tbuckley/cabot-search huggingface dataset:
Abstract 3279: All-<i>trans</i>-retinoic acid (ATRA) markedly augments anti-tumor immunity
Authors: Lu Huang, Zibo Chen, Leila Williams, Yulong Chen, Yunfei Wang, Masanori Kawakami, Jason Roszik, Patrick Hwu, Ethan Dmitrovsky, Weiyi Peng, Xi Liu
Journal: Cancer Research (2019)

Abstract All-trans-retinoic acid (ATRA) engages diverse actions on populations of immune cells. These include effects on regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), Th17 and other immune cells. Prior work found that ATRA can induce anti-tumor immunity through MDSCs and CD8+ T cells and pro-tumor immunity by increasing Treg cells. In this study, we explored how ATRA modulated anti-tumor immunity in solid tumors. To do this, syngeneic lung cancer and colon cancer models were independently developed by optimizing subcutaneous injections of ED1SQ4 lung cancer and MC38 colon cancer cells into immune-competent mice. ATRA-treatment markedly repressed both syngeneic lung cancer and colon cancer growth as compared to vehicle-treated mice. To exclude the possibility that ATRA directly suppressed growth of cancer cells, ED1SQ4 and MC38 cells were independently implanted subcutaneously into athymic mice in order to allow these lung and colon cancer xenografts to grow. Notably, ATRA-treatment did not reduce the growth of these respective xenograft tumors. Intriguingly, ATRA did not suppress in vitro proliferation of either ED1SQ4 or MC38 cells. This implicated ATRA as engaging mechanisms that affect the tumor microenvironment. To learn if the observed anti-tumorigenic activity was mediated by regulation of T cell immunity, CD4+ or CD8+ T cell populations were depleted in syngeneic mice before in vivo ATRA-treatment. CD4+ and CD8+ T cell depletion from syngeneic mice at least partially reversed the tumor suppressive activity of ATRA. Flow cytometry assays conducted on intratumoral immune cells revealed that ATRA-treatment decreased the CD8+ T to Treg cellular ratios while increasing the ratios of CD8+ T to Treg cells. Cytokine and chemokine assays were performed on these syngeneic cancers as well as on peripheral blood harvested from ATRA or vehicle-treated syngeneic mice in order to identify mediators of the observed anti-tumorigenic effects. Findings will be presented. Taken together, this study uncovered a previously unrecognized role for ATRA in augmenting immunotherapy. These preclinical immunotherapy findings can be translated into the cancer clinic. Citation Format: Lu Huang, Zibo Chen, Leila Williams, Yulong Chen, Yunfei Wang, Masanori Kawakami, Jason Roszik, Patrick Hwu, Ethan Dmitrovsky, Weiyi Peng, Xi Liu. All-trans-retinoic acid (ATRA) markedly augments anti-tumor immunity [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 3279.
Abstract MP001: The Number of Low and High Energy Dense Foods Consumed Affects Body Mass Index Reduction in a Randomized Controlled Weight Loss Trial
Authors: Maya Vadiveloo, Hollie Raynor
Journal: Circulation (2017)

Background: Decreasing dietary energy density is recommended to promote weight loss. However, it is unclear whether decreasing dietary energy density is best accomplished by increasing the number of low energy dense (LED) foods (≤1 kcal/g) or by decreasing the number of high energy dense (HED) foods (≥3 kcal/g) in the diet, and whether these actions have different effects on weight loss. We explored how the number of LED and HED foods consumed affected dietary energy density and change in BMI during the 6-month weight-loss phase of an 18-month weight loss trial. Methods: A secondary analysis of 202 adults 21-65y with a BMI between 27 and 45 kg/m 2 participating in a weight loss trial was conducted. Participants were randomized to 1 of 2 conditions – a standardized lifestyle intervention or a standardized lifestyle intervention plus a goal to limit consumption of non-nutrient-dense, energy-dense foods to 2 foods. Dietary intake, assessed via 3, 24-hour recalls, and BMI were measured at baseline and 6 months. Generalized linear models were used to examine the association between residualized changes in LED foods and HED foods and dietary energy density and change in BMI between baseline and 6 months. All analyses were adjusted for age, sex, race, education, treatment group, change in energy intake, and number of LED or HED foods. Results: At baseline, participants had a daily average energy density of 1.25 kcal/g, which decreased to 0.82 kcal/g at 6-months (p&lt;0.0001). Similarly, daily number of LED foods consumed increased from 4.46 to 5.64 foods/day while daily HED foods consumed decreased from 4.02 to 2.98 foods/day (p&lt;0.0001). In fully-adjusted models, a 1-unit increase in LED foods was associated with a 0.07 decrease in the overall energy density of the diet while a 1-unit decrease in HED foods was associated with a 0.08 decrease in energy density (p&lt;0.05); no significant changes in BMI were detected. However, when we examined changes in BMI among those who decreased (&gt;1 unit), maintained (&lt; 1-unit), or increased (&gt;1 unit) the number of LED or HED foods, significantly greater changes in BMI were observed among those with stable (-3.3 ± 0.4 kg/m 2 ) or increased LED food intake (-3.5 ± 0.4 kg/m 2 ) compared to those who decreased LED foods (-2.4 kg ± 0.5 kg/m 2 , p&lt;0.05). No differences in BMI were observed among those who decreased, maintained, or increased the number of HED foods, though similar decreases in energy density were observed among those who decreased HED foods or increased LED foods (-0.6 kcal/g). Conclusions: Decreasing HED foods and increasing LED foods both reduced the overall ED of the diet, but increasing LED foods was associated with significant reductions in BMI.
Model-based evaluation of the long-term cost-effectiveness of systematic case-finding for COPD in primary care
Authors: Tosin Lambe, Peymane Adab, Rachel E Jordan, Alice Sitch, Alex Enocson, Kate Jolly, Jen Marsh, Richard Riley, Martin Miller, Brendan G Cooper, Alice Margaret Turner, Jon G Ayres, Robert Stockley, Sheila Greenfield, Stanley Siebert, Amanda Daley, KK Cheng, David Fitzmaurice, Sue Jowett
Journal: Thorax (2019)

Introduction ‘One-off’ systematic case-finding for COPD using a respiratory screening questionnaire is more effective and cost-effective than routine care at identifying new cases. However, it is not known whether early diagnosis and treatment is beneficial in the longer term. We estimated the long-term cost-effectiveness of a regular case-finding programme in primary care. Methods A Markov decision analytic model was developed to compare the cost-effectiveness of a 3-yearly systematic case-finding programme targeted to ever smokers aged ≥50 years with the current routine diagnostic process in UK primary care. Patient-level data on case-finding pathways was obtained from a large randomised controlled trial. Information on the natural history of COPD and treatment effects was obtained from a linked COPD cohort, UK primary care database and published literature. The discounted lifetime cost per quality-adjusted life-year (QALY) gained was calculated from a health service perspective. Results The incremental cost-effectiveness ratio of systematic case-finding versus current care was £16 596 per additional QALY gained, with a 78% probability of cost-effectiveness at a £20 000 per QALY willingness-to-pay threshold. The base case result was robust to multiple one-way sensitivity analyses. The main drivers were response rate to the initial screening questionnaire and attendance rate for the confirmatory spirometry test. Discussion Regular systematic case-finding for COPD using a screening questionnaire in primary care is likely to be cost-effective in the long-term despite uncertainties in treatment effectiveness. Further knowledge of the natural history of case-found patients and the effectiveness of their management will improve confidence to implement such an approach.
Abstract 12586: Erythropoietin Given during CPR Increases Post-Resuscitation Myocardial O2 Consumption and Reduces Myocardial Stunning
Authors: Vesna Borovnik Lesjak, Kasen Whitehouse, Alvin Baetiong, Artin Bassel, Evyan Jawad, Jeejabai Radhakrishnan, Raúl J Gazmuri
Journal: Circulation (2012)

Background: We previously reported in a rat model of VF that erythropoietin (EPO) given during CPR reverses post-resuscitation myocardial dysfunction associated with preservation of cytochrome c ox...
Abstract 4641: Metabolic reprogramming of the breast contributes to a cancer promoting milieu
Authors: Natascia Marino, Rana German, Xi Rao, George Sandusky, Max Jacobsen, Sha Cao, Anna Maria Storniolo
Journal: Cancer Research (2019)

Abstract In addition to the accumulation of pro-oncogenic mutations in the epithelial cells, the tumorigenic process involves the dysregulation of the interactions between the epithelial cells and their microenvironment, as well as alterations within the microenvironment itself. The latter is composed of endothelial cells, immune cells, fibroblasts, unaffected epithelium, and adipocytes. Increasing evidences support that cell transformation progresses in a potentially cancer-promoting microenvironment context, also known as field cancerization model. Therefore, it is critical to investigate changes occurring in both the epithelial compartment and the surrounding microenvironment to understand how breast cancer initiates. In our preliminary study, we analyzed the transcriptome profile of microdissected breast tissue compartments (epithelium, stroma and adipose tissue) from tissue biopsies obtained from women who donated their histologically normal tissue two-to-five years before breast cancer diagnosis (here labeled pre-cancer), and matched healthy control donors. In the pre-cancer breast epithelium we detected a significant increase in lipid metabolism-related genes including lipases (HSL, LPL) and perilipins (PLIN1, PLIN4), which mediate the release of fatty acids from triacylglycerol storage, and ELOVL5 and ELOVL7, which generate oleic acid. Moreover, Acyl-CoA Synthetase Medium Chain Family Member 1, ACSM1, involved in the activation of lipoic acid, an essential cofactor for mitochondrial metabolism, is also upregulated in pre-cancer breast tissue. Upregulation of genes involved in metabolic activation is observed also in the stroma and adipose tissue compartments. Interestingly, the transcriptome profiling of the pre-cancer breast stroma shows the downregulation of genes coding for several immune cell markers as compared with the healthy controls. Immunohistochemical staining of CD45 confirms a significant reduction in immune cells in the pre-cancer versus matched healthy control breasts. This finding suggests the prevalence of an immune-suppressive environment in the breast long before the clinical diagnosis of breast cancer. Understanding the changes occurring in the cancerized field is critical for elucidating 1) the involvement of microenvironment in cancer initiation 2) the role of histologically normal yet genetically altered surgical margins in risk of disease recurrence upon lumpectomy for early breast cancer diagnosis, and 3) the mechanisms of field cancerization in the contralateral breast. Citation Format: Natascia Marino, Rana German, Xi Rao, George Sandusky, Max Jacobsen, Sha Cao, Anna Maria Storniolo. Metabolic reprogramming of the breast contributes to a cancer promoting milieu [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 4641.
A novel thrombopoietin mimetic RWJ-800088 increases megakaryopoiesis without causing malignant proliferation in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
Authors: Diego Andres Adrianzen Herrera, Gaurav Choudhary, Tushar Bhagat, Shanisha Gordon-Mitchell, Hui Zhang, Ulrich Steidl, Britta Will, Gary Eichenbaum, Chandan Guha, Amit Verma
Journal: Journal of Clinical Oncology (2019)

e18527 Background: In patients (pts) with AML and MDS, thrombocytopenia is a source of morbidity/mortality and there is a need for safer treatment options. RWJ-800088 (RWJ) is a novel pegylated thrombopoietin (TPO) mimetic peptide that increases megakaryopoiesis preclinically and in humans. Before using a TPO mimetic agent in AML and MDS pts, it is important to evaluate if the agent has potential stimulatory effects on malignant myeloid cells. To assess whether RWJ is likely to stimulate malignant myeloid cells, we evaluated its effects in vitro on primary human samples from healthy controls and AML/MDS pts. Methods: We studied the effect of various RWJ doses on proliferation of AML/MDS cell lines; clonogenic capacity for leukemic colony forming units (CFU) and megakaryocytic CFU (CFU-Mk) of mononuclear cells (MNC) from controls and several MDS and AML pts; and expression of differentiation markers in MNC cultures. Results: RWJ treatment had no effect on proliferation of THP1, MOLM13, MV411 and MDSL cell lines at doses up to 1000 ng/ml. A slight increase in proliferation of CMK, a megakaryocytic cell line, was seen at doses &gt; 5xEC50 (mean 12%, p = 0.03). Primary clonogenic assays from 18 AML/MDS pts did not show increased growth of leukemic CFU at RWJ concentrations up to 10 ng/ml and RWJ had a nonsignificant inhibitory effect in 4 pts. Notably, RWJ significantly increased normal CFU-Mk formation from MNC in 6 of 8 AML and all MDS pts (mean 2.6-fold, p = 0.02), as well as from healthy CD34+ stem cells and healthy MNC controls (mean 1.7-fold, p = 0.03). FACS analysis of primary cultures treated with RWJ showed no increase in the malignant blast compartment, no change in differentiation markers of granulocyte/monocyte or erythrocyte lineages but a significant increase in the number of CD41a+ megakaryocytic cells (mean 1.8-fold, p &lt; 0.01). RWJ treatment increased phosphorylation of STAT5 but not STAT3, demonstrating on target stimulation of the TPO receptor in hematopoietic cells. Conclusions: Our results show that the novel TPO mimetic RWJ stimulates megakaryopoiesis without causing proliferation of the malignant myeloid clone in MDS and AML.
Abstract 15805: Pneumothorax During CIED Placement is a Predictor of Mortality
Authors: Katrina Bidwell, Bridget Pagan, Mary Melissa Czarapata, Samy Claude Elayi
Journal: Circulation (2017)

Background: Pneumothorax (PTX) is a potential complication of vascular access during cardiac implantable electronic device (CIED) procedure and is under scrutiny as considered a healthcare-acquired...
Abstract LB-063: Validation of humanized PD-1 knock-in mice as an emerging model to evaluate human specific PD-1 therapeutics
Authors: Anya Avrutskaya, Fabiane Sonego, Jacob Hauser, Emily O’Koren, Gaëlle Martin, Julie Chaix, Robin Ball, Thi Bui, Ian Belle, Chassidy Hall, Kader Thiam, Paula L. Miliani De Marval
Journal: Cancer Research (2019)

Abstract Over the past decade there has been an increasing demand in the use of syngeneic models for evaluating the efficacy of checkpoint inhibition-based cancer immunotherapies. During tumor development, immune cells can became unresponsive to the presence of tumor cells due to chronic activation and expression of the programmed cell death protein-1 (PD-1) or the T-lymphocyte-associated antigen 4 (CTLA4) in T-cells or the presence of FoxP3+ Treg cells resulting in tumor immune-tolerance. Our previous studies have demonstrated that murine anti-PD-1 and CTLA-4 therapy can effectively re-activate the antitumor response against multiple syngeneic tumor models. While these models proved instrumental for evaluating murine immune-checkpoint inhibitors (ICI), there is a clear need for additional mouse models to evaluate the efficacy of ICI specific for human targets. To address this need, we describe the development of a humanized PD-1 knock-in (KI) mouse model. This mouse model has the advantage of expressing the human PD-1 protein in the context of a fully functional immune system. We also show the response to clinically relevant immune checkpoint inhibitors in two preclinical tumor models. We evaluated the anti-tumor activity of pembrolizumab in the MC38 colorectal carcinoma and the GL261 glioblastoma models. We observed significant tumor growth inhibition and growth delay in the MC38 tumor model when treated with pembrolizumab monotherapy, but not when treated with the murine counterpart (anti-PD-1 clone RPM1-14). To extend our validation studies to other tumor models, we implanted GL261 glioblastoma orthotopically in the brain of PD-1 KI mice and achieved a significant increased life span in the group treated with pembrolizumab compared to both the control group and the group treated with murine anti-PD-1 antibody. The immune profile from control and treated these animals were also characterized in these studies by flow cytometry. In summary, the results shown here underscore the value of the humanized PD-1 knock-in (KI) mouse model as a tool to evaluate human specific immune-checkpoint based therapeutics alone and in combination with other agents. Citation Format: Anya Avrutskaya, Fabiane Sonego, Jacob Hauser, Emily O’Koren, Gaëlle Martin, Julie Chaix, Robin Ball, Thi Bui, Ian Belle, Chassidy Hall, Kader Thiam, Paula L. Miliani De Marval. Validation of humanized PD-1 knock-in mice as an emerging model to evaluate human specific PD-1 therapeutics [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 LB-063.
Abstract 633: Association between saturated fat intakes and lung cancer risk among low-income populations in the Southeastern United States
Authors: Hyung-Suk Yoon, Hui Cai, Jae Jeong Yang, Danxia Yu, Harvey J. Murff, Xiao Ou Shu, Wei Zheng, William J. Blot, Qiuyin Cai
Journal: Cancer Research (2019)

Abstract Background: Lung cancer is the leading cause of cancer death in the United States. Previous studies have indicated that a higher intake of dietary saturated fat was associated with lung cancer risk. However, little is known about the association of specific classes of saturated fat with the risk of lung cancer. We conducted a nested case-control study to investigate the association of different classes of saturated fat with lung cancer risk among low-income African Americans (AAs) and European Americans (EAs) in the Southeastern United States. Methods: A total of 1,528 incident lung cancer cases and 5,699 matched controls from the Southern Community Cohort Study were included in this study. The controls were matched to the cases on age, sex, race, and recruitment site. Using validated food frequency questionnaires, saturated fat was estimated and classed to short-chain (SCSF, 2-4 carbon atoms), medium-chain (MCSF, 6-12 carbon atoms), and long-chain (LCSF, 14-18 carbon atoms). Multivariate logistic regression models were used to estimate odds ratios (ORs) and corresponding confidence intervals (95% CIs) for lung cancer risk associated with saturated fat after adjusting for age, smoking status, pack-years, alcohol consumption, total energy intake, education, household income, body mass index (BMI), and history of chronic obstructive pulmonary disease (COPD). Results: Total saturated fat intakes were associated with an increased lung cancer risk among EAs with an OR of 1.66 (95% CI: 1.06-2.60) for the highest vs. lowest quartiles (p-trend=0.03). The positive association was only observed for LCSF (highest vs. lowest quartile: OR=1.68, 95% CI: 1.07-2.64 for palmitic acid; OR=1.60, 95% CI 1.02-2.53 for stearic acid; and OR=1.63, 95% CI 1.04-2.56 for total LCSF; all p-trends&amp;lt;0.05). The association was more evident among heavy smokers, which was defined as smoke ≥ 30 pack-years, and for adenocarcinoma subtype. No association between saturated fat intakes with lung cancer risk were observed among AAs. In addition, no association between lung cancer risk and SCSF or MCSF was observed in our study. Conclusion: Our findings indicate that a high intake of LCSF was associated with an increased risk of lung cancer among low-income EAs. Further studies are needed to confirm our findings. Citation Format: Hyung-Suk Yoon, Hui Cai, Jae Jeong Yang, Danxia Yu, Harvey J. Murff, Xiao Ou Shu, Wei Zheng, William J. Blot, Qiuyin Cai. Association between saturated fat intakes and lung cancer risk among low-income populations in the Southeastern United States [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 633.
Abstract 4073: Novel BETi NHWD-870 synergizes with immune checkpoint inhibitor in preclinical model of non-small cell lung cancer
Authors: Yongchang Zhang, Ziyi Sun, Nong Yang
Journal: Cancer Research (2019)

Abstract Background: Small molecular inhibitors targeting bromodomain and extraterminal domain (BET) protein is promising in cancer therapy. NHWD-870 was a highly selective BETi and has been proved effective in lung cancer according to our previous findings. Combination of immune checkpoint inhibitors with BETi is now under investigation for lung cancer treatment. Method: We set up a fast track preclinical model with C57 mouse. Growth rate and survival data were measured in subgroups receiving single NHWD-870, single PD-1 antibody and combined treatment respectively. Finally, pathology sections, immunohistochemistry and inflammatory cell infiltration was applied to evaluate the pathological response. Result: Millions of mouse lung cancer cells were harvested and injected to the lateral leg. Lung cancer xenografts were visible in 3-5 days. And the total survival time was within 30 days without any treatment. Tumor volume was measured for effective evaluation. During the three groups, NHWD-870 combined with anti-PD-L1 showed robust efficacy in inhibiting tumor growth. And the survival time was also prolonged significantly. Pathological examination showed the lung cancer cells were filled with necrosis. Inflammatory cell infiltration and immunohistochemistry showed that PD-L1 was down regulated and CD4+/ CD8+ positive lymphocyte cells increased significantly. Conclusion: We established a useful method to evaluate tumor response to immune checkpoint inhibitor. And our data proved BETi plus immune checkpoint inhibitor to be a promising treatment of NSCLC. Citation Format: Yongchang Zhang, Ziyi Sun, Nong Yang. Novel BETi NHWD-870 synergizes with immune checkpoint inhibitor in preclinical model of non-small cell lung 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 4073.
Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex
Authors: Qihui Wang, Hao Song, Hao Cheng, Jianxun Qi, Gol Nam, Shuguang Tan, Junzhi Wang, Min Fang, Yi Shi, Zhigang Tian, Xuetao Cao, Zhiqiang An, Jinghua Yan, George F. Gao
Journal: Cellular and Molecular Immunology (2019)
Antimicrobial peptide derived from insulin‐like growth factor‐binding protein 5 activates mast cells via Mas‐related G protein‐coupled receptor X2
Authors: François Niyonsaba, Pu Song, Hainan Yue, Nutda Sutthammikorn, Yoshie Umehara, Ko Okumura, Hideoki Ogawa
Journal: Allergy (2019)

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