bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4211: Development of a prognostic gene expression signature for invasive bladder cancer
Authors: Chu In-Sun , Leem Sun-Hee 
Published: August 2012

Abstract
Bladder cancer comprises of highly heterogeneous tumors and is a malignancy requiring a high surveillance because of the frequent recurrences and the poor clinical outcome when tumors progress into invasive disease. Patients also with superficial and invasive tumors have remarkably different 5-year survival rates reflecting their biological differences. The profiles of gene-expression signatures have become an important and promising way for cancer prognosis and treatment. In addition to their application in cancer class prediction and discovery, microarray gene expression signatures can be used for the prediction of patient survival. Gene expression data were collected from tumor specimens from 165 patients with Korean bladder cancer. We selected then genes use Cox proportional hazard model whose expression patterns are proportionally associated the length of cancer-specific survival (CFS). The expression levels of 256 probes were correlated with CFS time (p&lt;0.005). In poor prognosis subtype, for example, the expression of STK6 (Aurora kinase A), AURKB (Aurora kinase B), and TPX2 (regulator of Aurora kinases) are all up-regulated. One of the best characterized phenomenon of invasion is Epithelial-to-Mesenchymal Transition (EMT). We can't see either vimentin nor Krt19 over-expressed in better prognosis subtype.
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 4211. doi:1538-7445.AM2012-4211
Abstract 4212: Characterization of the gene expression network that underlies cancer cell-platelet interactions and cancer progression
Authors: Tan Bertrand , Liu Hsuan , Wu Wen-Hsin 
Published: August 2012

Abstract
Understanding how cancer cells outgrow and escape from the primary site is important for development of novel therapeutic scheme. Our recent results from microarray-based gene expression profiling analysis demonstrate differential expression of a cohort of genes (∼220) in the circulating tumor cells, many of which play a role in haemostasis and thrombosis. To screen for putative transcription factors that might contribute to the metastasis-associated gene expression alterations (and possibly the upregulation of haemostatis-associated genes), we first undertook bioinformatics approach by analyzing differentially expressed genes using GeneGo. From the list of potential transcription factors that are identified from the bioinformatics approach, we selected two TFs (CREB and Sp1) for further studies. Consistent with the upregulation of selected genes, ChIP analyses demonstrated promoter occupancy by these two TFs, and further a greater degree of binding in the circulating/metastatic tumor cells. These results suggest their link to the transcriptional induction of the target genes in these cells. Interestingly, we also discovered that the levels of c-fos and Ser15 phosphorylation on p53 underwent an increase in these cells. To dissect the signaling pathways that may underlie the observed transcriptomic alteration, we again applied gene ontology analysis to pinpoint possible signaling networks. Such profiling demonstrated an elevation of the TGFβ2/BMP pathway and a downregulation of EGFR/ErbB signaling in circulating cells compared with the parental line, possibly suggesting a role of the corresponding pathways in the transcriptomic as well phenotypic changes in the metastatic cells. In addition, changes in the expression of several signaling cascade intermediates - Akt, Erk, JNK - were also evident based on immunoblotting results. Our preliminary results have revealed the potential involvement of several transcription factors and signaling pathways in our metastasis experimental model. Discussion of their implications and future work is also included.
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 4212. doi:1538-7445.AM2012-4212
Abstract 422: Nanog promotes PI3K/Akt and mTOR-mediated invasion in head and neck squamous cell carcinoma
Authors: Rahimy Elham , Yi David , Lew Daniel , Abhold Eric , Kiang Alan , Wang-Rodriguez Jessica , Ongkeko Weg 
Published: August 2012

Abstract
Head and neck squamous cell carcinoma (HNSCC) affects nearly 40,000 new patients annually in the United States with approximately 50% of these patients having a poor prognosis. Frequent metastasis of the primary tumor to nearby cervical lymph nodes and local critical structures poses a major problem in the treatment of HNSCC. To date, several molecular mediators of invasion and metastasis in HNSCC have been studied; however, with the emergence of the cancer stem cell hypothesis, other genes normally associated with self-renewal and pluripotency in stem cells would also need to be evaluated for their role in tumor invasion and metastasis. In the present study, we used various functional assays to determine the role of Nanog in HNSCC invasion and metastasis as well as identify the underlying pathway through which Nanog acts to regulate invasion and metastasis. We observed that Nanog overexpression increased invasion and cell migration in two cell lines (UMSCC-10B and UMSCC-22B) while Nanog knockdown using siRNA decreased invasion and cell migration in both cell lines and in a putative HNSCC cancer stem cell culture which expressed high levels of Nanog. Treatment with LY294002 or Rapamycin using doses that did not significantly affect cell viability and proliferation dramatically reversed both invasion and migration conferred by Nanog overexpression, indicating the effect is most likely dependent upon the PI3K/Akt/mTOR pathway. By western blot, we found that Nanog-overexpressing cells expressed higher levels of p-Akt and p-mTOR compared to control cells or Nanog-knockdown cells, confirming regulation of Akt by Nanog. In addition, Nanog overexpression resulted in the induction of MMP-2/MMP-9 as well as EMT genes Snail, Vimentin, and Twist. This enhanced expression of EMT was consistent with the observed increased migration as demonstrated by a wound healing assay. Nanog regulation in a mouse model is currently under way to confirm our results in vivo. The results of our study support the possibility of screening for Nanog expression as a prognostic tool. Meanwhile, further efforts aimed at elucidating the signaling pathway between Nanog and Akt may reveal novel treatment targets.
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 422. doi:1538-7445.AM2012-422
Abstract 4223: Gamma-tocotrienol and simvastatin target TIC and EMT populations in drug-resistant breast cancer
Authors: Gopalan Archana , Yu Weiping , Sanders Bob G. , Kline Kimberly 
Published: August 2012

Abstract
Background and significance: Breast cancer (BC) is the second leading cause of cancer deaths in women. Despite great advances in treatment of early and advanced BC, relapse with drug resistance and metastasis is the biggest impediment to successful remission. Accumulating evidence supports the emerging concept that cancer stem cells (CSCs, also called tumor initiating cells, TICs), a rare tumor cell population that exhibits self-renewal and differentiation properties, are responsible for tumor relapse and metastasis. Hence, identifying molecular mediators responsible for maintenance of TICs and metastasis in drug resistant breast cancer is important to develop better and successful therapeutic strategies. Model system and methods: Acquired tamoxifen resistant (MCF-7/TamR) and doxorubicin resistant (MCF-7/ADR) cell lines as well as their isogenic parental counterparts MCF-7/S and MCF-7/WT, respectively were used in this study. ALDH activity assay was used for characterization and enrichment of TIC population. Immuno-staining/FACS of CD44+/CD24- was used to determine the metastasis potential in-vitro. Western blot analyses were used to detect signal transduction mediators known to be important for maintenance of TIC and EMT populations. Results: Both drug resistant cell lines expressed a higher percentage of TIC population as detected by ALDH activity and elevated EMT population as detected by CD44+/CD24- and increased EMT marker Vimentin and decreased MET marker E-cadherin in comparison with the isogenic sensitive cell lines. Both drug resistant cell lines uniformly expressed higher levels of pStat-3, c-Myc and CyclinD1 in comparison with their respective parental cell lines. Knockdown of Stat-3 using siRNA and Stat-3 inhibitor reduced TIC populations, reduced EMT populations, and decreased c-Myc and CyclinD1, but did not affect Vimentin and E-cadherin protein expression. γT3 and SVA alone and in combination reduced TIC populations as measured by reduced ALDH population and inhibition of mammospheres. Both agents alone and in combination reduced the EMT populations and reduced the levels of p-Stat3, c-Myc and CyclinD1expressed in drug-resistant breast cancer cell lines. Conclusion: These in vitro data demonstrate that drug resistant breast cancer cell lines contain high levels of TIC and EMT sub-populations that are in part controlled by the Stat-3 pathway. Furthermore, αT3 and SVA alone and in combination show the ability to target TIC population and metastasis associated mediators. Supported by the Clayton Foundation for Research.
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 4223. doi:1538-7445.AM2012-4223
Abstract 4224: MiR-7 and its novel target regulate sensitivity to microtubule stabilizing agents
Authors: Liu Lingling , Rogler Charles E. , Horwitz Susan Band , McDaid Hayley M. 
Published: August 2012

Abstract
Microtubule stabilizing drugs, such as Taxol that is used in the treatment of numerous malignancies, cause distinct responses in cancer cells, including apoptosis, mitotic catastrophe, necrosis and accelerated senescence. However, drug resistance, a complex and mutlifactorial phenotype, is a major obstacle to therapy and the foremost cause of disease progression and cancer-related mortality. MiRNAs are small non-coding RNAs that regulate protein expression by targeting their 3′UTRs, and are emerging as key regulators of cancer pathogenesis that can influence sensitivity to chemotherapy and radiotherapy. We have identified miR-7 as a regulator of sensitivity to the microtubule-stabilizing agents, discodermolide and Taxol. Over-expression of miR-7 in the lung cancer cell lines A549 and H2122, strongly inhibited cell proliferation and sensitized the cells to drug-induced apoptosis. Over-expression of miR-7 also increased the number of acidic lysosomes, as measured by β-galactosidase activity, which likely reflects lysosomal stress. It also increased basal and drug-induced caspase activation, which most likely mediate the sensitizing effects of discodermolide and Taxol. In addition, we validated that the transcription factor, Kruppel like factor 4 (KLF4) is a target of miR-7, and that its expression also regulates sensitivity to discodermolide and Taxol. KLF4 is suppressed in discodermolide- and Taxol-treated A549 cells that have a strong senescent phenotype, and is over-expressed in A549 cells that are resistant to either drugs. ShRNA-mediated knockdown of KLF4 in A549 and H2122 also sensitized cells to discodermolide and Taxol though to a lesser degree than miR-7 overexpression, and also inhibited cell proliferation and increased lysosomal β-galactosidase activity and caspase activity. Thus, we hypothesize that suppression of KLF4 partially mediates the potent anti-tumor effects of miR-7 in A549 and H2122 lung cancer cells. In summary, we have identified miR-7 and its novel target, KLF4, as important regulators of sensitivity to discodermolide and Taxol, and suggest that miR-7 is a promising candidate for therapeutic development.
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 4224. doi:1538-7445.AM2012-4224
Abstract 4233: The protein ps20 increases resistance to docetaxel in PC3 and LNCAP prostate cancer cell lines
Authors: Galustian Christine , Hickman Oliver , Smith Richard A.G. , Dalgleish Angus G. , Ukimura Osamu , Gill Indebir S. , Vyakarnam Annapurna , Dasgupta Prokar 
Published: August 2012

Abstract
Introduction The protein ps20 encoded by the WFDC1 gene, is a member of a protein family containing conserved whey-4-disulphide-core (WFDC) domains. Ps20 is upregulated in prostate cancer epithelium and expression is thought to correlate with disease progression. The aim of this study was to determine whether ps20 expressed by prostate cancer cells also increases docetaxel resistance. Methods The cell-lines LNCaP and PC3 express low endogenous ps20, but were transfected with empty vector (EV) or WFDC1 gene vectors that increase WFDC1 RNA and ps20 protein expression by over 100% as measured by qPCR and ELISA. Docetaxel was added from 0.001nM –1µM with or without ps20 antibody (1G7) and cell-killing was assessed by MTT after 48 hours. Results EV-transfected PC3 and LNCaP cells have docetaxel IC50s of 0.223+/-0.05 and 0.16+/- 0.09nM respectively. In WFDC1-transfected PC3 and LNCAP, IC50s are increased to 0.677+/-0.11 and 0.326+/-0.05nM respectively (p&lt;0.001 by paired t-test). Therefore there is a 303% and 203% increase in docetaxel IC50s in PC3 and LNCaP respectively. However, when WFDC1-cells are incubated with docetaxel and ps20 antibody, IC50s are lower than those with EV cells (0.04+/-0.03 and 0.07+/-0.02nM for PC3 and LNCaP respectively, p&lt;0.01 by paired t-test). Therefore, endogenous WFDC1/ps20 on PC3 and LNCaP cells may contribute to docetaxel resistance. Conclusions Ps20 expression by prostate cancer cells is associated with increased resistance to docetaxel- a gold-standard chemotherapy for castrate-resistant prostate cancer. Inhibition of WFDC1/ps20 expression on prostate cancer cells may therefore represent one mechanism of restoring sensitivity in patients that are refractory to docetaxel.
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 4233. doi:1538-7445.AM2012-4233
Abstract 4237: Inhibition of prostate cancer associated kinases by Tillandsia recurvata: A Jamaican medicinal plant
Authors: Lowe henry , Toyang Ngeh J. , Bryant Joseph 
Published: August 2012

Abstract
Prostate cancer is the second most common cause of death from cancer in men of all ages. The three conventional treatment options include surgery, radiation and chemotherapy. In many cases, these treatments are used in combination. Chemotherapy is however the most widely used tool in prostate cancer treatment especially where the cancer has metastasized or spread to other organs of the body. Increased resistance to current chemotherapies by prostate cancer calls for an urgent need to discover and develop new therapeutics that can slow the growth of cancer cells while having lesser side effects on the patients. The development of target therapies for the treatment of human cancers is revolutionizing the concept of cancer treatment today. This type of therapeutic approach is directed to the inhibition of molecular targets that play a pivotal role in tumor progression such as the kinases. It is only in recent years that kinases have emerged as major targets for therapeutics, particularly for cancer related therapies. Relatively few kinase inhibitors have been identified to date and efforts are being made to discover new small molecules kinase inhibitors. The Island of Jamaica is known for its rich biodiversity and abundance of medicinal plants used in folk medicines. In an effort to discover new anticancer drugs from natural products several Jamaican medicinal plants were screened for anticancer activity. The Jamaican Ball Moss (Tillandsia recurvata L.) was one such plant that exhibited potent activity against the PC-3 prostate cancer cell line in vitro (IC50 = 2.4µg/ml) and was selected for further studies. The crude extract of Ball Moss was screened for interaction with 451 kinases. The crude Ball Moss extract showed potent kinase inhibitory activity against 5 kinases (kd = 8-14 µg/ml), of which 4 are implicated in prostate cancer growth and proliferation. The four kinases are; CSNK2A2, DRAK1, GAK and MEK5. The above results validate the folk use of this medicinal plant as well as make it a good candidate for development into a prostate cancer treatment or for the discovery of the bioactive molecules in the plant. Studies are currently underway to confirm the ability of Ball Moss to halt the growth of prostate tumors in mice as well as measure the inhibitory effects of the crude extract on the 4 related kinases in vivo. The isolation and characterization of the kinase inhibitors in ball moss is also in progress.
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 4237. doi:1538-7445.AM2012-4237
Abstract 4240: The translocator protein 18kDa in the morphogenesis of breast epithelial cells in 3D culture
Authors: Wu Xiaoting , Gallo Kathleen 
Published: August 2012

Abstract
Translocator protein (TSPO) is an 18 kDa mitochondrial membrane protein, first identified as a second binding site for benzodiazepine. Elevated levels of TSPO have been associated with breast cancer progression and with increased proliferation in cancer cells whereas TSPO ligands, PK11195 and Ro5-4864, which may serve as TSPO antagonists, inhibit proliferation in multiple cancer cell lines. Whether TSPO actually contributes to breast cancer progression is not known. In this study, the impact of TSPO up-regulation in breast epithelial cells is being assessed using a 3D Matrigel culture system. MCF10A mammary epithelial cells form well-polarized acini structures with a hollow lumen when grown in 3D Matrigel, whereas expression of oncogenes in MCF10A cells often induces phenotypes such as increased acinar size and filling of the lumen. In this study, a pool of stable TSPO expressing breast epithelial MCF-10A cells has been constructed. TSPO overexpressing MCF-10A cells when grown in 3D matrigel formed larger acini compared with control acini; and displayed abnormal lumen formation. Such a disruption of normal mammary epithelial morphogenesis by TSPO may resemble an early stage breast lesion leading to breast cancer. Immunofluorescent staining revealed increased levels of Ki-67 (a proliferative marker) in TSPO overexpressing acini compared with control acini, suggesting that TSPO promoted proliferation during mammary epithelial morphogenesis. TSPO ligands, including PK11195 and RO5-4864, inhibited proliferation of stable TSPO over-expressing MCF-10A cells in 2D plastic culture. Studies on the impact of TSPO ligands on the morphogenesis of MCF10A and breast cancer cells in 3D culture are being conducted.
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 4240. doi:1538-7445.AM2012-4240
Abstract 4243: Oncogenic K-Ras transforms three-dimensional colon epithelia through upregulation of ERK-MAPK signaling
Authors: Magudia Kirti , Hall Alan 
Published: August 2012

Abstract
Colorectal cancers have the third highest incidence and are the second most common cause of cancer-related death when considering tumors that affect both men and women in the United States. Interestingly, a third of these tumors harbor activating mutations in K-Ras and are associated with worse outcomes. Caco-2 cells, derived from a colorectal carcinoma, are noninvasive and do not harbor mutations in K-Ras, B-Raf or PI3KCA. This cell line has historically been used as a model to study normal, differentiated colonic epithelium in two-dimensional cell culture. Recent studies have used Caco-2 cells in a three-dimensional cell culture system to better model epithelial morphogenesis. In this study, we studied the effects of introducing oncogenic K-Ras into three-dimensionally cultured Caco-2 cells. Control Caco-2 cells seeded in extracellular matrix generate hollow, polarized structures after ten days. In contrast, Caco-2 cells expressing oncogenic K-Ras formed much larger and filled structures that lack a central lumen. Furthermore, western blot analysis of protein lysates made from day 1 and day 10 control structures revealed a strong decrease in cyclin B, suggesting a reduction in the proportion of cells undergoing mitosis. K-Ras structures, however, maintained cyclin B levels, providing evidence of prolonged proliferation. In addition, immunofluorescence of the apical marker aPKC and the tight junction protein ZO-1 revealed that K-Ras structures have disrupted polarity. Caco-2 cells expressing oncogenic B-Raf phenocopied our results with oncogenic K-Ras. Conversely, MEK inhibition with U0126 reverted K-Ras structures back to normal morphology, indicating that K-Ras acts through the ERK-MAPK signaling pathway. The expression of active versions of PI3KCA and RalGDS, other Ras effectors, in Caco-2 cells produced structures identical to control. Further work aims to elucidate a more specific mechanism of Ras downstream of the ERK-MAPK signaling pathway in our three-dimensionally cultured Caco-2 system.
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 4243. doi:1538-7445.AM2012-4243