bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4918: In vitro radiosensitization of human neuroblastoma cells with iron oxide - titanium dioxide core-shell nanocomposites conjugated with 3,4-Dihydroxyphenylacetic acid (DOPAC)
Authors: Mirzoeva Salida , Liu William , Bolling James R. , Shah Karna R. , Hirschmugl Carol , Sedlmair Julia , Paunesku Tatjana , Woloschak Gayle E. 
Published: May 2015

Abstract
Radiation therapy plays an important role in controlling tumor growth in cancers, including neuroblastoma, one of the most frequent extra cranial solid tumors in children. However, tumor radioresistance remains to be a major obstacle in clinical radiotherapy. In this study, we explored titanium dioxide core-shell nanocomposites conjugated with DOPAC (DOPAC-NCs) as radiosensitizers. Human neuroblastoma SK-N-AS and SK-N-DZ cell cultures were treated with or without of increasing concentrations of DOPAC-NCs (200-3000 nM) prior to irradiation. One hour later, cells were irradiated with a single dose of gamma radiation (0 - 10 Gy). Seventy-two hours following radiation treatment, cell proliferation/viability was assessed by MTS assay. Sham-irradiated cells served as a control. We have found that treatment of SK-N-AS and SK-N-DZ cells with DOPAC-NCs affected cell survival in a dose-dependent manner. Our data also demonstrated the evidence of DOPAC-NCs radiosensitization to gamma radiation. For examples, cell survival of SK-N-AS cells irradiated with 5 Gy and pre-treated with 1000 nM of DOPAC-NCs was as low as 35.6%. Oppositely, without radiation, treatment with the same concentration of DOPAC-NCs had no effect on cell viability.
These findings provide in vitro evidence that DOPAC-NCs may be developed and employed as radiosensitizers in neuroblastoma radiation therapy.
Citation Format: Salida Mirzoeva, William Liu, James R. Bolling, Karna R. Shah, Carol Hirschmugl, Julia Sedlmair, Tatjana Paunesku, Gayle E. Woloschak. In vitro radiosensitization of human neuroblastoma cells with iron oxide - titanium dioxide core-shell nanocomposites conjugated with 3,4-Dihydroxyphenylacetic acid (DOPAC). [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 4918. doi:10.1158/1538-7445.AM2014-4918
Abstract 4925: Targeted metabolic profiling of gliomas and glioma stem cells identifies methionine as a differentially regulated metabolite: Proof of principle supporting methionine-pet imaging
Authors: Palanichamy Kamalakannan , Krishnan Thirumoorthy , Sebastian Nikhil , Singh Rajbir , Kanji Suman , Chakravarti Arnab 
Published: May 2015

Abstract
Purpose: At present, 18F-Fluorodeoxyglucose(FDG)-positron emission tomography (PET) is the most commonly used diagnostic imaging modality in clinical practice for predicting prognosis in malignant brain tumors. The diffusive nature of glioblastoma (GBM) often makes FDG-PET detection inaccurate and there is no diagnostic gold-standard for GBM. Thus, it is necessary to find new criteria independent of conventional FDG-PET diagnosis to delineate tumor versus normal tissues. Molecular imaging using 11C-Methionine-PET (Met-PET) is one of the most promising approaches to this challenge.
Methods: We employed a targeted metabolomic approach to study the extracellular and intracellular levels of methionine in established (ATCC) and patient derived primary glioblastoma (GBM) cell lines, glioma stem cells (GSC) and normal human astrocytes (NHA) to gain a better understanding of methionine uptake. Methylthioadenosine phosphorylase (MTAP) is an enzyme that plays a vital role in polyamine metabolism and methionine salvage. Therefore, we determined the expression profile of MTAP in these cells using RT-qPCR. We then extracted the intracellular and extracellular metabolites of GBM, GSC and NHA to estimate their methionine levels using LC-MS Quadropole Time of Flight (Q-TOF) and LC-MS Triple Quad (QQQ) instruments. Thus, by using metabolic fingerprints of methionine, we quantified methionine accumulation / uptake in GBM, GSC and NHA.
Results and Conclusion: PET provides real-time information of metabolism through the behavior of single molecules. Despite clinical trials advocating Met-PET imaging as a superior imaging modality compared to FDG-PET for brain tumors, to date Met-PET has not been widely used in clinical diagnostics. Through this metabolic profiling of gliomas, we have shown for the first time that GBM and GSC accumulate methionine when compared to NHA. Uptake studies through exogenous addition of methionine in GBM, GSC and NHA show a significant uptake of methionine by GBM and GSC when compared to NHA. The results of our study establish the scientific basis for Met-PET imaging in GBM and provide a rationale for incorporating Met-PET imaging in future brain tumor clinical trials to evaluate its prognostic value.
Citation Format: Kamalakannan Palanichamy, Thirumoorthy Krishnan, Nikhil Sebastian, Rajbir Singh, Suman Kanji, Arnab Chakravarti. Targeted metabolic profiling of gliomas and glioma stem cells identifies methionine as a differentially regulated metabolite: Proof of principle supporting methionine-pet imaging. [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 4925. doi:10.1158/1538-7445.AM2014-4925
Abstract 4941: A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy
Authors: Dondossola Eleonora , Alexander Stephanie , Alexander Steve , Holzapfel Boris M. , Logothetis Christopher J. , Hutmacher Dietmar W. , Friedl Peter 
Published: May 2015

Abstract
Bone metastases are the initial site of progression and account for many of the complications experienced by men with metastatic prostate cancer (PCa), including resistance to therapy. The purpose of our study is to determine whether intravital multiphoton microscopy (iMPM) integrated with a novel mouse model can better inform clinical development of molecular therapeutics targeting bone metastases. iMPM can overcome limitations of existing models by monitoring the dynamic reciprocal cell-cell interplay at the center of PCa bone metastasis. To study PCa-stromal cell interactions and therapy response in bone, we established a humanized neo-bone in the mouse dermis, using grafted electrospun polycaprolactone scaffolds functionalized with human mesenchymal stem cells differentiated to osteoblasts. After in vivo maturation, bone scaffolds served for co-implantation of human fluorescent PCa cells (PC3) followed by multi-parameter iMPM through a body window, including: collagen and bone matrix (second harmonic generation), mineralized matrix (calcein blue), osteoblasts (H2B/mCherry in human mesenchymal stem cells), adipocytes and bone surface (third harmonic generation), blood vessels, stromal phagocytes and osteoclasts (fluorescence-labeled dextran), and PC3 cells (nuclear H2B eGFP with cytoplasmatic DsRed2). Using multi-parameter 3D reconstruction, tumor growth and invasion, reactive remodeling of the stroma and neovessel organization were monitored longitudinally, providing a baseline for evaluating preclinical disease and therapy response. The model provides new insight into PCa bone metastases and will be used to more efficiently develop and prioritize biologically founded therapy for clinical development.
Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris M. Holzapfel, Christopher J. Logothetis, Dietmar W. Hutmacher, Peter Friedl. A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy. [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 4941. doi:10.1158/1538-7445.AM2014-4941
Abstract 4952: Germline variation modulates susceptibility to aggressive disease development in a mouse model of prostate tumorigenesis
Authors: Williams Kendra A. , Bupp Sujata , Patel Shashank , Andreas Jonathan , Zhang Suiyuan , Molinolo Alfredo , Gutkind Silvio , Crawford Nigel 
Published: May 2015

Abstract
Although prostate cancer is common, with over 238,000 new cases being diagnosed in the US in 2012, it typically runs an indolent course with most men succumbing to unrelated disease processes. This is reflected in the low prostate cancer-specific mortality, with approximately 29,000 men succumbing in the same period. It is of critical importance to identify modifiers that increase susceptibility to aggressive disease to allow physicians to more accurately identify men at risk of fatal disease forms. The goal of this work is to map prostate tumor progression and metastasis modifier loci mapping using the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of aggressive neuroendocrine prostate carcinoma. We hypothesize that germline variation influences tumor progression and metastasis in prostate cancer.
The effect of germline variation in TRAMP mice was investigated by crossing it to Collaborative Cross progenitor strains and quantifying tumor progression and metastasis in transgene-positive F1 males. Those strains with the greatest phenotypic variation from the wildtype TRAMP C57BL6/J mice were chosen for modifier mapping using an F2 intercross approach. F2 mice were genotyped using a linkage panel consisting of 1,449 SNPs and modifier loci analyzed using j/qtl. The greatest number of loci achieving genomewide significance were observed in the TRAMPxNOD/ShiLtJ F2 cross (n=232). Modifier loci associated with primary tumor growth were observed on chromosomes 4, 7 and 8. Additionally, loci associated with metastasis were observed on chromosomes 1, 11, 13 and 17.
We have therefore identified multiple loci associated with aggressive disease development in a mouse model of prostate cancer. Candidate gene identification is ongoing, and focuses upon characterizing cis-eQTLs in TRAMPxNOD/ShiLtJ F2 primary tumors. Additionally, we are performing high resolution modifier mapping in TRAMPxJ:DO F1 mice. Our eventual aim is to confirm the relevance of candidate genes identified in the TRAMP mouse in human association cohorts.
Citation Format: Kendra A. Williams, Sujata Bupp, Shashank Patel, Jonathan Andreas, Suiyuan Zhang, Alfredo Molinolo, Silvio Gutkind, Nigel Crawford. Germline variation modulates susceptibility to aggressive disease development in a mouse model of prostate 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 4952. doi:10.1158/1538-7445.AM2014-4952
Abstract 4959: High-resolution MALDI imaging mass spectrometry demonstrated the correlation between phosphatidylinositol profiles and invasion/metastasis in human breast cancer
Authors: Kawashima Masahiro , Kawaguchi-Sakita Nobuko , Sugimoto Masahiro , Sato Taka-Aki , Tanaka Koichi , Toi Masakazu 
Published: May 2015

Abstract
High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI IMS) is an emerging application for lipid research that provides a detailed histological distribution of ionized lipids within tissue section. Phosphatidylinositol (PI) is one of the major classes of membrane phospholipid. The cellular membrane fluidity and signal transduction activity could be modulated by the alteration of fatty acid composition of PIs. Especially, PI-3kinase pathway, which can be activated by the phosphorylation of PIs, has become a great concern in breast cancer treatment. Although the amount of PIs is known to increase in human breast cancer tissues, it remains unclear how PIs are distributed in cancerous tissues. In this study, we investigated the detailed spatial distribution of PIs in breast tissues obtained from 24 patients, including 23 invasive ductal carcinoma (IDC), 4 ductal carcinoma in situ (DCIS), and 4 fibrocystic change lesions by using HR-MALDI IMS. The distribution of PIs was visualized at the resolution of 10um. 10 PIs with different fatty acid composition were detected in breast tissues. High-resolution analysis revealed the fatty acid composition of PIs was altered specifically in cancer cell clusters compared to stromal cells and non-malignant epithelia. PIs carrying monounsaturated fatty acid (MUFA) and PIs carrying polyunsaturated fatty acid (PUFA) showed the specific localization to cancer cell clusters. However, the proportion of PIs carrying MUFA and PIs carrying PUFA showed a clear inverse correlation in cancer cells. When we compared the PI profiles of IDC, DCIS, and FC, it was suggested that the accumulation of PIs carrying PUFA was occurred during the step of invasion. Moreover, lymph node metastasis well correlated with the accumulation of PIs carrying PUFA in cancer cells. HR-MALDI IMS firstly demonstrated the possible association between the PI profiles of breast cancer cells and their invasion/metastasis ability. Although this is a preliminary study, HR-MALDI IMS could be a useful modality to visualize the reprogramming of the lipid metabolism which reflects the cancer cell phenotype.
Citation Format: Masahiro Kawashima, Nobuko Kawaguchi-Sakita, Masahiro Sugimoto, Taka-Aki Sato, Koichi Tanaka, Masakazu Toi. High-resolution MALDI imaging mass spectrometry demonstrated the correlation between phosphatidylinositol profiles and invasion/metastasis in human breast 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 4959. doi:10.1158/1538-7445.AM2014-4959
Abstract 496: Adaptive response to chronic oxidative stress involves epithelial-mesenchymal transition in MCF-7 breast cancer cells
Authors: Mahalingaiah Prathap Kumar S. , Ponnusamy Logeswari , Singh Kamaleshwar P. 
Published: May 2015

Abstract
Though the increased oxidative stress by endogenous and exogenous factors has been hypothesized as a potential mechanism for breast cancer growth and progression, but there is no direct mechanistic evidence for adaptation to ROS-induced toxicity by the breast cancer cells. Therefore the objective of this study was to evaluate effects of chronic oxidative stress on the growth, survival and tumorigenicity of MCF-7 breast cancer cells. MCF-7 cells were exposed to hydrogen peroxide (H202) induced oxidative stress for both acute (48 hrs) and chronic (3 months) period. Cell growth and viability were evaluated by cell count and MTT assay and were confirmed by cell cycle analysis. Expression of genes related to cell cycle, cell survival, and metastasis were measured by quantitative real-time PCR. Effect of oxidative stress on tumorigenic phenotype was determined in-vitro by soft agar assay. Results of cell count, MTT and cell cycle analysis revealed increased growth, and survival of MCF-7 cells that was chronically exposed to H2O2. This was further confirmed at molecular level by increased expression of cell cycle and cell survival genes, whereas down-regulation of apoptotic genes. Chronic oxidative stress also increased tumorigenic phenotype and metastatic potential of MCF-7 cells as revealed by increase in soft agar grown colonies and expression of metastasis related genes. Additionally, fibroblast-like appearance with down regulation of epithelial markers, whereas up-regulation of mesenchymal markers in cells with chronic exposure to oxidative stress further suggest that adaptation to chronic oxidative stress by MCF-7 cells involves epithelial to mesenchymal transition (EMT). Dysregulation of epigenetic regulatory genes expression also suggest potential role of epigenetic mechanism in increased survival and tumorigencity of breast cancer cells.The findings of this study for the first time provided direct evidence for involvement EMT and epigenetic changes in adaptation of MCF-7 breast cancer cells to chronic oxidative stress. Results of this study are also highly significant in understanding the mechanism for acquired resistance to chemotherapeutic drugs that are known to produce ROS in breast cancer cells.
Citation Format: Prathap Kumar S. Mahalingaiah, Logeswari Ponnusamy, Kamaleshwar P. Singh. Adaptive response to chronic oxidative stress involves epithelial-mesenchymal transition in MCF-7 breast cancer cells. [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 496. doi:10.1158/1538-7445.AM2014-496
Abstract 4967: ESRP1 regulated alternative splicing of CD44mRNA enhances lung colonization of metastatic cancer cell
Authors: Tsuchihashi Kenji , Nagano Osamu , Yae Toshifumi , Ishimoto Takatsugu , Motohara Takeshi , Yoshikawa Momoko , Yoshida Go J , Wada Takeyuki , Masuko Takashi , Mogushi Kaoru , Tanaka Hiroshi , Osawa Tsuyoshi , Kanki Yasuharu , Minami Takashi , Aburatani Hiroyuki , Ohmura Mitsuyo , Kubo Akiko , Suematsu Makoto , Takahashi Kazuhisa , Baba Eishi , Akashi Koichi , Saya Hideyuki 
Published: May 2015

Abstract
Cancer metastasis is established by the seeding and successful colonization of stem-like cancer cells which show tumor-initiating ability at distant organs. CD44 is a cell surface marker protein which is highly expressed in stem-like cells of several human cancers including breast cancer. CD44 exists in various isoforms produced through alternative splicing of mRNA. Increased expression of CD44 variant isoform (CD44v) has been shown to correlate with metastatic potential and aggressive clinical behavior of various human cancers. We recently showed that CD44v contributes to reactive oxygen species (ROS)-defense in cancer cells by enhancing cystine uptake by the cystine transporter xCT. However, the functional relevance of CD44v and xCT in the metastatic spread of stem-like cancer cells has remained elusive.
In the present study, we show that metastatic breast cancer 4T1 cells consist of CD44v+ and CD44v- cells. The orthotopic transplantation of CD44v+ population but not that of CD44v-, in mice resulted in efficient lung metastasis. We found that CD44v expressing metastatic cancer cells highly express xCT and thereby maintain high reduced glutathione (GSH) level. A specific xCT inhibitor sulfasalazine suppressed lung metastatsis of CD44v+ cells. Alternative splicing of CD44mRNA in such metastatic cancer cells is regulated by Epithelial Splicing Related Protein1 (ESRP1) and short hairpin RNA (shRNA) targeting ESRP1 switched isoform from CD44v to CD44 standard (CD44s), leading to the suppression of lung metastasis. Furthermore, we found that ESRP1 expression is regulated epigenetically through histone modification by performing chromatin immunoprecipitation (ChIP) sequencing analysis of the ESRP1 locus in CD44v+ and CD44v- cells.
These findings establish a novel role of ESRP1-regulated alternative splicing program in the regulation of antioxidant status of stem-like cancer cells which is crucial for the metastatic ability.
Citation Format: Kenji Tsuchihashi, Osamu Nagano, Toshifumi Yae, Takatsugu Ishimoto, Takeshi Motohara, Momoko Yoshikawa, Go J Yoshida, Takeyuki Wada, Takashi Masuko, Kaoru Mogushi, Hiroshi Tanaka, Tsuyoshi Osawa, Yasuharu Kanki, Takashi Minami, Hiroyuki Aburatani, Mitsuyo Ohmura, Akiko Kubo, Makoto Suematsu, Kazuhisa Takahashi, Eishi Baba, Koichi Akashi, Hideyuki Saya. ESRP1 regulated alternative splicing of CD44mRNA enhances lung colonization of metastatic cancer cell. [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 4967. doi:10.1158/1538-7445.AM2014-4967
Abstract 4969: Hypo adenosine-to-inosine editing of microRNA-455 promotes melanoma metastasis
Authors: Shoshan Einav , Mobley Aaron , Braeuer Russell , Kamiya Takafumi , Huang Li , Vasquez Mayra , Jeong Lee H. , kim Sun Jim , Calin George , Sood Anil , Markel Gal , Fidler Isaiah , Bar-Eli Menashe 
Published: May 2015

Abstract
We have previously reported that activation of CREB in metastatic melanoma cells resulted in reduced expression of adenosine deaminase acting on RNA 1 (ADAR1), an RNA editing enzyme. We hypothesized that disruption of A-to-I editing of microRNAs alters expression of genes regulating melanoma progression. By sequencing miRs in primary vs. metastatic melanoma cells, we show that the overall microRNA editing frequencies were reduced in metastatic melanoma cells. Specifically, we found A-to-I editing in two sites of miR-455 in non-metastatic melanoma cells with accumulation of unedited miR-455 in metastatic melanoma cells. Using two animal models, we demonstrated that the unedited miR-455 promoted melanoma growth and metastasis, while the edited form suppressed these features. Unedited miR-455 promotes melanoma progression via suppression of the tumor suppressor cytoplasmic polyadenilation element binding protein (CPEB1). Thus, miR-455 A-to-I editing alters the selection of its target genes and directs its function to inhibit melanoma growth and metastasis. Taken together, our results provide a previously undescribed mechanism (microRNA editing) contributing to melanoma progression.
Citation Format: Einav Shoshan, Aaron Mobley, Russell Braeuer, Takafumi Kamiya, Li Huang, Mayra Vasquez, Lee Ho Jeong, Sun Jim kim, George Calin, Anil Sood, Gal Markel, Isaiah Fidler, Menashe Bar-Eli. Hypo adenosine-to-inosine editing of microRNA-455 promotes melanoma 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 4969. doi:10.1158/1538-7445.AM2014-4969