bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3109: A functional microRNA screening approach that identifies microRNAs affecting melanoma cell invasion
Authors: Weber Claudia E.M. , Luo Chonglin , Hotz-Wagenblatt Agnes , Osen Wolfram , Holland-Letz Tim , Eichmüller Stefan B. 
Published: August 2015

Abstract
Melanoma is a fast progressing tumor which tends to metastasize at small size and at early time point. miRNA profiling has been performed for a variety of cancer types, however, the results obtained differ substantially among published studies. Therefore, it is of major interest to unravel miRNA networks involved in melanoma progression as, for example, in tumor cell invasion. In order to follow this aim, we established a functional screening approach based on a high-throughput invasion assay using a human miRNA mimics library consisting of 988 miRNAs (miRBase Version 13.0). Applying this strategy, we could identify miRNAs that enhanced the invasive capacity of A375 melanoma cells (oncogenic miRNAs), as well as miRNAs with a lowering effect on invasiveness, latters found predominantly down-regulated in melanoma and thus considered as tumor-suppressors. miR-339-3p was one of the promising candidates which inhibited invasion when transfected into different melanoma cell lines. In addition, miR-339-3p expression was significantly decreased in melanoma cell lines compared to normal human melanocytes. Furthermore, the myeloid leukemia cell differentiation protein (MCL-1) was identified as a novel target of miR-339-3p and found to be down-regulated by miR-339-3p both on protein and on mRNA level. MCL1 down-regulation by siRNA could mimic inhibited invasion as observed after miR-339-3p transfection. Our findings indicate that miR-339-3p can act as a tumor suppressor in melanoma and its expression might contribute to the varying degrees of aggressiveness among different melanomas. We believe that our approach can unravel possible therapeutics checkpoints which might be used therapeutically, to counteract tumor spread.
Citation Format: Claudia E.M. Weber, Chonglin Luo, Agnes Hotz-Wagenblatt, Wolfram Osen, Tim Holland-Letz, Stefan B. Eichmüller. A functional microRNA screening approach that identifies microRNAs affecting melanoma cell invasion. [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 3109. doi:10.1158/1538-7445.AM2015-3109
Abstract 3115: miR-30a-5p functions as a tumor suppressor gene in gastric cancer
Authors: Min Jimin , Han Tae-su , Choi Boram , Hur Keun , Lee Hyuk-Joon , Yang Han-Kwang 
Published: August 2015

Abstract
Gastric cancer (GC) is the second leading cause of cancer-related death. MicroRNAs(miRNAs) are an abundant class of negative gene regulator and regulate multiple gene targets. miRNAs control a wide range of biological functions such as cellular proliferation, differentiation and apoptosis. Moreover, many miRNAs are highly conserved, and their deregulation is often associated with human malignancies. The aims of this study are to determine the miR-30a functions as a tumor suppressor gene and to evaluate whether the miR-30a-5p is able to use the diagnostic or prognostic marker in GC. To identify the gastric tumor-associated miRNAs, miRNA microarray was performed using the gastric cancer tissues. Among them, miR-30a-5p was down-regulated in GC tissues compared to normal mucosa. qRT-PCR was employed to confirm the microarray results. MiR-30a-5p expression was frequently down-regulated in our GC cohort, (n = 55, P&lt;0.0001). To determine the miR-30a-5p biological functions in GC, miR-30a-5p mimic or inhibitor was treated in GC cell lines. Ectopic expression of miR-30a-5p decreased cell growth, migration capacity and colony formation in vitro. Some previous studies have elucidated that miR-30a-5p is associated with metastasis in some cancer types. Accordingly, we confirmed its expression in our GC cohort with lymph node metastasis (n = 13) using qRT-PCR. MiR-30a-5p was significantly down-regulated in lymph node metastasis tissues than normal or tumor tissues. Taken together, the miR-30a-5p expression was frequently down-regulated in GC and lymph node metastasis. In addition, the miR-30a-5p suppressed tumorigenesis. Therefore, we suggest that miR-30a-5p activation may be a useful strategy of GC patient therapy and it can serve as a diagnostic or prognostic marker for GC.
Citation Format: Jimin Min, Tae-su Han, Boram Choi, Keun Hur, Hyuk-Joon Lee, Han-Kwang Yang. miR-30a-5p functions as a tumor suppressor gene in gastric 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 3115. doi:10.1158/1538-7445.AM2015-3115
Abstract 3123: miR-520b inhibits malignancy of head-neck cancer through suppression of cancer stemness by targeting to CD44 molecule
Authors: Lu Ya-Ching , Cheng Ann-Joy 
Published: August 2015

Abstract
MicroRNAs (miRNAs) have been implicated playing important role in regulating malignant progression of cancer. Here, we characterized the functional effects and regulatory mechanism of miR-520b in head-neck cancer (HNC). Without affecting cell growth, exogenous transduction of miR-520b into HNC cell lines significantly increased sensitivity to the therapeutic drug and radiation treatment, indicating that miR-520b possesses pro-apoptotic function. Transduction of miR-520b also decreased cell adhesion and mobile ability, accompanying with the reversion of epithelial- mesenchymal transition. Significantly, miR-520b suppressed the conversion of cancer stem cell (CSC) as demonstrated by reduced expressions of stemness markers (nestin and CD44), inhibiting sphenoid cell formation, and inhibiting pluripotent stemness regulators (Twist, Nanog and Oct4). Furthermore, CD44 was identified the direct target of miR-520b, which was shown by the response to miR-520b modulation via either exogenous or antigomir transduction. Functional analyses also confirmed this regulatory mechanism. The altered cell mobility and sphenoid forming ability by miR-520b modulation were rescued upon CD44 silencing. The miR-520b induced stemness regulators were also inhibited when simultaneously silencing CD44. Study in xenografted mice showed that miR-520b knockdown led to an acceleration of tumorigenesis. Reversely, miR-520b transduction dramatically restrained tumor growth, along with the inhibition of stem cell regulatory proteins. Taken together, our finding demonstrated that miR-520b inhibits malignancy of HNC through regulation of cancer stemness by targeting to CD44 molecule. Our finding provides molecular mechanism of miR-520b in HNC, which may also yield insights as novel targeting therapeutic strategy for HNC.
Citation Format: Ya-Ching Lu, Ann-Joy Cheng. miR-520b inhibits malignancy of head-neck cancer through suppression of cancer stemness by targeting to CD44 molecule. [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 3123. doi:10.1158/1538-7445.AM2015-3123
Abstract 3126: Survival in glioblastoma cancer patients is predicted by miR-340, that regulates key cancer hallmarks by inhibiting NRAS
Authors: Fiore Danilo , Quintavalle Cristina , Donnarumma Elvira , Roscigno Giuseppina , Iaboni Margherita , Russo Valentina , Adamo Assunta , De Martino Fabio , Greco Adelaide , Romano Giulia , Ylermi Soini , Brunetti Arturo , Croce Carlo Maria , Condorelli Gerolama 
Published: August 2015

Abstract
Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, patients survival remains poor. Nevertheless, a subset of patients survives longer than 3 years and they are classified as long-term survivors (LTS). The molecular and cellular mechanisms underlying the rare phenomenon of LTS are not well known. MicroRNAs (miRNAs or miRs) are a class of endogenous non-coding RNA of 19-24 nucleotides in length that have an important role in the negative regulation of gene expression. Deregulation of miRNAs is linked to the pathogenesis of many types of cancer. We performed a nanostring miRNA analysis on long and short glioblastoma survivors patients to individuate miRs potentially involved in LTS phenotype. Using this approach, we identified miR-340 as a novel tumor-suppressor-miR in glioblastoma. miR-340 expression was increased in LTS compared to short term survivors. Moreover, a log-rank test analysis on both the data collected from TCGA database and from a cohort of glioblastoma patients present in our lab revealed that low levels of miR-340 were a risk indicator for glioblastoma patients survival. miR-340 overexpression decreased cell proliferation, anchorage independent cell growth, cell cycle and response to temozolomide in different glioblastoma cell lines. We identified NRAS as a direct target of miR-340. Rescue experiments showed its essential role in mediating the onco-suppressive activity of miR-340. The overexpression of miR-340 decreased the activation of ERKs and AKT, the main pathways downstream NRAS. Furthermore, glioblastoma cells stably infected with a lentivirus encoding miR-340 exhibited a drastic reduction of tumor growth in nude mice. In conclusion, our findings reveal miR-340 as a new tumor-suppressor miRNA up-regulated in LTS in glioblastoma. Its expression inversely correlates with survival of glioblastoma patients. miR-340 is able to regulate multiple tumorigenic features of glioblastoma cells, offering a novel potential prognostic and therapeutical target for glioblastoma.
Citation Format: Danilo Fiore, Cristina Quintavalle, Elvira Donnarumma, Giuseppina Roscigno, Margherita Iaboni, Valentina Russo, Assunta Adamo, Fabio De Martino, Adelaide Greco, Giulia Romano, Soini Ylermi, Arturo Brunetti, Carlo Maria Croce, Gerolama Condorelli. Survival in glioblastoma cancer patients is predicted by miR-340, that regulates key cancer hallmarks by inhibiting NRAS. [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 3126. doi:10.1158/1538-7445.AM2015-3126
Abstract 3136: Adoptive transfer of bone marrow T cells induces antitumor immune responses in murine models of melanoma and neuroblastoma
Authors: Kodumudi Krithika N. , Weber Amy , Moore Ellen , Sarnaik Amod , Pilon-Thomas Shari 
Published: August 2015

Abstract
Bone marrow (BM) serves as a reservoir for a unique population of memory T cells. Tumor-specific T cells have been identified in the bone marrow of cancer patients. However, few direct functional analyses of tumor-specific responses in T cells isolated from BM have been performed. In this study, we investigated the ability of bone marrow T cells to induce anti-tumor immunity in mice bearing neuro2A neuroblastoma or B16 melanoma. To demonstrate the presence of antigen-specific T cells in BM, we first examined the percent of antigen-specific CD8+ T cells in vaccinated mice. The overall percent of antigen-specific CD8+ T cells was much higher in BM compared to spleen and lymph nodes of vaccinated mice. To investigate the ability of antigen-specific BM T cells to induce cytotoxic function, BM T cells were isolated from mice vaccinated with OVASIINFEKL peptide pulsed dendritic cells (DC). Expanded BM T cells from DC vaccinated mice co-cultured with M05 or irrelevant tumor cells led to tumor-specific cytotoxicity (p&lt;0.001). In B16 tumor-bearing mice, T cells isolated from BM produced IFN-gamma in response to gp100 peptide (1400+210 pg/ml). Adoptive transfer of BM T cells isolated from B16-bearing mice led to a delay in tumor growth compared to control groups (p&lt;0.001). In the neuroblastoma model, T cells isolated from BM of neuro2A-bearing mice produced higher levels of IFN-gamma and were tumor-specific (250+90 pg/ml, p&lt;0.01 compared to T cells cultured with irrelevant tumor cells). Adoptive transfer of expanded BM T cells and DC vaccination in the setting of BM transplant led to a significant delay in tumor growth and enhanced survival in neuro2A bearing mice compared to BM transplant + DC vaccination alone group (p&lt;0.02). These studies demonstrate that tumor-specific T cells can be isolated from the BM of tumor-bearing mice. Adoptive transfer of T cells expanded from the BM can delay tumor growth and improve survival. These studies support the isolation and expansion of T cells from the BM for use in adoptive cell therapy strategies in patients with neuroblastoma and melanoma.
Citation Format: Krithika N. Kodumudi, Amy Weber, Ellen Moore, Amod Sarnaik, Shari Pilon-Thomas. Adoptive transfer of bone marrow T cells induces antitumor immune responses in murine models of melanoma and neuroblastoma. [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 3136. doi:10.1158/1538-7445.AM2015-3136
Abstract 3170: IL17 favours carcinogenesis and limits the anti-tumor responses in pancreatic cancer
Authors: Cappello Paola , Curto Roberta , Mucciolo Gianluca , Rolla Simona , Tonoli Elisabetta , Novelli Francesco 
Published: August 2015

Abstract
Pancreatic ductal adenocarcinoma (PDA) is a fatal medical condition with few advances in therapy and patient survival. The role of IL17 and Th17 in cancer progression and anti-tumor immunity is still controversial. In this study we have investigated the role of IL17 and Th17 in PDA carcinogenesis and anti-tumor responses.
IL-17 production and Th17 percentage in blood from PDA patients and control subjects as well from genetically engineered mice (GEM) that spontaneously develop PDA, were analysed by ELISA and FACS respectively. Survival of GEM mice crossed with IL-17 KO mice (GEM/IL17KO) was analysed by Kaplan-Meier analysis. WT or IL17KO mice that were prophylactically vaccinated with a plasmid coding for the PDA-associated antigen α-enolase (ENO1) (1-3), were subsequently injected with PDA cell line derived from GEM. Tumor growth and the induction of an antigen-specific immune response were monitored.
We have found a statistically significant increase of peripheral Th17 cells and a decrease of Th1 in PDA patients compared to healthy subjects. GEM mice showed 3-fold more RORγT+ cells at the onset of duct transformation, which dropped to the level of control mice at 20 weeks and lasted until 35 weeks. Notably, GEM/IL17 KO mice survived significantly more than GEM mice, even if there were no changes in the tumor onset. In addition, in GEM/IL17 KO mice, we observed an increased fibrotic reaction compared to GEM mice starting from early stage of disease. Lastly, ENO-1 DNA vaccination in IL17KO mice significantly decreased PDA cells growth and enhanced the CD8 T cell response compared to that observed in WT mice.
Our data suggest that the absence of IL17 does not affect the tumor onset but the progression, likely affecting the immune response, which seems to be able to better counteract tumor growth in the absence of this cytokine.
Tomaino et al., J Proteome Res. 2007;6:4025-31; Cappello et al, Int. J. Cancer. 2009;125:639-48; Cappello P et al, Gastroenterology. 2013;144:1098-106.
Citation Format: Paola Cappello, Roberta Curto, Gianluca Mucciolo, Simona Rolla, Elisabetta Tonoli, Francesco Novelli. IL17 favours carcinogenesis and limits the anti-tumor responses in pancreatic 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 3170. doi:10.1158/1538-7445.AM2015-3170
Abstract 3171: IL-25/IL-17E does not induce breast tumor cell apoptosis and both IL-17A and IL-25/IL-17E contribute to breast cancer survival and proliferation associated with generation of pro-oncogenic low molecular forms of cyclin E
Authors: Giustiniani Jérôme , Curé Hervé , Garbar Christian , Merrouche Yacine , Bonnefoy Nathalie , Bastid Jérémy , Alberici Gilles , Eliaou Jean-François , Bensussan Armand 
Published: August 2015

Abstract
Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we focused our work on IL-17A and IL-17E which are found in the breast tumoral microenvironment. Cell proliferation and cytotoxic assays as well as Quantitative PCR and Western Blot analysis of oncogenic pathways were performed using several breast cancer cell lines and primary tumor cells. We report that IL-17A and IL-17E receptor subunits (IL17RA, RB and RC chains) are up-regulated in breast cancers versus normal samples. Moreover, IL-17E, which is undetectable in most normal breast tissues tested, is expressed at higher levels in tumors. We studied the molecular signaling following the stimulation of cell lines with IL-17A and IL-17E. We found that both cytokines induced cell proliferation and activation of pathways involved in cells survival. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel but failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorigenic low molecular weight forms of cyclin E (LMW-E), high levels of which correlate strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers.
Citation Format: Jérôme Giustiniani, Hervé Curé, Christian Garbar, Yacine Merrouche, Nathalie Bonnefoy, Jérémy Bastid, Gilles Alberici, Jean-François Eliaou, Armand Bensussan. IL-25/IL-17E does not induce breast tumor cell apoptosis and both IL-17A and IL-25/IL-17E contribute to breast cancer survival and proliferation associated with generation of pro-oncogenic low molecular forms of cyclin E. [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 3171. doi:10.1158/1538-7445.AM2015-3171
Abstract 3200: Acidic microenvironment activates endoplasmic reticulum stress pathways through GPR4 in human vascular endothelial cells
Authors: Dong Lixue , Krewson Elizabeth A. , Yang Li V. 
Published: August 2015

Abstract
The tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (“Warburg effect”), and defective vasculature that is inefficient to deliver oxygen and nutrients and to remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4, a member of the proton-sensing G protein-coupled receptors, has high expression in endothelial cells. We have previously reported that acidosis induces a broad inflammatory response in human vascular endothelial cells through the GPR4 receptor. Acidosis also increases the expression of several endoplasmic reticulum (ER) stress genes such as CHOP and ATF3. In the current study, we have thoroughly examined acidosis/GPR4-induced ER stress pathways in human umbilical vein endothelial cells (HUVEC). All three arms of the ER stress/unfolded protein response (UPR) pathways are activated by acidosis in HUVEC, as we observed an increased expression of phosphorylated eIF2α, phosphorylated IRE1α, and cleaved ATF6 upon acidic pH treatment. In addition, the expression of other downstream mediators of the UPR, such as ATF4, ATF3, CHOP and spliced XBP1, were also induced by acidosis at the mRNA and/or protein levels. Through genetic modifications and a small molecule inhibitor to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis stimulation. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in endothelial cells may regulate angiogenesis and inflammatory response in the acidic tumor microenvironment.
Citation Format: Lixue Dong, Elizabeth A. Krewson, Li V. Yang. Acidic microenvironment activates endoplasmic reticulum stress pathways through GPR4 in human vascular endothelial 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 3200. doi:10.1158/1538-7445.AM2015-3200
Abstract 3201: Complement component C3 and complement factor B regulate growth of cutaneous squamous cell carcinoma
Authors: Riihila Pilvi , Farshchian Mehdi , Kallajoki Markku , Kivisaari Atte , Meri Seppo , Grenman Reidar , Heljasvaara Ritva , Pihlajaniemi Taina , Peltonen Juha , Peltonen Sirkku , Kahari Veli-Matti 
Published: August 2015

Abstract
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and its incidence is increasing globally. We have examined the role of complement component C3 and complement factor B (CFB) in the progression of cSCC. Significantly elevated mRNA levels for C3 and CFB were detected din cSCC cell lines (n = 8) compared to normal human epidermal keratinocytes (n = 11) by quantitative real-time reverse transcriptase-PCR. Increased production of C3 and CFB by cSCC cell lines was detected by western blotting. The mRNA levels for C3 and CFB were also markedly higher in cSCC tumors (n = 6) than in normal skin (n = 10). Tumor cell specific staining for C3 and CFB was detected in cSCC tumors in vivo by immunohistochemistry and the staining intensity was stronger in invasive cSCCs (n = 71) than in cSCC in situ (n = 69), premalignant epidermal lesions (actinic keratoses, n = 65) and normal skin (n = 5). Significant upregulation of C3 and CFB mRNA expression was also noted in chemically induced mouse skin cSCCs (n = 27) compared to benign papillomas (n = 17). The expression of C3 and CFB at mRNA and protein level was markedly higher in invasive tumorigenic Ha-ras-transformed HaCaT cell line than in benign tumorigenic ras-transformed HaCaT cells and parental non-tumorigenic HaCaT cells. The expression of both C3 and CFB was significantly upregulated by IFN-γ and TNF-α in cSCC cells. Knockdown of CFB and C3 by specific siRNAs inhibited migration of cSCC cells. Knockdown of CFB inhibited proliferation of cSCC cells and this was associated with potent inhibition of ERK1/2 activation. Knockdown of C3 and CFB also significantly inhibited growth of human cSCC xenograft tumors in vivo in SCID mice. These results provide evidence for the role of C3 and CFB in progression of cSCC and identify them as specific biomarkers and putative therapeutic targets for invasive cSCC.
Citation Format: Pilvi Riihila, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grenman, Ritva Heljasvaara, Taina Pihlajaniemi, Juha Peltonen, Sirkku Peltonen, Veli-Matti Kahari. Complement component C3 and complement factor B regulate growth of cutaneous squamous cell carcinoma. [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 3201. doi:10.1158/1538-7445.AM2015-3201