bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3942: Cell death resistance promoted by radiotherapy in a colorectal cell line
Authors: Baptistella Antuani R. , Rodrigues Bruna , Dias Marcos , Giudice Fernanda , Lacerda Tonielli , Santos Tiago , Silva Felipe , Silva Petrus Paulo , Aguiar Samuel , Martins Vilma 
Published: May 2015

Abstract
Colorectal adenocarcinoma is the fourth more frequent cause of death by cancer in the world. Despite some similarities, the rectal cancer has characteristics that differentiate it from the colon cancer, resulting in different treatments and outcomes. The rectal cancer in stages II and III is treated with neoadjuvant chemoradiation followed by surgery, and the response to neoadjuvant treatment in patients is variable and unpredictable. Up to now, surgery intervention is required to assess the pathologic response to therapy. The identification of predictive biomarkers for response to therapy is of great importance, in order to identify the patients that will benefit from such treatment. To better understand the molecular alterations in cells that resist to the radiotherapy, we started our research using WiDr, a colon tumor cell line. Cell cycle synchronized WiDr cells were submitted to two cycles of irradiation (4Gy in each cycle and 2 week of interval between the cycles) and resistant cells were isolated. Irradiated WiDr cells (RxTWiDr) shown a better capacity to form colonies, in colony growth assays, when compared to parental WiDr cells. This characteristic was maintained when they were submitted to a new round of irradiation. In addition, WiDrRxT cells treated with Staurosporine presented a higher viability in MTT assays than WiDr cells. We also collected the conditioned medium (CM) from RxTWiDr and WiDr cells, and treated the parental WiDr cells. The parental cells treated with CM from RxTWiDr cells for 15 minutes shown an increase in the ERK1/2 activation when compared to cells treated CM from WiDr cells. These results demonstrated that radio resistant cells are more resilient than parental cells and that their secreted factors activated specific signaling pathways via ERK1/2 phosphorylation. The nature of these factors is under investigation using proteomics.
Supported by São Paulo State Foundation (FAPESP)
Citation Format: Antuani R. Baptistella, Bruna Rodrigues, Marcos Dias, Fernanda Giudice, Tonielli Lacerda, Tiago Santos, Felipe Silva, Petrus Paulo Silva, Samuel Aguiar, Vilma Martins. Cell death resistance promoted by radiotherapy in a colorectal cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3942. doi:10.1158/1538-7445.AM2014-3942
Abstract 3945: Inhibition of MMP2 expression enhances the efficacy of radiation therapy for a murine astrocytoma
Authors: Yu Ching-Fang , Yang Ying-Chieh , Hong Ji-Hong , Chiang Chi-Shiun 
Published: May 2015

Abstract
Radiation therapy (RT) remains the front-line treatment for high-grade gliomas; however, tumor recurrence remains the main obstacle for the clinical success of RT. Using a murine astrocytoma tumor cell line, ALTS1C1, we have previously shown that RT can effectively reduce primary tumor volume and increase mice surviving time, but the mice eventually died associated with increased tumor infiltration. In this study, we explore the role of MMP2 (Matrix metalloproteinase-2), a reported molecule associated with brain tumor invasion, on ALTS1C1 tumor response to RT. In this study, the MMP2 expression was inhibited by specific lentiviral-shRNA construct. Eight Gray of whole brain irradiation could only prolong the median survival days of brain tumor-bearing mice from 25 days to 28 days, but the inhibition of MMP2 expression by siRNA prolonged the median survival days of tumor bearing mice from 25 days to 42 days. The median survival days were further prolonged to 53 days when 8 Gy of radiation and MMP2 inhibition were concurrently applied. Immunohistochemical (IHC) results showed that the synergistic effect as a result of RT-caused vessel density decrease (inadequate vasculature) and the retardation of vessel maturation as a result of MMP2 inhibition-caused the decrease of pericyte-covered vessels (insufficient vessel function). This study provides a new treatment option for treating invasive brain tumors. (This study was supported by NHRI-EX103-10132BI and NSC 102-2314-B-007-003-MY3 grants)
Citation Format: Ching-Fang Yu, Ying-Chieh Yang, Ji-Hong Hong, Chi-Shiun Chiang. Inhibition of MMP2 expression enhances the efficacy of radiation therapy for a murine astrocytoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3945. doi:10.1158/1538-7445.AM2014-3945
Abstract 3958: Investigation of HMGB1 as a potential marker for radiation response in muscle invasive bladder cancer
Authors: Mansure Jose J. , Shrivastava Sanhita , Nassim Roland , Ferbeyre Gerardo , Kassouf Wassim 
Published: May 2015

Abstract
Purpose: Radical cystectomy remains the standard treatment for invasive Bladder Cancer (BC). Radiotherapy is an attractive alternative; however lack of local control of the disease and toxicity associated with it remain problematic. As HMGB1 plays a major role in the cancer associated radio-resistance pathways, our objective is to evaluate its role as a predictive marker for radiation response in BC.
Methods: Expression of HMGB1 was characterized in a panel of eight BC cell lines via RT-PCR and Western Blotting. Knockdown of HMGB1 was carried out via shRNA lentiviral system. Correlation of HMGB1 expression and radiation response was done using clonogenic assays in control and shRNA transduced cell lines. Alkaline Comet Assay was used to measure the extent of DNA damage and repair in different cell lines 24hr post 5Gy radiation. Olive Tail moment was used as to quantify the DNA Damage.
Results: All cell lines expressed different levels of HMGB1, with BV and UC3 having the lowest and the highest expression of HMGB1 simultaneously. Clonogenic assay results showed that UC3 was resistant to radiation while BV was sensitive. Knockdown of HMGB1 caused the radio-resistant UC3 cells to become highly radio-sensitive, with more than 60% cells dying at 2Gy. Comet assay suggest the involvement of HMGB1 in DNA repair, as a significant DNA damage post radiation was observed in the HMGB1 knockdown cell line.
Conclusion: Our results demonstrate that high levels of HMGB1 protein are linked to a more radio-resistant outcome and HMGB1 knockdown leads to an increase in radio-sensitivity. Hence HMGB1 could potentially be used as a radiation response marker in invasive BC.
Citation Format: Jose J. Mansure, Sanhita Shrivastava, Roland Nassim, Gerardo Ferbeyre, Wassim Kassouf. Investigation of HMGB1 as a potential marker for radiation response in muscle invasive bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3958. doi:10.1158/1538-7445.AM2014-3958
Abstract 3967: BET protein inhibitor OTX015 has selective anti-tumoral activity in preclinical models of MYCN- amplified neuroblastoma
Authors: Schulte Johannes H. , Althoff Kristina , Bell Emma , Odersky Andrea , Beckers Anneleen , Speleman Frank , Schäfers Simon , Schramm Alexander , Eggert Angelika , Westermann Frank , Riveiro Eugenia , Cvitkovic Esteban , Henssen Anton 
Published: May 2015

Abstract
Neuroblastomas harboring MYCN amplifications are highly lethal tumors. They are often resistant to standard chemotherapy, yet the development of targeted therapies has been hampered by a lack of compounds targeting MYCN. We and others have recently discovered that targeting BET bromodomain proteins, especially BRD4, disrupts epigenetic regulation of MYCN and its targets in neuroblastoma. OTX015, a new BET protein inhibitor, is the first lead into clinical phase I/II trials and has shown promising pharmacological properties in adults. Here, we investigate the preclinical efficacy of OTX015 in MYCN-amplified neuroblastoma.
We tested in vitro OTX015 efficacy in 6 established neuroblastoma (NB) cell lines. We performed cell cycle profiling and analyzed markers for apoptosis and proliferation after 72h-treatment at 500 nM OTX015. The effect of OTX015 on MYCN expression and global MYCN-associated transcriptional activity was assessed by quantitative real time PCR and gene expression microarray profiling, respectively. In vivo efficacy of orally OTX015 was assessed in IMR5 xenografts, a N-MYC driven NB model, using diffent treatment schedules (50mg/kg/day, 100mg/kg/day and 50mg/kg/bidaily).
Treatment of MYCN-amplified neuroblastoma cells with OTX015 resulted in decreased cell viability, induction of apoptosis and reduced proliferation. Concentrations of 50% inhibition (IC50) ranged between 50nM and 500nM. OTX015 treatment also resulted in an increase in the percentage of cells in G1 phase. This corresponded with the downregulation of MYCN mRNA and protein levels and MYCN-associated transcriptional activity. Interestigly, MYCN amplified cell lines were most sensitive to OTX015 treatment. In contrast, no effect was observed with OTX15 on normal cells. In vivo treatment with OTX015, significantly decreased tumor burden after 4 weeks and prolonged survival as compared to vehicle-treated mice. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYCN-driven neuroblastomas and serve as rationale to move forward with early phase clinical trials for children with these highly lethal tumors.
Citation Format: Johannes H. Schulte, Kristina Althoff, Emma Bell, Andrea Odersky, Anneleen Beckers, Frank Speleman, Simon Schäfers, Alexander Schramm, Angelika Eggert, Frank Westermann, Eugenia Riveiro, Esteban Cvitkovic, Anton Henssen. BET protein inhibitor OTX015 has selective anti-tumoral activity in preclinical models of MYCN- amplified neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3967. doi:10.1158/1538-7445.AM2014-3967
Abstract 3976: Expression of formyl peptide receptor 1 (FPR1) in neuroblastoma: Implications in tumorigenesis
Authors: Snapkov Igor , Kogner Per , Johnsen John-Inge , Sveinbjørnsson Baldur 
Published: May 2015

Abstract
The formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor with pattern recognition properties. It is mainly expressed by myeloid cells and is involved in a broad range of host defense mechanisms. However, a variety of host-derived agonists of FPR1 have been identified, including formyl peptides released from disrupted mitochondria of necrotic cells. In the present study, we demonstrate that FPR1 is expressed in neuroblastoma cell lines and primary tumors and high expression is correlated with poor overall survival. Addition of the FPR1 agonist N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to neuroblastoma cells in vitro causes enhanced proliferative activity, increase of intracellular calcium response and activation of STAT3 and MAPK/Erk signaling pathways. Currently, clonal neuroblastoma cell line with inducible activity of FPR1 gene is under testing in a mouse model to assess the significance of this receptor in vivo. Our findings so far suggest that FPR1 may play a significant role in neuroblastoma tumorigenesis and that therapeutic intervention of the FPR1 pathway may become an important clinical strategy in neuroblastoma therapy.
Citation Format: Igor Snapkov, Per Kogner, John-Inge Johnsen, Baldur Sveinbjørnsson. Expression of formyl peptide receptor 1 (FPR1) in neuroblastoma: Implications in tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3976. doi:10.1158/1538-7445.AM2014-3976
Abstract 4000: Biological basis of aggressive phenotype in African-American prostate cancer cell line
Authors: Nickkholgh Bita , Fang Xiaolan , Gyabaah Kenneth , Balaji K.C. 
Published: May 2015

Abstract
Introduction: It is well established that African American men (AAM) with prostate cancer (PC) present more frequently with higher grade tumors compared to Caucasians. While the disparity is likely multifactorial, the biological basis is perhaps the strongest contender. Protein kinase D1 (PKD1) is a tumor and metastasis suppressor in PC. Down regulation of PKD1 was shown to increased cell proliferation, migration and metastasis in PC. Aim and experimental procedure: In order to address the fundamental question whether PC in AAM is inherently aggressive, we compared the proliferation, invasion and the expression of PKD1-centered signaling based 13-biomarker panel in primary and metastatic AAM cell lines (E006AA and MDApca2b) to benign (RWPE) and metastatic Caucasian cell lines (LNCaP and C4-2) using Western blot within different cell compartments. The results were further validated by RT-PCR and immunofluoroscent staining. Results: The proliferation, viability and invasion assays showed that E006AA cells proliferate and invade matrigel significantly more rapidly than metastatic LNCaP and MDAPca2b cells. The 13-biomarker panel analysis showed PKD1-centered dysregulaiton in AAM prostate cancer cell lines. Although E006AA is a primary PC cell line, PKD1 was down regulated similar to more aggressive C4-2 cells. Nuclear androgen receptor (AR), which shows active AR, was higher in LNCaP and MD2Pca2b; Vimentin showed higher expression in C4-2 and E006AA. Localization of E-Cadherin, N-Cadherin, T120 phosphorylated ß- Catenin, MMP-2 and S11 phosphorylated snail in MD2Pca2b was similar to LNCaP cells but different to C4-2 and E006AA. Conclusion: Our Data demonstrates that the dysregulaiton of PKD1-centered signaling occurs in primary AAM prostate cancer cell line E006AA is akin to other metastatic PC cell lines suggesting an inherently aggressive nature of PC in AAM.
Acknowledgment: Authors would like to thank Dr. Shahriar Koochekpour (Roswell park institute, University at Buffalo,State University of NewYork) for his kind gift E006AA cell line.
Citation Format: Bita Nickkholgh, Xiaolan Fang, Kenneth Gyabaah, K.C. Balaji. Biological basis of aggressive phenotype in African-American prostate cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4000. doi:10.1158/1538-7445.AM2014-4000
Abstract 4027: Traditional Chinese Medicine herbal mixture LQ prevents cyclophosphamide-induced metastasis and toxicity
Authors: Zhang Lei , Wu Chengyu , Li Lingna , Zhang Yong , Hoffman Robert M. 
Published: May 2015

Abstract
Cyclophosphamide (CTX) can enhance metastasis (Cancer Res. 66, 303-306, 2006; Cancer Res. 68, 516-520, 2008) and has toxic side effects such as immune-suppression, weight loss, and hair loss. In the present study, the traditional Chinese medicine (TCM) herbal mixture LQ (J. Cell. Biochem. 114, 2131-2137, 2013) was tested to determine if it could enhance CTX efficacy and reduce side effects. HT1080 human fibrosarcoma cells, labeled with GFP in the nucleus and RFP in the cytoplasm, were injected into the epigastric cranialis vein of nude mice that were pre-treated with CTX and LQ. Lewis lung carcinoma (LLC)-RFP cells were injected into the tail vein of mice that were pre-treated with CTX and LQ. Efficacy was monitored with dynamic subcellular imaging of trafficking of cancer cells in blood vessels (Cancer Res. 68, 516-520, 2008) and imaging metastasis to the lung. LQ significantly reduced CTX-induced lung metastasis and cancer-cell adhesion to the inner wall of blood vessels. LQ also reduced kidney toxicity induced by CTX. Treatment with LQ induced hair growth after CTX administration. This result demonstrates that LQ provides safe and effective prevention of metastasis and toxicity in combination with chemotherapeutic agents such as CTX.
Citation Format: Lei Zhang, Chengyu Wu, Lingna Li, Yong Zhang, Robert M. Hoffman. Traditional Chinese Medicine herbal mixture LQ prevents cyclophosphamide-induced metastasis and toxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4027. doi:10.1158/1538-7445.AM2014-4027
Abstract 405: Mbd3 localizes at promoters, gene bodies and enhancers of active genes
Authors: Shimbo Takashi , Du Ying , Grimm Sara A. , Dhasarathy Archana , Mav Deepak , Shah Ruchir R. , Shi Huidong , Wade Paul A. 
Published: May 2015

Abstract
The structure of chromatin is tightly regulated; its disregulation is causal for developmental abnormalities and for cancer. The nucleosome remodeling and deacetylase (NuRD) complex regulates chromatin structure and gene expression via its nucleosome remodeling and histone deacetylase activities. MBD3, a component of NuRD, has pleiotropic roles in embryonic stem (ES) cells and tumor biology. However, the results of recent studies are conflicting, resulting in an unclear model for NuRD function. Here, we investigated the localization of MBD3 in two human breast cancer cell lines (MCF-7 and MDA-MB-231) with two independent genomic technologies (DamID and ChIP-seq). DamID and ChIP-seq data were in an excellent agreement and led consistent conclusions in both cell lines. MBD3 localized not only at promoters and enhancers of active genes but also accumulated at gene bodies; this previously undescribed localization suggests an active role of MBD3 in transcription. MBD3 preferred hypomethylated, CpG rich promoters marked by H3K4me3. We also noted a subset of MBD3 that localized at silent promoters marked by H3K9me3 or H3K27me3, consistent with biochemical studies. Another subset of MBD3 co-localized with H3K27ac and was in physiological proximity with promoters, suggesting a role of MBD3 in the regulation of high-order structure of the genome. Functional analysis of chromatin demonstrated that MBD3 regulates nucleosome occupancy near promoters and in gene bodies. These data suggest multiple roles of MBD3/NuRD in the regulation of chromatin structure and gene expression for both active and silent genes. The findings serve as an important initial step in defining regulatory mechanism of MBD3/NuRD in ES cells and in tumor biology.
Citation Format: Takashi Shimbo, Ying Du, Sara A. Grimm, Archana Dhasarathy, Deepak Mav, Ruchir R. Shah, Huidong Shi, Paul A. Wade. Mbd3 localizes at promoters, gene bodies and enhancers of active genes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 405. doi:10.1158/1538-7445.AM2014-405
Abstract 4050: A central role for mTORC1 in CXCR4-mediated directional migration and metastasis
Authors: Dillenburg-Pilla Patricia , Patel Vyomesh , Mikelis Constantinos M. , Zarate-Blades Carlos Rodrigo , Amornphimoltham Panomwat , Wang Zhiyong , Martin Daniel , Leelahavanichkul Kantima , Doçi Colleen L. , Dorsam Robert T. , Masedunskas Andrius , Nohata Nijiro , Weigert Roberto , Molinolo Alfredo A. , Gutkind J. Silvio 
Published: May 2015

Abstract
Tumor cells can co-opt the promigratory activity of chemokines and their cognate G protein-coupled receptors to disseminate to regional lymph nodes and distant organs. Indeed, the migration to SDF-1 of tumor cells expressing its receptor, CXCR4, is implicated in lymphatic and organ-specific metastasis in multiple human malignancies. However, the critical role of CXCR4 in bone marrow stem cell retention has hampered the development of CXCR4 inhibitors for metastasis prevention. Therefore the study of CXCR4 downstream signaling circuitry may provide new opportunities for the treatment of many human malignancies that depend on CXCR4 for their metastatic spread. The PI3K/mTOR pathway represents a major player in normal and aberrant cell growth. Consistently, mTOR inhibitors targeting its complex 1 (mTORC1) alone or mTORC1/mTORC2 have already shown promising therapeutic responses in many tumor types. Our data show that mTOR is activated upon SDF-1 stimulation of CXCR4 on epithelial-derived cancer cells, and that the disruption of mTORC1 or mTORC2 abrogates CXCR4-mediated directional migration. To study the CXCR4/mTOR axis in vivo we developed a simple and robust model for CXCR4-mediated spontaneous metastasis. Surprisingly, disruption of mTORC1 alone was sufficient to decrease tumor cell proliferation, angiogenesis, lymphangiogenesis, and CXCR4-mediated metastasis, whereas mTORC2 impairment had no effect on tumor dissemination or growth in vivo. Taken together, our data suggest that mTORC1 blockade could inhibit the migration of CXCR4 expressing cancer cells to their secondary sites, while disrupting the establishment of a permissive tumor microenvironment thereby halting the spread of highly aggressive tumors that require CXCR4 to metastasize.
Citation Format: Patricia Dillenburg-Pilla, Vyomesh Patel, Constantinos M. Mikelis, Carlos Rodrigo Zarate-Blades, Panomwat Amornphimoltham, Zhiyong Wang, Daniel Martin, Kantima Leelahavanichkul, Colleen L. Doçi, Robert T. Dorsam, Andrius Masedunskas, Nijiro Nohata , Roberto Weigert, Alfredo A. Molinolo, J. Silvio Gutkind . A central role for mTORC1 in CXCR4-mediated directional migration and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4050. doi:10.1158/1538-7445.AM2014-4050