bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1263: TGF-ß inhibition as a novel strategy to prevent breast cancer brain metastases
Authors: Pinti Mark V. 
Published: August 2018

Abstract
Background: Incidence of breast cancer brain metastases (BCBM) is on the rise due to improved management of systemic disease and ranges from 15-20% in women with disseminated breast cancer. Common chemotherapeutic strategies have limited efficacy for brain metastases due to the presence of the blood brain barrier (BBB). Prevention of metastasis after diagnosis of primary breast tumors may lead to new treatment strategies. TGF-ß is a biomolecule in the metastatic pathway and inhibition of its expression can be achieved by treatment with the antihypertensive agent Losartan. Herein we hypothesized that treatment with Losartan will decrease metastatic burden and improve survival in a preclinical model BCBM.
Methods: Athymic female nude mice were separated into four groups as follows: Vehicle, (saline, 50µL/day), SB431542 (Inhibitor, 5mg/kg/day), Low Dose Losartan (10mg/kg/day) and High Dose Losartan (25mg/kg/day). On day 7 mice were intracardially injected with 175,000 cells of either JIMT-1-Br-LUC-GFP (HER2+) or MDA-MB-231Br-LUC (TNBC) breast cancer cell lines. Tumor burden was monitored once weekly utilizing bioluminescent imaging. Mice were allowed to progress until neurological symptoms arose. Following euthanasia, brains were extracted, sectioned and analyzed to determine number of metastatic lesions and size.
Results: With regard to survival, no significance was shown in the JIMT-1 (HER2+) metastatic model. The MDA-MB-231Br (TNBC) model demonstrated an increase in survival in all treatment groups compared to vehicle. End time-point analyses showed no difference in metastases number in either model, however, the low dose treatment group in the MDA-MB-231Br model had a smaller brain burden of metastases than high dose treatment as well as inhibitor treatment.
Conclusions: Losartan reduced metastatic seeding in the MDA-MB-231Br (TNBC) brain metastasis model, but had little to no effect in the JIMT-1 (HER2+) model.
Citation Format: Mark V. Pinti. TGF-ß inhibition as a novel strategy to prevent breast cancer brain metastases [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 1263.
Abstract 1271: Restricted feeding of a high-fat diet to the dark phase of the day attenuates mammary tumorigenesis in MMTV-PyMT mice
Authors: Sundaram Sneha , Yan Lin 
Published: August 2018

Abstract
Obesity is a risk factor for breast cancer. Chronic overeating during the rest phase of the day leads to metabolic dysfunction and obesity. Lifestyle changes including restriction of meal times may be successful weight loss strategies. In the present study, we tested the hypothesis that restricted feeding of a high-fat diet to the dark phase (the active phase) of the day reduces diet-enhanced mammary tumorigenesis in an MMTV-PyMT transgenic mouse model. Mice (female) were fed the AIN93G diet (16% of energy from soybean oil) or the high-fat diet (45% of energy from soybean oil) with or without restricted feeding to the dark phase (12 hours) over eight weeks of the study. The body fat mass of the restricted feeding group was lower than the high-fat group but similar to the AIN93G control group. The mammary tumor latency was 5.8, 7.0, and 6.4 weeks for the control, high-fat and high-fat restricted groups, respectively. Restricted feeding reduced mammary tumor progression by 58% compared to the unrestricted feeding of the high-fat diet. Compared to the AIN93 diet, the high-fat diet significantly increased plasma concentrations of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, resistin, leptin, insulin, angiopoietin-2, hepatocyte growth factor and vascular endothelial growth factor. The restricted feeding reduced concentrations of the aforementioned variables in plasma, except resistin, leptin, and insulin. In summary, restricted feeding of the high-fat diet to the dark phase reduces diet-enhanced mammary tumorigenesis. This protection of the restricted feeding against breast tumorigenesis may be associated with its actions in attenuating adipogenesis and production of related inflammatory cytokines and angiogenic factors.
Citation Format: Sneha Sundaram, Lin Yan. Restricted feeding of a high-fat diet to the dark phase of the day attenuates mammary tumorigenesis in MMTV-PyMT mice [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 1271.
Abstract 1275: A role for FGF2 in visceral adiposity-associated mammary epithelial transformation
Authors: Benham Vanessa , Chakraborty Debrup , Bullard Blair , Bernard Jamie J. 
Published: August 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.
Abstract 1277: 3-Isothiocyanato-1-propene as biomodulatory agent in ameliorating phenobarbital induced alterations in profile of detoxifying enzymes in different metabolic sites of Wistar rats
Authors: Arora Saroj , Bhushan Sakshi , Vig Adarsh Pal , Kaur Pardeep , Shergill Robin 
Published: August 2018

Abstract
Backgound: Human exposure to xenobiotics is responsible for increased susceptibility to genetic and epigenetic changes. These changes are further accountable for disruption of pathways involved in cell proliferation, apoptosis, differentiation and senescence. Among array of plant products, that play an imperative role against such adverse catastrophes, the naturally occurring isothiocyanate known as 3-Isothiocyanato-1-propene (AITC) possesses abundant biological activities of therapeutic interest.
Purpose of the study: Hence, considering these facts, the present study was planned to analyse four metabolic sites viz., liver, kidneys, stomach and lungs for protective activities of AITC against phenobarbital induced damage in Wistar rats.
Methodology: The rats were divided into eight groups and treatments were given intraperitoneally for five days followed by sacrificing of animals on sixth day. The organs were homogenized and analysed for biochemical parameters and histopathology.
Results: AITC in all the metabolic sites attenuated the levels of cytochrome dependent oxygenases, phase II detoxifying enzymes (DT-diaphorase, γ-glutamyltranspeptidase and glutathione-S-transferase), cascade of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase), membrane bound ATPases (Na+/K+-ATPase, Mg2+-ATPase, Ca2+-ATPase) and serum marker enzymes (SGOT, SGPT, direct bilirubin, indirect bilirubin, alkaline phosphastase, creatinine, blood urea nitrogen). Futhermore, the different doses of AITC (50, 100 and 150 µM/kg bw) resumed the necroinflammatory score by improving the piecemeal necrosis, focal lytic necrosis and portal inflammation.
Conclusion: The maximum efficacy of amelioration by AITC was observed in liver due to the fact that amount of these enzymes in metabolic sites other than liver is quantitatively low. Hence, AITC emerged as potent candidate for ameliorating the harmful effects of non genotoxic carcinogen (phenobarbital) by regulating its metabolism efficiently in rats. Owing to its useful functions, AITC can act as an important bioprotective agent.
Citation Format: Saroj Arora, Sakshi Bhushan, Adarsh Pal Vig, Pardeep Kaur, Robin Shergill. 3-Isothiocyanato-1-propene as biomodulatory agent in ameliorating phenobarbital induced alterations in profile of detoxifying enzymes in different metabolic sites of Wistar rats [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 1277.
Abstract 1291: Master regulator analysis of paragangliomas carrying SDH, VHL, or MAML3 genetic alterations
Authors: Smestad John A. , Maher Louis J. 
Published: August 2018

Abstract
Background: Succinate dehydrogenase (SDH) loss and mastermind-like 3 (MAML3) translocation are two clinically important genetic alterations that occur in subtypes of human paraganglioma and pheochromocytoma (PPGL) neuroendocrine tumors that correlate with increased rates of metastasis. Although hypotheses exist for how global activation of pseudohypoxia and epigenomic hypermethylation are driven via dioxygenase poisoning in the context of SDH loss, it remains unclear how these defects drive tumorigenesis. Additionally, MAML3 translocation has recently been identified as a genetic alteration in PGL and is poorly understood. We hypothesize that a key to understanding the tumorigenic basis for these genetic alterations is the deconvolution of the gene expression profiles in these tumors and identification of the transcription factors responsible for the observed transcriptional changes.
Methods: In the present work, we leverage publicly-available human tumor gene expression profiling experiments (N=179) to reconstruct a PPGL tumor-specific transcriptional network. Inferred network structure was subsequently validated by examining the frequency of known transcription factor DNA-binding motifs in the inferred regulons. We subsequently use the inferred transcriptional networks and known gene expression signatures for specific PPGL subtypes to perform a master regulator analysis nominating specific transcription factors that may control observed oncogenic patterns of gene expression. The findings of the master regulator analysis were confirmed by duplication of the analysis on a second PPGL-specific inferred transcriptional network (N=188 specimens).
Results: A small number of master regulator transcription factors are likely drivers of the observed subtype-specific gene expression patterns in SDH loss- and MAML3 translocation-positive PPGL. Unexpectedly, hypoxia-inducible transcription factors were not identified as master regulators in SDH-loss tumors. Additionally, analysis of the MAML3 translocation subtype master regulators revealed that a single transcription factor, IRX4, may control 37% of the deferentially expressed genes in this highly malignant tumor subtype.
Conclusions: These observations from unbiased analyses suggest a basis for future development of targeted therapies for specific PPGL molecular subtypes.
Citation Format: John A. Smestad, Louis J. Maher. Master regulator analysis of paragangliomas carrying SDH, VHL, or MAML3 genetic alterations [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 1291.
Abstract 1305: A comprehensive investigation of immune infiltrates in hepatocellular carcinoma
Authors: Yoon Sangho 
Published: August 2018

Abstract
Hepatocellular carcinoma (HCC), a major form of primary liver cancer, is one of the leading causes of cancer-related death, and is caused by a myriad of risk factors from chronic inflammation by viral infection to genetic defects. Recent investigations shed light on the importance and role of immune cells in tumor microenvironment; however, since a majority of studies have focused only on tumor sites, the role of immune cells in tumor-surrounding (or precancerous) area with chronic inflammation was not investigated in HCC in detail. For the treatment of HCC patients, liver transplant (total hepatectomy) has been reported to offer much longer survival and better outcome compared to patients who had local tumor resection (partial hepatectomy). Nonetheless, the significance of tumor-infiltrating immune cells (TICs) established in patients who had suffered from chronic inflammation is still vague. Here, we collected total 122 Korean HCC samples, followed by high-throughput RNA sequencing (RNA-seq), from various premalignant stages—fibrosis and dysplastic nodules, tumors to noncacerous normal liver tissues—enhanced with public RNA-seq datasets including HCC from TCGA. Decomposing immune cell types using the RNA-seq data revealed that TICs are dynamically changed with showing no or weak correlations in the normal liver tissues, while being intertwined into dense and strong correlation networks as the disease progresses. Intriguingly, patients who had total hepatectomy showed different composition of immune cells and longer disease-free survival compared to the partial hepatectomy group; however, the presence of regulatory T cells (Tregs) before the transplantation dampened this outcome in the total hepatectomy patients. Tregs in the total hepatectomy group were found to be specific to tumor sites, and were enriched upon tumor progression, while pretreatment, such as embolization, increased the presence of Tregs. Besides the specific immune cells in tumor sites, the composition of certain types of immune cells in tumor-surrounding inflamed tissues was also important for predicting patients' outcomes in HCC. Particularly, alternatively activated macrophages (M2-type) have more predictive power in the patients' outcome when they were inferred from the tumor-surrounding inflamed samples. Our study not only provides a dynamic map of tumor-surrounding and -infiltrating immune cells, but also offers understanding about immune cell networks in the progression of HCC.
Citation Format: Sangho Yoon. A comprehensive investigation of immune infiltrates in hepatocellular carcinoma [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 1305.
Abstract 131: Neutrophil extracellular trap mediate mitochondrial biogenesis in cancer cells to promote growth of metastases
Authors: Yazdani Hamza , Tohme Samer , Roy Eva , Loughran Patricia , Windth Dirk Vander , Huang Hai , Tsung Allan 
Published: August 2018

Abstract
Neutrophils through the release of neutrophil extracellular traps (NETs) in response to surgical stress were shown to be able to capture circulating cancer cells, and in doing so, support the development of metastatic disease. In addition, NETs persist within the tumor microenvironment long after the surgical stress happens. The exact nature of the NETs-tumor interaction and the role that NETs play in dictating the tumor microenvironment is unclear. In vivo, subcutaneous and liver metastasis models of colorectal and hepatocellular cancer were performed in wild type and PAD4 KO mice that lack the ability to form NETs. In vitro, bioenergetics profiles of both HCC and CRC cancer cells were studied after co-culture with NETs, isolated from human and murine neutrophils. We found a 3-fold decrease in the tumor volume of PAD4 KO mice compared to control mice 3 weeks after tumor injection in both subcutaneous and liver metastatic models. PAD4 KO tumors showed significantly decreased neutrophil infiltration and no NET formation within the tumor compared to WT mice. PAD4 KO tumors had decreased proliferation rates and increased apoptosis. In vitro, stressed cancer cells release stress signals such as cytokines, chemokines, and DAMPs (HMGB1 and histones), that enhanced neutrophil migration towards them and subsequently triggered NET formation. In turn, NETs resulted in a 2-fold increase in the expression of mitochondrial biogenesis regulators in cancer cells. Increase mitochondrial mass was observed when treated cancer cells with NETs. A significant increase mitochondrial oxygen consumption rate (OCR) and ATP levels were observed when compared with DNase treatment. Taken together, we suggest that cancer cells help in recruiting NETs which in turn regulates mitochondrial bioenergetics for tumor growth and metastasis.
Citation Format: Hamza Yazdani, Samer Tohme, Eva Roy, Patricia Loughran, Dirk Vander Windth, Hai Huang, Allan Tsung. Neutrophil extracellular trap mediate mitochondrial biogenesis in cancer cells to promote growth of metastases [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 131.
Abstract 1311: Integrating network biology and polypharmacology to reveal TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis
Authors: Wang Neng , Wang Zhiyu , Zheng Yifeng , Wang Shengqi , Zhang Fengxue , Lin Yi 
Published: August 2018

Abstract
Purpose: Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer.
Experimental Design: The anti-metastasis ability of XIAOPI was validated by MMTV-PyMT mice and in vitro cell models. A network pharmacology-based method, which combined large-scale text-mining, drug-likeness filtering, target prediction and network analysis, was conducted to predict TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis, further supported by cytokine array analysis in vitro and in vivo.
Results: In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model. The herb-ingredient-target network analysis further identified a total of 81 genes closely correlated with the breast cancer chemoprevention effects of XIAOPI. Cytokine array analysis further validated CXCL-1 as the key target of XIAOPI both in vitro and in vivo. Evaluation of the mechanism demonstrated that CXCL-1 administration significantly abrogated the metastatic inhibition effects of XIAOPI on breast cancer migration, invasion, stem cells subpopulations, epithelial-mesenchymal transition(EMT), or mammosphere formation abilities.
Conclusions: Overall, our study not only provides experimental evidence and molecular mechanisms that may facilitate the safe and effective use of herbal medicine for the prevention of breast cancer growth or metastasis, and may lead to CXCL-1-based therapeutic strategies for mammary malignancies.
Citation Format: Neng Wang, Zhiyu Wang, Yifeng Zheng, Shengqi Wang, Fengxue Zhang, Yi Lin. Integrating network biology and polypharmacology to reveal TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis [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 1311.
Abstract 1317: Multi-scale mapping of the physical and functional architecture of the cancer cell
Authors: Zheng Fan , Yu Michael K. , Kim Minkyu , Ono Keiichiro , Flagg Mitchell , Kreisberg Jason F. , Krogan Nevan , Ideker Trey 
Published: August 2018

Abstract
Cancer is governed by modular systems of genes, the composition and organization of which remains poorly understood. Here, we integrate physical and functional networks from a wide range of molecular studies to assemble a comprehensive multi-scale map of human cancer cell biology. This map consists of a hierarchical catalog of protein complexes, signaling pathways and inter-pathway crosstalk implicated in cancer, and it suggests many uncharacterized functional modules as intriguing hypotheses for further validation. Analysis of the pattern of somatic mutations in The Cancer Genome Atlas (TCGA) reveals that these mutations target systems of varying scales above the level of individual genes. The map also provides a platform to integrate and interpret new 'omics data; we integrate new protein-protein interactions identified using AP-MS in multiple breast cancer cell lines, revealing how different functional modules are rewired in cancer cells. A general model browsing tool has been created to visualize and navigate these hierarchical cancer maps. This multi-scale mapping approach elucidates the molecular heterogeneity of cancer, connects tumor genotypes to phenotypes and, ultimately, enables a platform for cancer precision medicine.
Citation Format: Fan Zheng, Michael K. Yu, Minkyu Kim, Keiichiro Ono, Mitchell Flagg, Jason F. Kreisberg, Nevan Krogan, Trey Ideker. Multi-scale mapping of the physical and functional architecture of the cancer cell [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 1317.