bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3466: Mediated by cancer cell and stroma cell TGF-β signaling, the periostin / β-Ig-H3 expression ratio is altered during breast cancer progression
Authors: Coleman Michelle M. , Burman Anindita Das , Lance Amanda L. , Dreau Didier 
Published: May 2015

Abstract
Involved in the maintenance of normal breast tissue, the extracellular matrix (ECM) also supports the progression of several human cancers. In particular, both periostin and TGF-β-induced (β-Ig-H3) whose expression is regulated by transforming growth factor-β (TGF-β) signaling, are differentially expressed in many human cancers. While a link between increased periostin expression and poor breast cancer outcomes has been shown, our recent data suggest that overall periostin expression is variable and is poorly correlated with human breast cancer progression. Therefore, in this study we investigated the ratio between periostin and β-Ig-H3 expression and the relationship between TGF-β signaling and expression of these ECM proteins by cancer cells and stromal cells during human breast cancer progression. Expressions of periostin and β-Ig-H3 were determined in biopsy specimens collected from 61 breast cancer patients by immunohistochemistry and correlated with clinico-pathologic features. Additionally, periostin, β-Ig-H3, and TGF-β expression in multiple stroma and tumor cells were evaluated in vitro using western-blots and ELISAs. Increases in the periostin / ß-Ig-H3 ratio correlated with increased the AJCC stage and progesterone positive status of the breast cancer specimens tested (p&lt;0.05). In vitro, murine L929 fibroblasts and 4T1 mammary cancer cells secreted higher periostin concentrations compared to J774 and RAW macrophages (p&lt;0.05). Furthermore, the periostin / ß-Ig-H3 protein expression ratio of 4T1 cells was higher than those of J774 and RAW cells. Following treatment with TGF-ß that activated the SMAD pathway, L929 and 4T1 cells expressed higher periostin concentrations (p&lt;0.05). In contrast, the high ß-Ig-H3 secretion by L929 fibroblasts and J774 macrophages remained unchanged following TGFß treatment (n.s.). These observations support a role for TGF-ß and periostin signaling loops between stroma and cancer cells in the microenvironment and may indicate a role of the periostin / ß-Ig-H3 ratio as a predictor of breast cancer aggressiveness.
[This works was supported by grants from the Department of Defense Era of Hope research program (BC044778) and the National Science Foundation EFRI program (CBE0736007)]
Citation Format: Michelle M. Coleman, Anindita Das Burman, Amanda L. Lance, Didier Dreau. Mediated by cancer cell and stroma cell TGF-β signaling, the periostin / β-Ig-H3 expression ratio is altered during breast cancer progression. [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 3466. doi:10.1158/1538-7445.AM2014-3466
Abstract 3467: Progesterone inhibits endometrial cancer growth and invasiveness by modulating the TGF-ß pathway
Authors: Bokhari Amber A. , Lee Laura R. , Raboteau Dewayne , Hamilton Chad A. , Maxwell George L. , Turbov Jane M. , Thaete Larry G. , Rodriguez Gustavo C. , Syed Viqar 
Published: May 2015

Abstract
Objectives: Our group has shown previously that progesterone may exert a chemoprotective effect against endometrial cancer through modulation of TGF-β signaling and concomitant activation of apoptosis in the endometrium. In addition, it has been shown that increased expression of TGF-β isoforms in human endometrial cancer correlates with decreased survival and poor prognosis. These data suggest that the TGF-β pathway may be an attractive target for chemoprevention strategies. The goal of this study was to further characterize the effect of progesterone on TGF-β signaling pathway components (TGF-β isoform and Smads) and on TGF- β-induced pro-tumorigenic activities in endometrial cancer cell lines.
Methods: The expression levels of TGF-β ligands (TGF-β1, TGF-β2 and TGF-β3), TGF-β receptors (TGF-βR1, TGF-βR2, and TGF-βR3) and SMADs (pSMAD2/3, SMAD2/3 and SMAD-4) were determined by immunoblotting in HEC-1B endometrial cancer cells exposed to progesterone for 24, 72 and 120 h. Proliferation and cellular invasion assays were used to access the functional effects of progestin exposure in the HEC-1B and Ishikawa endometrial cancer cell lines.
Results: A marked decrease in TGF-β1and TGF-β3 expression was observed at 72 h after treatment with progesterone. Expression of TGF-βR1, TGF-βR2, SMAD2/3 and pSMAD2/3 were substantially reduced at 72 h while levels of SMAD4 and TGF-β2 expression were reduced at 120 h following progesterone. TGF-βR3 expression levels were not affected by any treatment at any time point. Furthermore, TGF-β1-induced cancer cell proliferation and invasion was effectively inhibited by progesterone. Cellular proliferation and invasion were significantly reduced by progestin compared to controls even in the presence of exogenous TGF-β.
Conclusions: These results suggest that the down-regulation of TGF-β signaling may be a key mechanism underlying progestin inhibition of endometrial carcinogenesis.
Citation Format: Amber A. Bokhari, Laura R. Lee, Dewayne Raboteau, Chad A. Hamilton, George L. Maxwell, Jane M. Turbov, Larry G. Thaete, Gustavo C. Rodriguez, Viqar Syed. Progesterone inhibits endometrial cancer growth and invasiveness by modulating the TGF-ß pathway. [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 3467. doi:10.1158/1538-7445.AM2014-3467
Abstract 3471: Gene expression profiling of a single laser capture microdissected (LCM) cell
Authors: Chu Shirley 
Published: May 2015

Abstract
Laser Capture Microdissection (LCM) is a technique providing a rapid and reliable method to procure purified cell populations, either as multiple single cells or a group of cells, from a heterogenic tissue sample allowing a targeted approach to genomic profiling. When analyzing gene expression profiles from a group of cells, the average profile may not be a true representation of the many different profiles that could exist even in a pure cell population (e.g., in different states of growth, differentiation, or activation). As a result, the transcriptional variability of individual cells and any insight into the relationship between specific genes in single cells are lost. To fully understand the complexity of tissue and cellular heterogeneity, it is necessary to measure molecular signatures at the single cell resolution. Here we developed a workflow for gene expression profiling of a single LCM cell that can also be applied to small number of LCM cells. The ArcturusXT™ LCM system was used to harvest single cells from frozen human tumor tissue sample which were then processed for quantitative RT-PCR (qRT-PCR) gene expression analysis.
Citation Format: Shirley Chu. Gene expression profiling of a single laser capture microdissected (LCM) cell. [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 3471. doi:10.1158/1538-7445.AM2014-3471
Abstract 3473: Identification of progesterone-dependent genes regulated by ablation of mitogen-inducible gene-6 (Mig-6) in the murine uterus
Authors: Kim Tae Hoon , Yoo Jung-Yoon , Jeong Jae-Wook 
Published: May 2015

Abstract
Mitogen-inducible gene-6 (Mig-6) is an important mediator of progesterone signaling to inhibit estrogen signaling in the uterus. Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. Although Mig-6 is an important tumor suppressor in endometrial cancer, relatively little is known about the molecular mechanisms of Mig-6 in endometrial cancer. To identify the molecular pathways regulated by Mig-6 in a steroid-hormone dependent manner, we performed microarray analysis on the uterus of ovariectomized PRcre/+Mig-6f/f (Mig-6d/d) mice treated with progesterone for 6 hours. In the analysis of GeneChip® Mouse Genome 430 2.0 Array, 2,034 genes, 1,062 genes were up-regulated and 972 genes were down-regulated, were altered by P4 treatment. To determine which pathways are regulated by P4 treatment, we performed pathway analysis using Ingenuity Systems Software. Genes that involved in Estrogen Receptor, IGF-1, PI3K/AKT, JAK/Stat, ERK/MAPK, ILK, p53, PTEN, and Wnt/β-catenin signaling were found to be P4 response. In addition, genes that regulated the molecular mechanisms of cancer were disproportionated. And in microarray, 2,236 genes, 1,883 genes were up-regulated and 356 genes were down-regulated, were regulated by Mig-6 ablation on P4 treatment. Genes involved in ILK, p53, PTEN, PI3K/AKT, and Wnt/β-catenin signaling were found to be deregulated upon Mig-6 ablation on P4 response. Furthermore 324 genes of the 2,034 genes were regulated by P4 treatment were dys-regulated in Mig-6d/d mice treated with P4 compared to Mig-6f/f control mice. These results showed that gene expression pattern was altered by the deletion of Mig-6 and the change of these genes was dependent on P4 in uterus. Thus the further investigation should be completed to identify molecules associated with Mig-6 and the identification of relation between these responsive genes will contribute to define the molecular pathways regulated by Mig-6 in uterine biology.
(This work was supported by NIH, R01 HD057873 and American Cancer Society Research Grant, RSG-12-084-01-TBG to J.W.J.)
Citation Format: Tae Hoon Kim, Jung-Yoon Yoo, Jae-Wook Jeong. Identification of progesterone-dependent genes regulated by ablation of mitogen-inducible gene-6 (Mig-6) in the murine uterus. [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 3473. doi:10.1158/1538-7445.AM2014-3473
Abstract 3482: A robust TALENs system for highly efficient mammalian genome editing
Authors: Zhang Siliang , Feng Yuanxi , Huang Xin 
Published: May 2015

Abstract
Recently, transcription activator-like effector nucleases (TALENs) have emerged as a highly effective tool for genomic editing. A pair of TALENs binds to two DNA recognition sites separated by a spacer sequence, and the dimerized FokI nucleases at the C terminal then cleave DNA in the spacer. Because of its modular design and capacity to precisely target almost any desired genomic locus, TALENs is a technology that can revolutionize the entire biomedical research field. Currently, for genomic editing in cultured cells, two plasmids encoding a pair of TALENs are co-transfected, followed by limited dilution to isolate cell colonies with the intended genomic manipulation. However, uncertain transfection efficiency becomes a bottleneck, especially in hard-to-transfect cells, reducing the overall efficiency of genome editing. We have developed a robust TALENs system in which each TALEN plasmid also encodes a fluorescence protein. Thus, cells transfected with both TALEN plasmids, a prerequisite for genomic editing, can be isolated by fluorescence-activated cell sorting. Our improved TALENs system can be applied to all cultured cells to achieve highly efficient genomic editing. Furthermore, an optimized procedure for genomic editing using TALENs is also presented. We expect our system to be widely adapted by the scientific community.
Citation Format: Siliang Zhang, Yuanxi Feng, Xin Huang. A robust TALENs system for highly efficient mammalian genome editing. [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 3482. doi:10.1158/1538-7445.AM2014-3482
Abstract 350: Virtualization of drug testing by predictive systems biology modeling for optimal drug treatment of cancer cells and drug repositioning
Authors: Kuehn Alexander , Dreher Felix , Peycheva Svetlana , Yildiriman Reha , Lehmann Verena , Kessler Thomas , Wierling Christoph , Lehrach Hans , Lange Bodo M. 
Published: May 2015

Abstract
Traditionally, tumors have been classified based on their tissue of origin and their histopathological characteristics and consequently patients are divided into groups where they are treated identically despite substantial differences in genetic profiles. Identification of genes causally implicated in cancer development has led to the development of ‘stratified’ medicine, which adjusts a patient’s therapy based on biomarkers that identify some of the patients expected not respond to a specific therapy. However, many tumor genome sequencing projects have shown that many more gene mutations drive the development of cancer than previously thought, making every tumor unique. These results in low success rates and thereby high cost in drug approval as the identified drugs are only effective for particular patient groups while large patient cohorts have no clear clinical benefit. In the early process of drug development, drugs are therefore screened on large cancer cell line collections to define drug applicability and to determine potential tumor targets.
Here, we report the results of a computational modeling platform, ModCell, allowing the prediction of individual drug effects using large-scale genomic and transcriptomic data to virtualize such cell line screening. We validated this approach two-fold: on publicly available data from the cancer cell line encyclopedia, that comprises pharmacological profiles for anti-cancer drugs across a library of cancer cell lines as well as on cancer cell line culture experiments. We provide evidence that ModCell is able to reproducibly predict the effects of individual drugs with a confounding 80% accuracy, to predict combinatory drug action and to identify new applications for existing drugs. Thus, computational modeling using ModCell can improve todays drug development by accelerating and partly replacing work which would have otherwise be conducted in the laboratory and in the clinic.
Citation Format: Alexander Kuehn, Felix Dreher, Svetlana Peycheva, Reha Yildiriman, Verena Lehmann, Thomas Kessler, Christoph Wierling, Hans Lehrach, Bodo MH Lange. Virtualization of drug testing by predictive systems biology modeling for optimal drug treatment of cancer cells and drug repositioning. [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 350. doi:10.1158/1538-7445.AM2014-350
Abstract 3509: Overexpression of 14-3-3γ contributes to chromosomal instability in human lung cancer
Authors: Gomes Cecil J. , Centuori Sara , Martinez Jesse D. 
Published: May 2015

Abstract
Lung cancer is the most common cause of cancer-related deaths, and nearly all lung cancers exhibit genomic instability which results in an abnormal number of chromosomes known as aneuploidy. In many lung cancers, 14-3-3 proteins have been shown to be aberrantly activated or suppressed, which implies that these proteins have potential roles in tumorigenesis. Our lab has demonstrated that over expression of one 14-3-3 family member, 14-3-3γ, in a non-small cell lung cancer cell line leads to an increase in the number of cells that exhibit polyploidy, suggesting that this 14-3-3 protein can disrupt normal chromosome segregation. Additionally, overexpression of 14-3-3γ leads to atypical DNA replication and cell cycle progression. Further evaluation of the polyploid population induced by overexpressing 14-3-3γ revealed that a majority of the cells were multinucleated, often with two or more nuclei of unequal size and morphology. Live cell microscopy shows that this nonlinear marked increase in nuclear content is due to unequal distribution of DNA to the daughter cells upon cellular division, promoting chromosomal instability. Our data indicates that 14-3-3γ may play an important role in maintaining normal diploidy, but when overexpressed, as seen in many lung cancers, can lead to increased levels of chromosomal instability and progression into aneuploidy.
Citation Format: Cecil J. Gomes, Sara Centuori, Jesse D. Martinez. Overexpression of 14-3-3γ contributes to chromosomal instability in human lung 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 3509. doi:10.1158/1538-7445.AM2014-3509
Abstract 3510: N-Myc positively influences mitochondrial biogenesis in neuroblastoma
Authors: Sharma Manika , Graves James A. 
Published: May 2015

Abstract
Background:
Neuroblastoma is the most common extracranial tumor of childhood., accounting for approximately 7% of all cancer in children. The morbidity and mortality are affected by a number of factors - perhaps most significantly by amplification of the oncogene, N-MYC. Advanced stage disease with N-MYC overexpression confers the highest mortality. The N-MYC gene product (N-Myc) regulates the transcription of many genes, and when overexpressed is thought to enhance the cell cycle and dysregulate apoptosis. The function of N-Myc is virtually identical to another oncoprotein of the same family, c-Myc, yet is restricted by developmental stage and cell type. Overexpression of c-Myc has been shown to increase mitochondrial biogenesis by alterations in mitochondrial dynamics. It has been proposed that these changes may contribute to c-Myc induced tumorigenesis. We hypothesize that N-Myc amplification will have similar effects on mitochondrial biogenesis in neuroblastoma.
Design/Methods:
To perform these studies we utilized a cell line with endogenous levels of N-Myc (SK-N-SH). In these cells we have ectopically overexpressed N-Myc and examined the cells for changes in the mitochondria with various assays, including: Western blots, electron microscopy, flow cytometry, ATP assay and confocal microscopy.
Results:
We found a X-fold increase in mitochondrial mass in cells that overexpress N-Myc,, as well as a more tubular appearance with less organized cristae. Additionally, N-Myc changed the expression of various mitochondrial fusion and fission proteins. The most dramatic change was seen in the expression of the fusion protein Opa1, which changed by ten-fold. This, combined with a decrease in expression of fission proteins DRP1 and MFF, may account for the more tubular appearance of mitochondria in N-Myc overexpressing cells.
Conclusions
N-Myc amplification appeared to increase mitochondrial mass. This may occur as a result of increased expression of mitochondrial fusion proteins, as previously observed in c-Myc overexpressing cells. Additionally, mitochondrial function is influenced by N-Myc overexpression. Therefore, N-Myc amplification appears to positively influence mitochondrial biogenesis in neuroblastoma. Further studies are needed to determine if this increase in mitochondrial mass and function is necessary for the development and maintenance of neuroblastoma.
Citation Format: Manika Sharma, James A. Graves. N-Myc positively influences mitochondrial biogenesis in neuroblastoma. [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 3510. doi:10.1158/1538-7445.AM2014-3510
Abstract 3515: Increased TSH signaling by overexpressed thyrotrophin receptor is essential for B-RafV600E induced thyroid carcinogenesis
Authors: Kim Young Hwa , Choi Yong Won , Kim Jang-Hee , Park Tae Jun 
Published: May 2015

Abstract
B-RafV600E oncogene mutation occurs most commonly in papillary thyroid cancer (PTC), and is associated with tumor initiation. However, a genetic modification by B-RafV600E in the thyrocytes results in oncogene induced senescence (OIS). In the present study, therefore, we attempted to evaluate the factors involved in the senescence overcome program in PTC. First of all, we observed downregulation of p-Erk1/2 and upregulation of dual specific phosphatase 6 (DUSP6) in the PTC with B-RafV600E mutation. In B-RafV600E expressing thyrocytes, although DUSP6 mRNA was upregulated, its protein and phosphatase activity were similar to those of normal thyrocytes. However, DUSP6 activity was reactivated when ROS was downregulated by thyroid stimulating hormone (TSH). Moreover, upregulation of MnSOD by TSH was observed in thyrocytes and PTC. Although serum TSH was not increased, its receptor was markedly upregulated in PTC with B-RafV600E. TSH together with DUSP6 inhibited B-RafV600E induced senescence in the thyrocytes, and reactivated Ras/Akt/GSK3β resulted in c-Myc protein stabilization by inhibition of its degradation. These observations led us to conclude that increased TSH signaling by overexpression of TSH receptor is essential for B-RafV600E induced papillary thyroid carcinogenesis.
Citation Format: Young Hwa Kim, Yong Won Choi, Jang-Hee Kim, Tae Jun Park. Increased TSH signaling by overexpressed thyrotrophin receptor is essential for B-RafV600E induced thyroid carcinogenesis. [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 3515. doi:10.1158/1538-7445.AM2014-3515
Abstract 3517: Role of primary cilia in breast and prostate cancer
Authors: Hassounah Nadia B. , Nunez Martha , Nagle Raymond , McDermott Kimberly M. 
Published: May 2015

Abstract
Primary cilia are microtubule-based organelles expressed on many mammalian cell types and help sense the extracellular environment. Signaling pathways important in development, tissue homeostasis, as well as cancer are known to be regulated by primary cilia, such as the Wnt and Hedgehog pathways. However, little is known about the role of primary cilia in cancer. We have previously demonstrated in a published study that primary cilia expression was significantly decreased through human prostate cancer progression (PLoS ONE 8 (7), 2013). We also discovered that primary cilia lengths were shorter through prostate cancer progression, which suggests dysfunction. In addition, we observed that primary cilia expression and length correlated with canonical Wnt signaling in normal human prostate tissue, premalignant lesions, and a subset of cancers. This data suggested that primary cilia dysfunction may alter Wnt signaling in the human prostate. We have also characterized primary cilia in human breast cancers, and similarly found a significant loss of primary cilia with breast cancer progression. We therefore hypothesize that primary cilia suppress tumorigenesis in these tissues, and consequently that primary cilia loss promotes cancer formation by altering signaling pathways. We are currently testing this hypothesis by knocking out primary cilia in a tumorigenic mammary mouse model and measuring changes in tumor growth, as well as changes in signaling pathways, like Wnt and Hedgehog signaling. Preliminary data demonstrates enhanced tumor growth in the absence of primary cilia, thus supporting our hypothesis that primary cilia may act as tumor suppressor organelles.
Citation Format: Nadia B. Hassounah, Martha Nunez, Raymond Nagle, Kimberly M. McDermott. Role of primary cilia in breast and prostate 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 3517. doi:10.1158/1538-7445.AM2014-3517