tbuckley/cabot-search huggingface dataset:
Abstract 1692: The impact of neutrophil/lymphocyte ratio as the predictive marker to anti-PD-1 antibody treatment in NSCLC patients
Authors: Keiko Tanimura, Tadaaki Yamada, Nobuyo Tamiya, Yoshiko Kaneko, Takayuki Takeda, Junji Uchino, Yutaka Kubota, Koichi Takayama
Journal: Cancer Research (2018)

Abstract Background: Anti-Programmed death 1 (PD-1) antibody which enhances anti-tumor activity of cytotoxic-T-lymphocytes by blockade of PD-1/PD-L1 pathway has demonstrated improvement of survival in the patients with advanced non-small-cell lung cancer (NSCLC). PD-1 and its ligand PD-L1 is also known as key players in the formation of tumor microenvironment, closely related with inflammatory cytokines. Here, we retrospectively analyzed the peripheral blood cells as a surrogate marker for predicting outcome of immune checkpoint inhibitors (ICI). Method: Total of 78 cases treated with anti-PD-1 antibodies, nivolumab or pembrolizumab from February 2016 to September 2017 were registered retrospectively. We investigated the differential leukocyte counts, C-reactive protein (CRP) and other peripheral blood parameter on the treatment progress with ICI, and evaluated correlation between response to ICI and peripheral blood cells. Result: Out of 78 cases, 56 cases (77%) were treated with nivolumab, 18 cases (23%) were treated with pembrolizumab, and 4 cases (5%) have treatment history of both agents. Median follow up period was 5.7 months (range: 0.4-18.7 months). Median progression free survival (PFS) and median overall survival (OS) were 2.4 and 8.7 months, respectively. Overall response rate was 21.8%. Of some parameters in peripheral blood cells, higher absolute neutrophil count (ANC), CRP at baseline were associated with shorter OS. Furthermore, we determined neutrophil / lymphocyte ratio (NLR), platelet / lymphocyte ratio (PLR), lymphocyte / monocyte ratio (LMR) and prognostic nutritional index (PNI), which were known as predictive biomarkers in various tumor type. In patients with longer PFS for ICI treatment, ANC, NLR and CRP remained low level until disease progression, whereas these markers increased during ICI treatment in the patients with shorter PFS for ICI. Conclusion: Our retrospective analysis showed that ANC, NLR and CRP may predict response and acquisition of resistance to anti-PD-1 therapy in NSCLC patients. These results suggest that peripheral blood findings might be promising as a predictive biomarker of ICI treatment. Citation Format: Keiko Tanimura, Tadaaki Yamada, Nobuyo Tamiya, Yoshiko Kaneko, Takayuki Takeda, Junji Uchino, Yutaka Kubota, Koichi Takayama. The impact of neutrophil/lymphocyte ratio as the predictive marker to anti-PD-1 antibody treatment in NSCLC patients [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 1692.
Abstract 13686: Implementing a Regionalized Integrated Network for ST-segment-Elevation Myocardial Infarction (STEMI) Care is Associated With Higher Use of Evidence-Based Medication and Better Survival Among STEMI Patients: Long-Term Results From the RESISST Registry
Authors: Nivaldo M Filgueiras Filho, Davi J Solla, Felipe C Argolo, Oddone F Braghiroli, Ivan M Paiva-Filho, Marina B Lima, Fernanda F Costa, Gilson S Feitosa-Filho, Lauren K Newby, Renato D Lopes
Journal: Circulation (2015)

Introduction: We have shown that implementing a Regional Network in developing countries is feasible. Purpose: Describe temporal trends in 30-Day mortality among STEMI patients enrolled in a prospective registry in Brazil. Methods: From Jan 2011 to Aug 2013, 520 patients received primary STEMI care at 23 non-specialized public health units (7 general hospitals; 16 community-based emergency units) with the option to be transferred to one of two public cardiology reference centers (CRC). These patients were identified through a Regional STEMI Network supported by telemedicine and the local prehospital emergency medical service. Results: Mean age was 62.0 ± 12.2y, and most patients were men (55.6%). Mean GRACE score was 145 ± 34. Overall mortality at 30 days was 15.0%. The median pain-to-admission time was 180 (IQR 66-430) min and admission-to-ECG, 159 (IQR 70-379) min. We analyzed the differences of results over 2.5 year period, separating the patients in 5 6-month periods from 1/2011 to 1/2013. There were no differences in pain-to-admission or admission-to-ECG times and no difference in GRACE score over time. Use of several acute medical treatments increased significantly from baseline to period 5: dual antiplatelet therapy (1/2011, 61.8%; 1/2013, 93.6%; p&lt;0.001) and statin (1/2011, 60.4%; 1/2013, 79.7%; p&lt;0.001). Rates of primary reperfusion also increased (1/2011, 29.1%; 1/2013, 53.8%; p&lt;0.001) and more patients were transferred to CRC (1/2011, 44.7%; 1/2013, 76.3%; p=0.001). 30-day mortality rates decreased from 20.4% in 1/2011 compared with 7.5% in 1/2013 (p&lt;0.001) (Figure). Conclusion: Implementation of a regional STEMI system was associated with lower mortality rates at 30 days and higher use of evidence-based treatment. Our findings highlight opportunities to improve the care of STEMI patients in developing countries.
Abstract 12548: Expression of Let-7 Family microRNAs in Skin Correlates Negatively With Severity of Pulmonary Hypertension in Patients With Systemic Scleroderma
Authors: YasuhiroIzumiya, YuichiKimura, SatoruYamamura, YoshiroOnoue, ShinsukeHanatani, SatoshiAraki, HisaoOgawa
Journal: Circulation (2015)

Introduction: Pulmonary hypertension (PH) is a serious complication in patients with systemic scleroderma (SSc), therefore it is important to identify the factors that could predict the presence and progression of PH. Skin biopsy is performed in patients with SSc to examine the type and severity of the disease. MicroRNAs (miRNAs) are potential biomarkers for various cardiovascular diseases including PH. Hypothesis: In patents with systemic scleroderma (SSc), skin miRNAs expression profiles varies depending on the presence or absence of PH. Methods and Results: We determined the skin miRNA expression profile in 15 female SSc patients with (n=6) and without PH (n=9). Plasma BNP level was significantly higher in the PH group than non-PH group, but left ventricular function and dimension were not different between the two groups. A mixture of equal amounts of miRNAs from PH and non-PH patients were prepared and used for miRNA PCR array analysis. The analysis identified 591 upregulated miRNAs and 57 downregula...
Abstract 5141: <i>Streptococcus gallolyticus</i> in colorectal cancer development
Authors: Yi Xu, Ritesh Kumar, John Taylor, Juan Xu
Journal: Cancer Research (2018)

Abstract Streptococcus gallolyticus subsp. gallolyticus (Sg) has been reported to have a strong clinical correlation with colorectal cancer (CRC) for several decades. Our recent data indicates that Sg is able to actively promote the development of colon tumor and thus is also functionally important to CRC. Further investigations into the Sg-CRC connection revealed that there are variations among Sg strains with respect to their ability to stimulate target host cell proliferation and tumor growth. The ability of Sg to adhere to colon cancer cells and to colonize colonic epithelium in vivo appears to be important. The results suggest that direct interactions between specific Sg factors and colonic epithelial receptors/structures are required to trigger downstream signaling events leading to increased host cell proliferation. Furthermore, we observed that the effect of Sg is also dependent on the host genetic background, suggesting a dynamic and complex interactions between Sg and the host. In addition to the requirement for beta-catenin signaling as we previously reported, we observed that Sg activates yes-associated protein 1 (YAP1), a downstream effector in the Hippo signaling pathway. YAP1 activation is required for Sg to stimulate target host cell proliferation. YAP1 and the Hippo pathway are known to be involved in the development CRC. Bacterial activation of YAP1 has not been described before. Thus, our results suggest a novel mechanism by which bacteria contribute to the development of cancer. Studies are on-going to further investigate the molecular details of this mechanism. Citation Format: Yi Xu, Ritesh Kumar, John Taylor, Juan Xu. Streptococcus gallolyticus in colorectal cancer development [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 5141.
Abstract 4167: MUC3A promotes lung cancer progress via activating NFκB pathway and attenuates radiosensitivity
Authors: Yingming Sun, Chengcheng You, Shijing Ma, Yuan Luo, Yan Gong, Yu Xiao, Junhong Zhang, Conghua Xie
Journal: Cancer Research (2018)

Abstract MUC3A is highly expressed in 40% of lung adenocarcinoma, but its functions and effects on clinical outcomes are not well understood. Tissue microarray of 92 patients' tumor samples from Chinese National Human Genetic Resources Sharing Service Platform indicated that highly expression of MUC3A was associated with poor prognosis, advanced staging and low differentiation. IP-MS and co-IP results revealed that MUC3A interacted with RELA and activated the NFκB pathway via promoting RELA phosphorylation and interfering the binding of RELA to IκB. MUC3A knockdown significantly suppressed cell proliferation and induced G1 arrest via down-regulating cell cycle checkpoints such as CDK2/4/6 and Cyclin D1. MUC3A deficiency increased γ-H2AX phosphorylation and increased radiation-induced DNA double strain breaks. MUC3A knockdown inhibited the BRCA-1/RAD51 pathway and nuclear translocation of P53 and XCRR6, suggesting that MUC3A promote DNA damage repair and attenuate radiation sensitivity. Moreover, MUC3A deficiency induced autophagy in lung cancer cells and increased the protein levels of LC3 II and Beclin-1. MUC3A knockdown significantly suppressed tumor growth in H1975 xenograft model and had a synergistic effect with radiation. Less nuclear translocation of RELA and P53 was also observed in tumor tissue in vivo. Our studies indicated that MUC3A was a potential oncogene and its highly expression was associated with unfavorable clinical outcomes in patients with lung adenocarcinoma, who should be more frequently follow-up, and might benefit less from radiotherapy. Citation Format: Yingming Sun, Chengcheng You, Shijing Ma, Yuan Luo, Yan Gong, Yu Xiao, Junhong Zhang, Conghua Xie. MUC3A promotes lung cancer progress via activating NFκB pathway and attenuates radiosensitivity [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 4167.
Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype
Authors: Stephanie D. Davis, Margaret Rosenfeld, Hye-Seung Lee, Thomas W. Ferkol, Scott D. Sagel, Sharon D. Dell, Carlos Milla, Jessica E. Pittman, Adam J. Shapiro, Kelli M. Sullivan, Keith R. Nykamp, Jeffrey P. Krischer, Maimoona A. Zariwala, Michael R. Knowles, Margaret W. Leigh
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood.
Haploinsufficiency of Target of Rapamycin Attenuates Cardiomyopathies in Adult Zebrafish
Authors: YongheDing, XiaojingSun, WeiHuang, TiffanyHoage, MargaretRedfield, SudhirKushwaha, SridharSivasubbu, XueyingLin, StephenEkker, XiaoleiXu
Journal: Circulation Research (2011)

Rationale:Although a cardioprotective function of target of rapamycin (TOR) signaling inhibition has been suggested by pharmacological studies using rapamycin, genetic evidences are still lacking. We explored adult zebrafish as a novel vertebrate model for dissecting signaling pathways in cardiomyopathy. Objective:We generated the second adult zebrafish cardiomyopathy model induced by doxorubicin. By genetically analyzing both the doxorubicin and our previous established anemia-induced cardiomyopathy models, we decipher the functions of TOR signaling in cardiomyopathies of different etiology. Methods and Results:Along the progression of both cardiomyopathy models, we detected dynamic TOR activity at different stages of pathogenesis as well as distinct effects of TOR signaling inhibition. Nevertheless, cardiac enlargement in both models can be effectively attenuated by inhibition of TOR signaling through short-term rapamycin treatment. To assess the long-term effects of TOR reduction, we used a zebrafish t...
Abstract 2676: Radiotherapy-assisted tumor selective metronomic oral chemotherapy
Authors: Youngseok Cho, Seung Woo Chung, Youngro Byun
Journal: Cancer Research (2018)

Abstract Chemotherapy have commonly been used in maximum tolerated dose (MTD) to completely eradicate the cancer. However, such treatments often failed due to the complex and dynamic nature of cancer. Therefore, it has been suggested that cancer should be treated as a chronic disease, controlling its growth by providing continuous therapeutic pressure for long-term. Such an approach, however, requires a therapy that is non-toxic and orally available with sufficient potency. Herein, we propose a radiotherapy-assisted orally available metronomic apoptosis-targeted chemotherapy, which delivers doxorubicin continuously to the irradiated tumor with high selectivity while causing minimal toxicities to the normal tissues. DEVD-S- DOX/DCK complex is the anticancer prodrug for our strategy that could selectively release doxorubicin in the irradiated tumor tissue with sufficient oral bioavailability. The prodrug was completely inactive by itself, but displayed potent anticancer activity when coupled with radiotherapy. Consequently, the daily oral administration of DEVD-S-DOX/DCK in combination with the low-dose radiotherapy effectively suppressed the growth of tumor in vivo with no significant systemic toxicities despite that the accumulated dose of doxorubicin exceeded 150 mg/kg. Therefore, our novel therapy using DEVD-S-DOX/DCK complex is considered as an outstanding treatment option for treating cancer for long-term attributed to its oral availability and low-toxicity profile as well as the potent anticancer effect. Citation Format: Youngseok Cho, Seung Woo Chung, Youngro Byun. Radiotherapy-assisted tumor selective metronomic oral 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 2676.
Abstract 14300: Low-level Ganglionated Plexus (GP) Stimulation Facilitates Atrial Fibrillation: in vivo and in vitro Studies
Authors: Zhibing Lu, Bo He, Bo Cui, Xiaorong Hu, Wei Wu, Liu Wu, Congxin Huang, Hong Jiang
Journal: Circulation (2010)

Introduction: Clinical studies showed that GP ablation as an independent or adjunct strategy can increase the success rate of atrial fibrillation (AF) ablation not only in vagotonic AF patients but also in the other AF patients without noticeable increase in cardiac vagal tone. We hypothesized that long-term low level autonomic activation without marked change in sinus rate would cause significant alternations in atrial electrophysiology and contribute to AF. This study investigated the effects of six-hour low-level GP stimulation on atrial electrophysiological properties. Methods: In 16 anesthetized open-chest dogs, electrodes on the anterior right GP and superior left GP allowed six-hour low level GP stimulation at 1 V below that which slowed the sinus rate or atrioventricular conduction. Multi-electrode catheters were fixed at the right and left superior and inferior PVs and both atria and atrial appendages. At the end of 3rd and 6th hour of low level GP stimulation, the effective refractory period (ER...
Abstract 1411: Proteogenomic analysis of the syngeneic mouse gastric stem cell-like cancer cell line
Authors: Hanna Yang, Hark Kyun Kim
Journal: Cancer Research (2018)

Abstract Gastric cancer is the third main cause of cancer deaths worldwide. To understand molecular mechanism of gastric cancer incidence and metastasis, we generated NCC-S1M lacking Smad4, Trp53 and Cdh1, which is the unique syngeneic gastric cancer cell line transplant model in the scientific society. NCC-S1M showed cancer stem cell-like features and strong tumor-initiating potential. Using proteogenomic analysis of NCC-S1M, we elucidated the specific signaling pathways that control gastric cancer stem cell-like properties and immune checkpoint. Cd274, Ccne1 and Il1rl1 were overexpressed and their protein levels were higher than normal gastric tissues. Cd274 encodes PD-L1, which is one of the important immune checkpoint proteins. The growth rate of NCC-S1M allograft was reduced after treatment with anti-PD-1. When Smad4 was ectopically expressed in NCC-S1M, Cd274 expression was decreased. In addition, TGF-β treatment induced reduction in Cd274 expression of Smad4 overexpressed NCC-S1M cells even more comparing with normal Smad4 overexpressed NCC-S1M. The knockdown of Il1rl1 in NCC-S1M reduced tumorigenicity and in vivo chemoresistance. We demonstrated that NCC-S1M focally amplified Ccne1 gene through array comparative genomic hybridization. Ccne1 knocked down NCC-S1M showed reduced metastatic potential. The proteogenomic characterization of NCC-S1M explains that Smad4 is important for PD-L1 immune evasion and that Il1rl1 has a significant role in cancer stem cell-like properties. Furthermore, it could imply that Ccne1 regulates metastasis. Citation Format: Hanna Yang, Hark Kyun Kim. Proteogenomic analysis of the syngeneic mouse gastric stem cell-like cancer cell line [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 1411.
Abstract 5405: Multiplex profiling of miRNA biomarkers for discovery and verification using the FirePlex®platform
Authors: Elnaz Atabakhsh, Ivona Kelley, Michael Tackett, Izzuddin Diwan, Gensis Tejada, Conor Rafferty, Daniel Pregibon
Journal: Cancer Research (2018)

Abstract To address the needs for microRNA (miRNA) biomarker discovery and verification, we developed the FirePlex® miRNA assay. This assay enables the detection of 5-400 miRNA targets per sample in 96-well format, with readout on standard flow cytometers and analysis with an included bioinformatics software package. The FirePlex miRNA assay combines particle-based multiplexing, using patented FirePlex® hydrogel particles, with single step RT-PCR signal amplification using universal primers. Thus, the FirePlex miRNA assay leverages PCR sensitivity while eliminating the need for separate reverse transcription reactions and mitigating amplification biases introduced by target-specific qPCR. The miRNA assay can reliably detect as few as 1000 miRNA copies per sample with a linear dynamic range of ~5 logs, and without the need of prior RNA purification, making the assay ideally suited for profiling in serum, plasma, exosomes, urine, and directly from FFPE tissues. Furthermore, the ability to multiplex targets in each well eliminates the need to split valuable samples into multiple reactions. Results from the FirePlex miRNA assay are displayed and interpreted using the integrated FirePlex Analysis Workbench, which allows visualization, normalization, and export of experimental data with only a few mouse clicks. To aid biomarker discovery studies, we offer pre-designed panels of 400 miRNAs based on a research-curated list of miRNAs published to be found in circulating biofluids. For studies focused on specific research areas of interest, we offer pre-designed focus panels for Oncology, Cardiology, Neurology, Immunology, and Organ Toxicity. These carefully curated panels include hemolysis markers to assess sample quality, as well as critical normalization factors. Here we present the data from several studies investigating circulating miRNA profiles, as well as miRNA profiles obtained directly from FFPE tissues, using the FirePlex miRNA Assay Panels. Together, this novel combination of bioinformatics tools and multiplexed, high-sensitivity assays enables rapid discovery and verification of miRNA biomarker signatures from biofluid samples. Citation Format: Elnaz Atabakhsh, Ivona Kelley, Michael Tackett, Izzuddin Diwan, Gensis Tejada, Conor Rafferty, Daniel Pregibon. Multiplex profiling of miRNA biomarkers for discovery and verification using the FirePlex® platform [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 5405.
Abstract 17184: Exosomes From iPSC-Derived Cardiomyocytes Restore the Injured Murine Myocardium
Authors: Michelle Santoso, Atsushi Tachibana, Ji-Hye Jung, Raymond G Sierra, Andrew B Goldstone, Bryan B Edwards, Soichi Wakatsuki, Joseph Woo, Phillip C Yang
Journal: Circulation (2016)

Background: Pluripotent stem cell-derived cardiomyocytes (iCMs) represent a potential therapeutic to restore the injured myocardium; however, little is known about the underlying mechanism of action. Longitudinal studies of iCMs to treat myocardial injury (MI) show low engraftment despite significant functional restoration. Studies from our group demonstrated that the iCM secretome contains cardioprotective factors to restore the injured myocardium. We propose that the putative effects of iCMs are mediated by exosomes, which are enriched in cardioprotective microRNAs (miRNAs), to modulate the gene expression in the recipient cardiomyocytes and salvage the peri-infarct region. Methods: Serum-free supernatant of the contractile iCMs was collected. Exosomes were isolated by PEG precipitation and verified by CD63 immunoblotting and Nanosight. MiRNA cargo was detected by microarray and qRT-PCR. The resultant miRNA regulatory networks were determined by Affymetrix Expression Console and Ingenuity Pathway Analys...
Abstract 1275: A role for FGF2 in visceral adiposity-associated mammary epithelial transformation
Authors: Vanessa Benham, Debrup Chakraborty, Blair Bullard, Jamie J. Bernard
Journal: Cancer Research (2018)

Abstract Obesity is a leading risk factor for post-menopausal breast cancer, and this is concerning as 38% of Americans are obese. Furthermore, 40% of cancer diagnoses in 2014 were associated with overweight/obesity. Despite the epidemiologic link between obesity and breast cancer risk, the underlying mechanism responsible is unknown. We recently published that VAT releases FGF2 and stimulates the transformation of skin epithelial cells. As obesity is differentially associated with many cancer types, this mechanistic link could be translational to other cancers. Specifically, FGF2 and FGFR1 are implicated in breast cancer progression, but their role in tumor formation is unknown. Therefore, I hypothesize that VAT-derived FGF2 plays a translational role in promoting mammary tumor formation. Citation Format: Vanessa Benham, Debrup Chakraborty, Blair Bullard, Jamie J. Bernard. A role for FGF2 in visceral adiposity-associated mammary epithelial transformation [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 1275.