bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2713: Stem cell mutagenesis and carcinogenesis in the colon of wild type and immune compromised mice
Authors: Gold Barry , Whetstone Ryan 
Published: August 2015

Abstract
To test the hypothesis that a role of inflammation in the etiology of cancer is associated with the production of RONS and subsequent DNA damage, we determined the mutation frequency (MF) in colonic stem cells in C57Bl/6 mice exposed to dextran sulfate sodium (DSS), an inflammatory agent that is used in combination with azoxymethane (AOM) to produce colon tumors in mice. AOM produces promutagenic O6-methylguanine lesions in DNA but does not induce colon tumors in C57Bl/6 mice as a single agent. The MF's in the untreated and DSS treated WT and TCRβ-/- mice were &lt;10-5 indicating that DSS and subsequent inflammation does not generate stem cell mutations in mice that are WT for DNA repair. AOM yielded mutant crypts in WT and TCRβ-/- mice with MF's of ∼4×10-4 and 2×10-4, respectively, which represents a statistically significance decrease in the MF in the immune compromised mice. These results suggest enhanced survival of AOM damaged stem cells in WT vs. TCRβ-/- mice. The combined treatment of AOM+DSS afforded fully mutated crypts in both strains but with a lower MF than observed with AOM alone indicating that DSS induced inflammation destroyed pre-existing AOM mutated crypts. Using the MF in WT mice, the efficiency for the conversion of an O6-methylguanine lesion into a stem cell mutation was estimated to be 0.03%. The carcinogenicity of AOM and/or DSS was evaluated in WT, TCRβ-/-, TCRδ-/- and TCRβ-/-TCRδ-/- mice. At lower DSS exposure (1.5%), there was a significant reduction in tumor incidence, multiplicity and tumor progression in the TCRβ-/- and TCRβ-/-TCRδ-/- vs. WT B6 mice. However, at higher DSS concentration (2%) the difference between the mouse strains disappeared because of an increase in the TCR null mice without a concomitant increase in the WT mice.
Citation Format: Barry Gold, Ryan Whetstone. Stem cell mutagenesis and carcinogenesis in the colon of wild type and immune compromised mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2713. doi:10.1158/1538-7445.AM2015-2713
Abstract 2716: Epstein-Barr virus-encoded BARF1 downregulates SMAD4 and increases miR-146a in gastric carcinoma cells
Authors: Kim Dong Ha , Yoon Chan Jin , Rho Jin Kyung , Middeldorp Jaap M. , Woo Jun Hee , Chang Mee Soo 
Published: August 2015

Abstract
Recently, molecular analytic data from ‘The Cancer Genome Atlas’ (TCGA) (http://www.cbioportal.org) has re-confirmed that Epstein-Barr virus (EBV)-infected gastric carcinoma is a specialized subset of gastric carcinomas. However, viral oncogene has not yet been established in gastric carcinomas. Several reports have suggested that EBV-encoded BARF1 may be a putative viral oncogene in gastric carcinoma. The aim of this study was to investigate alterations of cellular microRNA and cellular protein by BARF1 in gastric carcinoma cells. We cloned BARF1 from naturally EBV-infected gastric carcinoma cell line, and transfected BARF1 into EBV-negative gastric carcinoma cells, thus produced a stable cell line of BARF1-transfected gastric carcinoma cells. BARF1-transfected gastric carcinoma cells revealed significantly increased cellular proliferation than its original cells. The MicroRNA array (Agilent release 16.0) data and Taqman RT-PCR results showed that cellular miR-146a was highly expressed in BARF1-transfected gastric carcinoma cells, comparing to that in original cells. In BARF1-transfected gastric carcinoma cells, transfection with BARF1-siRNA offset the increment effect of miR-146. Using bioinformatics analyses for miR-146a target (RNA hybrid 2.2 and TargetScan 5.2 sites), we found that miR-146a target seed sequence existed in the 3′ UTR of SMAD4 mRNA. The Western blot assay demonstrated that SMAD4 was remarkably reduced by BARF1 transfection. When immunohistochemistry for SMAD4 was performed on 343 cases of surgically resected, human gastric carcinoma tissues, 32 (9%) EBV-infected gastric carcinoma group disclosed more frequent loss of SMAD4 than EBV-negative group. In conclusion, EBV-encoded BARF1 could promote proliferation of gastric carcinoma cells, thereby contributing to EBV-induced cancer progression, in which SMAD4 downregulation, probably through miR-146a increase, may be entailed.
Citation Format: Dong Ha Kim, Chan Jin Yoon, Jin, Kyung Rho, Jaap M. Middeldorp, Jun Hee Woo, Mee Soo Chang. Epstein-Barr virus-encoded BARF1 downregulates SMAD4 and increases miR-146a in gastric carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2015-2716
Abstract 2729: Chronic stress promotes lung cancer development via IGF-1R pathway
Authors: Jang Hyun-Ji , Boo Hye-Jin , Jung Yujin , Min Hye-Young , Lee Ho-Young 
Published: August 2015

Abstract
Lung cancer is a leading cause of cancer death worldwide. Although smoking is a main cause, approximately 25% of lung cancer cases are not attributable to tobacco use. Epidemiological studies strongly suggest that chronic stress influences cancer development and progression. Recent mechanistic studies showed that biological signaling pathways could contribute to such effects. But the underlying mechanisms for the association between chronic stress and lung cancer development are poorly understood. The purpose of this study is to investigate whether chronic stress can induce lung cancer development and, if so, what is the mechanism underlying the chronic stress-induced lung cancer development. We observed that stress hormone, norepinephrine (NE) increased cell viability in the absence of growth factors, foci formation, and colony formation in human bronchial epithelial cells and activated the type 1 insulin-like growth factor receptor (IGF-1R) pathway. We found that chronic stress resulted in high levels of NE in serum, activation of IGF-1R in lung tissue and promoted urethane-induced lung tumor formation in vivo. Moreover, inhibition of the IGF-1R pathway suppressed NE-induced transformed phenotypes in vitro. We further confirmed that chronic stress-induced lung tumor formation was greater in mice carrying lung-specific human IGF-1R transgene (Tg) than in wild type mice. Our results indicate that chronic stress may promote lung cancer development via the IGF-1R pathway, suggesting that IGF-1R is an effective target for the chemoprevention of stress-induced lung cancer.
Citation Format: Hyun-Ji Jang, Hye-Jin Boo, Yujin Jung, Hye-Young Min, Ho-Young Lee. Chronic stress promotes lung cancer development via IGF-1R pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2729. doi:10.1158/1538-7445.AM2015-2729
Abstract 2738: Mechanisms of cadmium carcinogenesis
Authors: Nath Raghu G. , Sonawane BR , Vulimiri SV , Lin YS 
Published: August 2015

Abstract
Cadmium is a transition metal and an ubiquitous environmental and industrial pollutant. Laboratory animal studies and epidemiological studies have shown that exposure to cadmium is associated with various organ toxicities and carcinogenic effects. Several national and international regulatory agencies have classified cadmium compounds as carcinogenic to humans. In 2012, International Agency for Research on Cancer (IARC) reviewed the relevant information on cadmium exposure and concluded that there is sufficient evidence in humans for the carcinogenicity of cadmium and its compounds. However, the underlying molecular mechanism(s), especially for the carcinogenicity, are unknown. The mechanisms proposed for carcinogenicity include aberrant gene expression, induction of oxidative DNA damage, stimulation of cell proliferation, malignant cell transformation, inhibition of DNA damage repair, inhibition of apoptosis and epigenetic mechanisms including alteration of DNA methylation. Studies have shown that due to the slow elimination, cadmium is a cumulative toxicant and past exposures could result in toxic effect of the residual metal. To better understand the mechanisms of cadmium carcinogenicity we have reviewed in vitro experimental and in vivo animal studies focused on the proposed mechanisms of carcinogenicity as well as epidemiological evidence on carcinogenicity in lung and kidney following cadmium exposure.
Disclaimer: The views expressed are those of the authors and do not necessarily represent the views and/or policies of the U.S. EPA
Citation Format: Raghu G. Nath, BR Sonawane, SV Vulimiri, YS Lin. Mechanisms of cadmium carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2738. doi:10.1158/1538-7445.AM2015-2738
Abstract 2740: Familial Hodgkin lymphoma by relationship, sex, age and histology: a joint study from five Nordic countries
Authors: Fallah Mahdi , Kharazmi Elham , Pukkala Eero , Olsen Jørgen H. , Tryggvadottir Laufey , Sundquist Kristina , Tretli Steinar , Hemminki Kari 
Published: August 2015

Abstract
Background: We aimed to estimate lifetime (0-79 years) cumulative risk (CR) of Hodgkin lymphoma (HL) in relatives of patients with HL by relationship, sex, age and histology.
Design: A population-based cohort of 57,475 first-degree relatives of 13,922 HL patients diagnosed in 1955-2009 in Nordic countries was followed for cancer incidence. Standardized incidence ratios (SIRs) were calculated using histology-, age-, sex-, period-, and country-specific incidence rates as the reference.
Results: The overall CR of HL in first-degree relatives of a patient with Hodgkin lymphoma was 0.6%, which represents 3-fold (SIR = 3.3, 95%CI = 2.8-3.9) increase over the general population risk (men 0.3%; women 0.2%). Significantly high CR (1%) was found among sisters with early-onset HL and unlike-sex siblings with HL diagnosed at age 30-59. The familial risk in sisters (9-fold) was higher than in brothers (4.5-fold) or unlike-sex siblings (6-fold). In general, the risk in siblings (6-fold) was higher than in parents/children (2-fold). Very high risk of HL was found for few men with two HL first-degree relatives (3-8%) and for twin brothers (18%). For the first time we found high familial risk of concordant histological subtypes of HL [lymphocyte-rich (81-fold, n = 6) and nodular sclerosis (4.6-fold, n = 22)] and also discordant subtypes.
Conclusions: Lymphocytic-rich histology type of HL showed highest familial risk. The absolute risk of familial HL was generally less than 1.5%, except for men with multiple affected first-degree relatives (3-8%), twin brothers (18%), or brothers with early-onset HL (2%).
Citation Format: Mahdi Fallah, Elham Kharazmi, Eero Pukkala, Jørgen H. Olsen, Laufey Tryggvadottir, Kristina Sundquist, Steinar Tretli, Kari Hemminki. Familial Hodgkin lymphoma by relationship, sex, age and histology: a joint study from five Nordic countries. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2740. doi:10.1158/1538-7445.AM2015-2740
Abstract 2741: The risk of cancer among children with birth defects
Authors: Lupo Philip J. , Scheurer Michael E. , Plon Sharon E. , Spector Logan E. , Mueller Beth A. 
Published: August 2015

Abstract
Background: Although a few genetic syndromes are known to increase cancer risk in children, the presence of a structural birth defect in the absence of these syndromes is increasingly being recognized as a risk factor for childhood cancer. To better understand associations of specific defects and cancer types, we conducted a population-based assessment to avoid biases often present in studies relying on single clinics, referral centers, or treatment networks.
Methods: Records of those diagnosed with cancer &lt;20 years of age between 1984 and 2013 in Washington State were linked to their birth certificates (N = 4,043). Birth records of children without cancer were selected at a ratio of 10:1 for a comparison group. Information on birth defects was obtained from birth records. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for: 1) having any reported defect and the risk of childhood cancer; 2) having any reported defect and the risk of specific cancer types; and 3) having a specific defect and the risk of specific cancer types. All models were adjusted for birth year.
Results: Having any birth defect was associated with a 50% increased risk of childhood cancer overall (OR 1.5, 95% CI 1.2-1.8), and specifically for leukemia (OR = 1.7, 95% CI 1.2-2.4); neuroblastoma (OR = 1.9, 95% CI 1.0-3.5); soft tissue sarcoma (OR = 2.0, 95% CI 1.2-3.5); and germ cell tumors (OR = 3.0, 95% CI 1.6-5.5). Some specific defects were associated with specific cancer types: central nervous system (CNS) tumors with CNS defects (OR&gt;4.0); leukemia, neuroblastoma, renal tumors, and soft tissue sarcoma with gastrointestinal anomalies (ORs&gt;9.0); renal tumors and urogenital anomalies (OR&gt;4.0); and soft tissue sarcoma with adactyly, polydactyly, or syndactyly (OR&gt;8.0).
Conclusions: Consistent with prior studies, structural birth defects were associated with increased cancer risk. Pooling similar data from many regions will increase power to identify specific associations in order to inform molecular studies examining possible common developmental pathways in the etiologies of birth defects and cancer, and will provide information that can be translated into screening strategies for children at high risk of developing cancer.
Funding: Cancer Prevention Research Institute of Texas RP140258 and Alex's Lemonade Stand Foundation
Citation Format: Philip J. Lupo, Michael E. Scheurer, Sharon E. Plon, Logan E. Spector, Beth A. Mueller. The risk of cancer among children with birth defects. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2741. doi:10.1158/1538-7445.AM2015-2741
Abstract 2775: Prognostic significance of triple miRNAs, miR-9, miR-221, and miR-200c in breast cancer
Authors: Cheng Chun-Wen , Yu Jyh-Cherng , Hsieh Yi-Hsien , Chen Po-Ming , Wang Hsiao-Wei , Wang Hui-Chun , Shen Chen-Yang 
Published: August 2015

Abstract
MicroRNAs (miRNA) mediated epithelial-mesenchymal transition have been considered as a major event in cancer aggression and accounted for cancer progression. However, clinical association between synergistic effect of deregulated expression levels of the EMT-related miRNAs, including miR-9, miR-221, and miR-200c, and breast cancer prognoses remains underestimated. Initially, tissue samples were from 184 enrolled female patients, with invasive ductal carcinoma, followed up for more than ten years. miRNA expression levels between paired laser capture microdissected tumor and non-tumor cells from the primary tumor site was analyzed by quantitative real-time PCR (qRT-PCR). Differentially expressed status of the target miRNA in tumors relative to non-tumor parts (T/N ratio) was assessed their relationship with pathological characteristics and clinical outcomes of breast cancer. While miR-9 or miR-221 showed significantly higher expression level in tumor cells compared to the non-tumor ones, miR-200c exhibited the opposite (p&lt;0.05). Based on the ROC curve, T/N ratio of 2.80- and 1.96-fold increase for miR-9 and miR-221, whereas, 1.80-fold decrease for miR-200c as risk genotypes, respectively. According to these cutoffs, high miR-9 expression in tumors was associated with advanced tumor stages (p&lt;0.05); significant risk associations were shown between LNM-positive tumors and miR-9 (OR = 3.12) or miR-221 (OR = 1.88) (p&lt;0.05). A joint effect on risk elevation of tumor invasion and nodal metastasis was seen in tumors having miR-9 overexpression alongside increased miR-221 or reduced miR-200c expression (p-trend&lt;0.05). Considering the combined effect of these three miRNAs, patients harboring greater numbers of deregulated expression levels in tumors were found to have a higher risk of poor prognoses (high-stage (p-trend = 0.003) and LNM (p-trend = 0.028)) and reduced probability of 10-year overall survival, showing hazard ratio of 2.39 (p&lt;0001 for trend test). In conclusion, deregulated levels of miR-9, miR-221, and miR-200c, may serve as prognostic biomarkers to predict disease progression and shorter OS in breast cancer.
Citation Format: Chun-Wen Cheng, Jyh-Cherng Yu, Yi-Hsien Hsieh, Po-Ming Chen, Hsiao-Wei Wang, Hui-Chun Wang, Chen-Yang Shen. Prognostic significance of triple miRNAs, miR-9, miR-221, and miR-200c in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2775. doi:10.1158/1538-7445.AM2015-2775
Abstract 2792: Polymorphisms in vitamin D-related genes and risk of breast cancer
Authors: Shi Joy , Grundy Anne , Richardson Harriet , Brooks-Wilson Angela , Spinelli John , Aronson Kristan J. 
Published: August 2015

Abstract
Vitamin D is hypothesized to decrease breast cancer risk by controlling cell proliferation, differentiation and apoptosis, and estrogen synthesis and signalling in breast tissue. Transport of circulating vitamin D to sites of action is facilitated by vitamin D binding protein, encoded by the GC gene, whereupon it binds to the vitamin D receptor, encoded by the VDR gene. Given that polymorphisms in the GC and VDR gene have not been consistently associated with breast cancer risk, our objective was to assess the associations of vitamin D-related genes with breast cancer risk, accounting for ethnicity and menopausal status, and to determine these associations according to tumour receptor status defined by expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). A case-control study of 1,037 breast cancer cases and 1,050 controls age-frequency matched in Vancouver, British Columbia and Kingston, Ontario was used. The distribution and associations of 21 single nucleotide polymorphisms (SNPs) of the GC and VDR gene with breast cancer risk and breast tumour subtypes were investigated among premenopausal and postmenopausal European and Asian women in stratified analyses. Following false discovery rate adjustment, no SNP was associated with breast cancer risk among any subgroup. However, among European women, two SNPs in the VDR gene, rs1544410 (OR = 0.38, 95% CI: 0.21 - 0.70) and rs7967152 (OR = 2.80, 95% CI: 1.62 - 4.85) were associated with risk of ER-/PR-/HER2+ breast tumour subtype, but not with other breast tumour subtypes. Breast tumour subtypes are proposed to be etiologically distinct disease states, with different risk factors and prognostic outcomes. Interactions between variations in vitamin D-related genes and breast tumour subtypes are biologically plausible given our current understanding of anticarcinogenic properties of vitamin D elicited through the regulation of cell growth and reproductive hormone synthesis. These findings provide additional insight into the etiologic differences among breast tumour subtypes.
Citation Format: Joy Shi, Anne Grundy, Harriet Richardson, Angela Brooks-Wilson, John Spinelli, Kristan J. Aronson. Polymorphisms in vitamin D-related genes and risk of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2792. doi:10.1158/1538-7445.AM2015-2792
Abstract 28: Deregulation of NAC complex inhibits muscle differentiation and blocks apoptosis in rhabdomyosarcoma cells
Authors: Zhang Meiling , Davie Judith 
Published: August 2015

Abstract
Rhabdomyosarcoma (RMS) is a common malignant soft tissue sarcoma in children with limited treatment options and high failure rate during standard therapy. New therapeutic targets or strategies are therefore in high demand. The NAC complex performs many diverse biological functions, and the deregulation of its subunits has been correlated with many cancers. We sought to understand the function of NAC complex in normal muscle cells and rhabdomyosarcoma cells. With western blot, quantitative real time PCR (qRT-PCR), chromatin immunoprecipitation and immunostaining analysis, we found that the muscle specific subunit of NAC complex, skNAC, which is the alternatively spliced isoform of NACα, was downregulated in RMS cells. In normal cells, skNAC shuttled from the cytoplasm to the nucleus upon differentiation. We also showed that skNAC associated with muscle specific promoters together with BTF3 in differentiated cells, and this association is dependent on the expression of BTF3. The expression of skNAC was regulated by the splicing factor SRPK3, a serine arginine protein kinase. Overexpression of SPRK3 induced skNAC expression and muscle differentiation. We also detected the deregulation of another NAC complex subunit, NACβ (also known as BTF3). We found that BTF3 is highly overexpressed and localized in the nucleus in both RMS cell lines and human RMS tumor samples compared with normal samples. Depletion of BTF3 induced apoptosis as detected by the strong cleavage of PARP and caspase 3. BTF3 depletion also decreased the cell viability in RMS by a cologenic assay. We also confirmed that BTF3 downregulation promoted muscle gene expression and induced muscle differentiation in RMS cells. However, BTF3 played a different role in normal cells. With the deletion of BTF3 in C2C12 cells, no apoptosis signal was detected and cell differentiation was inhibited, which suggested that a precise level of BTF3 is important for normal cell function. In conclusion, we found that the NAC complex subunits, skNAC and BTF3, were deregulated in RMS cells. The restoration of skNAC by SRPK3 overexpression rescued muscle differentiation. BTF3 functioned as an anti-apoptosis factor in RMS cells and depletion of BTF3 induced apoptosis and promoted differentiation. With no apoptosis effect in normal cells, BTF3 could serve as a cancer specific therapeutic target in RMS cells.
Citation Format: Meiling Zhang, Judith Davie. Deregulation of NAC complex inhibits muscle differentiation and blocks apoptosis in rhabdomyosarcoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 28. doi:10.1158/1538-7445.AM2015-28