bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1183: Association of germline variants of the TGFβR1 gene in colorectal cancer patients
Authors: Schaeper James P. , Murray Kevin , DeBrosse Jessica L. , Vogt Briana , Lucas Denise , Colligan Bruce M. , Deddens James A. , Douglass Larry E. , Graff Jeremy R. , Carter Julia H. 
Published: February 2011

Abstract
Colorectal cancer is the second leading cause of cancer death in the United States and approximately 147,000 new cases of colorectal cancer (CRC) were expected in 2009. Most people with early colorectal cancer have no symptoms and symptoms usually only appear with more advanced disease. Therefore, susceptibility markers which could possibly identify patients at risk for colorectal cancer are important for earlier detection of the disease. Germline variations in the transforming growth factor beta (TGF-β) type I receptor (TGFβR1) have been found to be associated with several human cancers, in particular with advanced ovarian cancers, suggesting a role in advanced disease stage. We analyzed two genetic variants in the TGFβR1 gene for their association with colorectal cancer. One is an intronic variant, G→A polymorphism (Int7G24A), which is 24 base pairs downstream of the intron-exon 7 boundary. The other is a nine base pair deletion (TGFβR1*6A) in exon 1 of TGFβR1. Using capillary electrophoresis, we analyzed paraffin-embedded tissue specimens from 147 patients with CRC and 169 non-cancer controls. There was no difference between male and female non-cancer controls in the prevalence of either variant. When CRC cases were compared to non-cancer controls, it was found that the prevalence of TGFβR1*6A was not significantly increased (p = 0.11) but Int7G24A prevalence was significantly increased (p = 0.000039). For CRC cases and controls, the wild type genotype was compared to patients with either or both variants and a significant difference was found primarily due to the increased prevalence of Int7G24A in CRC patients (p = 0.000052). Int7G24A was more commonly found in invasive and metastatic CRC patients as compared to non-cancer controls (p = 0.00030). We conclude that Int7G24A is a potential susceptibility marker for CRC and is associated with advanced disease stage.
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 1183.
Abstract 1192: Impedance based kinetic cellular response profiling in drug discovery and development
Authors: Ke Ning , Wang Xiaobo , Xu Xiao , Abassi Yama 
Published: February 2011

Abstract
A novel cell-based kinetic profiling approach using impedance readout for monitoring the effect of small molecule compounds will be described. This non-invasive readout allows continuous sampling of cellular responses to biologically active compounds and the ensuing kinetic profile provides information regarding the temporal interaction of compounds with cells. The utility of this approach was tested in two approaches. First, compounds with similar mechanism of action produced similar impedance-based time-dependent cell response profiles (TCRP). The TCRP was used to identify novel mechanisms for existing drugs and also identified potential off-target activity for COX-2 inhibitor, celecoxib and the experimental compound, monastrol. The second approach entailed using this profiling approach to screen a 120,000 compound library. We identified novel anti-mitotic compounds as well as compounds interfering with DNA synthesis. Furthermore, we also identified compounds specific for oncogene addiction pathways. We will present data in support of both approaches in this presentation.
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 1192.
Abstract 1195: Oct-1 as a potential biomarker for oxaliplatin-based therapy in non-small cell lung cancer
Authors: Kadoch Orli , Li Tong , You Liang , Yee Sook-Wah , Giacomini Kathleen , Jablons David M. , Xu Zhidong 
Published: February 2011

Abstract
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death in the developed world. Platinum-based chemotherapy, including agents such as cisplatin and carboplatin, represents the standard therapeutic regimen in both adjuvant and metastatic settings. However, these treatments are often associated with profound dose-limiting toxicities in some patients. It is therefore important to develop a rational basis for individualized treatment of NSCLC. Recently, oxaliplatin, a third generation anti-neoplastic platinum-based agent has been explored as a component of therapy for NSCLC. Tumor-specificity and anti-tumor efficacy of oxaliplatin were correlated with active drug influx and OCT-1 expression in colon cancer, but expression of OCT-1 has not been evaluated in NSCLC until now. In this study, we hypothesize that OCT-1 is a major determinant of response to oxaliplatin in lung cancer expressing high levels of the gene and could serve as a predictive biomarker for oxilaplatin-based therapy. We investigated the expression of OCT-1 in lung adenocarcinoma and squamous cell carcinoma specimens using immunohistochemistry (IHC)-based methods. IHC staining was performed on 172 paired specimens on tissue microarrays (TMA) developed in our Thoracic Oncology Program. An anti-human OCT-1 monoclonal antibody and biotinylated anti-rabbit secondary antibody were used for hybridization. The IHC slides were then developed using ABC-DAB procedures and images were acquired using the Aperio ScanScope CS and XT digital slide acquisition systems.
We observed 65 of 91 (71%) adenocarcinomas and 41 of 71 (57%) squamous cell carcinomas to be positive for OCT-1 expression. We identified low levels or absence of OCT-1 expression in the majority of paired normal lung specimens (74%). The OCT-1 levels were significantly higher in both adenocarcinomas and squamous cell carcinomas than in matched normal lung (p&lt;0.001). In addition, the percentage of specimens expressing OCT-1 was significantly higher in adenocarcinomas than in squamous cell carcinomas (p&gt;0.05), suggesting more potential efficacy of oxilaplatin in patients with adenocarcinomas.
In conclusion, OCT-1 was more abundantly expressed in both lung adenocarcinomas and squamous cell carcinomas than in matched normal specimens. The expression status of OCT-1 could serve as a novel predictive biomarker for the selection of patients with NSCLC for oxaliplatin-based chemotherapy. (Supported by NIH grant CA 093708-01A3 and TRDRP grant 17FT-0126)
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 1195.
Abstract 1198: Adaptation to ER stress as a driver of increased expression of Mcl-1 with melanoma progression
Authors: Jiang Chen Chen , Zhuang Li Qing , Dong Li , Throne Rick , Lavis Christopher , Hersey Peter , Zhang Xu Dong 
Published: February 2011

Abstract
Past studies have shown that Mcl-1 expression increases with melanoma progression, which is an important mechanism of resistance of melanoma cells to apoptosis. We show here that up-regulation of Mcl-1 in melanoma is a consequence of adaptation of melanoma cells to endoplasmic reticulum (ER) stress. Exposure of cultured melanoma cells and fresh melanoma isolates to pharmacological ER stress inducers results in up-regulation of Bcl-2 and Mcl-1. Inhibition of Mcl-1 renders melanoma cells more sensitive to ER stress-induced apoptosis even when Bcl-2 is over-expressed, but inhibition of Bcl-2 does not increase the sensitivity to ER stress-induced apoptosis in melanoma cells over-expressing Mcl-1. Up-regulation of Mcl-1 by ER stress involves multiple mechanisms. The transcriptional increase is mediated by the transcription factor ETS-1 downstream of the XBP1 axis of the unfolded protein response, whereas down-regulation of GSK3α is responsible for reduced proteasomal degradation of Mcl-1 in melanoma cells under ER stress. Studies on a large cohort of melanocytic tumor tissue sections revealed that expression of GRP78, a classic marker of ER stress, and expression of LDH5, an indicator of hypoglycemia that is one of the causes of ER stress, correlate with Mcl-1 expression, indicating that the increase in Mcl-1 with melanoma progression in vivo is associated with ER stress. In addition, we demonstrate in this report that induction of apoptosis by ER stress in melanoma cells deficient in Mcl-1 is mediated by the BH3-only proteins PUMA and Noxa, whereas another BH3-only protein Bim does not appear to play a part in melanoma cells as it does in other cell types. In summary, our results indicate that adaptation to ER stress is a driver of up-regulation of Mcl-1 during progression of melanoma, and suggest that strategies aimed at inhibiting the activity of Mcl-1 may be important in the treatment of melanoma.
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 1198.
Abstract 12: Metastatic neuroblastoma cancer stem cells display a mixed phenotype of tumor and niche origin required for survival
Authors: Hansford Loen M. , Morozova Olena , Lipman Tatiana , Blakely Kim , Ohira Miki , Marrano Paula , Angelini Paola , Moffat Jason , Thiele Carol J. , Thorner Paul , Dick John , Nakagawara Akira , Irwin Meredith , Marra Marco , Kaplan David R. 
Published: February 2011

Abstract
Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and is the most common cancer of infancy. 50% of patients have metastases at diagnosis, of which 85% will die after multiple relapses from metastatic disease. We identified tumor-initiating cells (TICs) from bone marrow (BM) metastases of high-risk patients that are propagated as spheres and that have many properties of cancer stem cells, and form NB in mice with as few as 1 cell. To understand patient relapse and disease progression, we compared NB-TICs from BM with those from tumor and brain metastases and SKPs, a normal pediatric stem cell counterpart, by cDNA microarray, flow cytometry, and whole genome shotgun sequencing transcriptome analysis. BM-derived NB-TICs expressed primitive neural crest and neuronal markers as well as hematopoietic markers from primitive, myeloid, and B-cell lineages and contained VDJ gene rearrangements, which are normally associated with B-cell leukemias. Hematopoietic genes were not expressed or expressed at very low levels in tumor-derived sphere lines and a line from an NB brain metastasis, however brain metastasis-derived TICs expressed CD133, while BM-derived NB-TICs did not. Furthermore, we found that shRNA to CD74, which is upregulated in B-cell lymphoma and multiple myeloma and is a therapeutic target for those cancers, induced the rapid death of NB-TICs but not normal SKPs. Interestingly cells co-staining for the hematopoietic markers CD45 or CD74 and the neural neural progenitor marker nestin were found in BM smears of patients with relapsed NB in the bone marrow.
We suggest that metastatic TICs from some tumors adopt resident niche-specific gene expression signatures, which may aid diagnosis and the development of novel treatments. We hypothesize that drugs used for leukemia may be efficacious therapeutics for metastatic NB, and are currently testing this hypothesis in mouse models.
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 12.
Abstract 1212: PIN1 enhances the anti-apoptotic function of survivin in cancer cells
Authors: Cheng Chi Wai , Pang Roberta , Fok Elaine , Kwong Yok Lam , Tse Eric 
Published: February 2011

Abstract
Introduction: The peptidyl prolyl cis/trans isomerase 1 (PIN1) binds the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 catalyses isomerisation of the prolyl peptide bond, and subsequently induces conformational changes in the substrates and modulates their functions. Through this mechanism, PIN1 is involved in many cellular events, including cell cycle progression, cell proliferation and cell transformation. Our previous work has revealed that PIN1 is over-expressed in hepatocellular carcinomas (HCC) and enhances hepatocarinogenesis. In this study, we investigated the role of the interaction between PIN1 and Survivin, an inhibitor of apoptosis protein (IAP), in tumorigenesis.
Methods and Results: By co-immunoprecipitation experiments, we found that PIN1 interacted with Survivin via the phosphorylated Thr34-pro motif in Survivin. We then further investigated the effects of PIN1 on the anti-apoptotic function of Survivin using flow cytometry by staining the cells with Annexin V and 7-AAD. Both caspase-9 and caspase-3 activities were also detected by flow cytometry. Through these experiments, over-expression of PIN1 in cervical carcinoma HeLa and human nontumorigenic liver MIHA cells were found to suppress the apoptotic response induced by staurosporine through inactivation of caspase-9 and caspase-3. However, the expression of the PIN1 mutants that are catalytically inactive or defective for protein-binding activity did not result in an inhibition of apoptosis. Likewise, the targeted inhibition of PIN1 by small interfering RNA in HeLa and human hepatoma PLC/PRF/5 cells enhanced the apoptotic response induced by staurosporine through caspase-9 and caspase-3 activation. In addition, down-regulation of Survivin by small interfering RNA in PIN1 over-expressing cells abolished the anti-apoptotic effect induced by PIN1, suggesting that the inhibition of apoptosis is mediated through the PIN1-Survivin interaction.
Conclusion: Since phosphorylation of Thr34 in Survivin suppresses pro-caspase-9 activation by increasing the binding between Survivin and pro-caspase-9, our results suggest that PIN1 may further regulate the anti-apoptotic role of Survivin through modulation of its binding to pro-caspase-9.
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 1212.
Abstract 1220: Role of human sLZIP in PMA-induced apoptosis in LNCaP prostate cancer cells
Authors: Kim Yoonseo , Ko Jesang 
Published: February 2011

Abstract
Androgen and the androgen receptor (AR) play important roles in prostate cancer development, and androgen ablation has been the main therapeutic option for the treatment of locally advanced or metastatic prostate cancer. It has been reported that androgen-dependent LNCaP prostate cancer cells undergo apoptosis upon phorbol ester 12-myristate 13-acetate (PMA) treatment. In this study, we investigated whether transcription factor sLZIP is able to protect LNCaP cells from PMA-induced apoptosis. Results from cell morphology, cell cycle and apoptosis assay showed that PMA-induced apoptosis of LNCaP cells was inhibited in cells transfected with sLZIP. We also examined the effect of sLZIP on PARP cleavage and caspase 3 activation. PMA induced PARP cleavage and capase 3 activation, however, cells transfected with sLZIP exhibited reduced cleavage of PARP and caspase 3 in a dose dependent manner. sLZIP induced phosphorylation of ERK and increased cyclin D3expression. OverexpressionofsLZIPattenuatedPMA-mediatedTNF-α induction in LNCaP cells. These results indicate that human sLZIP negatively regulates PMA-induced apoptosis of prostate 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 1220.
Abstract 1222: Down-regulation of MEIS2 leads to apoptosis in human colorectal cancer cells
Authors: Hong Chang Soo , Zhao Xue-Feng , Moon Sung Min , Lee Hye Won , Lee Snag Rok , Park Yong Kyu 
Published: February 2011

Abstract
Three amino-acid loop extension (TALE) homeobox proteins MEIS2 is a transcriptional factor that regulates the expression of large sets of downstream target genes by direct binding to their promoter DNA. MEIS2 controls cell growth and differentiation during embryogenesis and carcinogenesis and is overexpressed in ovarian and pancreas cancer. However, the underlying cellular mechanisms remain largely unsolved. In this study, we report that MEIS2 is aberrantly expressed in colorectal adenocarcinoma cells and is profound proliferative and anti-apoptotic effects against colon cancer cells. In immunohistochemical staining, MEIS2 is positively stained in colorectal adenocarcinoma cells and has strong intensity in its nucleus, compared to normal colonic crypt cells. We found that down-regulation of MEIS2 by specific shRNA inhibited the cell growth (50% decrease as compared with control cultures, P&lt;0.001) of HCT-116 colon cancer cell, due to an increase apoptosis (from 3% in control cultures to 65% after 72 hour from transient transfection of MEIS2 shRNA, P&lt;0.001) as determined by MTT and FACScan apoptosis assay. Knockdown of MEIS2 by specific shRNA transfection reduced the expression of Akt, and decreased the phosphorylation of its downstream target proteins such as forkhead transcription factors (FoxO) and p27, and increased the nuclear localization of nonphosphorylated FoxO and p27, which result in activation of apoptosis. In summary, our data indicate that MEIS2 promotes cell growth and plays critical role as novel anti-apoptotic factor through regulation of Akt expression within Akt/PKB signaling pathway in colorectal 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 1222.
Abstract 1236: Interferon consensus sequence binding protein (ICSBP)-induced cell proliferation mediated by TGF-β signaling pathway and MAPKs activation in HL-60 cells
Authors: Park Byung-Kiu , Kim Hee Jung , Sung Jee Young , Kim Yong Nyun 
Published: February 2011

Abstract
Interferon consensus sequence binding protein (ICSBP), also known as IRF-8, is a member of the interferon (IFN)- regulatory factors (IRFs) induced by IFN-γ. ICSBP is mostly associated with differentiation of hematopoietic cells and known as a tumor suppressor. ICSBP contains the conserved transactivation domain which is shared by Smad4, suggesting a possible connection of IRF and TGF-β signaling. To test this connection, ICSBP was stably expressed in acute promyelocytic leukemia cell line, HL-60, that expresses little ICSBP. Although TGF-β receptor expression was undetectable in HL-60 cells, the expression of ICSBP in HL-60 (ICSBP-HL-60) resulted in an increased TGF-β receptor expression. Interestingly, even without TGF-β stimulation, both Smad and non-Smad pathways were activated in ICSBP-HL-60 cells compared with Mock-HL-60 cells, indicating ligand-independent activation of TGF-β receptor signaling. In addition, ICSBP expression augmented cell growth and suppression of ICSBP using siRNA specific for ICSBP abolished TGF-β receptor expression and attenuated cell growth. Consistently, reduction of TGF-βRI using siRNA or TGF-β receptor inhibitor, SB431542, also attenuated growth of ICSBP-HL-60 cells compared with Mock cells. Furthermore, MAPK pathways appeared to be involved in ICSBP-mediated cell growth because MAPKs are activated in ICSBP-HL-60 cells and specific inhibitor of this pathway was able to decrease the growth of ICSBP-HL-60 cells more sensitively than Mock-HL-60 cells. Suppression of ICSBP by siRNA effectively inhibited phosphorylation of MAPKs. All these data suggest that ICSBP up-regulates TGF-β receptor, activates ligand-independent TGF-β mediated signaling pathways, such as MAPKs activation, leading to cell proliferation. This study provides a new function of ICSBP in the regulation of cell proliferation
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 1236.
Abstract 1241: Tcf7, a mediator of Wnt/β-catenin signaling, is upregulated in mammary glands of BK5.ATF3 mice, without prior development of mammary tumors
Authors: Yan Leqin , Powell K. Leslie , MacLeod Michael C. 
Published: February 2011

Abstract
We previously showed that in a transgenic model (BK5.ATF3) in which the transcription factor ATF3 is overexpressed in cytokeratin 5 (CK5)-expressing cells, parous female mice develop mammary carcinomas with about 70% incidence between 6 months and one year of age. In these mice, ATF3 is overexpressed in cell nuclei in the myoepithelial cell layer (basal layer) of normal mammary glands, and in the basal cell layers of the tumors, in addition to expression in epidermis and other CK5-expressing epithelia. Non-parous, female transgenic mice exhibited a high incidence of squamous metaplastic lesions in the mammary glands between 14 and 32 weeks of age. These lesions showed dysregulation of cytokeratin expression, but no other molecular defects in non-parous mammary glands have been described. Several genes in the EGFR-MAPK pathway and in the Wnt/β-catenin pathway are misregulated in the mammary tumors that arise in parous transgenic mice. When expression of these genes was compared between normal mammary glands from transgenic and non-transgenic mice, the only genes that showed significant differences were Lef1 and Tcf7, two members of the family of transcription factors that dimerize with β-catenin to mediate Wnt-induced transcription. These genes were overexpressed by 2.5-3-fold in the transgenic mammary glands. A mouse mammary tumor cell line, EMT6, was found to have high levels of expression of both Atf3 and Tcf7, but not Lef1. Expression of Atf3 was knocked down by 97% in EMT6 cells 48 hrs post-treatment with Atf3-specific siRNA. This resulted in about a 70% decrease in expression of Tcf7, and a similar decrease in expression of cJun, a known target of Wnt/β-catenin signaling. This is consistent with the possibility that Tcf7 is a target gene for Atf3, and may be involved in the early stages of tumorigenesis in this model.
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 1241.