tbuckley/cabot-search huggingface dataset:
Abstract #2169: Brain-derived Neurotrophic Factor (BDNF) induces anoikis suppression in a nasopharyngeal cancer cell line, HONE-1-EBV
Authors: Yuen Ng, Elaine Wong, Cecilia Lau, Cesar Wong, Daisy Yau, Andrew Chan, Maggie Kwan, Chi-Man Tsang, Sai-Wah Tsao, Anthony Chan, Vivian Lui
Journal: Cancer Research (2009)

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southeast Asia. It is characterized by its strong etiologic association with Epstein-Barr virus (EBV) infection, and its highly invasive and metastatic nature. The underlying mechanism for its high metastatic potential is poorly understood. To enable spreading (metastasis), cancer cells need to detach from their primary sites and survive in the absence of extracellular matrix (ECM). Anoikis is a programmed cell death resulted from the loss-of-contact with ECM. Proliferation/survival of normal epithelial cells is guarded by anoikis to ensure its survival in a matrix-dependent status. However, many cancer cells acquire anoikis resistance for their survival in the detached status for metastasis. The neurotrophin receptor TrkB and its ligand, brain-derived neurotrophic factor (BDNF), are key players in anoikis suppression in cancer. BDNF/TrkB overexpression, which is often associated with poor prognosis in many malignancies, has been reported in NPC. Here, we investigated the possible involvement of BDNF/TrkB signaling in NPC tumorigenesis. BDNF mRNA expression was detected in 7/11 (~64%) NPC patient biopsies. TrkB and BDNF were expressed in a representative NPC cell line, HONE-1-EBV. Several NPC cell lines, when grown on neutrally charged plates, were able to proliferate in a detached status. For HONE-1-EBV, BDNF (50 ng/ml) enhanced cellular proliferation in suspension. This effect was blocked by the pan-Trk inhibitor, K252a (300nM). BDNF also induced HONE-1-EBV cellular migration through the transwell chamber in a dose-dependent manner. Therefore, BDNF/TrkB signaling enhances the migration and survival of the anoikis resistant NPC cells, which may contribute to NPC invasiveness.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2169.
A Phase Ib, Open-Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of AZD1775 Monotherapy in Patients with Advanced Solid Tumors: Expansion Cohorts.
Authors: Todd Michael Bauer, Suzanne Fields Jones, Carol Greenlees, Carl Cook, Philip John Jewsbury, Ganesh Mugundu, Tim French, Andrew J Pierce, Mark J. O'Connor, Naomi Laing, J Carl Barrett, Dawn Michelle Stults, Melissa Lynne Johnson, J. Thaddeus Beck, Kathleen N. Moore, Jeffrey R. Infante, Howard A. Burris, David R. Spigel
Journal: Journal of Clinical Oncology (2016)

TPS2608 Background: Many cancers are associated with DNA repair and cell cycle mutations that result in G1/S checkpoint deficiencies and high levels of endogenous damage and replication stress. This can lead to dependence on WEE1 kinase, which provides an important G2/M checkpoint, allowing repair of DNA damage prior to mitosis. AZD1775 is a highly selective, small-molecule WEE1 inhibitor being developed for the treatment (tx) of advanced solid tumors. It has previously shown single-agent activity in patients (pts) with BRCA-1/2 mutations (Do, JCO 2015). We described initial safety and efficacy of the dose escalation portion of an open Phase Ib study (NCT02482311) of AZD1775 in pts with refractory solid tumors, and a dose of AZD1775 175 mg PO BID was identified (submitted to AACR 2016). Here we describe the expansion portion of this study in 6 matched cohorts: BRCA-1/2-mutant and wildtype (WT) ovarian cancer (OvC); cyclin-E (CCNE1)-amplified and non-amplified triple-negative breast cancer (TNBC); and any of MYC/MYCL/MYCN-amplified and all non-amplified small-cell lung cancer (SCLC). The objective of this portion of the study is to evaluate the safety, tolerability, and efficacy of AZD1775 monotherapy in these cohorts. Methods: 140 pts will be enrolled in the expansion portion: 20 pts with recurrent BRCA-1/2 WT OvC following > 3 prior therapies, ≥ 20 BRCA-1/2 mutant OvC pts following failure of PARP inhibitor therapy, 50 with recurrent TNBC following > 2 therapies ( ≥ 15 with cyclin E (CCNE1) amplified TNBC); and 50 with SCLC following > 1 therapy ( ≥ 15 with any of MYC/MYCL/MYCN amplified SCLC). All pts must have measurable advanced solid tumors per RECIST, and adequate organ function. Pts will receive AZD1775 175 mg PO BID D1-3, 8-10 of a 21-day cycle. All pts will receive prophylactic antiemetics. Pts will be restaged every 2 cycles the first year, every 4 cycles thereafter, and continue until disease progression or intolerable toxicity. Tumor samples will be collected for correlative biomarker analysis. Clinical trial information: NCT02482311.
Effect of General Anesthesia and Conscious Sedation During Endovascular Therapy on Infarct Growth and Clinical Outcomes in Acute Ischemic Stroke
Authors: Claus Z. Simonsen, Albert J. Yoo, Leif H. Sørensen, Niels Juul, Søren P. Johnsen, Grethe Andersen, Mads Rasmussen
Journal: JAMA Neurology (2018)

Endovascular therapy (EVT) is the standard of care for select patients who had a stroke caused by a large vessel occlusion in the anterior circulation, but there is uncertainty regarding the optimal anesthetic approach during EVT. Observational studies suggest that general anesthesia (GA) is associated with worse outcomes compared with conscious sedation (CS).To examine the effect of type of anesthesia during EVT on infarct growth and clinical outcome.The General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center prospective, randomized, open-label, blinded end-point evaluation that enrolled patients from March 12, 2015, to February 2, 2017. Although the trial screened 1501 patients, it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded. Primary analysis was unadjusted and according to the intention-to-treat principle.Patients were randomized to either the GA group or the CS group (1:1 allocation) before EVT.The primary end point was infarct growth between magnetic resonance imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis formulated before data collection was that patients who were under CS would have less infarct growth.Of 128 patients included in the trial, 65 were randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean (SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic and clinical variables were balanced between the GA and CS treatment arms. The median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). Four patients (6.3%) in the CS group were converted to the GA group. Successful reperfusion was significantly higher in the GA arm than in the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct growth among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs 19.4 [2.4-79.0] mL; P = .10). There were better clinical outcomes in the GA group, with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56).For patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation, GA did not result in worse tissue or clinical outcomes compared with CS.clinicaltrials.gov Identifier: NCT02317237.
Reply to Christian D. Fankhauser, Nico C. Grossmann, Joerg Beyer, and Thomas Hermanns’ Letter to the Editor re: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, et al. Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer. Eur Urol 2018;73:262–70.
Authors: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, Mark A. Preston, Quoc-Dien Trinh, Lindsay A. Frazier, Toni K. Choueiri, Neil E. Martin, Paul L. Nguyen, Clair J. Beard
Journal: European Urology (2018)
EGFR–TKI-Associated Interstitial Pneumonitis in Nivolumab-Treated Patients With Non–Small Cell Lung Cancer
Authors: Yasuo Oshima, Tetsuya Tanimoto, Koichiro Yuji, Arinobu Tojo
Journal: JAMA Oncology (2018)

Nivolumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents.To determine whether nivolumab increases EGFR-TKI-associated interstitial pneumonitis (IP).A database study of 20 516 participants with NSCLC in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, performed between April 2015 and March 2017.We compared the incidence of EGFR-TKI-associated IP in patients receiving and not receiving nivolumab treatment.The mean (SD) age of participants treated with EGFR-TKI, with and without nivolumab, was 64.4 (15.5) and 68.9 (11.8) years, respectively, and the proportion of men was 40.0% and 53.8%, respectively. Of the 20 516 participants with NSCLC, 985 cases (4.80%; 95% CI, 4.51-5.10) developed IP. Of 5777 patients treated with EGFR-TKI, 265 developed IP (4.59%; 95% CI, 4.06-5.16). Of 70 patients treated with both EGFR-TKI and nivolumab, 18 developed IP (25.7%; 95% CI, 16.0-37.6). The adjusted odds ratio for an interaction between EGFR-TKI and nivolumab was 4.31 (95% CI, 2.37-7.86; P < .001), suggesting the existence of an interaction. When we further stratified the patients by treatment with and without nivolumab, the odds ratio of EGFR-TKI-associated IP in cases with and without nivolumab treatment was 5.09 (95% CI, 2.87-9.03) and 1.22 (95% CI, 1.00-1.47), respectively.We found a higher proportion of reports of IP for nivolumab in combination with EGFR-TKI vs treatment with either drug alone. Owing to the limitations of this study, the results warrant further confirmation. However, careful consideration should be given to the possibility of an increased risk of IP when EGFR-TKI is administered in combination with nivolumab, including concomitant and sequential use, and careful monitoring for IP is recommended.
Intertriginous Condyloma-like Plaques and Ulcers
Authors: Elizabeth N. Ergen, Michael Slade Stratton, Carlos Prieto Granada
Journal: JAMA Dermatology (2018)

A woman in her 50s with a medical history of hypertension and depression was evaluated by the inpatient dermatology consult service for a 1.5-year history of painful intertriginous wounds; she was previously diagnosed with hidradenitis suppurativa. What is your diagnosis?
Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates
Authors: Keyang Zhu, Qiang Wu, Cheng Ni, Peng Zhang, Zhiwei Zhong, Yan Wu, Yingchao Wang, Yinchuan Xu, Minjian Kong, Haifeng Cheng, Zhihua Tao, Qian Yang, He Liang, Yun Jiang, Qingju Li, Jing Zhao, Jijun Huang, Fengjiang Zhang, Qi Chen, Yi Li, Jinghai Chen, Wei Zhu, Hong Yu, Jianyi Zhang, Huang-Tian Yang, Xinyang Hu, Jian’an Wang
Journal: Circulation Research (2018)

Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials.The main of this study is to clarify whether hPSC-CVPCs can engraft for long time in the heart of primates after myocardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cyclosporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus monkeys that had received intramyocardial injections of 1×107 EGFP (enhanced green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of animals received the immunosuppression MDR but without cell therapy after MI (MI+MDR group).Measurements of EGFP gene levels and EGFP immunofluorescence staining indicated that the hPSC-CVPC engraftment rate was greater in the MI+MDR+CVPC group than that in the MI+cyclosporine+CVPC group. However, even in the MI+MDR+CVPC group, no transplanted cells could be detected at 140 days after transplantation. Concomitantly, immunofluorescent analysis of CD3, CD4, and CD8 expression indicated that T-lymphocyte infiltration in the CVPC-transplanted hearts was less in the MDR-treated animals than in the cyclosporine-alone-treated animals. The recovery of left ventricular function on day 28 post-MI in the MI+MDR+CVPC group was better than that in the MI+MDR group. Apoptotic cardiac cells were also less common in the MI+MDR+CVPC group than in the MI+MDR group, although both immunosuppression regimens were associated with transient hepatic dysfunction.This is the largest study of hPSCs in nonhuman primates in cardiovascular field to date (n=32). Compared with cyclosporine alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in primates; this is associated with less apoptosis of native cardiac cells and better recovery of left ventricular function at 28 days. However, even with MDR, transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after transplantation, thereby excluding remuscularization as a mechanism for the functional effect.
Mobilization of type1 and type2 dendritic cells (DC1 and DC2) in non-Hodgkin’s lymphoma (NHL) patients mobilized with G-CSF, GM-CSF or GM-CSF followed by G-CSF
Authors: Yair Gazitt, Cagla Akay, Charles Thomas
Journal: Cancer Research (2004)

4670  Dendritic cells (DC) are the most efficient antigen presenting cells and are important in the immune reconstitution process post allogeneic and autologous peripheral blood stem cell transplantation (PBSCT). Recent reports suggested that G-CSF polarizes DC into DC2 type cells which stimulate Th2 response resulting with decreased graft vs host disease (GVHD), as compared to DC1 which stimulate Th1 response resulting with increased GVHD and graft vs. tumor (GVT) effect. Previously, we have shown that NHL patients (pts) given GM-CSF mobilized up to 5 fold more immature DC (CD14+CD80+ cells) compared to G-CSF mobilized pts. (Gazitt et al. J. Hematother. Stem Cell Res. 10:177, 2001). In light of the recently identified subpopulations of DCs, we decided to analyze subpopulations of DCs in banked samples from 27 NHL patients who underwent high dose chemotherapy and PBSCT. Patients were randomly mobilized with G-CSF (8 pts); GM-CSF (8 pts); and GM-CSF followed by G-CSF (11pts). We compared the yield and ratio of DC1 and DC2 within the same group of patients and between the 3 arms of the study. Patients received for mobilization cyclophosphamide followed by 14 days of G-CSF (10ug/kg/day); GM-CSF (500ug/msq./day); or 8 days of GM-CSF followed by 6 days of G-CSF. Patients were collected for 4 days and were transplanted with >2x106 CD34+cells/Kg. DC1 cells were defined as CD11c+HLADR+lin- cells. DC2 cells as CD123+HLADR+lin- cells. Analysis was done by flow cytometry using a 3-color assay. Patients mobilized with G-CSF plus GM-CSF had significantly higher levels of DC1+DC2 cells (mean=4.2x106+1.5/DC/kg/day) compared to pts mobilized with GM-CSF (2.6+ 1.4) (p=0.019). Patients mobilized with G-CSF had intermediate level of DCs/Kg/day (3.5+1.6). The mean mobilization of DC1 vs. DC2 in pts mobilized with G-CSF was 1.2+0.4; vs. 2.2+ 1 x106 DCs/kg/day), whereas pts mobilized with GM-CSF collected a mean of 1.1+0.5 vs. 1.5+0.8; and pts mobilized with GM-CSF +G-CSF collected a mean of 2.2+1.1vs. 1.8+0.5x106DCs/kg/day. Thus pts mobilized with GM-CSF received relatively higher levels of DC1cells. Survival rate in pts with a median follow-up of 5 years was 0.125; 0.65 and 0.6 in patents who received G-CSF; GM-CSF and GM-CSF+G-CSF, respectively. Kaplan Meier analysis indicated a trend for a higher survival rate for the group who received the combination of G-CSF+GM-CSF, despite the small number of patients in the study, indicating an overall advantage for the GM-CSF containing mobilization protocol. These results taken together suggest that higher levels of DCs, preferably DC1 are associated with prolonged survival of auto transplanted NHL patents.
Risks of Statins for Lower-Risk Individuals
Authors: William T. Regenold
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Intracoronary echocontrast evaluation of myocardial viability after PTCA: A comparison with echo dobutamine low dose stress test
Authors: A Petronio, Baglini, R. Baglini, R Limbruno, U. Limbruno, U Mengozzi, G. Mengozzi, G Delledonne, Mg DelleDonne, Vaghetti Mg, M. Vaghetti, M Cantarelli, A. Cantarelli, A Amoroso, G. Amoroso, G Mariani, M. Mariani
Journal: Journal of the American College of Cardiology (1997)
Diagnosis-to-Treatment Interval (DTI) Remains Associated with Adverse Clinical Characteristics and Outcome in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma Treated on Clinical Trials
Authors: Matthew J Maurer, Hervé Ghesquières, Brian K Link, Jean-Philippe Jais, Thomas M Habermann, Carrie A Thompson, Corinne Haioun, Cristine Allmer, Patrick B Johnston, Richard Delarue, Ivana N Micallef, Frederic Peyrade, David J Inwards, Nicolas Ketterer, Umar Farooq, Olivier Fitoussi, William R Macon, Thierry Jo Molina, Sergei Syrbu, Andrew L Feldman, Susan L Slager, George J Weiner, Stephen M Ansell, James R. Cerhan, Gilles Andre Salles, Thomas E Witzig, Herve Tilly, Grzegorz S Nowakowski
Journal: Blood (2017)
Correlation between Overall Allergy Symptom Visual Analog Scale (VAS) Scores and Total Symptom Scores (TSS) in Subjects with Ragweed-Induced Allergic Rhinitis in an Environmental Exposure Chamber (EEC)
Authors: Anne Marie Salapatek, Cherrie Small, Holly Lorentz, Erin Beattie, Victoria Nelson, Peter R. Couroux
Journal: Journal of Allergy and Clinical Immunology (2018)
Identification and characterization of Bcl-2 inhibitors based on alpha-helix mimetics.
Authors: Vesna Schauer-Vukasinovic, S Hess, W Antuch, N Brusis, P Baums, C Burkhart, B Beck, N Yehia, S Agarwal, YF Keng, D Yu, QZ Chen, YC Lu, S Sakamuri, S Menon, A Domling
Journal: Clinical Cancer Research (2003)
Hope, Fantasy, and Communication in the ICU: Translating Frameworks into Clinical Practice
Authors: Christy L. Cummings
Journal: The American Journal of Bioethics (2018)

In the target article “From ‘Longshot’ to ‘Fantasy’: Obligations to Patients and Families When Last Ditch Medial Efforts Fail” (Weiss and Fiester 2018), the authors elegantly highlight an important...
Abstract 17680: Effectiveness of a New Smartphone Application “AED-SOS” to Call Co-rescuers Carrying an AED for Cardiac Arrests: A Randomized Controlled Trial
Authors: Toshihiro Hatakeyama, Chika Nishiyama, Tomonari Shimamoto, Kosuke Kiyohara, Tetsuhisa Kitamura, Takashi Kawamura, Taku Iwami
Journal: Circulation (2015)

[Introduction] Although earlier shock with an automated external defibrillator (AED) is the key to increase survival after out-of-hospital cardiac arrests (OHCA), it is not easy to find out an AED in emergency settings. We recently developed a new smartphone application “AED-SOS.” This application sends a special signal to the smartphone of potential co-rescuers existing in the neighborhood and indicates the OHCA scene and AED locations on the display. According to these notifications, co-rescuers find out and deliver an AED to the OHCA scene. [Objective] To elucidate how this new application can shorten the process to find out an AED and bring it to the OHCA scene. [Methods] Design: Randomized controlled trial (UMIN000016506). Participants: Lay persons aged 18 years or older. Randomization: Participants were randomly assigned to either the AED-SOS group or the control group using permuted blocks after stratification by sex. Intervention: We provided an OHCA scenario to the study participants of both groups. Participants assigned to the AED-SOS group were encouraged to use the AED-SOS application. Data collection: We observed the process until the participants or their co-rescuers brought an AED to the scene. Outcomes: The primary outcome was the time from the recognition of OHCA to AED delivery by either the participant or the co-rescuers. The secondary outcome was their travel distance. [Results] Among 61 participants enrolled, 52 were analyzed. The time from recognition of OHCA to AED delivery was significantly shorter in the AED-SOS group than in the control group (133.6±44.4 versus 202.2±122.2, p=0.01). The travel distance was similar between the groups (Table). [Conclusion] The smartphone application to prompt potential co-rescuers in the neighborhood to deliver an AED, would shorten the time from recognition of OHCA to AED delivery. It will help increase the survivors after OHCA.
CAR T Cells Targeting FLT3 on AML Confer Potent Anti-Leukemic Activity and Act Synergistically with the FLT3 Inhibitor Midostaurin
Authors: Hardikkumar Jetani, Irene García-Cadenas, Thomas Nerreter, Julian Rydzek, Simone Thomas, Wolfgang Herr, Jordi Sierra, Halvard Bönig, Hermann Einsele, Michael Hudecek
Journal: Blood (2017)