tbuckley/cabot-search huggingface dataset:
DRES-01. ROLE OF HISTONE LYSINE DEMETHYLASE KDM2B IN GLIOBLASTOMA TUMOR CELL MAINTENANCE AND CHEMORESISTANCE
Authors: Mikkel Staberg, Signe Regner Michaelsen, Rikke Rasmussen, Henriette Pedersen, Mette Villingshøj, Hans Skovgaard Poulsen, Petra Hamerlik
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most deadly and malignant of all brain tumors in adults partly due to acquired resistance to conventional drugs leading to recurrence. Emerging evidence indicate that aberrant expression of epigenetic enzymes, resulting in altered gene transcription, may be responsible for cell maintenance and drug resistance in several cancers including GBM. In cancer, epigenetic inhibitors have been shown both to have direct anti-neoplastic functions as well as being able to sensitize cancer cells towards radio- and chemotherapy. As epigenetic dysregulation has been suggested to be involved in the progression and development of glioblastoma (GBM), regulation of epigenetic factors could potentially improve current treatments of GBM. A histone lysine demethylase enzyme termed KDM2B, a regulator of H3K36 methylation, is involved in cellular processes including transcription, cell growth, and DNA repair. In addition, recent studies have shown that KDM2B is involved in cell maintenance and tumorigenesis in leukemia, pancreatic cancer and breast cancer. In this study we sought to elucidate the role of KDM2B in GBM. In vitro assays performed on patient derived GBM cell cultures showed increased expression of KDM2B compared to normal brain tissue. Knockdown of KDM2B by siRNA resulted in induced apoptosis, attenuated cell growth, induction of DNA damage and increased sensitivity towards the conventional chemotherapies lomustine and etoposide. In parallel, chemical inhibition of KDM2B by a histone demethylase inhibitor (GSK-J4) lead to increased apoptosis, DNA damage and inhibition of GBM cell viability at low micro molar concentrations. Combined administration of GSK-J4 and the chemotherapies lomustine or etoposide displayed synergistic inhibition of GBM cell viability. In summary, our results indicate that KDM2B promotes GBM cell maintenance and chemoresistance, proposing KDM2B as a novel therapeutic target for the treatment of GBM.
P2.02-011 Clinical and Molecular Features of Lung Cancers with Increased FGFR1 mRNA and/or Gene Copy Number
Authors: T. Ng, H. Yu, E. York, S. Leedy, D. Gao, L. Heasley, F.R. Hirsch, D.R. Camidge
Journal: Journal of Thoracic Oncology (2017)
Abstract 12810: Defining the Role of Mitral Regurgitation on Left Atrial Function During Exercise in Left Heart Disease: Insights From CPET Combined With Exercise Echocardiography
Authors: Tadafumi Sugimoto, Francesco Bandera, Greta Generati, Eleonora Alfonzetti, Vincenzo Tufaro, Marco Guazzi
Journal: Circulation (2016)

Background: The role of mitral regurgitation (MR) on left atrial dynamics has not been characterized especially during exercise. Its definition might provide additional clues on the pathogenesis of exercise intolerance in patients with cardiac disorders. We aimed at this goal. Methods: 73 heart failure with reduced (n=51) and preserved (n=21) ejection fraction, 53 aortic stenosis, 27 primary mitral regurgitation, 14 hypertrophic cardiomyopathy, and 42 control subjects underwent cardiopulmonary exercise testing evaluation combined with Echo-Doppler with assessment of left atrial strain (LAS) and MR entity. Patients were divided according to the severity of MR and no MR. Results: LAS during exercise compared to rest was significantly increased in no MR (n=92, 27 ± 10 vs 33 ± 13%, P &lt;0.001) and mild MR (n=41, 24 ± 11 vs 26 ± 15%, P &lt;0.05) group but not in mild-moderate MR (n=31, 20 ± 9 vs 23 ± 14%, P=0.05), moderate-severe MR (n=23, 18 ± 12 vs 19 ± 16%, P=0.4), and severe MR (n=19, 17 ± 14 vs 19 ± 14%, P=0.01) group by visual assessment of the severity of MR during exercise (figure). In 54 patients with MR assessed using proximal isovelocity surface area method both at rest and exercise, effective regurgitant orifice (ERO: 19 ± 12 vs 26 ± 16 mm 2 , P &lt;0.001) and regurgitant volume (31 ± 19 vs 40 ± 24 mL, P &lt;0.001) were significantly increased during exercise, and there was no change in LAS during exercise (17 ± 11 vs 18 ± 14%, P=0.4). A progressive impairment in exercise ventilation efficiency assessed by minute ventilation-carbon dioxide production (VE/VCO2 slope) was observed according to ERO entity (ERO: &lt;20 mm 2 , VE/VCO2 slope: 30 ± 7; ERO: 20-40 mm 2 , VE/VcO2 slope: 33 ± 6; ERO: &gt;40 mm 2 , VE/VCO2 slope: 39 ± 17, P &lt;0.05). Conclusions: In left heart disease patients of any origin, an impaired LAS response during exercise is associated with the presence of MR during exercise. This unfavorable pathophysiological and functional response leads to an impaired exercise tolerance and ventilatory inefficiency.
TMOD-30. TARGETING AN OLIG2-DEPENDENT PATHWAY TO INHIBIT TUMOR GROWTH IN PRIMARY AND RECURRENT MEDULLOBLASTOMA
Authors: Xuelian He, Liguo Zhang, Richard Lu
Journal: Neuro-Oncology (2017)

Medulloblastoma represents the most common childhood malignant brain tumor. Despite aggressive multimodal therapy, a significant proportion of surviving patients suffer from severe treatment-related side effects, including tumor relapse. Thus, there is an urgent need for novel therapeutic modalities that can improve medulloblastoma patient survival while minimizing tumor recurrence. Our recent study identified GNAS as a novel tumor suppressor gene in Sonic hedgehog-driven medulloblastomas (He et al., Nature Medicine 2014). We show that low expression or mutation of GNAS was tightly correlated with poor prognosis of Sonic hedgehog-group tumors and their resistance to the treatment of Sonic hedgehog signaling inhibitors alone. Ablation of the single GNAS gene in anatomically-distinct progenitors in the ventricular zone of the cerebellum and dorsal brainstem is sufficient to induce the formation of medulloblastomas, which recapitulate their human counterparts. Gsα activation suppresses Sonic hedgehog signaling by regulating both the cAMP-dependent PKA pathway and ciliary trafficking of Hedgehog pathway components. Elevation of a Gsα effector, cAMP, effectively inhibits tumor growth in GNAS mutants. Strikingly, we find that in the drug-resistant tumor lesion and recurrent tumors after radiation therapy, there is an increase of Olig2 expression and Olig2+ progenitor cells. High levels of Olig2 are correlated with poor prognosis of medulloblastomas in human patients. We show that elimination of the mitotic Olig2-expressing cells blocks tumor progression in Olig2-thymidine kinase (TK) transgenic mice. In addition, cell type-specific deletion of Olig2 halts tumor progression. Moreover, we find that Olig2 activates gene regulatory networks inferred for tumor cell stemness and regulates chromatin accessibility of oncogenic factors by altering epigenome landscapes. Furthermore, our single cell analyses reveal that Olig2-expressing progenitors are the distinct tumor-initiating cells during the onset of primary and recurrent medulloblastoma, highlighting potential therapeutic avenues for treating recurrent medulloblastomas by targeting Olig2-expressing progenitors.
P2.03-032 Efficacy and Safety of Osimertinib as Third-Line or Later Therapy for T790M-Positive Advanced Non-Small Cell Lung Cancer
Authors: H. Shimada, S. Endo, Y. Sasahara, T. Shinmura, T. Ozawa, H. Majima, T. Hara, R. Imase, S. Yamauchi, Y. Sakakibara, A. Kobayashi, K. Yamazaki, Y. Jin, K. Yamanaka, O. Matsubara
Journal: Journal of Thoracic Oncology (2017)
Vigilância da sífilis na França, 2000-2003
Authors: E Couturier, A Michel, M Janier, N Dupin, C Semaille
Journal: Eurosurveillance (2004)

Este artigo descreve as tendencias da sifilis e as caracteristicas dos pacientes em Franca entre 2000 e 2003, assim que as tendencias das vendas de Extencilline® (bencilpenicilina benzatina) 2,4 MUI, entre 2001 e 2003. Desde 2001 existe um sistema de vigilancia da sifilis basado na notificacao voluntaria, provindo de centros que administram tratamentos para infeccoes sexualmente transmissiveis e dependem do sistema publico. Os dados clinicos estao complementados com dados sobre o comportamento sexual, colhidos por medio de um autoquestionario. 
De 2000 a 2003, foram declarados 1 089 casos de sifilis, passando de 37 casos em 2000 a 428 em 2003. Os casos de sifilis eram em mayoria homens (96%), de idade media de 36,5 anos e. nascido em Franca por 70%. A proporcao de casos de sifilis coinfectados pelo VIH baixou no tempo, passando de 60% em 2000 a 33% em 2003. A regiao mais afectada pelo surto de sifilis foi a regiao de Ile-de-France, principalmente Paris. Nesta area, a maioria dos casos de sifilis foram diagnosticados em homosexuais (87%), comparado com 75% em outras partes do pais. Entre os pacientes que preencherem o autoquestionario sobre o comportamento sexual, 83% declararam ter pares ocasionais nos treis meses anteriores ao diagnostico de sifilis. As tendencias das vendas de Extencilline® 2,4 MUI em farmacias privadas sao parecidas as que foram observadas no sistema de vigilancia, com um aumento entre 2001 e 2003. Em conclusao, a transmissao da sifilis continua na Franca en 2003. E preciso insistir no papel desempenhado pelo sexo oral sem proteccao na transmissao desta doenca.
PATH-28. CLINICAL AND GENETIC CHARACTERISTICS OF DIFFUSE MIDLINE GLIOMA IN THE SPINAL CORD
Authors: Shota Tanaka, Ryohei Otani, Hirotaka Hongo, Hazuki Matsuda, Masako Ikemura, Masashi Nomura, Shunsaku Takayanagi, Takahide Nejo, Satoshi Takahashi, Yosuke Kitagawa, Taijun Hana, Akitake Mukasa, Keisuke Ueki, Takashi Komori, Makoto Taniguchi, Nobuhito Saito, Pyo Kin
Journal: Neuro-Oncology (2017)

Histone H3 gene mutation is frequently noted in pediatric diffuse intrinsic brainstem glioma (DIPG) as well as other midline glioma, hence a new entity “diffuse midline glioma, H3 K27M-mutant” in the new WHO classification. Other than pediatric DIPG, however, its clinical picture remains largely unknown including prognostic implication of this gene mutation. Spinal cord glioma is extremely rare, comprising only 1-3% of all glioma. The objective of this retrospective study is to unveil clinical and genetic profiles of diffuse midline glioma in the spinal cord. Thirty-two patients with spinal cord astrocytoma treated in Dokkyo Medical University, Tokyo Metropolitan Neurological Hospital, or The University of Tokyo between 2000 and 2016 were included in the study. The tumor affected all age groups with slight male predominance; the median age was 43 years (range, 1-84). The cervical cord was most commonly affected. Pathological diagnosis was high grade astrocytoma in 19 cases and low grade astrocytoma in 13. Genetic analysis revealed H3-K27M mutation detected by immunohistochemistry in 9 cases (28%). Of note, some of these cases with immunopositivity failed to demonstrate K27M mutation in either H3F3A or HIST1H3B in Sanger sequencing. Survival analysis suggested possibly unfavorable prognostic effect of H3-K27M mutation. Clinical presentation of diffuse midline glioma in the spinal cord varies widely. H3-K27M mutation, seen in a subset of patients, may be a poor prognostic factor in this disease entity.
P3.02-089 Establishment of Highly Metastatic Lung Cancer Cell Sublines in Long-term Three-dimensional Low Attachment Cultures
Authors: T. Nakano, Y. Kanai, Y. Amano, T. Yoshimoto, D. Matsubara, T. Shibano, S. Endo, T. Niki
Journal: Journal of Thoracic Oncology (2017)
EPID-08. EPIDEMIOLOGY OF GERM CELL TUMORS IN THE CENTRAL NERVOUS SYSTEM
Authors: Haley Gittleman, Quinn Ostrom, Jonathan L Finlay, Carol Kruchko, Jill Barnholtz-Sloan
Journal: Neuro-Oncology (2017)

Primary germ cell tumors (GCTs) in the central nervous system (CNS) are rare, representing <5% of all CNS tumors in Western countries. These tumors represent 3–11% of pediatric brain tumors and more commonly occur in males. Approximately two-thirds of CNS GCTs are germinomas, which have 5-year survival rates exceeding 90%. The other third are non-germinomatous GCTs, which have poorer survival outcomes. The Central Brain Tumor Registry of the United States contains the largest aggregation of population-based data on primary CNS tumors in the US. These data were used to determine the incidence of GCTs from 2008–2013 by sex, race, and age at diagnosis. Survival by radiation status was calculated using SEER data. The most frequently occurring GCT histologies were germinoma (68.3%), mixed germ cell tumors (9.9%), and benign teratoma (9.1%). Incidence peaks between ages 10 and 19 years. The incidence rate (IR) for males (IR = 0.112 per 100,000) for all GCT histologies nearly tripled the IR for females (IR = 0.041 per 100,000). The IR for Asian and Pacific Islanders (API) (IR = 0.143 per 100,000) for all GCT histologies was significantly greater than for the other race categories (White IR = 0.080, Black IR = 0.049, American Indian/Alaska Native (AIAN) IR = 0.024 per 100,000). Radiation status was found to be significantly associated with increased survival (p = 0.016) for all malignant GCT histologies. GCTs are rare tumors that cause significant morbidity in affected individuals. Incidence of these tumors varies significantly by age, sex, and race and warrants examination of overall and histology-specific incidence and survival after diagnosis. Resulting information is important for clinicians focused on this disease, as well as for patients and their families, and may lead to clues as to etiology.
SRSF6-regulated alternative splicing that promotes tumour progression offers a therapy target for colorectal cancer
Authors: Ledong Wan, Wenying Yu, Enhui Shen, Wenjie Sun, Yuan Liu, Jianlu Kong, Yihua Wu, Fengyan Han, Lei Zhang, Tianze Yu, Yuwei Zhou, Sunzhe Xie, Enping Xu, Honghe Zhang, Maode Lai
Journal: Gut (2017)

Objective To investigate the molecular function of splicing factor SRSF6 in colorectal cancer (CRC) progression and discover candidate chemicals for cancer therapy through targeting SRSF6. Design We performed comprehensive analysis for the expression of SRSF6 in 311 CRC samples, The Cancer Genome Atlas and Gene Expression Omnibus (GEO) database. Functional analysis of SRSF6 in CRC was performed in vitro and in vivo . SRSF6-regulated alternative splicing (AS) and its binding motif were identified by next-generation RNA-sequencing and RNA immunoprecipitation sequencing (RIP-seq), which was validated by gel shift and minigene reporter assay. ZO-1 exon23 AS was investigated to mediate the function of SRSF6 in vitro and in vivo . Based on the analysis of domain-specific role, SRSF6-targeted inhibitor was discovered de novo by virtual screening in 4855 FDA-approved drugs and its antitumour effects were evaluated in vitro and in vivo . Results SRSF6 was frequently upregulated in CRC samples and associated with poor prognosis, which promoted proliferation and metastasis in vitro and in vivo . We identified SRSF6-regulated AS targets and discovered the SRSF6 binding motif. Particularly, SRSF6 regulates ZO-1 aberrant splicing to function as an oncogene by binding directly to its motif in the exon23. Based on the result that SRSF6 RRM2 domain plays key roles in regulating AS and biological function, indacaterol, a β2-adrenergic receptor agonist approved for chronic obstructive pulmonary disease treatment, is identified as the inhibitor of SRSF6 to suppress CRC tumourigenicity. Conclusions SRSF6 functions the important roles in mediating CRC progression through regulating AS, and indacaterol is repositioned as an antitumour drug through targeting SRSF6. Accession numbers The accession numbers for sequencing data are SRP111763 and SRP111797.
La sífilis en Dinamarca – un brote en hombres homosexuales en Copenhague, 2003-2004
Authors: S A Cowan
Journal: Eurosurveillance (2004)

Dinamarca esta experimentado actualmente un brote de sifilis que comenzo en 2003 y sigue en 2004. Los datos del sistema nacional de vigilancia muestran que la mayor parte de los casos son hombres que tienen relaciones sexuales con otros hombres (HRSH) y que una larga proporcion de estos pacientes tambien son positivos para el VIH. Sin embargo, la proporcion de co-infecciones por el VIH en HRSH declarados durante el brote de sifilis no vario de modo significativo comparada con los anos precedentes. La mayoria de los casos fueron notificados en la ciudad de Copenhague y el 70% fueron infectados en el pais. La epidemia no parece estar afectando a los menores de 20 anos. Se supone que la mayor parte de los HRSH que presentan co-infeccion sifilis/VIH ya estaban infectados por el VIH en el momento de adquirir la sifilis.
P2.02-034 PD-L1 Expression Can Be a Prognostic Marker in EGFR Mutant NSCLC Patients Treated with Erlotinib
Authors: N. Karachaliou, A. Cardona, M. González Cao, A. Giménez-Capitán, A. Drozdowskyj, E. Aldeguer, G. López-Vivanco, J.M. Sánchez-Torres, M. De Los Llanos Gil, M. Molina-Vila, R. Rosell
Journal: Journal of Thoracic Oncology (2017)
Challenges in Implementing Personalized Care Planning—Reply
Authors: Samuel T. Edwards, David A. Dorr, Bruce E. Landon
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
Enhanced oral absorption and anticancer efficacy of cabazitaxel by overcoming intestinal mucus and epithelium barriers using surface polyethylene oxide (PEO) decorated positively charged polymer-lipid hybrid nanoparticles
Authors: Tianyang Ren, Qian Wang, Ying Xu, Lin Cong, Jingxin Gou, Xiaoguang Tao, Yu Zhang, Haibing He, Tian Yin, Haotian Zhang, Yan Zhang, Xing Tang
Journal: Journal of Controlled Release (2017)
EPID-11. IDENTIFYING BARRIERS TO CLINICAL RESEARCH: A PILOT STUDY TO IMPROVE ACCESS AND ENROLLMENT TO NEURO-ONCOLOGY TRIALS AT COLUMBIA UNIVERSITY CENTER MEDICAL CENTER (CUMC)
Authors: Mary Welch, Leslie Segall, Grace Hillyer, Fabio Iwamoto, Teri Kreisl, Daniel Otap, Andrew B Lassman
Journal: Neuro-Oncology (2017)

Fewer than 3% of cancer patients participate in clinical trials. Among these, there is stark underrepresentation of racial and ethnic minorities, the economically disadvantaged, the elderly and those with limited access to academic centers. Nervous system involvement creates additional challenges to accrual including reduced capacity for informed decision-making and increased reliance on caregivers. To better identify barriers to trial enrollment, we designed and pre-tested a survey to elicit patient perceptions about clinical research and collect data on potential factors limiting participation. A 20-question survey was provided to patients at the time of their first outpatient visit. The survey was voluntary and administered over 10 weeks as part of a QI initiative conducted by Columbia's Division of Neuro-Oncology. Questions assessed demographics (race/ethnicity, education, language, employment, marital status); support (presence of family, home services); transportation (commute type and time); receptivity to participation in research and rationales for refusal. Information on disease status and trial candidacy were also noted. 71 patients received the questionnaire; 57 (80%) responded. Median age was 55 years (range: 17–80). There were 33 (58%) men; 35 (61%) self-identified as non-Hispanic White. Diagnoses included high grade glioma (26%), CNS metastases (26%), meningioma (11%), primary CNS lymphoma (4%) and low-grade glioma (2%). Of 52 responders, 14 (27%) were unwilling to participate in research a priori; 27 (54%) if a placebo was involved. Despite a limited sample size, we found that college education (OR: 8.8 CI: 1.5–31.8) and shorter commute time (OR: 4.0; CI: 1.2–13.3) were significantly associated with willingness to consider trial enrollment – findings that are consistent with prior studies. Further research is needed to better identify, understand, and overcome barriers to enrollment. To that end, steps will be taken in the coming months to refine the questionnaire, define a population of interest and streamline logistics.
P1.02-063 Tumor Heterogeneity Analyzes by Integrated Proteo-Genomics of Thoracic Tumors from Sequential Biopsies and Warm Autopsies
Authors: N. Roper, X. Zhang, T. Maity, S. Gao, A. Venugopalan, R. Biswas, C. Cultraro, C. Kim, E. Padiernos, A. Rajan, A. Thomas, R. Hassan, D. Kleiner, S. Hewitt, J. Khan, U. Guha
Journal: Journal of Thoracic Oncology (2017)
Breast cancer genomics and immuno-oncological markers to guide immune therapies
Authors: D. Hammerl, M. Smid, A.M. Timmermans, S. Sleijfer, J.W.M. Martens, R. Debets
Journal: Seminars in Cancer Biology (2017)

There is an increasing awareness of the importance of tumor – immune cell interactions to the evolution and therapy responses of breast cancer (BC). Not surprisingly, numerous studies are currently assessing the clinical value of immune modulation for BC patients. However, till now durable clinical responses are only rarely observed. It is important to realize that BC is a heterogeneous disease comprising several histological and molecular subtypes, which cannot be expected to be equally immunogenic and therefore not equally sensitive to single immune therapies. Here we review the characteristics of infiltrating leukocytes in healthy and malignant breast tissue, the prognostic and predictive values of immune cell subsets across different BC subtypes and the various existing immune evasive mechanisms. Furthermore, we describe the presence of certain groups of antigens as putative targets for treatment, evaluate the outcomes of current clinical immunotherapy trials, and finally, we propose a strategy to better implement immuno-oncological markers to guide future immune therapies in BC.