bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1436: TNF-alpha-dependent tumor reprogramming and promotion by microenvironment: Potential involvement of endothelial cells.
Authors: Khodarev Nikolai N. , Pitroda Sean P. , Weichselbaum Ralph R. 
Published: August 2014

Abstract
Interactions of tumor clones with the host microenvironment have profound effects on tumor growth, response to radio/chemotherapy and formation of metastases. TNFα is a potent factor driving and orchestrating such interactions. We used mice with disrupted TNFα receptor I/II signaling to investigate phenotypic and genomic changes induced in tumors by TNFα-deficient or wild type (WT) host microenvironment. At the basal level, disruption of host stromal TNFα signaling resulted in the over-expression of tumor genes involved in extracellular matrix remodeling and angiogenesis. Phenotypically, these tumors exhibited a reduced vascular density, which induced the expression of oxidative stress signaling pathways and increased levels of tissue hypoxia and necrosis. These alterations were paralleled by the suppression of genes involved in chromosomal stability and key effectors of the ATM-dependent/ non-homologous end-joining pathways, which resulted in greater DNA double-strand breaks and caspase 3 activation following IR treatment. We further investigated tumor-associated endothelial cells (TAEC) obtained from tumors grown in WT and TNFα RI/II-/- animals. Differentially expressed genes (DEGs) primarily represented TNFα/Type I IFN-signaling. These genes significantly separated cohorts of patients with chronic inflammation (RA, IBD and liver cirrhosis) from normal samples. We trained these genes in human cancer datasets and defined a six-gene inflammatory signature that predicted significantly reduced overall survival in breast cancer, colon cancer, lung cancer, and glioma. Consistent with these findings, conditioned culture media from human endothelial cells stimulated by pro-inflammatory cytokines accelerated the growth of human colon and breast tumors in immunodeficient mice as compared with conditioned media from untreated endothelial cells. Based on these studies we came to two important conclusions. First, the host stroma may determine phenotypic and transcriptomic properties of tumor cells, and TNFα might be an important component of such microenvironment-dependent tumor reprogramming (MDTR). Second, endothelial cells may be an important cellular component of MDTR and tumor promotion.
Citation Format: Nikolai N. Khodarev, Sean P. Pitroda, Ralph R. Weichselbaum. TNF-alpha-dependent tumor reprogramming and promotion by microenvironment: Potential involvement of endothelial 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 1436. doi:10.1158/1538-7445.AM2013-1436
Abstract 1468: Circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) from patients with small cell lung cancer (SCLC) show heterogeneity in epithelial to mesenchymal transition (EMT) phenotype and evidence of vasculogenic mimicry (VM).
Authors: Metcalf Robert , Booth Jessica , Swain Rajeeb , Bagley Steven , Morris Karen , Krebs Matthew , Hughes Andrew , Brady Gerard , Blackhall Fiona , Dive Caroline 
Published: August 2014

Abstract
Background: Circulating tumour cells (CTCs) and circulating tumour microemboli (CTM) are prevalent in patients with aggressive small cell lung cancer (SCLC). Heterogeneity in epithelial and mesenchymal phenotypes in CTCs and within CTM was investigated given evidence in preclinical models of epithelial and mesenchymal cell co-operativity advantageous for hematogenous spread and the role of epithelial to mesenchymal transition (EMT) in invasion and metastasis.
Methods: Four colour immunofluorescence assays were developed and applied to tumour cells enriched by filtration from peripheral blood of extensive stage SCLC patients prior to treatment. CTCs/CTM were assessed for expression of cytokeratins (CKs, epithelial marker) and vimentin (mesenchymal marker) with DAPI stained nuclei and negative selection of leukocytes and circulating endothelial cells (CECs) by CD45 and/or vascular endothelial-cadherin (VE-cadherin, CD144) expression respectively.
Results and Conclusions: CTCs were identified in all patients that expressed epithelial and/or mesenchymal markers. Individual CTM were detected comprised of tumour cells of heterogeneous EMT status and CTM were also observed containing leukocytes and/or CECs. There was substantial heterogeneity in CK and vimentin expression in CTCs and within CTM consistent with EMT plasticity and with co-operativity between epithelial and mesenchymal tumour cells. A subpopulation of CTCs co-expressed CKs and VE-cadherin that intriguingly, raises the possibility that vascular mimicry accompanies and may facilitate hematogenous spread in this aggressive tumor type. Further studies are required to explore this new hypothesis.
Citation Format: Robert Metcalf, Jessica Booth, Rajeeb Swain, Steven Bagley, Karen Morris, Matthew Krebs, Andrew Hughes, Gerard Brady, Fiona Blackhall, Caroline Dive. Circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) from patients with small cell lung cancer (SCLC) show heterogeneity in epithelial to mesenchymal transition (EMT) phenotype and evidence of vasculogenic mimicry (VM). [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 1468. doi:10.1158/1538-7445.AM2013-1468
Abstract 1478: The role of ERBIN in suppressing migration in colon cancer.
Authors: Stevens Payton D. , Yang Mike , Gao Tianyan 
Published: August 2014

Abstract
The LAP (leucine-rich repeat (LRR) and PDZ domain) family protein, ERBIN, is basolaterally localized protein that has previously been identified as a regulator of epithelial cell polarity and an ERBB2/HER2 binding protein. In addition, ERBIN inhibits RAF activation by disrupting by the RAS/RAF interaction. However, the functional importance of ERBIN in cancer remains elusive. In this study, we examined the role of ERBIN in regulating colon cancer progression and metastasis. Stable colon cancer cell lines, including SW480, LIM2405, and Caco2, were generated using lentiviral shRNA to deplete endogenous ERBIN expression. Our results showed that knockdown of ERBIN induced epithelial-mesenchymal transition (EMT)-like phenotype as marked by spindle-like morphology, a decrease in E-cadherin and an increase in vimentin expression. Moreover, the overall rate of cell migration was significantly increased in ERBIN knockdown cells as determined using Transwell assays. When tracking the movement of individual cells using live cell imaging, we found that ERBIN knockdown cells were considerably more motile with faster migrating speed when compared to control cells. Mechanistically, knockdown of ERBIN expression resulted in an increase in both Akt and ERK signaling activation. Taken together, we have identified a novel role of ERBIN in suppressing EMT and cell motility in colon cancer cells.
Citation Format: Payton D. Stevens, Mike Yang, Tianyan Gao. The role of ERBIN in suppressing migration in colon 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 1478. doi:10.1158/1538-7445.AM2013-1478
Abstract 1482: Caveolin is related to progression of malignant transformation in patients with breast tumors.
Authors: Bostanci Hasan , Sahin Tevfik Tolga , Dikmen Kursat , Albayrak Aynur , Yildirim Volkan , Kargici Hulagu 
Published: August 2014

Abstract
Aim: Caveolin seems to be an important factor in tumorigenesis and progression. It has a dual role in both tumor suppression and progression. The proponents of tumor suppression suggest that caveolin is the major protein of the cavea in the cells and these regions accumulate the growth stimulatory signals from certain growth factors such as epidermal growth factor family. Locus of caveolin gene on chromosome 7 is closely related to other tumor suppressor genes. Proponents of the oncogenic role state that caveolin is highly expressed in cancer tissues such as prostate, lung, and renal cell carcinoma when compared to normal counterparts. This type of expression in breast cancers has been ill defined in previous studies. We designed a detailed study in order to evaluate the expression of caveolin in breast cancers and investigation of its possible use as target of specific cancer therapy. The initial phase of the study consists of evaluation of caveolin in patients with benign and malignant breast disease with respect to normal controls. Here we present our preliminary results of the first phase of the study.
Materials and methods: Breast tissue from 202 benign breast tumors, 98 breast cancers and 20 normal controls (obtained from reduction mammoplasties with informed consent) in our center. Caveolin was evaluated by immunohistochemistry.
Results: Caveolin distribution was higher in malignant tissues when compared to control tissues and benign tumors. Furthermore caveolin antigen distribution was enhanced with more aggressive tumor behavior. We observed enhanced caveolin expression especially in myoepithelial cells. The benign tumors expressed higher caveolin when compared to normal controls. In both benign and malignant breast tumors the caveolin expression increased with stromal content of the tumor.
Conclusion: Tumor microenvironment influences the tumor tissue interms of proliferation and metastasis. Caveolin seems to be expressed in the stromal component of the tumor and seems to have increased expression with aggressive nature of the tumor. Results of this preliminary study suggests that caveolin plays a determinative role in tumorigenesis in breast cancer and furthermore correlates with the aggressiveness of the tumor. Caveolin may exert its oncogenic effects by promoting epithelial to mesenchymal transition. Therefore targeting caveolin may be logical strategy in breast cancer treatment.
Citation Format: Hasan Bostanci, Tevfik Tolga Sahin, Kursat Dikmen, Aynur Albayrak, Volkan Yildirim, Hulagu Kargici. Caveolin is related to progression of malignant transformation in patients with breast tumors. [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 1482. doi:10.1158/1538-7445.AM2013-1482
Abstract 1483: Bmi1 is required for Twist1-mediated breast cancer cell invasion.
Authors: Lin Yu-Huey , Jing Guihua , Liu Junjun 
Published: August 2014

Abstract
Metastasis is the spread of cancer cells from the site of primary tumors to distant organs and the establishment of secondary tumors there. It is a multistep process, and the initial step is cancer cell invasion during which cancer cells move into tissues surrounding the tumor and the vasculature. Transcription factor Twist1 has been identified as a key regulator of metastasis in a murine breast tumor model as suppression of Twist1 expression in metastatic mammary carcinoma cells specifically inhibits their ability to metastasize, and overexpression of Twist1 induces cell motility and promotes an epithelial-mesenchymal transition (EMT). Previous studies have shown that Twist1 works together with polycomb group protein Bmi1 to promote EMT. Here we show that in breast cancer cells, Bmi1 acts downstream of Twist1 to promote the cancer cell invasion. Suppression of Bmi1 in breast cancer cells expressing high level Twist1 reduces cell motility, and ectopic expression of Bmi1 in Twist1-knockdown cells promote cell invasion. The results delineate a novel pathway that leads to cancer cell invasion and metastasis, which may benefit the development of novel therapeutic approaches to treat advanced breast cancer.
Citation Format: Yu-Huey Lin, Guihua Jing, Junjun Liu. Bmi1 is required for Twist1-mediated breast cancer cell invasion. [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 1483. doi:10.1158/1538-7445.AM2013-1483
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1486: Role of Slug in chemoresistance, invasion and metastasis of CD133-expressing pancreatic cancer.
Authors: Tsukasa Koichirou , Ding Qiang , Yoshimitsu Makoto , Miyazaki Yumi , Obara Toru , Matsubara Shyuichiro , Maeda Koki , Takao Sonshin 
Published: August 2014

Abstract
Background: Pancreatic cancer is a devastating disease despite current development of therapy. Accumulating evidence suggests that cancer stem cells (CSCs) are responsible for recurrence and chemoresistance. CD133, a marker of CSCs in various solid tumors including pancreatic cancer, has been studied for recent decade. However, the role of CD133 is still obscure. Epithelial-mesenchymal transition (EMT), which is the essential process in the wound healing, development and cancer progression, is one of the CSC characteristics. However, the role of EMT in the pancreatic cancer progression is not sufficiently elucidated. Slug is a member of the Snail family of zinc finger transcription factors and plays a role in the EMT. Slug is demonstrated to be overexpressed in numerous cancers, and involved in migration and tumorigenesis. Recent study demonstrated that EMT was directly suppressed by downregulation of the transcription of Slug (Chakrabarti et al, Nat Cell Biol, 2012). In this study, we investigated the relationship between Slug and biological properties in pancreatic cancer cells.
Materials and Methods: We established a highly migratory cell population with endogenous CD133high derived from Capan-1 cells by migration assay system. Over 90% of CD133high cells expressed CD133 by flow cytometer. Consequently, we established CD133knock-down and Slugknock-down by lentiviral transduction method. We used gemcitabine (GEM) for chemosensitivity assay. To examine the role of Slug, we used migration and invasion assay, wound healing assay, DNA microarray, real-time RT-PCR and Western blot.
Results: 1) DNA microarray and real-time RT-PCR revealed higher expression of EMT-related genes, such as Slug and N-cadherin, in CD133high cells compared to CD133knock-down cells, suggesting that CD133knock-down related to downregulation of Slug. 2) Slugknock-down cells showed more sensitive to GEM by MTT assay compared to parental cells (CD133high cells), but no change of CD133 expression. 3) Slugknock-down cells showed less migratory and invasive abilities than CD133high cells. 4) CD133high cells showed more in vivo metastasis compared to CD133knock-down cells using immunodeficient mice. In vivo experiment using Slugknock-down cells is now ongoing.
Conclusion: Our results suggest that Slug plays an important role in chemoresistance, invasion and metastasis.
Citation Format: Koichirou Tsukasa, Qiang Ding, Makoto Yoshimitsu, Yumi Miyazaki, Toru Obara, Shyuichiro Matsubara, Koki Maeda, Sonshin Takao. Role of Slug in chemoresistance, invasion and metastasis of CD133-expressing pancreatic 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 1486. doi:10.1158/1538-7445.AM2013-1486
Abstract 1492: Systems analysis of epithelial-mesenchymal transition and cell invasion identifies functional gene signatures predictive of survival in lung cancer.
Authors: Schliekelman Mark J. , Taguchi Ayumu , Zhu Jun , Dai Xudong , Zhang Qing , Chin Alice , Wong Chee-Hong , Wang Hong , Gazdar Adi , Laird-Offringa Ite , Tewari Muneesh , Thiery Jean Paul , Hanash Samir 
Published: August 2014

Abstract
We have implemented a systems approach to identify molecular features associated with mesenchymal or epithelial phenotypes and cell behavior in 38 lung adenocarcinoma cell lines that encompassed common known genomic alterations that drive the development of lung adenocarcinoma. Cell line characterization based on morphology, invasiveness, motility and cell-cell adhesion was integrated with proteomic, gene expression, microRNA and methylation profiles. Signatures were established from differential expression of transcripts and proteins in subsets of cell lines with mesenchymal and epithelial characteristics as well as high or low invasion and motility. The mesenchymal, invasion and migration signatures had common upregulation of genes or proteins related to cytoskeletal and actin-binding proteins. Sets of 148 and 74 transcripts corresponding to proteins that were overexpressed in mesenchymal cell lines and high invasive cell lines, respectively, were highly predictive of survival in three independent lung adenocarcinoma datasets. Subsets of 39 and 21 transcripts corresponding to cytoskeletal and acting binding proteins in the mesenchymal and invasive signatures were found to also predict survival in the three independent lung adenocarcinoma datasets, pointing to an association between cytoskeletal and actin binding proteins, a mesenchymal phenotype and tumor progression in lung adenocarcinoma.
Citation Format: Mark J. Schliekelman, Ayumu Taguchi, Jun Zhu, Xudong Dai, Qing Zhang, Alice Chin, Chee-Hong Wong, Hong Wang, Adi Gazdar, Ite Laird-Offringa, Muneesh Tewari, Jean Paul Thiery, Samir Hanash. Systems analysis of epithelial-mesenchymal transition and cell invasion identifies functional gene signatures predictive of survival in lung 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 1492. doi:10.1158/1538-7445.AM2013-1492
Abstract 1510: Different change of LEF1/TCFs family members in colorectal carcinogenesis.
Authors: Han Wenxiao , Cao Bangrong , Wang Hongying 
Published: August 2014

Abstract
Wnt/β-catenin pathway is activated in many cancers, especially colorectal carcinoma (CRC). LEF1/TCFs family, which includes LEF1, TCF7(TCF1), TCF7L1(TCF3) and TCF7L2(TCF4), are required for β-catenin-induced transcription of target genes which are widely involved in the carcinogenesis. The aims of our study were to investigate the change of the members of LEF1/TCFs family in chronic inflammation associated colorectal carcinogenesis and the possible roles in carcinogenesis. Chronic inflammation-associated CRC was induced with the AOM-DSS mouse model. Gene expression array experiment was performed with the colonic tissue samples which were collected at different time points during the carcinogenesis. Data analysis strongly indicated that Wnt/β-catenin pathway was activated in chronic inflammation-related colorectal carcinogenesis. However, the members of LEF1/TCFs family showed different changes. The mRNA levels of LEF1 and TCF1 increased while the mRNA levels of TCF3 and TCF4 decreased with the formation of CRC, which were confirmed with real-time PCR. Although some of Wnt target genes were significantly up-regulated, such as MMP7 and Axin2, some were down-regulated, such as Nrcam. Most importantly, the members of LEF1/TCFs family showed the same expression profile in the human samples from normal colon, low grade adenoma, high grade adenoma and CRC. But the mRNA levels of the members were not correlated with the grade of CRC. Moreover, almost all of the target genes up-regulated in AOM-DSS model also increased in human CRC. Finally, prognosis analysis showed that up-regulation of LEF1, TCF1 and corresponding target genes were correlated with higher survival rate (p=0.0068). TCF3, TCF4 and the target genes down-regulated in AOM-DSS model were correlated with disease-free survival rate (p=0.03). Taken together, the members of LEF1/TCFs family changed differently in CRC independent of the status of inflammation. Members of LEF1/TCFs family combined with target genes may be potential prognostic biomarkers for CRC.
Citation Format: Wenxiao Han, Bangrong Cao, Hongying Wang. Different change of LEF1/TCFs family members in colorectal carcinogenesis. [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 1510. doi:10.1158/1538-7445.AM2013-1510
Abstract 1512: Role of Epstein-Barr virus in nasopharyngeal carcinoma under metabolic stress.
Authors: Lau VMY , Tsao SW 
Published: August 2014

Abstract
Most nasopharyngeal carcinoma (NPC) biopsies contain a human pathogen named as Epstein-Barr virus (EBV). EBV infection is considered as an early event involved in the pathogenesis of NPC. However, the close association of EBV with NPC is a paradox. EBV infection is common that occurs in ≥95% of the world's population, yet the incidence rate of NPC is rare worldwide and is only seen in Cantonese speaking ethnic groups in Southern Asia. The mechanisms that regulate EBV infection of NPC/pre-malignant NP cells including the events involved in latency and lytic activation (either in vitro or in vivo) are not well-defined. Expressions of latent and lytic EBV genes have been shown to have variable effects on the biology and malignant properties of EBV-infected cells. Hypoxia and nutrient-starvation are common physiological stresses within tumours and may have impact on regulation of latent and lytic EBV infection in NPC cells.
Here we report that the levels of hypoxia-inducible factor, HIF-1α protein, a prime hypoxic-stress responsive marker for mammalian cells, are higher in EBV-infected NPC/pre-malignant NP cell lines under hypoxia than their non-infected counterparts, which may imply an enhanced survival ability of EBV-infected NP cells. The alteration in gene expression profiles of host cells and expression of EBV genes observed in infected cells may be responsible for the stabilization of HIF-1α and vice versa. Moreover, EBV infection enhances the tumour growth rate and size of NPC cells xenografts in nude mice. The main stem of this study is to examine whether there is a differential response between EBV-infected and non-infected NP cells towards various metabolic stresses. Through studying this project, the mechanism and function of HIF-1α stability by EBV infection will be explored, which is expected to help characterizing the role of EBV in transformation of epithelial cells and how EBV infection may enhance NPC cells to survive inside a tumour core.
Citation Format: VMY Lau, SW Tsao. Role of Epstein-Barr virus in nasopharyngeal carcinoma under metabolic stress. [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 1512. doi:10.1158/1538-7445.AM2013-1512
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.