bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4050: Association of long term NK cell culture and TIMP3 over-expression with NK cell reduced susceptibility to leukemia and epithelial cancer cell induced damage
Authors: Sconocchia Giuseppe , Arriga Roberto , Caratelli Sara , Lanzilli Giulia , Coppola Andrea , Spagnoli Giulio C. , Venditti Adriano , Amadori Sergio , Lauro Davide , Del Principe Maria I. , Maurillo Luca , Buccisano Francesco , Capuani Barbara , Wang Xinhui , Ferrone Soldano 
Published: August 2015

Abstract
Allogeneic leukemia and cancer epithelial (CE) cells have been recently shown to induce,in vitro, NK cell abnormalities (NKCA). The latter include NK cell depletion and apoptosis as well as natural cytotoxic receptor (NCR) CD16 down-regulation. The potential negative impact of leukemia and CE cell induced NKCAs on the in vivo anti-tumor activity of NK cells and the limited information about strategies to protect NK cells from NKCAs have prompted us to characterize NKCAs and to develop strategies to counteract them. NKCA induction by leukemia and CE cells is influenced neither by interleukin-2 (IL-2) treatment nor by HLA class I antigen expression, but is abrogated by a long term culture of peripheral blood mononuclear cells (PBMCs) at 37 ºC. Following a 10 day culture of PBMCs, NK cells become resistant to cancer cell induced NKCA but maintain their cytotoxic activity. Actinomycin D restores the susceptibility of long term NK (LTNK) cells to NKCAs suggesting that the generation of resistance to NKCAs requires RNA transcription. TAPI-0, a functional analogue of the tissue inhibitor of metalloproteinases (TIMP) 3, inhibits cancer cell induced NKCAs indicating a role for a restricted number of metalloproteinases (MMPs) in the generation of this phenomenon. This conclusion is supported by the reduced susceptibility to cancer cell induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. Finally, subcutaneous infusion of IL-2 stimulated LTNK cells inhibited subcutaneous growth of the monoblastic leukemia cells, ML-2 in CB17scid mice while short term, IL-2 stimulated NK cells did not suggesting that LTNK cells have significant anti-leukemia capacity in vivo. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy for the treatment of myeloid leukemias with haploidentical or allogeneic NK cells.
Citation Format: Giuseppe Sconocchia, Roberto Arriga, Sara Caratelli, Giulia Lanzilli, Andrea Coppola, Giulio C. Spagnoli, Adriano Venditti, Sergio Amadori, Davide Lauro, Maria I. Del Principe, Luca Maurillo, Francesco Buccisano, Barbara Capuani, Xinhui Wang, Soldano Ferrone. Association of long term NK cell culture and TIMP3 over-expression with NK cell reduced susceptibility to leukemia and epithelial cancer cell induced damage. [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 4050. doi:10.1158/1538-7445.AM2015-4050
Abstract 406: Effects of an RGD peptide in osteoclast maturation and behavior as a therapeutic option for metastatic bone disease
Authors: Prager Gerald , Bianconi Daniela , Chillà Anastasia , Dorda Alexandra , Geetha Nisha , Unseld Matthias , Sykoutri Despoina , Poettler Marina , Redlich Kurt , Zielinski Christoph 
Published: August 2015

Abstract
Metastatic bone disease is a common feature of many types of cancer and has a severe impact on the quality of life of patients. Hence, specific therapeutic strategies inhibiting tumor induced osteolysis are urgently needed. In this study, we aimed to interfere with integrin adhesion receptors, which are central players of the bone resorption process, including osteoclastogenesis as well as osteoclast/bone matrix interaction. For this purpose, we used a cyclic RGD peptide which blocks integrin áVâ3 and áVâ5-ligand binding. Our results revealed that the RGD peptide blocked osteoclast maturation in a dose-dependent manner. In detail, pre-osteoclasts treated with the RGD peptide exhibited reduced cell spreading, migration and adhesion on RGD-containing matrix proteins, such as osteopontin and fibrinogen, which are ligands of integrin áVâ3. The activation of the most upstream signal transduction molecules of the integrin receptor-initiated pathway, such as FAK and c-Src, were consistently blocked by the RGD peptide. First evidence has suggested that the RGD peptide might interfere with metastatic bone disease in vivo and the evidence presented herein describes the underlying mechanisms of the inhibitory effect of the RGD peptide on áV-integrin expressing pre-osteoclasts by blocking integrin ligand binding and interfering with osteoclast maturation and cell behavior. In conclusion, our findings suggest that using an RGD peptide to interfere with áV-integrins on osteoclasts may represent a novel therapeutic strategy in the treatment of malignant bone disease.
Citation Format: Gerald Prager, Daniela Bianconi, Anastasia Chillà, Alexandra Dorda, Nisha Geetha, Matthias Unseld, Despoina Sykoutri, Marina Poettler, Kurt Redlich, Christoph Zielinski. Effects of an RGD peptide in osteoclast maturation and behavior as a therapeutic option for metastatic bone disease. [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 406. doi:10.1158/1538-7445.AM2015-406
Abstract 4068: In vivo analysis of the residual disease uncovers early and late response of cytarabine-resistant cells in human acute myeloid leukemia
Authors: Sarry Jean-Emmanuel 
Published: August 2015

Abstract
The major therapeutic barrier in acute myeloid leukemia (AML) is chemotherapeutic resistance. Resistant cells to conventional chemotherapy - which targets DNA synthesis - are thought to be rare and enriched in quiescent leukemic stem cells. In order to develop an improved understanding of chemotherapy resistance in AML, we analyzed the response to cytarabine (AraC) and disease regrowth in a xenograft model with 13 primary AML patient specimens. After demonstrating AML engraftment, mice are treated with AraC given IP daily for 5 days as a single agent at 60 mg/kg daily, which correlates with human dosing. In all mice treated with AraC, there was a strong cytoreductive effect at 1 week post-treatment with regrowth at 2-8 weeks post-treatment, demonstrating that there is a dose response relationship in the model in terms of nadir leukemic burden and time to relapse. While in vivo AraC increases in hypoxic CD34posCD38neg phenotype, this treatment does not induce any significant changes in cell cycle progression and kills both cycling and quiescent cells in AML-engrafted mice. We also observed that AraC decreases the frequency of leukemia-initiating cells. Furthermore, transcriptomic analysis of residual leukemic cells from three patients-derived xenografts during disease progression (1-2-4 weeks post-AraC) reveals that the AraC resistance is associated with enrichment in genes involved into the apoptosis regulation, inflammatory and metabolism at early stage (1 week), and in stem cell markers with adverse prognosis at the onset of the tumor regrowth (2 week). Altogether, these results suggest a novel model for cytarabine resistance in AML.
Citation Format: Jean-Emmanuel Sarry. In vivo analysis of the residual disease uncovers early and late response of cytarabine-resistant cells in human acute myeloid leukemia. [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 4068. doi:10.1158/1538-7445.AM2015-4068
Abstract 4071: Cancer stem cell-induced vascularization of skin cancer tumors
Authors: Grun Dan , Adhikary Gautam , Eckert Richard 
Published: August 2015

Abstract
Our previous studies identify a subpopulation of epidermal cancer stem (ECS) cells in human squamous cell carcinoma that are efficient tumor formers. These cells display enhanced invasion and migration, and form large, invasive and highly aggressive tumors. We now show that ECS cells produce highly vascularized tumors. This is confirmed visually and by detection of increased expression of the CD31 endothelial cell marker. To understand the molecular basis for increased vascularization, we assayed for ECS cell and non-stem cancer cell production of angiogenic factors. Pro-angiogenic factors, including VEGF-A, HIF-1α and MMP9, are produced at high level in ECS cell-derived tumors, as compared to non-stem cancer cell tumors. In addition, anti-angiogenic factor production (thrombospondin-1, endothelin-1, serpin B5) is reduced. This is consistent with the finding that ECS cell tumor extracts more efficiently stimulate HUVEC cell tube formation. Moreover, these ECS tumor-derived cells display enhanced spheroid formation, and cell migration and invasion. Knockdown of VEGF-A or VEGFR2, or treatment with anti-VEGF-A attenuates these events. In addition, treatment with bevacizumab (anti-VEGF-A) suppresses tumor formation in vivo. These studies suggest that the VEGF-A signaling pathway is enhanced in ECS cells and is in part responsible the ability of these cells to form aggressive and highly vascularized tumors.
Citation Format: Dan Grun, Gautam Adhikary, Richard Eckert. Cancer stem cell-induced vascularization of skin cancer tumors. [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 4071. doi:10.1158/1538-7445.AM2015-4071
Abstract 4074: Cancer stem cells in tobacco-induced carcinogenesis and subsequent effect of ATRA-based chemoprevention
Authors: Surendran Subin , Mimikos Christina , Suresh Amritha , Hicks Wesley L. , Seshadri Mukund , Kuriakose Moni A. 
Published: August 2015

Abstract
Introduction Chemoprevention is potentially the most effective method to lower the prevalence of head and neck squamous cell carcinomas (HNSCC), the sixth most common type of malignancy worldwide. The chemopreventive effects of retinoids against HNSCC have been previously reported. Retinoids however; relapse following cessation of medication is a critical problem that prevents its clinical use. The objective of this study was to determine the possible mechanism of retinoid resistance by exploring cancer stem cell mediated pathways.
Experimental Procedures.
In vitro cell line models of normal (NOK) and dysplastic oral keratinocytes (DOK) are being exposed to tobacco to assess the process of carcinogenic progression. The progression in the DOK and HOK cell lines will be assessed by proliferation, migration and invasion assays. The expression of stem cell markers/pathways (CD44/Hyaluronan, Wnt, Notch1, ALDH1A1) during the process of progression will be evaluated using QPCR and FACS. These cell lines will then be treated with ATRA and the subsequent effects on transformation and CSC-specific pathways further evaluated.
Summary To this end, immunostaining of normal oral mucosa, potentially malignant lesions (n = 93) and malignant lesions (n = 48) for the stem cell marker CD44 was performed. CD44+ cells were found at a density of 58.57/hpf in normal mucosa, 61.56/hpf in mild dysplasia, 119.44/hpf in moderate dysplasia, and 107.6/hpf in severe dysplasia. The density of CD44+ cells in WDSCC, MDSCC and PDSCC were 183.4, 105 and 160/hpf respectively, indicates CSC cells may represent a marker of malignant progression The cell lines are currently under exposure to tobacco and the transformational changes being documented. Apart from the studies on the changes specific to CSCs, high throughput secretome and proteomic studies are also being planned to evaluate the global changes effected due to tobacco as well as due to subsequent treatment with ATRA.
Conclusion This study hence attempts to provide novel insight into tobacco-induced carcinogenesis and mechanism of resistance to retinoid-based chemoprevention.
Note: This abstract was not presented at the meeting.
Citation Format: Subin Surendran, Christina Mimikos, Amritha Suresh, Wesley L. Hicks, Mukund Seshadri, Moni A. Kuriakose. Cancer stem cells in tobacco-induced carcinogenesis and subsequent effect of ATRA-based chemoprevention. [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 4074. doi:10.1158/1538-7445.AM2015-4074
Abstract 409: Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1α
Authors: Oh Eun-Taex , Song Min-Jeong , Lee Hyemi , Choi Yun-Jeong , Park Heon Joo 
Published: August 2015

Abstract
HIF-1α has been shown to regulate the expression of more than 70 genes involved in angiogenesis, tumor growth, metastasis, chemoresistance and radioresistance. There has been a growing interest in using HIF-1α inhibitors as anticancer drugs. Recently, docetaxel, which has been approved by the FDA for treatment of various cancers, has been reported to enhance the degradation of HIF-1α, but its molecular mechanism is unclear. In this study, we investigated the molecular mechanism underlying the docetaxel-induced degradation of HIF-1α and cell death in cancer cell under hypoxia. Pretreatment of docetaxel increased the polyubiquitination and proteasome mediated-degradation of HIF-1α and cell death in cancer cells under hypoxia. Under hypoxia, pharmacological inhibitors or siRNAs for PHD1 (prolyl hydroxylase 1) effectively prevented HIF-1α degradation and cancer cell death through inhibiting docetaxel-mediated activation of PHD1. In addition, siRNA-mediated knockdown of JNK2 blocked docetaxel-induced degradation of HIF-1α and cancer cell death through inhibiting the activation of PHD1. Through a luciferase reporter assay, we observed that the inhibition of the JNK2/PHD1 signaling pathway significantly suppressed the transcriptional activity of HIF-1α. Our results collectively show that, under hypoxia, docetaxel contributes to cause apoptotic cell death under hypoxia by triggering the JNK2/PHD1 signaling pathway, thereby increasing the degradation of HIF-1α.
Citation Format: Eun-Taex Oh, Min-Jeong Song, Hyemi Lee, Yun-Jeong Choi, Heon Joo Park. Docetaxel induced-JNK2/PHD1 signaling pathway increases cell death in cancer cells under hypoxia through the degradation of HIF-1α. [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 409. doi:10.1158/1538-7445.AM2015-409
Abstract 4104: LIX1L, an EMT-correlated gene that behaves as if it inhibits the EMT
Authors: Yamade Mihoko , Pommier Yves , Kohn Kurt W. 
Published: August 2015

Abstract
Background: We previously reported that LIX1L (LIX1-like), a gene whose functions are unknown, has an expression pattern exhibiting strong negative correlation with the expression of genes of epithelial-specific functions in the NCI-60 human cancer cell line panel of the US National Cancer Institute (Kohn et al PLoS ONE 9:6, 2014). This observation suggested a possible role in the epithelial-to-mesenchymal transition (EMT) and led to the current investigation. Method]: We examined the correlation of LIX1L with gene expression in the data of the Broad Institute's CCLE cell lines and the cancer genome atlas (TCGA) tissues. We then investigated the functions of LIX1L in breast and colon cancer cell lines. We knocked down LIX1L expression by means of siRNA and overexpressed LIX1L by means of recombinant LIX1L-GFP plasmid. We also generated LIX1L knockout cell lines (LIX1L-KO) using the CRISPR/Cas system. We compared the expression levels of LIX1L with well-known EMT-related genes by Western blot and quantitative PCR. We examined the migration and invasion properties of these cell lines and constructs by means of wound healing assays, and migration and invasion assays. Results: LIX1L expression is correlated with non-epithelial or mesenchymal genes in analyses of the CCLE and TCGA gene expression data. Experiments suggested the surprising result that LIX1L-KO MDA-MB231 cell lines showed higher expression of ZEB1 and increased invasion ability. Conclusion: LIX1L gene expression is positively correlated with the expression of non-epithelial or mesenchymal genes in the NCI-60, CCLE and TCGA databases. Up- or down-regulation of LIX1L however seemed to produce the opposite of the expected phenotypic changes. Our findings suggest that LIX1L may be expressed coordinately with genes that favor epithelial-to-mesenchymal transitions in cancer cells while having a moderating effect on the transition.
Citation Format: Mihoko Yamade, Yves Pommier, Kurt W. Kohn. LIX1L, an EMT-correlated gene that behaves as if it inhibits the EMT. [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 4104. doi:10.1158/1538-7445.AM2015-4104
Abstract 4105: Cathepsin L inhibition reverts epithelial mesenchymal transition in prostate and breast cancer cells
Authors: Burton Liza J. , Smith Bethany , Platt Manu , Marah Valerie 
Published: August 2015

Abstract
The Epithelial Mesenchymal Transition (EMT) is a key event in tumor migration and invasion processes whereby epithelial cells lose polarity together with cell-cell contacts associated with loss of epithelial markers such as E-cadherin and then undergo a dramatic remodeling of the cytoskeleton associated with expression of mesenchymal markers such as vimentin, as well as increased production of extracellular matrix (ECM)-degrading proteases. Snail is a gene that promotes epithelial mesenchymal transition (EMT) by using its zinc finger domains to bind to target genes that would otherwise stop EMT. Cathepsin L (Cat L) is a cysteine protease involved in cell invasion and has recently been associated with poor prognosis in Colon and Breast Cancer with Cat L being localized in the nucleus. We have shown previously that Snail-mediated EMT can be antagonized by muscadine grape skin extract (MSKE), a natural product rich in anthocyanin. In preliminary data we found that Snail, an inducer of EMT, could up-regulate Cat L activity and expression in breast cancer cells. We hypothesized that antagonizing Cat L activity would lead to mesenchymal epithelial transition (MET). We utilized breast and prostate EMT models to analyze Cat L activity using gelatin zymography and subsequently treated mesenchymal cells with 1μM, 5μM or 20μM Z-FY-CHO (Cat L specific inhibitor) or MSKE for 72 hours. We performed western blot analysis and immunofluorescence for EMT markers as well as invasion and migration assays. Our data indicates that mesenchymal MDA-MB-231 breast cancer cells showed higher Cat L expression and activity as compared to epithelial MCF-7 breast cancer cells. Interestingly, immunofluorescence analysis revealed cells displaying a higher snail expression have an increase in Cathepsin L activity and expression as well as Cat L being localized in the cytoplasm and nucleus. Additionally, mesenchymal breast (MDA-MB-231, MCF-7 cells overexpressing Snail) and prostate (ARCaP-M, ARCaP-E cells overexpressing Snail) cells displayed decreased expression of vimentin and Cat L expression and activity when treated with Z-FY-CHO or MSKE, while E-cadherin increased suggestive of MET. This was associated with decreased cell migration and invasion. We also show for the first time that treatment with MSKE or Z-FY-CHO changes the localization of Cat L from nuclear to cytoplasmic. Based on these results, the inhibition of Cat L could play a role in reverting EMT and preventing tumor progression.
Citation Format: Liza J. Burton, Bethany Smith, Manu Platt, Valerie Marah. Cathepsin L inhibition reverts epithelial mesenchymal transition in prostate and 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 4105. doi:10.1158/1538-7445.AM2015-4105
Abstract 4107: CCR9/CCL25 mediates epithelial-mesenchymal transition in prostate cancer
Authors: Carriere Patrick P. , Mir Hina , Kapur Neeraj , Singh Rajesh , Sonpavde Guru , Lillard James W. , Singh Shailesh 
Published: August 2015

Abstract
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men, despite the treatment options offered in the clinics. Hence, it is important to further elucidate the molecular mechanisms of PCa progression in order to design more effective treatment strategies. PCa metastasis is a multi-step process that involves epithelial-mesenchymal transition (EMT), during which stationary epithelial cancer cells adopt a mesenchymal phenotype that better suits for survival and motility. We have previously shown that CCR9-expressing PCa cells migrate to and invade distal secondary sites under the influence of chemokine CCL25, its natural ligand. However, the precise molecular mechanisms facilitating EMT in PCa are still not fully understood. Here, we investigated the biological significance of CCR9/CCL25 signaling in inducing EMT in PCa. Modulation of several EMT markers was assessed by western blot and real time qPCR in metastatic PCa cell lines, with or without CCL25 activation. Our results show that following CCL25 stimulation, CCR9 signaling differentially modulates expression of the EMT markers E-cadherin and N-Cadherin in PCa cells, as compared to untreated controls. These findings suggest that the CCR9-CCL25 axis plays an important role in mediating EMT in PCa, thereby increasing the ability of PCa cells to metastasize.
Citation Format: Patrick P. Carriere, Hina Mir, Neeraj Kapur, Rajesh Singh, Guru Sonpavde, James W. Lillard, Shailesh Singh. CCR9/CCL25 mediates epithelial-mesenchymal transition in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4107. doi:10.1158/1538-7445.AM2015-4107