bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3747: The impact of lipid inflammatory mediators on colon cancer initiating cells.
Authors: Sjölander Anita , Bellamkonda Kishan , Sime Wondossen 
Published: August 2014

Abstract
Past studies links the lipid inflammatory mediators at the tumor microenvironment to the colorectal cancer, however their impact on the colon cancer initiating cells (CICs) is largely unknown. Accordingly, the present study aimed to identify the possible link between lipid inflammatory mediators and CICs. In lack of robust marker for identifying colon CICs, we initially screen five different colon cancer cell lines (HCT-116, Caco-2, SW-480 SW-620 and HT-29) for their percentage occurrence using well-established stem cell markers i.e. CD133, CD44 and ALDH. The Flow cytometeric sorting of CD133, CD44 and ALDH subpopulations showed large variation in their population size in these cell lines. Further we noted that ALDH is relatively better marker of these to identify CICs. This statement was based on our observation of markedly increased capacity of ALDH+ cells to produce colonies rather than ALDH− cells. We sorted ALDH+/CICs and investigated the effect of lipid inflammatory mediators such as leukotriene D4 (LTD4) or prostaglandin E2 (PGE2) on these cells. It was noted that LTD4 and PGE2 stimulations not only enriched the relative population of ALDH+ cells; it also greatly improved the colony forming capacity of these cells. Moreover, we observed that ALDH+ cells were more resistant to 5-Fluorouracil (5-FU) treatment compared to ALDH− cells. Furthermore the qPCR data revealed that Bcl-2, COX-2, Bcl-3, ALDH1B1, GLI1 and KLF4 genes were largely amplified in ALDH+ cells in presence of LTD4 or PGE2, indicating their probable impact on the stemness pool of these cells. In conclusion our study shows that lipid inflammatory mediators can affect the survival and stemness of CICs.
Citation Format: Anita Sjölander, Kishan Bellamkonda, Wondossen Sime. The impact of lipid inflammatory mediators on colon cancer initiating cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3747. doi:10.1158/1538-7445.AM2013-3747
Abstract 379: Evaluating tissue expression of RANTES with subtype specific breast cancer biomarkers found elevated in plasma.
Authors: Mansfield James , Xu Chuanbo , Gonzalez Rachel 
Published: August 2014

Abstract
Background: A previous analysis of 23 plasma proteins found that levels increased in cancer patients compared to benign-breast-disease controls when the cancer was analyzed based on tumor subtypes. Circulating levels of RANTES were significantly increased in cancer patients and were commonly associated with two or more of the following proteins; amphiregulin, EGF, HB-EGF, TGFa, PDGF, and VEGF in a tumor subtype specific pattern. However, it is unknown if expression of these proteins correlate in the tumor tissue of breast cancer subtypes thus contributing to the elevated expression seen in plasma. In this study, we evaluate the expression of 5 of plasma biomarkers in a 70-subject breast cancer tissue microarray (TMA) to determine if these proteins are increased differentially by tumor subtypes.
Design: A BioChain TMA containing 70 duplicated cores covering the common types of breast cancer, 5 normal, and 5 benign cases are assayed using GBI Labs triple stain kits to evaluate subtype specific expression of amphiregulin and HB-EGF or PDGF and VEGF with RANTES. Imaging and quantitative assessment of the distribution and intensity of each stain was evaluated using a multispectral imaging (MSI) approach, automated morphologic analysis software and compared to a visual screen.
Results: Results indicate that an algorithm can be develoed to accurately recognize tumor versus stromal tissue within each core. Furthermore, as compared to visual evaluation, the MSI approach has the added capability to separate the color of the three immunostains from the triple stain for precise quantification of each protein without crosstalk. The automated scoring algorithm compared well against visual assessment.
Conclusion: The knowledge gained from correlating these subtype-specific patterns of tissue antigens with circulating levels in plasma may provide important information about the contribution of specific markers of breast cancers. Application of MSI to the triple staining in the TMA screen provided a superior quantitative method for evaluation of multiple chromogens linked proteins within a tumor core compared to visual observations/grading of the complex multicolor immunostaining in this study.
Citation Format: James Mansfield, Chuanbo Xu, Rachel Gonzalez. Evaluating tissue expression of RANTES with subtype specific breast cancer biomarkers found elevated in plasma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 379. doi:10.1158/1538-7445.AM2013-379
Abstract 3792: WISP-1 increases cell migration and ICAM-1 expression in human oral squamous cell carcinomas.
Authors: Chang An-Chen 
Published: August 2014

Abstract
Oral squamous cell carcinomas (OSCC) have a striking tendency to migration and metastasis to cervical lymph nodes. Wnt-1 induced secreted protein 1 (WISP-1) belongs to the CCN family (CTGF/CYR61/NOV), which is secreted cysteine-rich proteins. However, the effects of WISP-1 on migration and Intercellular adhesion molecule-1 (ICAM-1) expression in human OSCC are largely unknown. First, we found that the expression of WISP-1 in human OSCC tissues was higher than in normal oral tissues. We also demonstrated that WISP-1 enhanced cell migration and ICAM-1 up-regulation in human OSCC. Transfection of cells with ICAM-1 siRNA reduced WISP-1-mediated cell migration. WISP-1 activated αvβ3 integrin, ASK1, JNK/p38, c-Jun, and AP-1 signal transduction pathway, and WISP-1-induced expression of ICAM-1 and migration activity was inhibited by the αvβ3 antibody or inhibitor of ASK1, p38, JNK, and c-Jun. In addition, human OSCC were infected with lentivirus containing human WISP-1 shRNA which reduced the migratory ability and ICAM-1 expression. Over all, we characterized an important role for WISP-1 which regulates cell migratoin by increasing ICAM-1 expression in human OSCC via the αvβ3 integrin, ASK1, JNK/p38, c-Jun, and AP-1 signaling pathway.
Citation Format: An-Chen Chang. WISP-1 increases cell migration and ICAM-1 expression in human oral squamous cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3792. doi:10.1158/1538-7445.AM2013-3792
Abstract 3834: Establishment and characterization of 3D multicellular tumor spheroids as preclinical in vitro models of human colorectal cancer.
Authors: Daester Silvio , Amatruda Nunzia , Calabrese Diego , Zajac Paul , Spagnoli Giulio Cesare , Iezzi Giandomenica , Mele Valentina , Muraro Manuele Giuseppe 
Published: August 2014

Abstract
Objective: Multicellular tumor spheroid is a well-known method for three-dimensional in-vitro culture that better represent in-vivo condition. We exploited this system to culture human established colorectal cell lines to investigate how the presence or absence of hypoxic and/or necrotic area, due to oxygen and nutrient gradients, can influence the gene expression profile and the responsiveness to drugs compared to 2D culture and in vivo xenografted cells. Methods: HT29 cell line was cultured as MCTS by hanging drop method. At size-defined time point spheroids were collected and analyzed for the presence of hypoxic and necrotic areas. The expression of a panel of genes related to tumor progression, metastatic behavior, and drug resistance was evaluated by real time PCR on MCTS at different growth stages in comparison to conventional 2D cultures and xenografts generated upon injection of HT29 cells in immunodeficient mice. Results: Based on the absence or presence of hypoxic and/or necrotic core, we identified three different MCTS growth stages: stage 1 (MCTS diameter size &lt;200μm) defined by the absence of hypoxia/necrosis, stage 2 (300-350μm) characterized by the presence of hypoxic, but not apoptotic or necrotic areas, and stage 3 (&gt;500μm) identified by the presence of both hypoxic and necrotic areas. The expression of a panel of genes, including KRAS, p53, and putative cancer stem cell markers CD133, CD44, CD24 was found to be upregulated in stage 1 MCTS, as compared to 2D cultures. Most interestingly a further upregulation of these genes was detected in stage 2 and especially in stage 3. Importantly expression levels in stage 3 were the most similar to those detected in xenografts. Conclusion: Our results showed that culture of established CRC cell lines offer the opportunity to investigate in standardized condition different MCTS stages possibly proving an improved model of in-vivo tumor growth. The drug-responsiveness of tumor cells cultured in 2D and 3D at different spheroid maturation stages is currently being assessed.
Citation Format: Silvio Daester, Nunzia Amatruda, Diego Calabrese, Paul Zajac, Giulio Cesare Spagnoli, Giandomenica Iezzi, Valentina Mele, Manuele Giuseppe Muraro. Establishment and characterization of 3D multicellular tumor spheroids as preclinical in vitro models of human colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3834. doi:10.1158/1538-7445.AM2013-3834
Abstract 3838: Stem-like cell characteristics of cancer spheroids grown in a microfabricated cell array three-dimensional culture system Cell-ableTM Oncology.
Authors: Yokota Koichi , Jomura Tomoko , Ozeki Emiko , Ikeya Takeshi 
Published: August 2014

Abstract
Recently, the cell biology field has come to appreciate the dissimilarity between two- (2D) and three-dimensional (3D) environments in which cells routinely operate in vivo. Efficacy of most anti-cancer drugs have been evaluated in 2D environment but it must be desirable to evaluate it in 3D environment. We developed a novel 3D cell culture system named Cell-ableTM Oncology utilizing photo-sensitive materials that change to hydro-gel after UV irradiation and the optimized molecular design not to allow the cells adhere to the hydro-gel. In multi-well plates, the Cell-ableTM Oncology has type I collagen-coated cell-attaching areas on the each well surface, which are circle in 100 μm diameter and arrayed in every direction at 100 μm interval. Most cancer cells are able to attach these circles and grow to form spheroids of uniform size on the Cell-ableTM Oncology. In this study, we investigated the stem-like cell phenotypes of cancer spheroids formed on the Cell-ableTM Oncology in comparison with that of the 2D monolayer cells. Various cancer cell lines and patient-derived primary cancer cells proliferated and formed spheroids on the Cell-ableTM Oncology in serum-containing or serum-free media. In contrast to the 2D monolayer cells, the inside of the spheroids formed on the Cell-ableTM Oncology was hypoxic condition like in vivo tumor tissues in patients. The spheroids grown on the Cell-ableTM Oncology showed chemo-resistance against conventional chemotherapy, gemcitabine and paclitaxel compared with cells grown on collagen-coated 2D plates. The chemo-resistance of the spheroid cells was associated with high population of stem-kike cells (CD44high/CD24low) and high expression of mRNA for a stem cell marker, NANOG and an ABC transporter ABCG2. The combination of the Cell-ableTM Oncology and serum-free media showed the highest population of stem-like cells. These results indicate that the spheroids characterized by 3D structure formed on the ECM-coated surface and the hypoxic condition confer enriched the cancer stem-like cells. Thus, the spheroids on the Cell-ableTM Oncology could be suitable for research and development of drugs targeting cancer stem cells. The pharmacodynamic and pharmacokinetic studies using the cancer stem cell-rich spheroids could provide meaningful information relevant to clinical conditions.
Citation Format: Koichi Yokota, Tomoko Jomura, Emiko Ozeki, Takeshi Ikeya. Stem-like cell characteristics of cancer spheroids grown in a microfabricated cell array three-dimensional culture system Cell-ableTM Oncology. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3838. doi:10.1158/1538-7445.AM2013-3838
Abstract 3869: MicroRNA-200b blocks breast cancer lung metastasis in an orthotopic mouse mammary xenograft tumor model.
Authors: Humphries Brock , Wang Zhishan , Yang Chengfeng 
Published: August 2014

Abstract
Triple negative, or basal-like, breast cancer is a highly invasive and metastatic form of breast cancer, and is difficult to treat due to the lack of target therapies. Epithelial to mesenchymal transition (EMT) refers to a developmental program that converts epithelial cells to mesenchymal cells, therefore enabling cells to migrate and invade. EMT is tightly controlled during development, and recent studies showed that EMT is often reactivated in cancer and plays an important role in cancer invasion and metastasis, and that EMT can also be regulated by microRNAs. MicroRNAs (miRs) are a large family of small non-coding RNAs that negatively regulate protein-coding gene expression posttranscriptionally. Although the miR-200 family members have been shown to be able to inhibit EMT, their effects on cancer metastasis continue to be controversial. We aim to investigate the effect of miR-200b on triple negative breast cancer lung metastasis and the underlying mechanism. It was found that stably expressing miR-200b in MDA-MB-231 cells blocked lung metastasis in an orthotopic mouse mammary xenograft tumor model. In vitro studies showed that stably expressing miR-200b significantly reduced triple negative breast cancer cell proliferation, migration, and invasion. Furthermore, stably expressing miR-200b also decreased tumor growth and angiogenesis in the orthotopic mouse mammary xenograft tumors. These findings suggest that miR-200b blocks breast cancer lung metastasis through its strong inhibitory effect on multiple-steps including proliferation, migration, invasion and angiogenesis.
Citation Format: Brock Humphries, Zhishan Wang, Chengfeng Yang. MicroRNA-200b blocks breast cancer lung metastasis in an orthotopic mouse mammary xenograft tumor model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3869. doi:10.1158/1538-7445.AM2013-3869
Abstract 3882: Myb contributes to pancreatic cancer growth and metastasis.
Authors: Srivastava Sanjeev K. , Singh Seema , Bhardwaj Arun , Arora Sumit , McClellan Steven , Grizzle William E. , Singh Ajay P. 
Published: August 2014

Abstract
Pancreatic cancer (PC) is a disease of insidious progression. In most cases, it is diagnosed late at a stage when it is either locally advanced or has already metastasized to distant sites, resulting in a poor prognosis of the patients. Therefore, there is an urgent need to identify novel molecular targets regulating PC progression and metastasis, so that an effective treatment strategy can be developed against this devastating disease. In this study, we investigated the role of Myb in pancreatic cancer pathogenesis. Myb/c-Myb, a cellular progenitor of v-Myb oncogenes, is amplified in a sub-set of PC and encodes for a transcription factor. Myb confers its oncogenic activity by regulating the expression of several target genes. To examine the pathological significance of Myb in pancreatic cancer, we silenced its expression in Myb-overexpressing pancreatic cancer cell lines (Panc1 and MiaPaCa), and ectopically overexpressed it in a poorly-tumorigenic low Myb-expressing cell line (BxPC3). Our data showed that short-hairpin RNA (shRNA)-mediated stable silencing of Myb in Panc1 and MiaPaCa cells led to diminished growth and clonogenic ability as compared to their respective scrambled-transfected control cells. Furthermore, Myb-silenced Panc1 and MiaPaCa cells also exhibited reduced, motility and invasion as compared to their respective controls. Accordingly, enhanced growth, clonogenicity, motility and invasion were observed in Myb-overexpressing BXPC3 cells as compared to vector only-transfected cells. Immunoblot analyses demonstrated altered expression of cell cycle- and apoptosis- associated proteins in Myb-silenced and overexpressing pancreatic cancer cells. Moreover, loss of mesenchymal and gain of epithelial markers was observed in Myb-silenced Panc1 and MiaPaCa cells, whereas Myb overexpressing BXPC3 cells exhibited an opposite pattern. These changes were also associated with actin reorganization, thus suggesting a role of Myb in epithelial to mesenchymal transition (EMT) of PC cells. In vivo studies in orthotopic mouse model of pancreatic cancer demonstrated decreased tumor growth and metastasis of the Myb- silenced MiaPaCa cells, while an increase was observed in Myb-overexpressing BXPC3 cells as compared to their respective control cells. Altogether, our studies provide the first experimental evidence for a functional role of Myb in progression and metastasis of pancreatic cancer.
Citation Format: Sanjeev K. Srivastava, Seema Singh, Arun Bhardwaj, Sumit Arora, Steven McClellan, William E. Grizzle, Ajay P. Singh. Myb contributes to pancreatic cancer growth and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3882. doi:10.1158/1538-7445.AM2013-3882
Abstract 3913: Hypoxia-mediated cancer imaging by a novel class of near-infrared (NIR) heptamethine cyanine dyes.
Authors: Wu Jason Boyang , Shao Chen , Li Xiangyan , Hu Peizhen , Chen Yi-Ting , Dou Xiaoliang , Sahu Divya , Li Wei , Harada Hiroshi , Wang Ruoxiang , Zhau Haiyen E. , Chung Leland W.K. 
Published: August 2014

Abstract
Near-infrared (NIR) fluorescence imaging has great potential for noninvasive tumor detection. In this study, we describe a novel hypoxia-mediated mechanism underlying a group of heptamethine cyanine dyes, MHI-148 and IR-783, which we developed previously that show tumor-specific targeting properties in cancer cells and living animals (Yang et al., Clin Cancer Res 2010, 16:2833-44 and J Urol 2013, in press). Hypoxia is a common condition found in a wide range of tumors, and mediates many aspects of cancer progression at both tissue and single-cell levels. Using a hypoxia-sensitive luciferase reporter construct (5HREp-ODD-luc) to assess dynamic and real-time tumor hypoxia, in vivo and ex vivo dual-modality imaging studies of human prostate cancer (PCa) growth in nude mice indicate superimposed distribution of NIR signals with hypoxia in tumors. Hypoxia and hypoxic mimickers augment NIR dye uptake in multiple human and murine cell lines representing different types of cancer. We determined that the increased dye uptake under hypoxic conditions was mediated by hypoxia-inducible factor 1α (HIF1α) both in vitro and in vivo. Using cDNA microarray analysis, we identified a group of organic anion-transporting polypeptide (OATP) genes (e.g. OATP1B3, OATP2B1 and OATP5A1), which were highly inducible by hypoxia/HIF1α in PCa cells. We further showed increased co-expression of HIF1α and a representative OATP1B3 gene upon PCa progression in clinical specimens. Pharmacological inhibition or genetic silencing of the OATP1B3 gene reduced the uptake of NIR dyes in tumor cells and tissues. Moreover, hypoxia/HIF1α up-regulates the transcriptional and translational expression of OATP1B3 in PCa, and HIF1α directly binds to a hypoxia response element in the OATP1B3 promoter determined by chromatin immunoprecipitation assays. In addition, we applied NIR dyes for clinical detection of renal cell carcinomas, which shows consistent results with clinical diagnostic tests, and importantly, the HIF1α/OATP1B3 signaling was manifested in these tumors. Together, we provide for the first time the molecular mechanisms of specific NIR dye uptake in cancer via tumor hypoxia and HIF1α/OATPs signals, and present clinical evidence for its potential future applications in cancer detection, prognosis, and therapy.
Citation Format: Jason Boyang Wu, Chen Shao, Xiangyan Li, Peizhen Hu, Yi-Ting Chen, Xiaoliang Dou, Divya Sahu, Wei Li, Hiroshi Harada, Ruoxiang Wang, Haiyen E. Zhau, Leland W.K. Chung. Hypoxia-mediated cancer imaging by a novel class of near-infrared (NIR) heptamethine cyanine dyes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3913. doi:10.1158/1538-7445.AM2013-3913