bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2413: Human glypican-3 promotes hepatocellular carcinoma progression via induction of epithelial-mesenchymal transition
Authors: Ogunwobi Olorunseun O. , Trinh Thu L. , Liu Chen 
Published: August 2012

Abstract
Hepatocellular carcinoma (HCC) is the third most important cause of cancer mortality worldwide. Epithelial-mesenchymal transition (EMT) has been shown to be an important biological process involved in the development and progression of HCC. The factors driving this process, however, are still largely unclear. Glypican-3 (GPC3) is upregulated in HCC and this is associated with poor prognosis. The details of the biological role of GPC3 in HCC are, however, yet to be fully elucidated. We hypothesized that GPC3 may promote HCC progression by inducing EMT. In this study we have examined the effect of human GPC3 in the progression of HCC using a murine HCC cell line (1MEA) derived from Balb/c mouse. We observed that the 1MEA cell line does not express GPC3 and we stably transfected human GPC3 into this cell line. 1MEA cells stably transfected with human glypican-3 (1MEAhGPC3) were then transplanted subcutaneously into 8 Balb/c mice. In comparison, wild type 1MEA was also transplanted into 8 separate Balb/c mice. Further, we performed a comparative analysis of the gene expression of E-cadherin, vimentin, collagen I, fibronectin, twist, slug and snail in both wild type 1MEA and 1MEAhGPC3. 18 days post-transplantation, tumor volume was analyzed. 5 mice transplanted with wild type 1MEA had not yet developed tumors whereas 3 mice transplanted with 1MEAhGPC3 developed tumors that had grown past the allowed tumor volume for the protocol and were sacrificed. Analysis of the remaining mice (3 transplanted with 1MEA and 5 with 1MEAhGPC3 revealed that tumors from 1MEA were 8-fold more voluminous than tumors from 1MEAhGPC3. Comparative analysis of the gene expression profile of 1MEA versus 1MEAhGPC3 revealed that transfection with hGPC3 had resulted in increased expression of mesenchymal markers (collagen I by 27.5-fold, fibronectin by 18-fold, vimentin by 3-fold), loss of epithelial marker (E-cadherin loss by 99%) and increased expression of transcriptional regulators of EMT (twist by 11.7-fold, slug by 148-fold and snail by 8.7-fold).These data clearly show that hGPC3 promotes HCC progression by inducing EMT in HCC cells. To our knowledge, this is the first experimental evidence that hGPC3's role in HCC is associated with induction of EMT and it suggests that therapeutic targeting of GPC3 in human HCC may be an effective approach to the treatment of advanced HCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2413. doi:1538-7445.AM2012-2413
Abstract 2418: NADPH Oxidase 1 over-expression enhances invasion via matrix metalloproteinase-2 and epithelial-mesenchymal transition in melanoma cells
Authors: Liu Feng , Garcia Angela , Meyskens Frank 
Published: August 2012

Abstract
Nox1 is a member of the NADPH Oxidase family which has not been well characterized in the melanocytic cell lineage. Here we demonstrated that Nox1 and Nox4 were detected in melanocytic lineage, with only Nox1 detected in normal human melanocytes and Nox4 in a subset of metastatic melanoma cell lines. The protein level and enzymatic activity of Nox1 was elevated in all melanoma cells as compared to normal melanocytes. Over-expression of GFP-Nox1 protein in Wm3211 primary melanoma cells increased invasion rate by 4-6 fold as measured by Matrigel invasion assay, while knocking down or inhibiting Nox1 decreased invasion by approximately 40 to 60%. MMP-2 was increased by Nox1 over-expression at the mRNA, protein and activity levels, and decreased by Nox1 knockdown. MMP-2 promoter activity was also regulated by Nox1 knockdown. In addition, stable clones over-expressing Nox1 exhibited an epithelial-mesenchymal transition (EMT) as examined by cell morphology and EMT markers; knockdown or inhibiting Nox1 led to a reversal of EMT. Supplementing MMP-2 to culture media did not induce EMT, suggesting that EMT induction by Nox1 was not through MMP-2 up-regulation. In summary, Nox1 was over-expressed in all melanoma cell lines examined, and enhanced cell invasion by MMP-2 up-regulation and EMT induction.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2418. doi:1538-7445.AM2012-2418
Abstract 2419: Irradiation of α-ionizing radiation to in vivo glioma model induced metastasis via occurrence of epithelial-mesenchymal transition
Authors: Park Jong Kuk , Jang Su Jin , Kang Sung Wook , Kim Jae-Sung , Park Sunhoo , Hwang Sang-Gu , Kang Joo Hyun , Um Hong Duck 
Published: August 2012

Abstract
α-Ionizing radiation (IR) therapy is known to be a one of major therapeutic tools of cancer treatment but α-IR also could be an inducer of tumorigenesis and metastasis. Metastasis is major obstacle and required to overcome for cancer treatment. Therefore, the aim of this investigation was to study whether radiation could induce metastasis our in vivo mouse system, and molecular mechanism behind α-IR-induced metastasis. C6L transfectant cell line expressing firefly luciferase (fLuc) was treated with α-IR and then immunoblotting, zymography and invasion assay in vitro. We also used C6L transfectant cell line to construct xenograft in nude mice and then IR was irradiated to xenograft with α-IR. The irradiated xenograft-containing mice were analyzed with survival curve, measurement of tumor size, and bioluminescence imaging in vivo and ex vivo. We also analyzed metastatic foci in organ of mice with RT-PCR analysis, H & E staining and immunohistochemistry. α-IR treatment to C6L cell induced ocurrence of epithelial-mesenchymal transition (EMT) and increase of cell invasion. In irradiated xenograft-containing mice, sizes of tumor were decreased dramatically and survival rate also extended. Almost all non-irradiated xenograft-containing control mice were dead within 4 weeks. But we also observed luminescence signals in about 20.9% of α-IR treated mice. Intestine or lung of luminescence signal-detected mice contained several foci, which expressed fLuc gene and presented histological features as a cancer tissue as well as expressions of EMT markers. Taken together, these findings indicate that α-IR treatment could induce metastasis in vivo via EMT including increase of MMP activity. We also propose that construction of metastasis animal model by α-IR treatment could use drug development to block cancer metastasis and increase understandings of metastasis mechanism.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2419. doi:1538-7445.AM2012-2419
Abstract 2420: Loss of hCLCA4 promotes EMT in breast cancer
Authors: Yu Yang , Walia Vijay , Elble Randolph C. 
Published: August 2012

Abstract
The epithelial to mesenchymal transition (EMT) is a developmental program in which epithelial cells downregulate their cell-cell junctions, acquire spindle cell morphology and exhibit cellular motility. In breast cancer, EMT facilitates invasion of surrounding tissues and correlates closely with cancer metastasis and relapse. Previous studies in our lab showed that the candidate tumor suppressor hCLCA2 is expressed in differentiated, growth-arrested mammary epithelial cells but is downregulated during tumor progression and EMT. We further showed that hCLCA2 is a p53-inducible growth inhibitor whose loss indicates an increased risk of metastasis. Subsequent studies have revealed that another member of the CLCA gene family, hCLCA4, is also expressed in mammary epithelial levels, albeit at lower levels than hCLCA2. We find that hCLCA4 is also induced by stress and is similarly downregulated in breast cancer cell lines. Like hCLCA2, hCLCA4 is downregulated when EMT is induced by TGF beta, ectopic expression of mesenchymal transcription factors, or dilution of immortalized cells. Furthermore, knockdown of hCLCA4 in HMLE by shRNAs caused EMT. RNA and protein profiling for EMT markers showed that knockdown cells have lower expression epithelial marker E-cadherin and higher expression level of mesenchymal markers vimentin and fibronectin. Moreover, we found that hCLCA4 is co-regulated with hCLCA2 in HMLE cells. Knockdown of hCLCA2 led to down-regulation of hCLCA4 and vice versa. These findings suggest that hCLCA4 is, like hCLCA2, a marker of epithelial differentiation whose loss contributes to EMT and possibly metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2420. doi:1538-7445.AM2012-2420
Abstract 2421: Iron deficiency suppresses EMT through down-regulation of N-cadherin in esophageal cancer.
Authors: Watanabe Shinichiro , Nishitani Seishi , Noma Kazuhiro , Ohara Toshiaki , Tomono Yasuko , Hashimoto Yuuri , Tazawa Hiroshi , Fujiwara Toshiyoshi 
Published: August 2012

Abstract
[Introduction] Epithelial-Mesenchymal-Transition(EMT) plays a great role in cancer metastasis and invasion. Mechanism of EMT still remains unclear, However E-cadherin and N-cadherin are known to have contribution to EMT. In particular, down-regulation of N-cadherin has been reported to reduce cancer metastasis and invasiveness. Iron metabolism and its relationship with cancer cell were studied for a long time. Iron overload is known to induce some kinds of cancer, and iron deficiency is also known to suppress the tumor growth in vivo study. But the correlation of iron metabolism and tumor progression isn't unclear. Recently, it was reported that iron metabolism was essential for EMT and iron deficiency down-regulated EMT differentiation. In this study, we hypothesized that iron deficiency down-regulated the expression of N-cadherin, and suppressed the ability of metastasis and invasiveness. Here we demonstrate our results. [Materials and Methods] In vitro study, TE-4 and TE-10 esophageal squamous cell carcinoma and OE19 esophageal adenocarcinoma cell line were used in this study. Cell viability was determined by XTT assay. Iron chelator deferasirox was used to simulate iron deficient condition. To determine that iron deficiency suppresses EMT and invasiveness of cancer cells, we investigated western blotting analysis, three-dimensional spheroid model analysis and migration assay. Moreover, to determine the expression N-cadherin in mRNA level, PCR assay was performed. In vivo study, iron depletion condition was made by iron deficient diet. Normal and iron deficient diet were fed for 3 weeks before implantation of TE-4 cells in athymic male nude mice(n=8/group). After implantation, each diet was fed continuously for a month. [Results] In vivo study, iron deficient diet suppressed the tumor growth(tumor volume: normal diet vs iron deficient diet = 30.7±1.1 mm3 vs 10.9±2.2 mm3). In vitro study, deferasirox reduces proliferation of all cell lines in a concentration manner. According to western blotting analysis, deferasirox induces reduction of N-cadherin protein in TE-4 and TE-10 cell lines. N-cadherin down-regulation declines invasiveness of TE-4 and TE-10 cell lines in the three-dimensional spheroid model analysis and migration assay. Real time PCR assay shows that down-regulation of N-cadherin is dependent on reduction of N-cadherin mRNA. [Conclusion] Iron controlled treatment can be a novel therapy for invasiveness of cancer under EMT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2421. doi:1538-7445.AM2012-2421
Abstract 2425: Collapsin response mediator protein 4 promotes tumor cell invasion and lethality of pancreatic cancer
Authors: Hiroshima Yukihiko , Nakamura Fumio , Miyamoto Hiroshi , Mori Ryutaro , Taniguchi Koichi , Matsuyama Ryusei , Takeda Kazuhisa , Akiyama Hirotoshi , Tanaka Kuniya , Ichikawa Yasushi , Nagashima Yoji , Goshima Yoshio , Endo Itaru 
Published: August 2012

Abstract
BACKGROUND: Pancreatic cancer is an aggressive malignancy with one of the worst outcomes among all cancers. Recently, Collapsin Response Mediator Proteins (CRMPs) were associated with proliferation, apoptosis, differentiation and invasion in several cancers. However, CRMPs expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer. METHODS: Pancreatic adenocarcinoma samples were obtained from 53 patients. Crmp expression in these samples was examined using realtime RT-PCR. CRMP4 protein expression was examined immunohistochemically and compared with the clinicopathological features of the tumors. Furthermore, knock down of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. RESULTS: Of all the CRMPs, the crmp4 gene was determined to be the only one differentially expressed in pancreatic cancer tissues (p = 0.008). The expression of CRMP4 was detected immunohistochemically in 34 of the 53 (64.1%) pancreatic cancer samples, and CRMP4 staining was highly correlated with poor differentiation (p = 0.003) and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival. CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. CONCLUSIONS: Our results suggested that CRMP4 overexpression was a strong prognostic factor for increasing pancreatic cancer invasiveness, and can be a novel therapeutic target for pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2425. doi:1538-7445.AM2012-2425
Abstract 2426: Role of fibroblast growth factor receptor 1 (FGFR1) in liver metastasis of colorectal cancer
Authors: Lee Myung Eun , Shin Yoo Kun , Jeung Hei-Cheul , Shin Sang Joon , Park Young Kyu , Zhao Xue-Feng , Kim Tae Soo , Ahn Joong- Bae , Chung Hyun Cheol , Rha Sun Young 
Published: August 2012

Abstract
Liver metastasis is one of the main cause of death among patients with colorectal cancer (CRC). However, accurate prediction of liver metastasis of CRC is difficult at the inception of diagnosis. Activated receptor tyrosine kinases (RTKs) are the main mediators of the signaling pathway related to cell survival, proliferation, differentiation or apoptosis. To determine if any of these RTKs are involved in liver metastasis from CRC, we performed phospho-receptor tyrosine kinase array with matched 20 colon normal mucosa, primary tumor, metastatic liver tumor, and liver normal tissue proteins using Human Phospho-RTK Array (2009 AACR, #4951). In RTK activation profiling, FGFR1 activation was increased in a high proportion of metastatic liver tumor (p &lt; 0.05). To evaluate the functional roles of FGFR1, DLD-1 and LoVo colon cancer cells were treated with FGFR1 specific siRNA or RTK inhibitor. Inhibition of FGFR1 inhibited phosphorylation of PI3K/AKT and ERK, a downstream cellular signaling molecule of FGFR; whereas, mTOR, p70S6K, JNK and Src activities were not affected. Also, we compared the cell migration and invasion ability by wound healing assay and invasion assay. The invasion capacity and wound closing were significantly delayed by FGFR1 inhibition (p &lt;0.05). To evaluate in vivo anti-metastatic effect of FGFR1, we used an orthotropic liver metastasis model, generated by injecting LoVo colon cancer cells into spleen of BALB/c nu/nu mice. In control group, multiple large metastatic foci were evident, whereas the extent of liver metastasis was dramatically reduced in TKI-258 (50mg/kg/d) treated group (48.9%, p&lt;0.05). Immunoexpression of the p-FGFR1 was much more intense in control than TKI-258 treated tumor tissues. Biological effects were also confirmed that FGFR1 inhibition resulted in a significant reduction of ERK activation and Ki-67 positive cells in tumor tissues. In conclusion, FGFR1 might be a good target for liver metastasis of CRC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2426. doi:1538-7445.AM2012-2426
Abstract 2429: An abdominal imaging window for long-term subcellular visualization of abdominal organs in living mice
Authors: Steller Ernst J. , Ritsma Laila , Rinkes Inne H. Borel , Kranenburg Onno , van Rheenen Jacco 
Published: August 2012

Abstract
Intravital imaging windows are powerful tools for long-term visualization of dynamic cell behaviour in living mice. However, the applications of the current windows are limited because they cannot be used for imaging of organs in the abdomen. In order to overcome this unmet need, we developed the abdominal imaging window (AIW). Using the AIW, we visualized stem cells in the small intestine, lymphocytes in the spleen, transplanted islets of Langerhans under the kidney capsule, and metastatic outgrowth of tumor cells in the liver. We discovered that liver metastases are grown from a single founder cell, and that tumor cells within a growing metastasis are highly motile. Strikingly, this migration appears to be a novel, limiting step during liver metastasis formation. We conclude that the AIW is a powerful tool to visualize distinct biological processes in a variety of abdominal organs with subcellular resolution over a time span of weeks.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2429. doi:1538-7445.AM2012-2429
Abstract 2435: Assessment of vascular disrupting properties of sodium meta-arsenite treatment using Dynamic contrast-enhanced MRI in colon cancer allograft model
Authors: Min Young Joo , Lee Hee-Soon , Cho Wha Ja , Lee Ho Yong , Lee Jong Cheol , Park Sungchan , Cha Hee-jung , Park Hyun Jin , Seo Jin , Lee Young Han , Song Ho Taek , Moon Chang Hoon 
Published: August 2012

Abstract
PURPOSE: Sodium meta-arsenite is an orally bioavailable arsenic compound that currently undergoing clinical evaluation. The sodium meta-arsenite leads to blood vessel congestion, the selective destruction of the vasculature, and extensive necrosis in experimental tumors. The aim of this study is to assess the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure the antivascular effects of sodium meta-arsenite in colon cancer allograft model. MATERIALS AND METHODS: Mice CT26 colon cell carcinoma allografts were treated with sodium meta-arsenite or saline. Changes in tumor vascularity were assessed by DCE-MRI. DCE-MRI data were analyzed calculating the k(ep). For histologic analysis, liver, spleen and tumor tissues were taken at 8, 24 and 48 hours after sodium meta-arsenite injection from CT26 tumor allograft models. RESULTS: DCE-MRI results showed comparison between pre-treatment and 24 hr post-treatment Gd-DTPA contrast enhancement T1-weighted MR image. Enhancement has been significantly decreased in sodium meta-arsenite treated group than sham injection group. We also showed extensive central necrosis of tumor by 24 h after treated with sodium meta-arsenite (10 mg/kg, i.p.). CONCLUSION: These results suggest that DCE-MRI could quantitatively visualized the perfusion efficacy of the sodium meta-arsenite acting as a VDA in colon caner allograft model
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2435. doi:1538-7445.AM2012-2435
Abstract 2446: Real-time molecular imaging of targeted therapies in patient-derived tumor cells by quantitative immunofluorescence microscopy
Authors: Rothenberg Stephen M. , Wargo Jennifer , Juric Dejan , Corcoran Ryan B. , Winokur Daniel , Flaherty Keith T. , Baselga Jose , Maheswaran Shyamala , Engelman Jeffrey A. , Haber Daniel A. 
Published: August 2012

Abstract
Serial radiographic imaging is the primary means for determining the efficacy of cancer treatments. However, a long time interval is required before changes are appreciated, and the direct effects of therapy on tumor cells cannot be measured. We have utilized highly multiplexed, quantitative immunofluorescence microscopy to monitor multiple signaling proteins simultaneously in direct tumor biopsies and circulating tumor cells obtained serially from patients with BRAF- and PIK3CA-mutant solid cancers undergoing treatment with agents that target these mutated oncogenes. Changes in signaling that accurately predict subsequent clinical response can be determined from small numbers (∼100) of tumor cells and are apparent within days of the first dose of therapy, and weeks before radiographic determination of response. Preliminary results suggest that therapeutic efficacy (or lack thereof) is correlated with both the degree and rapidity of downregulation of tumor cell signaling. The ability to measure the effects of therapy directly in patient-derived tumor cells may permit real time information about efficacy (or lack thereof) to be rapidly incorporated into the decision to continue an ongoing therapy or to switch to a new one, or in the identification of patient populations most likely to respond to a novel class of agents.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2446. doi:1538-7445.AM2012-2446