bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2906: Role of autophagy in Wnt5A-mediated melanoma invasion and metastasis
Authors: Ndoye Abibatou , Budina Anna , Webster Marie , Kaur Amanpreet , Behera Reeti , Murphy Maureen , Weeraratna Ashani T. 
Published: August 2015

Abstract
Melanoma is the most aggressive type of skin cancer and the leading cause of death from skin disease. With increasing incidence of the disease, it is crucial to further investigate the cellular mechanisms and molecular pathways that lead to invasion, metastasis, and drug resistance. Recent studies have revealed that high autophagy correlates with melanoma tumor aggressiveness and poor survival in clinical samples, as it is a common mechanism of resistance to therapy. Autophagy inhibition leads to reduced levels in Wnt5A in a breast cancer model, suggesting a cross-talk of Wnt5A and autophagy in cancer. β catenin, a mediator of canonical Wnt signaling, has been shown to act as a negative regulator of both basal and induced autophagy in a colorectal cancer model. Our laboratory showed that high levels of Wnt5A correlate with increased invasion and metastasis in melanoma and that Wnt5A downregulates β catenin; therefore, we hypothesize that autophagy might drive invasion and metastasis in aggressive melanoma through the regulation of Wnt signaling. To study the role of autophagy in Wnt5A-mediated melanoma invasion, we inhibited autophagy in highly invasive melanoma cells using lentivirus-mediated shATG5 knockdown or hydroxychloroquine and evaluated the effects of autophagy inhibition on Wnt5A expression, β catenin, and invasion using 3D spheroid models. Analysis of autophagy flux confirms that highly invasive melanoma cells have high autophagy compared to non-invasive cell lines. The inhibition of autophagy by hydroxychloroquine or shATG5 both resulted in significant decrease in invasion. By western blot analysis, we also observed a decrease in Wnt5A in these cells. These results demonstrate that autophagy inhibition in highly invasive melanoma leads to decrease in invasion in a 3D model that mimics the tumor microenvironment of melanoma. Further dissection of the molecular mechanisms that are involved in this process will enable the identification of novel autophagy targets in aggressive melanoma.
Citation Format: Abibatou Ndoye, Anna Budina, Marie Webster, Amanpreet Kaur, Reeti Behera, Maureen Murphy, Ashani T. Weeraratna. Role of autophagy in Wnt5A-mediated melanoma invasion and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2906. doi:10.1158/1538-7445.AM2015-2906
Abstract 2908: A sensitive immunohistochemistry method for in vivo autophagy biomarker detection and pharmacodynamic studies
Authors: Yang Yu , D'Amore Natalie Roy , Chouitar Jouhara , Yu Jie , Burke Kristine , Xiang Zhongmin , Yu Lunyin , Lasky Kerri , Brownell James , Simpson Chris , Luongo Evan , Bowman Doug , Tirrell Stephen , He Helen 
Published: August 2015

Abstract
Immunohistochemistry (IHC) is a powerful tool for studying pharmacodynamic biomarkers in tissue samples. However, IHC using standard methodologies to monitor autophagy has met with limited success due to the technical difficulties involved in detecting transient and low abundance autophagy markers. To address this issue, we have applied a highly sensitive IHC method using a tyramide-based signal amplification system to detect autophagy pathway proteins in paraffin sections of human tumor cell line and xenograft tissues. We were able to detect basal levels of punctate staining LC3B and NBR1 on both HCT116 and Calu-6 xenograft tumors using the tyramide-based signal amplification method whereas standard IHC showed little to no specific staining. Consistent with in vitro observations, lipidated LC3B, as detected by puncta formation, was elevated following autophagy induction using mTOR inhibitor treatment, and decreased following ATG7 knockout or knock down in both cell lines and xenograft tumors. As a result of autophagy pathway interruption following ATG7 inhibition, accumulation of the adapter proteins NBR1 and p62 was also detected. Our data demonstrate the feasibility of using high sensitivity IHC assays to reliably measure low abundant autophagy markers in xenograft tissues and may aid the exploration of autophagy regulation in cancer development.
Citation Format: Yu Yang, Natalie Roy D'Amore, Jouhara Chouitar, Jie Yu, Kristine Burke, Zhongmin Xiang, Lunyin Yu, Kerri Lasky, James Brownell, Chris Simpson, Evan Luongo, Doug Bowman, Stephen Tirrell, Helen He. A sensitive immunohistochemistry method for in vivo autophagy biomarker detection and pharmacodynamic studies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2908. doi:10.1158/1538-7445.AM2015-2908
Abstract 2914: Gold magneto nanoparticles induced apoptosis in liver cancer cells through changes of Ca channel pump detected by LIBS Technique and RT-PCR array
Authors: Ahmed Ola , Imam Hisham , Zekri Abdel-Rahman N. 
Published: August 2015

Abstract
Laser-induced breakdown spectroscopy technique (LIBS) was used in thesis study to address the effect of gold magneto nanoparticles on the liver cancer cells (HepG2) by examining the variation in genotoxicity and cytotoxicity.
HepG2 cell line was cultured at 105 cells/ml and expanded, after which, they were incubated with gold magneto nanoparticles at concentrations 10, 25, 50 μg/ml respectively for 12 hours. The effect of these nanoparticles in cell apoptosis as well as in autophagy was evaluated by acridine orange staining and Annexin V/propidium iodide double staining as well as apoptosis specific PCR array assay for evaluation of apoptosis in the treated cells.
At a concentration of nanocomposite 10, 25, 50 μg/ml, cells showed increase in the apoptosis figure from 11.25% ± 3.1% to 28% ± 2.04%, 39% ± 3.6%, 60% ± 4.3% respectively. Apoptosis specific PCR array also, showed very high expression of TNF, BIRC3 and NFKB1 with increasing in the fold regulation ratio of 155.03,158.03 and 149.2- fold respectively.
On the other hand, extra investigation of these treated cells by LIBS shows an increasing in the iron oxide nanoparticles concentration as well as calcium concentration. This increase in the calcium content in the treated cells may play an important role in the program cell apoptosis which was prove in our study by both Flow cytometry as well as by profile apoptosis PCR array.
Finally, our data showed the possibility of the using LIBS as inductor of cells apoptosis by measurement Ca concentration changes in liver cancer cells (HepG2 cells).
Keywords: Apaptosis, LIBS; HepG2 cell; Genotoxicity
Citation Format: Ola Ahmed, Hisham Imam, Abdel-Rahman N. Zekri. Gold magneto nanoparticles induced apoptosis in liver cancer cells through changes of Ca channel pump detected by LIBS Technique and RT-PCR array. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2914. doi:10.1158/1538-7445.AM2015-2914
Abstract 2935: A novel HSP70 inhibitor demonstrates potent anti-myeloma activity
Authors: Bailey Charvann K. , Budina Anna , Murphy Maureen , Nefedova Yulia 
Published: August 2015

Abstract
Multiple myeloma (MM) is a hematological cancer characterized by clonal proliferation of malignant plasma cells that produce monoclonal immunoglobulin. Because they secrete excess amounts of immunoglobulins, MM cells are typically under proteotoxic stress and utilize multiple mechanisms including molecular chaperones to maintain protein homeostasis. The chaperone HSP70 (heat shock protein 70) is overexpressed in MM. Therefore, we sought to evaluate whether targeting HSP70 with a novel HSP70 inhibitor would have a therapeutic benefit in MM. Toward this end, a panel of human MM cells lines including H929, RPMI-8226, MY-5, U266 and MM1s were tested for the IC50 to PET-16, an HSP70 inhibitor. Treatment with PET-16 resulted in a significant decrease in the viability of all MM cells tested with an IC50 value range from 3.5-7.2uM as was determined by the Alamar Blue assay. Decreased MM cell viability after treatment with PET-16 was due to induction of cellular apoptosis as was determined by Annexin V binding assay using flow cytometry. Because MM cells typically exist under hypoxic conditions, and hypoxia is known to decrease the efficacy of some chemotherapeutic agents, we analyzed the efficacy of PET-16 under hypoxia (1% oxygen). There was no difference in anti-MM effect of PET-16 in cells cultured under hypoxia as compared to those cultured in normoxic conditions. Taken together, our data suggest that targeting HSP70 with the novel HSP70 inhibitor PET-16 could be a viable potential strategy for treatment of MM.
Citation Format: Charvann K. Bailey, Anna Budina, Maureen Murphy, Yulia Nefedova. A novel HSP70 inhibitor demonstrates potent anti-myeloma activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2935. doi:10.1158/1538-7445.AM2015-2935
Abstract 2957: Investigating methyl-CpG DNA recognition in cancer
Authors: Terooatea Tommy W. , Wallace Megan J. , Szulik Marta W. , Chugg Alan C. , Miller Sven , Buck-Koehntop Bethany A. 
Published: August 2015

Abstract
DNA methylation is an essential epigenetic modification in eukaryotes required for genomic stability, control of gene expression and regulation of chromatin structure. Consequently, abhorrent alterations in methyl-CpG modifications across the genome, leading to inappropriate transcription, are associated with many diseases including cancer. Thus, an interest in discerning the regulatory mechanisms linking DNA methylation with gene expression in the disease state has emerged. The ZBTB methyl-CpG binding proteins (MBPs) are specialized transcription factors that mediate transcription by specifically targeting both methylated and sequence-specific DNA sites through a conserved set of Cys2His2 zinc fingers. While ZBTB MBP expression has become increasingly associated with higher grade tumors, we have only begun to understand the underlying complexities by which this family mediates gene expression. Here we combine interdisciplinary in cell genomic with in vitro biophysical approaches to begin to delineate the mechanisms by which this family of MBPs recognize DNA and regulate transcription in cancer. Specifically, for the founding member of this MBP family we utilized multiple genome-wide methodologies to identify its genomic targets, the methylation status at these sites and the transcriptional effect of this protein in cancer cell lines. We observed that protein expression levels, gene occupations and transcriptional responses were variable between cancer phenotypes. Additionally, ZBTB depletion results in variable phenotypic alterations between cell types indicating that protein presence may provide a means for defining these pathological states. Further, we have designed multiple protein constructs around the zinc finger domains of the ZBTB MBPs. Biophysical characterization of the binding interactions of these protein regions with various epigenetically modified DNAs has provided preliminary understanding for the differential mode of DNA recognition exhibited by the ZBTB MBP family members. Together, these findings provide initial insights into the molecular basis by which these proteins preferentially recognize, interpret and translate epigenetic signals into transcriptional responses in cancer cells.
Citation Format: Tommy W. Terooatea, Megan J. Wallace, Marta W. Szulik, Alan C. Chugg, Sven Miller, Bethany A. Buck-Koehntop. Investigating methyl-CpG DNA recognition in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2957. doi:10.1158/1538-7445.AM2015-2957
Abstract 2970: Whole genome sequencing analysis of multiple liver cancer nodules for determination of causal events for multi-occurrence
Authors: Furuta Mayuko , Fujimoto Akihiro , Ueno Masaki , Hayami Shinya , Kawakami Yoshi-iku , Gotoh Kunihito , Tsunoda Tatsuhiko , Miyano Satoru , Ohdan Hideki , Chayama Kazuaki , Yamaue Hiroki , Nakagawa Hidewaki 
Published: August 2015

Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite the recent progress in diagnostic accuracy and therapeutic efficacy, its five-year survival rate is still low. Characteristically, HCC shows a high rate of intrahepatic metastasis (IM) or multi-centric (MC) occurrence within the liver, and discrimination of IM/MC is difficult and important for therapeutic decision. Previously we reported that there were no common somatic mutations between whole genomes of MC tumors, indicating that MC tumors independently developed in their genetic aspect (Nat Genet, 44: 760-764, 2012). Here we performed whole genome sequencing (WGS) analysis on 43 multiple liver cancer nodules derived from 20 patients, which were clinically defined as IM or MC occurrence. We first analyzed common and unique somatic mutations in each individual and divided the cases into IM or MC by using the information of common somatic mutations between the multiple nodules. Interestingly, the clinical and pathological diagnoses of MC/IM in five of 20 cases were not concordant with the judgments from WGS, indicating the usefulness of WGS for a precise IM/MC judgment. Analysis of common somatic alterations in IM tumors enabled to extract early and late event in hepatocarcinogenesis among a large number of somatic events in each cases, while MC pairs shared only a few numbers of common alterations, including false positives. Importantly, one somatic mutation in non-coding region was exceptionally detected commonly among MC tumor pairs from three cases. Sanger sequencing confirmed that this mutation was also commonly detected in 10.9% (35/321) of liver cancer samples somatically. These results indicate the significance of this function-unknown and recurrent mutation in liver cancer development. To illuminate common driver events in MC tumors, we analyzed all detectable genetic alterations, including copy number alterations and rearrangements, on multi-time point or MC tumors derived from same individuals and extracted significant genetic alterations from them, which can help the understanding of driver genetic alterations in liver cancers.
Citation Format: Mayuko Furuta, Akihiro Fujimoto, Masaki Ueno, Shinya Hayami, Yoshi-iku Kawakami, Kunihito Gotoh, Tatsuhiko Tsunoda, Satoru Miyano, Hideki Ohdan, Kazuaki Chayama, Hiroki Yamaue, Hidewaki Nakagawa. Whole genome sequencing analysis of multiple liver cancer nodules for determination of causal events for multi-occurrence. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2970. doi:10.1158/1538-7445.AM2015-2970
Abstract 2978: An integrated comparative analysis of TCGA lung adenocarcioma and lung squamous cell carcinoma copy number and RNA-Seq expression data
Authors: OHara Andrea J. , Keshavan Raja , Che Zhiwei , Shams Soheil 
Published: August 2015

Abstract
The Cancer Genome Atlas (TCGA) contains various types of genomic data from a wide variety of cancers, several of which affect the same tissue site. Here we analyze copy number and RNA-Seq data from TCGA for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Level 1 (raw) data, rather than Level 3 (segmented) data, from TCGA was used for an integrated analysis of copy number and gene expression profiles of the two cancers. Using the copy number and SNP- probes, re-processed tumor profiles were more consistent with a control set in terms of median number of copy number events, sample ploidy, and breakpoint genes than with the published “level 3” TCGA data. Probe-level data were analyzed using Nexus Copy Number SNP-FASST2 (a multi-state HMM algorithm that uses both SNP and copy number probes in making state assignments), with systematic correction applied to correct for GC biases. Additionally we performed manual baseline adjustment to correct for sample ploidy based on whole-genome B-alelle frequency data for each sample. Overall, the median number of copy number events in the LUAD TCGA data set was reduced from 371 (in the level 3 set) to 299, and from 681 (in the level 3 set) to 177 in the LUSC TCGA data set. After manual inspection, more than 38% of the TCGA LUAD samples and 50% of the TCGA LUSC samples available at level 3 were found to have incorrect baseline ploidy assignments. The resultant re-analyzed copy number data sets were used for an integrated analysis between the two tumor types. Comprehensive comparative analysis using Fisher's Exact Test revealed statistically significant differences (percent differential = 25%, p&lt;0.001) in copy number profiles between the two lung tumor types; copy number changes include differential loss of chromosome 1p, loss of chromosome 3p, gain of chromosome 3q, loss of chromosome 4 and loss of chromosome 5. These correlated to changes in overall survival: individuals with loss of chromosome 1p and/or loss of 5q resulted in a significantly poorer prognosis (p&lt;0.05). While more frequent in the LUSC sample population, this change in overall survival outcome was extended to samples with chromosome 1p loss in LUAD samples as well. Integration with RNA-Seq expression data from each tumor type revealed statistically significant correlations (p&lt;0.05) with these copy number alterations, identifying potential driver genes of interest among each subtype and lung tumors in general.
Citation Format: Andrea J. OHara, Raja Keshavan, Zhiwei Che, Soheil Shams. An integrated comparative analysis of TCGA lung adenocarcioma and lung squamous cell carcinoma copy number and RNA-Seq expression data. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2978. doi:10.1158/1538-7445.AM2015-2978
Abstract 299: In vitro compound screening identifies enhancers of adenoviral oncolysis with Delta24-RGD in patient-derived glioblastoma stem cells
Authors: Berghauser Pont Lotte ME , Balvers Rutger , Kloezeman Jenneke , Nowicki Michal O. , Kremer Andreas , Chiocca E. Antonio , Leenstra Sieger , Dirven Clemens MF , Lawler Sean , Lamfers Martine LM 
Published: August 2015

Abstract
The tumor targeted oncolytic adenovirus Delta24-RGD is currently under phase I/II investigation for the malignant brain tumor glioblastoma. Despite encouraging results, the efficacy of oncolytic virotherapy still requires improvements due to heterogeneous or poor responses. In this study, we performed a screen of 446 clinically applied drugs to identify those that enhance Delta24-RGD oncolysis in glioblastoma. Cell viability was determined five days post-infection in Delta24-RGD resistant patient-derived glioblastoma stem cell (GSCs) cultures. Potential ‘hits’ were tested for synergistic viral sensitization using the Chou-Talalay method. Effects on viral infection and replication were investigated using Ad-Luc-RGD and Delta24-RGD-GFP viruses, and apoptosis and necrosis were evaluated using caspase-3/7 and lactate dehydrogenase (LDH) assays. Selection based on the efficacy of combination treatment led to the identification of ten drugs as potential Delta24-RGD sensitizers from the initial screen. Further analysis of effects on viral replication, synergistic interactions and ability to penetrate the blood-brain barrier narrowed this down to four remaining compounds, fluphenazine, indirubin, lofepramine and ranolazine. These four agents increased caspase-3/7 activity and fluphenazine also increased LDH levels in combination with Delta24-RGD. Fluphenazine, indirubin, lofepramine and ranolazine sensitized 12/12, 11/12, 9/12 and 11/12 distinct GSC cultures to Delta24-RGD, respectively. In conclusion, a clinical compound screen on glioblastoma stem cells in combination with in vitro mechanistic studies, revealed four highly effective compounds that sensitize GSCs to Delta24-RGD oncolytic therapy.
Citation Format: Lotte ME Berghauser Pont, Rutger Balvers, Jenneke Kloezeman, Michal O. Nowicki, Andreas Kremer, E. Antonio Chiocca, Sieger Leenstra, Clemens MF Dirven, Sean Lawler, Martine LM Lamfers. In vitro compound screening identifies enhancers of adenoviral oncolysis with Delta24-RGD in patient-derived glioblastoma stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 299. doi:10.1158/1538-7445.AM2015-299
Abstract 3006: Hyperoxia may be a treatment option for NSCLC
Authors: Hamamoto Junko , Yasuda Hiroyuki , Nakachi Ichiro , Edwards Michael G. , Miyawaki Masayoshi , Nishino Makoto , Kuroda Aoi , Tani Tetsuo , Arai Daisuke , Ishioka Kota , Kawada Ichiro , Naoki Katsuhiko , Betsuyaku Tomoko , Soejima Kenzo 
Published: August 2015

Abstract
Introduction: Many anti-tumor drugs have been developed, however, prognosis of NSCLC remains poor and new approaches for NSCLC treatment are expected. Lung is a unique organ whose epithelial cells are directly exposed to oxygen. Hyperoxia produces reactive oxygen species (ROS) and induces cell damage. Therefore we attempted to investigate the potential of hyperoxia as an anti-tumor treatment in NSCLC cells in this study.
Methods: We used oxygen-concentration-adjustable incubators and validated effect of hyperoxia on various lung cancer cell lines in vitro. The effect of hyperoxia on cell proliferation, apoptosis and gene expression was evaluated using MTS assay, flowcytometry and cDNA microarray, respectively.
Results: We found that the growth of lung cancer cell lines (A549, NCI-H1975) was inhibited by 50% of hyperoxia in a dose-dependent manner, while that of normal airway epithelial cells (NHBE, BEAS-2B) was not. Two independent pathway analysis using cDNA microarray revealed the activation of NF-kB and AMPK pathways, and the production of nitric oxide and ROS in hyperoxia (50%) treated lung cancer cell lines compared to untreated ones. The combined treatment with ABT-263, Bcl-2 inhibitor, and hyperoxia (50%) induced synergistic growth inhibition and apoptosis in NCI-H1975 and SK-MES-1 cells. Moreover, the combination of ABT-263 and activator of either ROS, NF-kB or AMPK also showed synergistic growth inhibition in those cells.
Conclusions: Hyperoxia (50%) showed anti-tumor effect in NSCLC cell lines through the activation of NF-kB and AMPK pathways, and the production of ROS. The effect was augumented in combination with Bcl-2 inhibitor. Hyperoxia may be a treatment option for NSCLC patients.
Citation Format: Junko Hamamoto, Hiroyuki Yasuda, Ichiro Nakachi, Michael G. Edwards, Masayoshi Miyawaki, Makoto Nishino, Aoi Kuroda, Tetsuo Tani, Daisuke Arai, Kota Ishioka, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima. Hyperoxia may be a treatment option for NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3006. doi:10.1158/1538-7445.AM2015-3006