tbuckley/cabot-search huggingface dataset:
Transcatheter Closure of Patent Foramen Ovale Without an Implant
Authors: HorstSievert, EvelynFischer, CorinnaHeinisch, NicoMajunke, AlbrechtRoemer, NinaWunderlich
Journal: Circulation (2007)

Background— Currently available catheter techniques for closure of a patent foramen ovale (PFO) rely on the placement of an implantable closure device. The objective of the Paradigm I study was to evaluate the safety and feasibility of transcatheter closure of PFO using radiofrequency energy without an implanted device in patients with cryptogenic stroke or transient ischemic attack. Methods and Results— Thirty patients were enrolled (15 females; mean age 48 years). Mean PFO size was 8.5±2.7 mm. Technical success (ie, successful application of radiofrequency energy) was achieved in 27 patients. The remaining 3 patients received an implantable closure device. All 30 patients were free from serious procedure-related adverse events. No recurrent strokes, deaths, or perforations occurred as a result of the procedure. The mean follow-up was 6 months, and 13 (43%) of the 30 patients experienced PFO closure after the first procedure. Nine of the patients whose PFOs remained patent after the first procedure elect...
Abstract 1584: Comparison of circulating tumor cell (CTC) capture/identification methods and NanoString evaluation of gene expression in CTCs and cell-free circulating tumor mRNA (cctmRNA) in patients with metastatic lung cancer
Authors: Yanis Boumber, Charu Aggarwal, Catherine Thrash-Bingham, Patricia Fittipaldi, Polina Guseva, Ramillya Vlasenkova, Chandra Rao, Jianming Pei, Brian L. Egleston, Hossein Borghaei, Massimo Cristofanilli, Ranee Mehra, Ilya Serebriiskii, R. Katherine Alpaugh
Journal: Cancer Research (2018)

Abstract Circulating tumor cells (CTC) and cell free circulating tumor mRNA (cctmRNA) can serve as biomarkers for prognosis and treatment response in lung and other cancers. A barrier to CTC use in some cancers is the low numbers of CTC captured, and the low percent of patients with detectable CTCs. Past comparisons of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients have shown larger cohorts of patients with detectable CTCs, and higher CTC numbers, for SCLCs. We compared methods for CTC capture/identification, and profiled mRNA from both the CTCs and cell free plasma RNA (cctmRNA) for to identify tumor-associated biomarkers. Peripheral blood was collected from 10 SCLC and 10 NSCLC patients prior to therapy, and from 4 normal controls. Capture using the standard EpCAM CellSearch reagent (unicapture) was run in parallel with EpCAM plus Her2, EGFR and MUC-1 combined ferrofluid (quadcapture) plus the use of anti-cytokeratin 7 (CK7) to assist in CTC identification. Unicapture detected CTCs in 40% of NSCLC and 60% of SCLC; whereas, quadcapture/CK7 identified 20% CTCs in NSCLC and 80% in SCLC. Overall, the quadcapture did not improve CTC capture efficiency. Exploratory NanoString analysis was performed on cell-free plasma from these patients and the ferrofluid isolated CTCs. Cancer-specific biomarkers were detected in mRNA from plasma and CTCs by NanoString included CCL5, CLU and SRGN. In summary, quadcapture ferrofluid reagent did not improve the capture efficiency, although the addition of CK7 may have the potential to identify additional CTCs. Nanostring analysis of cctmRNA and CTCs mRNA suggested potential new lung cancer biomarkers that require validation in larger studies. Citation Format: Yanis Boumber, Charu Aggarwal, Catherine Thrash-Bingham, Patricia Fittipaldi, Polina Guseva, Ramillya Vlasenkova, Chandra Rao, Jianming Pei, Brian L. Egleston, Hossein Borghaei, Massimo Cristofanilli, Ranee Mehra, Ilya Serebriiskii, R. Katherine Alpaugh. Comparison of circulating tumor cell (CTC) capture/identification methods and NanoString evaluation of gene expression in CTCs and cell-free circulating tumor mRNA (cctmRNA) in patients with metastatic lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1584.
The Next Phase of Human Gene-Therapy Oversight
Authors: Francis S. Collins, Scott Gottlieb
Journal: New England Journal of Medicine (2018)

The Next Phase of Human Gene-Therapy Oversight As gene therapy continues to change, so must the federal framework set up to oversee it. As new biotechnologies continue to emerge, the NIH and the FDA are proposing reductions in duplicative oversight and changes to the role of the Recombinant DNA Advisory Committee.
Physical Training Increases eNOS Vascular Expression and Activity and Reduces Restenosis After Balloon Angioplasty or Arterial Stenting in Rats
Authors: CiroIndolfi, DanieleTorella, CarmelaCoppola, AntonioCurcio, FranciscaRodriguez, AntonioBilancio, AntonioLeccia, OresteArcucci, MariacristinaFalco, DarioLeosco, MassimoChiariello
Journal: Circulation Research (2002)

The effects of dynamic exercise on restenosis after vascular injury are still unknown. The consequences of balloon dilation–induced injury on neointimal hyperplasia, vascular negative remodeling, and reendothelialization were assessed in sedentary and trained rats. Ex vivo eNOS vascular expression and activity were investigated in carotid arteries isolated from sedentary and exercised rats. The in vivo effects of eNOS inhibition by L-NMMA on vessel wall after balloon dilation were evaluated in sedentary and exercised rats. We also investigated the effects of exercise on neointimal formation in a rat stent model of vascular injury. Compared with sedentary group, the arteries isolated from trained rats showed higher levels of eNOS protein expression and activity 7 days after balloon dilation. A significant reduction of both neointimal hyperplasia and negative remodeling was observed 14 days after balloon injury in trained compared with sedentary rats. Moreover, we demonstrated that exercise training produce...
Economic burden of early progression in newly-diagnosed multiple myeloma patients.
Authors: Shivani Pandya, Zoe Clancy, Sulena Shrestha, Li Wang, Quanhong Ni, Onur Baser
Journal: Journal of Clinical Oncology (2018)

e20040 Background: Despite advancements in Multiple Myeloma (MM) treatment (Tx), 10-15% patients (pts) experience early relapse. We assessed the economic impact of early progression in newly diagnosed MM pts without autologous stem cell transplant (ASCT) using the US Medicare database. Methods: Pts with ≥2 MM claims (ICD-9-CM: 203.0x) ≥30 days apart and ≥1 Tx (index date: 1st prescription claim) during the study period (01JAN2011-31DEC2015) were identified from the 100% Medicare database. Pts were required to have continuous enrollment from ≥6 months prior to the earliest of index or initial MM diagnosis date through ≥12-month post-index date unless pts died in < 12-month follow-up period, ≥1 full cycle of therapy, no evidence of prior MM diagnosis or Tx (including ASCT), and no evidence of ASCT in the follow-up. The first line of therapy (LOT1) included all Txs prescribed within 60 days of the index date. Progression to the subsequent LOT was defined by the earliest of an addition/switch to new non-maintenance MM Tx > 60 days post-index, restart of any non-maintenance MM Tx after a > 180-day gap, or a dose increase from maintenance to relapse therapy. Pts who progressed prior to the median time to next Tx (TTNT) defined from Kaplan Meier curve, and those who did not progress during follow-up, were included in the early progression and no progression cohorts, respectively. Annual per patient health care costs were compared between early and no progression cohorts of pts initiating doublet therapy in LOT1. Results: Of 3,768 eligible MM pts with a median TTNT of 1,028 days, 81.3% (n = 3,065) initiated doublet therapy in LOT1. 35.4% and 63.4% of these pts were included in the early and no progression cohorts, respectively. Pts in the early progression cohort were younger (relative to the Medicare population) and incurred higher total costs ($120,604 vs $96,684) with outpatient, inpatient, office visits, emergency room, and pharmacy comprising overall costs (p < 0.0001). Costs were inclusive of all healthcare costs, including multiple myeloma costs. Conclusions: This study helps in quantifying the economic burden of early progression, thereby indicating the need for therapies that delay progression.
Abstract 1504: Opposing roles of FoxM1 and the hepatic specification genes FoxA1/A2 dictate differentiation state of liver cancer cells
Authors: Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Grace Guzman, Pradip Raychaudhuri
Journal: Cancer Research (2018)

Abstract The pro-proliferation transcription factor FoxM1 is over-expressed mainly in high-grade cancers. However, the significance of its over-expression in cancers, including poorly differentiated hepatocellular carcinoma (HCC), is not known. Here we provide evidence for a causal role of the over-expressed FoxM1 in driving high-grade progression of HCC. Immunohistochemical staining of human HCC specimens revealed opposite expression patterns of FoxM1 and the liver differentiation genes FoxA1/A2. Moreover, using a transgenic mouse model for oncogenic Ras-driven HCC as well as cell-based studies, we provide in vivo genetic evidence for a direct repression of FoxA1/A2 by FoxM1. Interestingly, FoxM1 represses these differentiation genes mainly in G1 phase, a phase in the cell cycle in which cells can undergo differentiation. Moreover, repression of FoxA1/A2 in G1 phase is important, as these genes are capable of inhibiting expression of the pluripotency genes that are mainly expressed in S/G2 phases. Also, we show that FoxA1/A2 inhibit expression of FoxM1 by inhibiting binding of FoxM1 to its own promoter and thus blocking its auto-activation. Our observations identify a significant new mechanism in which FoxM1 and the FoxA genes play opposing roles that determine the differentiation state of the HCC cells. Citation Format: Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Grace Guzman, Pradip Raychaudhuri. Opposing roles of FoxM1 and the hepatic specification genes FoxA1/A2 dictate differentiation state of liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1504.
Abstract 463: Glucose-regulated protein 94 modulates the response of osteosarcoma to chemotherapy
Authors: Huang Chien-Yu, Po-Li Wei, Yu-Jia Chang
Journal: Cancer Research (2018)

Abstract Background: Osteosarcoma (OS) is the most common and most aggressive primary solid malignant bone tumor in children and young adults and has high rates of recurrence and metastasis. The endoplasmic reticulum (ER) stress pathway is important in regulating chemo-responsiveness in cancer. However, the role of glucose-regulated protein 94 (GRP94) in regulating the chemotherapy response of OS has never been explored. Method: In this study, GRP94-knockdown (GRP94-KD) MG63 OS cells were generated using short hairpin RNAs, and the response to chemotherapy was assessed by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results: GRP94-KD cells were shown to be more resistant to chemotherapy than scrambled control cells, and the scrambled control cells had higher levels of apoptosis after chemotherapy than GRP94-KD cells. Conclusion: Therefore, silencing GRP94 may increase resistance to chemotherapy treatment in OS cells by inhibiting the activation of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS. Citation Format: Huang Chien-Yu, Po-Li Wei, Yu-Jia Chang. Glucose-regulated protein 94 modulates the response of osteosarcoma to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 463.
Cardiac Magnetic Resonance T1 Mapping in Cardiac Amyloidosis
Authors: Franz Duca, Andreas A. Kammerlander, Adelheid Panzenböck, Christina Binder, Stefan Aschauer, Christian Loewe, Hermine Agis, Renate Kain, Christian Hengstenberg, Diana Bonderman, Julia Mascherbauer
Journal: JACC. Cardiovascular imaging (2018)
Abstract 142: cdk5 inhibition promotes neurogenesis while reducing self-renewal of brain tumor stem cells
Authors: Subhas Mukherjee, Cheryl Olson, Daniel Brat
Journal: Cancer Research (2018)

Abstract Cancer stem cells are biologically potent and support tumor growth, in part by deregulating asymmetric stem cell division. Asymmetric cell division of stem cells is a type of mitotic division where a stem cell generates one stem and one differentiated cell. Cancer stem cells, however, tend to generate more stem-like dividing cells to promote neoplasm. To uncover mechanisms and potential therapeutic targets relevant to self-renewal in human glioma stem cells (GSCs), we performed a genetic screen for kinases that reverse the tumor phenotype of our novel adult Drosophila brain tumor model and found that knockdown of the brain-specific dCdk5 was highly effective in suppressing the self-renewing stem cell components. A highly specific CDK5 inhibitor is promoting neurogenesis among these fly brain cancer stem cells. These cancer stem cells, although they express glial markers in tumors, do not differentiate into glia upon CDK5 suppression. Additionally, while the tumor generation in adult flies completely disrupts the mushroom body, the main cognitive center in adult fly brain, the CDK5 inhibition partially rescues the mushroom body and extends life span of these flies. dCdk5 and its human ortholog CDK5 (79% identity) are aberrantly activated in some forms of cancer. We demonstrate that GBMs highly express CDK5 mRNA and protein, likely related to copy number gains of chromosome 7, with strong positive correlation with stem cell markers and marked effect on tumor-propagating properties. Using human GSCs isolated from tumor spheres and mouse xenografts, we found that CDK5 directly phosphorylates CREB1 independent of cAMP and stops stem cell renewal. These data together show that CDK5 inhibition not only can attenuate self-renewal properties of brain tumor stem cells, but also can promote neurogenesis, which could potentially become a better treatment strategy for patients and improve their cognitive function as well. Citation Format: Subhas Mukherjee, Cheryl Olson, Daniel Brat. cdk5 inhibition promotes neurogenesis while reducing self-renewal of brain tumor stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 142.
Measurements of Electrical Potentials and Ion Fluxes on Single Renal Tubules
Authors: Gerhardgiebisch
Journal: Circulation (1960)

Experimental technics are described which permit the measurements of stable electrical potential differences across the cell membrane of single renal tubule cells and across single tubules. The inside of the tubule lumen is normally found to be electrically negative to the outside, while the cell interior is found to be negative to both the peritubular fluid and the tubule lumen. Such electrical measurements, in conjunction with known concentration gradients and flux measurements of various ions across single renal tubules, permit some deductions to be made on the driving forces involved in the movement of various ion species across the luminal and peritubular cell membrane of renal tubule cells.
Naloxone Administration Frequency During Emergency Medical Service Events — United States, 2012–2016
Authors: Rebecca E. Cash, Jeremiah Kinsman, Remle P. Crowe, Madison K. Rivard, Mark Faul, Ashish R. Panchal
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

As the opioid epidemic in the United States has continued since the early 2000s (1,2), most descriptions have focused on misuse and deaths. Increased cooperation with state and local partners has enabled more rapid and comprehensive surveillance of nonfatal opioid overdoses (3).* Naloxone administrations obtained from emergency medical services (EMS) patient care records have served as a useful proxy for overdose surveillance in individual communities and might be a previously unused data source to describe the opioid epidemic, including fatal and nonfatal events, on a national level (4-6). Using data from the National Emergency Medical Services Information System (NEMSIS),† the trend in rate of EMS naloxone administration events from 2012 to 2016 was compared with opioid overdose mortality rates from National Vital Statistics System multiple cause-of-death mortality files. During 2012-2016, the rate of EMS naloxone administration events increased 75.1%, from 573.6 to 1004.4 administrations per 100,000 EMS events, mirroring the 79.7% increase in opioid overdose mortality from 7.4 deaths per 100,000 persons to 13.3. A bimodal age distribution of patients receiving naloxone from EMS parallels a similar age distribution of deaths, with persons aged 25-34 years and 45-54 years most affected. However, an accurate estimate of the complete injury burden of the opioid epidemic requires assessing nonfatal overdoses in addition to deaths. Evaluating and monitoring nonfatal overdose events via the novel approach of using EMS data might assist in the development of timely interventions to address the evolving opioid crisis.
Abstract 14680: Evaluation of the Protective Effects of Long-term Doxycycline Treatment on Progression of Marfan-associated Aortic Aneurysm by High-resolution Ultrasound Imaging
Authors: Jason Z Cui, Ling Lee, Xiaoye Sheng, Glen F Tibbits, Cornelis van Breemen, Mitra Esfandiarei
Journal: Circulation (2015)

Introduction: Aortic aneurysm is the most life-threatening complication in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene. We have previously reported that doxycycline, an antibiotic and a general inhibitor of matrix metalloproteinases (MMPs), could improve aortic contractility and elastin fibers structure and organization in a mouse model of MFS. However, the in vivo effects of MMPs inhibition on the progression of aneurysm and pulse wave velocity (PWV) have not been investigated. In this study, we assessed the hypothesis that a long-term treatment with a sub-antibiotic dose of doxycycline would delay the progression of aortic aneurysm and improve the PWV in the Marfan mouse. Methods: In this study, we have used a high-resolution, high-contrast ultrasound imaging technique to conduct a longitudinal study in order to measure aortic diameter (dilatation) and PWV (indication of aortic elasticity/stiffness) in the animals. Marfan (n=12) and control (n=13) mice were given a sub-antibiotic dose of doxycycline in their drinking water at a concentration of 0.24 g/L/day beginning at 6 weeks of age, whereas another group of Marfan (n=12) and control (n=12) mice were given plain drinking water for comparison. At 3, and 6 months of age, aortic diameter and PWV of the experimental animals were measured by ultrasound imaging. Results: At 3 months of age, measurement of aortic root diameter showed significant dilatation in both treated and non-treated Marfan mice as compared to control groups (p &lt; 0.01). However, at 6 months of age, the aortic root diameter in treated Marfan mice was not different from those in controls. The same observation was made for the Sinus of Valsalva region. Especially in this region, treated Marfan aorta showed significantly reduced diameter compared to non-treated Marfan groups (p &lt; 0.05). With respect to the measurement of PWV, a significant increase was observed in 3- and 6-month Marfan mice aorta vs. control (p &lt; 0.01). Interestingly, doxycycline treatment normalized the PWV in 6-month old Marfan mice compared to non-treated Marfan aorta. Conclusions: Our findings show that long-term doxycycline treatment has protective effects in terms of reduction of aortic dilatation and stiffness in Marfan mice.
Enzymatically Degraded, Nonoxidized LDL Induces Human Vascular Smooth Muscle Cell Activation, Foam Cell Transformation, and Proliferation
Authors: MariamKlouche, StefanRose-John, WaltherSchmiedt, SucharitBhakdi
Journal: Circulation (2000)

Background—Enzymatic, nonoxidative modification transforms LDL to an atherogenic molecule (E-LDL) that activates complement and macrophages and is present in early atherosclerotic lesions. Methods and Results—We report on the atherogenic effects of E-LDL on human vascular smooth muscle cells (SMC). E-LDL accumulated in these cells, and this was accompanied by selective induction of monocyte chemotactic protein-1 in the absence of effects on the expression of interleukin (IL)-8, RANTES, or monocyte inflammatory proteins-1α and -β). Furthermore, E-LDL stimulated the expression of gp130, the signal-transducing chain of the IL-6 receptor (IL-6R) family, and the secretion of IL-6. E-LDL invoked mitogenic effects on SMC through 2 mechanisms. First, an autocrine mitogenic circuit involving platelet-derived growth factor and fibroblast growth factor-β was induced. Second, upregulation of gp130 rendered SMC sensitive to transsignaling through the IL-6/sIL-6R activation pathway. Because E-LDL promoted release of bo...
Altered Stoichiometry of FKBP12.6 Versus Ryanodine Receptor as a Cause of Abnormal Ca2+ Leak Through Ryanodine Receptor in Heart Failure
Authors: MasafumiYano, KaoruOno, TomokoOhkusa, MasaeSuetsugu, MasateruKohno, TakayukiHisaoka, ShigekiKobayashi, YujiHisamatsu, TakeshiYamamoto, MichihiroKohno, NaoyaNoguchi, ShinTakasawa, HiroshiOkamoto, MasunoriMatsuzaki
Journal: Circulation (2000)

Background—In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca2+-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506–binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. Methods and Results—SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the Bmax values for [3H]dihydro-FK506 to those for [3H]ryanodine binding. In normal SR, the molar ratio was 3.6 (≈1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca2+ leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca2+ leak was observed even in the absence of FK506, ...