bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4230: The pro-inflammatory secretory phenotype and selection of stem-like cells in RAS-transformed ovarian epithelial cells
Authors: Shan Weiwei , Yang Gong , Mercado-Uribe Imelda , Liu Jinsong 
Published: February 2011

Abstract
Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer in the United States. Previously, our laboratory has successfully transformed human ovarian epithelial cells with oncogenic RAS carrying an activating mutation at valine12 (HRASV12) (T29H cells). By cDNA expression microarray we found that T29H cells exhibited marked activation of a wide spectrum of inflammatory genes and generated a pro-inflammatory phenotype. In this report, we identified a much more malignant phenotype in ovarian tumor explants derived from T29H (hereby denoted T29HT) cells, manifested by a significantly shorter latency of tumor onset after inoculation of T29HT cells back into nude mice than that of the parental T29H cells, suggesting that the T29H cells underwent a selective process in vivo that was favorable to the enhancement of tumorigenicity. By examining the ability of cells to form spheroids in suspension culture and staining spheroids with stem cell marker CD44, we showed that T29HT cells may contain a larger population of potential stem-like cells than do T29H cells. Western blot analysis confirmed higher expression levels of CD44 and genes involved in epithelial mesenchymal transition (EMT) in T29HT cells than in T29H cells. Our results suggest that T29H cells may acquire augmented malignancy in vivo by expanding the pool of potential cancer stem-like cells, and HRASV12-induced pro-inflammatory factors may play pivotal roles in mediating this effect.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4230.
Abstract 4246: Granulin-epithelin precursor (GEP) is an oncofetal protein involved in fetal liver development and liver cancer
Authors: Cheung Phyllis Fung Yi , Cheung Siu Tim 
Published: February 2011

Abstract
Background and objectives:
Granulin-epithelin precursor (GEP) is a novel pluripotent growth factor regulating embryo development, wound repair and tumorigenesis. Our group previously has showed that GEP was over-expressed in over 70% of liver cancer. Besides, functional studies demonstrated that GEP controlled liver cancer proliferation, invasion and tumorigenicity. In this study, we aim to examine the time-frame of GEP expression during fetal liver development, and to characterize the properties of GEP-expressing liver cells.
Methods:
GEP expression was examined by immunofluorescence using flow cytometry and immunohistochemistry. The properties of GEP-expressing cells were characterized by measuring the co-expression of GEP and various stem/progenitor cell markers using immunofluorescence and flow cytometry. Correlation of GEP level with the expression of stem/progenitor markers was studied by transfection experiments.
Results:
In murine model, GEP expression was observed to increase gradually from embryonic day (E) 11 to E17, with up to 49% fetal liver cells were GEP positive. Immediately after birth, GEP expression decreased abruptly from day 1, and by day 7, less than 1% neonatal liver cells were GEP positive, and GEP was not detectable in adult liver. In human, fetal liver at 10 weeks old were demonstrated to express GEP protein, while normal adult livers were devoid of GEP-expressing cells. GEP expression was up-regulated in liver cancer cells compared with the adjacent non-tumor liver cells. Moreover, we showed that GEP co-expressed with hematopoietic stem/progenitor cell marker CD34, liver cancer stem cell marker CD326, and stem cell-related signaling molecules β-catenin and Oct4, suggesting a stem/progenitor cell feature of the GEP-expressing cells. Furthermore, up-regulation of GEP level enhanced the expression of β-catenin and Oct4, and suppression of GEP level resulted in decreased expression of these molecules.
Conclusion:
The present data suggests that GEP is an oncofetal protein, and GEP regulates the expression of stem cell-related signaling molecules. This information advances our knowledge on the fundamental role of GEP in fetal liver development and liver carcinogenesis, and provides valuable insights on the use of GEP as a therapeutic target in the treatment of liver cancer.
Category: Tumor Biology
Sub-classification: TB2: stem cell biology/cancer stem cells/developmental oncobiology
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4246.
Abstract 4250: Cigarette smoke induces expression of the putative stem cell marker ABCG2 in cultured esophageal adenocarcinoma cells
Authors: Mathur Aarti , Rao Mahadev , Zhang Yuwei , Zhang Mary , Kemp Clint D. , Ripley Robert T. , Hong Julie , Liu Fang , Avital Itzhak , Schrump David S. 
Published: February 2011

Abstract
Limited information is available regarding epigenetic mechanisms by which cigarette smoke mediates initiation and progression of esophageal cancer. In order to examine this issue, esophageal adenocarcinoma cell (EsC) lines (NCI-EsC1 and NCI-EsC2) were cultured in normal media (NM) with or without cigarette smoke condensate (CSC) under clinically relevant exposure conditions. Microarray analysis revealed that CSC exposure significantly upregulated expression of ABCG2, which encodes a xenobiotic pump protein believed to be highly expressed in cancer stem cells, and recently shown to correlate with aggressive phenotype of primary esophageal squamous cell carcinomas. Analysis revealed an average of 11 fold upregulation of ABCG2 as well as a 4 fold upregulation of another ABC transporter, ABCC3. Quantitative reverse transcription-PCR (RT-PCR), western blot, and immunohistochemistry experiments confirmed upregulation of ABCG2 in esophageal cancer cells exposed to CSC. Interestingly, basal as well as CSC-induced levels of ABCG2 were considerably higher in NCI-EsC2 derived from a smoker, relative to NCI-EsC1, which was established from a never-smoker. Time course experiments revealed that induction of ABCG2 commenced approximately 8 hours and peaked 48 hours following initiation of CSC exposure; thereafter, ABCG2 expression was sustained at these levels with continuous CSC exposure. HDAC inhibitors such as TSA and depsipeptide repressed basal levels of ABCG2 expression, and reduced CSC-mediated induction of ABCG2 in EsC cells. HDAC inhibitors in combination with verapamil (a ABCC3 inhibitor) and Depsipeptide virtually abolished basal, as well as CSC-induced ABCG2 expression in these cells. Preliminary pyrosequencing and chromatin immunoprecipitation (ChIP) experiments revealed that CSC-mediated ABCG2 induction was independent of promoter DNA demethylation, and coincided with hyperacetylation of H3K9 within the ABCG2 promoter. Flow cytometry analysis utilizing hoescht dye with and without fumitremorgin C, an ABCG2 inhibitor, revealed an increased side population in CSC-treated ESC cells relative to untreated controls. Experiments are in progress to further delineate the mechanisms by which CSC induces ABCG2 expression, and to ascertain if ABCG2 induction enhances the malignant phenotype of esophageal adenocarcinoma cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4250.
Abstract 427: Targeted inhibition of the mTOR complex components, RAPTOR and RICTOR, attenuates progression of colorectal cancer
Authors: Pat Gulhati , Bowen Kanika A. , Liu Jianyu , Li Jing , Qiu Suimin , Weiss Heidi L. , Gao Tianyan , Evers B. Mark 
Published: February 2011

Abstract
Colorectal cancer (CRC) is the second leading cause of cancer deaths in the USA. The mammalian target of rapamycin (mTOR) acts downstream of PI3K to regulate cell growth, proliferation and survival. The mTOR kinase nucleates two distinct complexes, mTORC1 and mTORC2. The mTOR-RAPTOR complex (mTORC1) regulates translation initiation through the effectors S6K and 4E-BP1, while the mTOR-RICTOR complex (mTORC2) regulates the actin cytoskeleton and activates Akt, a key regulator of cell survival. Rapamycin inhibits the kinase activity of mTORC1; prolonged rapamycin treatment also inhibits mTORC2 assembly and Akt activation in certain cells. The purpose of the present study was to determine the effect of targeting mTORC1 and mTORC2 upon progression of CRCs. METHODS. HCT116 and SW480 human colon cancer cells were treated with rapamycin. Cells were also transfected with shRNA directed against RAPTOR or RICTOR. Effects on migration (measured by wound healing assay) and invasion (measured by transwell matrigel assay) were analyzed. Changes in actin cytoskeleton and cell-cell contacts were determined by immunofluorescence microscopy. RESULTS. (i) Immunohistochemical analysis showed that the mTORC1 and mTORC2 components, mTOR, RAPTOR and RICTOR, are overexpressed in primary CRCs and matched liver metastases compared to normal colonic tissue. (ii) Treatment with rapamycin significantly decreased the migration and invasion of HCT116 and SW480 cells. (iii) Stable shRNA-mediated knockdown of RAPTOR and RICTOR significantly decreased the migration and invasion of HCT116 and SW480 cells. (iv) Stable shRNA-mediated knockdown of RAPTOR and RICTOR leads to mesenchymal-to-epithelial transition, as evidenced by increased E-cadherin and decreased vimentin levels. (v) Stable shRNA-mediated knockdown of RAPTOR and RICTOR leads to characteristic rearrangements in actin cytoskeleton as well as increased cell-cell contact. CONCLUSIONS. The mTORC1 and mTORC2 components, mTOR, RAPTOR and RICTOR, are overexpressed in both primary CRCs as well as matched liver metastases. Although the mTOR signaling axis is primarily associated with growth of normal and cancer cells, we demonstrate that stable inhibition of both mTORC1 and mTORC2 decreases migration and invasion capabilities of CRC cells as well as causing a mesenchymal-to-epithelial change in phenotype. The mechanism for this decrease in migration and invasion may be via modulation of actin cytoskeletal rearrangement and cell-cell contact. Thus, targeted inhibition of mTOR signaling represents a novel therapeutic strategy to attenuate the progression and metastasis of CRCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 427.
Abstract 4290: The smoothened antagonist NVP-LDE225 targets stroma and cancer stem cells in primary human pancreatic tumor xenografts
Authors: Buonamici Silvia , Ospina Beatriz E. , Zhu Julia Xing , Yuan Jing , Hsiao Kathy , Vattay Anthony , Li Fang , Deeds James , Ostrom Lance , Monahan John , Williams Juliet , Kelleher Joseph , Peukert Stefan , Pan Shifeng , Wu Xu , Warmuth Markus , Mosher Rebecca , Yao Yung-mae , Sellers William R. , Dorsch Marion 
Published: February 2011

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality. Despite surgical intervention and treatment with Gemcitabine, the standard of care, the 5-year survival rate remains less than 5%. Because the aberrant activation of the Hedgehog (Hh) pathway in stroma cells and cancer stem cells in PDAC has become evident during the last few years, therapeutic agents able to inhibit Smoothened (Smo), the positive regulator of the pathway, are under vigorous investigation. We have developed a selective Smo antagonist, NVP-LDE225, which is orally bioavailable and potently inhibits Hh signaling in vitro and in vivo. Using a combination of in vitro and in vivo assays, we evaluated the effects of NVP-LDE225 alone or in combination with Gemcitabine in primary human tumor xenograft models. In these models, NVP-LDE225 dosed together with Gemcitibine resulted in a trend towards combination activity. Tumor samples collected at the end of the studies showed that the Hh pathway was completely inhibited in the stroma of the NVP-LDE225 treated animals. Moreover, analysis of the ratio of tumor to stroma area demonstrated no differences between the drug treated as compared to vehicle treated tumors. After subcutaneous implantation of the human tumors in mice, the mouse stroma replaces the human stroma. Using mouse and human Affymetrix analysis of tumors following in vivo treatment, we were able to differentiate the changes occurring in murine stromal cells versus human epithelial cells. This analysis revealed changes in the regulation of several key developmental and growth factor pathways in the mouse stroma. To study cancer stem cells, we isolated Aldehyde Dehydrogenase (ALDH) positive cells from untreated xenograft tumors and confirmed up regulation of the Hh pathway genes, and that ALDH positive cells were more tumorigenic than ALDH negative cells when implanted in animals. Furthermore, we used 2 different stem cell functional assays, in vitro sphere formation and in vivo serial transplantation to evaluate the effect of NVP-LDE225 on cancer stem cells. We observed that upon NVP-LDE225 treatment the cells had impaired ability to form spheres in vitro and similarly, tumor growth was delayed following in vivo serial transplantation. These experiments suggest that Smo inhibitors can have a high impact on the treatment of this very aggressive cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4290.
Abstract 4296: STAT3 is required for proliferation and tumor growth of breast cancer stem cells
Authors: Lin Li , Hutzen Brian , Peng Zhengang , Lin Huey-Jen , Li Pui-Kai , Li Chenglong , Wicha Max , Lin Jiayuh 
Published: February 2011

Abstract
Breast cancer is the leading type of cancer affecting women. It is estimated that breast cancer accounts for over a quarter of all newly diagnosed cancer cases in women. Despite advances in chemotherapy and hormonal treatment, at the present time, metastatic breast cancer remains an incurable disease. Although a large number of chemotherapeutic agents have been developed that are able to cause the regression of metastatic breast cancers, these tumors almost always recur following chemotherapy treatment. It is possible that breast cancer stem cells or breast cancer initiating cells are responsible for the drug-resistance, metastasis, and recurrence of cancer. Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in many types of cancers, including breast cancer, and has emerged as an attractive molecular target for cancer treatment. However, whether or not STAT3 is activated in breast cancer stem cells and what role STAT3 signaling plays in cancer stem cells is still unknown. If STAT3 is activated in breast cancer stem cells, targeting STAT3 may offer a promising opportunity to eliminate breast cancer stem cells and prevent the recurrence of cancer. We examined STAT3 activation in breast cancer stem cells, which are characterized by an aldehyde dehydrogenase (ALDH)-positive (ALDH+) and ALDH+/CD44+/CD24− subpopulations. Interestingly, we observed that the ALDH+ and ALDH+/CD44+/CD24− subpopulations of breast cancer cells expressed higher levels of phosphorylated STAT3, an active form of STAT3, as compared to the ALDH− and ALDH−/CD44+/CD24+ subpopulations and un-separated breast cancer cells, suggesting that STAT3 is activated in breast cancer stem cells. We also demonstrated that a novel STAT3 inhibitor, LLL12, inhibited STAT3 phosphorylation, cell viability, STAT3 downstream target gene expression, and induced apoptosis in breast cancer stem cells. In addition, the STAT3 inhibitors Stattic and LLL12 inhibited the tumorsphere forming capacity of breast cancer stem cells. Furthermore, in a mouse tumor model using breast cancer stem cells, we demonstrated that LLL12 can suppress tumor growth in vivo. This is the first report to demonstrate that persistent STAT3 phosphorylation is expressed in breast cancer stem cells and that this subpopulation of breast cancer stem cells is sensitive to STAT3 inhibitors. Our results suggest that STAT3 is a novel therapeutic target in breast cancer stem cells and inhibition of activated STAT3 in cancer stem cells may offer a more effective treatment for breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4296.
Abstract 4297: Selective enrichment of liver cancer stem cell by DNA methyltransferase inhibition
Authors: Raggi Chiara , Marquardt Jens U. , Andersen Jesper B. , Factor Valentina M. , Thorgeirsson Snorri S. 
Published: February 2011

Abstract
Background: Evidence is growing that many solid cancers, including liver cancer, contain small subpopulations of cells with stem cell-like properties known as cancer stem cells (CSCs) that are responsible for maintaining and propagating a tumor. Major obstacles in the research on CSC biology are the paucity and lack of specific markers of CSC. We have recently shown that human liver CSC can be enriched by modulating the epigenome of liver cancer cell lines with zebularine (Zeb), a potent DNA methyltransferase inhibitor.
Objective: In this study we exploited the impact of epigenetic modulation of cancer epigenome by Zeb in conjunction with the ability of stem/progenitor cells to grow as non-adherent spheres in serum-free media to provide further enrichment of the CSC fraction.
Methods: Huh7 cells were plated in high (HD, 13×103cell/cm2) and low (LD, 2.7×103/cm2) density and treated with 100 µM Zeb for 3days. The sphere forming ability and serial sphere formation were investigated in Matrigel and suspension culture, respectively. CSC and pluripotency markers preferentially expressed in cells grown under sphere conditions were examined by qRT-PCR and surface markers by FACS.
Results: Huh7 cells grown under LD failed to form tumorspheres when placed in Matrigel or non-adherent growth conditions. In striking contrast, Zeb-treated low density cells were capable of forming spherical clonal-expanding colonies which showed the stem cell-like properties such as strong induction of the stem cell-related genes NANOG and OCT4 and did not express EpCAM. Cells grown at high density possessed a similar sphere forming ability regardless of Zeb pretreatment. However, morphological characterization revealed a predominance of smaller sized spheres suggesting reduced proliferation potential and/or differences in cell type of origin, with smaller spheres originating from the progenitors, and larger spheres from the stem cells. Consistent with this, HD spheres showed a smaller induction of NANOG and OCT4, expressed high levels of EpCAM and exhibited reduced self-renewal in serial sphere formation assay. The sphere forming ability of LD and HD cells was associated with a presence of a subpopulation of CD133-/cKit+ cells.
Conclusion: The described “double selective” approach offers an in vitro model to enrich for cells with cancer stem cell properties. Both cell density and epigenetic modulation were able to affect the sphere-forming potential of Huh7 cells. Further studies are needed to characterize this cell population in more detail, to clarify their tumorigenic potential and the capacity to propagate tumor growth in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4297.
Abstract 4310: Prospective isolation of clongenic mantle cell lymphoma initiating cells
Authors: Chen Zheng , Ayala Paul , Wang Michael , Fayad Luis , Katz Ruth L. , Romaguera Jorge , Caraway Nancy , Neelapu Sattva S. , Kwak Larry W. , Simmons Paul , Nami McCarty 
Published: February 2011

Abstract
We have prospectively isolated and characterized clonogenic cells with self-renewal capacities from mantle cell lymphoma (MCL), a particularly deadly form of non-hodgkin's lymphoma (NHL). Self-renewal and tumorigenic activities were enriched in MCL cell fractions that lacked expression of the prototypic B cell surface marker, CD19. CD45+CD19- cells represented a relatively small fraction of the total MCL tumor cells, however, they recapitulated the heterogeneity of original patient tumors upon transplantation into immunodeficient mice. As few as 100 of these cells displayed self-renewal capacities in secondary and tertiary recipient mice by in vivo limiting dilution assays. Similar to leukemic stem cells, CD45+CD19- MCL cells also displayed a quiescent status as determined by dye efflux assays. In summary, this study is the first to isolate subpopulations of MCL cells that have self-renewal and tumorigenic capacities. Identification and characterization of MCL-ICs is an important first step toward understanding how self-renewal and tumorigenicity are regulated in MCL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4310.
Abstract 4317: Developing near infrared (NIR) optical retinoid analogue for cancer imaging
Authors: Wang Wei , McNees Adrienne L. , Cameron Arlin G. , Wendt Juliet A. , Mawad Michel E. , Ke Shi 
Published: February 2011

Abstract
Imaging technology plays an important role in early detection of cancers and improved prognoses. Among of the various imaging techniques used near infrared (NIR) optical imaging is an active and promising area for both in vitro and in vivo molecular imaging studies. However, NIR fluorophores normally only possess optical imaging properties without selectivity to diseased tissues. To address this problem, a targeting moiety can be introduced to help to deliver the imaging report to its target. It is know that retinoids, analogs of vitamin A, are assessed for multiple therapeutic uses. In practically, their potential chemopreventive and therapeutic roles in different kinds of cancers have attracted much attention. The cancer types include head and neck, lung, breast, esophagus, colon, kidney, prostate, bladder cancers and so on. Considering about important role of retinoids in cancer treatment developing retinoid derivatives as targeting imaging agents should be a useful strategy for noninvasive detection and characterization of solid tumors. Herein, we developed fluorescent retinoid derivatives for cancer imaging. Several different cancer cell lines and cancer xenograft models were used in this study. The data demonstrate that this new imaging agent can be used to imaging different kinds of cancers from cell level to whole body. Furthermore, these imaging agents have the potential to develop into special therapeutic agents that can be used for diagnosis, treatment and monitor of retinoid positive diseases.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4317.