bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2250: Aberrant leukocyte infiltration as a trigger for tumor metastasis
Authors: Hsiao Yi-Hsuan , Man Yan-Gao 
Published: February 2011

Abstract
Our previous studies have led to a novel hypothesis that aberrant leukocyte infiltration is a trigger for tumor invasion. Our hypothesis and supporting data have been published in multiple peer-reviewed journals. Our current studies attempted to further expand our previous observations, and to test a novel hypothesis that aberrant leukocyte infiltration may also represent a trigger for tumor metastasis. Tissue sections from human breast, prostate, cervical, and lung tumors were analyzed with multidisciplinary approaches with a panel of tumor metastasis-related biomarkers. Our study revealed that pre-invasive tumors surrounded by or immediately adjacent to leukocyte aggregates displayed a number of unique features: [1] significantly reduced expression of cell surface adhesion molecules, [2] significantly elevated blood vessels and lymphatic ducts at the intersection between the tumor core and leukocyte aggregates, [3] the presence of isolated individual tumor cells or cell clusters within the leukocyte aggregates, [4] physical attachment or fusion of tumor cell membrane and condensed chromosomes of mitotic tumor cells with leukocytes, and [5] the presence of co-joined tumor cells and leukocytes within vascular structures or lymphatic ducts. Together, our findings suggest that leukocyte infiltration may trigger tumor metastasis through three correlated mechanisms: (1) to physically disrupt the inter-cellular junctions and cell surface adhesion molecules, [2] to interfere with the mitotic process or physically drag tumor cells to different sites during their migration, and [3] to stimulate growth of vascular structures that facilitate tumor metastasis.
(Supported in part by grants DAMD17-01-1-0129, DAMD17-01-1-0130, PC051308 from Congressionally Directed Medical Research Programs, grant BCTR0706983 from The Susan G. Komen Breast Cancer Foundation, and grant 2008-02 from The US Military Cancer Institute and Henry M. Jackson Foundation to Dr. Yan-gao Man, and by grant 2006CB910505 from The Ministry of Chinese Science and Technology Department to Drs. Xichen Zhang and Yan-gao Man).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2250.
Abstract 2253: Proteases and cytokines in the transition from preinvasive DCIS to invasive breast carcinoma
Authors: Sameni Mansoureh , Anbalagan Arulselvi , Sloane Bonnie F. 
Published: February 2011

Abstract
The transition from preinvasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) involves alterations in proteolytic pathways of both epithelial and stromal cells. Infiltration of macrophages, angiogenesis and secretion of chemotactic molecules by DCIS and surrounding stromal cells also facilitate this transition. We have developed a 3D coculture model, MAME (mammary architecture and microenvironment engineering), to study the role of proteases and cytokines in the progression from pre-invasive DCIS to IDC. MAME-A recapitulates the architecture of normal human breast tissue with the epithelial and stromal components growing in overlays of basement membrane and stromal collagen, respectively. In MAME-B, the stromal collagen is eliminated.
The cells used in our studies were human MCF10.DCIS cells, WS-12Ti human breast tumor-associated fibroblasts, U937 human monocytes and human umbilical vein endothelial cells (HUVEC). We analyzed proteolysis through live cell imaging of the degradation of quenched fluorescent matrix proteins [DQ-collagen I™ mixed with collagen I and DQ-collagen IV™ mixed with reconstituted basement membrane (rBM)].
DCIS cells in MAME-A cocultures with fibroblasts exhibited invasiveness at 24 days, yet at only 16 days in MAME-B cocultures. Expression and secretion of cytokines, especially IL-6, were elevated in these cocultures. The invasiveness of the DCIS cells in the cocultures with fibroblasts could be reduced by addition of neutralizing antibody to IL-6. Addition of either monocytes or endothelial cells reduced the time at which invasiveness occurred to as early as 4 days in MAME-B cocultures. Addition of monocytes increased secretion of monocyte chemoattractant protein-1 (MCP-1), IL-8 and GRO. The combination of a neutralizing antibody to hMCP-1 and a receptor-blocking antibody to hCXCR2 (a receptor for IL-8 and GRO) reduced invasiveness more effectively than did either of the antibodies used alone. When HUVEC were grown in MAME-B cocultures with DCIS or DCIS and fibroblasts, the HUVEC grew into a network of tubules with distinct lumens over a period of 4 days. In 3D and 4D reconstructions of these same cocultures, DCIS cells could be seen to migrate toward the HUVEC tubules and invade into their lumens. These phenomena occurred in parallel with increases in proteolysis and in expression and secretion of the cytokines MCP-1, IL-8, RANTES and GRO.
The MAME models provide a system for the study of proteolytic and cytokine pathways and the interactions between these pathways that are associated with the transition from DCIS to invasive ductal carcinoma. This model could be used as an in vitro tool for screening drugs that target these pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2253.
Abstract 226: Aspirin alone or in combination with doxorubicin induced efficient apoptosis in human hepatocellular carcinoma cells
Authors: Hossain Mohammad Akbar , Kim Min Young , Kim Dong Hwan , Kim Jin-Ah , Kang Yong Jung , Moon Jeon Ok , Kim Gi Young , Choi Yung Hyun , Kim Nam Deuk 
Published: February 2011

Abstract
Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is refractory to most anticancer drugs. Doxorubicin offers a survival benefit to patients with intermediate hepatocellular carcinoma. However, the favorable therapeutic response to doxorubicin is often associated with severe toxicity. The present research was aimed at developing a strategy of increasing doxorubicin sensitivity so that lower doses may be used without compromising efficacy. Recently, aspirin (ASA) and some other nonsteroidal anti-inflammatory drugs (NSAIDs) have drawn much attention for their protective effects against colon cancer and cardiovascular disease. Several studies also found that regular ASA use is significantly associated with reduced risk of lung cancer. We investigated the effects of ASA on HepG2 human hepatocellular carcinoma cell line. Growth inhibition effect of aspirin was measured by MTT assay. Flow cytometry analysis revealed that aspirin can induce G2/M phase arrest which we observed by the level of cell cycle regulatory proteins and DNA ladder formation indicates apoptosis dose dependently. We found that ASA treatment followed both extrinsic and intrinsic pathways for apoptosis induction. In addition to this, when administered in combination, doxorubicin (DOX) and ASA produced synergistic effect in growth inhibition in human hepatocellular carcinoma cells and induced apoptosis in caspase-dependent pathway. Therefore, clinically achievable concentrations of DOX and ASA used in combination may produce a strong anticancer synergy that warrants investigation as a therapeutic strategy to enhance the efficacy of doxorubicin for treating HCC. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 226.
Abstract 2280: Endothelin axis in bladder cancer metastasis
Authors: Said Neveen A. , Theodorescu Dan 
Published: February 2011

Abstract
In bladder cancer, recurrence after surgical intervention for muscle invasive disease is problematic as nearly half of patients harbor occult distant metastases, mainly in the lungs, with poor 5-year survival rate. Our prior work has indicated that RhoGDI2 reduces tumor Endothelin 1 (ET-1) secretion and this may contribute to its metastasis suppressor function, however how the endothelin axis acts to promote lung metastasis is unclear. We have found from gene expression profiling of human bladder tumors that high ET-1 expression was correlated with poor survival. Here we also identify ET-1 as a novel mediator of bidirectional cross talk between tumor cells and inflammatory macrophages. Tumor-derived endothelin, through its cognate endothelin receptor A (ETAR) exerts autocrine and paracrine effects on tumor cells and macrophages, significantly inducing its own production, by both cell types, concomitant with triggering an early inflammatory response in the lungs, which progressively increases till development of lung metastases. Abrogation of ET-1/ETAR axis by knock down tumor cell ET-1 by short hairpin RNA (shRNA) or systemic administration of ETAR blocker (ZD4054) significantly suppressed the development and the progression of this lung inflammatory response, and decreased the development of microscopic and macroscopic lung metastases, together with improvement of animal survival. In vitro, genetic manipulation of ET-1, ETAR and ETBR in bladder cancer cell lines co-cultured with macrophages revealed that ET-1 augments the inflammatory response through activation of transcriptional factors NFκB and AP-1, key orchestrators of inflammation, in both cancer cells and macrophages. The reciprocal activation of both transcriptional factors was mediated by ET-1/ETAR axis in cancer cells, whereas in macrophages it was mediated by ET-1/ETAR and ETBR axis. These findings highlight a molecular mechanism that can be pharmacologically manipulated to enhance the efficacy of current adjuvant approaches to muscle invasive bladder cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2280.
Abstract 2283: The role of insulin-like growth factor-1 and insulin like growth factor-1 receptor in obesity and oesophageal cancer
Authors: Doyle Suzanne L. , Donohoe Claire , Lysaght Joanne , Lithander Fiona , Pidgeon Graham , Reynolds John V. 
Published: February 2011

Abstract
Introduction: The insulin-like growth factor pathway, which is involved in cell proliferation, differentiation and protection against apoptosis, has been implicated in esophageal cancer progression. This study examined the role of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) as a potential mechanism linking obesity with esophageal cancer.
Methods: IGF-1R expression in esophageal squamous cell carcinoma (KYSE, OE21) and adenocarcinoma (OE19, OE33) cell lines was measured by Western analysis and the effect of IGF-1 (0.1 − 1000 ng/ml) on survival of cell lines in relation to their expression of IGF-1R was assessed by MTT assay. Circulating levels of IGF-I were measured in 50 human serum samples by ELISA and immunohistochemistry determined IGF-1R expression in human tumor sections. Results were related to tumor type, BMI and survival.
Results: Higher IGF-1R expression was observed in squamous cell carcinoma cell lines, however only adenocarcinoma cell lines showed significantly increased cell survival in response to IGF-1 (p &lt;0.001). Significantly higher circulating levels of IGF-1 were observed in patients with adenocarcinoma (p = 0.02). In resected esophageal tumor sections, no statistical difference between intensity of IGF-1R expression and BMI or survival was observed, however reduced survival was observed in patients with moderate-strong compared to weak-negative IGF-1R expression. Higher intensity IGF-1R staining was observed in the ‘immune cell rich’ leading edge of adenocarcinomas.
Conclusion: This study suggests an important role for IGF-1 in esophageal adenocarcinoma cell survival. Novel findings relating to high IGF-1R expression in the leading edge of esophageal adenocarcinoma and possible associations with obesity are also presented.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2283.
Abstract 2292: Loss of hCLCA2 promotes EMT in breast cancer
Authors: Elble Randolph C. , Walia Vijay 
Published: February 2011

Abstract
Epithelial cells acquire mesenchymal characteristics by undergoing phenotypic and genotypic changes during cancer progression. An early step in the epithelial to mesenchymal transition (EMT) is the disruption of intercellular connections due to loss of epithelial cadherins. We find that expression of tumor suppressor hCLCA2 is strongly associated with epithelial differentiation and that induction of EMT by mesenchymal transcription factors represses its expression. Moreover, we report here that knockdown of hCLCA2 by RNA interference results in disruption of cell-cell junctions by downregulating E-cadherin. This also imparts invasiveness and anoikis-resistance to epithelial cells but is insufficient to induce full EMT. However, activation of Ras oncogene in combination with hCLCA2 knockdown is sufficient to induce full EMT in vitro. These findings indicate that, like E-cadherin, hCLCA2 is required for epithelial differentiation and suggest that its loss during tumor progression contributes to metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2292.
Abstract 2296: Sorafenib inhibits hepatocyte growth factor-induced epithelial mesenchymal transition in hepatocellular carcinoma
Authors: tomoyuki nagai , Arao Tokuzo , Furuta Kazuyuki , Sakai Kazuko , Kudo Kanae , Kaneda Hiroyasu , Tamura Daisuke , Aomatsu Keiichi , Fujita Yoshihiko , Matsumoto Kazuko , Saijo Nagahiro , Kudo Masatoshi , Nishio Kazuto 
Published: February 2011

Abstract
Sorafenib is a multikinase inhibitor with activity against Raf kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor2, platelet-derived growth factor receptor. Epithelial mesenchymal transition (EMT) describes a process wherein static epithelial cells lose cell-cell contacts, acquire mesenchymal features and manifest a migratory phenotype, mediating malignant phenotypes for cancer cells. It remains unclear for involvement of Sorafenib against EMT, especially in hepatocellular carcinoma (HCC).
Hepatocyte growth factor (HGF) activated HGF/MET signaling pathway in HepG2 and Huh7 cells and resulted in cell scattering and spindle-shaped morphology, changes that are characteristic of EMT. SNAI1 is a key transcription factor known to be involved in EMT. HGF up-regulated SNAI1 and N-cadherin expression, and down-regulated E-cadherin in a dose- and time-dependent manner. Knockdown of SNAI1 by siRNA almost completely inhibited these morphological changes, indicating that SNAI1 was required for HGF-induced EMT in HCC cell lines. Similarly, Sorafenib and the MEK inhibitor U0126 markedly inhibited the HGF-induced SNAI1 expression and these morphological changes at 10 μM of concentration, whereas PI3 kinase inhibitor Wortmannin did not.
In conclusion, Sorafenib exerts a potent inhibitory activity against EMT via ERK/SNAI1 in HCC. This activity may provide an additional clinical benefit in patients with HCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2296.
Abstract 2314: Epithelial-mesenchymal transition derived cells exhibit multi-lineage differentiation potential similar to mesenchymal stem cells
Authors: Battula Venkata Lokesh , Evans Kurt , Hollier Brett G. , Shi Yuexi , Marini Frank C. , Ayyanan Ayyakkannu , Brisken Cathrin , Guerra Rudy , Andreeff Michael , Mani Sendurai A. 
Published: February 2011

Abstract
The epithelial-to-mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows stem cell traits to breast epithelial cells. Mesenchymal stem cells (MSC) have the capacity to self-renew and differentiate into multiple tissue lineages. We hypothesized that the activation of EMT by ectopic expression of Twist, Snail or TGF-β in immortalized human mammary epithelial cells (HMEC) will result in the generation of cells with a phenotype and functionality similar to MSC. We found that the EMT-derived cells not only showed similar morphology but also displayed the typical MSC phenotype i.e. CD44+, CD24− and CD45−. Alternatively, MSC expressed EMT inducing genes such as Twist, Snail and FOXC2. Interestingly, CD140b (PDGFR-β), a marker for naive MSC, was exclusively expressed in EMT-derived cells compared to their epithelial counterparts. Moreover, functional analysis revealed that EMT-derived but not the control cells differentiate into Alizarin Red S-positive mature osteoblasts, Oil Red O-positive adipocytes and Alcian Blue-positive chondrocytes similar to MSC. We also observed that EMT-derived but not control cells invade and migrate towards MDA-MB-231 tumor cells in-vitro similar to MSC, displaying the characteristic tropism of MSC for tumor cells as previously reported by us. In-vivo wound homing assays in nude mice revealed that the EMT-derived cells home to wound sites similar to MSC. In conclusion, we demonstrated that the EMT-derived cells are similar to MSC in gene-expression, multi-lineage differentiation, migration towards tumor cells and their ability to home to wounds. These results also suggest that EMT-derived MSC are active participants in cancer growth and invasion.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2314.
Abstract 2316: Epithelial to mesenchymal transition: Interplay between E-Cadherin and HGF/SF-Met signaling
Authors: Gao Chong-Feng , Haak Elizabeth A. , Su Yanli , Hudson Eric , Dykema Karl , Vande Woude George F. , Vande Woude George F. 
Published: February 2011

Abstract
During malignant progression, primary tumor cells switch from proliferative to invasive phenotypes and switch again at low frequency to form proliferating metastases. The acquisition of the invasive phenotype through epithelial-mesenchymal-transition (E-M-T) is a critical step in tumor progression, as is the mesenchymal-epithelial-transition (M-E-T) reverting to a proliferative colony or metastases. To study the mechanism(s) underlying phenotypic switching, we isolated HGF/SF-inducible invasive mesenchymal (M) and non-invasive epithelial (E) subclones from prostate and ovarian carcinoma cell lines based on three dimensional branching morphogenesis assays. We show that invasive M subclones can be generated from originally homogeneous non-invasive E subclones and phenotype switching occurs with loss of E-Cadherin and concomitant gain of Met signaling. By contrast, tumor xenograph formed by invasive M subclones partially revert to epithelial phenotype with gain of E-Cadherin and loss of HGF/SF-Met signaling, suggesting an interplay between E-Cadherin and HGF/SF-Met signaling in regulating reversible phenotypic switching. We have further studied the mechanisms regulating phenotypic switching. Our results explicate how intrinsic alteration in tumor cell properties (E-M-T) and extrinsic signals from microenvironment (HGF/SF) interact in regulating tumor phenotypic switching.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2316.
Abstract 2320: N-cadherin down-regulation has antitumor effects in esophageal cancer
Authors: Nishitani Seishi , Noma Kazuhiro , ohara Toshiaki , tanabe shunsuke , fujiwara yasuhiro , Motoki Takayuki , sakurama Kazuhumi , Takaoka Munenori , Shirakawa Yasuhiro , Yamatuji Tomoki , Matuoka Junji , Naomoto Yoshio , Haisa Minoru 
Published: February 2011

Abstract
Tumor microenviroment plays a critical role for cancer and their malignancy. Dynamic changes in tumor microenvironment have been observed in many tumors including esophageal cancer. And during the drastic change, some of tumor cells show EMT (epithelial mesenchymal transition) which means that epithelial cells lose their epithelial feature and acquire mesenchymal properties, as invasiveness and also communication with other kinds of mesenchymal cells. During those change, one of the marker of epithelial feature, E-cadherin is switch to N-cadherin, it has been known as “cadherin switch”. And it is thought that those changes have relations with cancer malignancy.
Previously we reported that esophageal cancer cells secrete TGF-b1 and activate mesenchymal fibroblasts, and those activated fibroblasts guided more endothelial cells into tumor and induced angiogenesis. In the other hand, we hypothesis cell-cell direct communication like cell-cell contact is also important role for cancer progression.
So in this report, firstly we analyze the expression of cadherins in surgical specimens in immunohistochemistry and determined expression patterns of N-cadherin in esophageal squamous cell carcinoma and Barrett's adenocarinoma. Some of those cancers showed N-cadherin expression and specifically expressed in their invasive front. Secondary we analyzed cancer cell lines as well, TE-1, TE-4, TE-10, OE19 and OE33. Those cell lines are squamous cell carcinoma cell lines and Barrett's adenocarcinoma cell lines, and those showed expression of E-cadherin and some of them showed expression of N-cadherin. And we used those cell lines and explored the behavioral differentiations of each cell lines.
Here, we report and show analysis of E- or N- cadherin expression in surgical specimens and cancer cell lines. And also we could show the potential of regulation of cadherins in esophageal cancer as a new therapeutic target, which is well recognized as one of the most aggressive malignancies in the world.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2320.