bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1918: Synergy between epithelial and mesenchymal cells in breast cancer: from mammospheres to predicting patient outcomes
Authors: Grosse-Wilde Anne , d'Herouel Aymeric , Kuestner Rolf , Ertaylan Gokhan , Skupin Alexander , Huang Sui , Ozinsky Adrian 
Published: May 2015

Abstract
Targeting breast cancer stem cells promises to eliminate the root of metastasis and recurrence and thus to eradicate the ultimate cause of cancer-related death of patients. However, the identity of epithelial cancer stem-like is still elusive; cancer stem-like and metastasis initiating cells have been described to be either epithelial (E) or mesenchymal (M), and thus their identity appears to critically depend on the context of the analyzed cell line.
Here, we have studied the heterogeneous HMLER cell line to identify the relationships between epithelial and mesenchymal cells while they are differentiated and selected under suspension culture conditions. We find that CD24+/CD44- epithelial cells and CD44+/CD24- mesenchymal cells synergize in causing the proliferation of both sub-populations, increasing mammosphere production, and causing the emergence of aggressive motile cells when replated. We observed that when grown in suspension, isolated epithelial as well as isolated mesenchymal cell populations converged towards a hybrid E/M state characterized by coexpression of genes of both lineages, from population down to the single cell level. For epithelial populations convergence at the hybrid state during growth in suspension was thus achieved by proliferation of the most mesenchymal cells resembling an epithelial to mesenchymal transition at the population level. For mesenchymal populations, the hybrid state was reached by the reverse, MET, involving proliferation of the most epithelial cells in a context dependent manner.We use these findings to resolve which genes are predictive of poor outcome in primary human breast tumors. Here we show for the first time that high expression of mesenchymal genes in luminal B/epithelial tumors predicts poor outcome of patients, whereas expression of epithelial genes in basal/mesenchymal tumors predicts poor outcome and thus increased metastasis. Therefore, functional synergy between E and M cells can explain how the tumor context determines whether a minority of mesenchymal or epithelial cells can serve as metastatic stem cells.
Citation Format: Anne Grosse-Wilde, Aymeric d'Herouel, Rolf Kuestner, Gokhan Ertaylan, Alexander Skupin, Sui Huang, Adrian Ozinsky. Synergy between epithelial and mesenchymal cells in breast cancer: from mammospheres to predicting patient outcomes. [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 1918. doi:10.1158/1538-7445.AM2014-1918
Abstract 1923: NF-κB signaling supports a sub-population of ovarian cancer tumor-initiating cells
Authors: House Carrie D. , Annunziata Christina M. 
Published: May 2015

Abstract
Although most patients respond favorably to first-line chemotherapy, ovarian cancer remains the most lethal gynecological cancer in the United States primarily because of a high incidence of disease recurrence. The inability of traditional chemotherapy to eradicate tumor-initiating cells (TICs) is a plausible explanation for tumor relapse and we have begun to characterize TIC populations in ovarian cancer cell lines. Importantly, we are investigating the role of the NF-κB pathway in regulating this system. We have identified conditions that sustain a highly tumorigenic TIC population. Preliminary data suggest that NF-κB promotes and sustains TICs in ovarian cancer and current efforts are underway to characterize the molecular mechanisms underlying this preference. We will correlate activity of this pathway with expression of ovarian TIC protein markers such as CD133, Sox2, Nanog, and Oct-4 in TIC cell cultures and xenografts. Moreover we will use TICs to investigate effects of inhibiting this pathway on marker expression, proliferation, resistance to chemotherapy, and the ability to form tumors in mice. Clarifying the specific role of the NF-κB network in TIC populations will further our understanding of ovarian cancer initiation, progression, and relapse and may lead to improved therapeutic strategies for women in first remission, to prevent subsequent relapse to incurable disease.
Citation Format: Carrie D. House, Christina M. Annunziata. NF-κB signaling supports a sub-population of ovarian cancer tumor-initiating cells. [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 1923. doi:10.1158/1538-7445.AM2014-1923
Abstract 1926: Identification of stem cell by immunohistochemistry in benign and malignant human esophageal mucosa
Authors: Vaiphei Kim , Sinha Saroj Kant , Kochhar Rakesh 
Published: May 2015

Abstract
Introduction: Esophageal squamous cell carcinoma (ESCC) response to treatment if still unsatisfactory with high mortality rate. Objective: to identify the role of cancer stem cell in ESCC by studying the tumor by immunohistochemistry, with the concept of identifying the possible cell for the progression of the tumor due to its uncontrolled proliferation. Materials and methods: endoscopic biopsy and resected specimens of confirmed ESCC tissue were used for the study - fresh tumor tissue with no treatment, post treated residual tumor tissue, recurrent tumor tissue and adjoining esophageal mucosa. Primary immunomarkers used in the study were : i) alpha 6 integrin, ii) CD71, iii) p63, iv) stem cell antigen1, v) cytokeratin 6, vi) Bim1, vii) oct4, viii) nucleostemin, ix) Ki67, x). CD133, x) CD44, xi) CD24 and xii) Aldehyde dehydrogenase. Study was done routine immunohistochemistry, double immunostaining and tissue micro array. Apropriate detection system was used. Results: There was 250 tumor tissue altogether majority with well differentiated morphology. All tumors showed variable range of positivity for the all the markers, lesser number of positive cells for CD24, CD44 and CD133. Even in double immunostaining, majority of the tumor cells showed co-expressions for the various immunomarkers. Different tumor samples from different patient population groups do not any significant differences. Mucosal dysplastic samples also showed similar pattern of positive staining as by the tumor cells. Ki67 posivity was variable, higher percentage of positivity in poorly differentiated tumor areas and related with the nucleostemin positive staining pattern. Conclusion: These observations indicate that these markers are non-specific and positivity does not specifically meant the presence of cancer stem cell. Possibly expression of these markers may indicate cell proliferative pathway markers.
Note: This abstract was not presented at the meeting.
Citation Format: Kim Vaiphei, Saroj Kant Sinha, Rakesh Kochhar. Identification of stem cell by immunohistochemistry in benign and malignant human esophageal mucosa. [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 1926. doi:10.1158/1538-7445.AM2014-1926
Abstract 1929: Tyrosine kinase inhibition with sorafenib but not pazopanib enriches for sarcoma cancer stem cells in diverse models of soft tissue sarcoma
Authors: Canter Robert J. , Ames Erik , Mac Stephanie , Grossenbacher Steve K. , Chen Mingyi , Tellez Joe , Monjazeb Arta M. , Murphy William J. 
Published: May 2015

Abstract
Purpose: Cancer stem cells (CSCs) are a putative source of resistance and relapse following conventional anti-proliferative therapies. We hypothesized that anti-proliferative, but not anti-angiogenic, tyrosine kinase inhibitors would enrich for CSCs in models of soft tissue sarcoma.
Experimental Design: We exposed multiple human sarcoma cell lines to sorafenib and pazopanib and assessed cell viability and expression of CSC markers. We exposed mice harboring lung/liver Ewing's sarcoma metastases to daily sorafenib and evaluated survival and CSC expression. We exposed dissociated primary sarcoma tumors to overnight sorafenib and pazopanib. We used tissue microarray (TMA) to evaluate the frequency and intensity of CSC markers in clinical sarcoma samples after neoadjuvant therapy with sorafenib.
Results: Viability following sorafenib exposure in vitro ranged from 1 - 20% with a corresponding 2 - 8.2 fold increase in ALDHbright cells from baseline (P&lt;0.05), while negligible effects from pazopanib were observed. In vivo, sorafenib treatment improved median survival by 10 days (P&lt;0.05), but increased the population of ALDHbright cells 2.5 - 2.8 fold (P&lt;0.05). Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib with a corresponding increase in ALDHbright cells (P&lt;0.05). Again, negligible effects from pazopanib were observed. TMA analysis of clinical sarcoma specimens demonstrated significant enrichment for ALDHbright cells in the post-treatment resection specimen following neoadjuvant therapy including sorafenib (P&lt;0.05).
Conclusions: Sorafenib, but not pazopanib, exerts a direct anti-proliferative effect on sarcoma cells with a corresponding enrichment in sarcoma CSCs. Sustained anti-sarcoma therapeutic effects may require targeting of the CSC population in combination with cytotoxic treatments.
Note: This abstract was not presented at the meeting.
Citation Format: Robert J. Canter, Erik Ames, Stephanie Mac, Steve K. Grossenbacher, Mingyi Chen, Joe Tellez, Arta M. Monjazeb, William J. Murphy. Tyrosine kinase inhibition with sorafenib but not pazopanib enriches for sarcoma cancer stem cells in diverse models of soft tissue sarcoma. [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 1929. doi:10.1158/1538-7445.AM2014-1929
Abstract 1931: Tumor spheres growing from circulating tumor cells exhibit stem cell features
Authors: Pachmann Katharina , Pizon Monica , Zimon Dorothea 
Published: May 2015

Abstract
Background: Among the cells that are disseminated from a malignant tumor some are capable of resettling in distant organs and growing into life-threatening metastases. Therefore, the question arises how and whether such cells which have the potential to grow into metastases can be detected.
Materials and Methods: Using a nondissipative approach with only one enrichment step of red blood cell lysis, cells were cultured under conditions favoring the growth of epithelial cells. At 7, 14 and 21days the cell cultures were inspected for the appearance of spheroids staining with anti-EpCAM, anti-CD24 and anti-CD44 antibody and.expressing ALDH1.
Results: Tumorspheres from peripherally circulating cells from patients with malignant tumors in different stages of disease could so far be grown from 79% of 100 patients in whom more than 1000 epithelial tumor suspect cells per ml were detected. Numbers of tumorspheres correlated with the aggressiveness of the tumor and were highest in patients after surgery who had not yet received any systemic therapy. The size of the spheres increased from day 7 to day 21. They were negative for CD24 and positive for CD44. They highly express ALDH1 and thus exhibite typical features of stem cells.
Conclusion: Here, we demonstrate that the circulating tumor cells, detected in our approach contain a subpopulation with stem cell-like properties capable of growing into tumorspheres.
The frequency in peripheral blood of cells capable of forming tumor spheres seems to be dependent on the aggressiveness of the primary tumor.
Citation Format: Katharina Pachmann, Monica Pizon, Dorothea Zimon. Tumor spheres growing from circulating tumor cells exhibit stem cell features. [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 1931. doi:10.1158/1538-7445.AM2014-1931
Abstract 1933: Novel roles of receptor tyrosine kinase AXL in the control of stem cell pluripotency and reprogramming
Authors: Cho Yee Sook , Son Mi-Young , Seol Binna 
Published: May 2015

Abstract
The extensive molecular characterization of human pluripotent stem cells (hPSCs), human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs) is required Binnbefore they can be applied in the future for personalized medicine and drug discovery. Despite the efforts that have been made with kinome analyses, we still lack in-depth insights into the molecular signatures of receptor tyrosine kinases (RTKs) that are related to pluripotency. Here, we present the first detailed and distinct repertoire of RTKs characteristic for hPSC pluripotency by determining both the expression and phosphorylation profiles of RTKs in hESCs and hiPSCs using RT-PCR with degenerate primers that target conserved tyrosine kinase domains and phospho-RTK array, respectively. Among the RTKs tested, the up-regulation of EPHA1, ERBB2, FGFR4, and VEGFR2 and the down-regulation of AXL, EPHA4, PDGFRB, and TYRO3 in terms of both their expression and phosphorylation levels were predominantly related to the maintenance of hPSC pluripotency. Notably, the specific inhibition of AXL was significantly advantageous in maintaining undifferentiated hESCs and hiPSCs and for the overall efficiency and kinetics of hiPSC generation. Additionally, a global phosphoproteomic analysis showed that approximately 30% of the proteins (293 of 970 phosphoproteins) showed differential phosphorylation upon AXL inhibition in undifferentiated hPSCs, revealing the potential contribution of AXL-mediated phosphorylation dynamics to pluripotency-related signaling networks. Our findings provide a novel molecular signature of AXL in pluripotency control that will complement existing pluripotency-kinome networks.
Citation Format: Yee Sook Cho, Mi-Young Son, Binna Seol. Novel roles of receptor tyrosine kinase AXL in the control of stem cell pluripotency and reprogramming. [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 1933. doi:10.1158/1538-7445.AM2014-1933
Abstract 1947: Plasticity of CD44+ colorectal cancer stem cells depends on TGF-beta-induced epithelial mesenchymal transition(EMT): Evidences from an ex vivo culture
Authors: Nakano Michitaka , Ariyama Hiroshi , Tamura Shingo , Isobe Taichi , Miyawaki Kohta , Okumura Yuta , Kusaba Hitoshi , Baba Eishi , Akashi Koichi 
Published: May 2015

Abstract
Background
EpCAMhigh CD44+ colorectal cancer (CRC) cells are thought to be cancer stem cells. Recently CD44- CRC cells are also suggested to gain a character of cancer stem cells, but the molecular mechanisms have not been clarified. Epithelial-mesenchymal transition (EMT), which is observed in several caner cell lines, could be a possible process of cancer cells to obtain stemness. However, whether primary human CRC cells underwent EMT has not been proven.
Patients and Methods
We obtained surgical specimens of 30 cases of advanced CRC, and cultured isolated primary cancer cells in matrigel-based medium containing several growth factors. For induction of EMT, TGF-beta was added into the culture of CD44+ and CD44- cells. Immunocytochemistry staining and flow cytometry of the spheroid cells and single cell PCR analysis of the cultured cells using 48-gene set that included EMT-related genes (BioMark HD System:Fluidigm Corporation) were performed.
Results
Cancer cells grew spherically (50 μm&gt; diameter) in 20 out of 30 samples after a week culture of whole isolated cancer cells. The sphere mostly consisted of CD44+ cells, and non-sphere forming single cells were CD44-negative. Isolated CD44+ cells from primary samples gave rise to CD44+ and CD44- cells in a week culture. Interestingly, 10% of CD44- cell from primary samples also expressed CD44. Similar to the previous findings of cell lines that TGF-beta-induced EMT could convert CD44- cells into CD44+ cancer initiating cells, increased number of CD44+ cells appeared from primary CD44- cells cultured with TGF-beta. In this culture, N-cadherin+ cells increased time-dependent manner and most of this N-cadherin expressing cells co-expressed CD44. In single cell PCR analysis, increased expression of EMT-related genes, vimentin and TWIST1, were preferentially detected in CD44+N-Cadherin+ cells.
Conclusions
To our knowledge, this is the first report that CD44- cells from primary samples undergo EMT and convert into CD44+ cells by TGF-β treatment. Investigation whether these CD44+ converted cells have cancer stem cell properties such as tumorigenic potential in immunodeficient mouse, self renewing ability and drug resistance is underway.
Citation Format: Michitaka Nakano, Hiroshi Ariyama, Shingo Tamura, Taichi Isobe, Kohta Miyawaki, Yuta Okumura, Hitoshi Kusaba, Eishi Baba, Koichi Akashi. Plasticity of CD44+ colorectal cancer stem cells depends on TGF-beta-induced epithelial mesenchymal transition(EMT): Evidences from an ex vivo culture. [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 1947. doi:10.1158/1538-7445.AM2014-1947
Abstract 1962: Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by up-regulating cytidine deaminase
Authors: Amit Moran , Weizman1 Noam , Binenbaum Yoav , Shabtay-Orbach Ayelet , Wong Richard J. , Gil Ziv 
Published: May 2015

Abstract
Resistance to pharmacologic agents used in chemotherapy is common in most human carcinomas, including pancreatic ductal adenocarcinoma (PDA), which is resistant to almost all drugs, including gemcitabine, a nucleoside analog used as first-line treatment. Poor survival rates of PDA patients have, therefore, not changed much over 4 decades. Recent data indicated that tumor-associated macrophages (TAMs), which are abundant in the microenvironment of several tumors, including PDA, secrete pro-tumorigenic factors which contribute to cancer progression and dissemination. In this study, we show for the first time that TAMs can also induce chemoresistance of PDA by reducing gemcitabine-induced apoptosis. Macrophages co-cultured with cancer cells or TAMs conditioned medium significantly reduced apoptosis and activation of the caspase-3 pathway during gemcitabine treatment. In vivo PDA models of mice, which have reduced macrophage recruitment and activation, demonstrated improved response to gemcitabine compared to controls. Similarly, inhibition of monocytes/macrophages trafficking by a CSF1-receptor antagonist GW2580 augmented the effect of gemcitabine in a transgenic mouse PDA model that was resistant to gemcitabine alone. Analysis of multiple proteins involved in gemcitabine delivery and metabolism revealed that TAMs induced upregulation of cytidine deaminase (CDA), the enzyme that metabolizes the drug following its transport into the cell. Decreasing CDA expression by PDA cells blocked the protective effect of TAMs against gemcitabine. These results provide the first evidence of a paracrine effect of TAMs, which mediates acquired resistance of cancer cells to chemotherapy. Modulation of macrophage trafficking or inhibition of CDA may offer a new strategy for augmenting the response of PDA to chemotherapy.
Citation Format: Moran Amit, Noam Weizman1, Yoav Binenbaum, Ayelet Shabtay-Orbach, Richard J. Wong, Ziv Gil. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by up-regulating cytidine deaminase. [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 1962. doi:10.1158/1538-7445.AM2014-1962
Abstract 1972: The sodium channel auxiliary subunit SCN1B promotes breast tumor growth and metastasis
Authors: Nelson Michaela , Millican-Slater Rebecca , Forrest Lorna C. , Brackenbury William J. 
Published: May 2015

Abstract
Voltage-gated Na+ channels (VGSCs) are heteromeric proteins composed of pore-forming α subunits and smaller β subunits. The β subunits are multifunctional channel modulators and are members of the immunoglobulin superfamily of cell adhesion molecules (CAMs). β1, encoded by SCN1B, is best characterized in the central nervous system (CNS), where it plays a critical role in regulating electrical excitability, neurite outgrowth and migration during development. β1 is also expressed in breast cancer cell lines, where it regulates adhesion and migration in vitro. Using the Oncomine database, we found that SCN1B mRNA was up-regulated in breast cancer, compared with normal breast. Similarly, β1 protein was up-regulated in a cohort of breast cancer tissue specimens compared with surrounding normal tissue. Over-expression of β1 in MDA-MB-231 cells substantially increased tumor growth and metastasis from orthotopic xenografts in immune-deficient mice. β1 had no effect on the density of Ki67-positive cycling cells in the primary tumors. However, β1 increased the density of CD31-positive vessel structures and reduced the density of apoptotic cells expressing activated caspase-3. β1-expressing MDA-MB-231 cells had an elongate morphology in tumors in vivo and in 2D culture in vitro. β1 potentiated the outgrowth of processes from MDA-MB-231 cells and MCF-7 cells co-cultured with fibroblasts, via trans-homophilic adhesion. Both the src family tyrosine kinase inhibitor PP2 and siRNA targeting fyn kinase blocked β1-mediated process extension in breast cancer cells. Thus, β1-mediated process outgrowth in breast cancer cells requires the presence and activity of fyn kinase. This recapitulates the mechanism by which β1 regulates neurite outgrowth in CNS neurons. We conclude that when present in breast tumors, β1 drives pathological growth and cellular dissemination by recapitulating its well-defined role in CNS ontogeny. This study is the first demonstration of a functional role for β1 as a CAM in tumor growth and metastasis. We propose that targeting β1-mediated adhesion interactions may have potential as a novel anti-cancer therapy.
Citation Format: Michaela Nelson, Rebecca Millican-Slater, Lorna C. Forrest, William J. Brackenbury. The sodium channel auxiliary subunit SCN1B promotes breast tumor growth and 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 1972. doi:10.1158/1538-7445.AM2014-1972