bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4882: Downregulation of core component of miRNA machinery, Tudor-SN, impedes NSCLC resistance to chemotherapy
Authors: Akbar Nadeem S. , Surova Olga , Zhivotovsky Boris 
Published: August 2012

Abstract
Lung cancer (LC) is among the most common tumors liable for worldwide highest mortality rate. It has a poor prognosis and symptoms related to disease occur at an advanced stage where therapy response becomes less effective. Resistance to radio- and chemotherapy of all tumors in general and LC, in particular, is a complex phenomenon. Evasion of cell death is one of the key hallmarks of both tumorigenesis and resistance to treatment. Differential expression of microRNAs (miRNAs or miRs), a class of small non-coding RNAs, 19-25 nucleotides in length, and proteins involved in miRNAs maturation (Drosha, Exportin-5, Dicer1, PACT, Tudor-SN, Argonaute-2, and FXR1) have been linked to carcinogenesis and therapy resistance. Nevertheless, comprehensive information is needed to better understand their function in tumor formation and resistance/sensitization to therapy. Therefore, the aim of this study was to investigate the role of miRNA machinery in chemoresistance of a selected panel of non-small cell lung carcinoma (NSCLC) cell lines (U1810, H661 and A549) resistant to treatment. It was revealed that knockdown of Drosha, Dicer-1 and Ago-2 was not sufficient to sensitize them to subsequent treatment with either cisplatin, 5-FU, etoposide or camptothecin (CPT), while silencing of Staphylococcal nuclease domain containing 1(SND1/p100/TSN), a key component of RISC complex, led to increased sensitivity of NSCLC cells to the DNA-damaging agents. Besides its function as a component of the multiprotein complex involved in miRNA functioning, TSN is known to act as a transcriptional activator and oncogene in many cancers. Additionally, it is cleaved during apoptosis, losing its pro-carcinogenic function. Our results show that these NSCLC cells with TSN-knocked down exhibited much stronger response to treatment with CPT and cisplatin compared to wild-type cells, as monitored by enhanced cleavage of PARP, increase in percentage of subG1 cells and potentiation of caspase-3-like activity. Overall, obtained data suggest that this nuclease can play an important role in the resistance of NSCLC cells to chemotherapy and can be used as a potential target to increase sensitivity of lung tumors to this type of treatment.
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 4882. doi:1538-7445.AM2012-4882
Abstract 4892: EBV infectivity determines sensitivity to bortezomib in hematopoietic malignancy cells
Authors: Kim Areumnuri , Lee Jung-Eun , Park Sunhoo , Lee Seung-Sook 
Published: August 2012

Abstract
Epstein-Barr virus (EBV) is closely associated with several human malignancies where it expresses limited subsets of latent proteins. Of the latent proteins, latent membrane protein 1 (LMP1) is a potent transforming protein that constitutively induces multiple cell signaling pathways. C-terminal signaling domain of LMP1 (CTAR2) is known to engage the c-Jun N-terminal kinase (JNK) and NF-κB pathways, which contributes to EBV-associated oncogenesis. Bortezomib, proteasome inhibitor, blocks degradation of IκBα, thereby blocking not only NF-κB activation but also related cytokine production and the survival advantage for patients. However, to date, no study has examined that EBV infectivity is correlated with efficacy of bortezomib in the hematopoietic malignancies cells. Here, we used EBV-positive cell lines (Hank-1, Jijoye, Daudi and Granta519), EBV-negative cells (NK-92, Ramos, Jurkat and Rec1) and stable EBV-transfected cells (Ramos/EBV, Jurkat/EBV and Rec1/EBV) to evaluate the bortezomib sensitivity, highlighting the role of NF-κB. In the present study, we investigated that treatment with bortezomib significantly induced apoptosis and growth inhibition through blocking nuclear NF-κB signaling pathway in EBV-positive cells than EBV-negative cells. Thus, this data suggest that LMP1-induced NF-κB plays a critical role of survival and growth in EBV-positive cells. Additionally, treatment with bortezomib may provide a therapeutic advantage for patients with EBV-positive cells.
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 4892. doi:1538-7445.AM2012-4892
Abstract 4893: XIAP downregulation accompanies inhibition of melanoma xenograft growth by mebendazole
Authors: Doudican Nicole A. , Byron Sara , Pollock Pamela , Orlow Seth J. 
Published: August 2012

Abstract
Background: Melanoma's intrinsic resistance to therapy has been attributed to modulation of cellular survival pathways including apoptosis. We originally reported that mebendazole (MBZ), which acts as a microtubule-disrupting agent, is a potent inducer of apoptosis in melanoma cells in vitro via a Bcl-2 dependent mechanism (Molecular Cancer Research, 2008). Here, we show that MBZ is also able to effectively modulate another key anti-apoptotic factor, XIAP, to promote melanoma apoptosis both in vitro and in vivo. Methodology: Safety and efficacy of mebendazole was assessed using a human melanoma xenograft model established from M-14 cells. The effect of MBZ on XIAP expression and induction of apoptotic pathways was evaluated by immunoblotting and co-immunoprecipitation techniques along with densitometric quantification. The growth inhibitory effects of MBZ were determined in a panel of melanoma cell lines with the sulphorhodamine (SRB) assay. siRNA techniques were used to reduce expression of XIAP. Results: Oral MBZ is as effective as the current standard of care temozolomide (TMZ) in reducing melanoma growth in vivo, with no notable toxicities observed. Inhibition of melanoma growth in vivo is accompanied by MBZ specific reduced expression of XIAP and cleavage of caspase 9. In response to MBZ treatment, sensitive cell lines display reduced levels of XIAP expression whereas resistant cell lines do not. Moreover, down-regulation of XIAP expression by siRNA in the MBZ-resistant melanoma cell line UACC1097 was accompanied by a reduction in the IC50 for MBZ from &gt;10 μM to 3.7 μM. Exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating inhibition of apoptosis by XIAP. Conclusions: In addition to demonstrating efficacy and safety in vivo, our preclinical studies of the promising anti-melanoma agent mebendazole provide insight into characterization of an apoptotic promoting mechanism of action.
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 4893. doi:1538-7445.AM2012-4893
Abstract 4894: Effect of lysosome destabilization on response to ceramide in prostate cancer cells over-expressing acid ceramidase
Authors: Turner Lorianne S. , Dungee Stephen , Pezzimenti Frank , Weatherford Margot 
Published: August 2012

Abstract
Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stress, to sphingosine, which can then be converted to the pro-survival molecule sphingosine-1-phosphate. In addition to the ability to metabolize ceramide produced in response to stress, prostate cancer cell lines over-expressing AC also have increased lysosomal density and increased levels of autophagy. Autophagy is a cellular mechanism for recycling proteins and organelles which can be used as a survival mechanism in response to stress. Therefore, in addition to the increased capacity to metabolize ceramide produced in response to insult, the increased basal level of autophagy results in cells that have a heightened resistance to cellular stress. Preliminary results suggest that prostate cancer cell lines over-expressing AC have increased expression of lysosomal-stabilizing proteins, which highlights lysosome stability as a potential therapeutic target for cancer therapy. We have evaluated the effect of chloroquine, an FDA-approved drug that localizes to lysosomes, on the response of these cells to ceramide treatment. Pre-treatment with chloroquine increased the sensitivity of the cells to ceramide treatment, possibly due to AC disruption. These studies suggest that chloroquine may increase the efficacy of treatments that induce ceramide.
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 4894. doi:1538-7445.AM2012-4894
Abstract 4895: Caveolin-1 modulates docetaxel activity by inducing p53 expression in breast cancer.
Authors: Park Joo Hee , Kang Jin Ho , Jo Uk Hyun , Gil Eun Young , Park Jong Kuk , Lee Eun Sook , Kim Yeul Hong , Kim In Sun , Park Kyong Hwa 
Published: August 2012

Abstract
Caveolin-1 is reported to be down-regulated in breast cancers compared with normal mammary tissue. More recent data showed that high caveolin-1 expression is more associated with basaloid cancers than ER and/or PR or HER-2 expressing cancers. Investigatirs have reported that Caveolin-1 promoted resistance to chemotherapy-induced apoptosis in Ewing's sarcoma cells. However, the biologic relevance of caveolin-1 in breast cancer remains unclear. Thus, the aim of this study is to investigate its potential biologic relevance of Caveolin-1 to cell survival after docetaxel chemotherapy, one of the most important drug in breast cancer treatment. In this current study, we first showed that Caveolin-1 protein expression was suppressed in the ER(+) human breast cancer cell lines (MCF-7, T47D, and ZR75-1), but not in triple negative cancer cells (MDA-MB-231 and HS578T) and one of the HER-2 type cell (HCC1954) using Western blot analysis. Better cytotoxic effect of docetaxel was observed in the caveolin-1-expressing triple negative cells and HER-2 type cell than the other caveolin-1-deficient HER-2 type and luminal type of cancer cells. Next, caveolin-1 gene was reintroduced into caveolin-1 deficient luminal type breast cancer cells (MCF-7 and ZR75-1) to investigate its potential modulatory effect on docetaxel-induced cytotoxicity. The cell proliferation and MTT assay showed that the overexpressed caveolin-1 had further modulated docetaxel-induced anti-proliferative and cytotoxic effect in the luminal type cells. The anti-proliferative effect of docetaxel in the caveolin-1 gene over-expressed breast cancer cell lines was accompanied by decreasing cyclin D1 expression and inducing cyclin B1 accumulation, then resulting in cell cycle arrest at G2/M phase in the FACS analysis. In addition, re-introduction of caveolin-1 further increased docetaxel-induced cell death by synergistically inducing p53 expression and subsequent induction of p21, then finally apoptosis of breast cancer cells. These results were verified in the mouse model using SCID mice implated with either Caveolin-1-MCF-7 cells or control MCF-7 cells. When each group of tumor-bearing mice were treated by docetacel, mice with Caveolin-1-MCF-7 tumors showed a signiflcantly smaller tumors than those of control group. These results suggest that caveolin-1 may have a modulating factor for docetaxel activity by inducing p53 expression in breast cancer patients.
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 4895. doi:1538-7445.AM2012-4895
Abstract 4901: Impact of the TGF-β1 isoform on p53 signalling in ovarian cancer cell lines in response to cisplatin
Authors: Baribeau Sébastien , Chaudhry Parvesh , Asselin Éric 
Published: August 2012

Abstract
Transforming growth factor β is a pleiotropic cytokine which inhibits cell growth, induces cellular differentiation, and can lead to cellular apoptosis under certain conditions. TGF-β is also involved in epithelial-mesenchymal transition (EMT), a phenomenon by which cells acquire a dedifferentiated phenotype and gain motility and invasive properties. In the present study, we investigated the impact of TGF-β1 on p53 mediated cellular signalling in ovarian cancer cell lines in response to cisplatin. Four cell lines with different p53 status: A2780 (wild-type p53), A2780CP (derived from A2780, resistant to cisplatin, one p53 allele mutated V172F and one p53 allele wild-type), OVCAR-3 (p53 mutated R248Q) and SKOV-3 (p53 negative) were used in the present study. Cells were co-treated with TGF-β1 (10ng/mL) and cisplatin (10μM) for 24 hours and protein levels were analysed by western blotting. Our results show that TGF-β1 inhibits cisplatin-induced apoptosis in SKOV-3 cells as demonstrated by reduced PARP cleavage and caspase-3 activation. However, the inhibition of cisplatin-induced apoptosis was not observed in cells with wild type or mutated p53. Co-treatment of TGF-β1 and cisplatin decreased the levels of phosphorylated/active Akt compared to cisplatin alone, suggesting that TGF-β1 promotes cisplatin-induced apoptosis in A2780 cells in part through p53. In addition, Mdm2 was cleaved in response to cisplatin treatment only in p53 wild-type expressing A2780 cells. The levels of the caspase inhibitor XIAP were also decreased in A2780 cells when treated with cisplatin. Together, these results suggest that TGF-β1 promotes apoptosis when used in combination with cisplatin in p53 wild-type ovarian cancer cells.
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 4901. doi:1538-7445.AM2012-4901
Abstract 4973: Telomerase-specific replication-selective oncolytic viruses for adenoid cystic carcinoma cell lines
Authors: Sato Daisuke , kurihara Yuji , Kondo Seiji , shirota Tatsuo , Urata Yasuo , Fujiwara Toshiyoshi , Shintani Satoru 
Published: August 2012

Abstract
There is no effective treatment of adenoid cystic carcinoma (ACC) in oral region, which low sensitivity of chemotherapy and radiation therapy. We previously showed that telomerase-specific replication-competent adenovirus (Telomelysin, OBP-301), in which the human telomerase reverse transcriptase (hTERT) promoter controls the adenoviral E1 gene expression, induces a selective antitumor effect in oral squamous cell carcinoma (OSCC) cells in vitro and in vivo orthotopic graft model. We conducted to evaluate the effectiveness of OBP301 against ACC. First, we could confirm that the expression of hTERT in two types of ACC cell lines (ACC2, ACCM) by Western blotting. Then, we examined the antitumor effect of OBP301 in human ACC cells in vitro. OBP-301 infection induced cell death in human ACC cells in a dose-dependent manner. We also examined the expression levels of coxsackievirus and adenovirus receptor (CAR) on the cell surface of each type of cell by flow cytometric analysis. Apparent amounts of CAR expression were detected on human ACC cells. Relative hTERT mRNA expression in ACC was analyzed by real-time RT-PCR, which showed high expression time dependent. In addition, OBP-401 is a genetically engineered adenovirus that expresses GFP by inserting the GFP gene under the control of the cytomegalovirus promoter at the deleted E3 region of OBP-301. Human ACC cells expressed bright GFP fluorescence as early as 12 h after OBP-401 infection. The fluorescence intensity gradually increased in a dose-dependent manner, followed by rapid cell death due to the cytopathic effect of OBP-401, as evidenced by floating, highly light-refractile cells under phase-contrast photomicrographs. In conclusion, our data clearly indicate that telomerase-specific oncolytic adenoviruses have a significant therapeutic potential against human ACC in vitro. These results suggested that treatment of OBP-301 and OBP-401 are possible to improvement of QOL of oral cancer patients.
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 4973. doi:1538-7445.AM2012-4973
Abstract 4974: Metformin has an anti-cancer effect by repressing TWIST/N-cadherin signaling
Authors: Ge Rongbin , Wang Zongwei , Olumi Aria 
Published: August 2012

Abstract
Introduction and Objective Metformin, one of the most commonly used medications for treatment of type 2 diabetes, has emerged as a potential anticancer agent. The molecular mechanisms associated with the anti-cancer effect of metformin are poorly understood. We demonstrate, for the first time, that metformin inhibits prostate cancer proliferation through suppression of TWIST/N-cadherin signaling pathway. Methods RTαPCR, Western blot, immunofluorescence assays and confocal microscopy were applied to evaluate protein expression level. MTS assay and FACS analysis were applied to determine cellular proliferation. N-cadherin expression vectors were transfected into PC3 prostate cancer cells to establish stable cells with over-expression of N-cadherin. Metformin-resistant prostate cancer cells were established by exposure to higher concentrations (10mM) of metformin over 4 weeks. Results Treatment with metformin (5mM) inhibited proliferation in three different types of cancer cells (PC3-prostate cancer cells; T24-bladder cancer cells and 786-O- kidney cancer cells). Metformin treatment suppressed expression of N-cadherin in all cell types. Similar findings were observed by confocal microscopy. Expression of E-cadherin was not affected by metformin. Metformin-mediated repression of N-cadherin was dose and time- dependent in prostate cancer cells. PC3 prostate cancer cells with stable over-expression of N-cadherin became resistant to metformin-mediated inhibition. Stable PC3 prostate cancer cells after selection for metformin became resistant to metformin-mediated inhibition, and the metformin-resistant cancer cells had slightly higher baseline level of N-cadherin. In addition, in the metformin-resistant cells, N-cadherin levels were unchanged after treatment with metformin. The expression of AKT and AP-1, the downstream molecules of N-cadherin, closely correlated with expression of N-cadherin after treatment with metformin. Moreover, we also found that metformin inhibited expression of TWIST-1, a transcriptional activator of N-cadherin. Similar findings were observed by confocal microscopy. Conclusions We demonstrate that Metformin's anti-cancer therapeutic effect may be mediated through repression of the TWIST/N-cadherin signaling pathway.
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 4974. doi:1538-7445.AM2012-4974
Abstract 4976: Telomerase-specific replication-selective virotherapy combined with radiation therapy for oral squamous cell carcinoma cells
Authors: Kurihara Yuji , Sato Daisuke , Shirota Tatsuo , Kondo Seiji , Kataoka Masafumi , Urata Yasuo , Fujiwara Toshiyoshi , Shintani Satoru 
Published: August 2012

Abstract
Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We previously, investigated the antitumor effect of the hTERT-specific replication-competent adenovirus (Telomelysin: OBP-301) on oral squamous cell carcinoma (OSCC) cells in vitro and in vivo orthotopic graft model. OBP-301 replicated efficiently and induced more over 50% cell killing in a panel of human OSCC cell lines, but not in normal human fibroblasts, which were lacking telomerase activity. In orthotopic graft model, intratumoral injection of OBP-301 resulted in a significant inhibition of tumor growth and prolongation of survival. Moreover, OBP-301 in use has limited potency when administered alone; however, combination therapy using these agents and conventional anticancer agents, such as radiation exhibits encouraging levels of efficacy. Here, we describe the mechanistic basis for synergy of irradiation and OBP-301. This combination therapy was more effective compared with OBP-301 alone in OSCC cells. These results illustrate the potential of combining oncolytic virotherapy and ionizing radiation as a promising strategy in the management of human oral cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4976. doi:1538-7445.AM2012-4976
Abstract 4979: Co-operative role for Notch and fibroblast growth factor FGF2 signaling pathways in maintaining malignant phenotype of neuroblastoma: Potential targets for neuroblastoma growth inhibition.
Authors: Wesley Umadevi V. , Wesley Cedric S. , Dempsey Robert J. 
Published: August 2012

Abstract
Neuroblastoma, an extracraniel tumor of childhood generally progresses to therapy resistant metastatic tumor. Increased expression and activities of mitogenic FGF and the Notch signaling have been extensively correlated with highly malignant behavior and poor prognosis of many cancers including neuroblastoma, making FGF2-Notch3 as rational targets for therapeutic intervention. We have previously shown that a cell surface protease called dipeptydyl peptidase IV (DPPIV) induces apoptotic cell death of neuroblastoma cells thereby inhibiting their tumorigenic potential. In this study, we further examined if tumor suppressor activity of DPPIV is linked to decreased FGF2 and notch signaling pathways. We utilized Affymetrix microarray gene expression analysis, RNA interference and pharmacological inhibitor approaches, western blot and immunofluorescence analysis in these studies. Our results show that either endogenous up-regulation of DPPIV or exogenous treatment of DPPIV leads to decreased FGF2 and Notch3 levels. Furthermore, inhibition of FGF2 expression using FGF2-targeted small interfering RNA decreased the levels of Notch3 and matrix metalloproteinases leading to down regulation of p-Akt, an important survival factor for tumor cells. Blocking of Notch3 function either through a pharmacological inhibitor gamma secretase, or through shRNA also resulted in decreased p-Akt levels, and increased p21/waf1 and cleaved caspase 3 that are apoptosis inducers. Decreased levels of FG2 and Notch3 were associated with induction of differentiation, apoptosis and growth inhibition of neuroblastoma cells (SK-N-AS). In summary, our studies suggest a cooperative role for FGF2 and Notch3 signaling pathways in maintaining tumor phenotype and blocking of these pathways can lead to neuroblastoma tumor cell death. Thus these studies identify FGF2-Nothch 3 signaling pathways as potential targets for inhibiting growth and survival of neuroblastoma cells.
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 4979. doi:1538-7445.AM2012-4979