tbuckley/cabot-search huggingface dataset:
Abstract 5750: Underlying inflammatory processes in non-neoplastic female thyroid serve as an immunological basis for the sex disparity in papillary thyroid cancer
Authors: Anvita Gupta, Karnika Singh, Timmy J. O'Connell, Melanie Jones, JK Rasamny, Monica Schwarcz, Augustine Moscatello, Edward Shin, Raj Tiwari, Jan Geliebter
Journal: Cancer Research (2018)

Abstract Background: The American Cancer Society (ACS) estimated 56,870 new cases of thyroid cancer in the United States in 2017, with roughly 2,010 deaths attributed to the disease. The incidence of thyroid cancer has been increasing steadily over the past three decades, with Papillary Thyroid Cancer (PTC) being the most prevalent form of this endocrine malignancy, comprising of about 90% of all cases. Appreciably, Surveillance, Epidemiology, and End Results (SEER) and the ACS indicate that the incidence of PTC in the age group of 20-49 years is three to four times more prevalent in women than in men. This epidemiologic finding suggests that the female thyroid is at a higher risk of developing PTC. Methods: The Cancer Genome Atlas (TCGA) database provides the means to address the differences between male and female thyroids on the molecular level. Using the normalized Level 3 RNA Seq Data and patient pathology reports available on the TCGA Data Portal, differential gene expression of 56 non-neoplastic/normal thyroid samples (40 women; 16 men) was investigated using the biological analysis software, Subio platform, version v1.20.5031. (Subio Inc., Tokyo, Japan). Results: Immune/inflammatory genes exhibited a higher expression in uninflamed, normal thyroid tissue of women than in men (&amp;gt;1.5 fold; p&amp;lt;0.05). The expression levels of these genes were increased in male PTC samples, compared to their matched normal tissue. The level of expression of immune/inflammatory genes in women approximated their expression levels in matched PTC tissue of women and men, indicating that normal thyroid tissue in women exhibits a neoplastic level of inflammation. Conclusions: Our data suggest that the female thyroid may be “at-risk” for developing PTC due to underlying and on-going immune/inflammatory processes. Citation Format: Anvita Gupta, Karnika Singh, Timmy J. O'Connell, Melanie Jones, JK Rasamny, Monica Schwarcz, Augustine Moscatello, Edward Shin, Raj Tiwari, Jan Geliebter. Underlying inflammatory processes in non-neoplastic female thyroid serve as an immunological basis for the sex disparity in papillary thyroid 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 5750.
Loading Manipulations Improve the Prognostic Value of Doppler Evaluation of Mitral Flow in Patients With Chronic Heart Failure
Authors: MassimoPozzoli, EgidioTraversi, GiovanniCioffi, RachelStenner, MaurizioSanarico, LuigiTavazzi
Journal: Circulation (1997)

Background Mitral flow velocity patterns (MFVPs) evaluated by Doppler echocardiography are strong predictors of survival in various cardiac diseases. However, MFVPs may change over time according to loading conditions. We performed this prospective study to assess whether changes in MFVP induced by loading manipulations provided additional prognostic information in 173 patients with chronic heart failure. Methods and Results Simultaneous Doppler echocardiographic and right-sided hemodynamic recordings were obtained at baseline in all patients, during nitroprusside infusion in the 98 patients who had a baseline restrictive (early-to-late flow velocity ratio >1 and deceleration time ≤130 ms) MFVP, and during passive leg lifting in the 75 patients who had a baseline nonrestrictive MFVP. Patients were categorized, according to changes in MFVP, into four groups: 61 patients with an irreversible restrictive, 37 with a reversible restrictive, 48 patients with a stable nonrestrictive, and 27 patients with an unst...
Abstract 1507: Multiple mechanisms of Myb gene activation revealed through transcriptome analysis of salivary gland adenoid cystic carcinoma
Authors: Candace Frerich, Kathryn Brayer, Brandon Painter, Scott Ness
Journal: Cancer Research (2018)

Abstract Adenoid cystic carcinoma (ACC) of the salivary gland is a rare head and neck malignancy with poor long-term prognosis. Hallmark chromosomal translocations result in MYB to NFIB (t(6;9)) and MYBL1 to NFIB (t(8;9)) gene fusions. Gene rearrangement and aberrant expression of the MYB and MYBL1 genes, along with the encoded transcription factors, are the oncogenic driver in the majority of ACC tumors. Previous RNA-sequencing (RNA-seq) data collected from FFPE fixed ACC tumors illustrated MYB and MYBL1 elicit similar gene expression profiles in ACC, suggesting these transcription factors drive ACC oncogenes via similar mechanisms. Using these RNA-seq data we have identified EN1 and SOX4 as important Myb regulated genes and demonstrated activation of their promoters in reporter gene assays. We hope to utilize these reporters in high-throughput screens to identify new drug candidates for ACC. We have utilized RNA-seq data to identify an additional mechanism leading to MYB overexpression that appears unique to ACC tumors. In these tumors transcription of the MYB gene is aberrantly activated through use of an alternative promoter located within the first intron of the gene. Transcripts originating from this promoter have been confirmed in an ACC tumor via 5'RACE and the resulting Myb protein has a small N-terminal truncation eliminating the epitope recognized by a common Myb antibody. The alternative promoter is active and regulated in a cell type specific manner in reporter gene assays. Previous studies have shown chromosomal translocations juxtapose NFIB enhancers to activate MYB gene transcription. ChIP and 3C assays in fresh frozen ACC tumors will be utilized to test the hypothesis that NFIB enhancers are specifically recruited to the alternative MYB promoter, thereby activating gene transcription. Thus, multiple mechanisms lead to the aberrant over-expression and truncation of MYB and drives ACC oncogenesis. Citation Format: Candace Frerich, Kathryn Brayer, Brandon Painter, Scott Ness. Multiple mechanisms of Myb gene activation revealed through transcriptome analysis of salivary gland adenoid cystic carcinoma [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 1507.
Serum Biomarker Signature-Based Liquid Biopsy for Diagnosis of Early-Stage Pancreatic Cancer
Authors: Linda D. Mellby, Andreas P. Nyberg, Julia S. Johansen, Christer Wingren, Børge G. Nordestgaard, Stig E. Bojesen, Breeana L. Mitchell, Brett C. Sheppard, Rosalie C. Sears, Carl A.K. Borrebaeck
Journal: Journal of Clinical Oncology (2018)

Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of &lt; 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signature of early-stage PDAC. The signature was derived from a large patient cohort, including patients with well-defined early-stage (I and II) PDAC. This biomarker signature was validated subsequently in an independent patient cohort. Patients and Methods The biomarker signature was derived from a case-control study, using a Scandinavian cohort, consisting of 16 patients with stage I, 132 patients with stage II, 65 patients with stage III, and 230 patients with stage IV PDAC, and 888 controls. This signature was validated subsequently in an independent case-control cohort in the United States with 15 patients with stage I, 75 patients with stage II, 15 patients with stage III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray platform was used to identify the serum biomarker signature associated with early-stage PDAC. Results Using the Scandinavian case-control study, a biomarker signature was created, discriminating samples derived from patients with stage I and II from those from controls with a receiver operating characteristic area under the curve value of 0.96. This signature, consisting of 29 biomarkers, was then validated in an independent case-control study in the United States. The biomarker signature could discriminate patients with stage I and II PDAC from controls in this independent patient cohort with a receiver operating characteristic area under the curve value of 0.96. Conclusion This serum biomarker signature might represent a tenable approach to detecting early-stage, localized PDAC if these findings are supported by a prospective validation study.
CD14+CD34low Cells With Stem Cell Phenotypic and Functional Features Are the Major Source of Circulating Endothelial Progenitors
Authors: PaolaRomagnani, FrancescoAnnunziato, FrancescoLiotta, ElenaLazzeri, BenedettaMazzinghi, FrancescaFrosali, LorenzoCosmi, LauraMaggi, LauraLasagni, AlexanderScheffold, ManuelaKruger, StefanieDimmeler, FabioMarra, GianfrancoGensini, EnricoMaggi, SergioRomagnani
Journal: Circulation Research (2005)

Endothelial progenitor cells (EPCs) seem to be a promising tool for cell therapy of acute myocardial infarction, but their nature is still unclear. We show here that EPCs obtainable from peripheral blood (PB) derive from the adhesion-related selection in culture of a subset of CD14+ cells, which, when assessed by the highly-sensitive antibody-conjugated magnetofluorescent liposomes (ACMFL) technique, were found to express CD34. These CD14+CD34low cells represented a variable proportion at individual level of CD14+ cells, ranging from 0.6% to 8.5% of all peripheral-blood leukocytes, and constituted the dominant population among circulating KDR+ cells. By using the ACMFL technique, virtually all CD14+ cells present in the bone marrow were found to be CD14+CD34low double-positive cells. EPCs, as well as purified circulating CD14+CD34low cells, exhibited high expression of embryonic stem cell (SC) markers Nanog and Oct-4, which were downregulated in a STAT3-independent manner when they differentiated into end...
Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6‐11
Authors: Karen F. Murray, William F. Balistreri, Sanjay Bansal, Suzanne Whitworth, Helen M. Evans, Regino P. Gonzalez‐Peralta, Jessica Wen, Benedetta Massetto, Kathryn Kersey, Jiang Shao, Kimberly L. Garrison, Bandita Parhy, Diana M. Brainard, Ronen Arnon, Lynette A. Gillis, Maureen M. Jonas, Chuan‐Hao Lin, Michael R. Narkewicz, Kathleen Schwarz, Philip Rosenthal
Journal: Hepatology (2018)

Currently, there are no interferon-free treatments available for hepatitis C virus (HCV)-infected patients younger than 12 years. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir-sofosbuvir ± ribavirin in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg-sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety-two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration-time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.
Abstract 5695: Use of certain antihistamines among breast cancer patients confers survival benefit
Authors: Hakan L. Olsson
Journal: Cancer Research (2018)

Abstract H1-antihistamines have not been widely studied in relation to cancer therapy, despite being among the most common medications used globally, and having become increasingly sophisticated, cheap and safe. In a nation-wide study of the entire Swedish population using the Drug Prescription Registry, Cancer Registry and Cause of Death Registry- the first of its kind - we investigated the effects of the six major antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) on breast cancer-related (as well as all-cause) mortality. Our study includes 61,627 Swedish women with breast cancer diagnosed between July 1st 2005 and December 31st 2013. 14,711 used at least one of the six major antihistamines. Both peri- and post-diagnostic antihistamine use was analyzed, as well as the use among different subgroups of patients, divided according to age, stage and estrogen receptor status, was analyzed. Here, we show a consistently beneficial effect of desloratadine and ebastine use on breast cancer survival (in the peri-diagnostic analysis, for desloratadine, HR=0.79 [95% CI 0.63-0.99], P=0.044; and for ebastine users, HR=0.57 [95% CI 0.32-1.03], P=0.064; relative to non-users) and a consistently negative effect on breast cancer survival of clemastine use (in the peri-diagnostic analysis, HR=1.24 [95% CI 1.05-1.47], P=0.013; relative to non-users). Loratadine use is associated with better survival in the peri-diagnostic analysis (HR=0.78 [95% CI 0.63-0.97], P=0.022) relative to non-use. No significant effects were seen for cetirizine use or fexofenadine use. Post diagnostic use. A woman with breast cancer using desloratadine will lower her relative risk of breast cancer-related death with 15% after one year's use and 17% after two years' use (both risks relative to a woman of the same age and the same tumor status). Conclusion. Use of desloratadine and ebastine may may significantly improve survival in breast cancer with few side effects. Citation Format: Hakan L. Olsson. Use of certain antihistamines among breast cancer patients confers survival benefit [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 5695.
Long-Term Inhibition of Rho-Kinase Suppresses Angiotensin II–Induced Cardiovascular Hypertrophy in Rats In Vivo
Authors: MidorikoHigashi, HiroakiShimokawa, TsuyoshiHattori, JunkoHiroki, YasushiMukai, KeikoMorikawa, ToshihiroIchiki, ShosukeTakahashi, AkiraTakeshita
Journal: Circulation Research (2003)

Intracellular signaling pathway mediated by small GTPase Rho and its effector Rho-kinase plays an important role in regulation of vascular smooth muscle contraction and other cellular functions. We have recently demonstrated that Rho-kinase is substantially involved in angiotensin II–induced gene expressions and various cellular responses in vitro. However, it remains to be examined whether Rho-kinase is involved in the angiotensin II–induced cardiovascular hypertrophy in vivo and, if so, what mechanisms are involved. Long-term infusion of angiotensin II for 4 weeks caused hypertrophic changes of vascular smooth muscle and cardiomyocytes in rats. Both changes were significantly suppressed by concomitant oral treatment with fasudil, which is metabolized to a specific Rho-kinase inhibitor, hydroxyfasudil, after oral administration. Angiotensin II caused a perivascular accumulation of macrophages and Rho-kinase activation, both of which were also significantly suppressed by fasudil. Vascular NAD(P)H oxidase ...
Abstract 1397: The regulation of DNMT3B expression by lncRNA-NCRMS in cancer
Authors: Wan-xin Peng, Yin-yuan Mo
Journal: Cancer Research (2018)

Abstract 5-aza-2'-deoxycytidine (decitabine; DAC) is an inhibitor of DNA methyltransferases which catalyze the transfer of a methyl group to DNA. It is well known that aberrant hypermethylation occurs in many types of tumors and often contributes to suppression of important genes such as tumor suppressor genes. Reactivation of the methylated genes by DAC has been shown to induce cytotoxicity and cell cycle dynamics. Increasing evidence indicates that lncRNAs may play critical roles in cancer development through epigenetic regulation of gene expression. However, little is known whether and how lncRNAs are involved in regulation of methylation pathways. In present study, we applies the CRISPR/Cas9-based synergistic activation mediator (SAM) system to a DAC-induced cytotoxicity model to identify potential lncRNAs capable of conferring the resistance to DAC in breast cancer. This screen identified several potential lncRNA candidates and among them is NCRMS which is capable of promoting resistance to DAC. We further confirmed that ectopic expression of NCRMS causes resistance to DAC whereas knockout of NCRMS increases the sensitivity to DAC. Mechanistically, NCRMS functions as a positive regulator of DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B). Further characterizations demonstrated that NCRMS promotes the stability of DNMT3B mRNA. Together, these results suggest that NCRMS may serve as a potential target for cancer therapy. Studies are underway to delineate the detailed mechanism of how NCRMS regulates the stability of DNMT3B mRNA. Citation Format: Wan-xin Peng, Yin-yuan Mo. The regulation of DNMT3B expression by lncRNA-NCRMS in 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 1397.
Utilization rates and outcomes of short-course radiotherapy for nonmetastatic rectal adenocarcinoma for patients in the National Cancer Database.
Authors: Hesham Elhalawani, Pamela Allen, Omar Mohammed Abdel-Rahman, Emma Brey Holliday
Journal: Journal of Clinical Oncology (2018)

774 Background: Short-course radiation therapy (SCRT) has been studied in European trials but is not often utilized in the US. We aim to describe the utilization and outcomes of SCRT compared to the more widely used long-course (LCRT) neoadjuvant regimen. Methods: The National Cancer Database (NCDB) was queried for patients treated with preoperative RT followed by surgical resection for non-metastatic rectal adenocarcinoma from 2004-2014. Patient, tumor and treatment-related characteristics were compared between those treated with SCRT (defined as patients receiving &lt; 26 Gray (Gy) in &lt; 7 fractions) and those treated with LCRT. Survivals were compared using the Log-Rank test. Univariate and multivariate Cox regression analyses were used for univariate analysis of factors associated with overall survival (OS). Results: 48898 patients were included for analysis: 48396 patients (99.0%) treated with LCRT and 502 (1.0%) treated with SCRT. Patients treated with SCRT were older (median [range] age 67 [21-90] vs 60 [18-90]; p &lt; .001), had more comorbidities (Charlson/Deyo score 1+ N = 155 (30.9%) vs N = 9795 (20.2%); p &lt; .001), had earlier T-stage (T1-2 N = 141 (28.1%) vs N = 5774 (11.9%); p &lt; .001) and were more likely to be clinically node-negative (N = 324 (64.5%) vs N = 22701 (46.9%); p &lt; .001). Patients treated with SCRT were more likely to be treated after 2009 (N = 303 (60.4%) vs N = 24834 (51.3%); p &lt; .001) and were more often treated at an academic center (N = 318 (63.3%) vs N = 20375 (42.1%); p &lt; .001). Patients treated with SCRT had a 2- and 5-year OS of 85.8% and 65.7%, respectively, compared with 90.9% and 73.5% in patients treated with LCRT (log-rank p &lt; .001). On univariate analysis, receipt of SCRT was associated with worse OS (HR 1.40 95% CI 1.18-1.65; p &lt; .001). However, when entered into a multivariate model including other patient and tumor-related factors, SCRT was actually associated with improved OS (HR 0.77 95% CI 0.59-1.00; p = .048). Conclusions: SCRT is utilized for approximately 1% of patients treated with preoperative treatment of non-metastatic rectal cancer in the US. The results of recently completed randomized trials may further inform patterns of practice in the US and abroad.
Abstract 19791: Echocardiography Derived Velocity Time Integral is Associated with Double Switch Outcomes in Congenitally Corrected Transposition of the Great Arteries
Authors: ShreyaMoodley, SowmyaBalasubramanian, TheresaTacy, FrankHanley, FrandicsChan, RajeshPunn
Journal: Circulation (2014)

Introduction: Congenitally corrected transposition of the great arteries (CCTGA) is a rare form of congenital heart disease characterized by atrioventricular and ventriculoarterial discordance. Management is controversial; options include observation, physiologic repair and anatomic repair by the double switch operation (DSO). Assessment of morphologic left ventricle (LV) preparedness is key in determining DSO timing, although exact criteria are lacking. Cardiac MRI is the current standard technique to assess LV adequacy prior to DSO. The purpose of our study was to determine if echocardiographic (echo) or MRI measures of the LV predict outcomes. Methods: A retrospective review of CCTGA patients eligible for DSO at Lucile Packard Children’s Hospital from 2000-2014 was conducted. Inclusion criteria were: 1) age &lt18 years, 2) adequate pre-surgical echo and MRI images and 3) clinical follow-up information available. Post-processing of echo images was performed to obtain measurements of LV structure and fun...
Cardiac Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-α
Authors: DeboraBryant, LisaBecker, JamesRichardson, JohnShelton, FatimaFranco, RonaldPeshock, MaritaThompson, BrettGiroir
Journal: Circulation (1998)

Background—Tumor necrosis factor-α (TNF-α) is a multifunctional cytokine that has been detected in several human cardiac-related conditions, including congestive heart failure and septic cardiomyopathy. In these conditions, the origin of TNF-α secretion is, at least in part, cardiac myocytes. Methods and Results—To determine the consequences of TNF-α production by cardiac myocytes in vivo, we developed transgenic mice in which expression of a murine TNF-α coding sequence was driven by the murine α-myosin heavy chain promoter. Four transgenic founders developed an identical illness consisting of tachypnea, decreased activity, and hunched posture. In vivo, ECG-gated MRI of symptomatic transgenic mice documented a severe impairment of cardiac function evidenced by biventricular dilatation and depressed ejection fractions. All transgenic mice died prematurely. Pathological examination of affected animals revealed a globular dilated heart, bilateral pleural effusions, myocyte apoptosis, and transmural myocardi...