bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 462: The role of miR-24 as a race-related genetic factor in prostate cancer
Authors: Hashimoto Yutaka , Shiina Marisa , Kato Taku , Yamamura Soichiro , Tanaka Yuichiro , Majid Shahana , Saini Sharanjot , Shahryari Varahram , Kulkarni Priyanka , Dasgupta Pritha , Mitsui Yozo , Sumida Mitsuho , Deng Guoren , Tabatabai Laura , Kumar Deepak , Dahiya Rajvir 
Published: July 2017

Abstract
The incidence of prostate cancer (PCa) among African-Americans (AfA) is significantly higher than Caucasian-Americans (CaA) but the genetic basis for this disparity is not known. To address this problem, we analyzed miRNA expression in AfA (n=81) and CaA (n=51) PCa patients. Here, we found that miR-24 is differentially expressed in AfA and CaA PCa patients and attempt to clarify its role in AfA patients. Also, the public sequencing data of the miR-24 promoter confirmed that it was highly methylated and down-regulated in PCa patients. Utilizing a VAMCSF and NDRI patient cohorts, we discovered that miR-24 expression was linked to a racial difference between AfA/CaA PCa patients. Interestingly, miR-24 was restored after treatment of PCa cells with 5Aza-CdR in an AfA cell line (MDA-PCa-2b), while restoration of miR-24 was not observed in CaA cells, DU-145. Ectopic expression of miR-24 showed decreased growth and induced apoptosis, though the effect was less in the CaA cell line compared to the AfA cell line. Finally, we found unique changes in biological pathways and processes associated with miR-24 transfected AfA cells by quantitative PCR-based gene expression array. Evaluation of the altered pathways showed that AR, PDPK1, IGF1, and IGFBP5 were markedly decreased in the AfA derived cell line compared with CaA cells, and there was a reciprocal regulatory relationship of miR-24/target expression in prostate cancer patients. These results demonstrate that miR-24 may be a central regulator of key events that contribute to race-related tumorigenesis and has potential to be a therapeutic agent for PCa treatment.
Citation Format: Yutaka Hashimoto, Marisa Shiina, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Varahram Shahryari, Priyanka Kulkarni, Pritha Dasgupta, Yozo Mitsui, Mitsuho Sumida, Guoren Deng, Laura Tabatabai, Deepak Kumar, Rajvir Dahiya. The role of miR-24 as a race-related genetic factor in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 462. doi:10.1158/1538-7445.AM2017-462
Abstract 4621: Metabolic activation of macrophages by CpG stimulates anti-tumor activity and overcomes CD47-independent inhibition by tumor cells in pancreatic ductal adenocarcinoma
Authors: Liu Mingen , Beatty Gregory 
Published: July 2017

Abstract
Macrophages dominate the immune infiltrate present in pancreatic ductal adenocarcinoma (PDAC). Although tumor-infiltrating macrophages have the potential to mediate anti-tumor activity, they most commonly acquire an immunosuppressive role in cancer. We have found that CpG oligonucleotides - containing unmethylated cytosine-guanine motifs - potently induce macrophages to phagocytose PDAC cells and mediate anti-tumor effects. When delivered in vivo, in a fully immunocompetent murine model of PDAC, CpG increased the presence of macrophages within PDAC tumors and suppressed tumor outgrowth in a macrophage-dependent manner. Though CpG did not polarize macrophages toward classical anti-tumor (M1) or pro-tumor (M2) phenotypes, CpG treatment increased the basal rate of oxygen consumption in macrophages. Reversing this metabolic shift by inhibiting fatty acid oxidation abolished pro-phagocytic and anti-tumor effects by macrophages in vitro and in vivo. We investigated the impact of CpG in overcoming anti-phagocytic signals from CD47, a membrane protein overexpressed in multiple malignancies, including PDAC. While targeted knockout of CD47 in PDAC cells was not sufficient to activate in vitro phagocytosis by macrophages or anti-tumor effects in vivo, delivery of CpG potentiated anti-tumor and phagocytic activity that was independent of CD47 expression by tumor cells. However, the combination of CD47 loss in tumor cells and systemic CpG treatment enhanced the survival of tumor-bearing mice, indicating that disruption of CD47 can sensitize tumors to macrophage-directed immunotherapy. Together, our findings demonstrate a key role for cellular metabolism in directing the anti-tumor functions of macrophages and overcoming negative regulatory signals imposed by malignant cells.
Citation Format: Mingen Liu, Gregory Beatty. Metabolic activation of macrophages by CpG stimulates anti-tumor activity and overcomes CD47-independent inhibition by tumor cells in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4621. doi:10.1158/1538-7445.AM2017-4621
Abstract 4631: Enhanced glycolysis promotes function of tumor associated macrophages in mouse breast cancer model
Authors: Liu Yan , Zhou Wei , Wang Wei , Bai Lipeng , He Huiwen , Guo Jian , Luo Yunping 
Published: July 2017

Abstract
Tumor associated macrophages(TAMs) represent a major part of immune cells in tumor microenvironment(TME) and play crucial roles in promoting tumor progression by secreting cytokines or enzymes that could remodel TME or enhance envision or migration capabilities of tumor cells. Given their indispensable effect on tumor, the mechanisms underlying TAMs’ tumor-promoting phenotype and function remain unclear. Glucose metabolism in tumor cells has been intensively studied; however, the status of glucose metabolism of TAMs is still unclear. In this study, we aim to identify glucose metabolism status in TAMs, and explore how glucose metabolism regulates phenotype and function of TAMs. In the begining, we isolated TAMs from 4T1 mouse breast tumor, spleen macrophages from normal mouse as a control, and performed RNA sequencing to analyze the expression pattern in glucose metabolism related genes. The results from transcriptomics showed that TAM shown up regulation of glycolysis genes pattern. Then we analyzed and found that HK’s activity was increased while IDH’s activity was decreased in mouse breast cancer moel. Furthermore, In vitro, we found that up regulation of impotent glycolysis genes including HK2, PFK-L and LDHA in mouse peritoneal macrophages (CMPM) and mouse bone marrow derived macrophages (CMBMDM) conditionally cultured with 4T1 supernatants. Glucose consumption or production of lactate and ATP were also increased in CMPM or CMBMDM. Then we monitored lactate producing rate with seahorse energy metabolism detector, and found that either CMPM or CMBMDM produced lactate faster than that of control. Moreover, inhibition of LDHA activity by oxamate ( inhibitor) also decreased glucose consumption and lactate production. Importantly, the expression of Arg1 and CD206, positively correlated with glycolysis and function of TAMs. Finally, we search the underneath mechanism and found PI3K/AKT pathway was activated in CMPM or CMBMDM. In detail it was found that p-p85 and p-AKT was upregulated at 8 hour after 4T1 supernatants stimulation. Inhibition of PI3K/AKT pathway by LY294002 (PI3K inhibitor), notably inhibited the expression of glycolysis genes and markers of TAMs, which indicated that PI3K/AKT pathway maybe involved in glycolysis of TAMs. Together, we identified that TAMs adopted glycolysis as a major way to consume glucose and glycolysis was directly contributed to the phenotype and function of TAMs, which was regulated by PI3K/AKT signaling pathway.
Citation Format: Yan Liu, Wei Zhou, Wei Wang, Lipeng Bai, Huiwen He, Jian Guo, Yunping Luo. Enhanced glycolysis promotes function of tumor associated macrophages in mouse breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4631. doi:10.1158/1538-7445.AM2017-4631
Abstract 4637: Activation of toll-like receptor-2 promotes proliferation in human lung adenocarcinoma cells
Authors: Kohtz Patrick 
Published: July 2017

Abstract
Objective: Toll-like receptors (TLR) have been implicated in tumor progression by affecting the immune response in the tumor microenvironment. Toll like receptors have been described to be present in human cancer cells but the presence and the role of these receptors in the growth and proliferation of human lung cancer cells is not known. We analyzed human lung cancer cells for the presence of TLR-2 receptors and evaluated the proliferation response to a specific TLR-2 agonist.
Methods: Human non-small cell cancer cell (NSCLC) lines A549, (adenocarcinoma) H125 adenosquamous, and H1650 adenocarcinoma (American Type Culture Collection), were cultured using standard techniques. Cells were treated with Pam3CSK4, a specific agonist of TLR2, at doses of 0ug/ml, 5ug/ml, and 10ug/ml for 72 hours. Baseline protein levels of TLR2 were assessed using standard western blotting techniques. Proliferation assays were completed using the MTS assay in response to treatment with the agonist
Results: Protein analysis demonstrated varying but consistently detectable levels of TLR2 protein in each cell line. After treatment with Pam3CSK4 we found that proliferation was significantly promoted in the human lung adenocarcinoma cell lines (p=.03), but not in the adenosquamous cell line (p=0.001).
Conclusion: Toll-like receptor -2 is consistently present and detectable on human lung adenocarcinoma cells. Toll Like receptor -2 activation results in increased proliferation in human lung adenocarcinoma cells and this effect appears to be specific to adenocarcinoma cells. Further study is necessary to elucidate the downstream pathways responsible for the increased proliferation we see in these human lung adenocarcinoma cells, however these findings may suggest TLR-2 to be a possible therapeutic target in human lung cancer.
Citation Format: Patrick Kohtz. Activation of toll-like receptor-2 promotes proliferation in human lung adenocarcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4637. doi:10.1158/1538-7445.AM2017-4637
Abstract 4641: Wild type APC is an independent marker of poor prognosis in late stage colorectal cancer
Authors: Siraj Abdul K. , Bu Rong , Beg Shaham , Masoodi Tariq , Al-Kuraya Khawla S. 
Published: July 2017

Abstract
Background: Colorectal cancer (CRC) is one of the commonest cancer worldwide and ranks as the most common cancer in males and the third most common among females in Saudi Arabia. Wnt pathway alteration is well known in colorectal cancer. In this study we aimed to comprehensively study Wnt pathway alterations in a large cohort of Middle Eastern colorectal patients and to know its role in this unique ethnic group.
Methods: 426 CRC cases were analyzed for APC, AXIN2 and CTNNB1 somatic mutations by targeted capture sequencing and protein expression status by immunohistochemistry in tissue microarray format. Results were analyzed for association with any clinicopathological parameters and for prognostic significance.
Results: The incidence of APC, AXIN2 and CTNNB1 mutations in our patient cohort were 58.2%, 4.2% and 3.8% respectively. APC mutation was associated with grade 2 tumors (p=0.0494) and male sex (p=0.0349). AXIN2 mutation were associated with grade 3 tumors (p=0.0231), MSI-high tumors (p&lt;0.0001) and AXIN2 protein expression loss (p=0.0056). CTNNB1 mutations were associated with MSI-high tumors (p=0.0076). AXIN2 and CTNNB1 mutation were significantly associated with each other (p=0.0263). Wild type APC was associated with poor overall survival and was an independent marker of poor prognosis in late stage CRC (p=0.0200).
Conclusion: We reported the incidence of Wnt pathway alterations in this unique ethnic group on which such data is lacking. APC mutation plays major and other genes minor role in Wnt pathway activation. Incidence of APC mutation in this group is comparatively high compared to reported incidence worldwide. Wild type APC independently predicts poor prognosis in Middle Eastern late stage colorectal patients.
Citation Format: Abdul K. Siraj, Rong Bu, Shaham Beg, Tariq Masoodi, Khawla S. Al-Kuraya. Wild type APC is an independent marker of poor prognosis in late stage colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4641. doi:10.1158/1538-7445.AM2017-4641
Abstract 465: Downregulation of miR-193a and its correlation with clinical and pathological behavior of colorectal cancer
Authors: Mamoori Afraa M. , Wahab Riajul , Islam Farhadul , Lee Katherine , Smith Robert A. , Gopalan Vinod , Lam Alfred Ky 
Published: July 2017

Abstract
Aim: Deregulation of miR-193a expression was reported to have significant roles in cancer development and progression. This study aimed to investigate the expression pattern and clinicopathological implication of miR-193a-3p in patients with colorectal cancer. Also, the bio-physiological effects of miR-193a in colon cancer cells were examined.
Methodology: Fresh frozen tissues from 70 matched colorectal cancers (adenocarcinomas) and adjacent noncancer tissue were prospectively collected with no selection bias. Expression level of miR193a-3p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical staining was used to detect the expression level of K-ras protein as a predicted downstream target for miR-193a. Restoration of the miR-193a level in the cell lines was achieved by permanent transfection. Multiple functional and immunological assays were performed to analyze miR-193’s cellular implications and target affinity in colon cancer cell lines.
Results: Downregulation of miR-193a-3p was noted in the majority of the colorectal cancer tissues when compared to nontumor colorectal tissues (70%, n= 49/70). In addition, high prevalence of miR-193a downregulation was noted in early stage colon cancer tissues and cell lines (SW480) when compared to advanced staged colorectal carcinomas. Immunohistochemical analysis revealed inverse correlation between miR-193a and K-ras expression in which high K-ras protein expression was reported in 28/49 cases with miR-193a downregulation. Analogues findings were also observed in cell lines using Western blot (P value&lt; 0.05). Overexpression of miR-193a in colon cancer cell lines resulted in reduced cell proliferation, increased apoptosis and a less accumulation of cells in the G0-G1 phase cell cycle.
Conclusion: The current study confirms the downregulation of miR-193a-3P in colorectal cancer and its tumour suppressor effects in vitro plays a key role in the modulation of K-ras regulated molecular signalling pathways in colon cancers
Note: This abstract was not presented at the meeting.
Citation Format: Afraa M. Mamoori, Riajul Wahab, Farhadul Islam, Katherine Lee, Robert A. Smith, Vinod Gopalan, Alfred Ky Lam. Downregulation of miR-193a and its correlation with clinical and pathological behavior of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 465. doi:10.1158/1538-7445.AM2017-465
Abstract 4659: Detection of autoantibodies against tumor-associated antigens (TAAs) improving immunodiagnosis in human osteosarcoma by serological proteome analysis
Authors: Li Jitian , Huang Manyu , Luo Manli , Dai Liping , Xie Wen , Qin Xiaofei , Han Zongchang , Li Wuyin , Zhang Jianying 
Published: July 2017

Abstract
Osteosarcoma (OS) is the most common malignant primary solid bone-tumor. Despite its relatively low incidence rate among overall cancers, it remains one of the most harmful primary malignant tumors in childhood and adolescence. Thus, a critical need in the diagnosis and management of OS is to determine an optimal combination of clinical biomarkers that could detect tumors early with high specificity/sensitivity and with limited invasiveness. The objective of this study is to identify and characterize the targeted tumor-associated antigens (TAAs) as biomarkers in OS by serological proteome analysis (SERPA) approach, and further to analyze the frequency and specificity of anti-TAA antibodies in OS patients. In this initial study, autoantibodies to 29 TAAs were detected by ELISA and Western blotting in 90 sera from patients with OS, Osteochondroma (OC), and age matched normal individuals. Only 8 protein antigens including DSF70, HMGB1, HCC1, RalA, c-myc, AnnexinA1, IMP1, PBP, can induce significantly higher antibody responses in OS patients compared to normal individuals, achieving the highest sensitivity and specificity, 66% and 95%, respectively. The cumulative positive rate of autoantibodies against these eight selected TAAs in OS reached 70.7% with an observed AUC of 0.972 (95% CI: 0.867-0.988), significantly higher than that in normal control sera. Positive results were also confirmed by Western blotting. These preliminary data extensively evidence that not all proteins identified in cancer can be used as TAA biomarkers in OS, and only some of these proteins can induce immune responses, which could be potential TAAs in OS immunodiagnosis or prognosis, and further studies of novel targeted proteins in OS are currently in progress by SERPA approach. In addition, it supports the hypothesis that a customized TAA array can be used for enhancing anti-TAA antibodies detection, and it may constitute a promising and powerful tool for immunodiagnosis of OS.
Citation Format: Jitian Li, Manyu Huang, Manli Luo, Liping Dai, Wen Xie, Xiaofei Qin, Zongchang Han, Wuyin Li, Jianying Zhang. Detection of autoantibodies against tumor-associated antigens (TAAs) improving immunodiagnosis in human osteosarcoma by serological proteome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4659. doi:10.1158/1538-7445.AM2017-4659
Abstract 466: Role of miR-15b-3p in mitoquinone induced autophagy of breast cancer cells
Authors: Mascia Francesca , Pokrzywinski Kaytee , Rao Ashutosh 
Published: July 2017

Abstract
Mitoquinone, a redox-active mitochondrially targeted ubiquinone, activates autophagy more potently in breast cancer cells (MDA-MB-231) than in normal breast cells (MCF-12A). Mitoquinone induces the production of reactive oxygen species (ROS) and a concomitant activation of the Nrf2-dependent antioxidant response. MicroRNA are endogenous small double stranded RNA that bind to the 3’ UTR of several target mRNAs and function through translational repression or mRNA degradation. The goal of this study was to evaluate microRNA as a link between oxidative stress and autophagy signaling. We performed RNA sequencing analysis of the microRNAs modulated by mitoquinone treatment of MDA-MB-231 cells. miRNAs were identified using Illumina RNA sequencing. DEseq analysis revealed 97 miRNAs that were differentially expressed at an α &lt; 0.05. Within this set, 15 miRNAs were down-regulated by stimulation with mitoquinone making them attractive as potential autophagy inhibitors. We characterized the role of a miR-15b-3p by transfecting the cells with miR-mimic and anti-miR before inducing an autophagy response. Western blot analysis showed a reduction in the expression of the autophagy marker LC3, the autophagosome chaperon p62 and the transcription factor Nrf2 in presence of the miR-15b-3p mimic. Conversely, miR-15b-3p mimic pre-treatment increased the expression of the cell cycle inhibitor p27 both at the basal level and after mitoquinone stimulation for 48 hrs. The administration of the anti-miR-15b-3p did not change the expression level of these proteins suggesting that miR-15b-3p may work with other miRs toward regulating autophagy. Combining the action of miR-15b-3p mimic with redox active chemotherapeutic drugs could represent a novel strategy for breast cancer therapy by reducing survival signaling through autophagy.
Citation Format: Francesca Mascia, Kaytee Pokrzywinski, Ashutosh Rao. Role of miR-15b-3p in mitoquinone induced autophagy of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 466. doi:10.1158/1538-7445.AM2017-466
Abstract 4673: EZH2 as a therapeutic target in glioblastoma: a cellular and molecular study
Authors: Rosa Javier de la , Iraburu Marta , Gallo-Oller Gabriel , Urdiciain Alejandro , Fan Xing , Shahi Mehdi H. , Meléndez Bárbara , Rey Juan A. , Idoate Miguel A. , Castresana Javier S. 
Published: July 2017

Abstract
Glioblastoma is the most common and deadliest malignant brain tumor in adults. It is currently treated with a combination of surgery, radiotherapy and chemotherapy with temozolomide (TMZ). Resistance to TMZ is a challenge in the treatment of this type of brain cancer. Epigenetic modulation is a new possibility to be tested against glioblastoma. Inhibition of EZH2, a histone methyltransferase (H3K27met3) which is overexpressed in cancer cells, leading to angiogenesis and metastasis, might be a new strategy to treat this tumor. In this work, the EZH2 inhibitor DZNeP was tested in A172 glioblastoma cells and in A172-TMZ-resistant glioblastoma cells. Inhibition of cell proliferation, cell adhesion, colony formation, and cell migration was noted in A172 and A172-TMZ-resistant glioblastoma cells after DZNeP treatment. DZNeP also decreased EZH2 expression, and increased the expression of its target genes (E-cadherin and TIMP3), which might probably contribute to inhibiting the development of a cancer metastatic phenotype. Finally, DZNeP negatively regulated the TGFβ pathway: the expression of receptors involved in this pathway (TGFβR1 and TGFβR2) was decreased, and the expression of inhibitors of this pathway (BAMBI, SMAD6 and SMAD7) was increased. In order to support the results obtained by qRT-PCR about the TGFβ1 pathway, protein expression of SMAD2 and PSMAD2 was analyzed by Western blot. The ratio between PSMAD2/SMAD2 decreased in cells treated with DZNeP, which supports the possible therapeutic effect of this drug against the TGFβ pathway, as PSMAD2 is a negative prognostic marker in glioblastoma. In conclusion, we propose that inhibition of EZH2 might be considered as a therapeutic strategy against glioblastoma.
Citation Format: Javier de la Rosa, Marta Iraburu, Gabriel Gallo-Oller, Alejandro Urdiciain, Xing Fan, Mehdi H. Shahi, Bárbara Meléndez, Juan A. Rey, Miguel A. Idoate, Javier S. Castresana. EZH2 as a therapeutic target in glioblastoma: a cellular and molecular study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4673. doi:10.1158/1538-7445.AM2017-4673