bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1667: A novel method to identify radiosensitizers targeting hypoxic cancer cells by high-throughput screening
Authors: Tamari Keisuke , Seo Yuji , Takahashi Yutaka , Suzuki Osamu , Isohashi Fumiaki , Yoshioka Yasuo , Ogawa Kazuhiko 
Published: July 2016

Abstract
Tumor hypoxia correlates radioresistance and poor clinical outcomes after radiotherapy. Radiosensitizers have been studied for a long time especially to overcome the problem of hypoxic tumor cells. Until now, however, radiosensitizers for hypoxic tumors have had only limited success in clinic. High throughput screening is popular method to identify candidate compounds from a large number of compounds for drug discovery, but have not been established method to study new radiosensitizers. The aim of this study was to identify radiosensitizers targeting hypoxic cancer cells by high throughput screening and validate the efficacy of this method. We performed cell-based high throughput screening by using 384 well plates and 1280 compounds. After exposing compounds to HeLa cells, gamma-irradiation was delivered under hypoxic condition and incubated for 4 days. To identify candidate compounds, cell counting was performed by MTS assay. Then, radiosensitizing effect of these compounds was validated by clonogenic survival assay. We performed high throughput screening and identified 22 compounds as candidates. We selected Ro90-7501 and dicyclomine hydrochloride which were not reported as radiosensitizers. Clonogenic survival assay showed their significant radiosensitizing effect in hypoxic condition. In conclusion, we identified novel radiosensitizers by high throughput screening. This method may be useful for identifying radiosensitizers targeting hypoxic cancer cells.
Citation Format: Keisuke Tamari, Yuji Seo, Yutaka Takahashi, Osamu Suzuki, Fumiaki Isohashi, Yasuo Yoshioka, Kazuhiko Ogawa. A novel method to identify radiosensitizers targeting hypoxic cancer cells by high-throughput screening. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1667.
Abstract 1671: Local release of combretastatin A-4 from NIR-light activatable prodrugs overcomes areal and temporal limitations of photodynamic therapy
Authors: Rajaputra Pallavi , Bio Moses , Nkepang Gregory , Thapa Pritam , Woo Sukyung , You Youngjae 
Published: July 2016

Abstract
A unique prodrug strategy for treating localized cancers, in which NIR light-illuminated prodrug effectively ablates tumors through the combined effects of photodynamic therapy (i.e., singlet oxygen [SO]) and locally released anticancer drugs has been proposed. Due to short distance of action (&lt; 0.04 μs) and short lifetime (&lt; 0.02 μm) of SO, direct damage of PDT is both areally and temporally limited. We hypothesized that the locally released anticancer drugs would overcome the areal and temporal limits of SO. Near IR-activatable prodrug of combretastatin A-4 (CA4), Pc-(L-CA4)2, and its pseudo-prodrug, Pc-(NCL-CA4)2, were evaluated in vitro and in vivo. After partial illumination of a 24 well, all the cells in the prodrug-treated well were killed by the released CA4. Limited areal damage was observed in the pseudo-prodrug-treated wells. A time-dependent cell survival study revealed more extensive cell death in the prodrug-treated cells, due to the sustained damage from the released CA4. Cell cycle analysis and microscopic imaging data demonstrated the typical damage patterns of CA4 in the prodrug-treated cells. A time-dependent histological study showed that prodrug-treated tumors lacked mitotic bodies. The prodrug caused broader and more long-lasting tumor size reduction than did the pseudo-prodrug. These data consistently support that the released CA4 overcomes the areal and temporal limits of SO, providing far superior antitumor effects.
Citation Format: Pallavi Rajaputra, Moses Bio, Gregory Nkepang, Pritam Thapa, Sukyung Woo, Youngjae You. Local release of combretastatin A-4 from NIR-light activatable prodrugs overcomes areal and temporal limitations of photodynamic therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1671.
Abstract 1672: Photodynamic therapy using photosensitizer and light emitting diodes (LEDs) demonstrates oncolytic activity against prostate cancer
Authors: Gheewala Taher , Skwor Troy , Munirathinam Gnanasekar 
Published: July 2016

Abstract
Prostate cancer (PCa) affects over 2 million Americans and its treatment options include surgery, anti-hormonal drugs for androgen sensitive tumors, and radiotherapy. However, patients undergoing androgen deprivation therapy develop resistance leading to development of castration resistant or androgen independent PCa. It is clear there is an urgent need to find an effective treatment strategy to manage aggressive PCa. An alternative treatment is the use of photodynamic therapy (PDT), which involves the activation of a photosensitizer by a defined wavelength of light in the presence of oxygen, generating transient concentrations of reactive oxygen species. We hypothesize that PDT via a photosensitizer (pheophorbide) in combination with light emitting diodes (LEDs) [670 nm] will demonstrate oncolytic activity against PCa cells, thus suggesting an alternative, less toxic cancer treatment. To test our hypothesis, we used C4-2 and DU-145 PCa cell lines as an in vitro model in this study. To explore the anti-cancer effects of PDT on PCa, cell viability assay and wound healing assay were performed. Western blotting was employed to identify the signaling molecules modulated by PDT. Our cell viability assay results demonstrated significant oncolytic activity against PCa cell lines using PDT with pheophorbide as a photosensitizer combined with 670 nm LEDs in as little as an 88 second pulse with increased lytic activity correlating with elevated energy intensities. We also observed variability in cell line PDT susceptibility; wherein, C4-2 cells were more susceptible than DU-145 PCa cells. The wound healing assay results with pheophorbide and 670 nm LEDs demonstrated significant inhibition of migration abilities of both C4-2 and DU-145 PCa cells. These findings implicate the anti-metastatic activity of PDT on PCa. Further, our mechanistic analysis showed activation of BiP/GRP78, an endoplasmic reticulum (ER) chaperone, in C4-2 as well as DU-145 PCa cells. This suggests that the anti-cancer activity of PDT with pheophorbide and 670 nm LEDs is via ER stress. In conclusion, our results show PDT using pheophorbide and 670 nm LEDs as a promising therapeutic strategy for PCa.
Citation Format: Taher Gheewala, Troy Skwor, Gnanasekar Munirathinam. Photodynamic therapy using photosensitizer and light emitting diodes (LEDs) demonstrates oncolytic activity against prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1672.
Abstract 1675: Activation of phosphatase toward the retinoblastoma protein inhibits invasion in MDA-MB-231 breast cancer cells
Authors: Egger Jacklynn , Lane Maria , Dedi Brixhilda , Krucher Nancy A. 
Published: July 2016

Abstract
Excessive phosphorylation of the Retinoblastoma protein (Rb) is found in most cancer tumor types. Several cyclin dependent kinase (cdk) inhibitors are in development or in clinical trials at the present time. Our previous studies have focused on the regulation of Rb phosphorylation by the phosphatase, PP1. In proliferating cells, PP1 is regulated by a protein called PNUTS (Phosphatase Nuclear Targeting Subunit). PNUTS is a competitive inhibitor of Rb binding to PP1 and siRNA mediated knockdown of PNUTS in several cancer cell types (breast, colon, ovarian) leads to an increase in Rb directed PP1 activity, Rb dephosphorylation on several sites, and a dramatic induction of apoptosis. In this study we have used MDA-MB-231 breast cancer cells grown in Matrigel. By lentiviral-mediated doxycycline inducible expression of PNUTS siRNA, expression of PNUTS protein is blocked and phosphorylation of Rb cells is reduced. Cells become less invasive and expression of mesenchymal markers N-cadherin, Zeb and Slug is lost. A reversion to the epithelial phenotype is suggested by an increase in E-cadherin expression. PNUTS knockdown has no effect on cells that do not contain highly phosphorylated Rb such as non-transformed MCF-10A cells or Rb-negative MDA-MB-468 cells. Further experiments using highly invasive HT-1080 cells show that reduction of Rb phosphorylation appears to reduce invasiveness in this cell model, supporting the idea that Rb phosphorylation plays a critical role in the regulation of invasion.
Citation Format: Jacklynn Egger, Maria Lane, Brixhilda Dedi, Nancy A. Krucher. Activation of phosphatase toward the retinoblastoma protein inhibits invasion in MDA-MB-231 breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1675.
Abstract 1676: 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate cancer
Authors: Alfardan Rana K. , Boral Debasish , Nie Daotai 
Published: July 2016

Abstract
Introduction
15-lipoxygenase-2 (15-LOX-2) is a lipid oxidizing enzyme which converts the unsaturated fatty acids (Arachidonic and linoleic acid) to bioactive lipids with anti-inflammatory properties. Abundantly expressed in normal prostate, 15-LOX-2 expression and activities were found reduced in prostate tumors. 15-LOX-2 has been suggested as functional tumor suppressor since restoration of its expression was found to reduce prostate tumor formation and growth and induce tumor dormancy. However, it is unknown how 15-LOX-2 modulates prostate tumor progression and metastasis.
Methods
Silico analyses of gene array data, Inducible Tet-on system to express 15-LOX-2 in PC3MM cells in an inducible manner, qPCR to check the expressions, western blot, wound healing assay, immunohistochemistry.
Result
Through in silico analyses of gene array data, we found 15-LOX-2 expression was markedly reduced in metastatic prostate tumors when compared to normal or primary prostate tumor tissues. To determine whether 15-LOX-2 can modulate metastatic potentials of prostate cancer, we used an Inducible Tet-on system to express 15-LOX-2 in PC3MM cells. Treatment with 750ng/ml of doxycycline led to induced expression of 15-LOX-2 in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells caused re-expression of several epithelial markers including claudin, desmocollin, desmoglein, Jam, EPCAM, β-Catenin molecules involved in the tight and desmosomal junctions. At mean time, 15-LOX-2 expression led to a decrease in the levels of mesenchymal markers, vitronectin and fibronectin, in PC3MM cells. Restoration of 15-LOX-2 expression in PC3MM cells reduced cell migration and reduced MMP2 and MMP3 expression.
Conclusion
Our data suggest that 15-LOX-2 is a barrier for prostate tumor cells to acquire metastatic potentials through inhibiting epithelial to mesenchymal transition.
Citation Format: Rana K. Alfardan, Debasish Boral, Daotai Nie. 15-Lipoxygenase-2 inhibits epithelial-to-mesenchymal transition (EMT) in metastatic prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1676.
Abstract 1685: Identification and characterization of EMT/MET signatures in circulating tumor cells isolated from patients with metastatic breast cancer using graphene oxide nano-chip
Authors: Kim Tae Hyun , Yoon Hyeun Joong , Nagrath Sunitha 
Published: July 2016

Abstract
Disseminated cancer cells identified in the circulatory system of cancer patients has implied to be the key drivers of tumor metastasis. These cells known as circulating tumor cells (CTCs) are emerging as an alternative to tissue biopsies to predict prognostic values, and to monitor evolving tumor heterogeneity through serial drug treatments. Recent technological advances have enabled the detection of CTCs in patient blood samples. However, the enumeration alone seems to be insufficient to obtain information that could benefit any clinical decisions. The limited sensitivity as well as the specificity of current approaches struggle from realizing the full promise of CTCs. We developed a sensitive microfluidic chip using functionalized graphene oxide (GO) nano-sheets to isolate CTCs with improved sensitivity and purity. Blood samples collected from metastatic breast cancer patients were processed through the chip within 6 hours of sampling and the CTCs were identified by the presence of cytokeratin with the absence of CD45 expression. EMT/MET signatures were characterized in the isolated CTCs to investigate its role by assessing gene expression profiles. Protein markers known to be up regulated during the EMT such as Vimentin and N-cadherin was examined along with HER2. mRNA expression
of EMT markers were studied simultaneously using a multiplex TaqMan-based qRT-PCR method and compared to healthy controls. CTCs were successfully detected in &gt;95% of patients examined in this study. Cell-to-cell intrapatient heteroheneity was observed in the isolated CTCs. Markers of EMT/MET phenotypes including Vimentin, EpCAM, HER2, CDH1, CDH2 and cytokeratin in the CTC samples were differentially expressed. These studies demonstrate the feasibility of utilizing the GO nano-chip in CTC isolation and characterization from metastatic breast cancer patients. Given the high sensitivity and the reproducibility to measure protein/gene expression levels of CTC biomarkers, we envision that our GO nano-chip may provide potential tool for real-time monitoring of cancer patients on clinical trials.
Citation Format: Tae Hyun Kim, Hyeun Joong Yoon, Sunitha Nagrath. Identification and characterization of EMT/MET signatures in circulating tumor cells isolated from patients with metastatic breast cancer using graphene oxide nano-chip. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1685.
Abstract 1688: Mutation and gene expression analysis of circulating tumor cells (CTCs) enriched and retrieved by a sensitive microfluidic device
Authors: Wang Yixin 
Published: July 2016

Abstract
Molecular characterization of CTCs is hindered by low sensitivity and high level of background leukocytes of currently available CTC enrichment devices and assays. We have developed a novel technology to enrich and retrieve CTCs from blood samples using a microfluidic chip. The Celsee PREP100 device captures CTCs with high sensitivity and then allows the captured CTCs to be retrieved for subsequent molecular analysis. The Celsee PREP100 system uses the microfluidic chip which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood cells such as red blood cells and most leukocytes escape while larger CTCs are trapped and isolated in the chambers. In the work we used the Celsee PREP100 to capture breast and lung cancer cells spiked into normal donor blood samples, including SKBR3 and NCI-H1975. We were able to show that the device can capture 20 cells with high reproducibility. The captured CTCs were retrieved from the microfluidic chip and further purified with anti-CD45 magnetic beads. Our results suggest that the cell recovery rate of this back-flow procedure is greater than 80% and the level of remaining background leukocytes is very low (about 100 cells). Work in progress to extract DNA and RNA. The resulting DNA samples are subjected to mutation analysis of a panel of cancer markers by using PCR and sequencing. The resulting RNA samples are converted to cDNAs, and gene expression analysis of selected cancer markers are carried out by using RT-QPCR. Specific DNA mutations such as EGFR exon 21 (L585R) in NCI-H1975 and mRNA expression markers including CK-19, TTF1 are tested in the retrieved cells. The sensitive and easy-to-use Celsee PREP100 system represents a promising technology for CTC capturing and molecular characterization. Clinical blood samples from patients with metastatic cancer are being tested on the Celsee PREP100 device and the results will be discussed.
Citation Format: Yixin Wang. Mutation and gene expression analysis of circulating tumor cells (CTCs) enriched and retrieved by a sensitive microfluidic device. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1688.
Abstract 1696: Mitochondrial haplotype alters metastasis in a non-cell autonomous manner
Authors: Brinker Amanda E. , Vivian Carolyn J. , Welch Danny R. 
Published: July 2016

Abstract
Mitochondrial Nuclear Exchange (MNX) mice, created by transferring the nucleus from an oocyte from strain x into an enucleated oocyte of strain y, showed that mammary tumor formation and metastasis can be regulated by inherited mitochondrial polymorphisms (PMID26471915). Besides genetic (cell autonomous) changes observed, we asked whether mitochondrial polymorphisms in non-cancer compartments could exert effects on tumor formation or metastasis. Tumor cells were injected into syngeneic wild type mice and tumor growth and metastasis were compared to similarly injected cells into MNX mice sharing the same nuclear but different mtDNA backgrounds. Orthotopic tumor growth rates were equal for all of the cell lines tested. However, the ability to form experimental lung metastases following i.v. injection were dramatically altered. Compared to injections into wild-type, syngeneic mice, E0771 mammary carcinoma and B16-F10 melanoma cells (both syngeneic to C57BL/6J), formed significantly (P&lt;0.01) more lung metastases in C57BL/6J-mtMNX(C3H/HeN) and K1735-M2 melanoma cells (syngeneic to C3H/HeN) formed significantly fewer lung metastases in C3H/HeNmtMNXC57BL/6J. These results have been replicated at least three times using &gt;10 mice per experiment. Interestingly, C57BL/6J mitochondria confer resistance to metastasis in both cell autonomous and non-cell autonomous experiments. Basal metabolic differences comparing mouse embryonic fibroblasts isolated from wild-type and MNX mice are among mechanisms being explored. Together, our findings highlight the striking influences that mitochondrial haplotypes can exert on tumorigenicity and metastasis via both intrinsic and extrinsic mechanisms. Support: Susan G. Komen for the Cure (SAC11037), Natl Fndn Cancer Res, Steiner Family Fund for Metastasis Research, Kansas Bioscience Authority, CA134981, P30-CA168524
Citation Format: Amanda E. Brinker, Carolyn J. Vivian, Danny R. Welch. Mitochondrial haplotype alters metastasis in a non-cell autonomous manner. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1696.
Abstract 17: Metabolic analysis of IDH mutant gliomas in Drosophila
Authors: Brown Michaela , Buccetti Jenna , Tipping Marla 
Published: July 2016

Abstract
Metabolic reprogramming is a common hallmark shared by nearly all proliferating cancer cells and has emerged as an exciting new direction in cancer research. Many signaling pathways have been implicated in mechanisms leading to the shift of metabolic programs in tumors, but more recently a small number of metabolic enzymes have also been identified in this process. Genes encoding the metabolic enzymes Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) were found to be mutated in up to 70% of low-grade and medium grade gliomas, and in 15-20% of adult acute leukemia samples. These findings were the first to link the IDH gene to tumorigenesis. IDH1 and IDH2 function to irreversibly catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Although these are important metabolic enzymes, little is known about the metabolic impact harboring mutant IDH protein has on cells. Our goal is to model the IDH mutant phenotype in Drosophila glial cells for further characterization of both metabolic status, and IDH enzymatic activity. To this end, we have generated Drosophila cell lines and transformant flies that express the most commonly identified IDH mutations under control of the UAS-Gal4 system. We have also investigated the metabolic flux of Drosophila cell lines expressing IDH mutant protein, and loss of IDH function, and glycolytic enzyme expression analysis. Currently, we are investigating the metabolic flux analysis (MFA) using labeled metabolites as well as comparing the protein interactions of the wild type to the mutant IDH cells. The results of these investigations will identify potential new targets for the treatment of aggressive gliomas at the level of cellular metabolism.
Citation Format: Michaela Brown, Jenna Buccetti, Marla Tipping. Metabolic analysis of IDH mutant gliomas in Drosophila. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 17.
Abstract 1701: CCR6 associates with colon cancer metastasis
Authors: Kapur Neeraj , Mir Hina , Clark Clarence E. , Krishnamurti Uma , Beech Derrick J. , Lillard James W. , Singh Shailesh 
Published: July 2016

Abstract
Despite established benefits of screening, colon cancer remains a leading cause of cancer death in the U.S. Majority of colon cancer deaths result from metastasis. Effective treatments are not available for advanced disease because molecular mechanisms of initiation and progression of this disease are yet to be defined. Chemokine-chemokine receptor interaction plays an important role in cancer progression. In this study, using colon cancer tissue microarray, we have shown that expression of CCR6 was significantly higher in advanced colon cancer (p&lt;0.0001) with distant and regional lymph node metastasis as compared to non-metastatic and adjacent normal tissues. Expression of CCR6 was further confirmed in cell lines derived from Dukes's type C and type D colon cancer patients using flow cytometric analysis. Like tissues, CCR6 expression was significantly (p&lt;0.0001) higher in colon cancer cell lines compared to normal colon epithelial cells. Furthermore, colon cancer cells showed higher migratory potential toward chemotactic gradient of its only known natural ligand, CCL20. Cell proliferation was also inhibited in presence of CCL20. Significant decrease in E-cadherin, increased expression of vimentin, β-catenin, N-cadherin, α-SMA, SNAIL and ZEB1 was observed following CCL20 treatment. These results suggest the importance of CCR6-CCL20 axis in the etiopathogenesis of colon cancer and highlight its potential as therapeutic target.
Citation Format: Neeraj Kapur, Hina Mir, Clarence E. Clark, Uma Krishnamurti, Derrick J. Beech, James W. Lillard, Shailesh Singh. CCR6 associates with colon cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1701.