bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4923: Myofibroblasts induce specific epithelial-to-mesenchymal transition (EMT) patterns in colorectal cancer cells by enhanced secretion of bone morphogenic protein (BMP) inhibitors
Authors: Karagiannis George S. , Musrap Natasha , Diamandis Eleftherios P. 
Published: June 2012

Abstract
Epithelial-to-mesenchymal transition (EMT) is dictated by both cell-autonomous and stromal oncogenic signals. We hypothesized that colon cancer desmoplasia provides multiple signals, inducing EMT in cancer cells. To address this issue, we first developed cell-contact cocultures of SW480 and SW620 cell lines with normal fibroblasts. Cocultured fibroblasts (myofibroblasts) acquired the myofibroblastic phenotype with increased alpha-SMA and MMP2 expression, which was reversed by TGF-beta disruption. We identified oncogenic signals from myofibroblasts, after subjecting mono- and cocultures to secretome analysis with mass spectrometry (LC-MS/MS). In a total of 1551 identified proteins (&gt;2 peptides), a) secretome algorithms based on prediction of secretion, were deployed, allowing the removal of intracellular contaminants from the generated coculture lists and b) monoculture datasets were used as exclusion datasets to denote the non-specific-to-desmoplasia proteins. Subsequent bioinformatic analysis in this “desmoplastic” dataset (124 proteins) was used for protein clustering and recovery of a potential EMT cluster. We deployed: a) Ingenuity pathway analysis, b) Gene ontology, c) Smooth muscle enrichment analysis with Genevestigator d) Protein-protein interaction network analysis with STRING. Interestingly, this integration revealed GREM1, FST and FSTL3, three Bone Morphogenic Protein (BMP) inhibitors, as potent MET disruptors in colorectal cancer. We thus hypothesized that cancer cells recruit stromal fibroblasts to disrupt unfavorable BMP signaling (through generation of multiple BMP inhibitors), which supports a cancer cell undifferentiated state. To test this, a colon cancer cell line (HT29; active BMP signaling), was treated with human BMP7 and decreased cell migration (p&lt;0.05) and proliferation (p&lt;0.05) were shown. These lysates were further used for proteomic analysis (LC-MS/MS) with label-free quantitation to investigate differential protein expression. Using gene expression meta-analysis from fetal tissues, a significant (p&lt;0.01) shift from mesenchymal to epithelial protein dominance was noticed, after 200 ng/mL BMP7 treatment. Differentially expressed proteins remain to be validated, to better characterize the “BMP-7-disrpuption” EMT signatures in colon cancer. In conclusion, integrative “systems biology” approaches may support the identification and validation of EMT signatures with important causative links to cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4923. doi:10.1158/1538-7445.AM2011-4923
Abstract 4929: Dissection of protein-protein interaction-mediated cross-talk pathways in hepatocellular carcinoma
Authors: Chen Tzu-Chi , Liu Chia-Hung , Lee Pei-Ying Lee , Lin Kuan-Ting , Liu Yu-Wen , Huang Chi-Ying 
Published: June 2012

Abstract
Multiple dys-regulated cell signaling pathways and extensive cross-talks, which can be depicted via protein-protein interactions (PPIs), among individual signaling pathways, characterize cancer development and progression. However, systematic analysis of the cross-talk events from distinct pathways via PPIs remains fragmentary, and the reliability of PPI datasets, particularly at the cellular level, remains to be vigorously examined. Here, we first build the cross-talk pathway map of heptocellular carcinoma (HCC) through overexpression patterns in HCC among 23 pathways. By detecting endogenous PPIs in two HCC cell lines, Huh7 (low invasive cells) and Mahlavu (high invasive cells), we validate 50 PPI events within pathway and 19 PPI-mediated cross-talk events among 23 pathways in HCC. Not surprisingly, many distinct PPIs are present between Huh7 and Mahlavu, providing the opportunity to characterize tumor invasion. By analyzing topology of cross-talk PPI network, CRKL has a pivotal role in cross-talk pathway. This initial attempt to map the cross-talk pathways in HCC may represent the first step in deciphering hepatocarcinogenesis at the systems level and might reveal a novel strategy for HCC treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4929. doi:10.1158/1538-7445.AM2011-4929
Abstract 4931: Cancer stem cells in solid tumors: Symmetric division, niche size, and invasive tumor morphology
Authors: Enderling Heiko , Hlatky Lynn , Hahnfeldt Philip 
Published: June 2012

Abstract
In recent years cancer stem cells have been identified as a minor subpopulation in numerous solid tumors that drives tumor initiation, development and metastasis. Although cancer stem cells have yet to be reliably isolated, populations enriched for tumor-initiating cells give an indication of the order of magnitude of the stem cells niche within primary tumors. Here we develop and discuss the predictions of a simple theoretical model of cancer stem cells and tumor growth dynamics. We evaluate the impact of cancer stem cell symmetric/asymmetric division and progeny cancer cell proliferation capacity on tumor progression and morphology. The model predicts that the frequency of symmetric cancer stem cell division determines the resulting stem cell pool size, and that the symmetric division frequency and the stem cell fraction are both typically small, consistent with the cancer stem cell hypothesis. At the same time, we show that intrinsic competition for space and environmental confinement can lead to an increasing stem cell fraction over time despite a fixed, low symmetric division probability. These findings offer a novel explanation for the apparent differences in reported stem cell numbers for different tumors as well as tumors of the same organ, and thus challenging the hypothesis of a fixed stem cell ratio for different tumors. The pivotal role of stem cell division strategies and stem cell ratio on spatio-temporal morphology evolution and self-organizing tumor patterning is discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4931. doi:10.1158/1538-7445.AM2011-4931
Abstract 4933: Modeling the sequence-sensitive gemcitabine/docetaxel combination using the Virtual Tumor
Authors: Fernandez Eric , Orrell David , Mignard Caroline , Koob Zina , France Damien , Hoffman Nicolas , Bichat Francis , Fell David , Chassagnole Christophe 
Published: June 2012

Abstract
In recent years there has been great interest in determining synergistic drug combinations. A difficulty, however, is that the number of different possible schedules increases combinatorically when more than one drug is considered, so it is very hard to know what schedules should be tested. Physiomics, a computational biology company based in Oxford UK, has therefore developed a predictive PK-PD “Virtual Tumor” model that allows us to rationally design schedules for drug combination. This poster presents simulations of xenograft experiments, performed in collaboration with Oncodesign, for the sequence-sensitive gemcitabine/docetaxel combination regimen, which is widely used to treat various types of cancer. By producing xenograft and biomarker data of each drug in isolation, we have built a Virtual Tumor capable of simulating the outcome of various regimens using this combination, and proposed new optimal administration schemas. This technology can be used to design new regimens with proprietary compounds as well as standard of care, small molecules or biotherapeutical agents; help test possible schedules for combinations of different drugs that would be effectively impossible to investigate experimentally; and allow prioritisation of the most effective drug combinations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4933. doi:10.1158/1538-7445.AM2011-4933
Abstract 4934: Up-regulation of microRNA-21 correlates with lower survival of kidney cancer
Authors: Zaman Mohd Saif , Deng Guoren , Shahryari Varahram , Singh Kamaldeep , Sandhu Herman , Dahiya Rajvir 
Published: June 2012

Abstract
MicroRNA-21 is up-regulated in a variety of cancers, such as breast, colorectal, lung, head and neck, etc. However, the regulation of miR-21 in kidney cancer has not yet been studied systematically. We measured miR-21 levels in 40 pairs of kidney cancers and their normal matched tissues by real-time PCR. In 36 cases (90%), miR-21 was increased (ratios of miR-21 levels in tumors to normal tissues T/N were greater than 1.5). The expression level of miR-21 was correlated with 5 year survival and the stage of the patients. For patients with low miR-21 expression, all survived 5 years after the operation, while in case of high miR-21 expression, only 59% survived. In groups of patients having low expression (T/N &lt;1.5), moderate high expression (T/N 1.5-10) and very high expression (T/N &gt;10), the percent of early stage (Stage I) decreased: 100%, 76% and 43%, respectively. To study the biological effect of miR-21 up-regulation, a kidney cancer cell line A498 was transfected with miR-21 anti-miRNA inhibitor. The miR-21 level was reduced by more than 99%, as compared to the negative control. Flow cytometry analysis of the cell cycle showed a significant increase in G0/G1 phase (9.1%), with a concomitant reduction in the G2/M phase (6.8%), indicating that the forced reduction of miR-21 expression in A498 cells could inhibit the cell growth and cause G0/G1 arrest. Apoptosis assay using flow cytometry showed a significant increase in the number of total apoptotic cells in the miR-21 anti-miRNA inhibitor transfected cells as compared to the negative control. MiR-21 gene was mapped to chromosome 17q23, and increased copy numbers of this section, which includes oncogenes like erb-B2/HER-2, RPS6KB1, etc., were frequently present in cancers. We compared the miR-21 expression levels with the amplification of this section in 30 cancer cell lines, including 5 kidney cancer, 6 breast cancer, 15 colorectal cancer, 3 prostate cancer, and 1 bladder cancer. We observed a significant correlation between the amplification of 17q and high miR-21 expression. In conclusion, the up-regulated miR-21 in kidney cancer could be used as a tumor marker for diagnosis. The inhibition of miR-21 and/or its adjacent oncogenic genes may prove to be useful in controlling cancers with up-regulated miR-21.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4934. doi:10.1158/1538-7445.AM2011-4934
Abstract 4945: Androgen-mediated phenotypic change produces a miRNA fingerprint in prostate carcinoma cells
Authors: Segal Corrinne V. , Powell Christopher J. , Gooderham Nigel J. 
Published: June 2012

Abstract
Activation of the androgen receptor (AR) results in phenotypic change in androgen-responsive cells; for example, in the human prostate carcinoma cell line (LNCaP) androgens mediate cell proliferation. Factors controlling the range of phenotypic responses mediated by androgens are only partially understood, but include both transcriptional and post-transcriptional mechanisms. One such mechanism that appears to offer wide ranging, yet highly selective control, is microRNA-mediated post-transcriptional regulation. In the present study, we assessed the influence of endocrine-active compounds that act via the AR pathway on the microRNA (miRNA) profile. As negative regulators of gene expression, miRNA are short non-coding RNA that are able to suppress translation or induce degradation of their target mRNA transcripts leading to decreased protein expression.
The effect of exposure of LNCaP cells to a model synthetic AR agonist, a physiological androgen and a therapeutic AR antagonist was determined at various time points up to 120 hours. Phenotypic response to exposure was assessed as an alteration of proliferative ability, expression of prostate-specific antigen (PSA) and alteration of the miRNA-ome. As expected, the agonists significantly induced proliferation and PSA expression, compared to vehicle control, whilst the antagonist itself had no effect on proliferation and PSA expression except when cultured in the presence of the natural ligand resulting in potentiation of the ligand's effects.
The temporal effects of the compounds on the expression profile of 866 miRNAs were assessed using Agilent's miRNA microarray version 3. A number of miRNAs were found to be altered in a compound-specific and temporal manner, including some implicated in cell cycle control. qRT-PCR of select miRNAs proceeded to validate the fold changes observed by microarray. Targets for altered miRNAs were deduced using bio-informatic approaches and immunoblotting of target proteins has confirmed that protein levels are inversely correlated. These data describe an androgen-mediated miRNA ‘fingerprint’ that is compound and temporally dependent and provides mechanistic insights into the biological responses of cells to such compounds.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4945. doi:10.1158/1538-7445.AM2011-4945
Abstract 4947: microRNA expression in soft tissue sarcomas is associated with prognosis
Authors: Greither Thomas , Würl Peter , Grochola Lukasz , Bond Gareth , Bache Matthias , Kappler Matthias , Lautenschläger Christine , Holzhausen Hans-Jürgen , Eckert Alexander , Taubert Helge W. 
Published: June 2012

Abstract
The levels of miR-210 known as hypoxia regulated microRNA were analyzed by quantitative RT-PCR in a cohort of 78 soft tissue sarcomas (STS). The microRNA levels were separated according to the tercentile in low, intermediate and high expression and possible association of microRNA expression and patients’ survival was examined using multivariate Cox's regression hazard analyses. A significant correlation between intermediate miR-210 expression and disease specific death of female STS patients was observed compared to patients with a high expression level in their tumors (RR=11.28; P=0.010). Furthermore, expression of miR-210 was significantly associated with age of tumor onset in a gender-specific manner. Male patients with an intermediate expression of miR-210 showed a 9.6 years later age of tumor onset compared to males with a low expression of miR-210 in their tumors. However, this was not the case for female patients. This study provides the first evidence for a correlation of expression levels of a single microRNA (miR-210) with prognosis and a gender specific association with age of tumor onset for soft tissue sarcoma patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4947. doi:10.1158/1538-7445.AM2011-4947
Abstract 4962: Assessing serum miRNA as putative biomarkers for serous epithelial ovarian cancer
Authors: Kan Casina W. , Hahn Michael A. , Marsh Deborah J. , Howell Viive M. 
Published: June 2012

Abstract
Serous epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy; due in part to vague and non-specific symptoms resulting in delayed diagnosis. The biomarker in routine clinical use for EOC is CA-125, with the OVA1 test (Quest Diagnostics) recently available to aid in predicting the likelihood that an ovarian mass is malignant. Current diagnostic tests have limitations which may be improved by expansion of biomarker panels. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate important cellular processes. They exhibit distinct expression profiles in cancers and have recently been discovered in serum and other body fluids. Tumor miRNAs may be shed into the circulation, raising the possibility of their use as serum biomarkers for the detection of EOC.
Exiqon LNA miRNA microarrays were performed using RNA from cell line models of serous EOC. Over-expressed miRNAs were selected as candidates for assessment in serum. These were measured in RNA extracted from serum of patients with serous EOC (n=30) and healthy age-matched volunteers (n=30) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). As there are currently no routine methods for the normalization of miRNA in serum, a group of highly and uniformly expressed miRNAs with no reported involvement in cancer was selected for assessment as endogenous controls.
Five miRNAs, miR-182, miR-96 and miR-200a, miR-200b and miR-200c were identified as highly expressed in a panel of serous EOC cell lines consistent with previous reports, and therefore selected for investigation as putative serous EOC biomarkers. In addition, miR-92a, miR-103, miR-638 and RNU48 were selected as candidate endogenous controls given that they were consistently expressed at high levels in the cell line panel. qRT-PCR data will be presented on the expression of these 8 candidate miRNAs and RNU48 either with or without pre-amplification of target sequence.
In conclusion, miR-92a, miR-103 and miR-638 were observed to show little variation between patients and healthy volunteer serum. These results identify the potential for these miRNAs to be used as endogenous controls for the expression of miRNA in serum. Reliable detection of specific miRNAs in serum from women with serous EOC may improve the detection of this malignancy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4962. doi:10.1158/1538-7445.AM2011-4962
Abstract 4968: TNF-alpha promotes genome-wide replacement of TAp73 chromatin occupancy by cREL and DeltaNp63
Authors: Lu Hai , Si Han , Yang Xinping , Burnett Jeffery , Davis Sean , Sun Hongwei , Xiao Wenming , Wei Lai , Meltzer Paul , Van Waes Carter , Chen Zhong 
Published: June 2012

Abstract
cREL, DeltaNp63, and TAp73, members of NFkappaB and TP53 transcription factor (TF) families, together regulate broad biological processes critical for inflammation and cancer survival. However, the underlying mechanisms explaining their cross-regulation of transcriptome and interactive signal network have not been revealed. Here, we demonstrate that inflammatory cytokine TNF-alpha induces a dynamic, genome-wide increase in cREL and DeltaNp63 chromatin occupancy after replacing TAp73 binding activity, using ChIP-seq and fitting the data into a negative binomial distribution model integrated in CisGenome. Globally, most of the binding peaks were localized in intergenic and intronic areas, with 4.2% and 5.6% peaks significantly enriched into promoter regions (3000 bp upstream of transcription starting sites) of cREL and DeltaNp63 bound DNAs in response to TNF-alpha respectively, and co-localized peaks for any of the two TFs are prevalent within a distance of ∼200 bp. De novo motif search using Gibbs Sampler identified TP53 and novel binding motifs. A total of 188 differentially expressed genes are associated with the TNF-alpha-induced chromatin occupancy shift by the three TFs. These genes are enriched in cancer-related transcription factors and TP53 signaling pathways. Our data reveal a novel mechanism of genome-wide replacement of TAp73 by cREL and DeltaNp63, supporting cross-regulation and an interactive network between NFkappaB and TP53 families.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4968. doi:10.1158/1538-7445.AM2011-4968
Abstract 497: Loss of Notch-1 expression in human prostate epithelial cells results in reduced PTEN expression and altered differentiative capacity
Authors: Angus C. William , Willis David F. , Salvador Wenimar D. , Bertrand Fred E. 
Published: June 2012

Abstract
Notch-1 is part of an evolutionarily ancient cell surface receptor signaling pathway that functions in the determination of stem/progenitor cell fate. The human genome encodes four Notch-receptors (Notch-1, -2, -3, and -4) and at least five Notch-ligands (Delta-1, -3, -4, Jagged-1, and-2). Signaling is initiated upon ligand binding to the Notch receptor, which results in a series of proteolytic cleavages that release constitutively active intracytoplamsic Notch (ICN). Nuclear translocation of ICN results in activation of the CBF-1 transcription factor which in turn increases expression of developmentally regulated transcription factors such as Hes-1 and Hey-1. The PTEN tumor suppressor gene is a recently identified Notch-1 target. We have reported that Notch-1 signaling increases expression of the PTEN tumor suppresser gene in prostate tumor cell lines and that Notch-1 signaling is lost in the tumor foci of prostate adenocarcinoma patients. To test the hypothesis that loss of Notch-1 will result in deregulation of normal prostate epithelial cell differentiation and promote tumorigenesis, a lentiviral vector bearing a Notch-1 shRNA (shN1) was used to stably knockdown Notch-1 expression in the benign human prostate epithelial cell line, RWPE-1. Western blotting revealed that RWPE-1/shN1 cells lacked Notch-1 expression, and exhibited reduced expression of Hes-1, confirming that loss of Notch-1 expression resulted in loss of Notch signaling. PTEN protein expression was also reduced, consistent with our previous studies demonstrating that Notch-1 signaling regulated PTEN expression. RT-PCR experiments verified that loss of PTEN expression was mediated at the level of transcription. RWPE-1/shN1 cells lacking Notch-1 expression exhibited a more rounded morphology, as compared with the parental cell line. Rhodamine-phalloidin staining revealed that RWPE-1/shN1 cells had less numerous and shorter cell surface actin projections. RWPE-1/shN1 cells lacking Notch-1 expression exhibited a 2-fold increase in acinar differentiation upon 3-D culture in matrigel as compared with the parental cell line. Flow cytometric analysis revealed that RWPE-1 cells without Notch-1 expression had reduced surface expression of TROP2 and CD149f. Preliminary RT-PCR results indicate that expression of the basal cell marker keratin-5 is reduced in RWPE-1/shN1 cells as compared with parental RWPE-1 cells. Our data suggest that loss Notch-1 expression, and hence loss of signaling, may promote developmental plasticity in prostate epithelial cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 497. doi:10.1158/1538-7445.AM2011-497