bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1476: Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β.
Authors: Mele Valentina , Muraro Manuele Giuseppe , Calabrese Diego , Amatruda Nunzia , Amicarella Francesca , Pfaff Dennis , Kvinlaug Brynn , Bocelli-Tyndall Chiara , Martin Ivan , Resink Therese J. , Terracciano Luigi M. , Spagnoli Giulio Cesare , Iezzi Giandomenica 
Published: August 2014

Abstract
Mesenchymal stem/stromal cells (MSC) are multipotent precursors endowed with the ability to home to primary and metastatic tumor site. Because of this feature, they are currently being used in preclinical models and in clinical trials as potential vehicles for delivery of targeted anti-cancer therapies. Clinical applications of MSC however, require a deeper understanding of their biology and, in particular, of their interaction with cancer cells. In this study we have investigated the effects mediated by human bone marrow-derived MSC on human colorectal cancer (CRC) cells in vitro and in vivo. We found that MSC induced upregulation of epithelial-to-mesenchymal (EMT)-related genes and downregulation of E-cadherin in tumor cells. These effects required cell-to-cell contact and were mediated by expression of surface-bound TGF-β, induced in MSC upon coculture with tumor cells. CRC cells exposed to MSC formed larger tumor masses in vivo, characterized by higher vessel density and increased mesenchymal marker expression, and displayed enhanced invasive capacity. Thus, by promoting cell expansion, EMT-related phenomena and tumor angiogenesis, MSC appear to favor the acquisition of an aggressive phenotype by CRC cells. These findings raise concerns regarding the safety of MSC administration for clinical purposes in patients with cancer.
Citation Format: Valentina Mele, Manuele Giuseppe Muraro, Diego Calabrese, Nunzia Amatruda, Francesca Amicarella, Dennis Pfaff, Brynn Kvinlaug, Chiara Bocelli-Tyndall, Ivan Martin, Therese J. Resink, Luigi M. Terracciano, Giulio Cesare Spagnoli, Giandomenica Iezzi. Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β. [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 1476. doi:10.1158/1538-7445.AM2013-1476
Abstract 1477: Protein Tyrosine Kinase 6 promotes peripheral adhesion complex formation, cell migration, and the epithelial mesenchymal transition in prostate cancer.
Authors: Tyner Angela L. , Zheng Yu 
Published: August 2014

Abstract
Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that is evolutionarily related to Src kinases. In the normal prostate, total and active PTK6 is localized within the nucleus, but nuclear localization is lost in prostate tumors. While the majority of total PTK6 is localized within the cytoplasm of PC3 cells, a human prostate cancer cell line, the active pool of PTK6 that is phosphorylated on tyrosine residue 342 is membrane associated. Ectopic expression of membrane targeted PTK6 leads to enhanced activation of PTK6 at the membrane and formation of peripheral adhesion complexes and increased migration of PC3 cells. Ectopic expression of PTK6 in SYF cells, a nontransformed mouse embryonic fibroblast cell line lacking Src, Yes, and Fyn kinases leads to cell transformation and tumor growth in vivo. Ectopic expression of active membrane-targeted PTK6 in PC3 cells promotes the epithelial mesenchymal transition (EMT). PTK6 regulates the EMT through AKT, as knockdown of AKT or inhibition of AKT activity by knockdown of p130CAS partially rescues the phenotype. PC3 cells expressing active membrane targeted PTK6 exhibit increased migration in vitro and form more metastases in a xenograft mouse model, while knockdown of PTK6 promotes an epithelial phenotype and impairs tumorigenesis in vivo. In prostates of Probasin-Cre, Pten flox/flox mice, striking activation of endogenous mouse PTK6 is observed at the membrane in Pten-null prostates, and this is accompanied by deregulated expression of E-cadherin and vimentin. We found a reverse correlation between PTK6 and E-cadherin expression in normal and metastatic human prostate cancer samples, and show PTK6 is activated at the membrane in some high-grade prostate tumors. Our studies reveal novel functions for PTK6 in prostate cancer, and define it as a potential therapeutic target.
Citation Format: Angela L. Tyner, Yu Zheng. Protein Tyrosine Kinase 6 promotes peripheral adhesion complex formation, cell migration, and the epithelial mesenchymal transition in prostate 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 1477. doi:10.1158/1538-7445.AM2013-1477
Abstract 1495: Regulation of the epithelial-mesenchymal transition by claudin-3 and claudin-4.
Authors: Shang Xiying , Lin Xinjian , Manorek Gerald , Howell Stephen 
Published: August 2014

Abstract
The mechanisms that control intracellular adhesion are central to the process of invasion and metastasis. Claudin-3 (CLDN3) and claudin-4 (CLDN4) are major structural molecules of the tight junctions that link epithelial cells. Our prior work has demonstrated that knockdown of the expression of either CLDN3 or CLDN4 produces marked changes in the phenotype of ovarian carcinoma cells including increases in growth rate in vivo, migration, invasion, metastasis and drug resistance, similar to those produced by the epithelial-to-mesenchymal transition (EMT). We postulated that these changes may result from the ability of CLDN3 or CLDN4 to suppress EMT. In this study we found that knockdown of either CLDN3 or CLDN4 increased cell size and resulted in elongated, fibroblastic morphology. While knockdown of CLDN3 or CLDN4 did not alter the expression of vimentin, it significantly down-regulated the level of E-cadherin and up-regulated N-cadherin expression. Conversely, over-expression of CLDN3 or CLDN4 in a cell line that does not express endogenous CLDN3 or CLDN4 decreased N-cadherin expression. Re-expression of E-cadherin in the CLDN3 or CLDN4 knockdown cells reduced migration, invasion and tumor growth in vivo. Loss of either CLDN3 or CLDN4 resulted in activation of the PI3K pathway as evidenced by increased Akt phosphorylation, and up-regulation of the mRNA and protein levels of the transcription factor Twist. Taken together, these findings suggest that CLDN3 and CLDN4 function in the ovarian cancer cells to sustain an epithelial phenotype and that their loss promotes EMT.
Citation Format: Xiying Shang, Xinjian Lin, Gerald Manorek, Stephen Howell. Regulation of the epithelial-mesenchymal transition by claudin-3 and claudin-4. [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 1495. doi:10.1158/1538-7445.AM2013-1495
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 15: Association of topoisomerase II expression and cancer-specific death in patients with surgically-resected clear cell renal cell carcinoma.
Authors: Joseph Richard W. , Serie Dan , Hilton Tracy , Parasramka Mansi , Eckel-Passow Jeanette , Cheville John , Leibovich Bradley C. , Parker Alexander S. 
Published: August 2014

Abstract
PURPOSE: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death.
METHODS: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/16/1990 and 9/27/2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features we employed Kruskal-Wallis tests and for associations with cancer-specific survival we generated Cox proportional hazard regression models.
RESULTS: Higher TOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p &lt; 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend &lt; 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p&lt;0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ∼95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p =0.01).
CONCLUSION: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.
Citation Format: Richard W. Joseph, Dan Serie, Tracy Hilton, Mansi Parasramka, Jeanette Eckel-Passow, John Cheville, Bradley C. Leibovich, Alexander S. Parker. Association of topoisomerase II expression and cancer-specific death in patients with surgically-resected clear cell renal cell carcinoma. [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 15. doi:10.1158/1538-7445.AM2013-15
Abstract 1501: Pan-cancer PathSeq analysis on TCGA data for pathogen discovery.
Authors: Jung Joonil , Pedamallu Chandra Sekhar , Kostic Aleksander D. , Freeman Samuel , Ojesina Akinyemi I. , Berger Alice , Bhatt Ami , Duke Fujiko , Getz Gad , Meyerson Matthew 
Published: August 2014

Abstract
An estimated 15-20% of all human malignancies is caused by infectious agents, such as human papillomavirus (HPV), Epstein-Barr virus (EBV) or Helicobacter pylori (H. pylori). The recent development of massively parallel next generation sequencing technology led to the discovery of Merkel cell polyomavirus, and more recently a significant enrichment of Fusobacterium nucleatum (F. nucleatum) and related Fusobacterium species in colorectal carcinomas compared to non-neoplastic colon tissue from the same patients. However, these studies involved relatively small number of samples and there are likely many additional cancer-associated microbes that are yet to be discovered. TCGA sequencing data from over 20 human cancer types provide an unprecedented opportunity for cancer-associated pathogen discovery. Using PathSeq, software for pathogen discovery by computational subtraction, we have begun analyzing TCGA sequencing data for the presence of viral, fungal or bacterial sequences. We will present our preliminary data from the analysis of mRNA-seq data including evidence for (1) a greater role of viral integration into tumor suppressor gene loci in HPV-driven tumors and (2) complex interplay between viruses, bacteria and host cancer cells in various cancer types. We will also discuss our discovery efforts for previously unannotated pathogens in the TCGA dataset.
Citation Format: Joonil Jung, Chandra Sekhar Pedamallu, Aleksander D. Kostic, Samuel Freeman, Akinyemi I. Ojesina, Alice Berger, Ami Bhatt, Fujiko Duke, Gad Getz, Matthew Meyerson. Pan-cancer PathSeq analysis on TCGA data for pathogen discovery. [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 1501. doi:10.1158/1538-7445.AM2013-1501
Abstract 1506: Changes in the expression profile of microRNAs and their predicted targets in fibroblasts associated with breast carcinoma compared to fibroblasts from normal breast tissue.
Authors: Costa Simone V. , Roela Rosimeire A. , Pasini Fatima S. , Katayama Maria L H , Mazzotti Tatiane K. F. , Gebrim Luiz H. , Resende Vanessa C.L. , Neto Miguel S. , Brentani M Mitzi 
Published: August 2014

Abstract
Background: Cancer-associated fibroblasts (CAFs) contribute to tumor growth and progression in breast cancer. CAFs are functional and phenotypically distinct from normal breast tissue (NAFs). Epigenetic modifications and post-transcriptional gene regulation by microRNAs may contribute to the phenotype of CAFs.
Objective: To identify the changes in microRNAs expression profile in fibroblasts associated with breast cancer as compared to those observed in fibroblasts obtained from samples of mammoplasty.
Methodology: Fibroblast primary culture from breast carcinoma (n= 04) and normal breast (n= 06) tissues were established and characterized by Immunohistochemistry. Total RNA extraction and purification were realized using Mirvana kit and miRNAs differentially expressed were identified by qPCR TaqMan® Low Density Array. Potential targets of these miRNAs were identified by in sílico analysis using DIANAm T, Miranda, miRWalk, PICTAR5 and TargetScan databases and compared to microarray profile determined using the U133 plus v.2 Affymetrix chip.
Results: All primary cultures from fibroblast were characterized by presence of vimentin, total absence of CD31 and pan-cytokeratin expression but CAFs exhibited a higher proportion of cells positive for alpha-actin and S100A4. The five microRNAs differentially expressed identified by statistical analysis and grouped hierarchically (hs_miR_655, hs_miR_383, hs_miR_129_3p, hs_miR_15b, hs_miR_489) (FDR≤10% and p&lt;0.05) allowed the separation of the samples into two distinct groups: NAFs and CAFs. The Gene Ontology analysis of predicted target genes to each one of the microRNAs listed above and also identified by microarray, revealed their involvement in important biological processes including cellular morphogenesis and protein localization.
Further detailed studies of these miRNAs and their targets in CAFs may help to better understand the contribution of the mammary tumor microenvironment to breast carcinogenesis and progression.
Financial Support: FAPESP 09/100088-7, FAPESP 2011/08194-3
Citation Format: Simone V. Costa, Rosimeire A. Roela, Fatima S. Pasini, Maria L H Katayama, Tatiane K. F. Mazzotti, Luiz H. Gebrim, Vanessa C.L. Resende, Miguel S. Neto, M Mitzi Brentani. Changes in the expression profile of microRNAs and their predicted targets in fibroblasts associated with breast carcinoma compared to fibroblasts from normal breast tissue. [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 1506. doi:10.1158/1538-7445.AM2013-1506
Abstract 1516: Melanocyte activation by UVR-induced calprotectin.
Authors: von Maltzan Kristine , Shirley Stephanie H. , Kusewitt Donna F. 
Published: August 2014

Abstract
Melanoma is the most common cause of skin cancer death, although it accounts for only 5% of all skin cancers. Epidemiologic and clinical observations have shown that the ultraviolet (UVR) component of sunlight is the most important etiologic factor in melanoma; however, the precise mechanisms by which UVR drives melanomagenesis are unknown. Mutations in oncogenes and tumor suppressor genes have been identified in melanomas, but most of these are not the UVR signature mutations found in non-melanoma skin cancers. This suggests an indirect role for UVR in melanomagenesis, likely as a tumor promoter. UVR is a potent inducer of keratinocyte-derived paracrine and melanocyte/melanoma cell-derived autocrine factors that profoundly affect melanocyte/melanoma cell gene expression and behavior. Many of these mediators are also potent proinflammatory signals that create an inflammatory environment with additional effects on untransformed and transformed melanocytes. We have identified calprotectin, a secreted heterodimer of S100A8 and A9, as one of these mediators. UVR exposure induces S100A8 and A9 transcription in and calprotectin release from human keratinocytes and melanocytes. Human melanocytes and melanoma cells constitutively express TLR4, one of the receptors for calprotectin. Treatment of human melanocytes and melanoma cells with exogenous calprotectin enhances their proliferation, migration, and invasiveness. UVR-induced calprotectin secretion by melanocytes/melanoma cells and surrounding keratinocytes activates melanocytes/melanoma cells and may thus promote melanomagenesis.
Citation Format: Kristine von Maltzan, Stephanie H. Shirley, Donna F. Kusewitt. Melanocyte activation by UVR-induced calprotectin. [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 1516. doi:10.1158/1538-7445.AM2013-1516
Abstract 1539: Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo.
Authors: Hiroshima Yukihiko , Momiyama Masashi , Hassanein Mohamed , Maawy Ali , Menen Rhiana , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Endo Itaru , Hoffman Robert M. 
Published: August 2014

Abstract
Macrophages promote tumor growth by stimulating tumor-associated angiogenesis, cancer-cell invasion, migration, and intravasation, as well as suppression of antitumor immune responses. We previously defined the macrophages which were harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as “tumor-educated macrophages (EMϕ)” and demonstrated EMϕ promoted tumor growth and metastasis in orthotopic mouse models. The aim of this study is to elucidate the mechanism of tumor promotion by EMϕ. Transgenic nude mice ubiquitously-expressing GFP were injected subcutaneously with the human pancreatic cancer cell line XPA1 stably expressing RFP in the cytoplasm and GFP in the nucleus. GFP-expressing macrophages from the GFP mice with the dual-color pancreatic tumor were harvested and defined as EMϕ. Macrophages were also harvested from transgenic
GFP mice without tumors and identified as “naïve macrophages (NMϕ)”. EMϕ and NMϕ were compared for their ability to enhance cancer-cell proliferation. Using a skin-flap-window imaging model, the mitotic index of the cancer cells significantly increased after injection of EMϕ compared to NMϕ (p = 0.001). Next, we cultured cancer cells in 3-D on Gelfoam® and found that the cancer cells cultured with EMϕ proliferated to a greater extent compared to those cultured with NMϕ (p = 0.014). We also found that the cancer cells cultured in the conditioned medium harvested from EMϕ had enhanced proliferated compared to cancer cells cultured in the conditioned medium from NMϕ (p = 0.016). These results suggest that EMϕ secrete factors which increase cancer cell growth and can serve as a novel therapeutic target for pancreatic cancer.
Citation Format: Yukihiko Hiroshima, Masashi Momiyama, Mohamed Hassanein, Ali Maawy, Rhiana Menen, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo. [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 1539. doi:10.1158/1538-7445.AM2013-1539
Abstract 1543: Tumor associated macrophages are associated with poor survival in epithelial ovarian cancer.
Authors: El Masri Wafic , Hillerup Caroline , Topka Charlotte , Santiskulvong Chintda , Chiang Alexander , Wu Lily , Rao Jianyu , Dorigo Oliver 
Published: August 2014

Abstract
Background
Tumor associated macrophages have been associated with poor outcomes in several solid tumors, but their impact on the outcome of patients with epithelial ovarian cancer has not been well established.
Methods
We constructed a tissue microarray of 142 epithelial ovarian cancer specimens. Immunohistochemistry was performed for the presence of CD68+ macrophages. The distribution of macrophages was evaluated separately in tumor and stromal tissue. Clinical characteristics were recorded and presence or absence of intratumoral macrophages was correlated with clinical characteristics including survival.
Results
Median follow-up for the entire cohort was 32.0 months (range, 1.7-170 months), and median progression-free survival (PFS) and overall survival (OS) were 14.1 months and 47.8 months, respectively. Intratumoral macrophages (ITMs) were present in 132/142 patients (91.5%) and absent in 12/142 (8.5%). Patients whose tumor tissue did not contain ITMs had a significantly longer median PFS (not reached, p = 0.009) and median OS (150.1 months, p=0.03), compared with the median PFS and OS of 11.7 and 47.7 months, respectively, among patients with ITMs. Interestingly, we could not demonstrate differences in PFS and OS when stromal macrophages were evaluated separately. The presence of ITMs was an independent prognostic factor for OS in a multivariate analysis (p=0.009). The Cox proportional hazard ratios for presence of ITMs were 3.55 for PFS (95% CI, 1.38-12.13) and 3.62 for OS (95% CI, 1.33-13.08).
Conclusions
Our study shows that the presence of intratumoral but not stromal macrophages correlates with poor prognosis in epithelial ovarian carcinoma.
Citation Format: Wafic El Masri, Caroline Hillerup, Charlotte Topka, Chintda Santiskulvong, Alexander Chiang, Lily Wu, Jianyu Rao, Oliver Dorigo. Tumor associated macrophages are associated with poor survival in epithelial ovarian 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 1543. doi:10.1158/1538-7445.AM2013-1543