bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4045: Urban-rural disparity of overweight/obesity distribution and its potential association with breast cancer among Chinese females
Authors: Gao Ying , Huang Yubei , Dai Hongji , Wang Peishan , Li Haixin , Song Fengju , Zheng Hong , Dong Henglei , Han Jiali , Wang Yaogang , Chen Kexin 
Published: July 2016

Abstract
Background: Disparity of overweight/obesity distribution had been investigated in developed countries, but rarely been investigated in developing countries, especially for China with rapid socio-economic development in the past decades.
Methods: A total of 1 210 762 participants were recruited from the Chinese National Breast Cancer Screening Program. Overweight and obesity were defined as body mass index (BMI) ranged 24.0-27.9 kg/m2 and BMI ≥ 28.0kg/m2, respectively.
Results: The prevalence of overweight/obesity for Chinese rural women (35.2%, 29.2% for overweight and 6.0% for obesity) was significantly higher than that for Chinese urban women (33.4%, 27.7% for overweight and 5.7% for obesity) (P &lt;0.001). For either rural or urban women, the prevalence of overweight/obesity was highest in north region, followed by east region for rural women and north-east region for urban women. For rural women, higher prevalence of overweight/obesity was significantly positively associated with elder age, Han nationality, low level of education, no occupation, high family income, less number of family residents, insurance, and elder age at marriage. Similar positive associations were also found for urban women, except negative associations for high family income, less number of family residents, and elder age at marriage. A non-significant positive association between overweight/obesity and breast cancer was found for rural women [odds ratio (OR) = 1.06; 95% confidence interval (CI): 0.87-1.29], but a significant positive association for urban women (OR = 1.55; 95%CI: 1.19-2.02).
Conclusions: There was an obvious urban-rural disparity of overweight/obesity distribution among Chinese females, which could also lead to an obvious disparity of breast cancer distribution.
Citation Format: Ying Gao, Yubei Huang, Hongji Dai, Peishan Wang, Haixin Li, Fengju Song, Hong Zheng, Henglei Dong, Jiali Han, Yaogang Wang, Kexin Chen. Urban-rural disparity of overweight/obesity distribution and its potential association with breast cancer among Chinese females. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4045.
Abstract 4046: The role of TFPI2 and FGF2 in asbestos-induced mesothelial to fibroblastic transition
Authors: Thompson Joyce K. , Miller Jill , MacPherson Maximilian B. , Shukla Arti 
Published: July 2016

Abstract
Mechanisms involved in the tumorigenesis of the devastating cancer, malignant mesothelioma (MM) are poorly understood. We have recently shown that interleukin-1β (IL-1β), an inflammatory cytokine is upregulated by asbestos via the activation of the inflammasome (a molecular platform that assembles for the activation of caspase-1) in mesothelial cells. Furthermore we have demonstrated that IL-1β secretion may lead to the activation of downstream signaling cascades involved in malignant transformation of mesothelial cells.
Preliminary data from our lab indicate that in addition to IL-1β, asbestos exposure upregulated the secretion of basic fibroblast growth factor (bFGF/FGF2) and tissue factor pathway inhibitor 2 ((TFPI2) a kunitz type protease inhibitor). These factors were also regulated by the inflammasome and have never before been implicated in asbestos-induced mesothelial to fibroblastic transition (MFT). Based on our preliminary data, we hypothesized that upregulation of IL-1β by asbestos-induced inflammasome activation increases FGF2 secretion and signaling. Furthermore, we hypothesize that FGF2 together with increased TFPI2 secretion induces transition of mesothelial cells to a fibroblastic phenotype that facilitates MM carcinogenesis. In the proposed study we will delineate the role of TFPI2 (siRNA) and FGF2 (pan FGFR inhibitor, BGJ398) in the process of asbestos-induced MFT.
Data from this study will provide added insight into the mechanisms involved in the initiation of MM and indicate whether TFPI2 and FGF2 can serve as drugable targets for combination therapy against MM. This work is supported by NIH grant, RO1 ES021110.
Citation Format: Joyce K. Thompson, Jill Miller, Maximilian B. MacPherson, Arti Shukla. The role of TFPI2 and FGF2 in asbestos-induced mesothelial to fibroblastic transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4046.
Abstract 4058: DNA damage and tumour burden in mouse colon is increased in response to carcinogen exposure after induction of chronic inflammation - a more disease relevant model of colitis-associated colorectal cancer
Authors: Lannagan Tamsin RM , Mano Mark T. , Head Richard J. , Lockett Trevor , Ernst Matthias , Cosgrove Leah J. 
Published: July 2016

Abstract
Chronic inflammation (CI) such as inflammatory bowel disease increases the risk of developing colorectal cancer (CRC). Tumorigenesis is supported by inflammatory cytokines through increased cell proliferation and inhibiting apoptosis of neoplastic cells. The classic mouse model of colitis-associated CRC (CA-CRC) requires treatment with a mutagen (azoxymethane, AOM) followed by induction of inflammation through ingestion of a luminal irritant (dextran sulfate sodium, DSS). AOM is metabolized by colonic epithelium causing DNA damage through formation of mutagenic DNA adducts. Although the AOM + DSS model of CA-CRC is a valuable research model, it “reverses” events that take place in humans where CI typically precedes CRC. We hypothesise that CI sensitises colonic epithelium to DNA damage and predisposes the epithelium to neoplastic transformation.
In order to investigate this we reversed the AOM + DSS model to more accurately represent the disease process in humans. Using two experimental approaches we treated wildtype (WT) mice with AOM alone or with DSS then AOM and collected colonic tissue after 6 and 48 hours (short-term) or colonic tumours (long-term). Tumour number and size were quantified. Immunohistochemistry was used to analyse DNA damage, apoptosis, and proliferation. Formation of the DNA adduct O6MeG was measured by a modified method of HPLC, and qPCR was used to analyse expression of DNA damage signalling pathway components.
Compared with an AOM challenge alone, prior CI induction by DSS treatment increased DNA damage, reduced apoptosis, and increased tumour number and tumour size. This data reveals how prior CI modulates the colonic epithelial response to mutagen exposure in the short-term and how it promotes tumour formation in the long-term. In addition, this data demonstrates that the “reverse” model of CA-CRC can be successfully used as a more appropriate experimental framework to better understand the molecular mechanisms underpinning CA-CRC and will allow us to further investigate the relationship between prior CI, DNA damage, and tumour development.
Citation Format: Tamsin RM Lannagan, Mark T. Mano, Richard J. Head, Trevor Lockett, Matthias Ernst, Leah J. Cosgrove. DNA damage and tumour burden in mouse colon is increased in response to carcinogen exposure after induction of chronic inflammation - a more disease relevant model of colitis-associated colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4058.
Abstract 406: Enhancer templated RNAs as predictors of therapeutic response to epigenetic therapy
Authors: Firestein Ron , McCleland Mark , Mesh Kathryn , Gnad Florian 
Published: July 2016

Abstract
Colon tumors arise in a stepwise fashion from either discrete genetic perturbations or epigenetic dysregulation. To uncover the key epigenetic regulators that drive colon cancer growth, we utilized a CRISPR loss of function screen and identified a number of essential genes, including the Bromodomain and Extraterminal (BET) protein, BRD4. We find BRD4 is critical for colon cancer proliferation and its loss leads to differentiation effects in vivo. JQ1, a BET inhibitor, preferentially reduced growth in a subset of epigenetically dysregulated colon cancers, characterized by the CpG island methylator phenotype (CIMP). Integrated transcriptomic and genomic analyses defined a distinct super-enhancer in CIMP(+) colon cancers that regulates cMYC transcription. We find that the CCAT1 long non-coding RNA (lncRNA) is transcribed from this super-enhancer and is exquisitely sensitive to BET inhibition. Concordantly, cMYC transcription and cell growth were tightly correlated with the presence of CCAT1 RNA in a variety of tumor types. Taken together, we propose CCAT1 as a clinically tractable biomarker for identifying patients likely to benefit from BET inhibitors.
Citation Format: Ron Firestein, Mark McCleland, Kathryn Mesh, Florian Gnad. Enhancer templated RNAs as predictors of therapeutic response to epigenetic therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 406.
Abstract 4060: The role of p62-dependent regulation of COX-2 in UVA response and skin tumor progression
Authors: Sample Ashley , Qiang Lei , Zhao Baozhong , He Yu-Ying 
Published: July 2016

Abstract
Skin cancer is the most common type of cancer in the US, with an estimated 3.5 million cases diagnosed each year. Exposure to ultraviolet (UV) radiation, namely UVA (320-400 nm) and UVB (290-320 nm), is the major risk factor for the development of skin cancer. UVA is 20-fold more abundant in sunlight than UVB and is the major component of tanning beds. However, the mechanism of UVA's contribution to skin cancer remains unclear. One putative effector of UVA in skin cancer is p62, a selective autophagy cargo protein and substrate. We have found that UVA upregulates p62 expression, independent of autophagy, by inducing transcription of p62. p62 is upregulated in many types of cancer, including squamous cell carcinoma (SCC) and melanoma, and can facilitate the activation of a number of pathways to promote cell proliferation, invasion, inflammation, and survival. We have previously shown that p62 stabilizes Twist1 to promote invasion and proliferation, indicating p62 can function independent of autophagy to promote tumor progression. However, the function of p62 in UVA-induced tumor progression is unknown. Using a candidate gene approach, we identified a novel interaction between p62 and cyclooxygenase-2 (COX-2), which suggests a putative function for p62 in UVA-induced skin cancer. COX-2 is a prostaglandin synthase often overexpressed in cancer, where it correlates with poor prognosis. COX-2 promotes cell proliferation and survival, and inhibition of COX-2 prevents skin cancer development. COX-2 protein expression is induced concomitantly with p62 in response to UVA and knockdown of p62 prevents induction of COX-2 by UVA. As COX-2 transcription is not induced by UVA in skin cancer cells along with p62, we assessed a possible protein-level regulatory mechanism. Co-immunoprecipitation of endogenous p62 and COX-2 in skin cancer cells reveals a novel physical interaction between these proteins. Therefore, we hypothesize that p62 transcription is induced by UVA to promote stability of cyclooxygenase-2 (COX-2) and consequently, tumor progression. This project aims to further understand how UVA regulates p62 and thus COX-2 availability, and the functional significance for skin tumor progression. As both p62 and COX-2 are critical for skin tumor progression, understanding the link between these proteins will unravel a signaling axis central to skin cancer progression.
Citation Format: Ashley Sample, Lei Qiang, Baozhong Zhao, Yu-Ying He. The role of p62-dependent regulation of COX-2 in UVA response and skin tumor progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4060.
Abstract 4082: Epithelial-stromal interactions are altered at the earliest stages of colon cancer development
Authors: Mo Allen , Jackson Stephen , Varma Kamini , Carpino Alan , Giardina Charles , Devers Thomas J. , Rosenberg Daniel W. 
Published: July 2016

Abstract
While progression of nonmalignant colonic cells carrying somatic mutations to early malignancy is dependent upon interactions between mutated epithelium and surrounding stroma, the nature of these interactions is poorly understood. Here we report the development of an ultra-sensitive laser capture microdissection/RNA-seq approach for profiling the epithelial and stromal compartments of mutated aberrant crypt foci (ACF). ACF are the earliest detectable pre-neoplastic lesion found in human colon and were identified using high-definition endoscopy with contrast dye-spray. We focused on epithelial and stromal cells of ACF carrying somatic mutations to either KRAS, BRAF or APC, and compared these to control samples from each patient. By comparing the gene expression from each group, we identified an increase in a number of pro-inflammatory NF-κB target genes that are specific to ACF epithelium (including TIMP1, RELA and RELB). We confirmed distinct transcriptional changes associated with each somatic mutation and demonstrate that a subset of ACF display a BRAFV600E-mediated senescence-associated transcriptome, characterized by increased expression of CDKN2A (p16). Furthermore, ACF-associated stroma is transcriptionally distinct from adjacent normal stroma and genes related to immune cell infiltration and activation of fibroblasts are up-regulated. Immunofluorescence analysis confirms the abundance of activated fibroblasts in ACF stroma regardless of mutational status. These results provide new insight into the cellular interplay that occurs at the very early stages of colon cancer development, highlighting the role of activated stromal fibroblasts and inflammation.
Citation Format: Allen Mo, Stephen Jackson, Kamini Varma, Alan Carpino, Charles Giardina, Thomas J. Devers, Daniel W. Rosenberg. Epithelial-stromal interactions are altered at the earliest stages of colon cancer development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4082.
Abstract 4085: Notch1 signaling determines melanoma-regulating role of tumor stromal fibroblasts
Authors: Shao Hongwei , Kong Ranran , Moller Mecker , Ferrari Massimiliano L. , Zhang Leiming , Radtke Freddy , Capobianco Anthony J. , Liu Zhao-Jun 
Published: July 2016

Abstract
Objectives. Tumor stromal fibroblasts are crucial in regulating tumor growth, invasion and metastasis, yet the molecular mechanisms that determine the tumor regulatory role of stromal fibroblasts remains unknown. Here, we uncover the Notch1 signaling pathway as a molecular determinant that controls the tumor regulatory role of tumor stromal fibroblasts in melanoma growth and invasion. Methods. Murine melanoma cells B16-F10, stably transduced with Luciferase 2 (Luc2)/lentivirus, were xenografted on the skin of two new mouse lines: the Gain-Of-Function of Notch1 (GOFNotch1: Fsp1.Cre+/-;ROSALSL-N1IC+/+) and Loss-Of-Function of Notch1 (LOFNotch1: Fsp1.Cre+/-;Notch1LoxP/LoxP+/+), respectively. GOFctrl (FSP1.Cre-/-;ROSALSL-N1IC+/+) and LOFctrl (FSP1.Cre-/-; Notch1LoxP/LoxP+/+) mice were used as control. Tumor growth was measured based on tumor weight and melanoma local invasion were examined by H&E staining of resected tumor tissue.
Results. Using a mouse melanoma model in which exogenous melanoma cells were grafted on the skin of two lines of mice where the genetic activation or inactivation of Notch1 signaling specifically occurs in natural host stromal fibroblasts, we demonstrated that Notch1 pathway activity could determine the tumor-promoting or tumor-suppressing phenotype in tumor stromal fibroblasts. Tumor stromal fibroblasts carrying elevated Notch1 activity significantly inhibited melanoma growth and invasion, while those with a null Notch1 promoted melanoma invasion.
Conclusions. These findings identify the Notch1 pathway as a molecular determinant that controls the regulatory role of tumor stromal fibroblasts in melanoma skin growth and invasion, unveiling Notch1 signaling as a potential therapeutic target for melanoma and potentially other solid tumors.
Citation Format: Hongwei Shao, Ranran Kong, Mecker Moller, Massimiliano L. Ferrari, Leiming Zhang, Freddy Radtke, Anthony J. Capobianco, Zhao-Jun Liu. Notch1 signaling determines melanoma-regulating role of tumor stromal fibroblasts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4085.
Abstract 4092: High mast cell density is associated with improved prognosis in colon cancer patients
Authors: Sjölander. Anita 
Published: July 2016

Abstract
Background. Inflammatory cells and inflammatory mediators play an important role in colon cancer. However, the role of mast cells (MCs) in colon cancer progression remains unclear. Pro-inflammatory cysteinyl leukotrienes (CysLTs) have been associated with colorectal cancer (CRC) development. In particular, previous studies have shown that CRC patients with increased expression of cysteinyl leukotriene receptor 1 (CysLTR1) have poorer prognoses, and Cysltr1−/− mice display fewer intestinal polyps. The aim of the present study was to investigate the clinical and prognostic significance of mast cell density (MCD) in patients with CRC and to determine the significance of CysLTR1 on MCD in a mouse model of colitis-associated colon cancer (CAC).
Materials and methods. A tissue microarray (TMA) of primary colon cancers from 72 patients was stained with MC anti-tryptase and anti-chymase antibodies. Mouse colon tissue was stained with MC anti-tryptase antibody. Immunohistochemistry was used to identify MCD in cancerous and normal areas of patient tissues and in polyp/tumour, adjacent and normal areas of mouse tissues.
Results. In patient samples, the mean MCD was significantly higher in normal tissue than in cancer tissue (p = 0.0009). Patients with a high MCD in cancer tissue showed better overall survival compared with those with a low MCD (hazard ratio (HR) 0.575; 95% confidence interval (CI), 0.293 - 1.130). The same result was observed in patients aged 55-75 years (HR 0.332; 95% CI 0.121 - 0.911) and among patients without distant metastasis at diagnosis (HR 0.311; 95% CI 0.118 - 0.821). In the CAC mouse model, Cysltr1−/− mice had fewer intestinal polyps and significantly higher MCD in polyp/tumour areas compared with controls.
Conclusion. A high MCD in cancer tissue correlates with longer patient survival. In Cysltr1−/− CAC mice, a high polyp/tumour MCD also appears beneficial. Thus, these results indicate that a high MCD is a good prognostic factor.
Citation Format: Anita Sjölander. High mast cell density is associated with improved prognosis in colon cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4092.
Abstract 4099: Oligodendrocyte stimulates the invasion ability of glioblastoma cells
Authors: Kawashima Toshiyuki 
Published: July 2016

Abstract
Background & Aims: Glioblastoma (GBM, WHO Grade IV) is characterized by rapid cancer cell infiltration, and is one of the most lethal neoplasms among solid cancers. GBM might arise de novo, or following progression from lower grade gliomas. Recently, solid tumor progression has been recognized as the product of an evolving crosstalk between the cancer cells and its surrounding glial cells. The intensive invasion activity of GBM cells might be regulated by normal cells such as oligodendrocytes or fibroblasts. In this study, we evaluated the interaction between GBM cells and glial cells.
Methods: Two GBM cell lines, T98G and U251, were used. Two oligodendrocyte cell lines, ODC1 and ODC2, were derived from surgical tissues of each patient with low-grade glioma (WHO Grade II). Two fibroblasts cell lines, GF1 and GF2, were derived from surgical tissues of each patient with GBM. The culture medium was composed of DMEM with 10% fetal calf serum. We examined the effects of glial cells on the invasion ability of GBM cells by wound-healing assay and invasion assay. Using IncuCyte invasion assay and matrigel invasion assay, the invasiveness of T98G and U251 cells was analyzed in the presence or absence of conditioned medium from oligodendrocyte cells or fibroblasts. The effect of the proliferation of T98G and U251 cells was examined by MTT assay or cell count.
Results: ODC1 and ODC2 cells were positive for Olig2 staining but not for GFAP staining, suggesting that ODC1 and ODC2 were oligodendrocyte cells. GF1 and GF2 cells were spindle-shape and were negative for both Olig2 staining and GFAP staining, suggesting that GF1 and GF2 cells were fibroblasts. Oligodendrocyte cells, ODC1 and ODC2 cells, from grade II glioma significantly (p&lt;0.01) increased the migration and invasion ability of GBM cells, T98G and U251 cells. In contrast, GF1 and GF2 fibroblasts from GBM did not affect on the migration and invasion ability of GBM cells. Both oligodendrocyte cells and fibroblasts did not stimulate the proliferation of T98G and U251 cells.
Conclusion: Oligodendrocytes might up-regulate the invasiveness of malignant glioma cells. An invasion-stimulating factor(s) from oligodendrocyte cells might be partially associated with the progression from lowe-grade gliomas to GBM.
Citation Format: Toshiyuki Kawashima. Oligodendrocyte stimulates the invasion ability of glioblastoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4099.