tbuckley/cabot-search huggingface dataset:
NCOG-50. CLINICAL AND GENOMIC FACTORS ASSOCIATED WITH SEIZURES IN MENINGIOMAS
Authors: Trisha Gupte, Lan Jin, Chang Li, Kanat Yalcin, Mark Youngblood, Danielle Miyagishima, Ketu Mishra, Robert Fulbright, Zeynep Erson-omay, Murat Gunel, Jennifer Moliterno
Journal: Neuro-Oncology (2020)

Abstract Clinical and genomic sequencing data of 394 patients surgically treated for meningioma were reviewed to better understand the relationship between seizures and meningiomas. Correlations of clinical and genomic variables and occurrence of preoperative (PRESZ) and postoperative (POSTSZ) seizures were analyzed. 17% of patients presented with PRESZ and used AEDs preoperatively for 46.5 months on average as they were more likely to be treated in the setting of a recurrent tumor (p = 0.042). PRESZ patients were at higher risk for worse progression free survival (HR 2.68, 95% CI 1.30-5.50) and were also more likely to have meningiomas with an NF2-mutation (p = 0.032), higher grade (p = 0.030) and brain invasion (p = 0.009). On multivariate analysis, edema (OR 3.11, 95% CI 1.46-6.65; p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03-3.90; p = 0.041) were positive predictors of PRESZ, while genomic subgroup was not, such that the effect of NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort. 20% of all seizure-free patients were able to discontinue AED use postoperatively and they were more likely to have undergone a GTR (p = 0.031). Edema (OR 13.69, 95% CI 1.19-14.88; p = 0.026), recurrent tumors (OR 7.41, 95% CI 1.27-8.68; p = 0.015), and postoperative radiation (OR 6.37, 95% CI 1.16-7.53; p = 0.023) were significant predictors of POSTSZ. Hedgehog-pathway mutated tumors were associated with POSTSZ in Grade I meningiomas (p = 0.026). While NF2-mutated tumors are significantly associated with PRESZ, this appears due to corresponding edema and atypical histology. Patients who undergo radiation and/or suffer recurrence are at risk for POSTSZ, irrespective of extent of resection. PRESZ may portend a more potentially aggressive molecular entity and challenging clinical course with higher recurrence risk.
Cancer photo-immunotherapy: from bench to bedside
Authors: Miao Wang, Jie Rao, Meng Wang, Xiaosong Li, Kaili Liu, Mark F. Naylor, Robert E. Nordquist, Wei R. Chen, Feifan Zhou
Journal: Theranostics (2020)

Targeted therapy and immunotherapy in combination is considered the ideal strategy for treating metastatic cancer, as it can eliminate the primary tumors and induce host immunity to control distant metastases. Phototherapy, a promising targeted therapy, eradicates primary tumors using an appropriate dosage of focal light irradiation, while initiating antitumor immune responses through induced immunogenic tumor cell death. Recently, phototherapy has been employed to improve the efficacy of immunotherapies such as chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors. Phototherapy and immunoadjuvant therapy have been used in combination clinically, wherein the induced immunogenic cell death and enhanced antigen presentation synergy, inducing a systemic antitumor immune response to control residual tumor cells at the treatment site and distant metastases. This review summarizes studies on photo-immunotherapy, the combination of phototherapy and immunotherapy, especially focusing on the development and progress of this unique combination from a benchtop project to a promising clinical therapy for metastatic cancer.
NIMG-11. IMPACT OF INVERSION TIME FOR FLAIR ACQUISITION ON THE T2-FLAIR MISMATCH DETECTABILITY FOR IDH-MUTANT, NON-CODEL ASTROCYTOMAS
Authors: Manabu Kinoshita, Hideyuki Arita, Masamichi Takahashi, Takehiro Uda, Junya Fukai, Kenichi Ishibashi, Noriyuki Kijima, Ryuichi Hirayama, Mio Sakai, Astuko Arisawa, Hiroto Takahashi, Katsuyuki Nakanishi, Naoki Kagawa, Kouichi Ichimura, Yonehiro Kanemura, Yoshitaka Narita, Haruhiko Kishima
Journal: Neuro-Oncology (2020)

Abstract PURPOSE The current research tested the hypothesis that TI shorter than 2400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. EXPERIMENTAL DESIGN We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL LrGGs, 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI &amp;lt; 2400 ms for 3T or 2016 ms for 1.5T, and 103 MRI from 103 patients from the TCIA/TCGA dataset for LrGG. The presence or absence of the “T2-FLAIR mismatch sign” was evaluated, and we compared diagnostic accuracies according to TI used for FLAIR acquisition. RESULTS The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2400 ms under 3T for FLAIR acquisition (p = 0.0009, Fisher’s exact test). The T2-FLAIR mismatch sign was positive only for IDHmt, non-CODEL astrocytomas even if we confined the cohort with FLAIR acquired with shorter TI (p = 0.0001, Fisher’s exact test). TCIA/TCGA dataset validated that the sensitivity, specificity, PPV, and NPV of the T2-FLAIR mismatch sign to identify IDHmt, non-CODEL astrocytomas improved from 31%, 90%, 79%, and 51% to 67%, 94%, 92%, and 74%, respectively if we acquired FLAIR with TI shorter than 2400 ms. CONCLUSIONS We revealed that TI for FLAIR impacts diagnostic accuracy of the T2-FLAIR mismatch sign and that FLAIR scanned with TI &amp;lt; 2400 ms in 3T is necessary for LrGG imaging.
CSIG-08. TARGETING ION TRANSPORT-REGULATORY KINASES AS A NOVEL TREATMENT FOR GLIOBLASTOMA
Authors: Paula Schiapparelli, Paola Suarez Meade, Pierre Miranda-Herrera, Alexandra R Bechtle, Farren Issacs, Andre Levchenko, Jesse Rinehart, Alfredo Quinones-Hinojosa
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Currently, treatment is focused on achieving maximal safe resection, followed by chemo- and radiotherapy. Although surgery remains the most important therapeutic component, complete surgical resection is virtually impossible, as GBM cells readily infiltrate the adjacent brain parenchyma. One fundamental mechanism for GBM cell migration is the ability of these cells to use cell volume regulation as a driving force of cell infiltration and potentially interfering with apoptosis and cell cycle progression. In this work, we targeted the master regulators of cell volume, the kinases STE20/SPS1-Related Proline-Alanine-Rich Protein Kinase (SPAK) and Oxidative stress-responsive kinase-1) (OSR1) by using a novel proprietary small molecule inhibitor. In order to study the effects of inhibiting SPAK and OSR1, we analyzed cell proliferation and migration. First, we determined the IC50 using six different patient-derived GBM cell lines; we found IC50 values ranging from 0.2–2μM. Next, cell proliferation was determined by cell cycle analysis through Edu labeling. We found a significant decrease in S phase and cell cycle arrest in G2M (p= 0.001, n=6). In addition, cell migration was determined using boyden chamber assay. We found a dose-dependent reduction in cell migration (p=0.001, n=3). These results correlated with the phenomenon observed in an orthotopic murine model of GBM, in which the inhibitor showed a decrease in tumor growth (p=0.0026, n=4) and greater survival rates in vivo (p=0.0046, n=8). When used in combination with radiation therapy, this small molecule inhibitor was capable of radio-sensitizing GBM cells decreasing clonogenicity (p=0.01, n=3) were observed in vitro. In summary, by targeting the SPAK/OSR1 kinases with a small molecule inhibitor, GBM cells become less aggressive, mainly by interfering with cell migration and proliferation and becoming more sensitive to radiation.
CRISPR/Cas9 from bench to bedside: what clinicians need to know before application?
Authors: Zi-Qing Li, Chao-Hong Li
Journal: Military Medical Research (2020)

In October 2020, Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna won the Nobel Prize in Chemistry for their pioneering work in precise genome editing using the CRISPR technology. Although CRISPR technology has developed rapidly in the last decade, there are still many uncertainties before eventual use in clinical settings. In this mini review, we summarize the current efforts in addressing the limitations of CRISPR technology and future directions.
INNV-07. THE ROLE OF BIOPSY IN MOLECULAR DIAGNOSIS OF DIFFUSE INTRINSIC PONTINE GLIOMA PATIENTS
Authors: Julia Epelbaum, Julie Krystal, Mark Atlas, Steven Schneider, Mark Mittler, Shaun Rodgers
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Diffuse intrinsic pontine glioma (DIPG) is an aggressive and fatal pediatric brain tumor. Due to its difficult anatomic location and infiltrative nature, DIPGs are not surgically resectable and more than 90% of children die within two years of diagnosis. Historically, standard of care has consisted of clinical and radiological diagnosis followed by palliative radiation for symptomatic relief. Although tumor biopsy is not necessary for diagnosis, there is debate as to whether the procedure provides benefits that outweighs its risk. Recent studies have proposed that biopsy-driven molecular characterization of these tumors can inform prognosis and identify potential treatment targets that could lead to clinical breakthroughs. METHODS This study was a retrospective chart review of 26 patients treated for a DIPG diagnosis between July 1998 and July 2019 at Cohen Children’s Medical Center. We compared outcomes of biopsied vs. non-biopsied DIPG patients through quantitative data analyzing the number and types of treatment given. We analyzed post-surgical data regarding safety of DIPG biopsies which were performed by optical stereotactic needle biopsy or robot-assisted stereotactic biopsy procedures. RESULTS There were no permanent biopsy complications in any patient and biopsy did not delay treatment as average hospital stay was 1.5 days. All biopsies collected sufficient material for next generation sequencing analysis and revealed targetable mutations for available clinical trial therapies. 67% of patients were subsequently enrolled in clinical trials, 75% of which required biopsy results for enrollment. MGMT promoter methylation assay results in all tested DIPG biopsy cases indicated resistance to temozolomide, the most common treatment agent given to non-biopsied patients. CONCLUSION Biopsy of DIPG tumors is a safe and accurate procedure that does not delay treatment and identifies molecular targets for individualized therapy. The role of biopsy in DIPG patients allows for molecular characterization of DIPG tumors which informs and increases treatment options.
EPID-32. SURVIVAL OF INTRACRANIAL TUMOR IN CIPTO MANGUNKUSUMO GENERAL HOSPITAL
Authors: Tiara Aninditha, Putra Pratama, Jonathan Odilo, Henry Sofyan, Darma Imran, Renindra Aman, Retno Werdhani, Teguh Ranakusuma
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Intracranial tumor is a debilitating health burden that cause sever disability. The incidence rate for intracranial tumor is 4.63 per 100,000 populations. Through the development of diagnostic and therapeutic modalities, the survival of intracranial tumor improved although modest. There were several factors such as demographic, clinical, and histopathological affect intracranial tumor survival. However, there were no study about intracranial tumors and factors affecting it survival in Indonesia. This study provides insight of intracranial tumor patients and factor affecting 1-year survival in Cipto Mangunkusumo General Hospital from 2014–2016. METHODS The design of this study is retrospective cohort. The subjects were followed-up 1 year after diagnosis. The data retrieved from Dept. of Neurosurgery and Dept. of Neurology Cipto Mangunkusumo General Hospital neuro-oncology registry. Subjects with intracranial tumors underwent surgery/biopsy were included in this study. The factors analyzed in this study were demography, clinical characteristics, histopathology, and treatment types. Analysis of survival were done with Kaplan-Meier curve and cox regression. RESULTS There were 317 subjects in this study. Overall 1-year survival of intracranial tumors were 75.4%. There was increased risk of death (HR 1.88; CI95% 1.2–2.94; p = 0.005) in subjects &amp;gt;46 years old. There was no different of risk of death (HR 0.66; CI95% 0.92–1.03; p = 0.067) between men and women. There was no different of risk of death (HR 1.39; CI95% 0.72–2.70; p = 0.333) between supratentorial and infratentorial tumor. There was difference of survival among histopathology (p &amp;lt; 0.001) and therapeutic approaches (p &amp;lt; 0.001). DISCUSSION This is the first study in Indonesia that analyze survival of intracranial tumor. Several factors such as age, histopathology, and therapeutic approaches were found to affect 1-year survival of intracranial tumor. To get a representative insight of intracranial tumor in Indonesia, a larger cohort study should be conducted.
The Measurable Residual Disease Status of Acute Myeloid Leukemia in First Complete Remission at Allogeneic Hematopoietic Cell Transplantation Interacts with Conditioning Intensity to Predict Outcome
Authors: Maria Helena H. Gilleece, Myriam Labopin, Ibrahim Yakoub-Agha, Liisa Volin, Gerard Socie, Per Ljungman, Anne Huynh, Eric Deconinck, Depei Wu, Jean-Henri Bourhis, Mohamad Mohty, Jean-Yves Cahn, Emmanuelle Polge, Audrey Mailhol, Bipin N. Savani, Arnon Nagler
Journal: Blood (2017)
New Methods for Risk Stratification in Patients After Myocardial Infarction: Autonomic Control and Substrate Sensitivity⁎⁎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: Peter Sleight
Journal: Journal of the American College of Cardiology (2007)
EXTH-20. SYNGENEIC B7-H3-SPECIFIC CAR T-CELLS HAVE POTENT ANTI-BRAIN TUMOR ACTIVITY VIA LOCAL OR SYSTEMIC DELIVERY
Authors: Dalia Haydar, Zhongzhen Yi, Haley Houke, Martine F Roussel, Chris DeRenzo, Stephen Gottschalk, Giedre Krenciute
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND We and others have identified B7-H3 (CD276) as a promising target for CAR T-cell-based immunotherapies for pediatric brain tumors. So far, B7-H3-CAR T cells have only been studied in xenograft models for brain tumors, which do not recapitulate the immunosuppressive tumor microenvironment (TME). To overcome this obstacle, we decided to adapt the immune competent GL261 murine glioma model which mimics human disease and host immune barriers. METHODS To evaluate their safety and efficacy, murine B7-H3-CAR T-cells were generated using retroviral particles encoding a 2nd generation B7-H3-CAR with a CD28.z signaling domain. Expansion, persistence, and anti-tumor activity were evaluated in vitro and in vivo. Components of the brain TME were then evaluated using flow cytometry and immunostaining. RESULTS B7-H3-CAR T cells only killed B7-H3+ tumor cells, secreted significant levels of IFNγ and IL-2 in an antigen-dependent manner and expanded an average of 85-fold in repeat stimulation assay with B7-H3+ tumor cells in contrast to control CAR T-cells. In vivo, intratumoral (2x106) or systemic (3x106) injection of syngeneic B7-H3-CAR T-cells into mice with orthotopic GL261 glioma induced complete regression in 60% of treated mice resulting in a significant survival advantage. Mice showed no evidence of acute or long-term toxicities related to CAR T-cell infusions. We confirmed this encouraging safety profile by systemic administration of a high dose (1x107) B7-H3-CAR T-cells and performing histological analyses of all major organs on day 14 post T-cell injection, which showed no notable signs of injury or on-target/off-tumor toxicities. CONCLUSIONS We successfully generated syngeneic B7-H3-CAR T-cells and have demonstrated that these cells have potent anti-tumor activity in the immune competent GL261 glioma model via local or systemic delivery without apparent toxicities. Our study paves the way for future testing of B7-H3-CAR T-cells in early phase clinical studies.
Trajectory of chemical cocktail-induced neutrophil reprogramming
Authors: Yi Zhou, Chuijin Wei, Shumin Xiong, Liaoliao Dong, Zhu Chen, Sai-Juan Chen, Lin Cheng
Journal: Journal of Hematology & Oncology (2020)

Hematopoietic reprogramming holds great promise for generating functional target cells and provides new angle for understanding hematopoiesis. We reported before for the first time that diverse differentiated hematopoietic cell lineages could be reprogrammed back into hematopoietic stem/progenitor cell-like cells by chemical cocktail. However, the exact cell types of induced cells and reprogramming trajectory remain elusive. Here, based on genetic tracing method CellTagging and single-cell RNA sequencing, it is found that neutrophils could be reprogrammed into multipotent progenitors, which acquire multi-differentiation potential both in vitro and in vivo, including into lymphoid cells. Construction of trajectory map of the reprogramming procession shows that mature neutrophils follow their canonical developmental route reversely into immature ones, premature ones, granulocyte/monocyte progenitors, common myeloid progenitors, and then the terminal cells, which is stage by stage or skips intermediate stages. Collectively, this study provides a precise dissection of hematopoietic reprogramming procession and sheds light on chemical cocktail-induction of hematopoietic stem cells.
Влияние применения метформина и снижения массы тела на концентрацию церамидов C16:0, C18:0, C24:1 в плазме крови у пациентов с неалкогольной жировой болезнью печени в сочетании с инсулинорезистентностью и сахарным диабетом 2 типа
Authors: L.L. Pavlovskyi
Journal: GASTROENTEROLOGY (2020)

Актуальность. Церамиды — это жиры семейства сфинголипидов, которые принимают участие в развитии инсулинорезистентности (ИР), неалкогольной жировой болезни печени (НАЖБП) и сахарного диабета 2 типа (СД). Несмотря на стандарты лечения этих заболеваний, на сегодняшний день недостаточно информации относительно их влияния на концентрацию церамидов в плазме крови. В связи с этим мы исследовали, как прием метформина и снижение массы тела влияют на концентрацию церамидов C16:0, C18:0, C24:1 у данных больных. Цель исследования: изучить и сравнить концентрацию церамидов С16:0, С18:0, С24:1 в плазме крови у пациентов с НАЖБП до и после проведения лечения. Материалы и методы. В исследовании приняли участие 50 пациентов с НАЖБП, которые были разделены на две группы: 24 человека с IP и 26 человек с СД 2 типа. В качестве лечения пациентам с ИP рекомендовано было снижение массы тела. Пациенты с СД 2 типа принимали метформин в дозе 500 мг 2 раза в сутки. Контрольную группу составили 10 здоровых лиц. Церамиды определялись с помощью жидкостной хроматографии с масс-спектрометрией (Shimadzu Nexera X2 UHPLC, Shimadzu LCMS-8045 mass-spectrometer). Результаты. При сравнении концентрации церамидов С16:0, С18:0, С24:1 в обеих группах выявлено их достоверное повышение по сравнению с конт­рольной группой (р &lt; 0,001). После проведенного лечения у пациентов обеих групп наблюдалось достоверное уменьшение концентрации церамидов (р &lt; 0,001). Кроме того, было обнаружено, что фракции церамидов С16:0, С18:0, С24:1 в обеих группах коррелировали с основными лабораторными и инструментальными показателями. Выводы. У пациентов с НАЖБП, IP и СД 2 типа концентрация церамидов С16:0, С18:0, С24:1 была повышенной. На фоне соответствующего лечения концентрация церамидов уменьшилась.
EXTH-21. INTRAINFUSION CATHETER MOVEMENT FACILITATES INCREASED INFUSATE VOLUME DISPERSED IN AGAROSE GEL
Authors: Jason Mehta, Gabrielle McRoberts, Christopher Rylander
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma has a 5 year survival of only 5.5% and a median patient survival of 12 to 15 months even with gold standard treatment. One potential method of improving treatment of glioblastoma is the use of convection-enhanced delivery (CED) which utilizes local delivery of therapeutics to the brain. However, clinical trials have shown an inability of standard catheters to deliver therapeutics to the entire target area. In this study, we explore the potential of controlled catheter movement to increase the volume dispersed (Vd) of indigo carmine dye in agarose gel brain tissue phantoms. We use four catheter control protocols: stationary, continuous retraction, continuous insertion, and intermittent insertion using a single port stepped catheter. The continuous retraction group resulted in consistent catheter clogging caused by the continued insertion of the catheter and therefore was removed from further analysis. Vd and backflow distance was quantified for all other catheter movement protocols using optical images captured throughout the infusion. Catheter retraction resulted in an increase in Vd of 51% while intermittent insertion resulted in a Vd increase of 24% compared to the stationary catheter. Additionally, a 37% reduction in backflow distance was seen with the retracting catheter when compared to the stationary catheter. These results are further supported by a simplified computational model that we have created. The computational model simulates the infusion of indigo carmine dye through an agarose gel brain tissue phantom and shows an increase in Vd of over 100% with catheter retraction. The increased Vd and decreased backflow distance afforded by the retracting catheter, suggests that the use of catheter movement may be a useful technique in increasing drug dispersal in tumorous tissue. Additional work in live and excised tissue should be conducted to confirm these results and an exploration of optimal needle movement protocols is necessary.
SURG-19. COMPLETE RESOLUTION OF ADHD AFTER GROSS TOTAL RESECTION OF DYSEMBRYIOPLASTIC NEUROEPITHELIAL TUMOR
Authors: Luis Angel Arredondo Navarro, Regina Malinali Navarro Martín del Campo, Lorelay Livier Gutiérrez Oliva, Juan Luis Soto Mancilla, Maria De Lourdes De La Mora Carnalla, Daniel Perez-Rulfo Ibarra, Fernando Sánchez Zubieta
Journal: Neuro-Oncology (2020)

Abstract A 3-year-old boy with a history of attention-deficit/hyperactivity disorder (ADHD) presented a single focal tonic seizure. A thorough physical examination revealed no neurological deficit. A contrast enhanced MRI showed an isointense lesion in the anterior part of the cingulate gyrus extending through the left frontal lobe. After initial evaluation, the parents refused surgical treatment and a close follow up was then considered. At the age of five, the ADHD become more evident and the patient was started on methylphenidate. Poor clinical response was seen with the initiation of stimulant. The boy presented a second generalized seizure and the parents agreed surgical management. An interhemispheric approach was then performed and a gross total resection was achieved. The histopathological diagnosis corresponded to a dysembryoplastic neuroepithelial tumor (DNET). Four years after the resection, the patient is seizure free and the ADHD has also resolved without the need of medication. The disappearance of seizures is common after surgical resection of DNET tumors, but this case establishes an association with ADHD.
64MO A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM)
Authors: J.J. Sacco, R. Carvajal, M.O. Butler, A.N. Shoushtari, J.C. Hassel, A. Ikeguchi, L. Hernandez-Aya, P. Nathan, O. Hamid, J.M. Piulats Rodriguez, M. Rioth, D.B. Johnson, J.J. Luke, E. Espinosa, S. Leyvraz, H.M. Goodall, C. Holland, S. Abdullah, T. Sato
Journal: Annals of Oncology (2020)