bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 179: Impact of diet-induced obesity on inflamatory pathways during prostate cancer progression in Hi-Myc mice.
Authors: Blando Jorge M. , Kiguchi Kaoru , Fernandez Irina , DiGiovanni John 
Published: August 2014

Abstract
We have previously reported that diet induced obesity (DIO) enhanced prostate cancer progression and associated inflammation in the ventral prostate of the Hi-Myc mice (Blando et al, CAPR, 2011). Here, we further investigated changes in inflammatory genes as well as cellular changes associated with DIO effects on prostate cancer progression in the Hi-myc mouse model. Initial studies were conducted to look at specific cell populations that are present in the ventral prostate (VP) of Hi-Myc mice on the 30% CR, overweight control (AIN76A) and DIO diets (60 Kcal% fat). Staining for perilipin revealed that adipocytes were restricted to the periphery of the VP of Hi-Myc mice on the 30% CR diet. In contrast, adipocytes could be seen infiltrating the VP of Hi-Myc mice on the overweight control diet and especially in mice on the DIO diet. In this regard, many of the glands in the VP were completely surrounded by adipocytes. Double IF staining was performed for both perilipin and CD3 (T-lymphocytes) or perilipin and RM0029-11H3 (macrophages). Few if any inflammatory cells were seen in VP of Hi-Myc mice on the 30% CR diet. In contrast, adipocytes and inflammatory cells (both T-cells and macrophages) were seen in close proximity to adipocytes that had infiltrated into the VP in the overweight control group and this was particularly prominent in the DIO diet group. Aditionally, staining for B-cells also showed an increased number in the DIO groups as compared to the control and CR diet groups. Sections of VP from Hi-Myc mice on the different diets were also stained for both the IL-23 receptor (IL-23R) and Cox-2. IL-23R expression was dramatically upregulated in the epithelial cells of the VP from Hi-Myc mice on the DIO compared to the other diet groups. Cox-2 expression was also dramatically upregulated in VP of Hi-Myc on the DIO diet. This finding is consistent with the high level of NFκB activation seen in prostate tissues for the same mice and diet group. The VP from mice on DIO diets also showed an increase in the staining of tissue specific cancer stem cell (CSC) markers (SCA-1 and CD49f) when compared to VP from mice on the overweight control and 30% CR diets. In summary, changes in the levels of IL-23R and COX-2 and the increased presence of inflammatory cells together with changes in the adipose tissue, suggest that the tumor microenvironment may play an important role in DIO effects on prostate cancer progression in Hi-Myc mice.
Citation Format: Jorge M. Blando, Kaoru Kiguchi, Irina Fernandez, John DiGiovanni. Impact of diet-induced obesity on inflamatory pathways during prostate cancer progression in Hi-Myc mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 179. doi:10.1158/1538-7445.AM2013-179
Abstract 1791: Tristetraprolin downregulates AHRR expression through mRNA destabilization.
Authors: Lee Hyun Hee , Kim Won Tae , Kim Dong Hee , Leem Sun-Hee 
Published: August 2014

Abstract
Background. The aryl hydrocarbon receptor repressor (AHRR) inhibits the transcription activity of the aryl hydrocarbon receptor (AHR) by competing for dimerization with the AHR nuclear translocator (ARNT) and subsequently binding to XRE. Interestingly, the AHRR has two AU-rich elements (AREs) in its 3’UTR which relates to the post-transcriptional regulation by ARE-binding proteins including Tristetraprolin (TTP), BRF1, HuR and so on. In previous study, we determined that TTP plays a critical role in the decaying of VEGF, LATS2, cIAP2, COX2 and Pim-1 through binding these AREs in 3’ UTR.
Methodology/principal Findings. We investigated the post-transcriptional regulation of the AHRR expression by TTP. Our results show that the expression level of AHRR is inversely correlated with TTP expression in human breast cancer cell lines using the real-time PCR and western blot. The overexpression of TTP decreased the expression level of AHRR and inhibited the proliferation of MDA-MB435 human breast cancer cells. On the contrary, the treatment with a small interfering RNA against TTP increased the expression of AHRR mRNA and protein. AHRR mRNA contains two AREs within the 3’UTR and TTP destabilized a luciferase mRNA containing AHRR ARE. Moreover, RNA electrophoretic mobility shift assay revealed that TTP binds directly to the ARE of AHRR mRNA.
Conclusions/Significance. These studies demonstrated that the TTP expression is inversely correlated with AHRR expression in several human breast cancer cell lines using the real-time PCR and western blot. We suggest that TTP acts as a negative regulator of the AHRR gene expression and it may have an effect on tumor development through inducing AHR activation and the expression of tumor suppressors containing XRE in human breast cancer cells.
Citation Format: Hyun Hee Lee, Won Tae Kim, Dong Hee Kim, Sun-Hee Leem. Tristetraprolin downregulates AHRR expression through mRNA destabilization. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1791. doi:10.1158/1538-7445.AM2013-1791
Abstract 1798: The human mammary circadian transcriptome.
Authors: Combs Joseph , Mandichak Tracy , Ferree Elizabeth , Hoffman Aaron E. 
Published: August 2014

Abstract
The circadian rhythm, a phenomenon present in all of Eukaryota and in some members of Prokaryota, describes the processes within an organism that fluctuate throughout a daily cycle. Within peripheral tissues, clock gene expression is organized into a roughly 24-hour period by an elaborate feedback loop mechanism developed around a core set of circadian genes. In addition to maintaining rhythmicity within the molecular clock, key circadian genes such as CLOCK and ARNTL1 are also transcription factors that regulate the expression of a number of additional transcripts; the so-called clock-controlled genes (CCGs). This transcriptional control forms the backbone of circadian rhythmicity and is critical for the maintenance of proper cellular function in a variety of physiological processes, ranging from cell cycle regulation to cellular metabolism. Despite the importance of this regulatory clockwork system, little is known about the extent of molecular circadian control in human peripheral tissues. In fact, the majority of our knowledge of molecular oscillatory systems is derived from studies of model organisms which consistently demonstrate that outside of the core circadian genes; there is virtually no overlap in the compendium of CCGs across tissue types. Based on this critical observation, it is reasonable to expect that if CCGs vary considerably across tissues within the same organism, there may also be considerable heterogeneity across organisms, even within the same tissue type. Here we use next-generation sequencing analyses to provide the first circadian transcriptome in pre-stasis non-immortalized primary human mammary epithelial tissue. Using the non-parametric JTK_CYCLE algorithm, we found that approximately 6% of all expressed genes within this tissue are CCGs. We also find considerable evidence for circadian control in RNA processing events, including splice isoform usage and alternative polyadenylation, and a pathway analysis of all CCGs indicates circadian involvement in multiple signaling and growth pathways. These results demonstrate, for the first time, that a significant and important proportion of the human mammary transcriptome is regulated by the circadian system. Given the importance of circadian disruption in the pathophysiology of a range of human disorders, from metabolic disease to breast cancer, we believe that categorization of the circadian rhythm in human peripheral tissue will lay an important foundation for future breakthroughs in disease prevention, as well as in the development of novel therapeutic strategies.
Citation Format: Joseph Combs, Tracy Mandichak, Elizabeth Ferree, Aaron E. Hoffman. The human mammary circadian transcriptome. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1798. doi:10.1158/1538-7445.AM2013-1798
Abstract 1800: Expression analysis of PI3K pathway genes in head and neck cancer.
Authors: Buyru Nur , Ekizoglu Seda , Karaman Emin , Enver Ozgun 
Published: August 2014

Abstract
Head and neck cancer (HNC) is a heterogenous group of malignant tumors which includes neoplasias of the oral cavity, the pharynx, the larynx and paranasal sinuses. Squamous cell carcinomas comprise more than 95% of all head and neck cancers. The vast majority of HNC is related to exposure to carcinogens, including tobacco, alcohol, betel nut, and sexually transmitted viral pathogens such as human papilloma viruses (HPV). However, only a small fraction of tobacco and alcohol users develop the disease suggesting that genetic factors may play a key role in HNC.
Increasing evidence indicate that mTOR is a central regulator of cell growth, proliferation, survival and dysregulation of the PI3K/Akt/mTOR signaling pathway that occurs in many tumors including head and neck cancer. The TSC complex (TSC1/TSC2) negatively regulates mTOR by inhibiting a small GTP binding protein, Rheb, considered to be the direct activator of mTOR. On the other hand, the Ras protein upregulates PI3K signaling which is an upstream effector of mTOR. When PI3K activates Akt, the dual function phosphatase PTEN negatively regulates it. Human cancers frequently harbor activating mutations in the p110 catalytic subunit of PI3K or genomic amplification of Akt. Activated Akt also promotes survival under conditions of cellular stress.
In this study we investigated the expression of the critical genes (mTOR, K-ras, PI3KCA, TSC1, RHEB, PTEN and AKT1) acting in this pathway. For this purpose, we analyzed expression levels of these genes in 49 matched HNC tumor and non-cancerous tissue samples by quantitative RT-PCR. We observed a significant downregulation of the mTOR (p=0.005), TSC1 (p=0.001), and PTEN (p=0.000) mRNA expressions. On the other hand, a slight decrease was also observed in K-ras, Akt1 and PI3KCA mRNA levels in tumor tissues compared to the non-cancerous ones. However, the difference in the expression levels of these genes between the two groups were not statistically significant. Whereas we didn't observe any difference in Rheb mRNA expression level in tumor tissue when compared to the non-cancerous tissue samples. mTOR, TSC1, and PTEN mRNA expression levels were decreased 0.48, 0.44 and 0.32 % in HNC tumor tissue samples compared to non-cancerous tissue samples, respectively .
Our result indicate that, the PI3K pathway has an important function in HNC progression with the contribution of more than one gene of this pathway.
Citation Format: Nur Buyru, Seda Ekizoglu, Emin Karaman, Ozgun Enver. Expression analysis of PI3K pathway genes in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1800. doi:10.1158/1538-7445.AM2013-1800
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1811: Cancer/testis antigens: Comprehensive expression analysis and correlation with survival in glioblastoma.
Authors: Freitas Marcelo , Biassi Thaís P. , Malheiros Suzana M.F , Stávale João N. , Zamunér Fernando T. , Begnami Maria D.F.S , Soares Fernando A. , Vettore André L. 
Published: August 2014

Abstract
Glioblastoma (GBM) is a highly invasive and aggressive tumor which confers a dismal prognosis despite advances of current therapy. Cancer vaccines have been utilized as treatment of other tumors and might be an option for brain tumors. Cancer/testis (CTA) genes represent promising targets for immunotherapeutic approaches. They are expressed in tumors and expression in normal tissues is exclusively or preferentially restricted to testis. The expression of 31 CTA genes was investigated in 48 glioblastomas and 5 normal brain samples using RT-PCR. A tissue microarray was made and expression of a CTA was detected by immunohistochemical staining. Among the genes with no expression in normal brain CTA1 (57%), CTA2 (54%), CTA3 (44%) and CTA4 (15%) were the most expressed in glioblastomas. At least one of these four selected CTA genes was found expressed in 86% of the GBM cases. Coexpression of two, three and four CTA genes occurred in 25%, 17% and 5% of the examined GBM cases, respectively. CTA4 protein expression was identified in 13% (12/92) of GBM and was negative in all anaplastic astrocytomas (0/15), diffuse astrocytomas (0/48), pilocytic astrocytomas (0/38) and normal brain samples (0/40) evaluated. We found that CTA2-positive GBMs and tumors expressing 3-4 CTA genes presented a significantly better outcome (P = 0.032; hazards ratio = 0.53; 95% CI; 0.28 to 1.0 and P = 0.017, hazards ratio = 0.36; 95% CI, 0.17 to 0.74; respectively). Furthermore, multivariate survival analysis revealed that coexpression of 3-4 CTA genes (P = 0.044, hazards ratio = 0.3, 95%CI = 0.093-0.963), radiotherapy (P = 0.010, hazards ratio = 0.16, 95%CI = 0.04-0.65) and chemotherapy (P = 0.001, hazards ratio = 0.10, 95% CI = 0.03-0.41) remained as independent predictors of overall survival. In conclusion, CTAs are potential targets for immunotherapy in patients with GBM, 86% of the cases examined expressed at least one of four selected CTA genes. The presence of 3-4 CTA genes was associated with better survival, suggesting that these genes might elicit an immune response against GBM. Supported by FAPESP(Grant 2010/20218-2 and 2011/15118-1).
Citation Format: Marcelo Freitas, Thaís P. Biassi, Suzana M.F Malheiros, João N. Stávale, Fernando T. Zamunér, Maria D.F.S Begnami, Fernando A. Soares, André L. Vettore. Cancer/testis antigens: Comprehensive expression analysis and correlation with survival in glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1811. doi:10.1158/1538-7445.AM2013-1811
Abstract 183: Beta-endorphin neuron transplants suppress mammary tumor growth and progression: role of immune cells.
Authors: Sarkar Dipak K. , Zhang Changqing , Murugan Sengottuvelan , Boyadjieva Nadka , Ortigüela María 
Published: August 2014

Abstract
We have recently identified that a set of hormone secreting nerve cells in the hypothalamus, called beta-endorphin (BEP) neurons, have the ability to prevent the growth, progression and metastasis of mammary and prostate tumors in laboratory animals. How these neuronal cells prevent tumor cell growth and progression is not apparent. In order to better understand the mechanism by which endorphin neurons control tumor growth, we determined the growth and clearance of breast cancer derived MADB106 cells in Fisher rats, which are immune intact, and in athymic Nude rats, which are T cells deficient. Adult female Fischer rats or Nude rats were transplanted with either BEP neurons or cortical neurons (control) in the hypothalamus for 4 weeks and then inoculated with MADB106 cells in the jugular vein or under the skin in the back. These animals were sacrificed after 6 weeks to determine the volume of the tumor at the site of inoculation for determining the growth of tumors and the number of other tumors at the distant sites for determining tumor metastasis. Tumors were also collected for histopathology. Blood samples were collected and used for measurements of cytokines and immune cells. In Fischer rats, after tumor inoculation, animals with control cell transplants had tumor colonization in the lung and some on the skin at the site of cell injection. However, BEP neurons treated Fischer rats had no tumor colonization in the body. In the Nude rats, tumor colonization occurred both at the site of injection and at the distant site under the skin as well as in the lung of control transplanted rats. In BEP neurons transplanted Nude rats, tumor colonization only occurred at the site of inoculation. The mean volume of tumor at the inoculation site was smaller in BEP neurons transplanted rats than in control cells transplanted rats. In BEP neurons transplanted rats, corticosterone and inflammatory cytokines levels were lower, whereas anti-inflammatory cytokines and chemokines levels were higher. In addition, NK cell and macrophage cell numbers and their cytolytic functions in peripheral blood of BEP neurons transplanted rats were elevated. These data suggest that the antitumor action of BEP neuron transplants is due to the activation of primarily NK cells and macrophages and also in lesser extent T cells. The data also identify the potential use of BEP cell therapy for cancer prevention. (Supported by R37 AA08757)
Citation Format: Dipak K. Sarkar, Changqing Zhang, Sengottuvelan Murugan, Nadka Boyadjieva, María Ortigüela. Beta-endorphin neuron transplants suppress mammary tumor growth and progression: role of immune cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 183. doi:10.1158/1538-7445.AM2013-183
Abstract 1838: nc886, a putative tumor suppressive non-coding RNA in gastric cancer.
Authors: Kim Seon-Young , Park Jong Lyul , Kim Yong Sung , Lee Kwang Soo , Jeon Sung Ho , Lee Yong Sun 
Published: August 2014

Abstract
nc886, a novel type of non-coding RNA, was originally recognized as a microRNA precursor (pre-miRNA) or a vault RNA (vtRNA), but it has been shown to be barely processed into mature microRNAs and be mostly dissociated from the vault complex. So far, nc886’s best studied role is as a cellular RNA ligand and regulator of PKR (Protein Kinase RNA-activated). When nc886 is suppressed, PKR is activated and this activation leads to apoptosis through the canonical PKR-eIF2α cell death pathway. Given that the expression of nc886 was found to be suppressed in a variety of cancer cells, nc886/PKR's such role is thought to be critical in eliminating pre-cancerous cells during certain stages of tumorigenesis. Thus, nc886 plays a sentinel role against tumorigenesis by controlling PKR activity in some cells.
We have found that nc886 is decreased also in gastric cancer. Our measurement of nc886 in 88 specimens from gastric cancer patients indicates that nc886 tends to be decreased in tumors relative to the adjacent normal tissues. Also, DNA methylation of the nc886 locus exhibits an anti-correlation to nc886 level, and therefore epigenetic silencing is likely to be the mechanism for the decrease of nc886 in gastric cancer. Moreover, hypermethylation of the nc886 promoter region is associated with poor survival of gastric cancer patients. All our data indicates a putative tumor suppressive role for nc886 and the possibility of a clinical application for nc886 as a prognostic marker for gastric cancer.
Citation Format: Seon-Young Kim, Jong Lyul Park, Yong Sung Kim, Kwang Soo Lee, Sung Ho Jeon, Yong Sun Lee. nc886, a putative tumor suppressive non-coding RNA in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1838. doi:10.1158/1538-7445.AM2013-1838
Abstract 1841: Characterizing long non-coding RNAs located within a replication origin at the human DBF4 locus.
Authors: Hughes Shawn , Kylie Kathleen , Romero Julia , Lee Hoyun 
Published: August 2014

Abstract
Faithful replication of the entire genome only once per cell cycle is crucial to cell homeostasis. The importance of proper replication is manifested by the presence of a large library of strict regulatory mechanisms that a cell employs to govern entry into the cell cycle. Failure to regulate this “licensing” process may result in a state of aneuploidy which is a driving force in cancer development. Besides the licensing proteins, the precise mechanism of how a cell chooses or activates replication initiation points is still poorly understood in mammalian cells. We have been studying the replication origin located at the promoter region of the human DBF4 gene. This origin contains two replication initiation zones that fire in opposite directions sequentially in a time-dependant manner, which we've termed it asymmetrical bidirectional replication (ABR). We have recently discovered that the DBF4 origin region contains a unique distribution and modifications of histones, which appears to be relevant to the regulation of replication initiation. In addition, we also found high activities of long non-coding RNA (lncRNA) transcription up- and down-stream of the DBF4 origin. Our preliminary data suggest that the active transcription of the lncRNAs at this locus may have a regulatory function on the chromatin conformation, transcription and DNA replication. We are currently carrying out experiments to gain a better understanding of the mechanism how lncRNA transcription is regulated in the context of replication initiation and DBF4 transcription.
Citation Format: Shawn Hughes, Kathleen Kylie, Julia Romero, Hoyun Lee. Characterizing long non-coding RNAs located within a replication origin at the human DBF4 locus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1841. doi:10.1158/1538-7445.AM2013-1841