tbuckley/cabot-search huggingface dataset:
EXTH-46. A COMBINATORY IMMUNOTHERAPY AGAINST BRAIN TUMOUR: BLOOD DENDRITIC CELL BASED VACCINE THERAPY WITH CHECKPOINT INHIBITOR(S)
Authors: Julius Kim, Benjamin Kong, Tsun-Ho Lo, Michael S Papadimitrous, Jennifer Hsu, Phillip Fromm, Kimberley Kaufman, Michael Buckland, Georgina Clark, Derek Hart
Journal: Neuro-Oncology (2018)

Cancer vaccines represent a novel and promising approach for aggressive neoplasms such as glioblastoma multiforme (GBM) where other treatment modalities have not been effective. In this regard, cancer vaccines have been developed which exploit the key central immunoregulatory dendritic cell (DC) to maximize vaccine efficacy. Such “DC vaccine” strategies are currently being evaluated clinically and form the basis of a number of commercial initiatives. However, current monocyte derived DCs (Mo-DCs) based vaccines have shown limited efficacy, possibly due to insufficient antigen presentation capability as well as inability to migrate toward lymph nodes. In this regard, we have developed a novel antibody against the CMRF-56 antigen which preferentially selects for distinct blood derived dendritic cell (BDC) subsets including myeloid CD1c+ and the highly efficient cross-presenting CD141+ BDC subsets. Unlike commonly used Mo-DC vaccines, which require artificial induction of differentiation/activation to load tumour specific antigens, CMRF-56 antibody-based selected BDCs showed highly activated/matured status upon selection. BDCs also showed the better migratory capability in response to the lymph nodes-migratory signal (CCR7/CCL21). Most importantly, antigen processing and presentation capability and glioma specific cytotoxicity mediated by BDC activated T cells were superior to those of Mo-DCs, implying highly efficient immunotherapeutic efficacy against GBM. In addition, we will discuss a potential boosting combinatory immunotherapeutic approach against GBM; BDC based vaccine in combination with checkpoint inhibitor, anti-PD1. In this research, we will demonstrate a therapeutic potential of a novel immune-combinatory personalized medicine against GBM.
CMET-31. INTRACEREBRAL HEMORRHAGE FROM NEOPLASTIC ANEURYSM AS FIRST MANIFESTATION OF LUNG CANCER
Authors: Maria Diaz, Camilo Fadul
Journal: Neuro-Oncology (2018)

Metastatic cerebral aneurysms are an extremely rare complication of cancer. We present a case of an intracerebral hemorrhage (ICH) secondary to a neoplastic aneurysm as the initial manifestation of lung cancer. CASE REPORT: A 63-year-old man presented with acute aphasia and was found to have a left parieto-temporal ICH on brain imaging. Angiography demonstrated a fusiform dilation of the distal left middle cerebral artery suspicious for a mycotic aneurysm. Patient underwent hematoma evacuation and aneurysmal clipping; pathology showed intravascular atypical cells determined by immunohistochemistry to be an embolus from a primary lung cancer. Chest imaging revealed a previously undiagnosed lung nodule with hilar adenopathies. Needle biopsy of one of the lymph nodes demonstrated neoplastic cells identical to those visualized in the aneurysm, with final pathology consistent with poorly differentiated lung adenocarcinoma (EGFR, ALK and KRAS negative). Patient subsequently received Gamma Knife radiosurgery to the surgical bed, followed by carboplatin, pemetrexed and pembrolizumab for treatment of his systemic disease. Tumoral intracerebral aneurysms are rare, with about 100 cases published in the literature, the majority of them arising from cardiac myxoma or choriocarcinoma. Only six cases of neoplastic cerebral aneurysms from metastatic lung cancer have been reported, all presenting as ICH. Four of them died as a result of the hemorrhage, and the remaining two had complications that precluded the administration of further therapy, making ours the first case to receive cancer-directed treatment aimed at the aneurysmal metastatic lesion. Neoplastic cerebral aneurysms are rare, but should be considered in patients with malignancy presenting with a pattern of ICH suspicious for aneurysmal origin. There are no guidelines regarding the treatment of these uncommon aneurysms, but based on our case, we suggest approaching them as any other cerebral metastasis, with complete resection whenever possible, followed by stereotactic radiosurgery.
C1q-tumour necrosis factor-related protein-3 exacerbates cardiac hypertrophy in mice
Authors: Zhen-Guo Ma, Yu-Pei Yuan, Xin Zhang, Si-Chi Xu, Chun-Yan Kong, Peng Song, Ning Li, Qi-Zhu Tang
Journal: Cardiovascular Research (2018)

C1q-tumour necrosis factor-related protein-3 (CTRP3) is an adipokine and a paralog of adiponectin. Our previous study showed that CTRP3 attenuated diabetes-related cardiomyopathy. However, the precise role of CTRP3 in cardiac hypertrophy remains unclear. This study was aimed to clarify the role of CTRP3 involved in cardiac hypertrophy. Cardiomyocyte-specific CTRP3 overexpression was achieved using an adeno-associated virus system, and cardiac CTRP3 expression was knocked down using gene delivery of specific short hairpin RNAs in vivo. CTRP3 expression was upregulated in murine hypertrophic hearts and failing human hearts. Increased CTRP3 was mainly derived from cardiomyocytes and induced by the production of reactive oxygen species (ROS) during the hypertrophic response. CTRP3-overexpressing mice exhibited exacerbated cardiac hypertrophy and cardiac dysfunction in response to pressure overload. Conversely, Ctrp3 deficiency in the heart resulted in an alleviated hypertrophic phenotype. CTRP3 induced hypertrophy in cardiomyocytes, which could be blocked by the addition of CTRP3 antibody in the media. Detection of signalling pathways showed that pressure overload-induced activation of the transforming growth factor β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK) pathway was enhanced by CTRP3 overexpression and inhibited by CTRP3 disruption. Furthermore, we found that CTRP3 lost its pro-hypertrophic effects in cardiomyocyte-specific Tak1 knockout mice. Protein kinase A (PKA) was involved in the activation of TAK1 by CTRP3. In conclusion, our results suggest that CTRP3 promotes pressure overload-induced cardiac hypertrophy via activation of the TAK1-JNK axis.
PDCT-04. PHASE 1 TRIAL OF WEE1 KINASE INHIBITOR AZD1775 COMBINED WITH RADIATION THERAPY FOR CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP PHASE 1 PILOT CONSORTIUM (ADVL1217)
Authors: Sabine Mueller, Xiaodong Yang, Sharmistha Pal, Ralph Ermioian, Elizabeth Fox, Amar Gajjar, Charles Minard, Xiaowei Liu, Komal Prem, Joel Reid, Brenda Weigel, Daphne Haas-Kogan
Journal: Neuro-Oncology (2018)

OBJECTIVES: Children with diffuse intrinsic pontine glioma (DIPG) continue to have a dismal outcome and median survival remains stagnant at 9 months for decades. AZD1775 is an orally available inhibitor of Wee1 kinase, a key G2-M checkpoint regulator that has been shown to cross the blood brain barrier and has demonstrated efficacy in preclinical DIPG studies. AZD1775 was administered orally in newly diagnosed children with DIPG, only on days of radiation therapy. The protocol assessed 6 dose levels starting from 50 mg/m2/dose and escalated up to 200mg/m2/dose. Dose escalation occurred first by the number of days on which AZD1775 was administered and then by an increase of the actual dose. The entire length of radiation therapy constituted the dose limiting toxicity period. Correlative studies included pharmacokinetic (PK) analyses as well as determination of expression of p-CDC2, p-HH3 and g-H2AX in peripheral blood mononuclear cells (PBMC). In the late breaking abstract we will present results of this phase 1 study including PK analyses as well as results of the correlative studies. Results of this study will lay the groundwork for subsequent clinical trials using AZD1775 in pediatric brain tumors.
Abstract P361: Significant Inverse Association of Blood Levels of Marine Omega-3 Fatty Acids With Aortic Calcification in an International Multi-ethnic Cohort of 1335 Men Aged 40-49 Years: The ERA JUMP Study
Authors: Hemant D Mahajan, Jingchuon Guo, Siyi Shangguan, Bradley Willcox, Katsuyuki Miura, Akira Fujiyoshi, Aya Kadota, Jina Choo, Rhobert Evans, Emma Barinas-Mitchell, Lewis Kuller, Chol Shin, Kamal Masaki, Hirotusugu Ueshima, Akira Sekikawa
Journal: Circulation (2017)

Introduction: Aortic calcification (AC) is an independent predictor of future cardiovascular (CV) events. Marine omega-3 fatty acids (OM3) are reported to have anti-atherogenic properties. Hypothesis: We hypothesized that blood levels of OM3 have a significant inverse association with AC. Methods: ERA JUMP is a population-based study of subclinical atherosclerosis in 1335 men aged 40-49 without CVD (310 European American, 107 African American, 303 Japanese American, 313 Japanese in Japan and 308 Korean in South Korea). Participants were examined for AC, blood levels of OM3, CV risk and other factors in 2002-07 with rigorous standardization. AC was assessed by electron-beam CT and quantified using the Agatston method. OM3 were measured using gas chromatography, expressed as the percentage of total fatty acids and defined as the sum of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids. After excluding missing data for AC (n=36), OM3 (n=8) and heavy drinkers (ethanol &gt;69 g/day) (n=73), our final analytic sample was 1218. The association of the presence of AC with OM3 was analyzed using logistic regression adjusting for age, race, CV risk and other factors. We also performed Tobit regression and ordinal logistic regression to assess the relation between AC score (ACS) and OM3. Results: Mean [standard deviation (SD)] of age, LDL-C, and pack-years of smoking were 45.2 (2.8) years, 127 (35) mg/dl and 9.5 (13.6), respectively. Prevalence (%) of hypertension and diabetes was 22.4 and 8.0, respectively. Mean (SD) of OM3 was 6.1 (3.1) (%) and 58.1% had ACS&gt;0. In a fully adjusted model with stepwise backward elimination, odds of ACS&gt;0 was reduced by 10% with one SD increase in OM3 level (p &lt;0.001). Results of Tobit regression and ordinal logistic regression suggest a statistically significant lower ACS for every SD increase in OM3 level. There was no significant interaction on AC between race and OM3. Conclusions: This cross-sectional study showed a significant inverse association of OM3 with AC in an international multi-ethnic cohort.
A Diagnostically Challenging Infusion Reaction—Kounis, Takotsubo, or the ATAK!
Authors: Mohammad Hashim Mustehsan, Fathima Jahufar, Shitij Arora
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Therapeutic Potential of Axl Blockade in BCR-ABL Negative Myeloproliferative Neoplasms (MPN)
Authors: Antonia Beitzen-Heineke, Isabel Ben Batalla, Nikolaus Berenbrok, Sarina Paesler, Victoria Gensch, Gunhild von Amsberg, Philippe Schafhausen, Kristoffer Riecken, Thomas Fischer, Klaus Pantel, Carsten Bokemeyer, Sonja Loges
Journal: Blood (2018)
Abstract A14: Downregulation of desmin involves gene promoter hypermethylation in gallbladder cancer
Authors: Shushruta Bhunia, Mustafa Ahmed Barbhuiya, Sanjiv Gupta, Braj Raj Shrivastava, Pramod Kumar Tiwari
Journal: Clinical Cancer Research (2018)

Abstract Gallbladder cancer (GBC) is a fatal malignancy with widespread geographical variations in incidence worldwide. There are limited studies on systematic molecular profiling of gallbladder cancer in literature. Previously, we carried out differential proteomic and methylome-based analysis in gallbladder tumors and adjacent non-tumors to identify differentially expressed proteins and global methylation status of genes involved in gallbladder cancer. Quantitative tissue proteomics analysis using Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) based Liquid Chromatography-Mass Spectrometry (LC-MS/MS) showed that desmin protein was significantly downregulated (~3 folds) in tumors. Global methylation profiling using Illumina's Infinium Human Methylation 450 BeadChip array revealed hypermethylation in desmin in gallbladder tumors compared to non-tumor tissue. These findings lead us to further investigate the epigenetic regulation of desmin gene expression in gallbladder cancer. Real-time PCR analysis revealed significant downregulation of desmin (p=0.001) expression in tumors (n=12) as compared to the non-tumor tissue (n=12). Immunohistochemical analysis also showed significantly (p&amp;lt;0.0001) decreased level of desmin in 95% (26/27) of tumor cells in comparison to non-tumors 35.71% (5/14). This was again validated by Western blotting, showing downregulation of desmin (p=0.0081) at protein level in tumor tissues compared to the non-tumors. Methylation specific polymerase chain reaction analysis showed 86.67% methylation of desmin in corresponding gallbladder tumors compared to non-tumor tissue (p=0.004). Taken together, our observations showing decreased expression and hypermethylation of desmin gene suggest desmin as a potential epigenetically controlled biomarker for GBC. However, further studies are warranted to explore its role in tumorogenesis of gallbladder cancer. Citation Format: Shushruta Bhunia, Mustafa Ahmed Barbhuiya, Sanjiv Gupta, Braj Raj Shrivastava, Pramod Kumar Tiwari. Downregulation of desmin involves gene promoter hypermethylation in gallbladder cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A14.
EXTH-05. MicroRNA-138 SUPPRESSES GLIOBLASTOMA PROLIFERATION AND SENSITIZES CHEMOTHERAPY THROUGH FOCAL ADHESION KINASE INACTIVATION
Authors: Margaret Yeh, Ji Young Yoo, Balveen Kaur, Tae Jin Lee
Journal: Neuro-Oncology (2018)

Glioblastoma is one of the most deadly cancers and limited to only a few therapeutic options that are available in clinical settings, mainly due to the resistance to many chemotherapies. MicroRNAs are increasingly implicated in the tumor survival from chemotherapies, which may lead to a better therapeutic option by overcoming the resistance. Here, we found that miR-138 is significantly downregulated in human glioblastoma patient tissues compared to normal brain tissues. MiR-138 has been known to play as a tumor suppressor in many types of cancer, which may imply that miR-138 can benefit in the development of anti-glioblastoma therapy. Global proteomic analysis revealed that ectopic expression of miR-138 in patient derived glioblastoma primary cells suppressed FAK pathway, which has been known to be highly activated in many cancers including glioblastoma. FAK inactivation by miR-138 resulted inhibition of glioblastoma cell proliferation in vitro and improved tumor free survival in vivo. We also found that miR-138 induced FAK inhibition sensitizes glioblastoma cells to tyrosine kinase inhibitors, such as Imatinib. The studies are indicative of the clinical benefit of miR-138 based therapy of primary and even recurrent glioblastoma.
Test Detects One in a Million Cancer Cells
Authors: Rebecca Voelker
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
CMET-30. BRAIN METASTASES FROM EGFR-MUTATED NSCLC WHICH HAD ACQUIRED RESISTANCE TO EGFR-TKI. ~LESS-FREQUENT T790M AND PRESERVED RESPONSE TO OTHER TKIs~
Authors: Toshihiko Iuchi, Tsukasa Sakaida, Yuzo Hasegawa, Yasushi Yoshida, Hironori Ashinuma, Satoko Mizuno, Taiki Setoguchi, Masato Shingoji
Journal: Neuro-Oncology (2018)

Despite the favorable response, most brain metastases (MBs) acquire resistance to TKIs. T790M is the most common mechanism and accounts for approximately half of acquired resistance to TKIs. The aim of this study is to clarify the role of T790M in the acquired resistance of BMs, and optimal treatment for BMs progressed after TKI. METHOD: Upfront TKI was performed for BMs from EGFR-mutated NSCLC, and TKI was changed at progression. Gefitinib, erlotinib, afatinib and osimertinib were used and the selection of these TKIs were owing to the physicians’ decision. During the disease course, re-biopsies of progressed diseases were performed to verify mutations of EGFR, and the incidences of T790M were compared among the organs biopsied. The time to CNS-progression (TCP) were evaluated for each TKI. 141 cases were enrolled. Gefitinib was used only as the first line TKI (n=91). Erlotinib was selected for both the gefitinib-naïve patients (n=27) and after gefitinib (n=51). Afatinib (n=21) and osimertinib (n=17) were selected for only recurrent cases. TCPs after gefitnib, erlotinib, afatinib, and osimertinib were 13.4, 20.1, 19.9, and 13.8months, respectively. The history of treatment with gefitinib did not affect the TCP after erlotinib (HR:1.37, 95%CI:0.61–3.25, P=0.451). Re-evaluations of EGFR was performed using 107 samples (lung:51, serum:25, CNS:22, others:9) from 88 cases. The incidence of T790M from CNS samples was 9.1% (Tumor:1/6, CSF:1/16), and was significantly lower than that from the other organs (lung:50.1%, surum:28.0%, others:44.4%) (Odds ratio:0.130, P=0.001). The extremely low incidence of T790M and satisfied effects of TKIs even after TKI-failure suggested the different mechanism of acquired resistance of BMs to TKIs in compared with the extracranial lesions. CONCLUSIONS: T790M played only a limited role in acquired resistance of BMs to TKIs, and alterations of the types of TKIs were still recommended for the progressed BMs after TKI.
ATIM-17. PEMBROLIZUMAB BLOCKS PD-1 ON CAR T CELLS ADMINISTERED INTRAVENTRICULARLY TO GLIOBLASTOMA PATIENTS
Authors: Jana Portnow, Timothy Synold, Vivi Tran, Vivian Chiu, Darya Alizadeh, Dongrui Wang, Alfonso Brito, Julie Kilpatrick, Paige Mcnamara, Stephen Forman, Behnam Badie, Christine Brown
Journal: Neuro-Oncology (2018)

Checkpoint inhibitors have shown efficacy in other solid tumors and are being studied in glioblastoma. For patients treated with anti-PD-1 monoclonal antibodies, such as pembrolizumab, CSF concentrations and blockade of PD-1 on T cells present in the CSF have not been reported. Such information would provide valuable context for applying checkpoint inhibitors for the treatment of CNS malignancies. CSF and blood samples were obtained from 6 glioblastoma CAR T cell study patients who received intraventricularly administered CAR T cells. These patients were also treated with pembrolizumab 200 mg intravenously every 3 weeks. Pembrolizumab levels in CSF and blood were measured using an ELISA assay. FACS analysis for PD-1 blockade was performed on endogenous and CAR T cells detected in CSF samples, and the results were compared to cells in CSF without pembrolizumab treatment. Data analyzed from 3 patients samples so far show that average pembrolizumab levels in the CSF and serum were 330 ± 114 ng/mL and 64 ± 8 µg/mL, respectively. The average CSF/serum ratio was 0.5 ± 0.1%. In 1 patient from whom multiple CSF/blood samples were obtained over 3 months, steady-state CSF levels ranged from 155–394 ng/mL throughout each 21 day cycle of pembrolizumab. PD-1 was completely blocked on both endogenous T cells as well as CAR T cells that were delivered directly into the CSF. To our knowledge, this is the first report of pembrolizumab concentrations in the CSF after intravenous administration. CSF levels were 0.5% of serum concentrations and remained stable throughout a 21 day cycle of pembrolizumab. PD-1 was found to be blocked on endogenous T cells in the CSF. Furthermore, even though they were relatively low, pembrolizumab levels in the CSF were sufficient to block PD-1 on intraventricularly administered CAR T cells.
Abstract 16357: Association Between Obstructive Sleep Apnea and the Atrial Fibrillation Recurrence After Catheter Ablation
Authors: Chan Joo Lee, Jae Hyung Park, Hui-Nam Pak, Sungha Park
Journal: Circulation (2013)

Introduction: Obstructive sleep apnea (OSA) is known as a risk factor of atrial fibrillation (AF). However, the sole impact of OSA on AF is not fully elucidated because OSA usually accompanies other risk factors of AF. In this study, we investigated the association between OSA and the AF recurrence after catheter ablation. Method: A total of 194 patients (mean age 58.1±10.3 years, male 75.8%), who underwent catheter ablation of AF were enrolled. The patients underwent echocardiography and overnight ambulatory polysomnography before ablation procedure. These patients were followed every 3 months at the outpatient clinic. The AF recurrence was defined as any episodes of AF on ECG at the 6 months after catheter ablation. Results: We divide the study subjects into 3 groups defined as mild (AHI 30) OSA based on apnea-hypopnea index (AHI). The results showed that 64 (33%) and 31 (12.9%) of these patients had moderate and severe OSA, respectively. Patients with severe ...