tbuckley/cabot-search huggingface dataset:
Abstract 1368: Simultaneous cell-free RNA PD-L1 expression and MSI from the same single-tube of blood in solid tumors
Authors: Glen J. Weiss, Paul Walker, Dilek Aktas, Andrew Ford, Charmaine Brown, Chen-Hsiung Yeh, Nader Javadi
Journal: Cancer Research (2019)

Abstract Background: Liquid biopsy is a minimally invasive technique available in the clinic using next-generation sequencing (NGS) of plasma circulating cell-free DNA (cfDNA) and cfRNA. Here we report liquid biopsy results from solid tumors using the Circulogene Theranostics Personalized Gene Profile (CGP, 50-gene panel), as well as, microsatellite instability (MSI) testing. CGP uses proprietary in situ enrichment requiring minimal input volume of 20 uL plasma (cfDNA), 400 uL (cfRNA), and 100 uL buffy coat per case from the same single-tube of blood. Methods: cfRNA PD-L1 expression, MSI, and co-occurring cfDNA mutations were retrospectively compiled from CGP ordered at multiple centers. Ct value cutoff for 1 copy PD-L1 (positive) was 42. MSI was performed using paired buffy coat gDNA (normal) and plasma cfDNA (tumor) on 5 microsatellite mononucleotide markers, BAT-25, BAT-26, NR-21, NR-24 and MONO-27 (Promega; current an industry standard that has been used in KEYNOTE pembrolizumab trials) and analyzed by capillary electrophoresis genetic analyzer. Based on batched processing, Circulogene’s turnaround time (TAT) is 5 business days on average. Data was summarized and the correlation between PD-L1 and MSI was measured. Results: 397 patients (median age 67 years, range 27-96; 210 men: 187 women) underwent CGP testing for both PD-L1 and MSI (11/2017-10/2018). The majority of cancer types were lung (n=187), colorectal (n=43), breast (n=40), pancreatic (n=32), and prostate (n=30). 59/397 (14.9%) were PD-L1 positive, in the range of expected PD-L1 positivity across solid tumors. 110/397 (27.7%) were MSI-High (MSI-H). There was no correlation between PD-L1 and MSI results (r^2 &amp;lt;0.01). There was a median of 3 mutations/patient (range 0-19), with a 0% sample failure rate. Overall, 23 cases had no detectable mutations (5.8%), but 11 of these 23 (47.8%) had either PD-L1 positivity or MSI-H. Conclusions: Simultaneous cfRNA PD-L1 and MSI testing from the same single-tube blood is feasible in a liquid biopsy and their positivity has frequency in the expected range for solid tumors (Xang et al. Onco Targets Ther 2016, Zhang et al. AMP Conference 2018, Abstract ST009). Despite the low plasma sample input, there were no sample failures, suggesting CGP in situ enrichment is robust and has a rapid TAT. Assay results with linkage to clinical outcomes is warranted. Citation Format: Glen J. Weiss, Paul Walker, Dilek Aktas, Andrew Ford, Charmaine Brown, Chen-Hsiung Yeh, Nader Javadi. Simultaneous cell-free RNA PD-L1 expression and MSI from the same single-tube of blood in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1368.
Abstract 1456: MEDI5395: A recombinant oncolytic virus with oncolytic and immune modulatory properties
Authors: James A. Harper, Shannon Burke, Andrew Leinster, Nicola Rath, Xing Cheng, Hong Jin, Robert W. Wilkinson, Danielle Carroll
Journal: Cancer Research (2019)

Abstract MEDI5395 is a genetically modified attenuated Newcastle disease virus (NDV). A reverse genetic system has overcome environmental and regulatory concerns by uncoupling oncolytic potency from avian pathogenicity. MEDI5395 has the intrinsic ability to infect and kill tumor cells and has been inserted with a GM-CSF transgene to potentiate a stronger adaptive immune response. Described here is an extensive in vitro and in vivo pharmacology package that reveals the broad oncolytic activity and immune-modulatory properties of MEDI5395 in a variety of pre-clinical models. In vitro, MEDI5395 lytic activity in human tumor cells is associated with elevated levels of tumor selective viral replication and expression of the GM-CSF transgene. MEDI5395 infection of immune cells indicated preferential uptake of virus and subsequent self-limiting replication in myeloid cells. Infected myeloid cells expressed cell surface activation markers (e.g. PD-L1) after 24 hours and were effective carriers of virus and mediated the transfer of infectious NDV particles to tumor cells resulting in death through oncolysis. Further mechanistic studies, indicated NDV-killed tumor cells released antigens that were capable of cross-presentation by dendritic cells driving activation of tumor antigen-specific autologous T cells. In murine models, IV delivery of NDV leads to long lasting tumor selective replication and transgene expression. MEDI5395 administration results in significant anti-tumor activity, observed in patient-derived xenograft models, and in murine syngeneic cancer models. Together, the results suggest that MEDI5395 may act to positively transform the tumor microenvironment. This, coupled to its tumor-selective oncolytic capacity, further underscore NDV as a promising multimodal cancer therapeutic platform and why FTIH studies are planned to start in 2019. Citation Format: James A. Harper, Shannon Burke, Andrew Leinster, Nicola Rath, Xing Cheng, Hong Jin, Robert W. Wilkinson, Danielle Carroll. MEDI5395: A recombinant oncolytic virus with oncolytic and immune modulatory properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1456.
Post-traumatic toe deformity in a child
Authors: Tun Hing Lui
Journal: BMJ (2019)

A 5 year old boy experienced pain in the little toe of his right foot after falling down the last two steps of a flight of stairs.

Initially the diagnosis was a “sprained toe.” No radiograph was taken at that time.

Five days later he was referred to orthopaedics because the pain was persisting. On examination, the toe was tender and swollen with subtle lateral deviation, but circulation and sensation were intact. Radiography was …
Abstract 19812: Temporal Discordance of Atrial Fibrillation Burden With Major Bleeding and Intracranial Hemorrhage: Implications for Oral Anticoagulation Therapy
Authors: Mariam Askari, Paul D Ziegler, Jun Fan, Susan K Schmitt, Mintu P Turakhia
Journal: Circulation (2016)

Introduction: In atrial fibrillation (AF), oral anticoagulation, which is taken daily without regard to pattern or presence of AF, categorically increases risk of major bleeding and intracranial he...
Abstract 3942: Animal studies evaluating the safety of Tumor Treating Fields (TTFields) in the torso
Authors: Shiri Davidi, Mijal Munster, Shay Cahal, Moshe Giladi, Eilon D. Kirson, Uri Weinberg, Yoram Palti
Journal: Cancer Research (2019)

Abstract TTFields therapy is an anti-neoplastic treatment modality targeting dividing cells by disrupting microtubules and septin filaments localization. TTFields therapy received FDA approval for the treatment of glioblastoma based on phase 3 studies demonstrating efficacy and high safety profile. TTFields are currently being tested as a treatment option for solid tumors in the torso. The aim of this work is to study whether TTFields’ safety profile is maintained in the torso, and specifically in tissues with high cellular proliferation rates. TTFields (2-3 V/cm) were applied for 2 weeks using the Novo-TTF 100 system to the rat torso at 150 and 200 kHz, intensities and frequencies known to be effective for the treatment of NSCLC, mesothelioma, pancreatic cancer, ovarian cancer and hepatocellular carcinoma. Throughout the treatment course, all animals underwent daily clinical examination by a certified experienced veterinarian. At the end of treatment, animal were euthanized and an experienced independent pathologist performed histological comparative evaluation of all major internal organs. No changes in the following parameters were observed: activity level, food intake, drinking, stools, motor neurological status and respiration. Further, no changes in weight were observed between the treated and control groups. No significant changes were observed in complete blood count and differential between the different groups. Histological analysis did not reveal any increase in pathological findings in the TTFields treated animals group. Taken together, these results demonstrate that safety of TTFields application at frequencies of 150-200 kHz to the rat torso and specifically to tissues with high cellular proliferation rates. Additional work is now underway to better understand the specificity of TTFields’ effects on rapidly dividing tumor cells. Citation Format: Shiri Davidi, Mijal Munster, Shay Cahal, Moshe Giladi, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Animal studies evaluating the safety of Tumor Treating Fields (TTFields) in the torso [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3942.
Abstract P86: The Aed Enlightenment Animation Dvd Motivates Schoolchildren to Learn about Cardiopulmonary Resuscitation and Aed
Authors: Atsuko Nagatani, Kazunori Yamashita, Tetsuya Sakamoto, Naoki Shimizu, Tetsuo Hatanaka, Seishiro Marukawa
Journal: Circulation (2008)

We developed the AED enlightenment animation DVD (the AED Animation) as a readable and friendly educational material for learning cardiopulmonary resuscitation (CPR) and AED by citizens. The aim of the present study was to investigate how well did schoolchildren understand the contents of the AED Animation, and how the AED Animation has educational and ripple effects to schoolchildren. [Methods] Prior to the investigation of schoolchildren, 28 elementary school teachers watched the AED Animation and answered a questionnaire to see if the AED animation arouse schoolchildren, and to evaluate its psychological and educational impacts. Then in fourth, fifthand sixth grades elementary school students (total of 1189) watched the AED Animation and answered questionnaire-based survey. [Results] 94 percent of the students answered “ the AED Animation is good for me”, 80 percent of them wanted to be able to do CPR and use AED as the characters of the AED Animation did, and 67 percent of them wanted there parents to watch the AED Animation. [Conclusions] The AED Animation is a good educational material for schoolchildren that raises interest in AED/CPR, and its educational effects was more than elementary school teachers expected.
Abstract 2453: A new deconvolution algorithm for accurate assessing immune and stromal cell populations in mouse transcriptomic data
Authors: Xiaoyu Lu, Szu-wei Tu, Wennan Chang, Yan Huo, Pengcheng Wang, Yu Zhang, Chi Zhang, Sha Cao
Journal: Cancer Research (2019)

Abstract Multiple deconvolution methods have been developed for investigating the heterogeneous immune and stromal (I/S) cell types in human cancer tissue by deciphering their relative abundances using transcriptomic data. However, there is a lack of a user-friendly software for mouse transcriptomic data deconvolution. Key challenges for developing such a tool include: (1) limited training data sets for available for deriving signature genes of I/S cell types in sporadic mouse data; (2) mouse models of diverse geno-/pheno-types may have varied expressions of I/S cell marker genes; (3) the transcriptomic data may be collected from mouse with certain levels of immuno-deficiency; and (4) the transcriptomic data may come from highly diverse experimental platforms. To solve these challenges, we (i) developed a novel non-parametric analysis method to derive potential I/S cell signature genes from a large collection of mouse data sets; (ii) implemented a low rank sub matrix identification method with a non-negative matrix factorization (NMF) based deconvolution method; and (iii) enabled the flexibility that certain I/S cell types may be absent if their respective cell markers do not form a significant low rank structure. The new method is applied to mouse prostate cancer data sets to infer the level of anti-cancer immune cell populations. Genes expressed by cancer cells that are negatively associated with the anti-cancer immune cells are further inferred, and compared with the results derived in human data. A user-friendly R package of the deconvolution method is released through GitHub. Citation Format: Xiaoyu Lu, Szu-wei Tu, Wennan Chang, Yan Huo, Pengcheng Wang, Yu Zhang, Chi Zhang, Sha Cao. A new deconvolution algorithm for accurate assessing immune and stromal cell populations in mouse transcriptomic data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2453.
Antibiotic exposure and risk of breast cancer: A causal association or a skyfall?
Authors: Anna Koumarianou, Efrosyni D Manali, Archontoula Fragou, Panagiotis Katsaounis, Georgia Bouga, Sofia Karageorgopoulou, Marianna Christodoulou, Nikos Pantazis, George Athanasas, Nikos Arkadopoulos, Christina Tsionou, Spyros Papiris, Nikolaos Xiros, Anastasia Antoniadou, Helen Giamarellou
Journal: Journal of Clinical Oncology (2013)

e12524 Background: Although it has long been hypothesized that the use of antibiotics may increase the risk of breast cancer, through effects on inflammation, immunity and gastrointestinal microflora that alter the metabolism of phytochemicals, clinical data on this association are sparse. Methods: Matched case-control study among 158 women with newly diagnosed primary invasive breast cancer from a single cancer unit and 158 age-matched controls (± 12 months) from healthy individuals accompanying patients to the outpatient clinics between January 1, 2006 and December 30, 2007. Clinical examination and a standard questionnaire for the collection of baseline characteristics and known aggravating factors, such as body mass index, smoking, age of menarche and menopause, parity, breastfeeding, history of respiratory, urinary or other infections and previous estrogen use, were carried out in all individuals. All antibiotic classes, such as β-lactams, amoxyl and clavulanic acid, cephalosporins, macrolides, quinolones, tetracyclines, trimethoprim, clindamycin and imidazoles, were recorded. Type of antibiotic and dose was ascertained from health insurance’s pharmacy records. Data were analyzed using multivariable conditional logistic regression models including adjustments for potential confounding factors. Results: The age matched groups of patients and controls were found to have statistically significant differences in the considered parameters such as delayed age of menopause, less parity and less smoking in the control group and more antibiotic intake in the patient population. The cumulative use for more than 21 days of any antibiotic classes were found to statistically significant correlate with increased risk of breast cancer [odds ratio(OR):3.5, 95%confidence interval(CI):1.7-7.3, p=0.001]. By subanalyses according to antibiotic class this increased risk was mainly associated with β-lactams (OR:11.4, 95%CI:3.8, 34.1, p&lt;0.001) and less with macrolides (OR:2.8, 95%CI:1.1-7.5, p=0.039). Conclusions: Our study links β-lactam and macrolide consumption with increased breast cancer risk but further investigation of this association in large cohorts together with exploration of the underlying cause are needed.
Abstract 16851: Estradiol-Treated Cardiac Stem Cells Improve Myocardial Recovery Following Acute Ischemia/Reperfusion Through Enhanced Paracrine Protection
Authors: Chunyan Huang, Hongmei Gu, Mariuxi Manukyan, Meijing Wang
Journal: Circulation (2011)

INTRODUCTION: Cardiac stem cells (CSC) mediate cardioprotection following ischemia. However, prior research has mainly focused on studying differentiation capacities of CSC. Little is known about implication of paracrine action by CSC in protection of the ischemic heart. On the other hand, our group and others have shown that non-cardiac stem cells mediate their beneficial effects primarily via paracrine action and estrogen is implicated in promoting this stem cell-mediated protection. In this study, therefore, we hypothesized that 1) CSC are able to acutely improve cardiac function without cell differentiation following ischemia/reperfusion (I/R) and 2) 17β-estradiol (E2)-treated CSC provide greater protection of cardiac function. METHOD: CSC were isolated from C57BL mouse hearts, and identified by flow cytometry and mRNA-qPCR. Cardiac I/R was performed in isolated mouse hearts via Langendorff. 0.1x10^6/ml CSC or E2-treated CSC (CSC treated with 100nM of E2 for 24-hr) were infused immediately prior to ischemia. Secretion of VEGF, HGF and SDF-1 by CSC and E2-treated CSC was assessed using ELISA. Hypoxia-induced myocyte injury was detected by LDH assay. Data were analyzed with two-way ANOVA or t-test, p&lt;0.05=statistically significant. RESULTS: Flow cytometry data revealed that CSC expressed Sca-1, CD29 and CD44 (all &gt;90%), but did not express CD31, CD34, CD45 or CD106 (all &lt;5%). Cardiac specific transcription factors NKX2.5, Gata4, MEF2c and Tbx5 were detected in CSC. E2-treated CSC produced higher levels of VEGF, HGF and SDF-1 compared to untreated CSC. Infusion of CSC and E2-treated CSC improved myocardial function following acute I/R with greater protection in E2-treated CSC group (graph). CONCLUSION: Pretreatment of CSC acutely improved I/R-injured cardiac function and myocyte viability through paracrine action. E2-treated CSC may enhance this paracrine protection, suggesting that in vitro modification of CSC may improve therapeutic outcome.
Abstract 1868: B-125, a novel berberine derivative, acts as a better retinoid X receptor a agonist with stronger anti-tumor activity in colon cancer
Authors: Beibei Xu, Tian hui Hu, jing Xiong
Journal: Cancer Research (2019)

Abstract Our previous study showed that Berberine binds to RXRα to suppress colon cancer growth (Ruan et. al., Oncogene 2017, 36: 6906). To achieve better RXRα binding activity, stronger anti-tumor effect and higher bioavailability, 21 novel berberine derivatives were designed based on the binding information of berberine to RXRα. Among them B-125 performs the best solubility, RXRE luciferase activity and tumor suppressing ability. NMR and fluorescent titration results show that B-125 retain the similar binding ability to RXRα compared with Berberine. CD study suggests that B-125 has stronger allosteric effect on RXRα than berberine. The bioavailability of B-125 is 25 times higher than berberine. In KM12C colon cancer cells, B-125 performs stronger RXRα dependent inhibitory effects than berberine. In vivo results showed that B-125 inhibits the growth of colon cancer xenograft in nude mice, and the effect is stronger than that of berberine. All the above results indicate that B-125 is a better anti-cancer drug than berberine with better RXRα modulation ability, higher bioavailability and stronger tumor suppressing effect. The study promotes B-125 as a potential novel RXRα based anti-cancer drug in the treatment of colon cancer. Note: This abstract was not presented at the meeting. Citation Format: Beibei Xu, Tian hui Hu, jing Xiong. B-125, a novel berberine derivative, acts as a better retinoid X receptor a agonist with stronger anti-tumor activity in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1868.
Diagnostic value of FDG-PET/CT for peritoneal carcinomatosis (PC) before hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer.
Authors: Micheline Razzouk-Cadet, Colette Zwarthoed, Mariangela Desantis, Philippe Viau, Abakar Mahamat, Nicolas Mounier, Jean Marc Bereder
Journal: Journal of Clinical Oncology (2012)

e15574 Background: Evaluate FDG-PET/CT utility for the detection of peritoneal carcinomatosis from ovarian cancer treated by chemotherapy by using surgical and histopathological findings as the standard of reference. Methods: 38 patients (46 to 68 years) with recurrent (n=35) or primary (n=3) ovarian cancer were reviewed for the presence of peritoneal lesions on FDG-PET/CT before cytoreductive surgery and HIPEC treatment. 30 had adenocarcinomas (13 papillary serous, 7 moderately differenciated, 6 poorly differentiated, 3 serous and 1 serous cystadenocarcinoma) and 2 endometrioid tumors. 9 had psammomatous calcifications. All were suspected cases of PC. 35 patients had received adjuvant chemotherapy and 3 neoadjuvant chemotherapy (primary cancer). FDG-PET/CT results were reinterpreted by two experienced nuclear medicine physicians who knew that PC was suspected. The FDG uptake was determined as SUVmax in the most active lesion in all abdomino-pelvic quadrants (average SUVmax= 6.1; range 1.1- 25). SUVmax in the liver was also measured (average SUVmax=2.9). All PET/CT exams were realised on the same machine. Results: FDG PET/CT diagnosed 18 in 32 patients with peritoneal metastases. There was no suspicious site of abnormal FGD uptake in the supradiaphragmatic regions. The sensitivity, specificity and accuracy of FDG PET/CT were respectively 59,100, 66% . The positive and negative predictive value of FDG PET/CT were 100 and 31%. 13 false negative PET/CT findings were due to millimetric or infracentimetric perihepatic, mesenteric and omental implants (unseen on PET/CT) and to nodules less than one centimeter with no significant FDG uptake (SUVmax lower than hepatic uptake). The true negative findings were found after chemotherapy. Conclusions: FDG-PET/CT can be considered as a useful tool for the selection of patients for HIPEC treatment in the absence of distant metastasis. It showed excellent results for the positive diagnosis and tumor burden for lesions more than 1 cm (PPV 100%). The sensitivity was low in the presence of millimetric disease with or without prior chemotherapy before HIPEC.
Abstract 18264: Membrane Repair by Poloxamer 188 Protects Isolated Cardiac Cells From Hypoxia/Reoxygenation Injury
Authors: Michele M Salzman, Frank S Bates, Benjamin J Hackel, Jason A Bartos, Demetris Yannopoulos, Matthias L Riess
Journal: Circulation (2017)

Introduction: Many patients who experience a cardiac arrest still die or suffer severe cardiac damage, even when the best CPR is delivered. Reintroduction of blood flow at the start of CPR may caus...