRIC LOW-GRADE GLIOMA CELLS IN VITRO
Authors: Karen D Wright, Emily Chadwick, Christopher Rota, Alexander Brown, Linda Stockdale, Mark W Kieran, Keith Ligon, Liliana Goumnerova, Douglas Lauffenburger, Linda Griffith, Rosalind Segal
Journal: Neuro-Oncology (2018)

Gliomas are the most common solid tumor of childhood and while children with low grade gliomas (LGGs) are likely to survive their disease, their course is complicated by significant treatment-related neurocognitive and endocrinological sequelae. Few accurate preclinical LGG models exist, thereby limiting development and testing of novel targeted agents. We developed a 3D, hydrogel-based co-culture system utilizing mouse astrocytes to support growth of primary human pediatric LGG cells in vitro. This tunable hydrogel system recapitulates many features of brain extracellular matrix, while the co-cultured astrocytes provide growth factors and other components normally present in vivo. In this system, patients’ tumor cells are dissociated, and functionalized polyethylene glycol-based hydrogels are produced to surround tumor cells. These tumor-containing hydrogels are then placed adjacent to adherent layers of primary mouse astrocytes and the co-cultures grown for an extended period of time. Using this system, multiple types of human LGG cells and other pediatric tumor cells can be successfully cultured in hydrogels for up to one month. Moreover, these hydrogels can be enzymatically dissolved, releasing tumor cells to passage into new gels. Fluorescent 5-ethynyl-2’-deoxyuridine labeling followed by confocal microscopy of co-cultures reveals viable, proliferating cell clusters even one month later. While high grade gliomas in this setting proliferate rapidly, cultured LGG cells proliferate slowly, much like their original tumor counterparts. These methods can be used to provide patient-specific avatars to identify the best personalized targeted therapies. Moreover, the system enables investigations of the brain tumor microenvironment as a modulator of tumor growth.
Three strong moves to improve research and replications alike
Authors: Roger Giner-Sorolla, David M. Amodio, Gerben A. van Kleef
Journal: Behavioral and Brain Sciences (2018)

Abstract We suggest three additional improvements to replication practices. First, original research should include concrete checks on validity, encouraged by editorial standards. Second, the reasons for replicating a particular study should be more transparent and balance systematic positive reasons with selective negative ones. Third, methodological validity should also be factored into evaluating replications, with methodologically inconclusive replications not counted as non-replications.
DEV-05. INCIDENCE OF BRAIN TUMOUR IN PAEDIATRIC POPULATION AT A TERTIARY CANCER CENTRE IN NEPAL
Authors: Shivaji Poudel
Journal: Neuro-Oncology (2018)

Nepal is a developing country with limited resources for neuro surgical intervention for diagnosis and treatment of Pediatric Brain Tumours. B P Koirala is the only government funded comprehensive cancer centre which caters to treat pediatric brain tumours. Brain Tumour registered in 2016 & 2017 were retrospectively studied from the Medical Record Department. 14 cases were identified with 11 male and 3 Female and the age ranging from 3–15 years. The pediatric brain tumour patient are less reported in developing country due to poor socioeconomic status of the family or minimal access to health care or poor medical record keeping.
HGG-22. PHASE 1b STUDY POLIO VACCINE SABIN-RHINOVIRUS POLIOVIRUS (PVSRIPO) FOR RECURRENT MALIGNANT GLIOMA IN CHILDREN
Authors: David M Ashley, Eric M Thompson, Daniel Landi, Annick Desjardins, Allan H Friedman, Stevie Threatt, James E Herndon, II, Susan Boulton, Frances McSherry, Eric S Lipp, John H Sampson, Henry S Friedman, Darell D Bigner, Matthias Gromeier
Journal: Neuro-Oncology (2018)

BACKGROUNDPrognosis of recurrent World Health Organization (WHO) grade IV malignant glioma (GBM) in children is dismal with no effective therapy. We have recently performed a dose-finding and toxicity study within adults with GBM, evaluating the recombinant non-pathogenic polio/rhinovirus chimera (PVSRIPO) by intratumoral convection-enhanced delivery (CED). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of tumor stroma. We have commenced a Phase Ib study to evaluate feasibility, safety, and preliminary evidence of efficacy of the optimal adult dose in a pediatric population.
TBIO-23. INTRACRANIAL EXTRA-SKELETAL MESENCHYMAL CHONDROSARCOMA: CASE REPORT AND META-ANALYSIS OF REPORTED CASES IN ADULTS AND CHILDREN
Authors: Saman Shabani, Ha Son Nguyen, Jeffrey Knipstein, Sean Lew, Bruce Kaufman, Michael Lawlor, Andrew Foy
Journal: Neuro-Oncology (2018)

Intracranial extra-skeletal mesenchymal chondrosarcoma (IEMC) is a rare tumor that accounts for only 0.16% of primary intracranial tumors. We review our experience and the medical literature for patients with IEMC. Case report and meta-analysis of reported IEMC. Kaplan-Meier survival test was used for statistical analysis. Total of 71 reported cases including ours. Follow-up ranged from 3 days to 216 months. Age at diagnosis ranged from 2 month to 71 years, however the majority were under 18. There was strong female predominance. 55% had GTR versus 22% with STR. 36 (51%) patients received radiation therapy, 9 (12.7%) had chemotherapy, and 9 (12.7%) had both XRT and chemotherapy. 52/71 (73.2%) of tumors had dural attachment and the rest were purely intraparenchymal. Median overall survival was 25 months (+/- 5.392). Improved survival was noted for the first 50 months in XRT group (P= 0.032). Survival was worse with recurrence (p= 0.002). Dural based tumors had better survival compared to purely intraparenchymal tumors, but not statistically significant (p=0.071). GTR seemed to improve survival compared to STR, but was not statistically significant (p=0.455). IEMC is a malignant tumor with 45% mortality and median overall survival of 25 months. Radiation significantly increases the survival in these patients especially in the first 50-month after diagnosis. Recurrence significantly decreases survival. Although GTR seems to increase survival, this was not statistically significant. The effect of chemotherapy on survival cannot be determined.
NQO1 inhibits the TLR-dependent production of selective cytokines by promoting IκB-ζ degradation
Authors: Akihiro Kimura, Masayuki Kitajima, Kyoko Nishida, Satoshi Serada, Minoru Fujimoto, Tetsuji Naka, Yoshiaki Fujii-Kuriyama, Satoshi Sakamato, Takumi Ito, Hiroshi Handa, Takashi Tanaka, Akihiko Yoshimura, Harumi Suzuki
Journal: The Journal of Experimental Medicine (2018)

NAD(P)H:quinone oxidoreductase 1 (NQO1) protects cells against oxidative stress and toxic quinones. In this study, we found a novel role of NQO1 in suppressing Toll-like receptor (TLR)–mediated innate immune responses. NQO1-deficient macrophages selectively produced excessive amounts of IL-6, IL-12, and GM-CSF on LPS stimulation, and the deletion of NQO1 in macrophages exacerbated LPS-induced septic shock. NQO1 interacted with the nuclear IκB protein IκB-ζ, which is essential for the TLR-mediated induction of a subset of secondary response genes, including IL-6, and promoted IκB-ζ degradation in a ubiquitin-dependent manner. We demonstrated that PDLIM2, known as the ubiquitin E3 ligase, participates in NQO1-dependent IκB-ζ degradation. NQO1 augmented the association between PDLIM2 and IκB-ζ, resulting in increased IκB-ζ degradation. Collectively, this study describes a mechanism of the NQO1–PDLIM2 complex as a novel and important regulator in the innate immune signaling and suggests the therapeutic potential of NQO1 in TLR-mediated inflammation and disorders.