tbuckley/cabot-search huggingface dataset:
ATRT-10. SPATIO-TEMPORAL DELETION OF SMARCB1 DETERMINES MOUSE AT/RT SUBTYPES
Authors: Zhi-Yan Han, Mamy Andrianteranagna, Arnault Tauziède-Espariat, Paul Fréneaux, Julien Masliah-Planchon, Christine Bourneix, Gaelle Pierron, Amaury Leruste, Céline Chauvin, Pascale Varlet, Didier Surdez, Olivier Delattre, Franck Bourdeaut
Journal: Neuro-Oncology (2018)

The cell(s) of origin of AT/RTs remains unclear. We previously developed a mouse model consisting in tamoxifen inducible system in a Smarcb1Flox/Flox;Rosa26-CreERT2 background. We obtained two subgroups of intracranial tumors, one with neuronal and the other with non-neuronal features, in keeping with the diversity observed in human AT/RTs. To investigate the potential cell(s) of origin of those various AT/RTs, we first endeavored to specify whether different time points of Smarcb1 inactivation correlated with specific anatomic location and/or molecular subgroups. Thereby, we identified that the neuronal group, mostly developing from the sub-ventricular zone and the spinal cord, was almost exclusively obtained with the earliest inactivation time point(E6-E7). In contrary, the non-neuronal group emerged after Smarcb1 inactivation at any time point(E6-E10), and showed intracranial but extra-parenchyma/meningeal origins. In order to more specifically identify the cell(s) of origin for the neuronal group, we next generated developmental stage-specific conditional knockout mice carrying Smarcb1 inactivation by restricting Cre expression upon promoters characteristic for various neural stem cells/progenitors. While Smarcb1Flox/Flox;Atoh1CreERT2 showed ataxia but failed to give rise to any tumor whatever the embryonal time point, targeting Nestin-expressing cells led to tumors with morphological rhabdoid features; these again showed some molecular diversity as observed in human AT/RTs. The study of the impact of Smarcb1 inactivation in other promoter-restricted backgrounds is ongoing. In conclusion, we show that spatio-temporal deletion of Smarcb1 determines mouse AT/RT subtypes. Our new mouse models not only give insight on the cell(s) of origin, but also provide interesting preclinical models.
Re-deployment of a dislodged lumen-apposing metal stent (LAMS): avoiding the sacrificial LAMS
Authors: Vinay Chandrasekhara, Mark Topazian, Barham Abu Dayyeh, Michael Levy
Journal: Endoscopy (2018)

Lumen-apposing metal stents, or LAMS, have been increasingly used for endoscopic drainage of walled-off pancreatic necrosis (WON). However, these can become dislodged during endoscopic necrosectomy and are expensive to replace. This video highlights a technique to reuse a LAMS after it has become dislodged ([Video 1]).
GERM-14. ADVANCED MR IMAGING OF GERMINOMA
Authors: Fumiyuki Yamasaki, Yasuyuki Kinoshita, Takeshi Takayasu, Satoshi Usui, Manish Kolakshyapati, Motoki Takano, Naoto Yamada, Kazuhiko Sugiyama, Kaoru Kurisu
Journal: Neuro-Oncology (2018)

The differentiation of germinoma from other tumors can be very difficult. We evaluated the usefulness of advanced MRI for the differentiatial diagnosis of germinoma. MATERIALS AND Our IRB approved this retrospective study. We reviewed the images of 26 patients with histologically confirmed germinoma who were treated in our institution between 2003 and 2016. We also studied 25 patients with pineal tumors which included 14 non-germinomatous germ cell tumors (NGGCT), 9 pineal parenchymal tumors (PPT) and 2 meningioma. Patients underwent CT and conventional MRI and advanced MRI including diffusion-weighted imaging (DWI) and/or arterial spin labeling based perfusion-weighted imaging and single voxel proton MR spectroscopy (1HMRS). In germinoma patients group, age ranged from 9.1 to 37.7-years (average 17.5, median 14.6). 24 were male, and 2 were female patients. High lipids peak at 1HMRS was observed in 16 of 16 examined tumors. On the other hand, in the PPT and meningioma, lipid peaks were small or absent in 10 of 10 examined tumors. In NGGCT group, high lipids peak at 1HMRS was also observed in 11 of 12 examined tumors, while they did not show high intensity on DWI, rather, they showed low to high mixed intensity. ADC was statistically lower in germinoma group than in NGGCT group (P=0.0002). Relative tumor blood flow (rTBF) was statistically lower in germinoma group than in NGGCT group (P=0.0087). Lower ADC value, low rTBF and high lipids peak at 1HMRS are characteristics of germinoma.
Integrating Radiosensitivity and Immune Gene Signatures for Predicting Benefit of Radiotherapy in Breast Cancer
Authors: Yi Cui, Bailiang Li, Erqi L. Pollom, Kathleen C. Horst, Ruijiang Li
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Breast cancer is a heterogeneous disease and not all patients respond equally to adjuvant radiotherapy. Predictive biomarkers are needed to select patients who will benefit from the treatment and spare others the toxicity and burden of radiation. Experimental Design: We first trained and tested an intrinsic radiosensitivity gene signature to predict local recurrence after radiotherapy in three cohorts of 948 patients. Next, we developed an antigen processing and presentation-based immune signature by maximizing the treatment interaction effect in 129 patients. To test their predictive value, we matched patients treated with or without radiotherapy in an independent validation cohort for clinicopathologic factors including age, ER status, HER2 status, stage, hormone-therapy, chemotherapy, and surgery. Disease-specific survival (DSS) was the primary endpoint. Results: Our validation cohort consisted of 1,439 patients. After matching and stratification by the radiosensitivity signature, patients who received radiotherapy had better DSS than patients who did not in the radiation-sensitive group [hazard ratio (HR), 0.68; P = 0.059; n = 322], whereas a reverse trend was observed in the radiation-resistant group (HR, 1.53; P = 0.059; n = 202). Similarly, patients treated with radiotherapy had significantly better DSS in the immune-effective group (HR, 0.46; P = 0.0076; n = 180), with no difference in DSS in the immune-defective group (HR, 1.27; P = 0.16; n = 348). Both signatures were predictive of radiotherapy benefit (Pinteraction = 0.007 and 0.005). Integration of radiosensitivity and immune signatures further stratified patients into three groups with differential outcomes for those treated with or without radiotherapy (Pinteraction = 0.003). Conclusions: The proposed signatures have the potential to select patients who are most likely to benefit from radiotherapy. Clin Cancer Res; 24(19); 4754–62. ©2018 AACR.
DEV-11. OUTCOMES OF MALIGNANT BRAIN TUMORS IN YOUNG CHILDREN TREATED WITH CHEMOTHERAPY AND DELAYED RADIOTHERAPY IN A RESOURCE LIMITED SETTING
Authors: Ananda KC, Hari Sankaran, Vasudev Bhat, Prakash Shetty, Jayanth Shastry, Ayushi Sahay, Epari Shridhar, Abhishek Mahajan, Maya Prasad, Tushar Vora, Sona Pungaonkar, Aliasgar Moiyadi, Tejpal Gupta, Rakesh Jalali, Girish Chinnaswamy
Journal: Neuro-Oncology (2018)

A retrospective analysis of children less than 3 years diagnosed with malignant brain tumors was conducted from January 2011 to December 2016. Children with malignant brain tumors were treated with cyclophosphamide, etoposide and carboplatin (CEJ) upto 36months of age or till disease progression. Low grade gliomas were excluded from the analysis. An intention to treat analysis was performed to determine the outcomes and delay in radiotherapy (RT). ninety four children (median age: 26 months, median follow-up: 18.9 months) were diagnosed with malignant brain tumors of which 59 received the CEJ regimen. Twenty six children (44.0%) underwent a complete resection, 23 (38.9%) partial resection, and 10 (16.9%) debulking/biopsy. Progression free survival (PFS) and overall survival (OS) at 24months was 53.8% (95% CI: 38.6% - 66.9%) and 64.0% (95% CI: 48.7%- 78.8%) respectively.41 children (69.5%) received RT with a median time to delaying RT of 9.3months (inter-quartile range 6.5 -13.4 months). Among 39 cases of medulloblastoma (MB), molecular data was available in 24 (wnt-0, shh-11, group 3 and group4 – 13). The outcomes with shh and non-shh were similar. Chemotherapy regimens like CEJ are effective in delaying radiotherapy in young children with malignant brain tumors. This approach may be used in resource limited countries to improve the outcomes of young children with malignant brain tumors.
Spatial Intratumor Genomic Heterogeneity within Localized Prostate Cancer Revealed by Single-nucleus Sequencing
Authors: Fei Su, Wei Zhang, Dalei Zhang, Yaqun Zhang, Cheng Pang, Yingying Huang, Miao Wang, Luwei Cui, Lei He, Jinsong Zhang, Lihui Zou, Junhua Zhang, Wenqinq Li, Lin Li, Jianyong Shao, Jie Ma, Fei Xiao, Ming Liu
Journal: European Urology (2018)
Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study
Authors: John B. Buse, Satish K. Garg, Julio Rosenstock, Timothy S. Bailey, Phillip Banks, Bruce W. Bode, Thomas Danne, Jake A. Kushner, Wendy S. Lane, Pablo Lapuerta, Darren K. McGuire, Anne L. Peters, John Reed, Sangeeta Sawhney, Paul Strumph
Journal: Diabetes Care (2018)

OBJECTIVE Evaluate the efficacy and safety of the dual sodium–glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400 mg (n = 262) after 6 weeks of insulin optimization. The primary end point was HbA1c change from baseline at 24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks. RESULTS From a mean baseline of 7.57%, placebo-adjusted HbA1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all P &amp;lt; 0.001). Among patients with a baseline HbA1c ≥7.0%, an HbA1c &amp;lt;7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (P ≤ 0.003 vs. placebo) at 24 weeks. At 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were −1.08 mmol/L for fasting plasma glucose, −4.32 kg for weight, and −15.63% for bolus insulin dose and −11.87% for basal insulin dose (all P &amp;lt; 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P &amp;lt; 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo. CONCLUSIONS In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).
IMMU-10. NIVOLUMAB IN THE TREATMENT OF RECURRENT OR REFRACTORY PEDIATRIC BRAIN TUMORS: A SINGLE INSTITUTIONAL EXPERIENCE
Authors: Hamza Gorsi, Denise Malicki, Paritosh Khanna, Jennifer Elster, Valentin Barsan, Mark Tumblin, Lanipua Yeh-Nayre, Mehrzad Milburn, John Crawford
Journal: Neuro-Oncology (2018)

Tumor cells evade immune-mediated destruction through activation of checkpoints. Successful use of the immune checkpoint inhibitors in certain cancer types has generated interest in using this approach in pediatric brain tumors. Ten consecutive children (6 boys, 4 girls, mean age 11 years, range 2-17 years) with pediatric recurrent or refractory pediatric brain tumors (4 high grade glioma, 2 pineoblastoma, 1 disseminated low grade glioma, 1 medulloblastoma, 1 ependymoma, 1 primitive neuro-ectodermal tumor) were treated at Rady Children’s Hospital San Diego from 2015-2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 weeks). Eight had received prior chemotherapy and 9 received prior radiation therapy. Seven had radiographic progression of disease (total 36 doses, mean 3.6 doses) with mean time to progression of 5.4 weeks (range 1.6-13.7 weeks). One patient voluntarily discontinued treatment after stable disease at 24 weeks and 2 patients showed either transient stability or partial response of brain disease but worsening of metastatic disease. There were no dose limiting side effect observed, however there was a 10 % incidence of elevated ALT, hyperglycemia, pancreatitis and hypo-albuminemia. Although the tumor mutation burden (TMB) was low (mean 2, range 0-6.3), there was a trend between TMB and time to progression. PDL-1 immuno-histochemical analysis and next generation sequencing data on each tumor will be presented. Our findings suggest nivolumab is well tolerated in pediatric patients with recurrent brain tumors. Future randomized controlled studies stratifying for TMB may be necessary to demonstrate the efficacy of PD-L1 inhibitors in recurrent pediatric brain tumors.
Why the VA Needs More Competition
Authors: Kyle H. Sheetz, David J. Shulkin
Journal: New England Journal of Medicine (2018)

Interview with Dr. David Shulkin on strategies for enhancing the quality of care at VA medical centers. (07:33)Download If the Veterans Affairs health system receives funding for modernization, it can compete on quality and outcomes with the private sector. Rather than being a step toward privatization, such competition is a way of maximizing resources and promoting high-quality care.
포스터발표 : 컨벤션홀 특설 발표장 ; 1형 위정맥류(GOV1)에서 내시경 정맥류 결찰술의 치료 효과
Authors: 최원혁, 권소영, 김정환, 서태호, 고순영, 김병국, 이창홍
Journal: Clinical and Molecular Hepatology (2008)
Prolonged overall survival of metastatic gastric cancer patients with BRCA germline mutations
Authors: N. Halpern, A. Grinshpun, B. Boursi, T. Golan, O. Margalit, D. Aderka, Y. Laitman, E. Friedman, A. Hubert, T. Peretz, T. Hamburger, I. Kedar-Barnes, Z. Levi, I. Ben-Aharon, Y. Goldberg, E. Shacham-Shmueli
Journal: Annals of Oncology (2018)

Introduction: Gastric cancer is the fifth most frequently diagnosed malignancy worldwide and the third leading cause of cancer related death. The prognosis of gastric cancer remains poor with median overall survival rates of less than 12 months in the advanced setting. Significant efforts are made to identify prognostic and predictive markers to tailor treatment decisions. BRCA1 and BRCA 2 germline mutations are an established predictive marker to a favorable response to DNA-damaging agents (platinum agents and Poly(ADP-ribose)polymerase inhibitors) in ovarian, breast prostate and pancreatic cancers. There is limited clinical data in regard to the efficacy of DNA-damaging agents on BRCA germline mutation carriers with gastric cancer. Methods: A multi-center retrospective analysis of genetic databases and patient's files was performed in three medical centers to identify consecutive BRCA1/2 germline mutation carriers with gastric adenocarcinomas between the years 1994 to 2018. Patient's characteristics and disease course were collected and summarized. Results: Nine BRCA1/2 carriers with gastric adenocarcinomas were identified. Five of them were females. Six patients were from an Ashkenazi origin. Seven patients had BRCA2 mutation. Three patients had a personal history of a second malignancy. Two patients had a first-degree family member with gastric cancer. Mean age at diagnosis was 64 (range of 52-74 years). One patient demonstrated positive HER2 staining (IHC +3) in her tumor. We did not identify unique patterns in term of tumor location or histology. Six patients had metastatic disease. Five patients with metastatic disease received DNA-damaging agents. The median overall survival of the six metastatic patients was 25 months (range 13-43), three of them have ongoing durable responses. Conclusion: Germline BRCA1/2 mutations are associated with a relatively favorable prognosis in gastric cancer patients treated with DNA-damaging agents. Some patients in our cohort had a first degree relative with gastric cancer, possibly indicating a unique phenotype in some BRCA families. Further research is needed to determine the characteristics and long-term outcome of these patients.
EAPH-15. COMBINATION THERAPY WITH VINCRISTINE, IRINOTECAN, AND TEMOZOLOMIDE IN CENTRAL NERVOUS SYSTEM MALIGNANCIES
Authors: Amber Gibson, Abhishek Bavle, Naina Gross, Theresa Gavula, Rene McNall
Journal: Neuro-Oncology (2018)

Current therapeutic options for high grade gliomas including DIPG (HGG) and relapsed or refractory CNS malignancies (R-CNS), excluding low grade gliomas, are often of limited efficacy. We examined the combination of vincristine with extended dosing of irinotecan and temozolomide with an antibiotic for diarrhea prophylaxis (VITA) in a phase I study and have continued to use it after study closure. We often combine the regimen with radiation and/or bevacizumab. We treated 3 newly diagnosed HGG and 19 R-CNS patients with mild toxicity (see prior report). Here we report the efficacy. We conducted a retrospective chart review of pediatric patients treated with VITA to quantify the median time to progression (TTP) and median OS. Overall, the 22 patients had TTP of 8.25 (range 1.3 to >118 months) and OS 12 (range 3 to >118 months). By tumor type - medulloblastoma (8) 12 and 13.75 months, PNET (5) 20 and 27+ months (3 of 5 still alive), HGG (7) 5 and 7 months (8 and 12.5 months if newly diagnosed), primary CNS sarcoma (1 myxoid liposarcoma and 1 Ewing) 39 and 43 months. If radiation used in conjunction (8 patients), the outcomes improved with 20.5 months TTP and 36 months OS. Three are alive with no evidence of disease 27–118 months after VITA and radiation. These data suggest VITA can provide prolonged survival for many patients with challenging CNS malignancies but is rarely curative. We believe VITA is a promising backbone therapy on which to add novel therapies.
Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding
Authors: Hiroyuki Hosokawa, Jonas Ungerbäck, Xun Wang, Masaki Matsumoto, Keiichi I. Nakayama, Sarah M. Cohen, Tomoaki Tanaka, Ellen V. Rothenberg
Journal: Immunity (2018)
Ethical Guidelines for Genomic Research in Africa
Authors: M.J. Friedrich
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Adding oxaliplatin (OX) do neoadjuvant therapy of locally advanced rectal cancer (LARC): Still promising option?
Authors: W. Rogowski, L. Wyrwicz, V. Sulzyc-Bielicka
Journal: Annals of Oncology (2018)

Introduction: Fluoropyrimidine (5-fluorouracil or capecitabine, FU)-based regimens and radiation are standard-of-care in neoadjuvant treatment of patients with LARC. Meta-analysis (2012) showed, that adding OX to FU significantly improved pathologic complete response (pCR), and reduced peri-operative metastases with significantly higher toxicity rate. The aim of study was to review a literature published after 2012, assessing the role of OX in neoadjuvant treatment of LARC and to consider meta-analysis feasibility. Methods: We searched PubMed, EMBASE, and Cochrane library after 2012 to select the studies with neoadjuvant OX. We also searched trial registries and conference proceedings with variably combined key words. Results: We identified 66 different studies with numerous phase II and III trials, including more than 3000 patients in total. They evaluated adding OX to existing chemotherapy (CHT) regimens (mFOLFOX6), combinations with drugs from other class (antiangiogenic – bevacizumab) or new drugs (S-1), and also combination with radiotherapy (RTH) with CHT given prior to, concomitant with, or following g RTH. Other category includes studies with combination with surgical treatment. Unfortunately, there are very different endpoints analyzed: resection rate, sphincter rate, pCR, downstaging, local-regional tumor event rate, local-regional tumor recurrence, DFS, OS. Results from elected studies are contradictory; some studies show that: adding OX to mFOLFOX6 is safe, effective and reasonable option; increasing of proportion of patients eligible for invasive treatment; significant improvement of DFS. On the other hand, others show that adding OX does not improve local-regional disease control, DFS, and OS. Conclusion: Variety of studies published since 2012 till date will be presented and discrepancies regarding their results will be also discussed. We will also present some assumptions as regard to further up-dated meta-analysis.
LGG-11. REGULATION OF ONCOGENE-INDUCED SENESCENCE IN PILOCYTIC ASTROCYTOMA
Authors: Juliane L Buhl, Florian Selt, Thomas Hielscher, Felix Sahm, David Capper, Kathrin Schramm, Johannes Ridinger, Diren Usta, Jonas Ecker, Ina Oehme, Cornelis M van Tilburg, Marcel Kool, Andreas von Deimling, Martin U Schuhmann, Andrey Korshunov, Stefan M Pfister, Tilman Brummer, David T W Jones, Olaf Witt, Till Milde
Journal: Neuro-Oncology (2018)

The main challenge in the clinical management of pilocytic astrocytoma (PA) is its unpredictable growth behavior. PA cells are driven into oncogene-induced senescence (OIS) by aberrant MAPK activation. In other senescence models OIS was shown to be regulated and maintained by the senescence-associated secretory phenotype (SASP). In this study, the first patient-derived cell culture model DKFZ-BT66 was used to show presence of the SASP in PA and to analyze its impact on OIS. This model allows for shifting between proliferation and senescence via doxycycline-inducible inhibition of the OIS-relevant p53/RB pathway. Both states were studied using gene-expression profiling (GEP), Western blot, qPCR, ELISA, and automated trypan blue exclusion staining. The GEP shows significant upregulation of SASP factors during OIS in DKFZ-BT66 cells. Conditioned medium of senescent DKFZ-BT66 cells is sufficient to induce growth arrest of proliferating DKFZ-BT66 cells. Upregulation of the SASP factors IL-1B and IL-6 was validated on mRNA and protein levels and both pathways are active during OIS. Stimulation of the IL-1 pathway reduces growth of proliferating DKFZ-BT66 cells. While pharmacological inhibition of single cytokines is not sufficient to overcome growth arrest during OIS, treatment with the anti-inflammatory drug dexamethasone induces regrowth of senescent cells. Overall, the primary PA model provides evidence of the presence of OIS in PA and exhibits increased activity of the SASP during senescence. Our data suggest that the SASP has an important impact on the growth regulation of senescent PA cells. Alteration of SASP factors may result in spontaneous regrowth of senescent PA tumors.