tbuckley/cabot-search huggingface dataset:
Abstract IA10: Neuroblastoma is a biphasic tumor
Authors: Rogier Versteeg, Tim van Groningen, Jan Koster, Linda J. Valentijn, Johan van Nes
Journal: Cancer Research (2018)

Abstract Neuroblastoma is a pediatric tumor of the peripheral adrenergic lineage, which is neural crest derived. During embryogenesis cells delaminate from the neural crest, migrate ventrally, and differentiate to (nor)-adrenalin producing cells. Neuroblastoma typically expresses differentiation markers of the adrenergic lineage. High-stage neuroblastoma usually goes in complete remission upon therapy but often relapses as resistant disease. Several tumor types were recently found to include phenotypically divergent cell types, resembling lineage development stages. We have found that most neuroblastoma includes two types of tumor cells with shared genomic defects, but highly diverging gene expression profiles. Undifferentiated mesenchymal cells (MES-type) and more differentiated adrenergic cells (ADRN-type) can interconvert and may relate to normal lineage differentiation stages. ChIP-seq analysis of isogenic pairs of MES- and ADRN-type cells revealed distinct, highly consistent super-enhancer landscapes for each cell type. Lineage identity has been proposed to ensue super-enhancer (SE)-associated transcription factor (TF) networks. We identified two SE-associated TF networks that potentially master each cell type. Accordingly, the mesenchymal TF PRRX1 could reprogram the SE- and mRNA-profiles of ADRN-type cells towards an MES-state. Assessment of the clinical relevance of this biphasic system revealed that MES-type cells were more chemoresistant in vitro and were enriched in post-therapy and relapsed tumors. The super enhancer-associated TF networks, probably meant for lineage control in normal development, thus could impose two cellular states of neuroblastoma that shape intratumor heterogeneity. Citation Format: Rogier Versteeg, Tim van Groningen, Jan Koster, Linda J. Valentijn, Johan van Nes. Neuroblastoma is a biphasic tumor [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA10.
Abstract P123: The Physical Activity Built Environment: Evaluation of the Concordance of Perceived versus Measured Access to Parks and Bike Paths
Authors: Claire E Bollinger, Darryl B Hood, Julie K Bower
Journal: Circulation (2016)

Background: Approximately 80% of pregnant women in the US do not meet the CDC recommendation for moderate-intensity physical activity. The built environment is a key contributor to physical activity (PA) behavior. However, there may be a disconnect between physical attributes of the built environment and perceived access to an environment that supports PA. Use of a geographic information system (GIS) to objectively measure aspects of the built environment can yield important information about proximity of resources for supporting PA. We evaluated concordance of perceived access to multi-use bike paths (MUBP) and parks in a population of pregnant women. We also examined demographic characteristics associated with concordance between perceived and actual supports for PA. Methods: A population of 155 pregnant women in the greater Columbus, OH area reported perceptions of access to environmental supports within their neighborhood (defined as 0.5 mi. radius/ 10 min. walk) and community (10 mi. radius/ 20 min. drive), along with self-reported PA information. Addresses were abstracted from medical records and geocoded. Within ArcMap 10.2.2 (ESRI, Redlands, CA), buffers at distances of 0.5, 1, and 10 miles were created around MUBP and parks, respectively. Respondents were classified as “near” a resource if their address fell within those buffers. Logistic regression was used to examine the association between concordance of self-report with objectively measured proximity and demographic factors associated with higher concordance. Results: Within the study population of 155, 12% and 28% of women lived within 0.5 and 1 mile of a dedicated MUBP, respectively. More women lived within close proximity to a park (46% within a 0.5 mile radius, and 69% were within a 1 mile radius). The discordancy for parks ranged from 9.68%-49.03%, and from 16.77%-76.13% for MUBP. Concordance of report of parks within the community was higher among non-Hispanic white women (OR=4.2 [1.1, 15.3]) and that concordance or over-reporting of access to parks within the community was higher among married women (OR=5.3 [1.3, 21.5]). There were no significant differences in self-reported PA or changes in PA, however women living within 1 mile of a park reported more minutes of moderate-to-vigorous PA. A greater percentage of those with access reported increasing or maintaining levels of moderate PA from before pregnancy through the third trimester. Conclusions: The discordance between perception of access and objectively measured proximity to MUBP and parks suggests a substantial portion of women are not aware of their availability, or do not perceive them as relevant factors in influencing their PA behaviors during pregnancy. It may be that physical proximity is not a major driver in perceived access. Characteristics of the built environment, such as safety or social environment, may play a larger role in influencing PA behaviors.
Diffuse large b-cell lymphoma of the choroid plexus: a case report
Authors: Dr Francis James Gatdula
Journal: Neuro-Oncology (2018)

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma most commonly affecting the eyes, brain, spinal cord and leptomeninges. In the United States, it has a reported incidence of 51 cases per year. Among the subset of PCNSL are tumors arising primarily from the intraventricular regions including the choroid plexus. These cases are extremely rare and on literature review, only four cases have been documented worldwide. This is a case report of a confirmed B-cell lymphoma of the choroid plexus, the first reported case in the Philippines. CASE REPORT. This is a case of a 79-year-old-male with a 2 month-history of continuous headache accompanied by dizziness and seizures manifesting as blank stares and visual hallucinations. He was brought to the hospital with a decreased sensorium and dysarthria; his tongue deviated to the right; and has poor gag reflex. A cranial magnetic resonance imaging displayed enhancing frond-like structures with prominent lobulations in the body, frontal, and occipital horns of both lateral ventricles extending to the third and fourth ventricles with corresponding hydrocephalus. The primary diagnostic consideration on admission was CNS infection. He underwent left frontal burr, endoscopic biopsy of choroid plexus, exudates, and ependyma followed by septostomy and intraventricular lavage; and placement of an Ommaya reservoir. Histologic diagnosis was confirmed to be diffuse large B-cell lymphoma. A repeat cranial MRI, as well as neck, chest, mediastinum, and whole abdominal computed tomography scans showed no other neoplasm. Final diagnosis was diffuse large B-cell lymphoma of the choroid plexus. CSF cytology was negative for atypical cells. Systemic chemotherapy with methotrexate and rituximab was initiated. However, patient already had poor neurological response and the patient’s family eventually decided to put patient on palliative care. Patient was eventually transferred to a smaller hospital facility after being admitted for five weeks.
Abstract 19076: Treatment for Hypertension and Atrial Fibrillation in African Americans, Hispanics and Non-Hispanic Whites
Authors: Tina Shah, Eric Shulman, Faraj Kargoli, Jorge Romero, Jay Gross, Soo J Kim, John Fisher, Kevin Ferrick, Andrew Krumerman
Journal: Circulation (2017)

Background: Hypertension is well known to be a risk factor for development of atrial fibrillation (AF). However, it is unknown if patients who are treated for hypertension have the same risk for de...
CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia
Authors: Diogo Gomes-Silva, Erden Atilla, Pinar Ataca Atilla, Feiyan Mo, Haruko Tashiro, Madhuwanti Srinivasan, Premal Lulla, Rayne H. Rouce, Joaquim M.S. Cabral, Carlos A. Ramos, Malcolm K. Brenner, Maksim Mamonkin
Journal: Molecular Therapy (2018)

Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7KO) T cells effectively eliminates CD7+ AML cell lines, primary CD7+ AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7KO CD7 CAR T cells for the non-myeloablative treatment of CD7+ AML. Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7KO) T cells effectively eliminates CD7+ AML cell lines, primary CD7+ AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7KO CD7 CAR T cells for the non-myeloablative treatment of CD7+ AML.
p95HER2–T cell bispecific antibody for breast cancer treatment
Authors: Irene Rius Ruiz, Rocio Vicario, Beatriz Morancho, Cristina Bernadó Morales, Enrique J. Arenas, Sylvia Herter, Anne Freimoser-Grundschober, Jitka Somandin, Johannes Sam, Oliver Ast, Águeda Martinez Barriocanal, Antonio Luque, Marta Escorihuela, Ismael Varela, Isabel Cuartas, Paolo Nuciforo, Roberta Fasani, Vicente Peg, Isabel Rubio, Javier Cortés, Violeta Serra, Santiago Escriva-de-Romani, Jeff Sperinde, Ahmed Chenna, Weidong Huang, John Winslow, Joan Albanell, Joan Seoane, Maurizio Scaltriti, Jose Baselga, Josep Tabernero, Pablo Umana, Marina Bacac, Cristina Saura, Christian Klein, Joaquín Arribas
Journal: Science Translational Medicine (2018)

T cell bispecific antibodies against an isoform of HER2 effectively target many HER2-expressing tumors but not normal tissues.
THE SURVIVAL OF GLIOBLASTOMA MULTIFORME PATIENTS AFTER BURR HOLE BIOPSY BASED ON THEIR POST BIOPSY TREATMENT WITH OR WITHOUT CHEMOTHERAPY AND OR RADIOTHERAPY
Authors: Georgios Zilidis, Ahmed Ramadan Sadek, Julian Cahill, Paul Grundy
Journal: Neuro-Oncology (2018)

Maximal safe resection of high-grade glioma is the recommended standard of care and the outcomes following surgery and chemoradiotherapy are well described in the current era. However, for some patients only a biopsy is feasible or is their preference. It is essential to understand the outcomes in this cohort in order to support shared decision making and informed consent. To study the survival of patients with biopsy only confirmed glioblastoma (GBM). Retrospective series over a three year period (2012–14). All patients who underwent burr-hole biopsy for GBM were included. Median survival was calculated from the time of biopsy until the time of death. Patients were stratified according to post-biopsy treatment. 84 patients were identified. Significant complications resulting in death or disability did not occur in any patients. The median survival of 33 patients who received best supportive care after biopsy was 1.66 months (mean 1.96 SEM 0.24); for those 15 patients receiving radiotherapy alone was 4.66 months (mean 7.68 SEM 2.11); 10 patients with chemotherapy alone was 4.26 months (mean 9.16 SEM 2.59); and for those 25 patients who received chemoradiotherapy was 9.73 months (mean 11.36 SEM 1.30). There is obviously a selection bias, with younger patients in best performance status and with favourable molecular profiles being offered more radical treatment. Nonetheless, this study provides valuable information for the consent process and shared decision making to help specialists and patients understand the outcomes following biopsy alone with different forms of adjuvant treatment and to compare these outcomes with other options such as resection.
Gut Microbes May Account for the Anti-Seizure Effects of the Ketogenic Diet
Authors: Tracy Hampton
Journal: JAMA (2018)

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Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections
Authors: Thomas M. Hooton, Mariacristina Vecchio, Alison Iroz, Ivan Tack, Quentin Dornic, Isabelle Seksek, Yair Lotan
Journal: JAMA Internal Medicine (2018)

Increased hydration is often recommended as a preventive measure for women with recurrent cystitis, but supportive data are sparse.To assess the efficacy of increased daily water intake on the frequency of recurrent cystitis in premenopausal women.Randomized, open-label, controlled, 12-month trial at a clinical research center (years 2013-2016). Among 163 healthy women with recurrent cystitis (≥3 episodes in past year) drinking less than 1.5 L of fluid daily assessed for eligibility, 23 were excluded and 140 assigned to water or control group. Assessments of daily fluid intake, urinary hydration, and cystitis symptoms were performed at baseline, 6- and 12-month visits, and monthly telephone calls.Participants were randomly assigned to drink, in addition to their usual fluid intake, 1.5 L of water daily (water group) or no additional fluids (control group) for 12 months.Primary outcome measure was frequency of recurrent cystitis over 12 months. Secondary outcomes were number of antimicrobial regimens used, mean time interval between cystitis episodes, and 24-hour urinary hydration measurements.The mean (SD) age of the 140 participants was 35.7 (8.4) years, and the mean (SD) number of cystitis episodes in the previous year was 3.3 (0.6). During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% CI, 1.5-1.8) in the water group compared with 3.2 (95% CI, 3.0-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001). Overall, there were 327 cystitis episodes, 111 in the water group and 216 in the control group. The mean number of antimicrobial regimens used to treat cystitis episodes was 1.9 (95% CI, 1.7-2.2) and 3.6 (95% CI, 3.3-4.0), respectively, with a difference in means of 1.7 (95% CI, 1.3-2.1; P < .001). The mean time interval between cystitis episodes was 142.8 (95% CI, 127.4-160.1) and 84.4 (95% CI, 75.4-94.5) days, respectively, with a difference in means of 58.4 (95% CI, 39.4-77.4; P < .001). Between baseline and 12 months, participants in the water group, compared with those in the control group, had increased mean (SD) urine volume (1.4 [0.04] vs 0.1 [0.04] L; P < .001) and voids (2.4 [0.2] vs -0.1 [0.2]; P < .001) and decreased urine osmolality (-402.8 [19.6] vs -24.0 [19.5] mOsm/kg; P < .001).Increased water intake is an effective antimicrobial-sparing strategy to prevent recurrent cystitis in premenopausal women at high risk for recurrence who drink low volumes of fluid daily.ClinicalTrials.gov identifier: NCT02444975.
Clinical study of intraperitoneal injection bevacizumab (BV) combined with intraperitoneal hyperthermic perfusion chemotherapy (CT) in treatment of malignant ascites of ovarian cancer (OC).
Authors: Hui Zhao, Nan Du, Yan Fu, Haibin Wang, Zhongyi Fan
Journal: Journal of Clinical Oncology (2013)

5558 Background: To study the efficacy and safety of intraperitoneal injection BV combined with intraperitoneal perfusion CT in treatment of malignant ascites of OC and to investigate the clinical significance of the concentration change of vascular endothelial growth factor (VEGF). Methods: Patients with malignant ascites of OC were randomly divided into treatment group (n = 31) and control group (n = 27). All enrolled patients received TC (paclitaxel 135mg/m 2 , iv d1+ carboplatin AUC=5, iv d1), 1 time/3 weeks for 6 weeks. Patients in the control group were treated with intraperitoneal perfusion CT combined with intraperitoneal cisplatin (40mg/m 2 )1 time/2 weeks for 6 weeks. Besides the treatment of the control group, patients in the treatment group received intraperitoneal injection with BV 300mg after each intraperitoneal perfusion CT for 6 weeks. The improvement of life quality, efficacy and adverse effects were evaluated. The concentrations of VEGF and CA-125 in ascites of the two groups were assayed by ELISA method. Results: No severe side effect was observed in all the patients. The response rate of the treatment group was higher than that of the control group (90.32% vs. 59.26%, p &lt; 0.05). The improvement rate of quality of life (QOL) of the patients in the treatment group was also higher than that of the patients in the control group (93.55 % vs. 48.15%, p &lt; 0.05). The concentration of VEGF in ascites of the treatment group after treatment was lower than that before treatment (p &lt; 0.05). And after treatment, the concentration of VEGF in ascites of treatment group was lower than that of the control group (p &lt; 0.05). Conclusions: Intraperitoneal injection BV combined with intraperitoneal perfusion CT in the treatment of malignant ascites of OC is effective and safe. The concentration of VEGF and CA-125 levels, in ascites may be used as monitoring index for treatment effect of malignant ascites of OC with intraperitoneal injection BV.
Exosome–transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression
Authors: Rui Zheng, Mulong Du, Xiaowei Wang, Weidong Xu, Jiayuan Liang, Wenying Wang, Qiang Lv, Chao Qin, Haiyan Chu, Meilin Wang, Lin Yuan, Jing Qian, Zhengdong Zhang
Journal: Molecular Cancer (2018)

Extracellular communication within the tumor microenvironment plays a critical role in tumor progression. Although exosomes can package into long non-coding RNAs (lncRNAs) to mediate extracellular communication, the role of exosomal lncRNA PTENP1 in bladder cancer (BC) remains unclear. We detected PTENP1 expression between patients with BC and healthy controls; the expression occurred in tissues and exosomes from plasma. We assessed the diagnostic accuracy by the receiver operating characteristic curve (ROC) and the area under curve (AUC). Cell phenotypes and animal experiments were performed to determine the effect of exosomal PTENP1. PTENP1 was significantly reduced in BC tissues and in exosomes from plasma of patients with BC (P < 0.05). We found that PTENP1 was mainly wrapped by exosomes. Exosomal PTENP1 could distinguish patients with BC from healthy controls (AUC = 0.743; 95% confidence interval (CI) = 0.645–0.840). Normal cells secreted exosomal PTENP1 and transmitted it to BC cells, thus inhibiting the biological malignant behavior of BC cells by increasing cell apoptosis and reducing the ability to invade and migrate (P < 0.05). Exosomal PTENP1 could suppress tumor growth in vivo. Furthermore, exosomal PTENP1 mediated the expression of PTEN by competitively binding to microRNA-17. Exosomal PTENP1 is a promising novel biomarker that can be used for the clinical detection of BC. Exosomes derived from normal cells transfer PTENP1 to BC cells, which reduce the progression of BC both in vitro and in vivo and suggest that exosomal PTENP1 participates in normal-cell-to-bladder-cell communication during the carcinogenesis of BC.
No Change in Determining Crohn’s Disease Recurrence or Need for Endoscopic or Surgical Intervention With Modification of the Rutgeerts’ Scoring System
Authors: Pauline Rivière, Séverine Vermeire, Marie Irles-Depe, Gert Van Assche, Paul Rutgeerts, Anthony de Buck van Overstraeten, Quentin Denost, Albert Wolthuis, Andre D’Hoore, David Laharie, Marc Ferrante
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 18171: HCN Channel Distribution in the Human Sinoatrial Node and Latent Atrial Pacemakers <i>(Best of Basic Science Abstract)</i>
Authors: Ning Li, Thomas A Csepe, Brian J Hansen, Halina Dobrzynski, Robert S Higgins, Ahmet Kilic, Peter J Mohler, Paul M Janssen, Michael R Rosen, Brandon J Biesiadecki, Vadim V Fedorov
Journal: Circulation (2015)

Background: The hyperpolarization-activated current, I f , plays an important role in cardiac pacemaker cells. However, the distribution and expression of HCN isoforms in the human SAN and latent atrial pacemaker clusters is unknown. Methods: Human atria and entire SAN complexes were isolated from failing (n=5) and non-failing (n=9) human hearts cardioplegically-arrested in the operating room. Three dimensional intramural SAN structure was identified as the fibrotic compact region around the SAN artery with Connexin43-negative pacemaker cardiomyocytes visualized in Masson’s trichrome and immunostained cryosections. Pure SAN tissue was precisely isolated from the frozen SAN cryo blocks using a 16G biopsy needle (Figure). Atrial tissues from different locations were fresh frozen in liquid nitrogen. Immunoblot and immunostaining were used to study the expression pattern of HCN isoforms. Results: Three HCN isoform proteins were detected in the atria and SAN (Figure). HCN1 was predominantly distributed in all the human SAN with a 125.1±40.2 (n=12) expression ratio of SAN to right atrial free wall (RAFW). HCN2 and HCN4 expression levels were higher in SAN than atria with ratios of 6.1±0.9 and 4.6±0.6 (n=12), respectively. HCN2 expression but not HCN1/4 in the latent atrial pacemakers from the right atrioventricular ring (RR) area was significantly higher than in RAFW, with the band density ratio of RR/RAFW= 2.4±0.4 (n=12). Conclusions: This is the first study to conduct precise molecular mapping of the human SAN by isolating pure pacemaker SAN tissue. HCN1 was almost exclusively expressed in SAN and may play a critical role in determining the leading pacemaker in human SAN. Even HCN2 and HCN4 expression is higher in the SAN than RAFW, these isoforms are less SAN-specific than HCN1. SAN and latent atrial pacemakers have different HCN expression patterns, suggesting the utility of HCN isoform specific blockers to selectively modify sinus rhythm or atrial ectopic rhythms.