bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C36: Dc917 inhibits the growth of mouse lung carcinoma both in vitro and in vivo through cell cycle arrest and ERK signaling pathway
Authors: Dong Hang , Jiang Zhihong , Wong Vincent Kam Wai , Zhou Hua , Liu Liang 
Published: June 2012

Abstract
Background: Chemotherapeutic agents often exhibit adverse effects to patients because of their nonspecific cytotoxic effect, and therefore we have screened anticancer compounds from a natural source. Dc917, a novel derivative from a Chinese medicinal plant, exhibited specific cytotoxic effect to a panel of cancer cells but no marked impairment to human normal lung fibroblasts, and it significantly suppressed tumor growth in xenograft-bearing mice. We thus aimed to further investigate molecular mechanisms of Dc917.
Methods: Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Immunoblotting was performed to determine changes in protein levels. Knockdown of desired protein was achieved by transfection with siRNA. Meanwhile, C57BL/6 mice bearing lung carcinoma cells were used to estimate the antitumor activity in vivo.
Results: Dc917-induced significant cell cycle arrest in S phase was concomitant with downregulations of cdks and cyclins, as well as upregulations of p21 and p27 expression. The complex formation between cdk2/cyclin E and cdk4/cyclin D1 was reduced; however, the recruitment of p21 or p27 to cyclin E/Cdk2 complex was increased by Dc917 incubation. In addition, Dc917-induced cell death and S phase arrest were significantly attenuated by knockdown of p21 or p27 protein. Dc917 also induced MAPK and p53 pathway, which activated p27/p21 and subsequently suppressed cyclin/cdk complexes activity, and the inhibitor of ERK (U0126) could suppress Dc917-induced cytotoxicity and upregulation of p53/p27 or p21 and egr-1/p27 or/p21 expression.
Conclusions: Our preclinical data indicated that Dc917 is a potential therapeutic agent in vitro and in vivo, and further development of this agent for cancer therapy is processing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C36.
Abstract C40: Recombinant viral protein suppresses metastasis of ovarian adenocarcinoma cells through negative Akt signaling
Authors: Peng Jei-Ming , Hung Shao-Wen , Chiu Ching-Feng , Ho Ming-Yi , Hsiao Michael , Liang Chi-Ming , Liang Shu-Mei 
Published: June 2012

Abstract
Ovarian cancer has a high fatality rate, mainly due to metastatic progression of tumor cells. Advances in the treatment of metastatic ovarian cancer are needed. Here, we studied the mechanism of action of a recombinant viral capsid protein (rVP1) and explored its effect against ovarian tumor growth and metastasis in vivo. We found that rVP1 was cytotoxic to several human ovarian cancer cell lines, namely doxorubicin-resistant SKOV3, cisplatin-resistant OVCAR-3, and TOV-21G. rVP1 was more potent than doxorubicin and cisplatin in inducing apoptosis and inhibiting growth of SKOV3 in vitro. Treatment of SKOV3 or peritoneal adapted SKOV3ip.1 cells with rVP1 at certain concentrations below IC50 resulted mainly in inhibition of cell invasion rather than apoptosis. This inhibitory effect of rVP1 on cell invasion was accompanied with activation of PTEN and GSK-3β as well as downregulation of FAK, Akt and MMP-2. Anti-integrin antibodies or overexpression of constitutively active Akt reversed the cellular effects of rVP1. In vivo studies confirmed that rVP1 attenuated survival and metastasis of SKOV3 cells through the selective regulation of Akt and GSK-3β activity in an orthotopic xenograft mouse model as revealed by bioluminescence imaging of mice and immunohistological analysis. In addition, rVP1 decreased the formation of ascites and metastatic tumor nodules formed by SKOV3 cells in an intraperitoneal xenograft mouse model. These results indicate that negative regulation of Akt signaling by rVP1 may have the potential to suppress ovarian tumor growth and metastasis in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C40.
Abstract C42: Survival signals differentially turn on during TRAIL or curcumin/TRAIL treatment
Authors: Oh Seeun , Kim Joo-Hang , Song Jae J. , Kim Jina , Yoon Hyo R. , Kang Sujin , Park Wungki , Hong Kijae , Kim So Y. , Choi Hye J. 
Published: June 2012

Abstract
Previously, we have shown that p38-HSP27 acted as modulators from survival to death depending on the apoptotic strength in prostate cancer cells. For example, if the apoptotic strength is in the moderate range, p38-HSP27 acted to increase Akt catalytic activity, whereas if in the stronger range, p38-HSP27 acted to decrease Akt catalytic activity as well as Akt dephosphorylation. Moreover, another survival signal, Src, a non-receptor tyrosine kinase was revealed to be highly phosphorylated (activated) during curcumin/TRAIL treatment, which leads to the conclusion of occurrence of more complex regulatory crosstalk between Akt and Src for the strict control of cell homeostasis. As a consequence, Akt dephosphorylation was regulated by protein phosphatase 1 (PP1), whose activity was subsequently controlled by dissociation from HSP27 (increase) and Src phosphorylation (deccrease). Src phosphorylation during curcumin/TRAIL was also positively regulated by TRAF6, whereas it was negatively regulated by HSP27. Taken together, the level of Akt dephosphorylation during curcumin/TRAIL could be decided by cumulative factors such as the levels of HSP27/TRAF6 and the activity of Src and PP1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C42.
Abstract C50: Dysregulation of microRNA-34a expression causes drug resistance to 5-FU in human colon cancer DLD-1 cells
Authors: Akao Yukihiro 
Published: June 2012

Abstract
MiR-34a was identified as one of the downregulated microRNAs (miRs) in human colorectal cancer 5-fluorouracil (5-FU)-resistant DLD-1 cells compared with those in the parental DLD-1 cells. Exposure to 5-FU at 30 μM activated phosphoinositide 3-kinase (PI3K)/Akt signaling markedly from 12 h up to 48 h in the 5-FU-resistant cells compared with that in the parental cells and resulted in an overt difference in growth at those times. Furthermore, the expression of miR-34a in the 5-FU-resistant cells was sustained at a low level, whereas it was upregulated in the parental cells after the 5-FU treatment. Sirt1, which is one of the target genes for miR-34a and related to drug resistance, was strikingly upregulated in the 5-FU-resistant cells. The ectopic expression of miR-34a in the 5-FU-resistant cells inhibited growth, as in the parental cells, and attenuated the resistance to 5-FU through the downregulation of Sirt1 and E2F3. Moreover, the silencing of Sirt1 significantly canceled the resistance to 5-FU in the 5-FU-resistant cells. These findings suggest that miR-34a targeting the Sirt1 and E2F3 genes could negatively regulate, at least in part, the resistance to 5-FU in human colorectal cancer DLD-1 cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C50.
Abstract C52: Collagen-mediated chromatin remodeling promotes chemoresistance in pancreatic cancer
Authors: Danqi-Garimella Surabhi Y. , Munshi Hidayatullah G. 
Published: June 2012

Abstract
Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer-related deaths in the U.S., is associated with a pronounced collagenrich stromal reaction that has been shown to contribute to chemoresistance. We recently published that PDAC cells grown in the collagen microenvironment are resistant to gemcitabine-induced proliferation and checkpoint arrest (Dangi-Garimella et al, Cancer Research 2011). The effects were mediated through upregulation of membrane type 1-matrix metalloproteinase (MT1-MMP)- and ERK1/2-dependent expression of high mobility group A2 (HMGA2), a well-known chromatin remodeling protein. We have now found that relative to cells grown on tissue culture plastic, PDAC cells grown in 3-D collagen display increased acetylation of lysines K9 and K27 on histone H3 along with a reduction in the levels of the heterochromatin binding protein HP1-α, suggesting that cells in collagen have a more open chromatin state. Decreasing MT1-MMP or HMGA2 expression or inhibiting ERK1/2 activity attenuates the effect of collagen on K9 and K27 acetylation. Collagen also increases Aurora kinase B-dependent phosphorylation of S10 on histone H3, which has been shown to reduce HP1-α binding to the chromatin and thereby promote more open chromatin state. 3-D collagen also increases expression of the histone acetyl transferase enzymes pCAF and GCN5. Finally, cells in 3D matrix demonstrate increased H2AX and a reduced tailing with the comet assay following gemcitabine treatment, suggesting that there is increased DNA repair associated with the more open chromatin state when cells are in the 3-D collagen microenvironment. Overall, our results increase our understanding of how growth in 3-D collagen contributes to chemoresistance and identify potential therapeutic targets against this deadly cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C52.
Abstract C64: Iron regulatory gene signature predicts outcome in breast cancer
Authors: Miller Lance D. , Coffman Lan G. , Chou Jeff W. , Black Michael A. , Bergh Jonas , D'Agostino Ralph , Torti Suzy V. , Torti Frank M. 
Published: June 2012

Abstract
Extensive experimental and clinical literature attests to the importance of iron in tumor cell growth. For example, high levels of dietary iron have been linked epidemiologically to the increased development of tumors in humans; in animal models, levels of dietary iron affect tumor growth. However, pathways that underlie the apparent demand for iron by tumors remain largely uncharacterized. We recently discovered that an iron efflux pathway plays a role in breast cancer growth and metastasis: expression of the iron efflux pump ferroportin and its regulator hepcidin were predictive of metastasis-free survival in multiple independent breast cancer cohorts. To determine the optimal “iron gene regulatory signature,” we used microarray datasets comprising 674 breast cancer cases to systematically investigate how expression of genes related to iron metabolism is linked to breast cancer prognosis. Of 61 genes involved in iron regulation, 49% were statistically significantly associated with distant metastasis-free survival (DMFS). Optimal risk stratification was achieved with a model comprising 16 genes, which we term the iron regulatory gene signature (IRGS). Multivariable analysis revealed that the IRGS contributes information not captured by conventional prognostic indicators (hazard ratio 1.61; 95% CI 1.16–2.24; p=0.004). The IRGS successfully stratified homogeneously treated patients, including ER+ patients treated with tamoxifen monotherapy, both with (p=0.006) and without (p=0.03) lymph node metastases. To test whether multiple pathways were embedded within the IRGS, we evaluated the performance of two gene dyads with known roles in iron biology in ER+ patients treated with tamoxifen monotherapy (n=371). For both dyads, gene combinations that minimized intracellular iron content (anti-import: TFRCLow/HFEHigh; or pro-export: FPHigh/HAMPLow) were associated with favorable prognosis (p&lt;0.005). Although the clinical utility of the IRGS will require prospective evaluation, its ability to both identify high risk patients within traditionally low risk groups and low risk patients within high risk groups has the potential to affect therapeutic decision-making.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C64.
Abstract C67: Gene expression profiling with human breast cancer cell lines exposed to gephyronic acid
Authors: Young Jeanette , Leliaert Amy , Schafer Zachary T. , Taylor Richard E. 
Published: June 2012

Abstract
Gephyronic acid is an antibiotic natural product isolated at the HZI (Helmholtz-Zentrum für Infektionsforschung) by Sasse and Höfle from the myxobacterium Archangium gephyra in 1995. Gephyronic acid has been shown to inhibit the growth of yeast and mold in the micromolar range; it also exhibits a cytostatic effect on mammalian cell cultures (human cervix, human leukemia, hamster kidney, hamster ovary, mouse connective tissue, and monkey kidney cancer cells) in the nanomolar range. An in vitro translation assay demonstrated that gephyronic acid is a specific inhibitor of eukaryotic protein synthesis. Interdisciplinary efforts within our laboratory are directed to the evaluation of gephyronic acid as a potential anticancer agent and its structural and biological relationship to the myriaporones and tedanolides. Our recent structural assignment and total synthesis of gephyronic acid incorporates a synthetic route that provides a means by which to access significant quantities of gephyronic acid efficiently and selectively, thus facilitating further biological evaluation. Additionally, we seek to identify the mode of action for gephyronic acid by screening various cancer cell lines through transcriptome and proteome profiling. Our proposed method will analyze mRNA expression levels of cells treated with gephyronic acid, or without for control, through the application of cDNA microarrays. Transcript profiling will then be coupled to proteomic profiling utilizing a method of protein labeling called iTRAQ. Identifying specific genes and their associated proteins will secure the mode of action of gephyronic acid selective activity and further defines potential as a chemotherapeutic lead.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C67.
Abstract IA12: Induction of pluripotency by defined factors
Authors: Yamanaka Shinva 
Published: June 2012

Abstract
Induced pluripotent stem (iPS) cells were originally generated from mouse and human fibroblasts by the retroviral introduction of Oct3/4, Sox2, c-Myc, and Klf4. iPS cells are similar to embryonic stem (ES) cells in morphology, proliferation, gene expression, and most importantly, pluripotency. Patient-specific iPS cells provide us with unprecedented opportunities in disease research, drug screening, toxicology, and cell transplantation therapies. Banks of iPS cells from individuals with HLA homozygous alleles may also provide another unprecedented source for regenerative medicine.
iPS cells have many variations in comparison to ES cells. In addition to fibroblasts, iPS cells can be generated from various somatic cells, such as hepatic cells, gastric epithelial cells, keratinocytes, neural cells, peripheral blood cells, and cord blood cells. In addition to retroviral transduction, iPS cells can be integration-freely generated by adenoviruses, sendaiviruses, plasmids, transposons, recombinant proteins, and synthetic mRNA. Several chemicals and inhibitors have been shown to enhance iPS cell generation. Some of the original four factors can either be omitted or replaced by other genes or chemicals. Finally, each induction experiment can result in 100 or more independent iPS cell clones.
These various iPS cells may vary significantly in regard to each cell's peculiar characteristics, such as the efficacy of in vitro directed differentiation and a propensity to produce tumors. In fact, the origins of iPS cells have a profound effect on their tumorigenicity. It is therefore necessary to determine the best origins, the best induction protocols, and the best methods to evaluate iPS cell clones and subclones for each application of iPS cells. Here, significance of epigenome analyses, including methylome, histone modifications, and imprinting increases as the integration-free method is becoming practical.
It is also important to note that an iPS cell clone can be heterogeneous despite the fact that all the cells within the clone are derived from a single progenitor cell. This is because the process requires multiple cell divisions which cannot be completed by the four exogenous factors alone. Additional factors including p53 and Rb pathways are considered to play various roles in achieving full reprogramming. Obtaining a better understanding of the reprogramming mechanisms will therefore facilitate the generation of more uniform iPS cells in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA12.
Abstract IA14: Reprogramming cell fate by mimicking natural mechanisms
Authors: Blau Helen M. 
Published: June 2012

Abstract
We are exploiting natural mechanisms to derive mammalian cell sources for regenerative medicine: (1) by recapitulating pathways used by newts and zebrafish, (2) by mimicking biophysical cues to which adult stem cells are exposed in the body, (3) and by gaining insights into the mechanisms such as DNA demethylation by which adult cells are reprogrammed to pluripotency (iPS) in heterokaryons. These approaches provide fundamental mechanistic insights into stem cell fate determination, provide novel cell sources, and enable clinical applications of cell therapies for regenerative medicine.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA14.
Abstract IA15: Measuring evolution in neoplasms
Authors: Malev Carlo C. 
Published: June 2012

Abstract
Neoplastic progression is a process of somatic evolution, yet few evolutionary tools have been adapted to measure the dynamics of progression. We have recently shown that traditional analyses of cross-sectional sampling of neoplasms usually infers the wrong order of events in progression. In contrast, phylogenetic methods applied to multiple samples within a neoplasm can accurately infer the order of events. Furthermore, longitudinal sampling can be used to estimate mutation rates, including chromosomal aberration rates, using phylogenetic methods developed to study viral evolution in vivo.
We have applied these tools to study the dynamics of progression in Barrett's esophagus and the effects of non-steroidal anti-inflammatory drugs on that somatic evolution.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA15.
Abstract IA17: Microfluidic measurements of single cell mass reveal how growth and division are coordinated
Authors: Manalis Scott 
Published: June 2012

Abstract
Cell growth during the cell cycle must be coordinated with genome replication and segregation, but the mechanisms underlying this coordination are poorly understood, particularly in mammalian cells. My lab is developing suspended microchannel resonators that can precisely measure the size of single cells – mass, volume and density – over time. Using a microfluidic system for culturing single cells over multiple generations while cell mass and cell cycle progression were continuously measured, we monitored over 1,000 hours of single cell growth from mouse lymphoblasts (L1210). I will present recent data from this system and discuss preliminary experiments where the precision cell sizing capabilities of the resonator are used for biomarker analysis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA17.
Abstract PR13: The canonical Wnt pathway participates in anchorage-independent growth in a subset of heterogeneous tumor cells derived from a single murine pancreatic tumor
Authors: Heung Man Yeung , Serrels Bryan , Morton Jennifer P. , Sansom Owen J. , Brunton Valerie , Frame Margaret C. 
Published: June 2012

Abstract
Pancreatic adenocarcinoma is a difficult cancer to treat with poor response rates to current therapies. Using a mouse model of pancreatic adenocarcinoma driven by endogenous expression of KRASG12D and p53R172H, we isolated heterogeneous tumor cell clones from a single tumor. Each of the cell clones has a unique genetic and protein expression signature, and they proliferate at different rates in vitro. Notably, only some of them are able to grow into colonies under anchorage-independent (AI) condition. We found that clones which can undergo AI growth have significantly higher phospho-ERK levels than the others, and the MEK inhibitors PD184352 and UO126 can suppress only some AI growth. We therefore looked for additional drivers of this cancer-associated AI growth and discovered that the canonical Wnt pathway, indicated by high transcription levels of Axin2 and Lgr5, is associated with AI growth in the pancreatic cancer cell clones that are less sensitive to the MEK inhibitors. In addition, two tankyrase inhibitors, XAV939 and IWR1, which stabilize Axin1 and enhance β-catenin degradation, inhibit AI growth in Wntactive cells, but not in ERK-dependent cells. Both tankyrase inhibitors downregulate Wnt-dependent Axin2 and Lgr5 transcription, without affecting phospho-ERK levels. Importantly, knockdown of β-catenin also impairs anchorage-independent growth only in Wnt-active cells. Thus, we have demonstrated for the first time that the canonical Wnt pathway is activated and contributes to AI growth in subclones of pancreatic cancer cells downstream of KRASG12D and p53R172H, and that Axin2 and Lgr5, but not all classical Wnt target genes (for example c-Myc), are involved. Hence, targeting Wnt in pancreatic cancer may be a viable option in treating KRAS- and p53-driven pancreatic cancer, but will probably need to be combined with multiple pathway inhibitors to deal with tumor heterogeneity.
This abstract is also presented as Poster A46.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR13.