tbuckley/cabot-search huggingface dataset:
QLIF-46. THE EXPERIENCE OF MEDICAL CARE-RELATED DECISIONS AMONG MALIGNANT BRAIN TUMOR PATIENTS IN JAPAN: QUALITATIVE INTERVIEWS
Authors: Hanako Numata, Maiko Noguchi-Watanabe, Shota Tanaka, Shunsaku Takayanagi, Akitake Mukasa, Nobuhito Saito, Noriko Yamamoto-Mitani
Journal: Neuro-Oncology (2017)

To elucidate the experiences of medical care-related decisions among patients with malignant brain tumor in their active treatment from the patients’ perspective. DESIGN AND Qualitative design based on grounded theory was used. Participants were 14 in/outpatients with malignant brain tumor in their active treatment. Twenty-two semi-structured interviews regarding experience of medical-care related decisions were conducted. All interview transcripts were coded line-by-line and the codes sorted to form categories while examining the relationship among the categories. We particularly focused on comparing multiple decision points to derive a typology of those decisions. Forty-eight decision points regarding surgery, radiotherapy, chemotherapy, and hospital selection were found. Patients faced multiple decisions in their desperate vulnerable struggling due to fear-causing symptoms and an uncertain future. Under this context, the combination of two issues, namely 1) What/who decided and 2) Whether the participant decided what/who would decide, yielded four decision patterns: (1) Led by the situation, (2) Controlled by others, (3) Entrusted someone with the decision, and (4) Myself as a decision-making agent. In their perspective, most decisions were not decided actively by the patients themselves, largely because their hands were already full in struggling with those symptoms and the anxiety. They did not have enough mental tenacity to be an active decision agent. Most participants experienced multiple decision patterns. At the time of the interviews most seemed satisfied with their decisions even when they were not the active decision agent, but the perception change over time with disease/treatment progression. To better support patients with malignant brain tumor, healthcare professionals may need to appreciate their desperate vulnerable struggling and Japanese cultural attitude of not deciding themselves. Healthcare professionals should also assess whether the patient is aware of their own decision preference—the contents of decision and level of participation—first at each decision.
DDIS-16. A MOLECULAR IMAGING BIOSENSOR MONITORS THE EFFECTS OF ANTI-MISFOLDING DRUGS THAT RESTORE MUTANT p53 FUNCTION AND ENHANCE COMBINATION CHEMOTHERAPY FOR GLIOBLASTOMA
Authors: Ramasamy Paulmurugan, Rayhaneh Afjei, Husam Babikir, Thillai Sekar, Tarik Massoud
Journal: Neuro-Oncology (2017)

Small molecule drugs that induce refolding of mutant p53 conformations may restore tumor suppressor function in glioblastoma. We developed a molecular imaging biosensor to monitor drug modulated changes in p53 folding in cells and in vivo. We evaluated the role of drugs that bind to mutant p53 proteins in different glioblastoma cells engineered to stably express four different genetic backgrounds (wt-p53 or three other mutant p53s). We developed separate Ln229 cells (endogenously mt-p53P98L) to each stably express one of four varieties of a split-Renilla luciferase reporter protein complementation biosensor (NRLuc-p53-CRLuc), to thus achieve four different cellular p53 statuses (wt-p53, mt-p53Y220C, mt-p53G245S and mt-p53G282W). We first studied if these transduced fusion proteins could induce changes in background p53 status. We then tested these cells for luciferase complementation after exposure to anti-misfolding drugs (PhiKan083 and SCH-529074, with high affinity for p53Y220C and p53G245S, respectively). Further, we studied the apoptotic effects of these drugs when combined with chemotherapies in all transduced Ln229 and U-87MG cells (the latter endogenously wt-p53 status). Ln229 cells adopted p53 phenotypes that reflected the transduced biosensor fusion proteins. There was activation of p53 structural change upon PhiKan083 and SCH-529074 treatments. Cells treated with PhiKan083 showed significant levels of p53 refolding for mt-p53Y220C. Cells treated with doxorubicin (Dox) or temozolomide (TMZ) in combination with PhiKan083 (12.5–50μM) or SCH (1.25–5.0μM) showed significant dose dependent enhancement of apoptotic effect (>40% increase) within 24h after treatment. A p53 protein folding biosensor maintains its particular p53 function within cells, and induces a change in their p53 genetic background. The use of PhiKan083 and SCH-529074 improves the therapeutic effects of Dox and TMZ in glioblastoma cells. Applications of this biosensor will be useful for discovery and screening of new p53 anti-misfolding drugs and subsequent validation of hits in small animal models.
Sample Size Matters When Drawing Conclusions on Alternate-Day Fasting Diet—Reply
Authors: John F. Trepanowski, Eric Ravussin, Krista A. Varady
Journal: JAMA Internal Medicine (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 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
EXTH-11. PD-1 ANTAGONISM WITH CONCURRENT COMPETITIVE INHIBITION OF PP2A PROMOTES ENHANCED REGRESSION OF INTRACRANIAL GLIOBLASTOMA
Authors: Dominic Maggio, Winson Ho, Herui Wang, Rongze Lu, John Heiss, Mark R Gilbert, Zhengping Zhuang
Journal: Neuro-Oncology (2017)

Checkpoint inhibition using monoclonal antibodies against PD-1 is currently under evaluation for treatment of glioblastoma (GBM). Inhibition of protein phosphatase 2A (PP2a) was recently identified as a novel strategy to enhance cancer immunity. We hypothesized that pharmacologic inhibition of PP2a utilizing a novel small-molecule inhibitor, LB100, could enhance the therapeutic effect of anti-PD-1 checkpoint inhibition in a syngeneic murine GBM model. C57BL/6 mice were inoculated with 130,000 GL261-Luc+ cells in their right striatum. When tumors reached a size of 1.3–2.6 million photon/sec*mm2 in the region of interest (ROI) on bioluminescent imaging, mice were randomized into treatment groups: control (PBS), anti-PD-1, LB100, and combination. For in-vitro studies, CD4 and CD8 cells were isolated from mouse splenocytes. FACS analysis was performed. 0.4m polyethylene terephthalate transwell cell culture inserts were utilized for lymphocyte-GL261 co-culture experiments. Mice treated with the combination therapy demonstrated a significant increase in survival vs monotherapy or control (p<0.005). Tumors in the combination therapy group displayed a significant decrease in relative ROI after the first treatment compared to control (p<0.05) or LB100 alone (p<0.01). A long-term durable cure occurred in 25% of combination treated mice, but not in any other group. In-vitro analysis demonstrated a dose-dependent inhibition of PP2a by LB100 in CD4 and CD8 cells. LB100 increased the proliferation index of activated CD4 and CD8 cells. LB100-treated CD8 cells, but not CD4 cells, induced a higher expression of PDL-1 on GL261 cells co-cultured in transwell culture. These data suggest that PP2a inhibition and PD-1 mAb checkpoint inhibition act synergistically against intracranial GBM. This finding supports further preclinical investigation of the LB100 and anti-PD-1 combination.
Le Centre européen de prévention et de contrôle des maladies
Authors: G Gouvras
Journal: Eurosurveillance (2004)

La ceremonie d'ouverture du Centre europeen de prevention et de controle des maladies a eu lieu a Stockholm le 27 septembre 2004. Cet evenement a marque le debut d'une nouvelle epoque en termes de surveillance et de controle des maladies transmiss
P3.02-024 Role of FBXW7 in the Maintenance of Quiescent Cancer Stem Cells Resistant to Gefitinib in EGFR Mutation-Positive Non-Small Cell Lung Cancer
Authors: M. Hidayat, F. Takahashi, K. Tajima, F. Nurwidya, A. Wirawan, R. Kanemaru, Y. Koinuma, H. Ihara, M. Tajima, N. Matsumoto, K. Kanamori, I. Takeda, M. Haraguchi, D. Hayakawa, R. Ko, M. Kato, R. Shibayama, R. Koyama, M. Takahashi, N. Shimada, K. Takahashi
Journal: Journal of Thoracic Oncology (2017)
P2.01-010 Risk Score for Predicting Acute Exacerbation after Chemotherapy in Lung Cancer Associated with Interstitial Pneumonia
Authors: K. Isobe, K. Kaburaki, H. Kobayashi, G. Sano, K. Sugino, S. Sakamoto, Y. Takai, T. Makino, N. Tochigi, A. Iyoda, S. Homma
Journal: Journal of Thoracic Oncology (2017)
STEM-08. RNA BINDING PROTEIN ZFP36L2 REGULATES GLIOMA STEM CELL MAINTENANCE
Authors: Tanwarat Sanvoranart, Leo Kim, Qiulian Wu, Xun Jin, Deobrat Dixit, Sisi Lai, Lisa C Wallace, Jeremy Rich
Journal: Neuro-Oncology (2017)

Post-transcriptional regulation of gene expression is well-controlled across normal tissues. Dysregulation of these regulatory events contributes to tumorigenesis and progression of cancer. RNA binding proteins (RBPs), as trans-acting factors, play a pivotal role in post-transcriptional RNA modification. We interrogated the TCGA glioblastoma microarray dataset, comparing glioblastoma to non-tumor with a differential expression level of at least twofold for RBP genes to identify candidate RBP genes that could contribute to glioblastoma malignancy. 36 RBP genes were significantly upregulated and 12 RBP genes were downregulated in glioblastoma. Among these RBP candidates, the Zinc Finger Protein 36, C3H1 Type-Like 2 or ZFP36L2, significantly correlated with poor survival. However, the biological function of ZFP36L2 is poorly understood. Here, we found that ZFP36L2 was highly expressed in the stem-like glioma cells, glioma stem cells (GSCs), compared to normal brain tissues. Targeting ZFP36L2 by short hairpin RNAs inhibited GSC proliferation, decreased self-renewal capacity in vitro, and inhibited tumor formation in vivo. Depletion of ZFP36L2 caused S-phase and G2/M-phase cell cycle arrest. Interrogating the upstream regulation of ZFP36L2 expression, we found CEBP/β overexpressed in GSC as a transcription factor binding to the ZFP36L2 promoter and regulated the ZFP36L2 expression. Downstream, HuR, another RNA binding protein encoded by the ELAVL1 gene, regulated ZFP36L2 at the mRNA level. Collectively, we are elucidating a novel RNA binding protein network essential for GSC maintenance, informing gene-regulatory mechanisms offering new opportunities for developing mechanistic based target therapeutics in neuro-oncology.
PUB056 Smoking History Affects the Production of Tumor Antigen Specific Antibodies NY-ESO-1 in Patients with Lung Cancer
Authors: D. Myšíková, I. Adkins, N. Hradilova, O. Palata, J. Šimonek, J. Kolařík, J. Pozniak, A. Fialová, R. Špíšek, R. Lischke
Journal: Journal of Thoracic Oncology (2017)
STEM-02. CHARACTERIZATION OF PATIENT-DERIVED BONE MARROW MESENCHYMAL STEM CELLS AS VIRUS CARRIERS FOR THE TREATMENT OF GLIOBLASTOMA
Authors: Yuzaburo Shimizu, Joy Gumin, Anwar Hossain, Feng Gao, Elizabeth J Shpall, Akihide Kondo, Frederick F Lang
Journal: Neuro-Oncology (2017)

Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and lysing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow human mesenchymal stem cells (BM-hMSCs) derived from normal healthy donors have been investigated as virus carriers. However, it is not clear whether BM-hMSCs can be derived from patients with gliomas previously treated with marrow-toxic chemotherapy and whether such BM-hMSCs can deliver oncolytic viruses as effectively as BM-hMSCs from normal donors. In order to determine the feasibility of obtaining BM-MSCs from patients with recurrent malignant glioma who had been exposed to marrow-toxic chemotherapy, we undertook a prospective clinical trial evaluating the ability of obtaining BM-MSCs from patients with recurrent gliomas. We enrolled 5 consecutive patients who had been previously treated with radiation therapy and chemotherapy and who were undergoing surgical resection for their recurrent glioma. BM aspirates were obtained from the iliac crest of each patient. Aspirates were cultured to obtain hMSCs. By passage 3, the patient derived BM-hMSCs (PD-hMSCs) cells had the morphology of normal BM-hMSCs. Flow cytometry revealed that all 5 cell lines expressed canonical surface markers characteristic of normal BM-hMSCs (positive for CD105, CD73, and CD90 and negative for CD45, CD34, and CD11b). Importantly, all 5 PD-hMSC cultures could be differentiated into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as normal BM-hMSCs. PD-hMSCs could be loaded with Delta-24-RGD (PD-MSC-D24) and effectively killed human gliomas in vitro and in vivo. Specifically, intravascular administration of PD-hMSC-D24 increased the survival of mice harboring U87 gliomas. We conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-hMSCs are effective vehicles for delivering oncolytic viruses.
MA 20.12 Longitudinal Evaluation of Pulmonary Function in Patients with Advanced NSCLC Treated with Concurrent Chemo-Radiotherapy
Authors: M. Arroyo Hernandez, L. Torre Bouscoulet, L. Bacon, F. Lozano-Ruiz, L. Gochicoa-Rangel, C. García-Sancho, E. Vergara, D. Martínez Briseño, A. Guzmán-Barragán, R. Fernández Plata, M. Blake Cerda, F. Maldonado, O. Arrieta
Journal: Journal of Thoracic Oncology (2017)
MA 03.02 Timing of B12/Folate Supplementation in NSCLC Patients on Pemetrexed Based Chemotherapy: Final Results of the PEMVITASTART Randomized Trial
Authors: N. Singh, M. Baldi, J. Kaur, K. Prasad, R. Kapoor, D. Behera
Journal: Journal of Thoracic Oncology (2017)
Garlic-derived compound S-allylmercaptocysteine inhibits hepatocarcinogenesis through targeting LRP6/Wnt pathway
Authors: Jia Xiao, Feiyue Xing, Yingxia Liu, Yi Lv, Xiaogang Wang, Ming-Tat Ling, Hao Gao, Songying Ouyang, Min Yang, Jiang Zhu, Yu Xia, Kwok-Fai So, George L. Tipoe
Journal: Acta Pharmaceutica Sinica B (2017)

Whether and how garlic-derived S-allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of β-catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. In vivo administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.
Biomarkers for immunotherapy in bladder cancer: a moving target
Authors: David H. Aggen, Charles G. Drake
Journal: Journal for ImmunoTherapy of Cancer (2017)

Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30&nbsp;years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression.
ACTR-62. A PHASE II STUDY OF TUMOR TREATING FIELDS (TTFIELDS) WITH TEMOZOLOMIDE IN PATIENTS WITH LOW-GRADE GLIOMAS
Authors: Tiffany Juarez, Najee Boucher, Annie Heng, Jaya Gill, Minhdan Nguyen, Judy Truong, Marlon Saria, Achal Achrol, Garni Barkhoudarian, Daniel Kelly, Santosh Kesari
Journal: Neuro-Oncology (2017)

Approximately 2,000 to 3,000 adults are diagnosed with low-grade gliomas (LGGs) annually in the United States, with a median overall survival ranging from 3–9 years. Radiation and chemotherapy are used to treat LGGs but can increase the risk of transformation to high-grade tumors (HGG) and cause cognitive impairment. Therefore, management of LGGs remains controversial with a need for more effective treatments with decreased side effects. This Phase II study [NCT02507232] investigates TTFields plus metronomic chemotherapy in LGGs. The Optune System delivers TTFields that disrupts rapid cell division by cancer cells. This prospective, single-center, 2-arm, open-label study randomizes 42 patients with newly diagnosed LGGs 1:1 (21/arm) to TTFields alone or with daily-temozolomide (50mg/m2). The primary endpoint is the objective response rate (ORR=CR+PR) at 12 months assessed per RANO criteria. Secondary objectives include progression-free survival (PFS), overall survival at 24 months, adverse events (CTCAE), seizure activity, quality-of-life (FACT-Br), and HGG transformation frequency. This study will also explore the association between patient response/survival and molecular profiling and device compliance, as well as activation of a systemic immune response. Inclusion criteria include age >18 years, histologically confirmed LGG (grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma), measureable and supratentorially-located tumor, and no prior radiation, radiosurgery, or chemotherapy. Patients will continue monthly cycles of treatment for 12 cycles or until disease progression or unacceptable toxicity (whichever occurs first). Patients may continue TTFields if temozolomide is discontinued early for toxicity. Patients discontinuing study treatment will be followed at months 18 and 24 with tumor assessments if they discontinued from study treatment without disease progression and for survival. Based on a 12-month ORR of 13%, the sample size of N=42 assumes an 80% power at significance-level 2.5% to conclude if ORR is significantly different from historical control. The study is open to enrollment and updated data will be presented.
Review of Calvin Wai-Loon Ho, Juridification in Bioethics: Governance of Human Pluripotent Cell Research
Authors: Edward S. Dove
Journal: The American Journal of Bioethics (2017)

"Review of Calvin Wai-Loon Ho, Juridification in Bioethics: Governance of Human Pluripotent Cell Research1." The American Journal of Bioethics, 17(11), pp. W12–W13
ACTR-94. TOXICITY OF SINGLE AGENT CARMUSTINE VERSUS CARMUSTINE PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT OR PROGRESSIVE HIGH GRADE GLIOMAS
Authors: Prakirthi Yerram, Samantha Reiss, Lisa Modelevsky, Igor Gavrilovic, Thomas Kaley
Journal: Neuro-Oncology (2017)

An increased incidence in hematologic toxicity has been reported with the addition of bevacizumab to lomustine for patients with recurrent or progressive high grade gliomas (HGG). Data regarding incidence of toxicity with combination bevacizumab and carmustine (BCNU) is limited. The purpose of this study is to compare toxicity of single agent BCNU versus BCNU plus bevacizumab for patients with HGGs. This IRB approved single center retrospective study at Memorial Sloan Kettering Cancer Center included pathologically confirmed HGG with an age ≥18 years who received BCNU between 6/2014 and 5/2017. Forty-six patients with HGGs collectively received 72 doses of BCNU during the specified time period. Median age was 52 years (range 21–77), 65% were men, median KPS was 70 (range 50–100). Histologies included glioblastoma (n=37; 80.4%), anaplastic astrocytoma (n=8; 17.4%), and gliosarcoma (n=1; 2.2%). Patients received a median of 2 prior lines of therapy (range 1–5). Twelve patients received single agent BCNU (16 doses); 34 patients received combination bevacizumab with BCNU (56 doses). There was no significant difference in incidence or grade of toxicity between single agent and combination therapy with respect to hepatotoxicity, leukopenia, lymphopenia, neutropenia, anemia, and thrombocytopenia. Rates of grade 3 and 4 neutropenia (18.8% vs 10.7%, p=0.37) and thrombocytopenia (18.8% vs 17.9%, p=1) did not differ between single agent BCNU versus combination therapy. When stratified based on dose (<150mg/m2, 150mg/m2, >150mg/m2), there was no statistically significant difference between the two groups with respect to grade 3 and 4 neutropenia or thrombocytopenia. The addition of bevacizumab to BCNU did not increase incidence or grade of hematologic toxicity when compared to single agent BCNU.
Leptospirosi in Portogallo: epidemiologia dal 1991 al 1997
Authors: J M Falcão, P J Nogueira, C MatiasDias, Z. P. Pimenta
Journal: Eurosurveillance (1999)

Il termine leptospirosi descrive un insieme di malattie provocate da membri dell'ordine degli Spirochaetales, principalmente della specie Leptospira interrogans. L'infezione puo essere asintomatica ma possono presentarsi anche casi con gravita e sintomi clinici diversi (spesso confondibili con meningiti, encefaliti o influenze). La durata della leptospirosi va da pochi giorni a molte settimane, a seconda della gravita e della cura. La mortalita e bassa ma puo superare il 20% nei pazienti che sviluppano insufficienza epatica e renale (malattia di Weil) e nelle persone anziane.