bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 996: Loss of alpha-dystroglycan laminin binding in epithelium-derived cancers is caused by silencing of LARGE
Authors: Beltran Daniel , Inamori Kei-ichiro , Moriguchi Takako , Weydert Christine J. , Harper Hollie A. , Willer Tobias , Muller William J. , Henry Michael D. , Campbell Kevin P. 
Published: February 2011

Abstract
Dystroglycan is a ubiquitously expressed cell membrane receptor that mediates interactions between cells and basement membranes in various epithelia. Dystroglycan is synthesized as a preprotein that is cleaved in two peptides: the transmembranal beta-dystroglycan, and the extracellular laminin receptor alpha-dystroglycan. In many epithelium-derived cancers, beta-dystroglycan is detected but alpha-dystroglycan has been reported to be absent. Here we report that alpha-dystroglycan is correctly expressed and trafficked to the cell membrane but lack its laminin-binding capabilities as a result of the silencing of the glycosyltransferase LARGE in a cohort of highly metastatic epithelial cell lines derived from breast, cervical, and lung cancers. As a result of this glycosylation defect, alpha-dystroglycan presents a lower MW on Western blot analysis. Exogenous expression of LARGE in these cancer cells restores the normal glycosylation and laminin-binding of alpha-dystroglycan leading to enhanced cell adhesion and reduced cell migration in vitro. The relevance of alpha-dystroglycan glycosylation in breast cancer is highlighted by the loss of the functionally active form of the receptor during mammary tumor growth in the mouse model for breast cancer MMTV-Neu(YD). Our findings demonstrate that LARGE repression underlies the defective dystroglycan-mediated cell adhesion that is observed in epithelium-derived cancer cells and uncovers dystroglycan hypo-glycosylation as factor in cancer progression.
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 996.
Abstract 997: PKD1-β3-integrin complex increases E-cadherin shedding through MMP-2 and −9 secretion in prostate cancer
Authors: Biswas Md. Helal U. , Du Cheng , Zhang Chuanyou , Balaji K.C. 
Published: February 2011

Abstract
Introduction: We have previously reported that Protein Kinase D1 (PKD1), a serine threonine kinase, is down regulated in advanced prostate cancer (PC) and known complex with cell adhesion protein β3-integrin to influence cell motility. Cell motility in facilitated by degradation of extracellular matrix, which is accomplished through secretion of proteins such as Matrix Metalloproteinases (MMPs), which are neutral proteinases that catalyze degradation of various transmembrane and extracellular matrix proteins including E-cadherin at cell surface. Here, we demonstrate the presence of PKD1-β3-integrin complex in PC cells that increases MMP-2 and −9 secretion and consequently enhances E-cadherin shedding.
Methods: Protein expression, phosphorylation and secretion studies using PC cell lines were done by western blot analysis or gelatin zymography. Cell proliferation was measured by MTS assay. In silico analysis was done to validate correlation between PKD1 and MMPs expression in human PC.
Results: To find out the complex formation among PKD1 and β3-integrin in PC cell, we immunoprecipitated the PKD1 protein and immunoblotted with β3-integrin antibody and observed that the PKD1 and β3-integrin proteins were in same protein complex. Then we found that overexpression of PKD1 also colocalized in PC3 cells and that was suppressed with RGD peptide, a specific β3-integrin inhibitor, treated same cells. Additionally, we found that PKD1 overexpressed cell increased in secretion of MMP-2 and −9 as well as activation of Erk and Akt those were suppressed in RGD peptide treated cells. In contrast, we observed that downregulation of PKD1 by shRNA could suppress the phosphorylation of Erk and Akt as well as MMP-2 and MMP-9 secretion in DU145 cells. Interestingly, PKD1 enhanced the expression of E-cadherin and secretion of extracellular part of E-cadherin (sE-cadherin) in conditioned media of DU145 cells, which was suppressed by treatment by MMP-2 and −9 inhibitors. In addition, suppression of cell proliferation by PKD1 was augmented by recombinant MMP-2 and −9 proteins and rescued by MMP-2 and MMP-9 inhibitor in DU145 cells, suggesting a surprising antiproliferative role for MMP-2 and −9 in PC cells. In silico analysis of publicly available DNA microarray data set derived from human PC confirmed that expression of PKD1 and MMP-2 correlated directly in metastatic PC compared to benign prostate tissue. Conclusions: Our study has identified a novel role of PKD1-β3-integrin complex for secretion of MMP-2 and −9 in prostate cancer, which is associated with E-cadherin shedding. Our data also suggested that the proteins complex limits PC cell proliferation by modulation MMP-2 and −9 secretion.
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 997.
Abstract LB-11: Clinical and genetic analysis of Peutz-Jeghers syndrome patients in Taiwan
Authors: Weng Meng Tzu , Wei Shu Chen 
Published: February 2011

Abstract
Background/Purpose: Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder characterized by intestinal hamartomatous polyps and mucocutaneous pigmentation. Recently, germline mutations in the LKB1 gene have been reported to underlie PJS. The gene encoding this serine/threonine kinase is located at 19p 13.3. The aim of this study was to investigate the clinical and genetic characteristics of PJS patients in Taiwan.
Methods: We searched the database in the National Taiwan University Hospital, a tertiary medical center in Taiwan, between January 1990 and November 2005. Patients’ clinical information, demographic data, endoscopic pictures, and outcome details for these cases were reviewed and analyzed. After obtaining informed consent, DNA and RNA were extracted from peripheral blood mononuclear cells and the LKB1 gene was sequenced.
Results: A total of 14 non-related patients fulfilling the diagnostic criteria of PJS were included, and seven of them had genetic analysis performed. Mucocutaneous pigmentation was the most frequent presentation. Hamartomas occur most commonly in the small intestine (86%). The frequent abdominal complications include intussusceptions and gastrointestinal bleeding. Four germline mutations were found (57.1%). Three resulted in stop codons at codon 60, 162 (novel mutation), and 308. The fourth mutation was a missense mutation at codon 239 (novel mutation).
Conclusions: Compared to other reports, PJS patients in Taiwan tended to have more extensive polyps in the GI tract, causing intussusceptions as the most common abdominal symptoms. The genetic mutations in the LKB1 gene were identified in 57% of the probands in Taiwan.
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 LB-11.
Abstract LB-12: Inhibition of the proliferation and invasion of hepatocellular carcinoma cells by lipocalin 2 through blockade of JNK and PI3K/Akt signaling
Authors: Lee Eun-Kyoung , Kim Hyun-Jun , Lee Kong-Ju , Lee Ho-Jeong , Kim Dae-Ghon , Hong Soon-Won , Yoon Yeup , Kim Jang-Seong 
Published: February 2011

Abstract
Lipocalin 2 (Lcn2) has long been regarded to induce cellular proliferation because expression of Lcn2 has been associated in a variety of proliferative cells. Consistent with this, it has been demonstrated in the present study that Lcn2 was significantly elevated in human HCC (hepatocellular carcinoma) tissues compared with the non-tumor liver tissues. However, the roles of Lcn2 in hepatocarcinogenesis are far from clear. To investigate the effects of Lcn2 expression on the hepatocarcinogenesis, Chang liver and SK-Hep1, the HCC cell lines, were genetically manipulated to express Lcn2 and their effects on the proliferation and invasion of HCC cells were analyzed. Ectopic expression of Lcn2 in HCC cells significantly inhibited the growth of HCC cells in vitro and in vivo. In addition, its expression reduced the invasive potential of cells and inhibited the expression of matrix metalloproteinase 2 (MMP-2). Lcn2 may exert its function partly through the inhibition of the c-Jun N-terminal kinase (JNK) and phosphatidyl inositol 3′-kinase (PI3K)/Akt signaling pathways in HCC cells, since selective inhibition of those pathways using pharmacological inhibitors significantly inhibited the proliferation, invasion and MMP-2 expression, whereas Lcn2 expression suppressed the JNK and PI3K/Akt pathways. In conclusion, these results clearly indicate that Lcn2 may play a protective role in the progression of HCCs by suppressing the proliferation and invasion of HCC cells, although clinical significance of the present findings remains to be evaluated.
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 LB-12.
Abstract LB-126: A pooled shRNA screen for erlotinib sensitizers in Kras-mutant non-small cell lung cancer
Authors: Cordes Shaun , Dompe Nick , Lee James , Li Li , Rivers Celina , Tang Zhijun , Luk Wilman , Bennett Greg , Shames David , Modrusan Zora , Davis David P. 
Published: February 2011

Abstract
Erlotinib is a small-molecule inhibitor of the epithelial growth factor receptor (EGFR) that provides a survival benefit in patients with chemoresistant non-small cell lung cancer (NSCLC). In the second and third line setting, patients whose tumors harbor activating mutations in Kras showed less benefit than patients with tumors harboring wild type Kras.
To identify genes whose inhibition sensitizes Kras-mutant NSCLC cells to erlotinib, we performed a whole-genome pooled-shRNA screen and identified 337 shRNAs that were selectively depleted in erlotinib-treated cells. We subsequently validated 148 of the top 200 hits in an siRNA-based viability assay and selected 37 hits for further analysis. We are currently characterizing these hits in a panel of ∼10 additional NSCLC lines to identify targets with broad cell line activity that synergize with erlotinib to induce apoptosis. Our current understanding of the relationships between our top hits and erlotinib sensitivity will be discussed.
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 LB-126.
Abstract LB-129: CAFET algorithm reveals WNT/PCP specific signature in squamous cell carcinoma of lung cancer
Authors: Hu Yue 
Published: February 2011

Abstract
We analyzed the global gene expression patterns of 138 lung cancer samples containing Squamous Cell Carcinoma (SCC) and Adenocarcinoma (AC). Gene set enrichment analysis revealed developmental and cell cycle functional groups were specifically overexpressed in SCC samples. To refine and focus our analysis on specific signaling pathways, we developed a complementary algorithm called Coverage Analysis with Fisher Exact Test (CAFET). In our analysis, the WNT signaling pathway had the most significant enrichment of overexpressed genes in a cluster of predominantly SCC. Most interestingly, the differential expression pattern in this cluster had a strong tendency to inhibit the WNT canonical pathway while enhancing the WNT/PCP pathway. The non-canonical WNT/PCP pathway is obligatory for cell migration during embryogenesis, and it has also been proposed to be involved in cancer metastasis. While the WNT canonical pathway has been reported to be important in metastasis of AC in lung cancer, our results suggest SCC of lung makes use of a different branch of the WNT pathway for survival and development. This WNT/PCP signature for lung SCC was also confirmed in several independent sample sets. It is also present in some cell lines derived from lung SCC. To find potential clinical biomarkers, we identified 174 genes present in blood and highly expressed in samples carrying this WNT/PCP signature. These results demonstrate that the new algorithm CAFET is a promising approach for mining large gene expression data sets to identify pathways with differential activity, and could be particularly useful in exploring cancer expression datasets.
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 LB-129.
Abstract LB-161: Colospheres: 3D ex vivo microtumors with more aggressive phenotype than original human colon cancer tissues
Authors: Weiswald Louis-Bastien , Massonnet Gérald , Richon Sophie , Guinebretiere Jean-Marc , Bellet Dominique , Bieche Ivan , Dangles-Marie Virginie 
Published: February 2011

Abstract
The ex vivo colospheres are a newly characterised three-dimensional colon cancer multicellular model, derived from mechanically dissociated human colon cancer tissue (Br J Cancer 2009, 101:473-82). We have previously demonstrated that this short term culture model is exclusively formed by cancer cells and associated with tumor aggressiveness.
To further investigate the potential interest of colospheres as micrometastasis or cancer stem cell model, we used 3 human colon cancer xenografts directly established from 3 patient colon adenocarcinoma in Nude mice (Cancer Res 2007, 67:398-407). These xenograft tissues are able to give rise to numerous colospheres in only 3 days after mechanical dissociation. This approach allows working with reproducible biological tumor material, in which all human part is known to be cancer cells.
Xenograft tissues and derived colospheres were collected for gene expression study. Expression of 78 genes, involved in stemness, proliferation, epithelial-to-mesenchymal transition and metastasis, has been studied using real-time RT-PCR. All the probes used are human specific and do not cross with mouse genome. Consequently, the comparison of gene expression profiles corresponds to the comparison of gene expression in colosphere-forming cells versus that in the cancer cell counterpart from xenograft tissue.
Gene expression clustering analysis clearly showed that for the 3 colon adenocarcinoma, colospheres matched with their parent xenografts. This first point is important because it demonstrated 1) the lack of ex vivo culture artefact (which would have led to classification into 2 groups: all xenografts opposed to all colospheres); 2) the relevance of colospheres for mimicking in vivo tumor cells. Nevertheless, in all 3 pairs xenograft/colospheres, 3 genes were found overexpressed: ALDH1, KLF4 and PLAUR. This overexpression has to be put in line with high tumorigenicity of these colospheres when injected into mice (Br J Cancer 2009, 101:473-82). Gene expression increase will be confirmed at protein level. To gain also information about location of the cells expressing ALDH1, KLF4 and PLAUR, we developed an immunostaining protocol for confocal microscopy and in situ protein detection (BMC Cancer, in revision).
In conclusion, these preliminary data underline the interest of colospheres as ex vivo microtumor model with cancer initiating-cell functions.
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 LB-161.
Abstract LB-175: Tumor regression in patients with metastatic synovial sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1
Authors: Paul Robbins F. , Morgan Richard A. , Feldman Steven A. , Yang James C. , Dudley Mark E. , Li Yong F. , El-Gamil Mona , Schwarz Susan L. , Rosenberg Steven A. 
Published: February 2011

Abstract
Discussant: To be announced.
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 LB-175.
Abstract LB-183: The predictive value of CYP2D6 genotypes for plasma levels of active tamoxifen metabolites in early breast cancer
Authors: Muerdter Thomas E. , Schroth Werner , Bacchus Liza , Simon Wolfgang , Eichelbaum Michel , Schwab Matthias , Brauch Hiltrud B. 
Published: February 2011

Abstract
Discussion
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 LB-183.
Abstract LB-190: RAF inhibitors transactivate RAF dimers and ERK signaling in a wild-type BRAF-dependent manner
Authors: Poulikakos Poulikos I. , Zhang Chao , Joseph Eric W. , Persaud Yogindra , Pratilas Christine A. , Bollag Gideon , Solit David B. , Shokat Kevan M. , Rosen Neal 
Published: February 2011

Abstract
Discussion
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 LB-190.
Abstract LB-196: Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects
Authors: Dubrot Juan , Palazon Asis , Milheiro Francisca , Martinez-Forero Ivan , Melero Ignacio 
Published: February 2011

Abstract
Discussion
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 LB-196.
Abstract LB-219: Elevated expression of cellular proliferative index MIB-1 in post-Chornobyl papillary thyroid carcinoma with coexisting thyroiditis
Authors: Dinets Andrii , Hulchiy Mykola , Sofiadis Anastasios , Höög Anders , Larsson Catharina , Zedenius Jan 
Published: February 2011

Abstract
Introduction: Most patients with papillary thyroid cancer (PTC) have an excellent prognosis. Ki-67 is marker of proliferation, and proliferative index more than 5% as calculated with the MIB-1 antibody indicates a worse prognosis in PTC. This study was performed in order to investigate and evaluate expression of MIB-1 in a cohort of adult PTC patients who were exposed in their childhood to radioactivity from the Chornobyl accident in 1986.
Materials and Methods: 70 patients (60 females and 10 males, mean age 30,5 (19-39)) operated on for PTC during 2004-2008 were identified for the study. Two groups were established according to diagnosis. Group 1 consisted of patients with PTC only (n=53). Group 2 consisted of patients with PTC and co-existing chronic lymphatic thyroiditis (n= 17). Proliferative activity was measured by immunohistochemistry using monoclonal MIB-1 antibody against nuclear factor Ki-67. A minimum of 2000 tumor cells were calculated and the percentage of positive cells (MIB-1 index) was compared with clinical data.
Results: MIB-1 index was higher in Group 2 (mean 3,65) compared with Group 1 (mean 1,97) (p=0,005). No other clinical features could be correlated with the MIB-1 index. 26% of patients in Group 1 had lymph node metastases, and 23% in Group 2. The mean tumor size was slightly higher in Group 1 (2 cm) compared with Group 2 (1,75 cm). Age at diagnosis (30,5) and age at the Chornobyl accident (11) were identical between the groups.
Conclusions: The clinical features of this cohort of adult PTC patients exposed to the radioactive fallout from the Chornobyl accident seem no different to other PTC cohorts. However, a rather large proportion of patients showed signs of coexisting thyroiditis. Whether the elevated MIB-1 index in this group of patients reflects a worse prognosis is yet not possible to say due to the short follow-up time. Still, a closer follow-up may be justified.
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 LB-219.
Abstract LB-225: EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity
Authors: Zhu Hu , Cao Xinyu , Keir Steve , Ali-Osman Francis , Lo Hui-Wen 
Published: February 2011

Abstract
Glioblastoma is the most common and most intractable brain malignancy in adults. Patients with glioblastoma have dismal prognosis with a median survival of 12-14 months. This unfortunate poor prognosis is, in part, due to the aggressive nature of these tumors and the lack of effective therapy. EGFR and its constitutively activated variant EGFRvIII are linked to glioblastoma resistance to therapy, the mechanisms underlying this association, however, are still unclear. We report here that in glioblastoma cell lines, xenografts and primary specimens, EGFR and EGFRvIII paradoxically co-express with p53-upregulated modulator of apoptosis (PUMA), a proapoptotic member of the Bcl-2 family of proteins primarily located on the mitochondria. Both EGFR and EGFRvIII bind to PUMA constitutively and under apoptotic stress, and subsequently sequester PUMA in the cytoplasm. The EGFR-PUMA interaction is independent of EGFR activation and is sustained under EGFR inhibition. A Bcl-2/Bcl-xL inhibitor that mimics PUMA activity sensitizes EGFR- and EGFRvIII-expressing glioblastoma cells to EGFR kinase inhibitor, Iressa. Collectively, we uncovered a novel kinase-independent function of EGFR and EGFRvIII that leads to drug resistance of glioblastoma and potentially other tumor types.
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 LB-225.