tbuckley/cabot-search huggingface dataset:
Abstract 4471: Pax9 regulates squamous cell differentiation and alcohol-associated carcinogenesis in the oro-esophageal epithelium
Authors: Zhaohui Xiong, Shuang Ren, Hao Chen, Yao Liu, Caizhi Huang, Yawan Lyvia Zhang, Joab Otieno Odera, Tong Chen, Ralf Kist, Heiko Peters, Katherine Garman, Zheng Sun, Xiaoxin Luke Chen
Journal: Cancer Research (2018)

Abstract Pax9 is a transcription factor of the Pax family characterized by a DNA-binding paired domain. Previous studies have suggested a potential role of Pax9 in squamous cell differentiation and carcinogenesis of oro-esophageal epithelium. However, its functional role in differentiation and carcinogenesis remains unclear. In this study, Pax9 deficiency in mouse esophagus promoted cell proliferation, delayed cell differentiation and altered the global gene expression profile. Ethanol exposure down-regulated Pax9 expression in human esophageal epithelial cells in vitro and mouse forestomach and tongue in vivo. We further showed that PAX9 was down-regulated in human oro-esophageal squamous cell carcinoma (OESCC), and its down-regulation was associated with alcohol drinking and promoter hypermethylation. Moreover, ad libitum feeding with an isocaloric Lieber-DeCarli liquid diet containing ethanol for 40 weeks or Pax9 deficiency promoted NMBA-induced squamous cell carcinogenesis in mouse tongue, esophagus, and forestomach. In conclusion, Pax9 regulates squamous cell differentiation in the oro-esophageal epithelium. Alcohol drinking and promoter hypermethylation are associated with PAX9 silencing in human OESCC. Pax9 down-regulation, at least in part, contributes to alcohol-associated oro-esophageal squamous cell carcinogenesis. Citation Format: Zhaohui Xiong, Shuang Ren, Hao Chen, Yao Liu, Caizhi Huang, Yawan Lyvia Zhang, Joab Otieno Odera, Tong Chen, Ralf Kist, Heiko Peters, Katherine Garman, Zheng Sun, Xiaoxin Luke Chen. Pax9 regulates squamous cell differentiation and alcohol-associated carcinogenesis in the oro-esophageal epithelium [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 4471.
Disparities in Cervical Cancer Screening Among Women With Disabilities: A National Database Study in South Korea
Authors: Dong Wook Shin, Jeong-Won Lee, Jin Hyung Jung, Kyungdo Han, So Young Kim, Kui Son Choi, Jong Heon Park, Jong Hyock Park
Journal: Journal of Clinical Oncology (2018)

Purpose Using the linked administrative database in Korea, we investigated (1) whether cervical cancer screening participation differed by the presence of varying degrees and types of disability; (2) trends in the cervical cancer screening rate relative to disabilities over time; and (3) factors associated with cervical cancer screening. Methods We linked national disability registration data with national cancer screening program data. Age-standardized participation rates were analyzed for each year during the period 2006 to 2015, according to the presence, type, and severity of disabilities. Factors associated with undergoing cervical cancer screening were examined by multivariate logistic regression with the most current data (ie, 2014 to 2015). Results The age-adjusted screening rate for cervical cancer screening in women with disabilities increased from 20.8% in 2006% to 42.1% in 2015 (change, +21.3%); however, among women without disabilities, it increased from 21.6% to 53.5% (change: +31.9%) during that time. Disability was associated with a lower screening rate (adjusted odds ratio [aOR], 0.71; 95% CI, 0.71 to 0.72). Screening rates were markedly lower in women with severe disabilities (aOR, 0.42; 95% CI, 0.42 to 0.42) and women with autism (aOR, 0.06; 95% CI 0.03 to 0.11), intellectual disability (aOR, 0.25; 95% CI, 0.25 to 0.26), brain injury (aOR, 0.311; 95% CI, 0.31 to 0.32), ostomy (aOR, 0.36; 95% CI, 0.33 to 0.38), or mental disorder (aOR, 0.43; 95% CI, 0.42 to 0.44). Conclusion Despite the availability of free screening, a significant disparity was found in cervical cancer screening participation, especially in women with severe disabilities and those with mental disabilities. The identification of barriers associated with decreased screening rates in women with disabilities has important implications for the design of tailored interventions and health care policies to improve cervical cancer screening and outcomes in this vulnerable population.
Interleukin-18 and the Risk of Coronary Heart Disease in European Men
Authors: StefanBlankenberg, GéraldLuc, PierreDucimetière, DominiqueArveiler, JeanFerrières, PhilippeAmouyel, AlunEvans, FrançoisCambien, LaurenceTiret
Journal: Circulation (2003)

Background— Interleukin (IL)-18 promotes atherosclerotic plaque growth and vulnerability. It is unknown, however, whether elevations of circulating IL-18 precede the onset of coronary events in apparently healthy individuals. Methods and Results— We evaluated the relationship between baseline plasma levels of IL-18 and the subsequent incidence of coronary events over a 5-year follow-up in the Prospective Epidemiological Study of Myocardial Infarction (PRIME),which included 10 600 healthy European men aged 50 to 59 years at baseline. Analysis was performed in a nested case-control manner comparing 335 cases with a coronary event to 670 age-matched controls. Baseline levels of IL-18 were significantly higher in men who developed a coronary event than in controls (225.1 versus 203.9 pg/mL, P=0.005). After adjustment for most potential confounders, including C-reactive protein, IL-6, and fibrinogen, the relative risk of future coronary events associated with increasing tertiles of IL-18 was 1.65 (95% CI 1.14 ...
Abstract 5874: Targeting DDX3 in medulloblastoma by RK-33
Authors: Saritha Tantravedi, Farhad Vesuna, Allison Martin, Michael Lim, Charles G. Eberhart G. Eberhart, Paul J. van Diest, Venu Raman
Journal: Cancer Research (2018)

Abstract Introduction: Medulloblastoma is the most common form of pediatric brain cancer. Current treatments of surgical resection, craniospinal irradiation, and chemotherapy increase survival but around 40% of patients experience disease recurrence. Classically, four molecular subgroups of medulloblastoma have been identified: Wnt; Sonic hedgehog (SHH); Group 3; and Group 4. More recent work has subtyped up to seven molecular subgroups. The RNA helicase DDX3 is involved in many biological activities such as transcription, mRNA translation, splicing, and nuclear export. About 8% of medulloblastoma cases involve mutations in DDX3, of which 11% involve the pediatric Wnt and SHH subtypes. In addition, coinciding DDX3 and CTNNB1 mutations associated with dysregulated Wnt /β-catenin signaling in Wnt-type medulloblastomas have also been reported. Aims and Methods: The goal of this work was to study whether RK-33, a small molecule inhibitor of DDX3, would be effective against medulloblastoma as a single agent and in combination with radiotherapy. We studied DDX3 expression in medulloblastoma cell lines DAOY and UW228 and human tissue microarrays by immunohistochemistry, western blotting, and qRT-PCR. We targeted DDX3 by siRNA and by RK-33 and observed proliferation and viability changes by MTS assays. Flow cytometric analysis was used to determine effect of RK-33 on cell cycle and apoptosis. TOP/FOP promoter assay was utilized to study effect on TCF promoter activity. We used colony formation assays to study effect of combining radiation and RK-33 treatment on cells. DAOY tumors were generated in nude mice and treated with combination therapy to study effects in vivo. Results: High DDX3 expression was observed in 55% of pediatric and 66% of adult medulloblastomas. DDX3 knockdown resulted in reduced cellular proliferation. Both the medulloblastoma cell lines were sensitive to RK-33, with IC50 values of 2.5 µM and 3.5 µM, respectively and resulted in decreased levels of DDX3 expression, with no observable toxicity. RK-33 resulted in a G1 phase cell cycle arrest before the onset of apoptosis. DDX3 knockdown resulted in a significant decrease of TCF activity and reduced transcription of Axin2, CCND1, MYC, and Survivin. A combination of RK-33 and radiation resulted in a significantly higher inhibitory effect than using single treatment of either RK-33 or radiation. We conclude that inhibiting DDX3 via the small molecule inhibitor RK-33 is effective in reducing medulloblastoma tumors and that the effect is synergistic with radiation treatment. Citation Format: Saritha Tantravedi, Farhad Vesuna, Allison Martin, Michael Lim, Charles G. Eberhart G. Eberhart, Paul J. van Diest, Venu Raman. Targeting DDX3 in medulloblastoma by RK-33 [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 5874.
Abstract 5653: VMax™: A new platform for recombinant protein expression
Authors: Eric Hesek, Chris Wilson, Lindsey Wolf, Sanjay Vasu, Michael Sturges, Daniel Gibson, Matthew Weinstock
Journal: Cancer Research (2018)

Abstract Here we describe Vmax™, a next-generation protein expression platform based on the organism V. natriegens, an extremely rapidly growing gram-negative prokaryote capable of reaching high cell density. Vmax™ contains an IPTG inducible T7 expression system, enabling high levels of recombinant protein expression. By combining a robust expression system with a highly productive organism, Vmax allows researchers to perform experiments faster, shorten workflow times, and generate large amounts of recombinant protein. Citation Format: Eric Hesek, Chris Wilson, Lindsey Wolf, Sanjay Vasu, Michael Sturges, Daniel Gibson, Matthew Weinstock. VMax™: A new platform for recombinant protein expression [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 5653.
Phase III randomised controlled trial (RCT) comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer (CompARE).
Authors: Hisham Mohamed Mehanna, Mehmet Sen, John David Chester, Paul Sanghera, Vinidh Paleri, Piers Gaunt, Jaspreet Babrah, Andrew G. J. Hartley, Anthony Kong, H Al-Booz, Bernadette Foran, Elizabeth Miles, Max Robinson, Marcus Jepson, Jenny Donnovan, Christina Yap, Charlotte Firth, Claire Gaunt, Sarah Jane Bowden, Martin David Forster
Journal: Journal of Clinical Oncology (2017)

TPS6091 Background: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. The CompARE trial is designed to test alternative approaches to intensification of treatment for these patients to improve survival. Methods: CompARE is a pragmatic phase III open-label multicenter RCT with an adaptive multi-arm multi-stage design. Eligible OPC patients include those with; HPV negative, T1-T4, N1-N3 or T3-4, N0 or HPV positive current smokers (or ≥ 10 pack years previous smoking history) with T1-T4, N2b-N3. The primary outcome measure is overall survival. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complications and cost-effectiveness. The trial is powered to detect a hazard ratio of 0.69 (an improvement of 10% in OS at 3-years) requiring 128 control events. It is estimated that the study will take 6.5 years to recruit sufficient patients to experience the number of events needed. Planned interim futility analyses using event-free survival (EFS) will be performed when 70 and 114 control EFS events have occurred. Current treatment arms are; (1) control: standard treatment of 3-weekly cisplatin 100mg/m 2 or weekly 40mg/m 2 with Intensity Modulated Radiotherapy (IMRT) using 70Gy in 35F +/- neck dissection determined by clinical and radiological assessment 3-months post treatment. (3) IMRT 64Gy in 25F + cisplatin 100mg/m 2 day 1 of week 1 and week 5 or weekly 40mg/m 2 +/- neck dissection as per standard treatment. (4) Resection of primary + selective neck dissection followed by standard treatment. (5) One cycle of induction durvalumab 1500mg followed by standard treatment then durvalumab 1500mg every four weeks for a total of 6 months. Recruitment to arm (2) involving induction chemotherapy from the original protocol is suspended. Since July 2015, 42 patients have been randomised with 16 sites open to recruitment. The Data Monitoring Committee last reviewed progress and conduct of the trial in September 2016 and recommended continuation. ISRCTN Number: 41478539, CRUK CRUK/13/026 Clinical trial information: 41478539.
Impaired VE-Cadherin/β-Catenin Expression Mediates Endothelial Cell Degeneration in Dilated Cardiomyopathy
Authors: RomanaSchäfer, DietmarAbraham, PatrickPaulus, RolandBlumer, MichaelGrimm, JohannWojta, SeyedhosseinAharinejad
Journal: Circulation (2003)

Background— The cross-talk between vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang), and VE-cadherin coregulates endothelial cell (EC) survival. Cardiac expression of VEGF-A but not its receptor KDR is blunted in dilated cardiomyopathy (DCM). Whether VE-cadherin/Ang function is affected in DCM is unknown. Methods and Results— The myocardial expression of VE-cadherin/β-catenin, Ang-1, Ang-2, and their receptor Tie-2 was examined in DCM, ischemic cardiomyopathy (ICM), and in control subjects through the use of real-time RT-PCR, Western blotting, and immunocytochemistry. EC degeneration was quantified by TEM. RNA interference against VE-cadherin and VEGF deprivation and stimulation were applied to cultured DCM myocardium and human microvascular ECs to examine the interplay between VEGF, VE-cadherin/β-catenin, and Ang-2. Analysis of tissue sections with similar rates of EC degeneration in both patient groups showed that VE-cadherin/β-catenin expression was downregulated in DCM only (P<0.05). Al...
Abstract 561: Circulating DNA clean up and enrichment from liquid biological samples for rare biomarker detection
Authors: Samantha R. Lewis, Charles Cowles, Kathryn Oostdik, Curtis Knox, Brad A. Hook
Journal: Cancer Research (2018)

Abstract A major roadblock to using circulating cell free DNA (ccfDNA) for cancer biomarker detection is the difficulty of obtaining a pure sample. Contaminating genomic DNA (gDNA) can overwhelm already rare events within a CCF sample and prevent sensitive detection of these key mutations. Unfortunately, liquid biological samples often are not collected and processed in an ideal manner, resulting in decreased quality and purity. Many studies report difficulties in detecting mutations in ccfDNA which may originate from variable levels of gDNA background based how samples are processed. To this end, we present an effective method for purifying relevant small nucleic acids from larger genomic species after DNA purification from plasma. Using a simple magnetic bead based technique, we demonstrate efficient removal of gDNA even in highly contaminated samples. This method can be used to enrich liquid biological samples for improved detection of rare genetic events such as microsatellite instability and mutations in key oncogenes. Using plasma from three individuals with colorectal cancer tumors harboring known mismatch repair gene mutations, we compare detection of somatic mutations in ccfDNA before and after this gDNA clean up method. Microsatellite instability profiles were obtained from ccfDNA and compared to normal and tumor profiles to determine if evidence of mismatch repair abnormalities could be detected. Targeted amplicon sequencing was then performed to detect tumor associated mutations. DNA isolated from matched adjacent normal and tumor tissues were used as controls in these experiments to confirm mutations were of tumor not germline mutations. Effectively removing gDNA contamination from ccfDNA samples can improve biomarker detection consistency from liquid biological samples. We demonstrate a magnetic bead-based method for ccfDNA clean-up, which can be used prior to microsatellite instability detection by fragment analysis or rare variant detection by next generation sequencing. Citation Format: Samantha R. Lewis, Charles Cowles, Kathryn Oostdik, Curtis Knox, Brad A. Hook. Circulating DNA clean up and enrichment from liquid biological samples for rare biomarker detection [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 561.
Body Surface Distribution of Equipotential Lines during Atrial Depolarization and Ventricular Repolarization
Authors: Brunotaccardi
Journal: Circulation Research (1966)

In 15 normal male human subjects and 6 dogs, 200 chest electrocardiograms were sequentially recorded. The distribution of equipotential lines on the thoracic surface was determined at 20 to 30 instants of time during atrial activation and ventricular recovery. In humans, the potential pattern is constantly dipolar, with one maximum and one minimum, during the P wave. The motion of the potential maximum and minimum on the chest surface appears to be related to the progress of the excitation through the auricular walls. At the end of the QRS interval, the simultaneous presence of activation and recovery potentials is generally observed, giving rise to several simultaneous maxima and minima. During the ST and T interval, recovery potentials show a dipolar distribution in normal subjects, but tripolar patterns are observed when the recovery process is altered in a circumscribed myocardial region. In dogs, multipolar distributions are frequently observed during the P wave, the ST segment and the T wave. During...
Clinical Experience With a Novel Multielectrode Basket Catheter in Right Atrial Tachycardias
Authors: ClausSchmitt, BernhardZrenner, MichaelSchneider, MartinKarch, GjinNdrepepa, IsabelDeisenhofer, SonjaWeyerbrock, JürgenSchreieck, AlbertSchömig
Journal: Circulation (1999)

Background—The complexity of atrial tachycardias (ATs) makes the electroanatomic characterization of the arrhythmogenic substrate difficult with conventional mapping techniques. The aim of our study was to evaluate possible advantages of a novel multielectrode basket catheter (MBC) in patients with AT. Methods and Results—In 31 patients with AT, an MBC composed of 64 electrodes was deployed in the right atrium (RA). The possibility of deployment, spatial relations between MBC and RA, MBC recording and pacing capabilities, mapping performance, and MBC-guided ablation were assessed. MBC deployment was possible in all 31 patients. The MBC was left in the RA for 175±44 minutes. Stable bipolar electrograms were recorded in 88±4% of electrodes. Pacing from bipoles was possible in 64±5% of electrode pairs. The earliest activity intervals, in relation to P-wave onset, measured from the MBC and standard roving catheters were 41±9 and 46±6 ms, respectively (P=0.21). Radiofrequency ablation was successful in 15 (94%...
Protein Tyrosine Kinase Is Not Involved in the Infarct Size–Limiting Effect of Ischemic Preconditioning in Canine Hearts
Authors: MasafumiKitakaze, KoichiNode, HiroshiAsanuma, SeijiTakashima, YasuhikoSakata, MasanoriAsakura, ShojiSanada, YoshiroShinozaki, HidezoMori, TsunehikoKuzuya, MasatsuguHori
Journal: Circulation Research (2000)

Abstract—Protein kinase C (PKC) plays an important role in ischemic preconditioning (IP). Because (1) tyrosine kinase is located at the downstream of PKC for IP in the rabbit hearts and (2) we have reported that ecto–5′-nucleotidase is the substrate for PKC and plays a crucial role for the infarct size–limiting effect, we tested whether tyrosine kinase activation contributes to either activation of ecto–5′-nucleotidase or the infarct size–limiting effect of the early phase of IP in the canine heart. In dogs, the IP procedure (4 cycles of 5-minute occlusion of coronary artery) and exposure to 12,13-phorbol myristate acetate (PMA) each activated myocardial ecto–5′-nucleotidase and Lck tyrosine kinase. Genistein (10, 30, and 100 μg · kg−1 · min−1 IC), an inhibitor of tyrosine kinase, attenuated the activation of Lck tyrosine kinase but did not attenuate the activation of ecto–5′-nucleotidase due to either IP or PMA. In the other canine hearts, IP attenuated infarct size (49±5 versus 11±3 or 16±3%, P<0.01) du...
Fluorescent Cardiac Imaging
Authors: ChristianDetter, SabineWipper, DetlefRuss, AndreIffland, LarsBurdorf, EckartThein, KarlWegscheider, HermannReichenspurner, BrunoReichart
Journal: Circulation (2007)

Background— The purpose of the present study was to examine whether the effect of coronary stenoses of variable severity on myocardial perfusion can be quantitatively assessed in vivo by analysis of fluorescent cardiac imaging (FCI) compared with the gold standard, the fluorescent microsphere method. FCI is a novel technology to visualize coronary vessels and myocardial perfusion intraoperatively using the indocyanine green dye with an infrared-sensitive imaging device. Methods and Results— Graded stenoses and total vessel occlusion of the left anterior descending coronary artery were created in 11 open-chest pigs. Stenoses were graded to reduce resting left anterior descending coronary artery flow by 25%, 50%, 75%, and 100% of baseline flow measured by transit-time flowmeter. FCI images were analyzed with a digital image processing system. The impairment of myocardial perfusion was quantified by background-subtracted peak fluorescence intensity and slope of fluorescence intensity obtained with FCI and co...
Circulating Progenitor Cells Regenerate Endothelium of Vein Graft Atherosclerosis, Which Is Diminished in ApoE-Deficient Mice
Authors: QingboXu, ZhongyiZhang, FergusDavison, YanhuaHu
Journal: Circulation Research (2003)

Previously we showed that a large number of endothelial cells in vein grafts undergo apoptosis or necrosis during the first few days followed by endothelial regeneration. In the present study, we investigated endothelial cell death and regeneration in vein grafts using transgenic mice carrying LacZ genes driven by an endothelial TIE2 promoter. When a vein fragment from TIE2-LacZ was isografted into the carotid artery of wild-type mice, the number of β-gal+ cells were reduced at 3 days and disappeared completely by 4 weeks after grafting. Conversely, β-gal+ cells were observed on the surface of vein segments donated by wild-type mice isografted into TIE2-LacZ mice at 1 week and reached confluence by 4 weeks, suggesting recipient origins of endothelial cells. Interestingly, β-gal+ cells were evenly distributed on the surface of the whole vein segment grafted into TIE2-LacZ mice, indicating a contribution of circulating progenitor cells. When wild-type veins were grafted into a chimeric mouse carrying TIE2-L...