bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3056: Human ovarian cancer stem cells: In vitro cultivation and characterization
Authors: Ishiguro Tatsuya , Ohata Hirokazu , Nakagama Hitoshi , Okamoto Koji , Tanaka Kenichi , Enomoto Takayuki 
Published: May 2015

Abstract
Cancer stem cells (CSC) constitute a miniscule population within the heterogeneous cells of cancer tissues, but they can self-renew, differentiate and recapitulate the tumors. In the absence of serum, CSC from some solid tumors are capable of proliferation in vitro under sphere-forming conditions. We have now established spheroid culture conditions for cultivating ovarian cancer cells derived from surgical specimen. These spheroid cells are tumorigenic when explanted into NOD/Shi-scid, IL-2Rγnull mice, and immuno-histological analysis indicates that the resulting tumors are indistinguishable from the originals. When serum is added to the in vitro culture media, the spheroid cells differentiate, which is associated with the down-regulation of the stem cell-specific regulators Nanog, Sox2, and ALDH1A1 and the up-regulation of cytokeratin. Expression of two of the regulators was essential for the sphere cell maintenance because shRNA-mediated knockdown of either Sox2 or ALDH1A1 inhibited cell proliferation. The differentiated cells, when returned to the sphere-forming serum-free conditions, were capable of reforming spheroids and re-expression of the stem cell markers. Single cell gene expression analysis of spheroid cells and the differentiated cells revealed that these two cell populations were clearly different, and that the reverting spheroid cells were similar to the original spheroid population. These findings indicated that the differentiation of the spheroid stem cells was highly reversible. Unexpectedly, the serum-induced differentiation caused the cell population to become more resistant to paclitaxel, one of the key ovarian cancer chemotherapy drugs, whereas de-differentiation/reversion back to spheroids rendered the cells paclitaxel-sensitive again. The intriguing clinical implications of these findings will be discussed.
Citation Format: Tatsuya Ishiguro, Hirokazu Ohata, Hitoshi Nakagama, Koji Okamoto, Kenichi Tanaka, Takayuki Enomoto. Human ovarian cancer stem cells: In vitro cultivation and characterization. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3056. doi:10.1158/1538-7445.AM2014-3056
Abstract 3075: Ex-vivo expansion of circulating tumor cells in early lung cancer using a microfluidic model
Authors: Zhang Jennifer Zhuo , Shiratsuchi Hiroe , Lin Jules , Chen Guoan , Reddy Rishindra M. , Azizi Ebrahim , Fouladdel Shamileh , Chang Andrew C. , Lin Lin , Simeone Diane M. , Wicha Max S. , Beer David G. , Ramnath Nithya , Nagrath Sunitha 
Published: May 2015

Abstract
Circulating tumor cells (CTCs) have gathered much momentum in recent times with emerging micro and nanotechnologies enabling better recoveries of these rare cells. Future research directions in CTCs significantly depend on obtaining meaningful number of CTCs that are available for downstream assays. This can be achieved by expanding CTCs. However, in early stage cancer patients, the numbers of cells that circulate in the peripheral blood are rare. Therefore until now, expanding CTCs remains to be a serious challenge limiting clinical utility. Microfluidic technologies have demonstrated that these rare cells can be recovered with better efficiency, purity and high viability. Herein, we developed a strategy using microfluidic technology to isolate and expand CTCs. We have successfully expanded CTCs isolated from 16 out of 21 early stage lung cancer patients. Expanded CTCs expressed tumor specific markers and formed spheroids in culture. Furthermore, these expanded CTCs carried the identical cancer related mutations (e.g. TP53 mutation) as their primary tumors. We expect that our model opens up the unprecedented avenues to understand biology of these lethal drivers of metastasis offering opportunities for personalized medicine through target drug evaluations.
Citation Format: Jennifer Zhuo Zhang, Hiroe Shiratsuchi, Jules Lin, Guoan Chen, Rishindra M. Reddy, Ebrahim Azizi, Shamileh Fouladdel, Andrew C. Chang, Lin Lin, Diane M. Simeone, Max S. Wicha, David G. Beer, Nithya Ramnath, Sunitha Nagrath. Ex-vivo expansion of circulating tumor cells in early lung cancer using a microfluidic model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3075. doi:10.1158/1538-7445.AM2014-3075
Abstract 3985: Differential activation of unfolded protein response in metastatic vs. non-metastatic osteosarcoma cells following hypoxia and chemotherapeutic stress
Authors: Faraj Janine , Hingorani Pooja , Sertil Aparna R. 
Published: May 2015

Abstract
Osteosarcoma (OS) is the most common primary tumor of bone and the second highest cause of cancer-related death in the pediatric age group. Despite significant advances in diagnosis and treatment for this cancer, the overall survival has remained static over the past 20 years. This is due to the fact that little is known about the basic science mechanisms of the pathology of human osteosarcoma as well as the mechanisms of inherent drug resistance of OS. In particular lesser still is known regarding the role of tumor microenvironment that govern growth and progression of osteosarcoma in vivo. Recent clinical reports have demonstrated a negative correlation between tumor hypoxia and overall survival in osteosarcoma patients. In addition to the upregulation of HIFs, it has been shown that hypoxia can trigger an adaptive response such as the unfolded protein response (UPR) that allows tumor cells to avoid therapy-induced death.
Using in vitro experimental models of both the non-metastatic (SAOS-2) and metastatic (143-b) osteosarcoma cell lines, we now show that hypoxic signaling in these cells differentially activates a pro-survival mechanism via the up-regulation of the endoplasmic reticulum (ER) chaperone BiP and increased activation of the ER stress-activated eukaryotic translation initiator factor 2alpha kinase RNA-dependent protein kinase-like ER kinase (PERK) and ATF-6, markers of UPR allowing the cells to resist drug toxicity. Furthermore RNA interference and dominant-negative expression studies revealed that both ATF-6 and PERK signaling promote survival and drug resistance of OS cells,
Our findings shed light on the unknown mechanisms underlying chemotherapeutic drug resistance in osteosarcoma patients. We propose that hypoxic induction of UPR protects OS cells from stress insults, such as chemotherapy. Our research may lead to novel therapies that seek out and destroy the chemoresistant OS cells within the hypoxic core of tumors, thereby preventing survival and metastasis, and ultimately improving the chances of survival amongst OS patients.
Citation Format: Janine Faraj, Pooja Hingorani, Aparna R. Sertil. Differential activation of unfolded protein response in metastatic vs. non-metastatic osteosarcoma cells following hypoxia and chemotherapeutic stress. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3985. doi:10.1158/1538-7445.AM2014-3985
Abstract 3995: Quantitative protein profiling of tumor angiogenesis and metastasis biomarkers in mouse and human models
Authors: Lie Wen-Rong , Lipsey Jonathan , Warmke Tim , Yan Lin , Mistry Jehangir 
Published: May 2015

Abstract
Tumor and stromal cells secrete a variety of proteins acting as extracellular signals and creating a supportive microenvironment for tumor development, angiogenesis, and metastasis. We used the MILLIPLEX MAP cytokine/chemokine, cancer, angiogenesis, metastasis, MMP, bone metabolism, adipocyte, and cell signaling multi-pathway panels, based on the Luminex xMAP technology, to quantitatively evaluate the protein biomarker expression profiles on cultured mouse and human tumor cells and stromal cells as well as in vivo mouse and human tumor tissues. In the mouse system, biomarker profiling was performed to characterize secreted protein levels in Lewis Lung carcinoma (LLC) cells, B16.10 melanoma cells, b.End3 endothelial cells, and LLC tumors. The in vivo characterization, using primary tumors from mice bearing metastatic LLC, has identified differential expression of a panel of biomarkers, including amphiregulin (AREG), EGF, PECAM-1, KC, MCP-1, MIP-2, MMP-12, and resistin, between the high-fat (45% fat) and AIN-93G (15% fat) fed mice (p&lt;0.05, 8 mice per group). These putative biomarkers may be involved in molecular mechanisms of the high-fat enhanced metastasis. Cell signaling pathway analysis revealed the activation of multiple pathways (JNK, p38, ERK, and STAT) in this mouse LLC model. In the human system, a heat map was generated to summarize the secreted protein signatures and the soluble receptor tyrosine kinases (RTK) profile on a series of the cultured human tumor cells (lung, brain, breast, prostate, liver, and colon) and 3 other human cell lines, HUVEC (endothelial), THP-1 (monocyte), and HFF-1 (fibroblast). Lastly, expression profiling of tumor and adjacent normal tissues from 2 patients with metastatic breast cancer was analyzed. Elevated levels of protein biomarkers, including MDC, IL-1RA, IL-8, IP-10, MCP-1, MIP-1α, OPG, OPN, SPARC, periostin, endoglin, PLGF, VEGF-A, MMP-1, MMP-7, MMP-9, and MMP-12, were detected in the breast tumors analyzed compared to their matched adjacent normal breast tissue. In summary, our results demonstrated that multiplexing using the Luminex xMAP bead-based platform for simultaneous quantitative expression profiling is a useful proteomic research tool, providing insights into biomarkers related to tumor progression and metastasis.
Citation Format: Wen-Rong Lie, Jonathan Lipsey, Tim Warmke, Lin Yan, Jehangir Mistry. Quantitative protein profiling of tumor angiogenesis and metastasis biomarkers in mouse and human models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3995. doi:10.1158/1538-7445.AM2014-3995
Abstract 4: WISP-1 increases angiogenesis and VEGF-A expression in human oral squamous cell carcinomas
Authors: Tsao Ching-Wen , Tang Chih-Hsin , Chuang Jing-Yuan 
Published: May 2015

Abstract
Oral squamous cell carcinomas (OSCC) is most common metastasis to cervical lymph nodes by angiogenesis. Wnt-1 induced secreted protein 1 (WISP-1) is a cysteine-rich protein that belongs to the CNN family (CTGF / CYR61 / NOV). However, the effects of WISP-1 on angiogenesis and Vascular endothelial growth factor- A (VEGF-A) expression in human OSCC are not clear. First, we found that the expression of WISP-1 in human OSCC tissues were higher than in normal oral tissues. We also demonstrated that WISP-1 enhanced angiogenesis and VEGF-A up-regulation in human OSCC. WISP-1 induced VEGF-A expressio and angiogenesis through αvβ3 integrin, FAK, c-Src, EGFR, and ERK pathway. Knockdown WISP-1 decreased VEGF-A expression and also abolished human OSCC condition medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane (CAM) and matrix gel plug nude mice model in vivo. In addition, in the xenograft tumor angiogenesis model, knockdown of WISP-1 significantly reduced tumor growth and tumor-associated angiogenesis. We characterized an important role for WISP-1 which regulates angiogenesis by increasing VEGF-A expression in human OSCC via the αvβ3 integrin, FAK, c-Src, EGFR, ERK, and HIF1-α signaling pathway.
Citation Format: Ching-Wen Tsao, Chih-Hsin Tang, Jing-Yuan Chuang. WISP-1 increases angiogenesis and VEGF-A expression in human oral squamous cell carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4. doi:10.1158/1538-7445.AM2014-4
Abstract 40: Association of Interferon-induced protein with tetratricopeptide repeats 1 and 3 expression with regional metastasis and drug resistance in oral squamous cell carcinoma
Authors: Yen Ai-Hsin , Chen Ying-Chen , Pidugu Vijaya Kumar , Liu Chung-Ji , Lee Te-Chang 
Published: May 2015

Abstract
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) gene family, consisting of 4 members (IFIT1, IFIT2, IFIT3, and IFIT5) in humans, is one of most responsive interferon-stimulated gene families. We have previously demonstrated that IFIT2 silencing activates atypical PKC signaling and induces epithelial-mescenchymal transition, cell migration, invasion, and metastasis of oral squamous cell carcinoma (OSCC) cells in cultured or animal models. These results implicate that IFIT2 is potentially a prognosis biomarker of patients with OSCC. In the present study, we further explore the roles of other IFIT1 family proteins involved in the regulatory mechanism of metastasis and drug resistance in OSCC cells. We determined the expression levels of IFIT1 gene family proteins in 82 patients with OSCC by immunohistochemical technique. Our present results revealed a close association between IFIT1 and IFIT3 protein expression in OSCC patient-derived tumor specimens (p &lt; 0.001). However, the expression levels of IFIT1 or IFIT3 did not have a correlation with that of IFIT2 in tumor tissues. Intriguingly, IFIT5 was the only member of IFIT1 family displayed a well correlation with HPV E6 protein expression. Furthermore, we found that the expression levels of IFIT1 and IFIT3 were positively associated with age as well as regional lymph node metastasis status, whereas they were marginally and inversely associated with the differentiation features. We further demonstrated that IFIT1 and IFIT3 protein expression-induced by pre-treatment or co-treatment with IFN-β in Ca9-22 cells increased their resistance to Cisplatin and 5-flurouracil (5-FU). Silencing of IFIT1 and IFIT3 protein expression in SCC-25 cells by its specific shRNA, respectively, increased their susceptibility to Cisplatin and 5-FU. Since our present studies reveal that enhanced IFIT1 and IFIT3 expression associate with regional lymph node metastasis and drug resistance to Cisplatin and 5-FU, the roles of IFIT1 and IFIT3 expression associated with the clinicopathologic development in OSCC patients warrant our further investigation.
Citation Format: Ai-Hsin Yen, Ying-Chen Chen, Vijaya Kumar Pidugu, Chung-Ji Liu, Te-Chang Lee. Association of Interferon-induced protein with tetratricopeptide repeats 1 and 3 expression with regional metastasis and drug resistance in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 40. doi:10.1158/1538-7445.AM2014-40
Abstract 4010: MicroRNA regulator of NMI: implications for breast cancer
Authors: Pruitt Hawley C. , III Jack W. Rostas , Metge Brandon J. , Devine Daniel J. , Bailey Sarah K. , Shevde Lalita A. , Samant Rajeev 
Published: May 2015

Abstract
Recent investigations by our laboratory have demonstrated that NMI expression is down-regulated in patient breast tumors, especially those displaying invasive/metastatic features. In breast cancer and melanoma cell lines, restored expression of NMI suppresses tumor growth. Furthermore, NMI negatively impacts TGFβ-driven epithelial-mesenchymal-transition (EMT) and alsometastatic invasion of breast cancer. Thus the mechanisms that regulate NMI expression are of potential interest to understand the etiology of breast tumor progression, invasion, metastasis and to identify potentially novel therapeutic targets.
MicroRNAs are critical regulators of gene expression. MicroRNA target prediction searches revealed that the NMI transcript could be targeted by the miR-29 family, a group of miRNAs with multiple roles in diverse cancer types. We hypothesized that miR-29 will negatively regulate NMI expression. Luciferase reporter assays using pMIR-REPORTTM confirmed the projected interaction of miR-29 in the seed region of the 3′ UTR of NMI. Manipulation of miR-29 levels in breast cancer cells by overexpression or silencing showed its inverse relationship with NMI expression. Invasive mesenchymal-like breast cancer cell lines showed elevated endogenous levels of miR-29 relative to tumorigenic/non-metastatic (epithelial like) breast cancer cell lines. Moreover, transient overexpression of miR-29 enhanced breast cancer cell invasion as measured by modified Boyden chamber assay and silencing miR-29 using anti-miRs decreased invasion. Investigations on the impact of miR-29 modulation on EMT revealed that increasing miR-29 levels in epithelial-like breast cancer cell lines caused 3D morphological changes indicative of invasive mesenchymal-like growth, while decreasing miR-29 levels from mesenchymal-like cell types using anti-miRs reversed the phenotype and the growth pattern resembled acinar structures. The significance of our observation was realized when we compared RNA isolated from patient derived breast cancer tumors and compared with RNA from matched adjacent normal breast specimens. Analysis using the McNemar's test showed a strong, inverse relationship between the expression of NMI and the miR-29. We contend that aberrant miR-29 expression may account for reduced NMI in some invasive breast cancers.
Citation Format: Hawley C. Pruitt, Jack W. Rostas III, Brandon J. Metge, Daniel J. Devine, Sarah K. Bailey, Lalita A. Shevde, Rajeev Samant. MicroRNA regulator of NMI: implications for breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4010. doi:10.1158/1538-7445.AM2014-4010
Abstract 4021: A kinome screen identifies SRPK1 to mediate breast cancer metastasis
Authors: Water Bob van de , Roosmalen Wies van , Devedec Sylvia L. , Meerman John , Foekens John , Martens John , Geiger Benny 
Published: May 2015

Abstract
Tumor cell migration plays key role in cancer cell dissemination and metastasis and is controlled by signaling-mediated cytoskeletal and cell-matrix adhesion remodeling. Using a phagokinetic track (PKT) assay with migratory H1299 cells, we performed a siRNA screen of almost 1,500 genes encoding kinases/phosphatases, adhesome-related and migration-related proteins, with the aim of identifying genes that determine tumor cell migration speed, and persistence. Thirty candidate genes, showing significant effect were validated in live tumor cell migration assays, and eight of those had a significant association with metastasis free survival in breast cancer patients, ITGB3BP, MAP3K8, NEK2, SHC1 and SRPK1 being most significant .
Further examination indicated that the expression of SRPK1, the most interesting gene identified in this screen , was highest in basal-like breast cancer and its expression level was correlated with poor disease outcome and preferred metastasis to the lungs and brain. In two independent breast tumor metastasis models, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver and spleen and inhibited focal adhesion reorganization. We provide here a comprehensive information resource on the molecular determinants of tumor cell migration and identify SRPK1 as a potential candidate drug target associated with breast cancer metastasis.
Citation Format: Bob van de Water, Wies van Roosmalen, Sylvia Le Devedec, John Meerman, John Foekens, John Martens, Benny Geiger. A kinome screen identifies SRPK1 to mediate breast cancer metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4021. doi:10.1158/1538-7445.AM2014-4021
Abstract 4039: Exploration of a potent E-Selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung
Authors: Esposito Mark , Magnani John L. , Kang Yibin 
Published: May 2015

Abstract
The propensity of breast cancer to metastasize to the lung and bone with high frequency presents an attractive opportunity for specific therapeutic intervention. Targeting the initial steps of metastasis, such as survival in circulation, arrest, and extravasation, may constitute a more effective approach than treatment during the later steps. E-Selectin has been implicated as a pro-metastatic endothelial receptor which mediates the initial stages of tumor cell arrest and extravasation to the lung, liver and bone. We examined the ability of the potent E-selectin antagonist GMI-1271 (Kd = 0.54 μM) to inhibit E-selectin binding to lung and bone metastatic cells. Flow cytometry and ELISA analysis was used to evaluate the effects of GMI-1271 in vitro while treatment of bone and lung metastasis with GMI-1271 during the initial stages of metastatic seeding was used in xenograft models. Results demonstrated that metastatic breast cancer cells express carbohydrates ligands recognized by E-selectin as determined by interaction with E-selectin-Fc chimeric protein and the antibody HECA-452. GMI-1271 could significantly reduce metastatic breast cancer cell binding to E-selectin in vitro. Treatment of mice following intracardiac injection resulted in a significant reduction of mortality (HR = 0.29, p = 0.044) while treatment following tail vein injection demonstrated a directional increase in survival (p = 0.061 and p = 0.055). These results designate GMI-1271 as a potential therapeutic for treatment of late stage breast cancer.
Citation Format: Mark Esposito, John L. Magnani, Yibin Kang. Exploration of a potent E-Selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4039. doi:10.1158/1538-7445.AM2014-4039