tbuckley/cabot-search huggingface dataset:
DRES-15. IL11 SECRETION BY GLIOBLASTOMA ASSOCIATED MICROGLIA DEFINE A STAT3-MYC SIGNALING AXIS THAT IS SUPPRESSED IN “EXCEPTIONAL RESPONDERS”
Authors: Jie Li, Megan Kaneda, Jiangfei Wang, Johnny Akers, Valya Ramakrishnan, Siamak Amirfakhri, Brian Hirshman, Frank Furnari, Tao Jiang, Bob Carter, Christopher Glass, Bing Ren, Judith Varner, Clark Chen
Journal: Neuro-Oncology (2017)

Despite aggressive treatment, most glioblastoma patients succumb to the disease within two years of diagnosis. The molecular basis for the rare patients who exhibit “exceptional response” and survive beyond expectation remains poorly understood. Using three independent patient cohorts, we showed that decreased expression of an inflammation gene signature consistently associated with “exceptional response”. Integrated cell-based analysis suggests glioblastoma-associated microglia as the principle mediator of this inflammation signature. Co-culturing of freshly isolated murine microglia derived from GL261 glioblastoma enhanced glioblastoma tumorigenicity and resistance to temozolomide (TMZ), the standard-of-care therapy. The pro-tumorgenic and -TMZ resistance effects of microglia were recapitulated using microglia conditioned media. Proteomic analysis of microglia conditioned media revealed IL11 as the critical mediator, which induce glioblastoma STAT3-MYC signaling. PI3Kg activation in myeloid-derived cells, including microglia, is essential for its trafficking into the tumor microenvironment. We hypothesized that PI3Kg inhibition should impede microglia accumulation in the glioblastoma microenvironment and reduce glioblastoma tumorigenicity. Supporting our hypothesis, treatment with a PI3Kg inhibitor, TG100-115, suppressed glioblastoma tumorigenicity in vivo by reduced microglia density and IL11 release. These effects were recapitulated when murine glioblastoma GL261 were implanted into transgenic mice in which PI3Kg were genetically inactivated (p110g-/- mice). Importantly, ectopic expression IL11 in GL261 reversed the tumor-suppressive effect of TG100-115, supporting IL11 as a key mediator of these effects. PI3Kγ inhibition through TG100-115 augmented the anti-neoplastic effects of TMZ, suggesting that TG100-115 transformed the glioblastoma microenvironment from one associated with poor TMZ response to one mimicking the microenvironment of “exceptional responders”. Further supporting this hypothesis, TG100-105 treatment of GL261 decreased the expression of the poor-clinical response associated, inflammation gene signature. In contrast, ectopic IL11 expression or microglia induce the expression of this signature. In aggregate, our study suggests microglia-glioblastoma interaction as a determinant of clinical response and translational potential for therapies targeting microglia-mediated inflammation
Abstract 17832: A New Rapid Vector Technique to Localize the PVC Origin From the 12-lead Ecg Compared to Cips
Authors: Peter M van Dam, Jeff P Gordon, Roderick Tung, Noel G Boyle, Michael M Laks
Journal: Circulation (2015)

Introduction: Prior accurate PVC localization improves the time and outcome of ablative procedures. We developed a new manual Vector Technique (VcT) to localize the PVC origin to cardiac anatomy regions. In contrast, our Cardiac Isochrone Positioning System (CIPS) is a computer based system that localizes the PVC to patient specific cardiac anatomy from the MRI and electrode positions from the 3D Camera. Hypothesis: We hypothesize that this new VcT can rapidly quantitate the location of PVC to anatomical regions whereas CIPS localizes the PVCs to more specific cardiac anatomical segments. Method: The VcT assumes the frontal plane leads are formatted on the chest as an equilateral triangle and the horizontal leads as a partial sphere. Using the concept that a lead recording perpendicular to a dipole vector is zero, the QRS axis vectors of the PVC were calculated manually within 3.8 to 7.5 degrees in the frontal and horizontal planes. CIPS computed the electrode positions by registration of the MRI derived torso model with the 3D image of the patient. The ECG signals were used by both methods to localize the PVC origin to the cardiac anatomy. Result: In 12 patients (below), this manual VcT separated without overlap in the horizontal plane the PVC into Left Ventricle (LV 30-45°), Right Ventricular (RV 308-348°), and Papillary Muscle (PM 128-150°) regions, but not in the frontal plane. CIPS localized 10 PVCs to the same and 2 to adjacent anatomical segments while the vector technique cannot because of the need for a database to create a PVC anatomic segment model. Conclusion: This new VcT can be used by anyone to localize rapidly the PVC by a QRS vector plot to regions like the left &amp; posterior for the RV, left &amp; anterior for the LV, and right &amp; anterior for the papillary muscles while CIPS can localize PVCs more specifically to anatomical segments. Using the 12 lead ECG, this VcT creates a quantitative cardiac anatomical segment model of PVC locations integrated into CIPS that can improve the accuracy of VcT.
Multi-institutional Evaluation of Elective Nodal Irradiation and/or Androgen Deprivation Therapy with Postprostatectomy Salvage Radiotherapy for Prostate Cancer
Authors: Stephen J. Ramey, Shree Agrawal, Matthew C. Abramowitz, Drew Moghanaki, Thomas M. Pisansky, Jason A. Efstathiou, Jeff M. Michalski, Daniel E. Spratt, Jason W.D. Hearn, Bridget F. Koontz, Stanley L. Liauw, Alan Pollack, Mitchell S. Anscher, Robert B. Den, Kevin L. Stephans, Anthony L. Zietman, W. Robert Lee, Andrew J. Stephenson, Rahul D. Tendulkar
Journal: European Urology (2017)
ACTR-84. D-TERMINED: A PHASE 1 TRIAL IN NEWLY DIAGNOSED HIGH GRADE GLIOMA WITH TEMOZOLOMIDE, RADIATION, AND MINOCYCLINE FOLLOWED BY ADJUVANT MINOCYCLINE/TEMOZOLOMIDE
Authors: Adam Cohen, Karthik Sonty, Randy Jensen, Dennis Shrieve, Karen Salzman, Brett Johnson, Melissa Thomas, Whitney Moss, Amanda Behunin, Elizabeth Prystas, Howard Colman
Journal: Neuro-Oncology (2017)

Activated microglia in high grade gliomas secrete TNF, which activates NF-kappaB. Activation of NF-kB promotes transition to the mesenchymal phenotype of GBM, which is associated with increased radiation-resistance and poorer prognosis. Minocycline is a tetracycline-derivative capable of blocking microglia activation and release of TNF. Minocycline is known to cross the blood-brain barrier and has been shown in vitro and in vivo to inhibit GBM proliferation. D-TERMINED was a single arm, open label phase I trial sponsored by the Musella Foundation enrolling people with newly diagnosed grade 3 or 4 glioma with a 3 + 3 dose escalation followed by a 14 patient dose expansion cohort. All patients received standard chemoradiation with temozolomide plus continuous oral minocycline. Primary objectives were to define the MTD and adverse event rate of minocycline with radiation and temozolomide; secondary objectives included PFS. Efficacy was assessed by the percent of people whose PFS exceeded the predicted median PFS based on RTOG RPA class. Nine evaluable patients were enrolled to the dose escalation component, and the MTD was defined as 150mg PO BID. A total of 20 patients were treated at 150mg PO BID. All patients treated at 150mg PO BID had GBM. At the 150mg PO BID dose, one person (5%) had grade 3 nausea and dizziness, and two people (10%) had temozolomide interruptions for grade 3–4 thrombocytopenia. 11 of 20 patients treated at 150mg BID exceeded expected PFS, 55% (95% CI 32%-77%), which does not meet the prescribed efficacy endpoint of 70%. Minocycline can be safely combined with radiation and temozolomide in newly diagnosed high grade glioma. A signal of efficacy was not seen. Further investigation of minocycline in unselected high grade glioma is not warranted, though biomarkers of NF-kappaB activation and mesenchymal phenotype are being investigated.
P3.02-038 Diagnosis of Leptomeningeal Disease and Clonal Heterogeneity with Digital Droplet PCR (ddPCR) in EGFR Mutated NSCLC
Authors: G. Rivalland, H. Do, S. Arulananda, P. Mitchell, A. Dobrovic, T. John
Journal: Journal of Thoracic Oncology (2017)
P3.02-032 Spatial Heterogeneity of EGFR and KRAS Variant Allele Frequencies Correlates with Histological Patterns of Lung Adenocarcinomas
Authors: S. Dietz, A. Harms, V. Endris, F. Eichhorn, M. Kriegsmann, R. Longuespée, A. Stenzinger, A. Warth, D. Kazdal, H. Sültmann
Journal: Journal of Thoracic Oncology (2017)
Ketamine Minus the Trip: New Hope for Treatment-Resistant Depression
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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-34. COMPARING STEREOTACTIC RADIOSURGERY WITH WHOLE BRAIN RADIATION THERAPY IN THE TREATMENT OF RENAL CELL CARCINOMA BRAIN METASTASES
Authors: Gregor Manukian, Shivank Garg, James Mark, Maria Werner-wasik, David Andrews, James Evans, Kevin Judy, Christopher Farrell, Wenyin Shi
Journal: Neuro-Oncology (2017)

The management of brain metastases involves either definitive or post-operative whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). While radiation improves intracranial control, it is unclear whether this response is dependent on tumor type. We therefore performed a single institution, retrospective analysis of 52 patients with Stage IV renal cell carcinoma (RCC) with metastatic brain lesions who were treated with either WBRT or SRS between 1995 and 2016. Overall survival was defined as time from completion of radiation therapy until death of any cause. Univariate analysis was performed using the Kaplan Meier method, and differences between the groups was assessed with the log-rank test. The median age was 59 and 52.5 in the WBRT and SRS groups, respectively. The median RPA for both groups was 2. For both WBRT and SRS the average number of treated brain lesions was 3. The median dose of WBRT was 3750 cGy while the median dose delivered via SRS was 2100 cGy. The median overall survival of patients receiving SRS was 11.9 months while those receiving WBRT was 15 months (HR 1.14 95% CI 0.58 to 2.23). Progression free survival was 6.23 months and 7.5 months for SRS and WBRT, respectively (HR 1.55, 95% CI 0.78 to 3.05). While intracranial progression was delayed in those treated with WBRT, this difference was not significant (HR 0.56 CI 95% 0.19 to 1.61). 28% of patients who were treated with WBRT ultimately received salvage SRS, and 17% of those who received upfront SRS ultimately received salvage WBRT. From these data, we conclude that both WBRT and SRS remain viable options for the treatment of brain metastases in patients with metastatic renal cell carcinoma. While there was a numerical improvement in median overall survival, progression free survival, and intracranial progression, these findings were not significant.
NTOX-14. THE DEVELOPMENT OF NEUROLOGIC IMMUNE RELATED ADVERSE EVENTS (irAEs) IN PATIENTS WITH METASTATIC SOLID TUMORS TREATED WITH IMMUNE CHECKPOINT INHIBITORS: A SINGLE INSTITUTION RETROSPECTIVE ANALYSIS
Authors: Rachna Malani, Aya Haggiagi, Jenessa Holder, Yelena Shames, Samuel Briggs, Bianca Santomasso, Margaret Callahan
Journal: Neuro-Oncology (2017)

Immune checkpoint blockade has shown significant antitumor responses and is approved for the treatment of multiple cancer types. Immune checkpoint inhibitors (ICI) are associated with a unique set of toxicities termed irAEs. This study seeks to review the incidence and clinical manifestations of patients who developed neuro-toxicity with ICIs. An IRB approved retrospective study involved review of charts and institutional databases. We identified patients who developed neuro-toxicity while on at least one of the following ICIs: anti-CTLA4, anti-PD1 or anti-PD-L1 over a 6 year period (1/1/2010-5/15/2016). We identified a total of 3,804 patients who were treated with one or more ICI during the period of review. Neuro-toxicity was observed in 99 patients (2.6%) affecting both central and peripheral nervous systems. 35 patients (34.7%) received more than one ICI. Median number of cycles prior to developing toxicity was 3 (1-29). Ten patients had more than 1 neuro-toxicity. The various neurologic phenotypes observed in patients included: Sensory neuropathy (34), encephalopathy (18), headache (16), aseptic meningitis (13), Myasthenia Gravis like syndrome (6), myopathy (6), autonomic neuropathy (5), aphasia syndromes (3), radiculopathy (2), brachial plexitis (2), mononeuritis multiplex (2), AIDP (1), and PRES (1). 58 patients required hospital admission and 2 required ICU level of care. A diagnosis of neuro-toxicity was based upon the temporal association with ICIs and appropriate workup including but not limited to neurologic consultation, lumbar puncture, and neuro-imaging. Patients were treated with drug holiday, observation, corticosteroids, plasmapheresis and/or IVIG. As ICI’s are being used with increased frequency, treating oncologists should be aware of the varied manifestations of neuro-toxicity in order to ensure appropriate diagnosis, work up and treatment. Prompt treatment may relay a benefit in regards to outcome.
Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH
Authors: Atze van der Pol, Andres Gil, Herman H. W. Silljé, Jasper Tromp, Ekaterina S. Ovchinnikova, Inge Vreeswijk-Baudoin, Martijn Hoes, Ibrahim J. Domian, Bart van de Sluis, Jan M. van Deursen, Adriaan A. Voors, Dirk J. van Veldhuisen, Wiek H. van Gilst, Eugene Berezikov, Pim van der Harst, Rudolf A. de Boer, Rainer Bischoff, Peter van der Meer
Journal: Science Translational Medicine (2017)

OPLAH is cardioprotective for myocardial infarction, and its substrate 5-oxoproline is a putative circulating marker for heart failure.
ATIM-09. RETROSPECTIVE STUDY OF NIVOLUMAB FOR PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS
Authors: Ashley Pritchard, Frank Lieberman, Megan Mantica, Jan Drappatz
Journal: Neuro-Oncology (2017)

Patients with recurrent primary CNS malignancies have limited treatment options and poor clinical outcome. High grade gliomas use the PD-1 pathway to evade immune responses. Checkpoint inhibitors have recently demonstrated safety and encouraging clinical activity in patients with refractory glioblastoma. We retrospectively analyzed clinical outcomes of high grade glioma patients treated with nivolumab-containing regimens in our institution. Key inclusion criteria included patients with advanced high grade gliomas who received a nivolumab containing regimen at their treating physician’s decision. Patients received nivolumab 3 mg/kg every 2 weeks until confirmed progression, intolerable toxicity, death, or physician decision. Between April 2015 and June 2017, 62 patients with high grade gliomas had received a nivolumab containing regimen. All had received prior radiation and chemotherapy. All but nine patients received concurrent bevacizumab. Median age was 55 years (range 18–75); 60% were male; As of June 8, 2017, median follow-up duration was 5 months (range 0–17 months). 50 (81%) patients had discontinued nivolumab. 43 (69%) patients had experienced at least stable disease (SD) as best response. 1 patient with bevacizumab refractory disease achieved a partial radiographic response. 3 patients continued treatment beyond 1 year. 2 patients discontinued nivolumab because of treatment-related pneumonitis and one patient due to fatigue and abdominal pain. Survival analysis is planned. Treatment with nivolumab monotherapy was well tolerated without overlapping toxicities with bevacizumab. Promising antitumor activity was noted in a subset of patients. Updated response, survival and toxicity data will be presented.
Apoyo con Cariño: Strategies to Promote Recruiting, Enrolling, and Retaining Latinos in a Cancer Clinical Trial
Authors: Stacy M. Fischer, Danielle M. Kline, Sung-Joon Min, Sonia Okuyama, Regina M. Fink
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: We present and describe tailored strategies to address known barriers to minority participation in clinical trial research. The strategies used allowed our team to engage communities and successfully recruit, enroll, and retain a diverse underserved population of Latinos with advanced cancer for this clinical trial. Methods: Participants were recruited from 3 urban and 7 rural sites. We identified 4 critical barriers to recruitment for this underserved population: (1) mistrust; (2) language and communication barriers; (3) lack of access to academic cancer center; and (4) inability to participate due to transportation, childcare, or work responsibilities. We developed tailored strategies to engage referring sites and patients to participate in the clinical trial. Results: We identified 318 potentially eligible participants; 34 were found to be ineligible, and 223 consented to participate in the study, representing a 79.0% enrollment rate. All patients (100%) self-identified as Latino, and 47.5% spoke Spanish as their primary language. Patients were socioeconomically disadvantaged: 53.6% had an annual income <$15,000 USD, and 50.2% had less than a high school education. A total of 177 participants completed the 3-month follow-up; 26 died before the 3-month follow interview, and 20 did not complete the follow-up evaluation (9% withdrawal rate). Conclusions: Our community-informed strategies were highly effective for recruiting, enrolling, and retaining an underserved diverse population of Latinos. The barriers we identified and the strategies we used have the potential to inform research to increase minority participation in cancer clinical trials. ClinicalTrials.gov identifier: NCT01695382.
Vigilância sentinela das doenças sexualmente transmissíveis na Escócia
Authors: A Noone, J Chalmers, H Young
Journal: Eurosurveillance (1998)

A vigilância das doencas sexualmente transmissiveis (DST) permite a determinacao das prioridades em materia de planeamento dos meios de prevencao e do tratamento, a avaliacao das accoes e a formulacao de hipoteses de investigacao (1).
PUB038 Prognostic Impact of FOXP3-Positive Tumor Infiltrating Lymphocytes in Small-Cell Lung Cancers
Authors: L. Bonanno, A. Pavan, M.V. Dieci, M. Fassan, E. Di Liso, M. Schiavon, G. Comacchio, I. Attili, G. Pasello, F. Calabrese, A. Favaretto, G. Zago, V. Polo, S. Frega, M. Rugge, F. Rea, V. Guarneri, P. Conte
Journal: Journal of Thoracic Oncology (2017)
Infecciones por S. aureus resistente a la meticilina (SARM) adquiridas en la comunidad en niños en Grecia
Authors: S Vourli, D Perimeni, A Makri, M Polemis, A Voyiatzi, A Vatopoulos
Journal: Eurosurveillance (2005)

El estudio siguiente presenta las caracteristicas de 20 cepas de Staphylococcus aureus resistente a la meticilina (SARM) adquirido en la comunidad, aisladas en un hospital pediatrico de Atenas. Dieciocho de ellas, procedentes todas de infecciones dermatologicas y de tejidos blandos, llevaban genes para la leucocidina de Panton-Valentine (PVL). Estas 18 cepas presentan una resistencia al acido fusidico, a la tetraciclina y a la kanamicina, y su perfil de electroforesis en campo pulsado es igual al del clon de CA-SARM ST80 circulante en varios paises de Europa, ya descrito en la literatura.
P1.09-012 A Pre-Clinical Investigation of Intrapleural Curcumin Treatments as an Adjunct Therapy for Malignant Pleural Mesothelioma
Authors: A. Hocking, D. Elliot, J. Hua, M. Michael, S. Marri, S. Klebe
Journal: Journal of Thoracic Oncology (2017)

Malignant pleural mesothelioma (MPM) is an aggressive malignancy originating in pleural mesothelial cells with median survivals of approximately 12 months following diagnosis. Recently, anti-angiogenic therapies have been trialed with only a modest effect. This may be, in part, due to alternative mechanisms of tumor vascularization such as vasculogenic mimicry (VM), the ability of tumor cells to form fluid carrying vascular channels. Curcumin, a polyphenol extracted from the spice turmeric, has numerous anti-cancer and anti-inflammatory properties. Our aims were to investigate the effect of curcumin on vasculogenic mimicry and to determine if curcumin acts by disrupting microRNA profiles of mesothelioma cells. In preparation for future clinical trials, we evaluated the safety of curcumin treatments in vivo, when applied to the pleural cavity. Mesothelioma cell lines NCl-H226 and NCI-H28, as well as patient-derived primary mesothelioma cells isolated from pleural effusions were used for in vitro experiments. Matrigel tube formation assays were performed to assess if curcumin could inhibit VM in vitro. Small RNAseq was performed to determine if 6 h curcumin (20 mM) treatments had an effect on microRNA expression. Curcumin (80 mg/kg) was injected into the pleural cavity of Fischer 344 rats (n=6) and blood was taken at 1.5 h, 24 h, 48 h, 7 days, 14 days and 21 days. Rats were euthanized at 48 h, 1 week and 3 weeks (n=2). Parietal pleura, lung, kidney, liver brain and heart tissues were obtained and examined for signs of gross tissue damage and histopathological changes such as inflammation, and necrosis. Curcumin plasma and concentrations were measured using UPLC-MS to determine systemic distribution of curcumin following intrapleural treatments. Non-cytotoxic curcumin treatments (20-10 mM) significantly inhibited the ability of mesothelioma cells to perform vasculogenic mimicry in vitro in a dose dependent manner. The microRNA expression profiles differed greatly between each mesothelioma sub-type. Minimal curcumin-induced change was observed, however differential expression analysis revealed some potential microRNA targets. No adverse effects were observed following intrapleural curcumin administration. Encapsulated curcumin deposits were observed in the pleural cavity of rats at 1 and 3 weeks following curcumin administration. Histological analysis revealed focal reactive mesothelial hyperplasia and a histiocytic response towards curcumin. Lung, liver, heart, brain and kidney tissues all display normal histological appearances. Curcumin was detected in the plasma samples of rats receiving intrapleural curcumin with peak concentration observed at 1.5 h post curcumin treatment (387-100 μg/ml). Intrapleural curcumin treatments may be suitable as adjunct treatment for MPM.
MA 16.03 Health Utility Scores in Patients with Thymic Malignancies Treated with Multimodality Therapy
Authors: S. Soldera, H. Naik, S. Shakik, M. Moskovitz, A. Parajian, N. Mittman, W. Xu, A. Hope, A. Bezjak, S. Keshavjee, G. Liu
Journal: Journal of Thoracic Oncology (2017)