tbuckley/cabot-search huggingface dataset:
Abstract 2585: Immunoseroproteomic profiling in autoantibodies to ENO1 as potential biomarkers in immunodiagnosis of osteosarcoma by serological proteome analysis (SERPA) approach
Authors: Jitian Li, Manyu Huang, Liping Dai, Zongchang Han, Xiaofei Qin, Wen Xie, Wei Qian, Wuyin Li, Jianying Zhang
Journal: Cancer Research (2018)

Abstract Background: Osteosarcoma (OS) is the most common highly malignant primary solid bone-tumor. Despite its relatively low incidence rate among overall cancers, it remains one of the most harmful primary malignant tumors in childhood and adolescence. It is now evident that serum autoantibodies against tumor-associated antigens (TAAs) could be used as serological cancer biomarkers in types of cancers. Methods: Serological proteome analysis (SERPA) approach was applied to profile anti-TAA autoantibody responses in sera from patients with OS, and Normal Human, and explore differences of these responses. This approach can detect autoantibodies to TAAs that could serve as clinical biomarkers and immunotherapeutic agents. Sera from OS, Osteochondroma (OC) and Normal Human Sera (NHS) were probed by immunoblotting against cellular proteins extracted from U2-OS and Saos-2 cell lines, with OS sera showing stronger immunoreactivity. MALDI-TOF/TOF Mass Spectrometry (MS) analysis of immunoreactive protein spots revealed that several OS sera contained autoantibodies to a number of proteins, particularly to alpha-enolase (ENO1). Results: Analysis of 172 serum samples from patients with OS, OC and NHS by ELISA showed higher frequency of anti-ENO1 autoantibodies in OS sera compared to others. Interestingly, descant of ENO1 immunoreactivity was observed in most patients after treatments, which may imply a potential association between anti-ENO1 autoantibody titers and disease progression. Nine of twelve sera reacted strongly against purified ENO1, but 3 weakly against purified ENO1, which indicates 75.0% sera with positive optimal density values from ELISA were consistently positive in Western blotting. The expression of ENO1 in Osteosarcoma tissues was evaluated by immunohistochemistry in tumor microarray. Conclusion: Our intriguing findings firstly demonstrate that ENO1 is one of autoantigens that elicit autoimmune responses in OS and can be used as biomarkers in immunodiagnosis and progression of OS. Key words: Osteosarcoma (OS), Tumor-associated antigen (TAA), Serological proteome analysis (SERPA), ENO1, Immunodiagnosis. Citation Format: Jitian Li, Manyu Huang, Liping Dai, Zongchang Han, Xiaofei Qin, Wen Xie, Wei Qian, Wuyin Li, Jianying Zhang. Immunoseroproteomic profiling in autoantibodies to ENO1 as potential biomarkers in immunodiagnosis of osteosarcoma by serological proteome analysis (SERPA) approach [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 2585.
Abstract 18204: Ex Vivo Flow Culture Modeling of Aortic Insufficiency Reveals Additive Effects of Impaired Coaptation and Accelerated Flow on Leaflet Gene Expression
Authors: Katsuhide Maeda, Xiaoyuan Ma, Frank Hanley, Robert K Riemer
Journal: Circulation (2017)

Introduction: Aortic valve insufficiency (AI) is one of the more common valve disorders. It has a variety of causes and is known to get progressively worse once the insufficiency starts. The mechan...
Abstract 4487: Gene expression changes elicited by crosstalk between adipocytes and breast cancer cells
Authors: Leann A. Lovejoy, Nicholas S. Costantino, Craig D. Shriver, Geogre Iida, Rachel E. Ellsworth
Journal: Cancer Research (2018)

Abstract Background: No longer considered simply an inert energy depot, adipose in the breast is increasingly recognized as an active endocrine tissue. Given the increasing rates of obesity in the US, choice of breast conserving surgery and use of autologous fat grafting, it is critical to understand how signals from adipocytes affect breast tumor cells and vice versa. Methods: Human subcutaneous preadipocytes were co-cultured for 3 days. Triple negative cell lines MDA-MB-231, SUM-149 and HCC-38 were then added and grown for a total of 10 days, with exposure to mature adipocytes for 7 days. Adipocytes and tumors cells were lysed from the plate and total RNA was isolated. Libraries were prepared for RNAseq and sequenced using a HiSeq2000. Differentially expressed genes were detected using the edge R package in R (v 3.3.3). Results: Co-culturing breast tumor cells demonstrated 110 differentially expressed genes compared to unexposed tumor cells including 6-fold lower expression of CLCA2 and 9-fold higher expression ZBTB16 in exposed tumor cells compared to controls. Pathway analysis demonstrated upregulation of 23 pathways such in the FoxO signaling and longevity regulating pathways and downregulation of tryptophan metabolism. In co-cultured adipocytes, 89 genes, including 9-fold higher expression of WNT7B and 13-fold lower expression of ADIPOQ. Pathways such as ECM-receptor interaction were upregulated and fat digestion and absorption were downregulated in co-cultured adipocytes. Conclusions: Exposure of adipocytes to tumor cells alters pathways involved in lipolysis and fatty acid metabolism in the adipocytes which may serve as a fuel source for tumor cells. In conjunction, exposure to adipocytes alters gene expression profiles in tumor cells associated with proliferation, migration and metastasis. These data demonstrate that proximity of breast tumor cells to adipocytes elicit significant gene expression changes in both cell types which synergistically promote tumorigenesis. The views expressed in this abstract are those of the author and do not reflect the official policy of the Department of Army, Navy, Air Force, Department of Defense, or U.S. Government. The identification of specific products, scientific instrumentation, or organization is considered an integral part of the scientific endeavor and does not constitute endorsement or implied endorsement on the part of the author, DoD, or any component agency. Citation Format: Leann A. Lovejoy, Nicholas S. Costantino, Craig D. Shriver, Geogre Iida, Rachel E. Ellsworth. Gene expression changes elicited by crosstalk between adipocytes and breast 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 4487.
Pressure Overload Induces Cardiac Hypertrophy in Angiotensin II Type 1A Receptor Knockout Mice
Authors: KoichiroHarada, IsseiKomuro, IchiroShiojima, DoubunHayashi, SumiyoKudoh, TakehikoMizuno, KazuhisaKijima, HiroakiMatsubara, TakeshiSugaya, KazuoMurakami, YoshioYazaki
Journal: Circulation (1998)

Background—Many studies have suggested that the renin-angiotensin system plays an important role in the development of pressure overload–induced cardiac hypertrophy. Moreover, it has been reported that pressure overload–induced cardiac hypertrophy is completely prevented by ACE inhibitors in vivo and that the stored angiotensin II (Ang II) is released from cardiac myocytes in response to mechanical stretch and induces cardiomyocyte hypertrophy through the Ang II type 1 receptor (AT1) in vitro. These results suggest that the AT1-mediated signaling is critical for the development of mechanical stress–induced cardiac hypertrophy. Methods and Results—To determine whether AT1-mediated signaling is indispensable for the development of pressure overload–induced cardiac hypertrophy, pressure overload was produced by constricting the abdominal aorta of AT1A knockout (KO) mice. Quantitative reverse transcriptase–polymerase chain reaction revealed that the cardiac AT1 (probably AT1B) mRNA levels in AT1A KO mice were...
Fine Structural Localization of Acetylcholinesterase at a Cholinergic Vasodilator Nerve-Arterial Smooth Muscle Synapse
Authors: Christopherbell
Journal: Circulation Research (1969)

An electron-microscope study of the localization of acetylcholinesterase (AChE) has been made in the main uterine artery of the guinea pig, which is supplied by cholinergic dilator and adrenergic constrictor nerves. Large bundles of nonterminal axons were present in the outer adventitia, and terminal axons, containing numerous vesicles, were scattered through the inner adventitia up to 1µ away from the outer layer of smooth muscle cells. About 50% of these axons were within 0.2µ of a muscle cell; the minimum neuromuscular gap found was 0.05µ. No axons were within the media. The outer membranes of axons stained either heavily or lightly for AChE. These two distinct classes appear to represent cholinergic and noncholinergic axons, respectively. In late pregnancy, all cholinergic terminal axons which contained vesicles and were not separated from the muscle by Schwann or elastic tissue were associated with heavy postsynaptic staining which was restricted to that region of the muscle membrane adjacent to the ...
Increased Ventricular Preload Is Compensated by Myocyte Proliferation in Normal and Hypoplastic Fetal Chick Left Ventricle
Authors: AngeladeAlmeida, TimMcQuinn, DavidSedmera
Journal: Circulation Research (2007)

Hemodynamics influence cardiac development, and alterations in blood flow may lead to impaired cardiac growth and malformations. The developing myocardium adapts to augmented workload by increasing cell number (hyperplasia). The aim of this study was to determine the influence of alterations in ventricular preload on fetal myocyte proliferation by manipulation of intracardiac shunting at the atrial level. We hypothesized that partial clipping of the right atrial appendage would increase the blood flow to the left ventricle and, in turn, lead to an increase in chamber volume and myocardial mass based on myocyte proliferation. Using an ex ovo culture setup, we performed partial right atrial clipping on embryonic day 8 chick embryos. Ultrasound imaging was performed before and after the surgery to assess the changes in left ventricular volume. Sampling after 24 hours was preceded by 2 hour of pulse-labeling with 5-bromodeoxyuridine. Ultrasound imaging showed that partial right atrial clipping led to a signif...
The clinical role of purified protein derivative skin test reaction in patients with non-muscle invasive bladder cancer treated with bacillus-Calmette Guerin.
Authors: Eiji Kikuchi, Naoya Niwa, Nozomi Hayakawa, Ryuichi Mizuno, Mototsugu Oya
Journal: Journal of Clinical Oncology (2017)

4545 Background: We investigated the association between purified protein derivative (PPD) skin test reaction prior to BCG therapy and clinical outcomes, both oncological outcomes and occurrence of side effects, in BCG-naïve non-muscle invasive bladder cancer (NMIBC) patients. Methods: A total of 288 NMIBC patients who received PPD skin test prior to BCG therapy were included. The PPD skin test reaction was categorized into three groups: positive, slightly positive, and negative. The presence of an induration was positive. If an induration was absent, an erythema 10 mm or more and less than 10 mm corresponds to slightly positive and negative, respectively. Results: Sixty-six (22.9%), 149 (51.7%), and 73 (25.3%) patients had positive, slightly positive, and negative PPD skin test results, respectively. The 5-year recurrence-free survival rate of patients with a positive PPD skin test was 89.4±4.1%, which was significantly higher than that of patients with slightly positive (65.5±4.2%, p = 0.001) and negative (56.4±6.6%, p &lt; 0.001) results. Multivariate Cox regression analysis demonstrated that a positive PPD skin test was independently associated with tumor recurrence (Hazard ratio of 0.213, p &lt; 0.001) but not with stage progression. The occurrence rate of major side effects in patients with a positive BCG skin test (33.3%) was significantly higher than that in patients with slightly positive (26.8%) and negative PPD skin tests (13.7%). The incidence rate of fever persisting beyond 2 days or fever of ≥38°C in patients with a positive PPD skin test (18.2%) was significantly higher than that in patients with slightly positive (8.7%) and negative PPD skin tests (4.1%). Conclusions: NMIBC patients with a positive PPD skin test and who were treated with BCG therapy had a significantly lower tumor recurrence rate and higher incidence of major side effects such as fever persisting beyond 2 days or fever of ≥38°C. Our findings suggest that PPD skin test prior to BCG therapy can predict clinical outcomes following BCG therapy and provide useful information regarding who would experience a strong therapeutic effect for BCG therapy and BCG-related major side effects.
Abstract 18999: The Effects of the Connexin40 Mutations P88S and G38A on Cardiac Physiology in the Intact Animal
Authors: Ajita Kanthan, Peter Fahmy, Renuka Rao, Eddy Kizana
Journal: Circulation (2012)

Introduction: Prior patch clamping studies have revealed that the somatic human connexin40 mutations P88S and G38A, identified within the atria of patients with atrial fibrillation (AF), are associated with reduced gap junction conductances when compared to wild type connexin40 (wtCX40). Our aim was to phenotype the rat heart following expression of these mutations by somatic gene transfer. Methods: A mix of pluronic F127, trypsin, and 10 7 vector genomes of lentivirus was painted onto the left atrium of adult Sprague-Dawley rats via a left thoracotomy. Rats were randomised to receive lentivirus containing a transgene encoding either wtCX40, P88S, G38A or eGFP. Electrophysiology studies (EPS) consisting of surface and trans-oesophageal electrocardiograms (ECG) were performed under anaesthesia just prior to and 7 days after surgery. Following day 7 EPS, atria were excised, sectioned, and examined histologically with Sirius Red and Haematoxylin and Eosin. Data are expressed as means ± standard deviations. Results: At day 7, eGFP expression revealed approximately 5% heterogeneous atrial transduction. Rats transduced to express either P88S or G38A possessed significantly longer mean P wave durations and AF when compared to eGFP controls as shown in the table. There were no significant differences in all other characteristics. Conclusion: The human somatic connexin40 mutations P88S and G38A slow atrial conduction as evidenced by prolonged P wave durations at day 7. In addition, heterogonous expression of P88S and G38A within the atrial myocardium increases the propensity for inducible atrial fibrillation.
High-dose ifosfamide (HDI) in metastatic synovial sarcoma: The Institut Gustave Roussy experience.
Authors: Arslane Skander Rahal, Angela Cioffi, Chahinez Rahal, Julien Domont, Aurore Blesius, Anna Patrikidou, Sylvie Bonvalot, Cécile Le Pechoux, Philippe Terrier, Laurence Vilcot, Emilie Lanoy, Axel Le Cesne
Journal: Journal of Clinical Oncology (2012)

10044 Background: Synovial sarcoma (SS) is one of the most chemo-sensitive histological subtypes of sarcoma but with a dismal prognosis. In metastatic setting, Anthracyclin/ifosfamide-containing chemotherapy (CT) regimen is the gold standard of treatment in front-line therapy. Patients (pts) with resistant diseases are candidates to investigational drugs or higher dose ifosfamide regimen in selected pts. Methods: Pts treated in our institution, with histological confirmation of advanced SS, adequate organ function and in good condition (PS≤2) were included in this retrospective analysis. Pts who progressed after 1–2 chemotherapy lines received High-dose ifosfamide (HDI) in the form of 4 g/m 2 daily (over 24 hours CI) for 3 days for a total dose of 12 g/m 2 ; cycles were given with growth factor support and were repeated every 3 weeks. The primary endpoints were PFS and overall response rate (ORR); the secondary endpoints OS and toxicity profile. AE were assessed by NCI-CTC v. 3.0. Results: 34 pts (21 males) with a median age of 39 years (range 19-66) received this HDI regimen. PS was 0-1 in 90%. 95% of pts received prior doxorubicin, ifosfamide or both, 7 patients had 2 prior lines. Grade III monophasic pattern was seen in 21 patients, grade II in 13. 171 cycles were delivered, median number of cycles was 4 (2-10). The objective responses were CR 0; PR 15; SD 14; PD 2; and NE 3, resulting in an ORR of 44%. The clinical benefit rate was 85%. Median PFS: 11.6 months (95% CI: 9-14). Eleven pts were amenable to a subsequent resection of residual disease. Common adverse events included grade III/IV neutropenia: 47%, febrile neutropenia: 12%, thrombocytopenia: 12%, cystitis: 3%, neurologic: 3%. There was no treatment related death. Conclusions: HDI demonstrated clinically meaningful efficacy with manageable toxicity in pts who failed previous standard Ifosfamide dose. Ifosfamide remains the most active agents in SS and high dose regimen have to be considered in pts previously treated with ifosfamide.
Respiratory Sinus Arrhythmia
Authors: JunichiroHayano, FumihikoYasuma, AkiyoshiOkada, SeijiMukai, TakaoFujinami
Journal: Circulation (1996)

Background The primary mechanisms of respiratory sinus arrhythmia (RSA) are understood to be the modulation of cardiac vagal efferent activity by the central respiratory drive and the lung inflation reflex, and the degree of RSA increases with cardiac vagal activity. However, it is unclear whether RSA serves an active physiological role or merely reflects a passive cardiovascular response to respiratory input. We hypothesized that RSA benefits pulmonary gas exchange by matching perfusion to ventilation within each respiratory cycle. Methods and Results In seven anesthetized dogs, a model simulating RSA was made. After elimination of endogenous autonomic activities, respiration-linked heartbeat fluctuations were generated by electrical stimulation of the right cervical vagus during negative pressure ventilation produced by phrenic nerve stimulation (diaphragm pacing). The vagal stimulation was performed in three conditions: phasic stimulation during expiration (artificial RSA) and during inspiration (inver...
Abstract 14962: Weekend versus Weekday Admission and Morality from Acute Coronary Syndrome
Authors: MahdiKhoshchehreh, ElliottGroves, ShaistaMalik
Journal: Circulation (2014)

Introduction: ACS is a common condition requiring urgent diagnosis and intervention. Previous smaller studies show poor outcomes for time-sensitive medical conditions during weekend admissions, however whether these associations persist is not known. Hypothesis: We assessed in-hospital mortality and utilization of invasive cardiac procedures following acute coronary syndrome (ACS) admissions on the weekend versus weekdays in the United States. Methods: We used the 2009 Nationwide Inpatient Sample to examine differences in all-cause in-hospital mortality between weekend versus weekday admitted patients with a principal diagnosis of ACS. Adjusted logistic regression and hierarchical logistic regression analyses were used to identify if weekend admission was associated with decreased utilization of procedural intervention and increased subsequent complications as well. Results: We identified 1054674 ACS admissions of which 22.1% were weekend admissions. Adjusted mortality for patients with NSTEMI was higher ...
Abstract 5543: Low ATM expression is associated with improved progression-free and overall survival in advanced gastric cancer patients treated with platinum-based chemotherapy
Authors: Munveer S. Bhangoo, Hubert Y. Luu, Seung Tae Kim, Jeeyun Lee, Joseph Chao, Samuel J. Klempner
Journal: Cancer Research (2018)

Abstract Introduction: Platinum-based combination chemotherapy regimens represent standard approaches for locally advanced and metastatic gastric adenocarcinoma. Ataxia-teleangiectasia mutated protein (ATM) plays a critical role in repairing DNA damage to double-stand breaks. Tumors deficient in ATM (defined as pathologic loss measured by IHC) are hypothesized to demonstrate increased susceptibility platinum chemotherapy. Methods: We retrospectively reviewed patients from a single center (Samsung Medical Center, Seoul, South Korea) with advanced, unresectable gastric cancer (stage 3b or higher) receiving capecitabine/oxaliplatin (XELOX) from 2013-2017. Clinicopathologic data, treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed according to level of ATM expression by immunohistochemistry (IHC). Low-expression of ATM was defined as greater than 50% loss by IHC. Two-tailed, unpaired t-tests and Fisher's exact tests were used to compare outcomes between patients with preserved ATM versus low ATM expression. Kaplan-Meier survival analysis was used to compare disease-free survival and overall survival; the log-rank test was used to determine statistical significance. Results: During the study period, 138 patients underwent treatment with XELOX for a diagnosis of advanced gastric cancer. Median (IQR) follow-up time was 11.8 mo. (6.8-17.3). Between patients with ATMintact or ATMlow, there were no significant differences in mean age, sex, final pathologic diagnosis, or mean number of cycles of chemotherapy received. Kaplan-Meier analysis demonstrated that patients with ATM low were associated with a longer PFS (ATMlow 14.9 mo versus ATMintact 6.8 mo.) (HR 0.24, [0.18-0.34, 95% CI], p&amp;lt;0.0001), and longer OS (ATMlow 30.0 mo. versus ATMintact 14.7) (HR 0.23, [0.17-0.33, 95% CI], p&amp;lt;0.0001). There was no difference in response rates between the two groups. Conclusions: This retrospective, case-control study in patients with advanced gastric cancer shows improved survival in patients with ATMlow tumors compared with ATMintact tumors after treatment with platinum-based chemotherapy. Findings are suggestive and require prospective validation in cohorts of patients with ATMlow/ATMintact tumors. Citation Format: Munveer S. Bhangoo, Hubert Y. Luu, Seung Tae Kim, Jeeyun Lee, Joseph Chao, Samuel J. Klempner. Low ATM expression is associated with improved progression-free and overall survival in advanced gastric cancer patients treated with platinum-based 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 5543.
Proton therapy for adults with mediastinal lymphomas: the International Lymphoma Radiation Oncology Group guidelines
Authors: Bouthaina Shbib Dabaja, Bradford S. Hoppe, John P. Plastaras, Wayne Newhauser, Katerina Rosolova, Stella Flampouri, Radhe Mohan, N. George Mikhaeel, Youlia Kirova, Lena Specht, Joachim Yahalom
Journal: Blood (2018)