bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of soluble-viscous dietary fibre on coronary heart disease risk score across 3 population health categories: data from randomized, double-blind, placebo-controlled trials
Authors: Vuksan Vladimir , Sievenpiper John L. , Jovanovski Elena , Jenkins Alexandra L. , Komishon Allison , Au-Yeung Fei , Zurbau Andreea , Ho Hoang V.T. , Li Dandan , Smircic-Duvnjak Lea 
Published: March 2020

We applied the Framingham risk equation in healthy, metabolic syndrome, and diabetes populations, following treatment with viscous fibre from konjac-based blend (KBB). KBB yielded reduction in estimated risk score by 16% (1.04 ± 0.03 vs. 0.87 ± 0.04, p < 0.01) in type 2 diabetes, 24% (1.08 ± 0.01 vs. 0.82 ± 0.02, p < 0.01) in metabolic syndrome, and 25% (1.09 ± 0.05 vs. 0.82 ± 0.06, p < 0.01) in healthy individuals. Drivers for decreased risk were improvements in blood cholesterol and systolic blood pressure. The composite coronary heart disease risk across populations was reduced 22% (p < 0.01). Novelty Viscous fibre from konjac-xanthan reduced 10-year relative coronary heart disease using Framingham Risk Score across the glycemic status spectrum.
Imprints of an extended Chevallier–Polarski–Linder parametrization on the large scale of our universe
Authors: Pan Supriya , Yang Weiqiang , Paliathanasis Andronikos 
Published: March 2020

AbstractIn the present work we perform a systematic analysis of a new dark energy parametrization and its various corrections at first and higher orders around the presence epoch $$z=0$$z=0, where the first order correction of this dark energy parametrization recovers the known Chevallier–Polarski–Linder model. We have considered up to the third order corrections of this parametrization and investigate the models at the level of background and perturbations. The models have been constrained using the latest astronomical datasets from a series of potential astronomical data, such as the cosmic microwave background observations, baryon acoustic oscillations measurements, recent Pantheon sample of the supernova type Ia and the Hubble parameter measurements. From the analyses we found that all parametrization favor the quintessential character of the dark energy equation of state where the phantom crossing is marginally allowed (within 68% CL). Finally, we perform the Bayesian analysis using to quantify the statistical deviations of the parametrizations compared to the standard $$\Lambda $$ΛCDM cosmology. The Bayesian analysis reports that $$\Lambda $$ΛCDM is favored over all the DE parametrizations.
Collaboratively Learning the Best Option on Graphs, Using Bounded Local Memory
Authors: Su Lili , Zubeldia Martin , Lynch Nancy 
Published: March 2020

We consider multi-armed bandit problems in social groups wherein each individual has bounded memory and shares the common goal of learning the best arm/option. We say an individual learns the best option if eventually (as $t\diverge$) it pulls only the arm with the highest expected reward. While this goal is provably impossible for an isolated individual due to bounded memory, we show that, in social groups, this goal can be achieved easily with the aid of social persuasion (i.e., communication) as long as the communication networks/graphs satisfy some mild conditions. In this work, we model and analyze a type of learning dynamics which are well-observed in social groups. Specifically, under the learning dynamics of interest, an individual sequentially decides on which arm to pull next based on not only its private reward feedback but also the suggestion provided by a randomly chosen neighbor. To deal with the interplay between the randomness in the rewards and in the social interaction, we employ the \em mean-field approximation method. Considering the possibility that the individuals in the networks may not be exchangeable when the communication networks are not cliques, we go beyond the classic mean-field techniques and apply a refined version of mean-field approximation:
Using coupling we show that, if the communication graph is connected and is either regular or has doubly-stochastic degree-weighted adjacency matrix, with probability → 1 as the social group size N → ∞, every individual in the social group learns the best option.
If the minimum degree of the graph diverges as N → ∞, over an arbitrary but given finite time horizon, the sample paths describing the opinion evolutions of the individuals are asymptotically independent. In addition, the proportions of the population with different opinions converge to the unique solution of a system of ODEs. Interestingly, the obtained system of ODEs are invariant to the structures of the communication graphs. In the solution of the obtained ODEs, the proportion of the population holding the correct opinion converges to 1 exponentially fast in time.
Notably, our results hold even if the communication graphs are highly sparse.
Acquired Resistance to Alectinib in ALK-Rearranged Lung Cancer due to ABCC11/MRP8 Overexpression in a Clinically Paired Resistance Model
Authors: Funazo Tomoko , Tsuji Takahiro , Ozasa Hiroaki , Furugaki Koh , Yoshimura Yasushi , Oguri Tetsuya , Ajimizu Hitomi , Yasuda Yuto , Nomizo Takashi , Sakamori Yuichi , Yoshida Hironori , Kim Young Hak , Hirai Toyohiro 
Published: March 2020

Abstract
Alectinib is used as a first-line treatment for anaplastic lymphoma kinase (ALK)-rearranged non–small cell lung cancer (NSCLC). Whereas other ALK inhibitors have been reported to be involved in resistance to ATP-binding cassette (ABC) transporters, no data are available regarding the association between resistance to alectinib and ABC-transporters. To investigate whether ABC-transporters contribute to alectinib resistance, ABC-transporter expression in alectinib-resistant cell lines derived from a patient with ALK-rearranged NSCLC and from H2228 lung cancer cells was evaluated and compared with that in each parent cell type. ATP-binding cassette subfamily C member 11 (ABCC11) expression was significantly increased in alectinib-resistant cell lines compared with that in alectinib-sensitive lines. ABCC11 inhibition increased sensitivity to alectinib in vitro. ABCC11-overexpressing cells were established by transfection of an ABCC11 expression vector into H2228 cells, while control cells were established by transfecting H2228 cells with an empty vector. ABCC11-overexpressing cells exhibited decreased sensitivity to alectinib compared with that of control cells in vitro. Moreover, the tumor growth rate following alectinib treatment was higher in ABCC11-overexpressing cells than that in control cells in vivo. In addition, the intracellular alectinib concentration following exposure to 100 nmol/L alectinib was significantly lower in the ABCC11-overexpressing cell line compared with that in control cells. This is the first preclinical evidence showing that ABCC11 expression may be involved in acquired resistance to alectinib.
Abstract A001: Colorectal cancer cell-derived exosomes containing miR-183-5p regulate angiogenesis via FOXO1
Authors: SHANG ANQUAN , Gu Chenzheng , Wu Junlu , Ji Ping , Sun Zujun , Li Dong 
Published: March 2020

Abstract
Objective: Exosomes acted as important role in tumor proliferation and tumor microenvironment modulation, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells -derived exosomes in angiogenesis in vascular endothelial cell has not been fully discussed. In this study, the microRNA-183-5p (miR-183-5p) that promote the development of CRC, as well as the exosome secreted from the CRC cells were investigated. Methods: Microarray analysis was employed to determine the differentially expressed miRNAs. Exosomes derived from CRC cells were isolated and identified. Meanwhile, exosomes derived from CRC cells were isolated and then co-cultured with HMEC-1 cells to identify the role of exosomes in angiogenesis. Further, the effects of CRC cell-derived exosomal miR-183-5p on proliferation, invasion and tube formation abilities of HMEC-1 cells were assessed. The preventative effect of exosomal miR-183-5p in vivo was measured in nude mice. Results: It was found that FOXO1 was downregulated while miR-183-5p was upregulated in CRC. Additionally, the inhibition of miR-183-5p was suggested to suppress proliferation, invasion and tube formation abilities of HMEC-1 cells through upregulating FOXO1. Then, in vitro experiments demonstrated that CRC cell-derived exosomes overexpressing miR-183-5p contributed to an enhanced proliferation, invasion and tube formation abilities of HMEC-1 cells. Furthermore, in vivo experiments confirmed the promotive effects of CRC cell-derived exosomes overexpressing miR-183-5p. Conclusion: Our study demonstrates that the CRC cell-derived exosomes overexpressing miR-183-5p aggravates CRC through the regulation of FOXO1. Additionally, exosomes overexpressing miR-183-5p might be a potential treatment biomarker for CRC.
Citation Format: ANQUAN SHANG, Chenzheng Gu, Junlu Wu, Ping Ji, Zujun Sun, Dong Li. Colorectal cancer cell-derived exosomes containing miR-183-5p regulate angiogenesis via FOXO1 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A001. doi:10.1158/1535-7163.TARG-19-A001
Abstract A015: A kinetic analysis of tumor gene expression and cellular changes following immune checkpoint inhibition in the MC38 colon carcinoma model
Authors: Fadden Patrick , Bui Thi , Davis Kelli , Hurtado David , Belle Ian , Krontz Katherine , Hauser Jacob , Sokolowski Cristina , Li Na , Takayama Kyle , Marval Paula Miliani de , Harris David , Wood Edgar 
Published: March 2020

Abstract
The clinical success of immune checkpoint therapies such as PD-1, PD-L1, and CTLA-4 inhibitory antibodies has stimulated interest in a wide range of approaches to cancer immunotherapy. Development of these new modalities requires robust, well characterized preclinical animal models to evaluate efficacy and potential toxicities. Preclinical efficacy assessments of novel immune-oncology therapies requires a functional immune system which limits the usefulness of traditional xenograft models and drive the use of humanized (human immune cell engrafted animals) and syngeneic model systems. Syngeneic mouse tumors are popular model systems in which to evaluate these novel therapies due the presence of fully intact mouse immune system and ease of accessibility. The MC38 mouse colon cancer model is popular for efficacy assessment studies due to its responsiveness to typical immune checkpoint inhibitors (ICI). We endeavored to characterize the kinetic immune response to checkpoint inhibitors (anti-PD-1 + anti-CTLA-4) in MC38 tumors using flow cytometry and gene expression analysis. Gene expression analysis provided a signature of gene changes that correlate to immune driven changes in tumor growth and may be used in preclinical pharmacodynamics studies as evidence of mode of action for other novel immune-oncology therapies. In addition, gene over-representation analysis highlighted the presence and involvement of B cell populations in the MC38 tumor environment which was supported by IHC data that show distinctive B cell staining in what resemble tumor associated tertiary lymphoid structures. These findings provide a greater understanding of the ICI response in the MC38 tumor model and may inform mode of action study designs for other novel immuno-oncology therapies.
Citation Format: Patrick Fadden, Thi Bui, Kelli Davis, David Hurtado, Ian Belle, Katherine Krontz, Jacob Hauser, Cristina Sokolowski, Na Li, Kyle Takayama, Paula Miliani de Marval, David Harris, Edgar Wood. A kinetic analysis of tumor gene expression and cellular changes following immune checkpoint inhibition in the MC38 colon carcinoma model [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A015. doi:10.1158/1535-7163.TARG-19-A015
Abstract A021: Genipin enhanced apoptosis of gastric cancer by mitochondrial dysfunction and downregulation of Stat3/JAK2/Mcl-1 signaling pathway
Authors: Jo Min Jee , Jeong Soyeon , Yun Hye Kyeong , Kim Dae Yeong , Kim Bo Ram , Kim Jung Lim , Na Yoo Jin , Park Seong Hye , Jeong Yoon A , Kim Bu Gyeom , Ashktorab Hassan , Smoot Duane T , Heo Jun Young , Han Jeongsu , Lee Dae-Hee , Oh Sang Cheul 
Published: March 2020

Abstract
Genipin is known as a compound derived from gardenia fruit extract. Although Genipin is known to have an anti-tumor effects in various cancers, its effect and mechanism are unknown in gastric cancer. In our studies, Genipin induced apoptosis in gastric cancer cells including AGS and MKN45 cells. Genipin reduced Mcl-1 mRNA levels and confirmed with transfection of Mcl-1 siRNA. Furthermore, We found that phospho Stat3 is regulated by Genipin through proteome profiler phosphor-kinase array. In addition, protein level of phosphor JAK2 decreased in Genipin treatment. The results elucidate that Stat3/JAK2/Mcl-1 signaling pathway was suppressed with Genipin treatment in gastric cancer cells. Mcl-1 is known to be closely related to the function of mitochondria. Genipin has been shown to result in the collapse of mitochondrial function such as mitochondrial membrane potential. In conclusion, Genipin induced apoptosis by suppressing Stat3/JAK2/Mcl-1 pathway and led to mitochondrial dysfunction. Our finding implies that a novel mechanism of anti-cancer effect of Genipin in gastric cancer can be identified.
Citation Format: Min Jee Jo, Soyeon Jeong, Hye Kyeong Yun, Dae Yeong Kim, Bo Ram Kim, Jung Lim Kim, Yoo Jin Na, Seong Hye Park, Yoon A Jeong, Bu Gyeom Kim, Hassan Ashktorab, Duane T Smoot, Jun Young Heo, Jeongsu Han, Dae-Hee Lee, Sang Cheul Oh. Genipin enhanced apoptosis of gastric cancer by mitochondrial dysfunction and downregulation of Stat3/JAK2/Mcl-1 signaling pathway [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A021. doi:10.1158/1535-7163.TARG-19-A021
Abstract A022: Gasdermin E suppresses tumor growth by activating antitumor immunity
Authors: Zhang Zhibin , Zhang Ying , Xia Shiyu , Kong Qing , Li Shunying , Liu Xing , Junqueira Caroline , Ansara James , Sengupta Satyaki , Yao Yandan , Wu Hao , Lieberman Judy 
Published: March 2020

Abstract
Caspase-3 cleaves gasdermin E (GSDME) and converts noninflammatory apoptosis to inflammatory cell death (pyroptosis) in GSDME-expressing cells. GSDME expression is suppressed in many cancer lines and mutated in some others, and reduced GSDME is associated with metastasis and decreased survival in breast cancer, suggesting GSDME might be a tumor suppressor. Here we show reduced GSDME function of 7 of 8 tested cancer-associated mutations. Gsdme knockout in GSDME-expressing tumors enhances, while ectopic expression in Gsdme-repressed tumors inhibits, tumor growth. The GSDME tumor-suppressive effect is cell-extrinsic, mediated by cytotoxic lymphocyte killing and abrogated in perforin-deficient mice or mice lacking lymphocytes. GSDME expression enhances tumor-associated macrophage phagocytosis and the number and functions of tumor-infiltrating NK and CD8+ T lymphocytes. Killer cells also activate GSDME-mediated pyroptosis independently of caspase activation when Granzyme B directly cleaves GSDME at the same site as caspase-3 (Asp270). Thus, GSDME suppresses tumor growth by activating anti-tumor immunity.
Citation Format: Zhibin Zhang, Ying Zhang, Shiyu Xia, Qing Kong, Shunying Li, Xing Liu, Caroline Junqueira, James Ansara, Satyaki Sengupta, Yandan Yao, Hao Wu, Judy Lieberman. Gasdermin E suppresses tumor growth by activating antitumor immunity [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A022. doi:10.1158/1535-7163.TARG-19-A022
Abstract A055: Knockdown of E-cadherin gene in cervical cancer cells: An in vitro model for cancer stem cell phenotype?
Authors: Bhattacharyya Shalmoli , Sharma Anuka , Pal Arnab , Srinivasan Radhika 
Published: March 2020

Abstract
Background: Cervical cancer is one of the leading causes of cancer related morbidity and mortality amongst women, especially in developing countries. Recent studies suggest that Cancer stem cells (CSC) are critically involved in regulating the chemo resistant behavior of cancer cells and a relapse of the disease. So targeting CSC-like cells along with the bulk tumor cells can be a promising approach for therapeutics. In this context, we demonstrated that knockdown of E-cadherin gene in cervical cancer cells can generate stem cell-like phenotype and induce epithelial to mesenchymal transition. Interestingly, knockdown of E-cadherin gene in normal keratinocytes did not induce CSC-like cells. Methods: In our study the CSC phenotype cells were isolated by side population (SP) assay from cervical cancer cells and immortalized keratinocytes. The expression of stem cell marker and EMT genes were confirmed by qRT-PCR and immunostainings. Further, we performed SiRNA-mediated knockdown of E-Cadherin (E-Cad) and studied the tumorsphere formation, metastasis and invasion ability of cervical cancer cells. Next, using RTPCR based gene expression analysis and tumorsphere formation we studied the stem–like properties of cancer cells. We also performed dose dependent cell viability assay using clinically relevant drugs and inhibitors to analyze the drug resistance behavior of the tumorspheres (cervical organoids). Results: We found that E-Cad knockdown induces EMT in cervical cancer cells with stem cell-like characteristics along with enhanced tumorsphere formation, metastasis and invasion ability. These cells not only possess CSC-like phenotype at transcriptional and translational level but also functionally as shown by drug resistance behavior studies. Conclusion: Thus, we believe that this can be a promising model to study CSC-like characteristics in-vitro in cervical cancer to target the molecular pathways for therapeutics.
Citation Format: Shalmoli Bhattacharyya, Anuka Sharma, Arnab Pal, Radhika Srinivasan. Knockdown of E-cadherin gene in cervical cancer cells: An in vitro model for cancer stem cell phenotype? [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A055. doi:10.1158/1535-7163.TARG-19-A055
Abstract A057: The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma
Authors: Chesnokov Mikhail , Yousif Abdelrahman , Chefetz ilana 
Published: March 2020

Abstract
Rationale: High-grade serous ovarian carcinoma (HGSOC) is the deadliest of gynecological cancers due to high rates of recurrence and acquired chemoresistance. Recurrent tumors are suggested to originate from cancer stem-like cells (CSCs) which have been shown to have high MEK1/2 activity signaling pathway to survive and proliferate. Present work investigates the potential of selective MEK1/2 inhibition as a CSC-targeting HGSOC therapy approach. Methods: MEK1/2 pathway activity was evaluated in clinical HGSOC tissue samples and ovarian cancer cell lines using tissue microarray-based immunohistochemistry, immunoblotting and RT-qPCR. OVCAR8 and PEO4 HGSOC cell lines were used to assess the effect of MEK1/2 inhibition on cell viability, proliferation rate and stem-like characteristics in vitro. Mouse xenografts were used to investigate MEK1/2 inhibition effect on tumor growth in vivo. Drug washout experimental model was used to study the lasting effects of MEK1/2 inhibition therapy. Results: MEK1/2 signaling is active in majority of HGSOC tissue samples and cell lines and is further stimulated by cisplatin treatment. MEK1/2 inhibitor trametinib drastically inhibits activity of MEK1/2 downstream signaling, causes prominent cell cycle arrest in G1/0-phase in vitro and reduces tumor growth rate in vivo, but does not induce cell death. Cells treated with trametinib display high CD133+ fraction and increased expression of stemness-associated genes. Transient trametinib treatment causes long-term increase in high ALDH1 activity cells that possess capability of surviving and growing in non-adherent conditions. Conclusions: MEK1/2 inhibition in HGSOC cells efficiently inhibits cell proliferation and tumor growth and therefore may be promising approach to suppress ovarian cancer cell growth. As MEK1/2 inhibition promotes stem-like properties, including ALDH activity, it should be used in combination with CSC-targeting drugs, especially ALDH1 inhibitors.
Citation Format: Mikhail Chesnokov, Abdelrahman Yousif, ilana Chefetz. The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A057. doi:10.1158/1535-7163.TARG-19-A057
Abstract A060: Inhibition of Aurora B kinase activity triggers senescence that can be bypassed by blocking p53 and RB function, promoting replication stress
Authors: Andrews Ariel , Kumar Ramyashree Prasanna , Nazareth Deborah , Ehmann Anna , Hooper John , McMillan Nigel , Gabrielli Brian 
Published: March 2020

Abstract
Aurora B kinase has a major role in regulating progression through mitosis and partitioning the replicated genome at exit from mitosis and cytokinesis. We have previously reported that Aurora A and B inhibitors selectively targeted HPV-driven tumours, and that the HPV E7 oncogene is a major determinant of this selectivity. Another group has shown that sensitivity to Aurora B inhibitor AZD2811 is dependent on loss of the retinoblastoma protein (RB). Here we have investigated the outcomes of inhibition of Aurora B using selective and pan Aurora inhibitors. We show that inhibition of Aurora A and B promotes more cell death, although a subset of cells are protected from the cytotoxic effects as a consequence of Aurora A inhibition slowing the cell cycle. Aurora B inhibition promotes senescence, although this requires at least two cycles of failed cytokinesis in all cell types, including primary fibroblasts. Loss of RB function either by HPV E7 or CDK4 R24C mutant over-expression, and loss of p53 function have somewhat different effects on the outcomes of Aurora B inhibition, although both reduced the proportion of cells that entered senescence. Loss of either also promoted replication stress which was not observed in RB and p53 proficient cells, the level of replication stress was not enhanced by Aurora A co-inhibition. Selective Aurora B inhibitor was also less toxic to proliferating PBMC derive CD3+ T cells than the pan Aurora inhibitor. Together these data indicate that short term treatment with Aurora B selective inhibitor is sufficient to promote cell cycle arrest and senescence in RB and p53 proficient cells, although proliferating T cells appear to tolerate this. RB and p53 pathway defective cells are less sensitive to this senescence trigger, but undergo replication stress.
Citation Format: Ariel Andrews, Ramyashree Prasanna Kumar, Deborah Nazareth, Anna Ehmann, John Hooper, Nigel McMillan, Brian Gabrielli. Inhibition of Aurora B kinase activity triggers senescence that can be bypassed by blocking p53 and RB function, promoting replication stress [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A060. doi:10.1158/1535-7163.TARG-19-A060