bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 196: Targeting breast cancer stem cells with a panel of potential ALDH1A3 inhibitors
Authors: Thomas Margaret L. , Wallace Melissa , Giacomantonio Carman , Marcato Paola 
Published: May 2015

Abstract
Aldehyde dehydrogenase (ALDH) isoform ALDH1A3 is selectively expressed in breast cancer stem cells (CSCs) and is a key mediator in breast cancer progression via initiation of retinoic acid (RA) signaling and expression of RA-inducible genes. Expression of ALDH1A3 and its induced RA-inducible genes are associated with less favorable patient outcomes. This suggests that ALDH1A3 represents a novel anti-breast cancer therapeutic target. To target the specific ALDH1A3 isoform, a panel of general ALDH inhibitors was attained and the compounds’ effectiveness in targeting ALDH1A3 activity was quantified by their ability to decrease expression of the downstream genes retinoic acid receptor beta (RARβ) and retinoic acid receptor responder protein 1 (RARRES1). Eleven compounds were tested in total, and the essential oil citral was shown to significantly decrease ALDH1A3-mediated expression of both RA-inducible genes in a dose dependent manner. Citral is already used in cosmetics and food additives and recent work shows that it can induce apoptosis of breast cancer cells making it a promising therapeutic agent and a potential subject of a future xenograft study in mice to determine its effects on CSCs in vivo.
Citation Format: Margaret L. Thomas, Melissa Wallace, Carman Giacomantonio, Paola Marcato. Targeting breast cancer stem cells with a panel of potential ALDH1A3 inhibitors. [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 196. doi:10.1158/1538-7445.AM2014-196
Abstract 1974: Ovulatory wound: the site of origin for ovarian serous carcinoma
Authors: Yang-Hartwich Yang , Gurrea Marta , Sumi Natalia , Holmberg Jennie , Craveiro Vinicius , Alvero Ayesha , Mor Gil 
Published: May 2015

Abstract
Background: New clinical and molecular studies suggest that HGSOC originates from the neighboring fallopian tubes, rather than the surface epithelial layer of the ovary. However, very little is known about the process of tubal malignant cells migrating and implanting into ovary. Our research focuses on understanding how the extraovarian malignant cells implant into the ovary and how ovulation affects the process of their migration and implantation.
Method: Tumor initiating cells (TICs) isolated from human HGSOC were labeled by red fluorescent protein (RFP)-expressing lentivirus and subcutaneously or intrauterine injected to immunocompromised mice. Hormones (PMS and HCG) were interperitoneally injected to induce superovulation in mice. In the in vitro models, TICs were cultured with the granulosa cell conditional medium and the extra cellular matrix (ECM) extracted from ovarian stroma cells to evaluate their effects on the migration and attachment of TICs
Result: Superovulation increased the ovarian tumor-forming rate from 38% (15/39 in control group) to 100% (24/24 in supervolation group). The increased frequency of ovulation enhances the formation of ovarian tumors in mouse models. In the intrauterine injection model, we were able to trace the migration of TICs towards ovaries and capture the early implantation of TICs inside ovaries in 5-10 days after the injection. We detected stage I ovarian tumors in mice. The tumors are encapsulated in the ovary and covered by the intact surface epithelial layer. These tumor cells closely interacted with the stroma of ovary, particularly the structure of corpus luteum. The granulosa cells secreted stromal cell-derived factor 1 (SDF-1, also known as CXCL12). SDF-1 attracts TICs that express CXCR4 (the receptor of SDF-1) to ovulatory wounds. Upon ovulation the ovulatory wounds expose the stroma of ovary, which provides a collagen enriched ECM for TICs to attach.
Conclusion: The unique ovulatory wound microenvironment attracts the malignant cells to migrate towards the ovary and creates access for the malignant cells to implant in the collagen-enriched ECM in the stroma of ovary. The new mechanisms revealed by our data may explain why increased ovulation is associated with epithelial ovarian cancer. Our findings support the “extra-ovarian origin” theory and will help us better understand the initiation and progression of HGSOC.
Citation Format: Yang Yang-Hartwich, Marta Gurrea, Natalia Sumi, Jennie Holmberg, Vinicius Craveiro, Ayesha Alvero, Gil Mor. Ovulatory wound: the site of origin for ovarian serous carcinoma. [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 1974. doi:10.1158/1538-7445.AM2014-1974
Abstract 1976: MDR expression/ activity may serve as potential biomarker in developing therapeutic drugs for AML therapy
Authors: Rudra-Ganguly Nandini , Lowe Christine , Shiwalkar Mukta , Guevara Claudia I. , Kemball Christopher , Wu Min Michelle , Virata Cyrus , Verlinsky Alla , Hsu Ssucheng J , Mattie Michael , Yeh William , Yang Peng , Moon Sung-Ju , Joseph Ingrid , Stover David R. , Pereira Daniel S. , Jacksosn Dowdy 
Published: May 2015

Abstract
Multidrug resistance may play a critical role in developing cancer therapeutics for acute leukemia. The expression of the ATP binding cassette (ABC) transporter Pgp/MDR1 (also known as ABCB1) has been reported in AML patients and correlates with poor clinical outcome. Additional transporters like MRP1 and BCRP also appeared to contribute towards this resistance mechanism. We have profiled a panel of AML tumor cell lines and tumor xenografts for both expression and activity of Pgp/MDR1 via FACS and MSD;. Our profiling also includes analysis of the known SNPs associated with these transporters in key models. We have evaluated the sensitivity of the AML models to a series of standard of care therapies, including auristatins, in both in vitro and in vivo studies. These payloads alone or when conjugated to antibodies as antibody drug conjugates (ADCs) are known substrates of the ABC transporters, Using Pgp inhibitors, we could restore the sensitivity of the MDR expressing cells to the cytotoxic drugs and ADCs, which confirmed that the drugs were MDR substrates. These inhibitors could also block the activity of the Pgp pump. We have also observed limited activity in vivo with these ADCs when used in a MDR positive model. Our initial observation indicates that a threshold level of activity of MDR1 may be critical to confer resistance to these standard of care molecules and antibody drug conjugates using similar payloads. Currently, we are investigating the contribution of other efflux pumps in this mechanism of drug resistance MRP1 and BCRP, in similar manner. This can also aid in identifying cytotoxic drugs that are able to bypass the resistance mediated by these efflux pumps. Additional work is underway to characterize patient samples and identify MDR threshold level of activity as a potential predictive biomarker in developing AML therapeutics.
Citation Format: Nandini Rudra-Ganguly, Christine Lowe, Mukta Shiwalkar, Claudia I. Guevara, Christopher Kemball, Min Michelle Wu, Cyrus Virata, Alla Verlinsky, Ssucheng J Hsu, Michael Mattie, William Yeh, Peng Yang, Sung-Ju Moon, Ingrid Joseph, David R. Stover, Daniel S. Pereira, Dowdy Jacksosn. MDR expression/ activity may serve as potential biomarker in developing therapeutic drugs for AML therapy. [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 1976. doi:10.1158/1538-7445.AM2014-1976
Abstract 1979: Three-dimensional Gelfoam® histoculture enables cancer cells to mimic in vivo cancer cell cycling as visualized with FUCCI imaging
Authors: Yano Shuya , Miwa Shinji , Mii Sumiyuki , Hiroshima Yukihiko , Uehara Fuminari , Kishimoto Hiroyuki , Tazawa Hiroshi , Zhao Ming , Fujiwara Toshiyoshi , Hoffman Robert M. 
Published: May 2015

Abstract
Collagen sponge-gel histoculture was developed by Leighton (In: Encyclopedia of Life Sciences. John Wiley and Sons, Ltd.: Chichester, 2010, Published Online. DOI: 10.1002/9780470015902.a0002573.pub2). In the 1950s, Leighton showed that placing cells in histoculture enables them to form 3-dimensional structures. Because of its architectural resemblance to native tissue, sponge gel histoculture represents a unique in vivo-like model to study cancer-cell behavior (Brenner's Encyclopedia of Genetics, 2nd Ed., Vol. 7, pp. 73-76. Elsevier, 2013). For example, Leighton observed that when C3HBA mouse mammary adenocarcinoma cells were grown on sponge-matrix histoculture, the cells aggregated similar to the original in vitro tumor. Distinct structures were formed within the tumors such as lumina and stromal elements, with some of the glandular structures similar to the original tumor (above-reference). We have further developed sponge gel histoculture using Gelfoam to grow tumors, nerves, hair follicles, skin with growing hair (above-reference). In the present report, we use fluorescence ubiquitination cell cycle indicator (FUCCI) imaging and Gelfoam® collagen sponge gel histoculture to demonstrate that the cell cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is similar whereby only the surface cells proliferate and interior cells are quiescent in G1/G0. This is markedly contrary to 2D culture where most cancer cells cycle. This observation explains, at least in part, the resistance of solid tumors to chemotherapy which targets only cycling cells.
Citation Format: Shuya Yano, Shinji Miwa, Sumiyuki Mii, Yukihiko Hiroshima, Fuminari Uehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Ming Zhao, Toshiyoshi Fujiwara, Robert M. Hoffman. Three-dimensional Gelfoam® histoculture enables cancer cells to mimic in vivo cancer cell cycling as visualized with FUCCI 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 1979. doi:10.1158/1538-7445.AM2014-1979
Abstract 199: Increased killing potential of ex vivo differentiated human natural killer cells in the presence of HOXB4
Authors: Chouaib Salem , Nanbakhsh Arash , Pochon Cécile , Amsellem Sophie , Pittari Gianfranco , Bourhis Jean-Henri 
Published: May 2015

Abstract
We have previously shown that human umbilical cord blood CD34+ progenitor cells undergo in vitro differentiation into functional NK cells and that their co-culture in the presence of HOXB4 transduced stromal MS5 cells resulted in an increase in differentiated NK number. The present study was conducted to compare the stromal effect on NK lytic potential in the presence and absence of HOXB4. Our results provide evidence that HOXB4 transduced MS5 cells as compared to transduced, GFP (+) MS5 cells induced highly differentiated cytotoxic NK cells. Importantly, this difference was not due to the expression of activating NK receptors but was associated with an increased induction of granzyme B transcription and degranulation in response to stimulation with NK cell susceptible targets. DNA microarray-based global transcriptional profiling confirmed the up-regulation of Granzyme B. We provide evidence that HOXB4 is a crucial regulator of NK lytic function and that its use in generating functional NK cells with increased lytic potential may be significant for hematologic malignancies. Our findings provide further evidence that HOXB4 is a crucial regulator of NK function and that its use in generating functional NK cells with increased lytic potential may be significant for cancer immunotherapy.
Citation Format: Salem Chouaib, Arash Nanbakhsh, Cécile Pochon, Sophie Amsellem, Gianfranco Pittari, Jean-Henri Bourhis. Increased killing potential of ex vivo differentiated human natural killer cells in the presence of HOXB4. [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 199. doi:10.1158/1538-7445.AM2014-199
Abstract 1993: The role of metabotropic glutamate receptor 5 on the lymph node metastases in oral cancer
Authors: Kuribayashi Nobuyuki , Uchida Daisuke , Kinouchi Makoto , Tamatani Tetsuya , Nagai Hirokazu , Miyamoto Youji 
Published: May 2015

Abstract
We identified a metastasis-related gene, metabotropic glutamate receptor (mGluR)-5, as a target gene of stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer. In this study, we examined the role of mGluR5 on the lymph node metastasis of oral cancer. mGluR5-specific antagonists, 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) did not affect the growth of oral cancer cells, but did inhibit the SDF-1/CXCR4 dependent-migration of the cells. When the CXCR4 expressing-oral cancer cells were orthotopically transplanted into masseter muscle of nude mice, these antagonists significantly inhibited lymph node metastases of the cells. Immunohistochemical analysis revealed that there was a significant association between CXCR4 and mGluR5 protein expression. Furthermore, the mGluR5 protein expression in clinical specimen was significantly associated with the lymph node metastases and the modes of invasion. Moreover conditioned media derived from the oral cancer cells acquiring SDF-1/CXCR4 system enhanced the migration of lymphatic endothelial cells, which was significantly suppressed by the treatment with MPEP or MTEP. Although SDF-1/CXCR4 dependent-production of angiogenic factors, including interleukin-6, interleukin-8, and vascular endothelial growth factor (VEGF)-A were observed, mGluR5 antagonists did not affect the production of these factors. However, induction of a lymphangiogenic factor, VEGF-C was specifically impaired by the treatment with these mGluR5 antagonists. These results suggested that mGluR5 promotes the lymph node metastases of oral cancer cells by the SDF-1/CXCR4 system via enhancement of cancer cell migration and induction of lymphangiogenesis by VEGF-C.
Citation Format: Nobuyuki Kuribayashi, Daisuke Uchida, Makoto Kinouchi, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto. The role of metabotropic glutamate receptor 5 on the lymph node metastases in oral 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 1993. doi:10.1158/1538-7445.AM2014-1993
Abstract 2: Paxillin enhances angiogenesis through transcriptional regulation of Src in ovarian cancer
Authors: Choi Hyun Jin , Kim Seung-Wook , Pradeep Sunila , Dalton Heather J. , Rupaimoole Rajesha , Mangala Selanere , Lopez Gabriel , Anil Sood K. 
Published: May 2015

Abstract
Purpose: Paxillin (PXN) expression is increased in various cancer types, but its biological and clinical impact is not well understood. Here, we examined the biological effects of paxillin in ovarian cancer.
Methods: The in vivo (HeyA8 and HeyA8-MDR orthotopic mouse models of ovarian cancer) and in vitro (tube formation assays, reverse phase protein array (RPPA) analysis, RT-PCR chromatin-immunoprecipitation (ChIP) assay) effects of paxillin were examined in ovarian cancer.
Results: Paxillin silencing using siRNA incorporated in DOPC nanoliposomes resulted in 55% reduction in tumor growth in a HeyA8 orthotopic ovarian cancer mouse model (p&lt;0.05). There was an unexpected effect of marked reduction in vascular density (67%, p&lt;0.01). In addition, tumor proliferation was decreased by 60% (p&lt;0.01) in PXN-siRNA treatment group. This anti-proliferative effect of siPXN was not observed in vitro. In contrast, a significant anti-angiogenic effect was observed in vitro using a tube formation assay, where condition media collected from ovarian cancer cells treated with siPXN compared to siControl resulted in a prominent (60%,p&lt;0.01) reduction in tube formation ability of endothelial cells. RPPA analyses pointed to Src protein expression being significantly decreased following PXN silencing in HeyA8 cells. Using RT-PCR and western blotting techniques, we observed that Src mRNA and protein levels were significantly decreased in siPXN-treated cells. Moreover, p-Src protein level was also found to be decreased following PXN silencing. ChIP analysis showed direct PXN binding to the Src promoter.
Conclusion PXN exerts indirect effects on tumor angiogenesis, mediated through Src. These findings provide a new understanding of the role of PXN in malignant biology.
Citation Format: Hyun Jin Choi, Seung-Wook Kim, Sunila Pradeep, Heather J. Dalton, Rajesha Rupaimoole, Selanere Mangala, Gabriel Lopez, Sood K. Anil. Paxillin enhances angiogenesis through transcriptional regulation of Src in ovarian 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 2. doi:10.1158/1538-7445.AM2014-2
Abstract 2001: GATA2: Potential role as a prostate cancer metastasis-driving gene
Authors: Chiang Yan Ting , Wang Kendric , Crea Francesco , Collins Colin , Gout Peter , Wang Yuzhuo 
Published: May 2015

Abstract
Metastasis is thought to result from changes in the expression of specific metastasis-driving genes leading to a cascade of activated downstream genes that set the metastatic process in motion. The present study was aimed at identifying such metastasis-driving genes in prostate cancer for potential therapy and identification of primary prostate cancers that are likely to metastasize. To this end, a differential gene expression profile was established of metastatic LTL-313H and non-metastatic LTL-313B prostate cancer tissue xenografts, derived from one patient's specimen using sub-renal capsule grafting technology. The profile was then subjected to integrative analysis using the Ingenuity Upstream Regulator Analysis tool. Six candidate master regulatory genes were identified, including GATA2, a gene encoding a pioneer factor in prostate cancer. Elevated GATA2 expression in clinical metastatic prostate cancer tissues was found to correlate with poor patient prognosis. Furthermore, GATA2 gene silencing in human prostate cancer LNCaP cells led to a marked reduction in cell migration, tissue invasion, focal adhesion disassembly and to a drastic change in cell transcriptome. Furthermore, 582 genes were identified that are (i) differentially expressed after GATA2 gene silencing in LNCaP cells and (ii) whose changes in gene expression significantly correlated with changes in GATA2 expressions in a MSKCC prostate cancer patient cohort. Taken together, the data suggest that GATA2 could represent a prostate cancer metastasis-driving gene and that the expression patterns of GATA2 and its associated-genes could serve as signatures (biomarkers) for poor prognosis in prostate cancer.
Citation Format: Yan Ting Chiang, Kendric Wang, Francesco Crea, Colin Collins, Peter Gout, Yuzhuo Wang. GATA2: Potential role as a prostate cancer metastasis-driving gene. [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 2001. doi:10.1158/1538-7445.AM2014-2001
Abstract 2006: The role of neuronal predominant gene expression in breast cancer brain metastasis
Authors: Kanojia Deepak P. , Sarvaiya Purva , Qiao Jian , Zhang Lingjiao , Balyasnikova Irina , Lesniak Maciej S. 
Published: May 2015

Abstract
Breast cancer brain metastasis (BCBM) occur in about 10-30% of patients with breast cancer. It has been established that breast cancer is a heterogeneous disease with 3 predominant subtypes (1) ER/PR positive (3) HER2 positive (4) Triple negative breast cancer (TNBC)/Basal subtype. TNBC is associated with the highest incidence of metastasis to brain, mechanism of which is poorly understood. Therefore, in order to understand the proclivity of TNBC to the brain and identify potential targets for treatment BCMB, we employed two widely used paired cell model system, the MDA-MB-231/MDA-MB-231BrM2 and the CN-34/CN34BrM2. The levels of brain predominant markers [ST6GALNAC5 (ST6), Nestin, Tubulin β3 (TUBB3)] in brain-derived clones were assesed by qRT-PCR and found to be overexpressed in brain-derived MDA-MB-231BrM2 and CN34BrM2 in comparison with parental breast cancer cell lines. We also identified hyperactivated TGF-β signaling in brain derived clones in comparison with parental cells. Moreover, the treatment of parental cells with TGF-β increased the expression of ST6, Nestin and TUBB3 indicating that TGF-β plays role in the development of BCBM. To further delineate the role of these markers in BCBM, knockdown experiments using two different shRNA specific to TUBB3 (neuronal specific) were performed. TUBB3 knockdown resulted in a dramatic reduction in tumorspheres formation, migration, invasion and the ability to adhere to laminin in both MDA-MB-231BrM2. Furthermore, the downregulation of expression of β1 and β3 integrins in TUBB3 knockdown cells was discovered as assessed by qPCR and flow cytometry. These results implicate that overexpression of brain specific TUBB3 provides breast cancer cells with migration and invasion abilities and a possible survival advantage in the brain microenvironment.
Citation Format: Deepak P. Kanojia, Purva Sarvaiya, Jian Qiao, Lingjiao Zhang, Irina Balyasnikova, Maciej S. Lesniak. The role of neuronal predominant gene expression in breast cancer brain 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 2006. doi:10.1158/1538-7445.AM2014-2006