bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3371: Gastric cancer stem/initiating cells are enriched in the CD44 fraction of EpCAM expressing cells
Authors: Teng Eileen , Chong Hui Shan , Wang Ting Ting , Salto-Tellez Manuel , Tay Amy YL , So Jimmy BY , Chan Shing-Leng 
Published: February 2011

Abstract
Cancer stem cells (CSCs) have been discovered in cancers of many tissues but they have not been explored for gastric cancer. A candidate approach was taken to isolate putative gastric cancer stem cells from primary gastric cancer specimens because surface markers have been used to describe CSCs from different cancers. Cells dissociated from biopsy samples extracted from primary tumour and non-tumour sites of the same patient were analyzed by flow cytometry. Cell surface markers surveyed include CD45 for hematopoietic cells, CD31 for endothelial cells, CD44, CD133, CD34, CD117, CD166, CD90 and EpCAM as potential cancer stem cell markers.
EpCAM levels were found to be higher in cells isolated from the tumor than non-tumor sites. Using median fluorescence intensity, it was found that cells at the tumor site express 1.2-1.7 fold higher level of EpCAM. This was observed in histopathologically distinct types of gastric tumors, namely intestinal subtypes that are well, moderately and poorly differentiated. Data from diffused type gastric tumors were not as consistent mainly because of sampling difficulties. 100,000 EpCAM-positive cells form xenograft tumors in NOD/SCID mice whereas 500,000 EpCAM-negative cells from a fraction that was not hematopoietic (CD45-negative), endothelial (CD31-negative) nor fibroblastic (CD140b-negative) were unable to do so. To further enrich for gastric cancer stem cells, the EpCAM-positive cells were sorted based on EpCAM+CD44+ or EpCAM+CD133+ cells. To expand the tumor material, we generated xenograft tumors directly from fresh tumor pieces. Histological analyses verified that the xenograft tumors recapitulate those in the patient samples. Cells dissociated from the xenograft tumor were then subjected to CSC identification assays. To date, three lines of xenograft tumors were generated from tumor tissues of well, moderately and poorly differentiated histological subtype of gastric cancers.
As few as 1000 EpCAM+CD44+ cells were able to initiate tumors in NOD/SCID mice whereas 20,000 EpCAM+CD44- cells were required to do so. We are currently doing limiting dilution assays to estimate the number of cancer initiating cells in each fraction we isolate from the xenografts. We were unable to see differential tumorigenic potentials in EpCAM+CD133+ and EpCAM+CD133- fractions. In conclusion, we have identified a subpopulation of gastric cancer cells that potentially mark gastric cancer stem cells as characterized by their cancer-initiating potential.
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 3371.
Abstract 3375: Normal viability of Kai1/CD82 deficient mice
Authors: Risinger John I. , Custer Mary , Feigenbaum Lionel , Simpson R Mark , Hoover Shelley , Webster Josh , Chandramouli Gadisetti VR , Tessarollo Lino , Barrett J Carl 
Published: February 2011

Abstract
The KAI1 tetraspanin also known as CD82 is a widely expressed cell surface molecule involved in organizing many diverse cellular signaling processes. Importantly KAI1/CD82 was shown to suppress metastasis but not tumorigenicity in animal models of metastasis, establishing KAI1/CD82 as one of a class of metastasis suppressor genes. The function of KAI1/CD82 regarding its role in controlling metastasis is under scrutiny and many questions remain as to its function in regulating this and other cellular processes. In order to further assess the functions of KAI1/CD82 we examined the effect of germline deletion on viability, fertility, lymphocyte composition, blood chemistry and performed a detailed pathologic analysis of tissues in Kai1/CD82 deficient mice and their wild-type and heterozygote littermates. Interestingly mice deficient in KAI1/CD82 showed no obvious genotype associated defects in any of these processes as compared to their wild-type littermates and displayed no genotype associated abnormalities after 12 or 18 months of life. To further explore the lack of noticeable phenotypes in these mice we employed expression profiling of non-immortal MEF cultures to assess the effect of KAI1/CD82 on global gene expression. Gene expression of MEFs indicated distinct sex specific and genotype specific profiles suggesting some genes as compensatory candidates which might explain the lack of appreciable phenotypes in KAI1/CD82 deficient mice.
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 3375.
Abstract 3376: Human arrest defective 1 protein suppresses cancer cell metastasis by binding PIX/Cool proteins and inhibiting Cdc42/Rac1 activity
Authors: Hua Kuo-Tai , Hsiao Michael , Kuo Min-Liang 
Published: February 2011

Abstract
Human arrest defective 1 protein, ARD1, is an N-acetyltransferase known to be involved in cell cycle control. We found that ARD1 is highly expressed in the early stage of the cell cycle and less highly expressed in a variety of human malignancies that metastasize to lymph nodes. ARD1 expression favors survival in patients. ARD1 significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, ARD1 binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activities and decreased cell migration. Forced expression of PIX in ARD1-transfected tumor cells restored the migration and metastasis ability. We suggest that ARD1 functions as a novel tumor metastasis suppressor by disrupting the migratory complex, GIT-PIX-Paxillin, in cancer cells.
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 3376.
Abstract 3378: E-cadherin suppresses breast cancer cell growth and interleukin-6 production
Authors: Sullivan Nicholas J. , Schick Jonathan S. , Riggenbach Judith A. , Tober Kathleen L. , Hall Brett M. , Oberyszyn Tatiana M. 
Published: February 2011

Abstract
Carcinomas arise from epithelial tissues and represent the most common type of human cancer. E-cadherin is an epithelial-specific intercellular adhesion molecule, which localizes to epithelial cell adherens junctions and is a critical mediator of carcinoma cell invasion and metastasis. Although impaired E-cadherin expression can be clinically utilized to predict breast cancer cell invasiveness, metastasis, and patient survival, E-cadherin has received less attention for its role as a putative regulator of epithelial cell growth. We have previously shown that interleukin-6 (IL-6), a pleiotropic inflammatory cytokine associated with poor clinical outcome in breast cancer patients, is a potent growth factor and repressor of E-cadherin in human breast cancer cells. Consistent with clinical reports and our previous findings, we hypothesized that E-cadherin repression may be responsible for IL-6-induced breast cancer cell growth. The current study demonstrated that IL-6 enhanced the growth rates of estrogen receptor-alpha (ERα)-positive breast cancer cells in a three-dimensional (3D) tumor growth assay (TGA) in a dose-dependent manner. We showed that IL-6 also repressed E-cadherin protein levels in ERα-positive breast cancer cells in a 3D TGA in a dose-dependent manner. We have previously shown that IL-6 treatment does not affect E-cadherin-negative MDA-MB-231 cell growth, and the current study showed similar results in MCF-7 cells which express Twist and therefore lack E-cadherin. MDA-MB-231 cells lack E-cadherin and express IL-6, thus allowing us to express stable ectopic E-cadherin to evaluate its impact on cell growth and IL-6 production. Ectopic E-cadherin expression significantly suppressed MDA-MB-231 cell growth (P-value &lt; 0.005) and IL-6 production (P-value &lt; 0.00005) as measured by 3D TGA and ELISA, respectively. Our current findings reveal an association between enhanced breast cancer cell growth and E-cadherin repression following exposure to IL-6. Furthermore, we demonstrated that E-cadherin suppresses breast cancer cell growth and IL-6 production, which suggests a positive feedback loop in which IL-6 promotes E-cadherin repression, thereby inducing autocrine IL-6 production in breast cancer cells.
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 3378.
Abstract 3382: The roles of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatocellular carcinoma invasion and metastasis
Authors: Wu Yu-Ling , Yang Ching-Yao , Chung Wan-Chin , Chang King-Jen , Lee Po-Huang , Tsai Wan-Chi , Kuo Min-Liang 
Published: February 2011

Abstract
Vascular invasion is the major poor prognostic factor in hepatocellular carcinoma (HCC) progression, and the overall five year survival is only 40-50%. To elucidate the molecular pathogenesis of HCC, using high throughput technology suppression subtractive hybridization (SSH) and transmembrane/secreted protein (TMS) oligonucleotide microarray, we found that leukocyte cell-derived chemotaxin 2 (LECT2) correlated with low vascular invasion. Human LECT2 is a 16-kDa basic protein and specifically expressed in adult and fetal livers. However, its biological function has not been identified. Here, we show that LECT2 level was significantly reverse-correlated with vascular invasion, high tumor stage, early recurrence, and poor survival. LECT2 overexpression did not influence HCC cells growth property, but strongly reduced migration and invasion in vitro assay. LECT2 suppressed tumor growth, intrahepatic, and lung metastasis in orthotopic liver transplantation mice. The mechanism of LECT2 inhibited HCC cells invasion and metastasis might be mediated via affected multiple receptor tyrosine kinases. Taken together, these findings indicated that LECT2 suppress the invasiveness and suggest the feasibility of LECT2 expression as a promising prognostic molecular marker for 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 3382.
Abstract 3383: Role of BHLHB3 regulation of p53 and c-Jun during the induction of cancer cell dormancy in a model of HNSCC
Authors: Bragado Paloma , Estrada Yeriel , Aguirre-Ghiso Julio 
Published: February 2011

Abstract
Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer for which survival rates have improved marginally over the last 30 years. Majority of cancer patients will die of metastases that develop from disseminated tumor cells (DTCs). Using computational tools and the experimental model, HEp3 (HNSCC) cells, we have identified p53 and BHLHB3 as critical genes transcriptionally induced by p38α/β signaling and required for the induction of HEp3 cells quiescence in vivo. BHLHB3 is a transcriptional repressor and a regulator of the circadian rhythm. We have demonstrated that BHLHB3 upregulation is required for the quiescence of D-HEp3 cells. We further showed that overexpression of BHLHB3 in T-HEp3 cells inhibits proliferation and correlates with increase levels of p21 (cell cycle arrest marker and p53 target gene) in vivo. We next tested the possibility that BHLHB3 regulates p53 expression/activity. Our results show that overexpression of BHLHB3 in T-HEp3 cells induced p53 transcriptional activity of a p53-luciferase reporter construct and increased p53 protein levels in vitro. In addition, downregulation of BHLHB3 using RNA interference in D-HEp3 cells also reduced p53 protein levels in vitro. We had also demonstrated that p53 upregulation in dormant HNSCC D-HEp3 cells is dependent on c-Jun downregulation by p38α. Accordingly, BHLHB3 downregulation via RNAi in D-HEp3 cells correlates with an increase in c-jun expression in vitro, suggesting that BHLHB3 regulation of p53 may be mediated through c-Jun. We propose that induction of tumor cell quiescence by BHLHB3 may be mediated through p53 regulation, suggesting a strong crosstalk between both pathways for growth suppression.
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 3383.
Abstract 3387: Characterization of the role of the type 2C phosphatase Ppm1d (Wip1) in metastasis
Authors: Li Heng-Hong , Yang Qian , Wang Yi-wen , Chen Suzie , Fornace Albert J. 
Published: February 2011

Abstract
Ppm1d (Wip1) is a member of the magnesium-dependent serine/threonine protein phosphatase family, and is considered to be an oncogene. Previous work from our lab showed that Ppm1d null mice were remarkably more resistant to oncogene driven mammary tumorigenesis. In human tumors, PPM1D amplification and overexpression are observed in multiple tumor types. In addition PPM1D amplification has often been associated with poorer prognosis than the counterpart with normal PPM1D level. Overexpression of Ppm1d in mouse embryo fibroblasts (MEFs) and in transgenic mice showed enhanced cell transformation and accelerated cancer progress. However it remains to be determined whether Ppm1d facilitates the metastasis processes. In order to address this question our lab generated a cross strain of Wip1 null and Grm1 trangenic mice. Grm1 Tg is a well-characterized mouse model for melanoma and the mice with the Grm1 transgene develop metastasis of melanoma with high frequency. Ppm1d deficiency dramatically reduced the metastasis in Grm1 Tg mice. We observed less migration efficiency in the melanoma cells with Ppm1d gene knock-down. We are investigating the known Ppm1d downstream pathways and also other signaling events to determine the potential mechanism(s). We are also extending the study to another tumor type system to determine if the pro-metastatic effect of Ppm1d is melanoma specific or not.
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 3387.
Abstract 3400: Recurrent focal copy-number changes and loss-of-heterozygosity implicate two non-coding RNAs and one tumor-suppressor gene at chromosome 3q13.31 in osteosarcoma
Authors: Pasic Ivan , Shlien Adam , Durbin Adam , Stavropoulos Dimitrios , Baskin Berivan , Ray Peter , Novokmet Ana , Malkin David 
Published: February 2011

Abstract
Osteosarcomas are copy-number alteration (CNA)-rich malignant bone tumors. Using microarrays, fluorescence in-situ hybridization and quantitative polymerase chain reaction we characterize a focal region of chr3q13.31 (osteo3q13.31) harboring CNAs in 80% of osteosarcomas. As such, osteo3q13.31 is the most altered region in osteosarcoma and contests the view that CNAs in osteosarcoma are non-recurrent. Most (67%) osteo3q13.31 CNAs are deletions, 75% of which are mono-allelic, and are frequently accompanied by loss-of-heterozygosity (LOH) in flanking DNA. These CNAs often involve the non-coding RNAs (ncRNAs) LOC285194 and BC040587, and sometimes, the limbic system-associated membrane protein (LSAMP) tumor suppressor (TS). Change in expression of osteo3q13.31 genes is ubiquitous in osteosarcoma, usually involving loss of expression. Underscoring the functional significance of osteo3q13.31 CNAs, expression of LOC285194 and BC040587 and sometimes LSAMP, correlates with the presence of osteo3q13.31 CNAs. Focal osteo3q13.31 CNAs and LOH are also common in cell lines from other cancers, identifying osteo3q13.31 as a universal candidate TS region. Osteo3q13.31 genes may function as a unit, since we demonstrate significant correlation between the expression of distantly spaced LSAMP, LOC285194, and BC040587. Supporting this notion, depletion of either LSAMP or LOC285194 promotes proliferation of normal osteoblasts through regulation of apoptotic and cell cycle transcripts, and vascular endothelial growth factor (VEGF)/VEGF receptor 1 (VEGFR1). Furthermore, the presence of LOC285194 or BC040587 deletions in tumor DNA is associated with poor survival of osteosarcoma patients. Osteo3q13.31 therefore represents a novel universal TS region containing several cooperatively acting genes.
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 3400.
Abstract 3407: Induction of G-protein coupled receptor-64 (GPR64) in Ewing Tumors supports angiogenesis and metastatic spread
Authors: Richter Günther H. , Fasan Annette , Rössler Sabine , Löwel Diana , Staege Martin S. , Burdach Stefan 
Published: February 2011

Abstract
Metastatic spread in Ewing Tumors (ET) is mostly hematogenous and malignant features have been shown to correlate with hypoxia and angiogenesis. Our microarray analysis confirmed an endothelial signature of this tumor and revealed the G-protein coupled receptor-64 (GPR64), an orphan receptor with normal expression restricted to human epididymis, to be highly induced in ET. Down-regulation of GPR64 in ET lines by RNA interference did not reduce their proliferative capacity in vitro as measured by plastic adherence dependent proliferation or contact independent growth in colony forming assays. However, inhibition of GPR64 expression impaired endothelial differentiation of ET in tube forming assays. Furthermore, GPR64 suppression inhibited local tumor development and metastatic spread of ET in immuno-deficient Rag2−/−γC−/− mice. The observed inhibition of metastatic spread correlated with a reduced proteolytic activity and invasiveness of such cells in vitro. Further microarray analysis after GPR64 knock down revealed a GPR64-mediated induction of VGEF receptor 1 ligand Placental Growth Factor (PGF) in ET. PGF itself was found to be induced by EWS-FLI1 in mesenchymal stem cells. Subsequent repression of PGF expression resulted in a phenotype of ET similar to the one observed after GPR64 knock down. GPR64 induction in ET supports invasiveness and shapes angiogenesis by induction of critical effectors. It therefore seems to play a central role in the pathogenesis of this tumor.
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 3407.
Abstract 3408: RNAi screening identifies STK10 as a novel therapeutic target for Ewing's sarcoma
Authors: Arora Shilpi , Gonzales Irma M. , Sima Chao , Khan Javed , Mousses Spyro , Azorsa David O. 
Published: February 2011

Abstract
Ewing sarcoma family tumors (ESFT) represent ∼ 3% of pediatric cancers and are the second most common bone malignancy in children and adolescents. Rearrangement of the EWS gene on chromosome 22q12 with an ETS gene family member is the underlying molecular genetic abnormality for Ewing's sarcoma. These translocations provide a valuable tool for accurate diagnosis of ESFTs and also represent ideal targets for the development of targeted therapeutics. The most common translocation is t(11;22)(q24;q12), which involves the proteins EWS and Friend Leukemia Integration Site 1 (FLI1). The newly formed EWS-FLI1 fusion protein is a transcription factor that could then lead to aberrant transcription and gives the ES cells a specific tumorigenic context. We employed a functional genomics approach based on high throughput RNA interference (HT-RNAi) analysis to identify “Achilles heel” targets or genes who's silencing affect the proliferation and survival of Ewing's sarcoma cells. We used a human “kinome” library targeting 572 kinases and four ES cell lines, TC-32, TC-71, SK-ES-1 and RD-ES for the HT-RNAi screening. All the screens were done in duplicate and the data was normalized and analyzed using the Z-score method. One gene that was a significant “hit” across all the four cell lines was serine threonine kinase 10 or STK10. Our validation confirmed that reduction in ES cell growth by STK10 siRNA was due to specific STK10 silencing and was not an off target effect. Moreover, silencing of STK10 in ES cells resulted in increased apoptosis. We also showed that normal human fibroblasts did not depend on STK10 for cell growth. Our results have confirmed that STK10, which belongs to the polo like kinase family, is required for the growth of ES cells. After further validation we will use these results for the development of specific drugs targeting STK10 and thereby accelerate the development of improved therapeutics for Ewing's sarcoma.
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 3408.
Abstract 341: Effects of immunosuppressive cyclosporin A on epidermal keratinocytes
Authors: Han Weinong , Ming Mei , He Tong-Chuan , He Yu-Ying 
Published: February 2011

Abstract
Non-melanoma skin cancer, the most common neoplasia after solid organ transplantation, causes serious morbidity and mortality and is related to sun exposure. Cyclosporin A (CsA) has been used widely to prevent rejection in organ transplantation. The mechanism of CsA action in causing cancer was thought to be well understood via immunosuppression. Here, we show that CsA promotes primary skin tumor growth in immune-deficient mice. CsA treatment at therapeutic plasma concentrations promotes growth and survival from removal of extracellular matrix or UVB radiation. CsA treatment enhances AKT activation following serum treatment and UVB radiation. Furthermore we found that PTEN expression, the negative regulator of AKT activation, is reduced significantly upon CsA treatment in human HaCaT and A431 cells and in mouse skin in vivo. Accordingly, the enhanced AKT activation in CsA-treated cells upon UVB radiation is observed in PTEN knockdown keratinocytes. CsA-induced PTEN suppression is critical for increased AKT activation. Inhibition of AKT activation abolishes CsA-promoted growth and survival, indicating that AKT hyperactivation is essential for the enhanced growth and survival of CsA-treated cells. In addition, mTOR signaling as a known AKT downstream target is required for CsA-enhanced growth and survival. Taken together, we have identified PTEN/AKT pathway as new molecular targets of CsA in epidermal keratinocytes, suggesting a previously unknown mechanism in CsA-enhanced skin carcinogenesis. Our findings challenge assumptions about how CsA-associated tumors arise in skin.
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 341.