tbuckley/cabot-search huggingface dataset:
Calcium and zinc tune autoinflammatory Toll-like receptor 4 signaling by S100A12
Authors: Christoph Kessel, Sabrina Fuehner, Jana Zell, Bastian Zimmermann, Stephan Drewianka, Sonja Brockmeyer, Dirk Holzinger, Claas Hinze, Helmut Wittkowski, Dirk Foell
Journal: Journal of Allergy and Clinical Immunology (2018)
Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome
Authors: Claire E McKinley, Stephen John Richards, Talha Munir, Morag Griffin, Lindsay D Mitchell, Louise Arnold, Kathryn Riley, Nicola Copeland, Darren J Newton, Anita Hill, Peter Hillmen
Journal: Blood (2017)
Abstract 19839: Elevated ST2 is Associated With More Extensive Atrial Remodeling and Longer Ablation Procedure Duration in Patients With Atrial Fibrillation and Flutter
Authors: Jacqueline Denysiak, David E Krummen, Paula Anzenberg, Jonathan C Hsu, Lori B Daniels
Journal: Circulation (2016)

Introduction: ST2 is a biomarker associated with an increased risk of ventricular arrhythmias, however its predictive role in patients with atrial arrhythmias remains unclear. Hypothesis: We hypoth...
Antiretroviral Therapy for Prevention of HIV Transmission in HIV-Discordant Couples
Authors: Andrew Anglemyer, Tara Horvath, George Rutherford
Journal: JAMA (2013)

<h3>Clinical Question</h3> Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? <h3>Bottom Line</h3> Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.
Abstract 3175: Sulfated glycopeptide nanostructures activate and extend bone morphogenetic protein 4 ability to increase pediatric malignant glioma chemotherapeutic efficacy
Authors: Guifa Xi, Benjamin Best, Sonali Nayak, Mark McClendon, Barbara Mania-Farnell, John Kessler, Charles David James, Samuel Stupp, Tadanori Tomita
Journal: Cancer Research (2018)

Abstract Pediatric gliomas, particularly high-grade gliomas, are among the most formidable and devastating cancers in children. These tumors have remained incurable, regardless of the many treatment approaches attempted. We recently identified a small population of glioma cells with stem-like features in pediatric gliomas (glioma stem cells: GSCs), that may be responsible, for therapeutic resistance in pediatric gliomas. Signaling by bone morphogenetic protein 4 (BMP4), an essential molecule for central nervous system (CNS) development, increases GSC therapeutic sensitivity, and whose activation is a promising adjuvant for glioma treatment. Mechanisms through which BMP4 increases therapeutic sensitivity need to be elucidated as this can lead to the identification of additional targets for treating malignant gliomas in children. Delivery systems for administering BMP4 in a clinical setting also need to be developed. Here, we show that BMP4 increases chemosensitivity by decreasing H3 lysine 4 trimethylation (H3K4me3) at the promoter of multidrug resistant gene 1 (MDR1) that, in turn, results in increased BMP4 expression. This appears to be the result of BMP4 decreasing levels of hSETD1A, a critical methyltransferase for H3K4me3. Our work also demonstrates the first use of a novel sulfated glycopeptide (glycol-PA) nanostructure as a vector for delivery of BMP4. Glycol-PA markedly extended and enhanced BMP4 function, and increased chemotherapeutic anti-tumor activity against pediatric malignant glioma cells in culture. Overall, our results expand understanding of how BMP4 brings about glioma therapeutic sensitization through epigenetic mechanisms, and show that highly bioactive glyco-PA nanostructures have potential as a novel delivery mechanism for treating pediatric malignant glioma, as well as other tumors. Citation Format: Guifa Xi, Benjamin Best, Sonali Nayak, Mark McClendon, Barbara Mania-Farnell, John Kessler, Charles David James, Samuel Stupp, Tadanori Tomita. Sulfated glycopeptide nanostructures activate and extend bone morphogenetic protein 4 ability to increase pediatric malignant glioma chemotherapeutic efficacy [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 3175.
Abstract 2701: Proteogenomic analysis of endoscopy biopsy identifies alterations in apoptotic pathways in trastuzumab-resistant gastric cancers
Authors: Jeong Won Kang, Il Ju Choi, Hark Kyun Kim
Journal: Cancer Research (2018)

Abstract Although the combination of trastuzumab with cisplatin and fluoropyrimidine is standard therapy for metastatic HER2-positive gastric cancers, predictive biomarkers for this therapy need to be further refined. Given the multifactorial nature of clinical trastuzumab resistance, we performed nano-liquid chromatography (LC)-tandem mass spectrometry (MS/MS) proteomic analyses on 13 pairs of frozen HER2-positive tumors and adjacent normal tissue counterparts collected from patients who were treated with trastuzumab in combination with cisplatin and fluoropyrimidine (TCF). We quantified &amp;gt;6,000 protein groups per tumor on the average, and this number was almost comparable to those obtained by NCI's Clinical Proteomic Tumor Analysis Consortium projects, which characterized resected tumors using similar nano-LC-MS/MS technologies. Nano-LC-MS/MS data for differentially expressed proteins were successfully validated by our immunostaining analyses. When we correlated proteomic data with clinical outcome, underexpression of apoptosis pathway proteins was the prominent proteomic signature in TCF-resistant tumors, as compared with TCF-sensitive tumors. Proapoptotic proteins in FAS signaling and mitochondrial apoptosis pathways were less abundant in TCF-resistant tumors than in sensitive tumors. When iTRAQ reporter ion ratios were compared between pretreatment and acquired-resistant tumors from clinical responders, apoptosis pathways were significantly enriched in proteins that were overexpressed in the acquired-resistant tumors. Assuming that the pretreatment tumors of clinical responders were mostly composed of chemosensitive clones, these antiapoptotic proteins may confer survival advantage on resistant clones, resulting in the repopulation of resistant clones overexpressing these antiapoptotic proteins. For the first time to our knowledge, therefore, our proteogenomic study of frozen endoscopic biopsy samples revealed that alterations in apoptotic pathway proteins were most significantly associated with clinical trastuzumab resistance. Our study is also the first to demonstrate that nano-LC-MS/MS technology can be applied to small biopsy tissue samples for precision medicine research. Citation Format: Jeong Won Kang, Il Ju Choi, Hark Kyun Kim. Proteogenomic analysis of endoscopy biopsy identifies alterations in apoptotic pathways in trastuzumab-resistant gastric cancers [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 2701.
Abstract 4930: Epicatechin alleviates DOX-induced cardiovascular toxicity and improves its cytotoxic profile against breast cancer cells
Authors: Ohoud Y. Alshehri, Fahad A. Alabbasi, Islam F. Mahmoud, Alaa T. Abu-Sharib, Hany M. El-Bassossy, Hossam A. Abdallah, Ahmed M. Al-Abd
Journal: Cancer Research (2018)

Abstract Epicatechin (EPI) has a well known and robust antioxidant properties which could alleviate drug-induced cardiovascular toxicities. On the other side, Doxorubicin (DOX) is a cornerstone anticancer drug used to treat breast cancer. However, DOX-induced cardiovascular complications might limit its treatment course continuation. Herein, we evaluated cardiovascular protective effects of EPI against DOX in-vivo and ex-vivo using isolated aortic ring preparation; meanwhile we assessed the potential ameliorating effects of EPI against DOX-induced cytotoxicity in breast cancer cells. Animals were given DOX (12 mg/kg, single IV injection) which induced cardiac ischemia appeared as increased QT and QTc intervals (1.8 folds for both). EPI (12 mg/kg, orally for 6 days) completely aborted DOX-induced cardiac ischemia and corrected all ECG abnormalities. Using isolated aortic ring preparation, DOX (10µM) impaired aortic ring vasodilatation and induced excessive vasoconstriction. Co-incubation of EPI (10µM) with DOX (10µM) entirely blocked DOX-induced impaired aortic ring vasodilatation, without affecting DOX-induced elevated vasoconstriction. EPI (10µM) combination with DOX in MDA-MB-231, MCF7 and T47D breast cancer cells significantly decreased the IC50‘s from 70.0±17.3 to 44.0±14.0 nM, from 554.0±30 to 240.0±10.0 nM and from 700.0±36.0 to 561.0±170 nM, respectively. Under hypoxic condition, EPI (10µM) significantly increased DOX cytotoxicity against MCF-7 cells and decreased its IC50 from 8.9±1.2 to 6.1±1.9 μM. This effect could be partially attributed to the inhibitory effect of EPI to P-glycoprotein (P-gp) and related efflux protein which would enhance DOX intracellular concentration. EPI increased the intracellular accumulation of rhodamine (P-gp probe) within MDA-MB-231 cells by 3-4 folds at concentration range from 3 to 100 μM. Moreover, EPI combination with DOX significantly increased cell apoptosis and necrosis assessed by annexin-V/FITC. However, EPI did not influence DOX effect on cell cycle distribution. In conclusion, EPI possesses potential cardiovascular protective effects against DOX. Meanwhile, EPI does not interfere with DOX-induced cytotoxic profile against breast cancer cells. Citation Format: Ohoud Y. Alshehri, Fahad A. Alabbasi, Islam F. Mahmoud, Alaa T. Abu-Sharib, Hany M. El-Bassossy, Hossam A. Abdallah, Ahmed M. Al-Abd. Epicatechin alleviates DOX-induced cardiovascular toxicity and improves its cytotoxic profile against 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 4930.
Abstract 3962: Antitumor effects of the antiparasitic agent ivermectin via inhibition of yes-associated protein 1 expression in gastric cancer
Authors: Shotaro Kuramitsu, Sho Nanbara, Qingjiang Hu, Yousuke Kuroda, Takaai Masuda, Shuhei Ito, Hidetoshi Eguchi, Yoshihiko Mehara, Koshi Mimori
Journal: Cancer Research (2018)

Abstract [Background] Yes-associated protein 1 (YAP1) acts as an oncogene through dephosphorylation and nuclear translocation, and nuclear accumulation of YAP1 is associated with poor prognosis in gastric cancer (GC). We previously identified ivermectin, an antiparasitic drug, as a YAP1 inhibitor. Here, we aimed to clarify whether ivermectin had antitumor effects on GC through inhibition of YAP1. [Result] First, we evaluated the antiproliferative effects of ivermectin on human GC cells using in vitro proliferation assays and a xenograft mouse model. YAP1-knockdown assays were performed to assess whether the sensitivity to ivermectin depended on YAP1 expression. Next, we explored the mechanism through which ivermectin regulated YAP1 expression or localization by immunoblotting and reverse transcription-quantitative polymerase chain reaction for YAP1 and the downstream gene CTGF. Finally, the clinical significance of YAP1 expression was examined using three independent GC datasets. We found that MKN1 GC cells were most sensitive to ivermectin, whereas MKN7 cells were most resistant. In MKN1 xenografts, ivermectin suppressed tumor growth, and the sensitivity of MKN1 cells to ivermectin was decreased by YAP1 knockdown. Ivermectin inhibited YAP1 nuclear expression and CTGF expression in MKN1 cells but not MKN7 cells. Moreover, ivermectin decreased YAP1 mRNA expression, thereby inhibiting nuclear accumulation of YAP1 in MKN1 cells. In survival analysis, low YAP1 mRNA expression was associated with a better prognosis in three independent GC datasets. [Conclusion] Ivermectin suppressed the growth of GC in vitro and in vivo by inhibiting YAP1 expression. Furthermore, GC with low YAP1 expression had favorable clinicopathological features and good prognosis. These findings provided insights into the antiproliferative effects of ivermectin as a YAP1 inhibitor and established a theoretical basis for preclinical evaluations of ivermectin for management of GC. Citation Format: Shotaro Kuramitsu, Sho Nanbara, Qingjiang Hu, Yousuke Kuroda, Takaai Masuda, Shuhei Ito, Hidetoshi Eguchi, Yoshihiko Mehara, Koshi Mimori. Antitumor effects of the antiparasitic agent ivermectin via inhibition of yes-associated protein 1 expression in gastric 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 3962.
Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy
Authors: Kevin Shiue, Alberto Cerra-Franco, Ronald Shapiro, Neil Estabrook, Edward M. Mannina, Christopher R. Deig, Sandra Althouse, Sheng Liu, Jun Wan, Yong Zang, Namita Agrawal, Pericles Ioannides, Yongmei Liu, Chen Zhang, Colleen DesRosiers, Greg Bartlett, Marvene Ewing, Mark P. Langer, Gordon Watson, Richard Zellars, Feng-Ming Kong, Tim Lautenschlaeger
Journal: Journal of Thoracic Oncology (2018)
Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial
Authors: Chrisann Kyi, Vladimir Roudko, Rachel Sabado, Yvonne Saenger, William Loging, John Mandeli, Tin Htwe Thin, Deborah Lehrer, Michael Donovan, Marshall Posner, Krzysztof Misiukiewicz, Benjamin Greenbaum, Andres Salazar, Philip Friedlander, Nina Bhardwaj
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells. Patients and Methods: In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and blood. Results: Two patients completed 2 cycles of IT treatments, and 1 achieved clinical benefit (stable disease, progression-free survival 6 months), whereas the remainder had progressive disease. Poly-ICLC was well tolerated, with principal side effects of fatigue and inflammation at injection site (&amp;lt;grade 2). In the patient with clinical benefit, IHC analysis of tumor showed increased CD4, CD8, PD1, and PD-L1 levels compared with patients with progressive disease. RNA-seq analysis of the same patient's tumor and peripheral blood mononuclear cells showed dramatic changes in response to poly-ICLC treatment, including upregulation of genes associated with chemokine activity, T-cell activation, and antigen presentation. Conclusions: Poly-ICLC was well tolerated in patients with solid cancer and generated local and systemic immune responses, as evident in the patient achieving clinical benefit. These results warrant further investigation and are currently being explored in a multicenter phase II clinical trial (NCT02423863). Clin Cancer Res; 24(20); 4937–48. ©2018 AACR.
Abstract P231: Electrocardiographic Versus Echocardiographic Left Ventricular Hypertrophy as a Predictor of Cardiovascular Disease Events in the General Population
Authors: John A Leigh, Wesley T O’Neal, Elsayed Z Soliman
Journal: Circulation (2016)

Introduction: It is uncertain whether left ventricular hypertrophy (LVH) detected by the electrocardiogram (ECG) is able to be used as an alternative to LVH detected by imaging in population studies. Aim: We compared the risk of cardiovascular disease (CVD) associated with LVH as measured by Minnesota ECG classification (ECG-LVH), the most common ECG classification in population studies, with LVH detected by echocardiography, the most common tool to estimate left ventricular mass in clinical practice. Methods: This analysis included 4,076 participants (41% male, 86% white), aged 65 years or older from the Cardiovascular Health Study who were free of CVD at the time of enrollment. ECG-LVH was defined by the Minnesota ECG Classification criteria from baseline ECG data that were read centrally. Echocardiographic LVH (echo-LVH) was defined as left ventricular mass &gt;95th percentile using sex-specific cut-points. Results: ECG-LVH was detected in 144 (3.5%) participants and echo-LVH in 199 (4.9%) participants. Over a mean follow-up of 10.6 years, a total of 2,274 CVD events occurred. In a multivariate Cox regression analysis adjusted for age, sex, race, education, income, body mass index, HDL-cholesterol, total-cholesterol, smoking status, systolic blood pressure, diabetes, aspirin and blood pressure lowering drugs, the risk of CVD events associated with ECG-LVH (HR=1.84, 95% CI=1.51, 2.24) was higher than that associated with echo-LVH (HR=1.35, 95% CI 1.12, 1.62). The association between ECG-LVH and CVD events was not substantively altered with further adjustment for echo-LVH (HR=1.81, 95% CI=1.49, 2.21). Conclusion: The association of ECG-LVH with CVD events is not dependent on echo-LVH and provides additional support to the concept that ECG-LVH is an electrophysiologic marker with predictive properties independent of left ventricular anatomy.
Association of Attending Surgeon With Variation in the Receipt of Genetic Testing After Diagnosis of Breast Cancer
Authors: Steven J. Katz, Irina Bondarenko, Kevin C. Ward, Ann S. Hamilton, Monica Morrow, Allison W. Kurian, Timothy P. Hofer
Journal: JAMA Surgery (2018)

Genetic testing after diagnosis of breast cancer is common, but little is known about the influence of the surgeon on the variation in testing.To quantify and explain the association of attending surgeon with rates of genetic testing after diagnosis of breast cancer.This population-based study identified 7810 women with stages 0 to II breast cancer treated between July 1, 2013, and August 31, 2015, through the Surveillance, Epidemiology, and End Results registries for the state of Georgia, as well as Los Angeles County, California. Surveys were sent approximately 2 months after surgery. Also surveyed were 488 attending surgeons identified by the patients.The study examined the association of surgeon with variation in the receipt of genetic testing using information from patient and surgeon surveys merged to Surveillance, Epidemiology, and End Results and genetic testing data obtained from 4 laboratories.In total, 5080 women (69.6%) of 7303 who were eligible (mean [SD] age, 61.4 [0.8] years) and 377 surgeons (77.3%) of 488 (mean [SD] age, 53.8 [10.7] years) responded to the survey. Approximately one-third (34.5% [1350 of 3910] of patients had an elevated risk of mutation carriage, and 27.0% (1056 of 3910) overall had genetic testing. Surgeons had practiced a mean (SE) of 20.9 (0.6) years, and 28.9% (107 of 370) treated more than 50 cases of new breast cancer per year. The odds of a patient receiving genetic testing increased more than 2-fold (odds ratio, 2.48; 95% CI, 1.85-3.31) if she saw a surgeon with an approach 1 SD above that of a surgeon with the mean test rate. Approximately one-third (34.1%) of the surgeon variation was explained by patient volume and surgeon attitudes about genetic testing and counseling. If a patient with higher pretest risk saw a surgeon at the 5th percentile of the surgeon distribution, she would have a 26.3% (95% CI, 21.9%-31.2%) probability of testing compared with 72.3% (95% CI, 66.7%-77.2%) if she saw a surgeon at the 95th percentile.In this study, the attending surgeon was associated with the receipt of genetic testing after a breast cancer diagnosis. Variation in surgeon attitudes about genetic testing and counseling may explain a substantial amount of this association.
A prospective study on serum Cytokeratin (CK)-18 and CK18 fragments as biomarkers of acute hepato-intestinal GVHD
Authors: Sandra Sauer, Johannes Hüsing, Jacek Hajda, Frank Neumann, Aleksandar Radujkovic, Anthony D. Ho, Peter Dreger, Thomas Luft
Journal: Leukemia (2018)
Abstract 3076: Smoking behavior weakens the protective effect of mosaic loss of chromosome Y on lung cancer
Authors: Na Qin, Cheng Wang, Zijian Ma, Jiaping Chen, Hongbing Shen
Journal: Cancer Research (2018)

Abstract Mosaic loss of chromosome Y (mLOY) is the most commonly detectable mosaic chromosomal event in cancers, however, the underlying relationship with tumorigenesis is still unclear. We conducted a Mendelian randomization study to systematically investigate the effect of mLOY on lung cancer based on published GWASs study. We identified that genetically defined mLOY was a protective factor for lung cancer in non-smokers but not in smokers (lifelong non-smokers: OR=0.80, CI=0.69-0.93, P=4.03×10-3; ever-smokers: OR=0.96, CI=0.89-1.04, P=2.90×10-1; PHeterogeneity=3.83×10-2). A U-shaped curve between the copy-number level of chromosome Y and lung cancer risk was further fitted (P for Linearity Wald=8.81×10-10) to support that heavy mLOY caused by acquired damaging environmental factors may have different effects on lung cancer from the genetically defined mLOY, while genetically predicted mLOY was linearly associated with decreased lung cancer risk (P for Linearity Wald=0.15). Taken together, we proposed a two “sides” model: the “natural” mLOY reduced the lung cancer risk, while the effect can be abolished by aberrant loss of chromosome Y caused by environmental risk factors. Our results revealed a complex relationship between mLOY and lung cancer, and emphasized the importance of heterogeneity in the mLOY studies. Citation Format: Na Qin, Cheng Wang, Zijian Ma, Jiaping Chen, Hongbing Shen. Smoking behavior weakens the protective effect of mosaic loss of chromosome Y on lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3076.
Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma
Authors: Ghassan K. Abou-Alfa, Tim Meyer, Ann-Lii Cheng, Anthony B. El-Khoueiry, Lorenza Rimassa, Baek-Yeol Ryoo, Irfan Cicin, Philippe Merle, YenHsun Chen, Joong-Won Park, Jean-Frederic Blanc, Luigi Bolondi, Heinz-Josef Klümpen, Stephen L. Chan, Vittorina Zagonel, Tiziana Pressiani, Min-Hee Ryu, Alan P. Venook, Colin Hessel, Anne E. Borgman-Hagey, Gisela Schwab, Robin K. Kelley
Journal: New England Journal of Medicine (2018)

Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma.