bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5347: DNA repair protein Rev7 is required for primordial germ cell maintenance in the mouse
Authors: Murakumo Yoshiki , Watanabe Naoki , Mii Shinji , Asai Masato , Asai Naoya , Niimi Kaoru , Kato Takuya , Enomoto Atsushi , Takahashi Masahide 
Published: May 2015

Abstract
REV7 is involved in DNA repair, cell cycle regulation, gene expression and carcinogenesis. In vitro studies show that REV7 interacts with several proteins and regulates their function, and that downregulation of REV7 expression in human cancer cells results in enhancement of sensitivity to DNA damaging agents. It has been reported that human REV7 is highly expressed in the adult testis by northern blot analysis. However, the significance of REV7 in mammalian development has not been elucidated. Here, we present analyses of Rev7-deficient (Rev7-/-) mice to clarify the significance of Rev7 in mouse development. In wild-type mice (Rev7+/+), Rev7 expression was ubiquitously observed in the embryo and confined to germ cells in the testes after birth. Rev7-/- mice exhibited growth retardation and a partial embryonic lethal phenotype. Mice that survived to adulthood were infertile in both sexes and showed germ cell aplasia in the testes and ovaries. Analyses of Rev7-/- embryos revealed that primordial germ cells (PGCs) were present at embryonic day 8.5 (E8.5). However, progressive loss of PGCs was observed during migration, and PGCs were absent in the genital ridges at E13.5. An increase of apoptotic cells was detected not only among PGCs but also in the forebrain of the Rev7-/- embryo, while cell proliferation was unaffected. Gene expression analysis of E8.5 embryos showed upregulation of Oct4 and Nanog and downregulation of c-Kit and Rev3 in Rev7-/- embryos compared with those in Rev7+/- embryos. These findings indicate that Rev7 is essential for PGC maintenance by prevention of apoptotic cell death in the mouse.
Note: This abstract was not presented at the meeting.
Citation Format: Yoshiki Murakumo, Naoki Watanabe, Shinji Mii, Masato Asai, Naoya Asai, Kaoru Niimi, Takuya Kato, Atsushi Enomoto, Masahide Takahashi. DNA repair protein Rev7 is required for primordial germ cell maintenance in the mouse. [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 5347. doi:10.1158/1538-7445.AM2014-5347
Abstract 535: Expression of miR-21 in cancer associated fibroblasts in lung adenocarcinoma
Authors: Kunita Akiko , Morita Shigeki , Fukayama Masashi 
Published: May 2015

Abstract
Lung cancer is the leading cause of cancer mortality worldwide, and novel therapeutic targets and molecular diagnostic markers are highly warranted. Micro RNAs (miRNAs) are a class of small non-coding RNAs associated with a variety of cancer. miRNA-21 is an “oncomiR” and upregulated in many cancers, including lung cancer, and high miR-21 levels have been associated with poor prognosis. To determine the localization of miR-21 and to compare its expression levels, we performed in situ hybridization of miR-21 on 89 mixed subtypes of lung adenocarcinoma. miR-21 was predominantly expressed in cancer associated fibroblasts (CAF)s expressing α-SMA, with no difference in expression between non-invasive and invasive component. In addition, stromal miR-21 expression was significantly associated with decreased overall survival (p=0.0021). In functional analyses of miR-21 in vitro, miR-21 was overexpressed in lung fibroblasts to assess migration and invasion. miR-21 expression in lung fibroblasts promoted migration and invasion. Moreover, the proliferation of lung cancer cells was accelerated by conditioned medium of miR-21-expressing lung fibroblasts. These results suggest that miR-21 overexpression in CAFs of lung adenocarcinoma might serve as a prognostic biomarker and be involved in cancer cell proliferation through interactions with cancer cells.
Citation Format: Akiko Kunita, Shigeki Morita, Masashi Fukayama. Expression of miR-21 in cancer associated fibroblasts in lung adenocarcinoma. [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 535. doi:10.1158/1538-7445.AM2014-535
Abstract 5351: The carcinogenesis rate is increased in MAL knock-out mice
Authors: Chen Wantao , Wu Xiangbing , Cao Wei , Wang Xu 
Published: May 2015

Abstract
Background:
The MAL gene was originally identified by Alonso during a study for differentially expressed genes in T-cell development. The MAL protein, which spans the membrane four times, is involved in normal apical transport and accurate sorting in distinct epithelial cells. The recent study on MAL gene down-regulation in primary human epithelial malignancies suggest that the loss of the MAL gene may be closely linked with a variety of human epithelial malignancies. In our previous study, we revealed that MAL was remarkably down-regulated in human head and neck squamous cell carcinoma. Exogenous expression of MAL in HNSCC cell lines could inhibit the proliferation, invasion, and induce apoptosis of cancer cells in vitro and suppress tumor growth in vivo. These data support that MAL, as a candidate tumor suppressor, contributes to carcinogenesis and development of HNSCC.
Methods:
To further confirm the role of MAL gene in development of carcinoma, a MAL gene knockout mouse model was produced. And the genotype and phenotype was investigated by our study group. The genotypes of MAL-/- and MAL+/+ mice were identified by RT-PCR, Western blot and Immunohistochemistry. The histopathology of main organs and tissues (esophagus, stomach, small intestine, colon, oral mucosa, etc.) were analyzed with H & E staining. Chemical carcinogenesis agent (4-nitroquinoline-N-oxide, 4NQO) was used to induce oral mucosa carcinomas.
Results: MAL gene knockout mouse model was successfully established and passed on from generation to generation more than 3 years. The genotypes of MAL-/-, MAL+/-, MAL+/+ mice were identified. Phenotypic investigation found that MAL-/- mice raised no obvious spontaneous phenotype in 12 months and the incidence of spontaneous tumor was zero. Nevertheless, we found that there were significant differences between MAL-/- and MAL+/+ mice in the incidence rate, occurrence time and growth speed of tongue and esophageal squamous carcinoma which induced by a low dose of 4NQO water feeding for 16 weeks (P&lt;0.01). We also found that the occurrence of esophageal squamous cell carcinoma performed the same changes as oral mucosa.
Conclusions: Our results suggest that MAL gene knockout mouse significantly increased the susceptibility of cancer. The molecular mechanism about the tumor susceptibility becomes more important, and will be significant for developing cancer prevention and treatment methods.
Citation Format: Wantao Chen, Xiangbing Wu, Wei Cao, Xu Wang. The carcinogenesis rate is increased in MAL knock-out 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 5351. doi:10.1158/1538-7445.AM2014-5351
Abstract 5352: Ultraviolet radiation induces carcinogenesis in a novel transgenic mouse model of melanoma
Authors: Benaduce Ana Paula , Batista Deannys , Grilo Gabriel , Jorge Karen , Cardero Diana , Milikowski Clara , Kos Lidia 
Published: May 2015

Abstract
Melanomagenesis is caused by environmental factors, such as ultraviolet (UV) radiation, as well as genetic factors. The Nucleotide Excision Repair (NER) pathway repairs photoproducts induced by UV radiation. In humans, NER pathway disruption leads to the development of skin cancers, including melanoma. Upon UV exposure, mice deficient in Xpc, an important protein in the NER pathway, develop skin cancer; but not melanoma. The Endothelin 3 (Edn3) signaling pathway is essential for melanocyte precursor cell development. In humans, this pathway has also been associated with melanoma progression and its metastatic potential. The purpose of this study is the development of a UV-dependent melanoma mouse model that combines Xpc deficiency with the over-activation of the Edn3 pathway. Transgenic mice over-expressing Edn3 under the control of the keratin 5 promoter (K5-Edn3) and carrying a targeted mutation in Xpc were exposed to a single suberythemal neonatal dose of UV radiation. Immunostaining and histomorphology were used to confirm the melanocytic origin of primary skin tumors. Melanomas were only found in animals with the K5-Edn3 transgene. High penetrance was observed in Xpc null (67%, n=3) and Xpc heterozygous (67%, n=3) mice in comparison to Xpc wild type (33%, n=3) mice. RNA extracted from melanomas of Xpc null (n=2), Xpc heterozygous (n=1) and Xpc wild type (n=1) mice were screened for UV signature mutations in Hras, Kras and Nras. No mutations were found in any of these genes. These results indicate that UV radiation exposure, in conjunction with over-activation of the Edn3 pathway is sufficient to lead to melanomagenesis in mice independently of mutations in Hras, Kras or Nras.
Citation Format: Ana Paula Benaduce, Deannys Batista, Gabriel Grilo, Karen Jorge, Diana Cardero, Clara Milikowski, Lidia Kos. Ultraviolet radiation induces carcinogenesis in a novel transgenic mouse model of melanoma. [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 5352. doi:10.1158/1538-7445.AM2014-5352
Abstract 5354: Neuropeptide Y as a prognostic marker of colorectal cancer
Authors: Sarkar Chandrani , Chakroborty Debanjan 
Published: May 2015

Abstract
Introduction: Colorectal cancer affects a large population not only in the United States but worldwide and is one of the major causes of mortality due to cancer. Among the numerous risk factors that might lead to the incidence and development of this disease, inflammatory bowel diseases (IBD) have been identified as a very prominent factor and patients are at much higher risk of developing colorectal cancer in their lifetime.
Objective/Hypothesis: As chronic inflammation leads to colorectal cancer and among the various neuromediators, the neuropeptides, particularly neuropeptide Y (NPY) is associated with the development and progression of IBD and as NPY has the potential to augment inflammation and angiogenesis through its Y2 receptor we hypothesize that NPY is an important regulator of the process of development of colorectal cancer (CRC).
Results: Our results show that the expression of both NPY its Y2 receptor is upregulated in an axozymethane / dextran sodium sulphate (AOM/DSS) induced mouse model of inflammatory CRC. Upregulation of NPY in AOM/DSS induced CRC in mice is associated with increased angiogenesis. NPY Y2 receptors are expressed in these angiogenic vessels. Furthermore, this upregulation of NPY and Y2 receptor is also related to higher expression of the inflammatory cytokine, TNF-α, that has been shown to promote progression of carcinogenesis in AOM/DSS induced CRC mouse models. Our in vitro studies show that NPY can promote angiogenic potential of human umbilical vein endothelial cells (migration and permeability) through Y2 receptors present in these cells.
Conclusion: We here show for the first time that NPY might be associated with the progression of inflammatory colorectal cancer and hence may serve as a prognostic marker of the disease.
Citation Format: Chandrani Sarkar, Debanjan Chakroborty. Neuropeptide Y as a prognostic marker of colorectal 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 5354. doi:10.1158/1538-7445.AM2014-5354
Abstract 536: Elucidating the role of miRNA-31 in retinoblastoma
Authors: Montoya Vanessa , Bryar Paul J. , Mets Marilyn , Weinstein Joanna , Laurie Nikia 
Published: May 2015

Abstract
Retinoblastoma is the most common pediatric ocular cancer. Although early detection of the disease may have a favorable outcome for the patient, retinoblastoma can aggressively develop and become fatal. Current treatment strategies include focal therapies, chemotherapy and in more severe cases, enucleation (removal of the eye) is necessary. This cancer may initiate from acquired or inherited mutations in the RB1 gene. As a result, the mutant retinal cell is conferred an unrestrained proliferative ability that is facilitated by multiple genetic events. Determining the mechanism(s) responsible for tumor growth, invasion, and metastasis may provide an alternative treatment strategy that may delay enucleation, prevent toxic side effects from chemotherapy, or even prevent metastatic spread altogether. Genetic factors that are highly involved in both carcinogenesis and homeostasis are often regulated by miRNAs. miRNAs are small, non-coding molecules that negatively regulate gene expression by mediating mRNA cleavage and/or disrupting protein synthesis. Our rationale for this study is that investigating aberrant miRNA regulation in retinoblastoma will enable us to identify key genetic factors that can be targeted therapeutically. Our miRNA array suggests that there is a significant number of miRNAs whose expression is significantly downregulated between retinoblastoma tumors and normal human retinae. From this data, we have identified candidate miRNAs, such as miRNA-31, that have been previously reported to have an important anti-metastatic role in different cancer types. We are currently investigating the role of these miRNAs in regulating retinoblastoma progression. These functional studies will allow us to determine how increasing miRNA expression in retinoblastoma models can disrupt important signaling pathways associated with retinoblastoma progression and invasion.
Citation Format: Vanessa Montoya, Paul J. Bryar, Marilyn Mets, Joanna Weinstein, Nikia Laurie. Elucidating the role of miRNA-31 in retinoblastoma. [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 536. doi:10.1158/1538-7445.AM2014-536
Abstract 5360: Ethanol enhances arsenic-induced mutagenesis in colon
Authors: Wang Lei , Kuang Lisha , Son Young-Ok , Hitron John Andrew , Poyil Pratheeshkumar , Zhang Zhuo , Luo Jia , Wang Zhigang , Shi Xianglin 
Published: May 2015

Abstract
Health effects due to environmental exposure to arsenic are a major health concern world-wide. Arsenic has been known to induce carcinogenesis and enhance tumor development via complex and unclear mechanism. As one of the common nutritional factors, ethanol is also a well-documented risk factor for many malignancies. However, little is known on the effects of co-exposure to arsenic and ethanol in mutagenesis and carcinogenesis. In this study, we investigate the mutagenic effect of co-exposure to arsenic and ethanol in vivo and in vitro. Results show that ethanol could markedly enhance arsenic-induced mutagenesis in colon in Big Blue Mice. This response related to intracellular reactive oxygen species (ROS) generation, NAPDH oxidase activation, and DNA damage/repair functional changes.
We conclude that ethanol enhances arsenic-induced mutagenesis in colon in vivo. These results indicated that alcohol consumption should be taken into consideration in the investigation on arsenic-induced carcinogenesis in arsenic-exposure population.
Citation Format: Lei Wang, Lisha Kuang, Young-Ok Son, John Andrew Hitron, Pratheeshkumar Poyil, Zhuo Zhang, Jia Luo, Zhigang Wang, Xianglin Shi. Ethanol enhances arsenic-induced mutagenesis in colon. [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 5360. doi:10.1158/1538-7445.AM2014-5360
Abstract 5365: Cdt2-mediated XPG degradation promotes DNA repair synthesis following DNA damage excision in nucleotide excision repair
Authors: Han Chunhua , Zhao Ran , Qian Jiang , Sharma Nidhi , Wani Gulzar , He Jinshan , Zhu Qianzheng , Wang Qi-En , Wani Altaf A. 
Published: May 2015

Abstract
Xeroderma pigmentosum group G (XPG) protein is a structure-specific repair endonuclease, which cleaves DNA strands on the 3′ side of the DNA damage during nucleotide excision repair (NER). In addition, XPG plays a crucial role in initiating DNA repair synthesis through recruitment of PCNA to the repair sites. However, the fate of XPG protein subsequent to the excision of DNA damage has remained unresolved. Here, we show that XPG is degraded through proteasome-mediated proteolysis upon induction of bulky lesions from exposures to UV irradiation and cisplatin. NER process is required for XPG degradation because both UV and cisplatin treatment-induced XPG degradation is compromised in NER-deficient XP-A, XP-B, XP-C, and XP-F cells. In addition, the NER-related XPG degradation requires Cdt2, a component of an E3 ubiquitin ligase, CRL4Cdt2. Micropore local UV irradiation and in situ Proximity Ligation assays demonstrated that Cdt2 is recruited to the UV-damage sites and interacts with XPG in the presence of PCNA. Importantly, Cdt2-mediated XPG degradation is crucial to the subsequent recruitment of DNA polymerase δ and DNA repair synthesis. Collectively, our data supports the idea of PCNA recruitment to damage sites in conjunction with XPG, recognition of the PCNA-bound XPG by CRL4Cdt2 for specific ubiquitylation and protein degradation. Thus, XPG removal clears the space needed at the damage site for the subsequent recruitment of DNA pol δ and initiation of DNA synthesis. (This work was supported by grants from NIH).
Note: This abstract was not presented at the meeting.
Citation Format: Chunhua Han, Ran Zhao, Jiang Qian, Nidhi Sharma, Gulzar Wani, Jinshan He, Qianzheng Zhu, Qi-En Wang, Altaf A. Wani. Cdt2-mediated XPG degradation promotes DNA repair synthesis following DNA damage excision in nucleotide excision repair. [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 5365. doi:10.1158/1538-7445.AM2014-5365
Abstract 5367: DNA repair capacity, gene expression and epigenomic profiles in bladder cancer
Authors: Pardini Barbara , Allione Alessandra , Guarrera Simonetta , Turinetto Valentina , Fiorito Giovanni , Rosa Fabio , Russo Alessia , Modica Federica , Giachino Claudia , Vineis Paolo , Sacerdote Carlotta , Matullo Giuseppe 
Published: May 2015

Abstract
In Europe, bladder cancer (BC) is the sixth most commonly diagnosed tumor and the second most common cause of death among patients with genitourinary tract malignancies. The ability to repair DNA damage is strongly associated with the risk of cancer and inter-individual variation in DNA repair capacity (DRC) might account for different susceptibility of developing cancer. DRC represents a complex marker comprising the sum of several factors such as gene variants, gene expression, stability of gene products, and effect of inhibitors/stimulators. Individuals with low DRC will tend to accumulate more damage than those who have a better ability to repair such damage. This variability is modulated by the genetic background to which SNPs/haplotype combinations in DNA repair genes, as well as epigenetic regulation are likely to contribute. Phenotypic assays to evaluate DNA repair activity (in particular NER comet assay, H2AX phosphorylation and micronucleus assay) were performed on cryopreserved lymphocytes from 159 cases (collected before treatment) and 159 controls matched by age and smoking habits, enrolled in Turin Bladder Cancer Study (TBCS). We aimed at studying the relationship between DRC (evaluated by comet assay, micronuclei and H2AX phosphorylation assay) and bladder cancer integrating, gene expression and epigenetic profile data (methylation levels and microRNA expression). In particular, we performed an integrated analysis on the genotype/phenotype correlation in a population of bladder cancer cases and controls provided with detailed description of the follow-up for response to therapy/recurrence/survival. This integrated approach will help in elucidating the role of DRC (and its determinants) as predictive and prognostic marker and to identify combined biomarkers to be measured in blood cells as non-invasive predictive method.
Citation Format: Barbara Pardini, Alessandra Allione, Simonetta Guarrera, Valentina Turinetto, Giovanni Fiorito, Fabio Rosa, Alessia Russo, Federica Modica, Claudia Giachino, Paolo Vineis, Carlotta Sacerdote, Giuseppe Matullo. DNA repair capacity, gene expression and epigenomic profiles in bladder 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 5367. doi:10.1158/1538-7445.AM2014-5367
Abstract 5371: Drug repositioning with a bioinformatics platform that integrates the TCGA, cMap and CCLE
Authors: Lucas Francis A. San , Fowler Jerry , Kopetz Scott , Vilar Eduardo , Scheet Paul 
Published: May 2015

Abstract
Cancer In silico Drug Discovery Tools (CIDD) is a drug discovery platform that enables researchers to generate hypotheses for the following three general problems: 1) to determine if clinical phenotypes or gene mutations for a cancer are functional, inducing unique gene expression alterations, 2) to find candidate drugs to treat, or repress, these expression changes, and 3) to identify cell lines that resemble the tumors being studied for subsequent in vitro experimentation. CIDD integrates clinical and experimental data from The Cancer Genome Atlas (TCGA), the Connectivity Map (cMap) and the Cancer Cell Line Encyclopedia (CCLE) to perform in silico drug discovery experiments. CIDD generates gene expression signatures representative of the phenotypes or mutations being studied, characterizes the signatures using MSigDB, identifies candidate drugs to repress these signatures using data from the cMap, and finds optimal cell lines for in vitro drug testing using experimental data from the CCLE. The primary results of a CIDD execution are a biologically interpretable candidate drug list and a list of cell lines for subsequent drug experimentation. We applied CIDD for the identification of candidate drugs to treat BRAF V600E colorectal cancer (CRC). CIDD identified EGFR and proteasome inhibitors as candidate drugs, while proposing 7 large intestine cell lines from the CCLE for potential in vitro testing. CIDD is a command-line based tool written in Python and depends on R. We have developed a companion Python-based data management utility, tcga_util, which provides automated downloading and querying of TCGA data from the command-line, which we feel will be of substantial and independent interest to researchers wishing to use data from the TCGA. CIDD and tcga_util are available for download at http://scheet.org/software.
Citation Format: Francis A. San Lucas, Jerry Fowler, Scott Kopetz, Eduardo Vilar, Paul Scheet. Drug repositioning with a bioinformatics platform that integrates the TCGA, cMap and CCLE. [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 5371. doi:10.1158/1538-7445.AM2014-5371