bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1956: The basic helix-loop-helix (bHLH) transcriptional factor ATOH8 promotes the stemness of breast cancer cells via Oct4 and Nanog
Authors: Chang Antao , Chen Yanan , Shen Wenzhi , Gao Ruifang , Zhou Wei , Luo Yunping , Luo Na , Stupack Dwayne , Xiang Rong 
Published: May 2015

Abstract
Breast cancer is the leading cause of cancer mortality in women with a high incidence of recurrence and eventual treatment failure. The last decade has yielded substantial evidence that cancer stem cells (CSCs) contribute to tumor relapse, metastasis and chemoresistance. CSCs are regulated by complex interactions with the components of the tumor microenvironment through networks of cytokines and growth factors, including the IL6-STAT3 signaling pathway. Although the IL6 signaling pathway has been extensively characterized, the network of effector genes and proteins that regulates the CSC population remains poorly understood. Here, we show that ATOH8 is a downstream effector of IL6-STAT3 signaling which promotes the stemness of breast cancer cells. ATOH8 is significantly increased after IL6 stimulation and can be directly regulated by STAT3. Ectopic expression of ATOH8 in 4T1 or T-47D cells is sufficient to increases the CSC sub-population and enhances tumorogenesis in mice. Mechanistically, ATOH8 promotes the expression of Oct3/4 and Nanog, key regulators of CSC renewed. Accordingly, Knock-down of ATOH8 in EMT6 or MDA-MB-231 cells is associated with decreased expression of Oct3/4 and Nanog and reduces the CSC sub-population. In patients, ATOH8 expression is a negative prognostic indicator for overall survival. Together, the results identify ATOH8 as a downstream effector of IL6-STAT3 signaling that compromises long-term surviving in breast cancer.
Citation Format: Antao Chang, Yanan Chen, Wenzhi Shen, Ruifang Gao, Wei Zhou, Yunping Luo, Na Luo, Dwayne Stupack, Rong Xiang. The basic helix-loop-helix (bHLH) transcriptional factor ATOH8 promotes the stemness of breast cancer cells via Oct4 and Nanog. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1956. doi:10.1158/1538-7445.AM2014-1956
Abstract 2205: A three-gene signature predicts esophageal squamous cell carcinoma prognosis
Authors: Cao Huihui , Li Enmin , Xu Liyan 
Published: May 2015

Abstract
The 5-year survival rate of esophageal squamous cell carcinoma (ESCC) remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. To improve the clinical risk assessment for ESCC patients, we developed an immunohistochemistry-based predictor model by evaluating the prognostic value of a three-gene signature, i.e. epidermal growth factor receptor, phosphorylated Specificity protein 1, and Fascin, which constitute a regulatory axis in ESCC cells as revealed by our previously study. The presence of this three-gene signature and the association with clinical outcomes were analyzed in 185 esophageal curative resection specimens (generation dataset), and the findings were validated using an independent cohort of 130 specimens (validation dataset). We revealed that the protein expression of this three-gene signature was highly predictive of ESCC survival in both generation and validation datasets (P=0.001). Regression analysis showed that this three-gene signature was an independently predictor of overall survival (hazard ratio=1.990 [95% CI, 1.256-3.154], P=0.003 in generation dataset; hazard ratio=2.358 [95% CI, 1.391-3.996], P=0.001 in validation dataset). Importantly, the predictive ability of the 3-gene signature was more robust than that of each individual factor. In conclusion, this immunohistochemistry-based molecular model accurately predicts ESCC patient survival, and thus could serve as a complement to current approached in clinical risk stratification.
Note: This abstract was not presented at the meeting.
Citation Format: Huihui Cao, Enmin Li, Liyan Xu. A three-gene signature predicts esophageal squamous cell carcinoma prognosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2205. doi:10.1158/1538-7445.AM2014-2205
Abstract 2293: A fast and simple method for whole-genome bisulfite library preparation from ultra-low DNA inputs
Authors: Giang Karolyn , Chung TzuHung , Sun Xueguang , Eden Marc E. Van , Jia Xi Yu 
Published: May 2015

Abstract
The distribution of 5-methylcytosine (5-mC) in DNA within the eukaryotic genome is known to greatly affect gene regulation and is currently a major topic of research. Studies on DNA methylation have been aided by advancements in bisulfite conversion and Next-Gen sequencing technologies which can provide single-base resolution of 5-mC across the entire genome. Many whole-genome bisulfite sequencing (WGBS) library preparation protocols designed for analysis of 5-mC distribution employ bisulfite to chemically convert unmethylated cytosine bases into uracil following the library preparation step. While these protocols produce reliable results, degradation of DNA is always an inherent issue when dealing with bisulfite conversion, and a large proportion of the adapterized library is often fragmented and can no longer be amplified. This requires high levels of DNA to serve as the input material. However, by rearranging the order of library preparation and bisulfite conversion, we developed a streamlined protocol that necessitates less input material for accurate whole-genome methylation analysis at single-base resolution. This unique workflow accommodates picogram quantities of starting material, making it ideal for analysis of precious samples that are of limited availability (e.g., FFPE). Comparison of sequencing data generated using this new library preparation method and data generated with established Reduced Representation Bisulfite Sequencing demonstrated a correlation of 0.95 in CpG sites with &gt; 10X coverage in human DNA. Also, with only slight modification, this protocol is versatile enough to be used in the preparation of libraries for ChIP-Seq and RNA-Seq analyses.
Citation Format: Karolyn Giang, TzuHung Chung, Xueguang Sun, Marc E. Van Eden, Xi Yu Jia. A fast and simple method for whole-genome bisulfite library preparation from ultra-low DNA inputs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2293. doi:10.1158/1538-7445.AM2014-2293
Abstract 239: Capsaicin may reduce the metastatic burden in the transgenic adenocarcioma of the mouse prostate (TRAMP) model
Authors: Venier Natalie A. , Yamamoto Toshihiro , Sugar Linda , Fleshner Neil , Klotz Laurence , Venkateswaran Vasundara 
Published: May 2015

Abstract
Introduction and Objective: A large body of evidence supports the role of dietary factors in prostate cancer development and progression. We are interested in investigating the chemopreventive potential of capsaicin, the active compound in chilli peppers that is traditionally used topically to treat various pain-related syndromes. Recently capsaicin has been demonstrated to have anti-carcinogenic properties in vitro through a number of different mechanisms. In our study we aim to study the chemopreventive properties of capsaicin using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, a murine model that closely resembles the progression of human disease.
Methodology: Thirty-five six-week old TRAMP x C57Bk mice were randomized into two groups: control or capsaicin. Mice received either capsaicin (5 mg/kg body weight) or vehicle (saline) three times a week by oral gavage until the age of 30 weeks. Body weight was measured thrice weekly. All mice were sacrificed at 30 weeks. Body weight, genito-urinary (GU) weight, tumour burden were assessed. Prostate, seminal vesicles, lung, liver, esophagus, lymph nodes and pancreas were obtained for histological analysis. Serum was collected at the termination of the study for analysis of serum capsaicin concentration. Prostate tumours were analyzed by immunohistochemical analysis using proliferative and mechanistic markers. All tumours were scored by an on-site pathologist according to the histopathic grading scale described by Hurwitz AA, et al.
Results: Interim results revealed that higher percentage of high-grade cancer in control group (n = 18). The presence of PIN-like pre-cancerous lesions in only the treatment group and not the control group (n = 18). The capsaicin treated mice also demonstrated a reduced proportion of metastatic cancers compared to the control group. There were no significant changes in the GU wet weight between groups (n = 35). Immunohistochemical analysis of the prostate tumour is ongoing. Capsaicin was well tolerated, as there was no pathological liver or esophagus or gastrointestinal toxicities or difference in body weight between groups. Further results are currently under investigation.
Conclusion: Interim results suggest that oral administration of capsaicin is well tolerated and may reduce the metastatic burden in the TRAMP model. Ongoing studies are currently underway to delineate the mechanism of action.
Citation Format: Natalie A. Venier, Toshihiro Yamamoto, Linda Sugar, Neil Fleshner, Laurence Klotz, Vasundara Venkateswaran. Capsaicin may reduce the metastatic burden in the transgenic adenocarcioma of the mouse prostate (TRAMP) model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 239. doi:10.1158/1538-7445.AM2014-239
Abstract 2390: Identification of BRCA2 genetic interactors in an ES cell-based model
Authors: Ding Xia , Sharan Shyam K. 
Published: May 2015

Abstract
Mutations in breast cancer susceptible genes, BRCA1 and BRCA2 are the genetic factors conferring highest risk to develop breast cancer. Although BRCA proteins are known to maintain genomic stability mainly by homologous recombination-mediated DNA damage repair, detailed mechanisms of how BRCA loss induces tumorigenesis remain unclear. Interestingly, while inactivation of both alleles of BRCA1 or BRCA2 genes is necessary for tumor development, their loss in normal cells affects cell viability, indicating that cells lacking BRCA1 or 2 are able to survive and predisposed to tumorigenesis due to mutations in other genes such as those involved in cell cycle regulation or DNA damage response. In the current study, we identified some of the candidate genes using a mouse embryonic stem (mES) cell-based insertional mutagenesis screening. Overexpression of these genes rescued BRCA2 loss-induced lethality in mES cells. One candidate encodes a PDZ domain-containing protein, GIPC3. While overexpression of GIPC3 rescued BRCA2 loss efficiently, overexpression of its close homolog GIPC1 rescued much less efficiently. The GIPC3-rescued cells were hypersensitive to DNA damaging agents and exhibited an overall increase in genomic instability. Point mutation analysis showed several amino acids in the PDZ domain was critical for rescuing BRCA2 lethality, suggesting protein-protein interaction is responsible for the rescuing. We therefore performed IP-MS analysis and found that GIPC3 can interact with APPL1 and APPL2, two important mediators in AKT-mediated survival signal transduction pathway. We are now analyzing if these two molecules are potential down-stream factors of GIPC3 in rescuing BRCA2 loss-induced lethality. Meanwhile, we found that Gipc3 overxpression can partially rescue the lethality of Brca2ko/ko embryos. We are now also examining the expression of GIPC3 in human BRCA2-deficient tumors and we are monitoring tumorigenesis of GIPC3 transgenic mice in a K14-Cre;Brca2cko/cko mammary tumor model.
Citation Format: Xia Ding, Shyam K. Sharan. Identification of BRCA2 genetic interactors in an ES cell-based model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2390. doi:10.1158/1538-7445.AM2014-2390
Abstract 2408: Identification of R-Spondin fusions in various types of human cancer
Authors: Cardona Gabriela Martinez , Bell Katherine , Portale Joseph , Gaffney Dana , Moy Christopher , Platero Suso , Lorenzi Matthew V. , Karkera Jayaprakash 
Published: May 2015

Abstract
Autocrine or paracrine constitutive Wnt pathway activation occurs at a high frequency in several tumor types. The R-spondin (RSPO) protein family is comprised of four secreted growth factors. The four paralogs share 40-60% pairwise amino acid sequence identity and are predicted to share substantial structural homology. RSPO proteins are involved in vertebrate development and their ligand-type activities overlap substantially with those of canonical Wnt ligands. A characteristic feature of all four RSPO members is their ability to activate β-catenin signaling and enhance WNT-mediated β-catenin activation. It has recently been described that recurrent gene fusions involving RSPO family members RSPO2 and RSPO3 occur in ∼10% of colon tumors.
In this study we developed a TaqMan qRT-PCR-based approach to evaluate the expression of these three (3) RSPO fusion transcripts in formalin-fixed paraffin embedded tissue (FFPET) samples. We examined 324 lung cancer, 81 colorectal cancer, 71 head & neck, 11 esophageal, 92 ovarian cancer, and 103 breast cancer FFPET samples for the presence of EIF3E(e1)-RSPO2(e1), PTPRK(e1)-RSPO3(e2), and PTPRK(e7)-RSPO3(e2). EIF3E(e1)-RSPO2(e1), a fusion which is expected to produce a functional RSPO2 protein driven by the EIF3E promoter, was identified in ∼1-2% of most of cancer types with the exception of breast cancer. The PTPRK(e1)-RSPO3(e2) fusion was expressed by ∼1-11% of the samples in the different cancers, making it the most prevalent of the fusions. PTPRK(e1)-RSPO3(e2) fusion is an in-frame fusion that preserves the entire coding sequence of RSPO3 and replaces its secretion signal sequence with that of PTPRK. The PTPRK(e7)-RSPO3(e2) fusion is also an in-frame fusion in which the RSPO3 native signal peptide is replaced by the secretion signal of PTPRK. The PTPRK(e7)-RSPO3(e2) was the least prevalent of all the fusions, positive samples were found exclusively in the head and neck (∼2%) and breast cancer samples (∼2%). All of the fusions detected were mutually exclusive. The RSPO gene fusions identified may provide new potential opportunities for therapeutic intervention.
Citation Format: Gabriela Martinez Cardona, Katherine Bell, Joseph Portale, Dana Gaffney, Christopher Moy, Suso Platero, Matthew V. Lorenzi, Jayaprakash Karkera. Identification of R-Spondin fusions in various types of human cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2408. doi:10.1158/1538-7445.AM2014-2408
Abstract 2445: Estrogen promotes tumorigenesis by ADP-ribosyl-acceptor hydrolase 1 (ARH1)-deficient cells and mice
Authors: Kato Jiro , Bu Xiangning , Moss Joel 
Published: May 2015

Abstract
ADP-ribosylation, a post-translational modification in which the ADP-ribose of NAD is transferred to specific acceptors, is used by bacterial toxins to disrupt host cell biosynthetic, regulatory and metabolic pathways. Mammalian cells also use ADP-ribosylation reactions to regulate protein activity. The content of ADP-ribosylated acceptors is tightly regulated by enzymes that transfer ADP-ribose to acceptors i.e., ADP-ribosyltransferases (ARTs), and those that cleave the ADP-ribose acceptor bond, i.e., ADP-ribose-acceptor hydrolases (e.g., ARHs). ADP-ribosyl-acceptor hydrolase 1 (ARH1) is responsible for the hydrolysis of the α-ADP-ribosylarginine(protein) bond. We reported previously that ARH1-deficient mouse embryonic fibroblasts (MEFs) had greater proliferation rates, and formed more colonies in soft agar and tumors in nude mice than their wild-type (WT) counterparts. Consistent with these results with MEFs, ARH1-deficient (ARH1-/-) and heterozygous (ARH1+/-) mice developed tumors more frequently than their WT counterparts (Kato et al, 2011 Cancer Res.). Furthermore, the ARH1 gene from tumors isolated from ARH1+/- MEFs, and from tumors isolated from ARH1+/- mice contained mutations that affected function. Because loss of the functioning allele in ARH1+/- MEFs and mice resulted in tumorigenesis, we infer that ARH1 is a tumor suppressor gene.
Female ARH1-/- and ARH1+/- mice developed tumors and metastasis more frequently than male mice (e.g., adenocarcinomas, lymphomas), and developed tumors at a younger age than male mice. Consistent with the gender effect on incidence of tumors in ARH1-/- mice, tumor growth by ARH1-/- MEFs injected subcutaneously in an “estrogen group” (i.e., female, female ovariectomized [FO] supplemented with 17-β-estradiol [E2], male supplemented with E2) of nude mice was significantly faster than that seen in a “non-estrogen group” (i.e., male, FO) of mice. Pulmonary metastasis following intravenous injection of ARH1-/- MEFs in an “estrogen group” of nude mice were larger in size than those in a “non-estrogen group”. Further, estrogen promoted the survival of ARH1-/- MEFs in the circulation and thus enhanced metastatic potential. Our data demonstrate that control of protein-ADP-ribosylation by ARH1 is important for cell proliferation and tumorigenesis. Estrogen enhanced pulmonary metastasis, tumor growth and survival of circulating tumor cells.
Funding: Intramural Research Program, NIH, NHLBI.
Citation Format: Jiro Kato, Xiangning Bu, Joel Moss. Estrogen promotes tumorigenesis by ADP-ribosyl-acceptor hydrolase 1 (ARH1)-deficient cells and mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2445. doi:10.1158/1538-7445.AM2014-2445
Abstract 2477: Max inactivation in small cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1
Authors: Romero-Ferraro Octavio A. , Torres-Diz Manuel , Pros Eva , Moruno Antonio Gomez , Salama Sebastian Moran , Savola Suvi , Montuenga Luis M. , Pio Ruben , Yokota Jun , Sanchez-Cespedes Montse 
Published: May 2015

Abstract
Our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplification of L-MYC, N-MYC and C-MYC being some of the well established gene alterations. Here, we report our discovery of tumor-specific inactivation of the MYC-associated factor X gene, MAX, in SCLC. This is mutually exclusive with alterations at MYC and BRG1, the latter coding for an ATPase of the SWI/SNF complex. We demonstrate that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells, heralding a synthetic lethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programs and to up-regulate MYC-targets, such as glycolytic-related genes. Finally, we observed genetic inactivation of the MAX dimerization protein, MGA, in lung cancers with wild type components of the SWI/SNF or MYC pathways. Our results provide evidence that an aberrant SWI/SNF-MYC network is essential for lung cancer development.
Citation Format: Octavio A. Romero-Ferraro, Manuel Torres-Diz, Eva Pros, Antonio Gomez Moruno, Sebastian Moran Salama, Suvi Savola, Luis M. Montuenga, Ruben Pio, Jun Yokota, Montse Sanchez-Cespedes. Max inactivation in small cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2477. doi:10.1158/1538-7445.AM2014-2477
Abstract 2489: Glycoproteomic analysis of breast cancer cell lines for biomarker discovery
Authors: Arampatzidou Maria , Kullolli Majlinda , Pitteri Sharon J. 
Published: May 2015

Abstract
Glycosylation is one of the most ubiquitous protein post-translational modifications observed in eukaryotic organisms. In cancer, key cellular pathways and interactions, related to invasion and metastasis, are disrupted by altered protein glycosylation. Many current clinical cancer biomarkers are glycoproteins (i.e. CEA, CA15-5, CA125, and PSA). Glycosylation is known to be aberrant in breast cancer. However, systematic studies to identify glycoproteins in cancer have been limited, and typically focus on single proteins of interest or glycans released from proteins. We have developed a novel protein fractionation and enrichment strategy for glycoproteomic analysis of the secreted proteins, incorporating lectin affinity capture for glycoprotein enrichment, intact protein separation, and enzymatic digestion followed by LC-MS/MS analysis. Here, we apply this workflow to capture and analyze glycoproteins in the cancer secretome, which includes proteins secreted and/or shed from cancer cells into the extracellular space.
Four breast cancer cell lines (HCC70, HCC1806, BT474, and ZR75-1) and one normal mammary epithelial cell line (MCF10A) were subjected to glycoproteomic analysis. Proteins corresponding to 3360 unique gene names were identified. Subsequent data analysis yielded a variety of types of information about glycoproteins in the cell line secretomes. 1) Fucosylated and branched-sugar containing glycoforms of proteins were identified by lectin binding properties. For example, PHA-P/PHA-L lectins showed high affinity for aldolase, immunoglobulins, and inter-alpha-trypsin inhibitor, suggesting these proteins contain branched sugar structures. 2) Enrichment of some proteins was observed in breast cancer cell lines compared to the normal mammary epithelial cell line and vice versa. For example, high expression of fucosylated vimentin was observed in MCF10A, but not breast cancer cell lines. 3) Differences in glycosylation patterns of proteins were observed between cell lines. For example, the protease legumain was observed to be highly fucosylated in MCF10A, but had a higher affinity for PHA-P/PHA-L in HCC70. Additional substrates and inhibitors of legumain were also identified. Proteins of interest were further studied in additional follow-up experiments including western blotting and glycostaining. Additional proteins of interest were measured in plasma samples from women with (benign or malignant) breast lesions.
Citation Format: Maria Arampatzidou, Majlinda Kullolli, Sharon J. Pitteri. Glycoproteomic analysis of breast cancer cell lines for biomarker discovery. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2489. doi:10.1158/1538-7445.AM2014-2489