bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1530: Therapeutic efficacy of cancer stem cell vaccine in an adjuvant setting
Authors: Hu Yangyang , Lu Lin , Chang Alfred E. , Egenti Martin , Owen John , Moyer Jeffrey S. , Prince Mark E.P. , Xia Jianchuan , Huang Shiang , Wicha Max S. , Li Qiao 
Published: August 2015

Abstract
The inability to target cancer stem cells (CSC) may be a significant factor contributing to treatment failure. Novel therapeutic strategies are needed to immunologically target CSCs. We have developed a strategy to target the CSC populations in melanoma and squamous cell carcinoma using CSC lysate-pulsed dendritic cells (DC). Using mouse models we demonstrate that DC pulsed with CSCs enriched by virtue of their expression of the CSC marker ALDH (CSC-DC) significantly inhibited local tumor growth, reduced development of pulmonary metastases and prolonged survival in the minimal tumor models. The effect was associated with down regulation of CCR7 and CCR10 in tumor cells and decreased CCL27 and CCL28 expression in lung tissue. CSC-DC vaccine significantly reduced ALDHhigh CSCs. Direct targeting of CSCs was demonstrated by specific binding of IgG produced by ALDHhigh CSC-DC vaccine-primed B cells to ALDHhigh CSCs, resulting in lysis of these target cells in the presence of complement. When administered in the adjuvant setting after surgical excision of the bulk tumor mass, administration of CSC-DC vaccine reduced development of local tumor growth as well as systemic disease and prolonged survival demonstrating the efficacy of this approach. These data suggest that the CSC-DC vaccine approach may be useful in the adjuvant setting where local and systemic relapse are high after surgery.
Note: This abstract was not presented at the meeting.
Citation Format: Yangyang Hu, Lin Lu, Alfred E. Chang, Martin Egenti, John Owen, Jeffrey S. Moyer, Mark E.P. Prince, Jianchuan Xia, Shiang Huang, Max S. Wicha, Qiao Li. Therapeutic efficacy of cancer stem cell vaccine in an adjuvant setting. [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 1530. doi:10.1158/1538-7445.AM2015-1530
Abstract 1531: Distinct roles of CXCR3 isoforms in promoting breast cancer stem-like cell properties and metastasis
Authors: Li Yanchun , Reader Jocelyn C. , Ma Xinrong , Kundu Namita , Kochel Tyler , Fulton Amy M. 
Published: August 2015

Abstract
Growing evidence has demonstrated that the two major isoforms of chemokine receptor CXCR3 (CXCR3-A, CXCR3-B) both contribute to breast cancer pathogenesis and metastasis, however, in different ways. Understanding the relative contribution of each isoform is critical to optimize therapeutic strategies targeting CXCR3. Furthermore, the possible involvement of either CXCR3 isoform in cancer stem-like properties has not been reported. We examined the contribution of each isoform to metastasis using a panel of breast cell lines and a xenograft model of breast cancer; we also explored the role of major CXCR3 isoforms in the behavior of stem-like cells. CXCR3-A is more abundantly expressed than CXCR3-B in both primary human breast cancer tissue and in breast cancer cell lines. On the contrary, immortalized normal MCF-10A cells are CXCR3-B dominant. In basal-like MDA-MB-231 cells, CXCR3 ligand-stimulated proliferation is inhibited by CXCR3-B overexpression, with concurrent reduced activation of ERK1/2 and p38 kinases. Similarly, higher levels of CXCR3-B inhibit migration and invasion in vitro and metastasis in vivo. Accordingly, reduced CXCR3-B expression by gene-silencing enhances lung colonization in the xenograft model. Although exhibiting anti-proliferative and anti-metastatic roles in the non-stem cell population, CXCR3-B supports a cancer stem-like cell phenotype. In mammosphere-forming MDA-MB-231 cells, CXCR3-B is markedly up-regulated and mammosphere-forming capacity is further increased when overexpressing CXCR3-B. Likewise, soft agar growth is promoted by CXCR3-B overexpression. Accordingly, silencing CXCR3-B by shRNA inhibits stem-like properties. In conclusion, both isoforms need to be targeted to inhibit the pro-proliferative and pro-metastasis functions of CXCR3-A and the stem cell-promoting actions of CXCR3-B.
Citation Format: Yanchun Li, Jocelyn C. Reader, Xinrong Ma, Namita Kundu, Tyler Kochel, Amy M. Fulton. Distinct roles of CXCR3 isoforms in promoting breast cancer stem-like cell properties 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 1531. doi:10.1158/1538-7445.AM2015-1531
Abstract 1541: Secreted serglycin in tumor microenvironment promotes tumor malignancies in a CD44-dependent manner
Authors: Guo Jing-You , Tyan Shiaw-Wei , Hsu Han-Shui , Li Fen-Yau , Chen Jeou-Yuan 
Published: August 2015

Abstract
Tumor microenvironment (TME) plays an important role in cancer progression; however, the communication between TME and cancer cells remains largely unclear. CD44, a type I cell surface receptor functioning in cell-cell and cell-extracellular matrix interactions, has been implicated in tumor formation and progression. Using gain-of-function and loss-of-function approaches, we report in this study that serglycin (SRGN), a glycoprotein secreted from cancer-associated fibroblasts (CAFs) as well as aggressive cancer cells, works to promote the malignant behaviors of non-small cell lung cancer cells through its interaction with CD44. We showed that SRGN promotes cell transformation and tumor formation and metastasis using in vitro and in vivo tumorigenic assays. Furthermore, we showed that SRGN induced lung cancer cell stemness in a CD44-dependent manner. SRGN enhanced cancer cells sphere formation via Nanog induction, accompanied with increased drug resistance and resistance to anoikis. We also demonstrated that SRGN promotes cell migratory activity through promoting epithelial-mesenchymal transition (EMT) and enhancing adhesions turnover by upregulating vimentin expression and SRC activity via CD44/NF-KB/Claudin-1 axis. In support, Claudin-1 expression was tightly associated with SRGN expression in primary lung cancer tissues (p &lt; 0.0001). In summary, we demonstrate that the crosstalk between tumor cells and TME promotes malignant phenotypes through the interaction of tumor-borne CD44 and CAF- or tumor-derived SRGN, suggesting that targeting CD44 or its ligands may represent an attractive strategy for development of cancer therapy.
Citation Format: Jing-You Guo, Shiaw-Wei Tyan, Han-Shui Hsu, Fen-Yau Li, Jeou-Yuan Chen. Secreted serglycin in tumor microenvironment promotes tumor malignancies in a CD44-dependent manner. [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 1541. doi:10.1158/1538-7445.AM2015-1541
Abstract 1543: Wogonin suppresses the production of breast cancer-derived osteolytic factors
Authors: Kim Hyungkeun , Park Kwang-Kyun , Chung Won-Yoon 
Published: August 2015

Abstract
Breast cancer is the most frequent cancer in women and the main cause of its mortality is induced by metastasizing to distant organs. Breast cancer primarily metastasizes to the bone, lung, liver and brain, and the bone is the most susceptible to metastasis. When breast cancer metastasizes to the bone, the dominant lesion is osteolytic. This osteolytic bone metastasis is highly associated with the complex interaction between cancer cells and the bone microenvironment. Interleukin-1 beta (IL-1β) and IL-17 act as osteolytic factors and promote osteolytic lesions in breast cancer pateints by increasing osteoclastogenesis and decreasing osteoblastogenesis. Especially, both of IL-1β and IL-17 increase in patients with breast cancer and decrease disease-free survival in cancer patients. Wogonin, one of the major flavonoids in the roots of Scutellaria baicalensis Georgi, has been recognized as a potent anti-cancer agent through increased apoptosis and decreased proliferation. We investigated whether wogonin could reduce the cancer cell-induced osteolysis by controlling interaction between cancer cells and bone-related cells. Wogonin suppressed cell viability, DNA synthesis and migration in MDA-MB 231 cells. Wogonin reduced the secretion of IL-1β and IL-17 in MDA-MB 231 cells. Wogonin at non-cytotoxic concentrations inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast formation in mouse bone marrow-derived macrophages. Furthermore, wogonin blocked an increase in RANKL/osteoprotegerin mRNA ratio in the osteoblastic hFOB1.19 cells exposed to MDA-MB 231 cells-derived conditioned medium. Finally, oral administration of wogonin significantly inhibited osteolytic lesions in MDA-MB 231 cells-injected mice. Taken together, these results indicate that wogonin is a promising agent for preventing and treating cancer-cell mediated bone loss.
Citation Format: Hyungkeun Kim, Kwang-Kyun Park, Won-Yoon Chung. Wogonin suppresses the production of breast cancer-derived osteolytic factors. [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 1543. doi:10.1158/1538-7445.AM2015-1543
Abstract 1544: Association of tumor location with the breast and clinicopathological characteristics
Authors: Rummel Seth , Costantino Nick , Hueman Matthew T. , Shriver Craig D. , Ellsworth Rachel E. 
Published: August 2015

Abstract
Introduction Tumor location within the breast varies, with the highest frequency in the upper outer quadrant (UOQ) and lowest in the lower inner quadrant (LIQ). What is not well understood is whether tumor location is prognostic. To determine whether tumor location is prognostic, associations between tumor site and clinicopathological characteristics were evaluated.
Methods The Clinical Breast Care Project database was queried to identify all patients whose tumor site- UOQ, upper inner quadrant (UIQ), central, (LIQ), lower outer quadrant (LOQ) - was determined by a single, dedicated breast pathologist between 2001 and 2013. Patients with multicentric disease (n = 122) or tumors spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics evaluated included age at diagnosis, ethnicity, BMI, tumor stage, grade, and size, and hormone receptor, HER2 and lymph node status. Data was analyzed using chi-square and Mann-Whitney tests for univariate analysis with multivariate analysis performed using principal components analysis and multiple logistic regression. Significance was defined as P&lt;0.05.
Results Of the 980 patients with defined tumor location, 30 had bilateral disease. Tumor location in the UOQ (51.5%) was higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%) or LIQ (8.1%). Tumors in the central quadrant were significantly more likely to have higher tumor stage (P = 0.003) and size (P&lt;0.001), positive lymph node status (P&lt;0.001), and mortality rates (P = 0.011) compared to other quadrants. Analysis within each tumor size, however, found no difference in lymph node status by tumor location. After multivariate analysis, only tumor size and lymph node status remained significantly associated with mortality.
Discussion Although tumors in the central region are associated with less favorable outcome, this association was driven by significantly larger tumor size, which has been associated with positive lymph node status. Tumors in the central region are known to be more difficult to detect mammographically and the majority of tumors in this region are palpable, thus, tumor location is not an independent prognostic factor, but rather less favorable prognosis, including larger tumor size, higher grade and more lymph node involvement in the central region can be attributed to delayed diagnosis.
Citation Format: Seth Rummel, Nick Costantino, Matthew T. Hueman, Craig D. Shriver, Rachel E. Ellsworth. Association of tumor location with the breast and clinicopathological characteristics. [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 1544. doi:10.1158/1538-7445.AM2015-1544
Abstract 1549: Development and validation of a biomarker for prospective selection of Notch1 activation in patients with certain advanced solid tumors in a first-in-human phase1 study of the cancer stem cell targeting antibody OMP-52M51 (anti-Notch1)
Authors: Cancilla Belinda , Tam Raymond , Zhang Chun , Anderson Steve , Lewicki John , Hoey Tim , McCune Bryan , Johnson Lori , Idusogie Esohe , Kapoun Ann M. 
Published: August 2015

Abstract
The Notch pathway plays a key role in embryonic development, the regulation of stem and progenitor cells, and is implicated centrally in many forms of human cancer. Notch1 is known to be frequently activated in certain solid tumor types. OMP-52M51 is a humanized IgG2 antibody that inhibits the signaling function of the Notch1 receptor. Mouse xenograft studies using minimally-passaged, patient-derived xenografts have shown that OMP-52M51 impedes tumor growth and selectively eliminates CSCs in a range of tumor types particularly in tumors with activated Notch1 signaling.
We previously reported the frequency of Notch pathway activation across a large panel of human tumors (n&gt;600) by an Immunohistochemistry (IHC) assay that detects the activated form of Notch1 using an antibody that specifically recognizes the Notch1 intracellular domain (ICD). Using this test and a rigorous H-score cut-off, we found elevated Notch1 ICD in 7-53% of the following cancers: chemo-resistant breast (29%), gastric (13%), cholangiocarcinoma (20%), esophageal (27%), hepatacellular carcinoma (HCC, 7%), small cell lung cancer (SCLC, 12%), pancreatic (12%) and colorectal cancer (53%).
Here we developed a specific CLIA-validated IHC assay capable of identifying patients with Notch1 activation. The assay has a rapid turn-around time and shows robust precision, reproducibility and accuracy. The sensitivity of the method was confirmed by comparing results obtained on xenograft tumor tissue samples with known levels of Notch1 expression and response to anti-Notch1 therapy. From these results, the cut-off of the assay was set. This predictive biomarker was specifically designed to screen patients for prospective selection in the first-in-human Phase1 study of OMP-52M51 (anti-Notch1) in certain advanced solid tumors (NCT01778439). Detailed assay validation data and its application to the analysis of clinical trial samples will be highlighted.
Citation Format: Belinda Cancilla, Raymond Tam, Chun Zhang, Steve Anderson, John Lewicki, Tim Hoey, Bryan McCune, Lori Johnson, Esohe Idusogie, Ann M. Kapoun. Development and validation of a biomarker for prospective selection of Notch1 activation in patients with certain advanced solid tumors in a first-in-human phase1 study of the cancer stem cell targeting antibody OMP-52M51 (anti-Notch1). [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 1549. doi:10.1158/1538-7445.AM2015-1549
Abstract 1555: An automated cage-based method of randomized group distribution in pre-clinical in vivo studies
Authors: Ibsen Eric M. , Kumer Jeffrey L. 
Published: August 2015

Abstract
To more closely emulate clinical research methodology, researchers are increasingly utilizing clinically-similar group randomization and distribution methods for oncology studies in animals. It has been common practice to re-house animals into new cages with new cagemates following randomized group distribution. In male animals in particular, this frequently results in high levels of stress, injury and sometimes death due to fighting to re-establish social dominance hierarchies. Since some animals suffer more and others less, based on their relative position within the newly-established hierarchy, the levels of stress vary across the study subject population. The full impact of such stress on anticancer agent efficacy is not known but is widely believed to significantly diminish study integrity. For this reason, many researchers do not re-house male animals, choosing instead to co-house animals from various groups. It is believed that the exposure of cagemates to test agents in excreta and saliva during grooming as well as significantly increasing the risk of accidental mis-dosing can likewise negatively impact study integrity. The commonly-used manual and spreadsheet-based randomization methods do not enable cage-based randomized distribution based on qualitative or quantitative parameters. Commercially available pre-clinical trial applications now offer a solution to the above-mentioned problems.Randomization or distribution of animals based on the mean tumor volume or other parameters within the same cage allow for distribution to groups based on cage means. The variety of cage-based randomization methods available include: pure randomization, stratified sampling randomization and block randomization across multiple numeric parameters. Also, deterministic and matched-pair distribution methods can be used as well.Subjects in cages may be excluded initially based on recorded qualitative observations, and then by acceptable value ranges for numeric parameters. ANOVA results of group means are displayed instantly to ensure similarity between groups. Using software to perform standardized cage-based randomization and distribution is more clinically relevant, mitigating the negative impacts associated with post-randomization re-housing of animals. This significantly decreases the negative impact on study integrity relative to spreadsheet-based methods.
Note: This abstract was not presented at the meeting.
Citation Format: Eric M. Ibsen, Jeffrey L. Kumer. An automated cage-based method of randomized group distribution in pre-clinical in vivo 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 1555. doi:10.1158/1538-7445.AM2015-1555
Abstract 156: LncRNA BC200 is induced by estradiol and regulates apoptosis in MCF-7 breast cancer cells
Authors: Singh Ramesh , Mo Yin-yuan 
Published: August 2015

Abstract
LncRNA BC200 is a small functional RNA which has been implicated in the regulation of protein synthesis in neurons. It is dysregulated in invasive carcinomas of the breast. In this study, we reported that BC200 is upregulated in breast cancer, as detected by RT-PCR analysis of breast cancer tissue scan, suggesting its possible role as an oncogene. We then demonstrated that BC200 is transcriptionally induced by estradiol (E2) treatment in ER positive breast cancer cell lines through multiple functional estrogen response elements (EREs), including the full ERE sequence ∼800bp from transcriptional start site. Luciferase reporter assay combined with mutation analysis indicated that the full ERE region is critical to the estradiol-induced promoter activity. Furthermore, BC200 is crucial for cell growth and viability; its knockdown induces apoptosis in MCF-7 cells. This may explain in part why estrogen can promote cell proliferation in ER positive breast cancer cells. To better study its role in breast cancer development and progression, we generated BC200 knockout MCF-7 cell cells using CRISPR/Cas9 technique. BC200 knockout leads to the release of cytochrome c from mitochondria and promotes the cleavage of PARP-1, both of which are an indicator of cell apoptosis. This was further confirmed by TUNEL assay. It has been reported that hnRNP A2/B1 alters the bcl-X pre-mRNA splicing in favor of anti-apoptotic bcl-XL. Of great interest, BC200 knockout enhances expression of pro-apoptotic bcl-XS form at both mRNA and protein level. RNA pulldown assays using biotin-labeled BC200 probe suggested that BC200 can bind to hnRNP Q and hnRNP A2/B1. On the other hand, RNA immunoprecipitation using hnRNP A2/B1 antibody in BC200 knockout MCF-7 cells showed a significant reduction in enrichment of bcl-X mRNA as compared to control cells. We propose that the regulation of bcl-X alternative splicing depends upon endogenous expression of BC200 that would help hnRNP A2/B1 to position itself on bcl-X mRNA and modulate splicing in favor of bcl-XL. Thus, loss of BC200 leads to generation of bcl-XS protein synthesis and to apoptosis. Together, these results suggest that BC200 functions as a negative regulator of apoptosis in breast cancer and thus, it may serve as a potential target for cancer therapies.
Citation Format: Ramesh Singh, Yin-yuan Mo. LncRNA BC200 is induced by estradiol and regulates apoptosis in MCF-7 breast cancer 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 156. doi:10.1158/1538-7445.AM2015-156
Abstract 1560: FGFR4 is expressed in the tumor and stromal compartments of human gliomas of all grades and histologies
Authors: Gjerde Christiane H. , Mutlu Ercan , Leiss Lina , Kristensen Bjarne Winther , Rahman Mohummad Aminur , Enger Per Øyvind 
Published: August 2015

Abstract
BACKGROUND: Fibroblast growth factor receptor (FGFR) 4 is reportedly expressed in several cancer types, and is a high-affinity transmembrane receptor for FGF2 which is expressed human astrocytomas. However, the expression of FGFR4 across gliomas of different grades and histologies has not been extensively investigated.
METHODS: We performed immunohistochemistry (IHC) of 178 grade II-IV human gliomas from our tumor bank, including 117 GBMs and 61 lower grade gliomas of astrocytic and oligodendroglial lineage. The samples were scored (0-2) separately for staining intensity and fraction of area that was stained and whether staining was predominantly cytoplasmic or nuclear. This scoring was performed separately for tissue from tumor center and periphery, as well as in tumor areas around pseudopalisading (PP) and large necroses. We also performed western blot analysis (n = 22) and real-time qPCR (n = 37). On one tumor sample we performed FISH for EGFR (red)/Centromere chromosome 7 (green), combined with immunofluorescence (IF) for FGFR4.
RESULTS: I) FGFR4 is uniformly expressed in human gliomas, although at a varying degree, as confirmed by IHC, western blotting and RT-qPCR. II) FGFR4 expression was detected both in the nuclei and cytoplasm. III) Both a homogenous and a granular staining pattern was observed the cytoplasm, suggesting involvement of different cell types, whereas FISH demonstrated expression in the tumor and stromal cell compartments. IV) Tumors of grade II and III show a statistically significant higher expression than tumors of grade IV as shown by RT-qPCR. V) There is no difference in expression by IHC between tumors of grade II, III and IV.
Citation Format: Christiane H. Gjerde, Ercan Mutlu, Lina Leiss, Bjarne Winther Kristensen, Mohummad Aminur Rahman, Per Øyvind Enger. FGFR4 is expressed in the tumor and stromal compartments of human gliomas of all grades and histologies. [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 1560. doi:10.1158/1538-7445.AM2015-1560