bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3375: The epithelial to endotheliod transition (EET): A cellular modulation that promotes the head and neck squamous cell carcinoma tumorigenic phenotype
Authors: Tong Meng , He Lingli , Han Byungdo , Holpuch Andrew , Pei Ping , Mallery Susan R. 
Published: June 2012

Abstract
The presence of the EMT (epithelial-mesenchymal transition) and EndMT (endothelial-mesenchymal transition) demonstrates the extent of phenotypic plasticity in cancers. Previous findings in head and neck squamous cell carcinoma (HNSCC) cells, i.e., VEGF's autocrine-paracrine function and their responsiveness to endostatin, imply that HNSCC cells share some functional characteristics with endothelial cells and suggest the potential for an “epithelial-to-endotheliod transition (EET)”. Such a transition would facilitate HNSCC tumorigenesis by augmenting release of proangiogenic factors and facilitating tumor cell migration and invasion. Consequently, these studies elucidated whether or not an EET occurs in HNSCC cells and tumors, and evaluated cellular parameters to uniquely characterize this epithelial-endotheliod transition. Our results demonstrate that cultured HNSCC cells express a variety of endothelial-specific markers, and assumption of the endotheliod phenotype has functional consequences including uptake of acetylated low density lipoprotein and enhanced invasion and migration. Selective HNSCC cells were also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the EET is not restricted to cultured HNSCC cells per se as tumor cells in resected human HNSCC tumors and proliferating epithelia at the margins of ulcers demonstrate a similar phenotype. These data suggest that, similar to EMT, the EET enhances epithelial cell migration. Also, the regulation of this transition-transient (wound healing) versus sustained (invasive cancers)-impacts clinical outcome. Finally, recognition of the EET as a distinct entity provides impetus for future clinical trials to concurrently assess the antitumorigenic as well as the angiostatic properties of therapeutic agents formally regarded as exclusively angiostatic in scope.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3375. doi:10.1158/1538-7445.AM2011-3375
Abstract 3384: The effects of mono- and combination-treatment of phytochemicals and antimicrotubule chemotherapeutic agents on prostate cancer cell proliferation and expression of EMT markers
Authors: Smith Basil A. 
Published: June 2012

Abstract
PURPOSE: Treatment of androgen-independent metastatic prostate cancer with chemotherapeutic agent Estramustine showed diminishing success. Epidemiological studies showed an association between reduced cancer risk and dietary intake rich in phytochemicals from fruits and vegetables. We studied the molecular mechanisms through which phytochemicals muscadine grape skin extract (MSKE) and camalexin act individually, or in combination with Estramustine, to affect epithelial-mesenchymal transition (EMT), a process involved in prostate cancer progression. EMT can be induced by transcription factors such as Snail, and is associated with decrease in cell adhesion molecules like E-cadherin, and increase in mesenchymal markers such as vimentin. METHODOLOGY: MSKE, Camalexin, and Estramustine, were used in varying concentrations individually, and in combination, to conduct MTS proliferation assay on C4-2 and ARCaP prostate cancer EMT model overexpressing constitutively active Snail cDNA. EMT markers, E-cadherin and vimentin, were examined by Western Blot Analysis following treatments. RESULTS: MSKE or Camalexin with or without Estramustine significantly decreased cell proliferation of C4-2 cells. Surprisingly, ARCaP-Snail cells were more sensitive to MSKE and Estramustine treatments, and showed significant decrease in viability, as compared to control ARCaP-Neo cells. ARCaP-Snail cells treated with 5µg/ml MSKE showed a reversal in EMT as shown by increased E-cadherin and decreased vimentin levels. CONCLUSION: Both mono and combination treatments retarded prostate cancer cell proliferation and may show promise as a therapeutic agent to abrogate EMT and prostate cancer metastasis in the future. Supported by grants P20MD002285-01 & G12RR003062-22.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3384. doi:10.1158/1538-7445.AM2011-3384
Abstract 3394: A gamma secretase inhibitor reduces large neurosphere formation in glioma cell lines which correlates with decreased tumorigenicity
Authors: Lopez-Molina Javier , Rao Sudhir , Angagaw Minilik , Wexler Roseanne , Cristescu Razvan , Demuth Tim , Sun Hong , Toniatti Carlo 
Published: June 2012

Abstract
Notch signaling regulates many aspects of development, cell fate and tissue renewal. Recent work has implicated the pathway in regulating and maintaining tumor initiating cells. Phase 1 clinical trial results have recently shown responses in patients with brain tumors. The objective of the current study is to evaluate the effect of a potent and specific gamma-secretase inhibitor (GSI, MRK-003) on the growth of a neurosphere stem cell-like population from glioblastoma cell lines. Our studies demonstrate glioma cell lines grown in serum-free neurosphere culture conditions have 10-40 fold higher expression of Notch pathway direct target genes Hes5, Hey1 and Hey 2, as compared to their expression in standard 2D serum-cultured cells. Using a novel imaging based readout with the Isocyte platform, we have collected multiple neurosphere colony parameters, such as colony size, colony number, colony shape, frequency and fluorescence intensity, before and after drug treatment. In vitro GSI treatment of U251 neurospheres as compared to DMSO and inactive enantiomer controls yields a 5 fold reduction in the number of large colonies with a correlated increase in the number of small colonies, suggesting a cytostatic effect. This effect translates into a 40 day delay in tumor formation and a 5 fold decrease in tumor volume after subcutaneous injection of 5-day GSI pre-treated neurospheres (p-value&lt;0.0001, 1way-ANOVA). This data suggests that GSI inhibits the growth of tumor initiating cells that are present in neurosphere culture and that this change is specifically mediated by the Notch pathway. Furthermore, this imaging based assay will allow for the validation of Notch pathway related gene signatures for their ability to predict response to GSI in this cancer context.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3394. doi:10.1158/1538-7445.AM2011-3394
Abstract 34: Microenvironmental independence or co-option: How tumour-stromal interactions influence prostate cancer lethal outcomes
Authors: Basanta David , Hashim Arig Ibrahim , Gillies Robert J. , Gatenby Robert A. , Ayala Gustavo E. , Hayward Simon W. , Anderson Alexander RA 
Published: June 2012

Abstract
The role of the tumour-microenvironment interactions in tumor progression has been the extensively studied in the last few years. Recently, the key role that stromal interactions in both cancer initiation and progression has become an important focus. Both of these interactions, cell-cell and cell-microenvironment, can fundamentally affect the outcome of tumour progression. In prostate cancer this is particularly true, with the tumour microenvironment being an independent predictor of patient prognosis. There are two main lethal outcomes for prostate cancer:
(i) early in its genesis the tumour acquires a highly malignant lethal phenotype, growing rapidly and displacing the original stromal population. These less common aggressive tumours are independent of much of the local microenvironment.
(ii) the tumour co-opts the local stroma taking on a classic stromagenic phenotype where the local microenvironment facilitates cancer growth.
Using an integrated approach we have investigated the influence of tumour stroma interactions in driving these outcomes. With the help of a mathematical model based on evolutionary game theory, we considered three distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources (such as growth factors, nutrients and space) but can also co-opt stroma. The results from this mathematical model highlight the importance of carcinoma associated fibroblasts in stromagenic outcomes and that the resulting cooperation between certain stromal cells and the tumour could be disrupted as a result of changes in the microenvironment leading to a stromal independent outcome. Subsequently we have employed a biological model using TRAMP mice (TRansgenic Adenocarcinoma of the Mouse Prostate). TRAMP mice develop prostate cancer spontaneously after a few weeks and recapitulate many features of prostate cancer in humans. This mouse model allowed us to investigate the differences between the tumour populations driving the two distinct outcomes as well as the importance of microenvironmental changes in diverting this progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 34. doi:10.1158/1538-7445.AM2011-34
Abstract 340: Predictive value of KRAS mutations in advanced non-small cell lung cancer (NSCLC) patients (pts) treated with chemotherapy (CT)
Authors: Dingemans Anne-Marie C. , Smit Egbert F. , Derks Jules , Mellema Wouter , Heideman Danielle , Van Suylen Robertjan , Thunnissen Erik 
Published: June 2012

Abstract
Introduction: KRAS mutation is thought to be related with poor outcome of NSCLC pts. The predictive value of KRAS mutation for response to chemotherapy (CT) has not been established
Patients and methods: From a retrospective database from 2 university hospitals all pts with advanced NSCLC treated with palliative platinum containing chemotherapy were selected. Pts were included when archive tumor tissue was available for DNA extraction. High resolution melting followed by PCR sequencing was performed for KRAS exon1 and 2.
Results: KRAS mutation analysis was evaluable for 122 pts. All pts had advanced NSCLC and were no candidate for treatment with curative intent. Mean age 61 years (range 24-80 years), 81 males and 41 females. All pts received platinum-containing CT. Response was evaluable for 110 pts: 1 complete response, 21 partial response, 54 stable disease and 54 progressive disease. Median progression free survival (PFS) was 5.7 months (m) (95% CI 4.2-7.2 m), median overall survival (OS) was 7.5 m (94% CI 5.2-9.9 m). 44 pts (36%) had a KRAS mutation. 38% of pts with a KRAS mutation had as best response PD on CT, and 27% of pts without a KRAS mutation had PD, this difference was not significant. No difference in PFS and OS was observed for pts with a KRAS mutation (median PFS 5.3 m, 95% CI 3.2-7.3 m and median OS 6.2 m, 95% CI 4.8-7.3 m) and without a KRAS mutation (median PFS 6.1, 95% CI 5.0-7.2m and median OS 8.9 m, 95% CI 6.4-11.4).
Conclusion: In our series KRAS mutation was not predictive for response to platinum containing CT in pts with advanced NSCLC. Furthermore, KRAS mutation was not prognostic. Additional data on specific KRAS mutations will be presented.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 340. doi:10.1158/1538-7445.AM2011-340
Abstract 3414: EMT-associated genes are altered in giant cell tumor of bone
Authors: Rahal Paula , Babeto Erica , de Freitas Calmon Marilia , Conceição Andre , Zuccari Débora 
Published: June 2012

Abstract
The giant cell tumor of bone (GCT) is a benign bone-destructive neoplasm, with uncertain biological behavior, with features such as a large number of multinucleated giant cells and aggressive behavior. The local recurrence of GCT is often observed, especially in the first three years after treatment, giving a rate of recurrence ranging from 20% to 50% of cases. Further aggravating the recurrence, is the fact that after a relapse, patients often also presents metastasis in other organs, mainly in the lungs. In this study we investigate the expressions of epithelial and mesenchymal (EMT) markers (ADAM23, CDH1, CDH3, MMP14, p16, TIMP2 and VIM) in GCTs by quantitative qPCR. The expression of the MMP14, TIMP2 and VIM genes increased in more than 96% samples and ADAM23, CDH1, CDH3 and p16 genes had expression reduced in more than 91% of GCTs samples. Since ADAM23, CDH1, CDH3 and p16 have CpG islands in their promoter regions and low expression in tumor tissue, their methylation patterns were analyzed by MSP-PCR. For ADAM23 and p16 genes were detected a high frequency of hypermethylation. The lower expression of ADAM23 and p16 are directly related to the recurrence and metastasis in GCTs. The genes MMP14, TIMP2 and VIM are related to angiogenesis, degradation of extracellular matrix and cell migration and presented with increased expression in GCT, also confirmed by immunohistochemistry. These observations suggest that dysregulation of these genes may be a key factor responsible for the initiation and perpetuation of EMT in GCT, leading to cellular migration and malignant transformation, contributing to development of metastases and tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3414. doi:10.1158/1538-7445.AM2011-3414
Abstract 3415: Diverse roles for Snail transcription factor in epithelial-mesenchymal transition (EMT) and neuroendocrine differentiation (NED) in human prostate cancer
Authors: McKeithen Danielle , Graham Tisheeka , Morrissey Colm , Zhang Xiaotun , Chung Leland W K , Odero-Marah Valerie 
Published: June 2012

Abstract
Snail transcription factor induces epithelial-mesenchymal transition (EMT) via decreased cell adhesion-associated molecules like E-cadherin, and increased mesenchymal markers like vimentin. We previously established Snail-mediated EMT model utilizing androgen-dependent LNCaP cells. These cells express increased vimentin protein and relocalization of E-cadherin from the cell membrane to the cytosol. Interestingly, Snail transfection in LNCaP cells resulted in cells acquiring a neuroendocrine-like morphology with long neurite-like processes. We tested for expression of neuroendocrine markers neuron specific enolase (NSE) and chromogranin A (CgA) by Western blot analysis, and performed proliferation assays to test for paracrine cell proliferation. LNCaP cells transfected with Snail displayed increase in the neuroendocrine markers, NSE and CgA as well as translocation of androgen receptor to the nucleus. We found that LNCaP C-33 cells that have been previously published as a Neuroendocrine Differentiation (NED) model exhibited increased expression levels of Snail protein as compared to LNCaP parental cells. Functionally, conditioned medium from the LNCaP-Snail transfected cells increased proliferation of parental LNCaP and PC-3 cells. In addition, NED in LNCaP-C33 cells or that induced in parental LNCaP cells by serum starvation could be inhibited by knockdown of Snail with siRNA. Knockdown of NSE and CgA with siRNA abrogated Snail induced paracrine cell proliferation in parental LNCaP and PC3 cells. Immunohistochemical staining of prostate cancer patient tissue revealed increased expression of Snail with prostate cancer progression and bone metastasis. Higher Snail staining was observed in primary prostate cancer tissue containing a neuroendocrine component (identified by CgA staining) as compared to primary cancer with no neuroendocrine differentiation. However, in metastatic tissue, Snail was highly expressed in both neuroendocrine and non-neuroendocrine cancer tissue. Overall our data provide evidence that Snail transcription factor may promote tumor aggressiveness in the prostate cancer cells through multiple processes; induction of EMT may be required to promote migration, while NED may promote tumor proliferation by a paracrine mechanism. Therefore, therapeutic targeting of Snail may prove beneficial in not only abrogating EMT but also NED.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3415. doi:10.1158/1538-7445.AM2011-3415
Abstract 3425: Interleukin-27 inhibits epithelial mesenchymal transition in lung carcinogenesis
Authors: Lee Jay M. , Zhang Ling , Kachroo Puja , Cui Xiaoyan , Hazra Saswati , Walser Tonya C. , Minna John D. , Sharma Sherven , Dubinett Steven M. 
Published: June 2012

Abstract
Interleukin-27 (IL-27), the newest member of the IL-6/IL-12 family, is secreted by antigen presenting cells and has anti-tumor activity through its activation of the JAK-STAT pathway. Transcriptional factors STAT1 and STAT3 have been implicated in the balance of tumor suppressor and oncogenic functions. Epithelial mesenchymal transition (EMT) is a process whereby cells undergo changes from a highly polarized epithelial phenotype to a mesenchymal, migratory phenotype, which plays an important role in tumor metastasis. The role of IL-27 in EMT was evaluated in lung carcinogenesis. Human bronchial epithelial cells (HBECs), genetically modified HBEC to over-express Snail and K-ras (HBEC-Snail, HBEC-K-ras), and non-small cell lung cancer (NSCLC) lines (A549, H2122) were treated with IL-27 at multiple time points. Phosphorylation of STAT1 and STAT3 measured by Western Blot demonstrated activation of both pathways in these cell lines treated with IL-27. However, the STAT1 pathway was attenuated in HBEC-K-ras cells exposed to IL-27. Western analysis of markers for epithelial to mesenchymal transition (EMT) (E-cadherin, γ-catenin, N-cadherin, Vimentin, and Snail) showed up-regulation of E-cadherin and γ-catenin, important for the epithelial phenotype, which peaked 8 hours after IL-27 exposure, while markers important for the mesenchymal phenotype (N-cadherin, Vimentin, and Snail) were all down-regulated at similar time points. The addition of a STAT3 inhibitor to IL-27 treatment led to continued down-regulation of Vimentin beyond 8 hours. A wound healing functional assay to study cell migration after IL-27 treatment of cancer cell lines for up to 48 hours, demonstrated overall decrease in cell migration. In summary, IL-27 inhibits epithelial mesenchymal transition in NSCLCs and oncogenically manipulated HBECs through the regulation of STAT1 and STAT3 pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3425. doi:10.1158/1538-7445.AM2011-3425
Abstract 3429: Mesenchymal hepatocellular carcinoma cells acquire cancer stem cell characteristics through Snail1
Authors: Dang Hien , Ding Wei , You Hanning , Emerson Dow , Rountree Carl B. 
Published: June 2012

Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality and the incidence of HCC is rising in the United States. Cancer stem cells (CSCs) are a subset of neoplastic cells that possess distinct survival mechanisms and plasticity crucial for tumor maintenance and propagation. The induction of epithelial-mesenchymal-transition (EMT) by Transforming Growth Factor-β (TGF-β) has been linked to the acquisition of CSC characteristics in breast cancer. In patients with HCC, either a CSC or EMT phenotype correlates with a worse prognosis. In this report, we aim to link EMT to CSCs and to further elucidate the mechanism by which cells acquire CSC characteristics during EMT. We utilized human (Huh7, MHCC97-L) and murine (P2E, P2M; Ding et al Hepatology. 2010) liver cancer cell lines, and analysis included gene and protein expression, FACS, migration and invasion assays, and chemotherapy resistance assay. Human mesenchymal MHCC97 cells demonstrate decreased E-cadherin, increased Snail1, and enhanced migration and invasion compared to epithelial Huh7 cells. MHCC97 cells demonstrate significant upregulation of stem cell markers (Oct4, Nanog, BMI-1, and CD44; p&lt;0.01), increased CD44high population (95% vs. 2% Huh7, p&lt;0.01), resistance to chemotherapy, resistance to TRAIL-induced apoptosis, increased tumor-sphere formation and slower cell cycle compared to epithelial Huh7 cells. We recently reported EMT in murine epithelial liver cell lines, P2E and P2M (post EMT). Mesenchymal P2M cells demonstrate loss of E-cadherin, gain of Snail1, increased tumor-sphere formation, and increased expression of stem cell markers (Nanog, Oct4, CD44, and EpCam; p&lt;0.001). As TGF-β induces EMT through Snail1, we hypothesize that Snail1 signaling plays a role in the induction of an EMT and CSC phenotype in HCC. TGF-β treatment, epithelial P2E cells demonstrate fibroblastic-like morphology, 14-fold increase in Snail1 (p&lt;0.01) and 8 fold increase in Nanog expression (p&lt;0.01), increased tumor-sphere formation and migration. siRNA knockdown of Snail1 in mesenchymal P2M cells resulted in significant decrease in EMT and CSC characteristics, with decreased tumor-sphere formation, decreased migration, and decreased stem cell gene expression (Nanog and CD44, p&lt;0.01). In conclusion, both murine and human mesenchymal HCC cells possess multiple CSC characteristics compared to epithelial counterparts. The transient knockdown of Snail1 in mesenchymal HCC cells results in the reversal of EMT as well as loss of CSC characteristics. We propose that Snail1 may play an important role in the regulation of EMT and CSC phenotypes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3429. doi:10.1158/1538-7445.AM2011-3429