bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3060: The role of miR-135b in clinical outcome and metastasis in colorectal cancer
Authors: Wang Wei-Ran , Cheng Yawen , Hsu Nan-Yung Hsu 
Published: August 2015

Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer death in both the Western world and Taiwan. Age, gender, and genes are important risk factors for colorectal cancer. Activation of Wnt signaling pathway is an important step involved in the pathogenesis of colorectal cancer. Approximately 70-80% of sporadic colorectal carcinomas have somatic mutations that inactivate APC. But, only 30% CRC patients in Taiwan have APC gene mutation that was significantly lower than the other countries. Thus, the other mechanism involved in APC gene inactivation may contributed to CRC progression in Taiwan. Here, we focus on the Wnt signaling associate microRNAs. Four wnt signaling-associated microRNAs were selected in this study, including miR-21, miR-200a, miR-135a and miR-135b. A total of 156 colorectal cancer patients were enrolled in this study. The expression of miR-21, miR-200a, miR-135a, miR-135b and wnt signaling association genes were analyzed by quantitative RT-PCR and immunohistochemistry. The expression levels of miR-21, miR-200a and miR-135a were not correlated with clinical parameters of CRC patients. The expression of miR-135b were positive correlated with gender, tumor stage, and lymph node metastasis. No any significantly correlation were found between miR-135b, Wnt, β-catenin and APC. But the expression levels of miR-135b were positive correlated with the upstream gene STAT3, β-catenin and C-Myc. Thus, we suggested that upregulation of miR-135b may through β-catenin mediated STAT3 activation.
Citation Format: Wei-Ran Wang, Yawen Cheng, Nan-Yung Hsu Hsu. The role of miR-135b in clinical outcome and metastasis in colorectal 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 3060. doi:10.1158/1538-7445.AM2015-3060
Abstract 3107: MicroRNA-1289 is a novel tumor suppressive microRNA in human oral squamous cell carcinoma
Authors: Iwamoto Kazuki , Nakashiro Koh-ichi , Tnaka Hiroshi , Tokuzen Norihiko , Hamakawa Hiroyuki 
Published: August 2015

Abstract
MicroRNAs (miRNAs) are small non-coding double-stranded RNA with sizes of approximately 22 nucleotides, and those inhibit protein translation by binding the 3′-untranslated region of target mRNAs. Each miRNA generally can regulate multiple mRNAs and each mRNA can be inhibited by a number of miRNAs. MiRNAs can behave as not only oncogenes but also tumor suppressive (TS) genes in human malignancies. In fact, a number of TS miRNAs (TS-miRs) were found in human many types of cancer, such as let-7, miR-1, miR-34, miR-145, miR-200, miR-206 and more. In this study, we have attempted to identify a novel TS-miR in human oral squamous cell carcinoma (OSCC) using function-based screening. First, we transfected human OSCC cells (GFP-SAS) with approximately 1,000 synthetic mimicking human mature miRNAs at the concentration of 20 nM complexed with Lipofectamine RNAiMAX. After transfection for 72 hours, the growth of these cells was evaluated by WST-8 assay. As a result, miR-1289 had the most potent growth inhibitory effect against GFP-SAS cells. The growth rate of these cells transfected with miR-1289 was reduced by 86.4%. MiR-1289 also remarkably inhibited the growth of other human OSCC cells (Ca9-22, HSC2, HSC3 and primary cultured cells). Subsequently, we assessed the growth inhibitory effect of miR-1289 in vivo using a mouse model. GFP-SAS cells (2 × 106) complexed with matrigel in 100 μl aliquots were injected subcutaneously in nude mice. After tumor formation, we administered 100 ng of miRNA with 0.5% atelocollagen complexes (100 μl) around tumor every 3 days for a total of 5 injections. MiR-1289/atelocollagen complex administration group significantly reduced the size of subcutaneously xenografted GFP-SAS tumors compared with the control group. Next, we investigated the expression of miR-1289 in OSCC tissues by real-time quantitative RT-PCR. The expression levels of miR-1289 were significant decreased in OSCC tissues compared to adjacent normal oral mucosa tissues. Finally, target genes of miR-1289 were explored by microarray and Ingenuity Pathway Analysis (IPA). Microarray analysis revealed that the expression levels of 51 genes were commonly down-regulated in OSCC cells (GFP-SAS, Ca9-22 and HSC2) by transfection with miR-1289. Among these genes, 15 genes were identified as target genes of miR-1289 by IPA. These results suggest that miR-1289 functions as a novel TS-miR in OSCC, and may be a useful therapeutic tool for the patients with OSCC.
Citation Format: Kazuki Iwamoto, Koh-ichi Nakashiro, Hiroshi Tnaka, Norihiko Tokuzen, Hiroyuki Hamakawa. MicroRNA-1289 is a novel tumor suppressive microRNA in human oral 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 3107. doi:10.1158/1538-7445.AM2015-3107
Abstract 3127: Small but lethal, miR-137 acts as a tumor suppressive microRNA in colorectal cancer
Authors: Smith Amber Rae , Marquez Rebecca , Tsao Bryan , Roy Alexandria , Wilkerson Bailey , Pathak Surajit , Neufeld Kristi , Sun Xiao-Feng , Xu Liang 
Published: August 2015

Abstract
Colorectal cancer is the 3rd most common cause of cancer-related deaths for men and women in the United States. Understanding the mechanisms associated with the initiation and progression of colorectal cancer is needed to develop precise therapies. Multiple regulatory processes are responsible for maintaining cellular homeostasis, including microRNA (miRNA) regulation. We previously demonstrated that miR-137 expression was significantly decreased in 84% of tumors as compared to adjacent mucosal tissue from patients with rectal cancer (n = 68). Restoration of miR-137 reduced colon cancer growth, measured by colony formation and tumorsphere assays. Induction of miR-137 expression significantly decreased tumor growth in our xenograft tumor model by approximately 50% (n = 10). To understand the mechanism associated with the tumor suppressive function of miR-137, we transfected miR-137 mimic into HCT-116 cells and performed microarray analysis to identify changes in gene expression and identify key regulatory pathways effected by miR-137 restoration. Multiple miR-137 targets were down regulated, as compared to cells treated with a negative control mimic. The data was validated using quantitative real-time PCR (qPCR). Finally, the expression of miR-137 target genes was analyzed in a panel of colon cancer cell lines using qPCR. In summary, miR-137 acts as a tumor suppressive microRNA by negatively regulating multiple targets that are overexpressed in colorectal cancer.
Citation Format: Amber Rae Smith, Rebecca Marquez, Bryan Tsao, Alexandria Roy, Bailey Wilkerson, Surajit Pathak, Kristi Neufeld, Xiao-Feng Sun, Liang Xu. Small but lethal, miR-137 acts as a tumor suppressive microRNA in colorectal 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 3127. doi:10.1158/1538-7445.AM2015-3127
Abstract 3146: T cell therapy targeting a neoantigen reduces in vivo tumour growth
Authors: Inderberg-Suso Else M. , Wälchli Sebastien , Myhre Marit R. , Wang Mengyu , Almåsbak Hilde , Kvalheim Gunnar , Gaudernack Gustav 
Published: August 2015

Abstract
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to avoid on-target, off-site toxicity. A safer alternative to targeting tumour-associated self-antigens may be to direct engineered T cells against mutated proteins such as frequently occurring frameshift mutations. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance. The transforming growth factor β Receptor II frameshift mutation (TGFβRIImut) is found in Lynch syndrome cancer patients and in around 15% of sporadic colorectal and gastric cancers displaying microsatellite instability.
The -1A mutation within a stretch of 10 adenine bases (nucleotides 709-718) of the TGFβRII gene gives rise to immunogenic peptides previously used for vaccination of MSI+ colorectal cancer patients in a Phase I clinical trial. From a clinically responding patient we isolated a CD8neg/CD4neg CTL clone from which we cloned an HLA-A2-restricted TGFβRIImut-specific TCR. We showed that both CD8+ and CD4+ T cells transiently redirected with this TGFβRIImut-TCR recognised colon carcinoma cell lines harbouring the frameshift mutation, indicating CD8+ co-receptor independency.
Cysteine modification of the TCR enhanced its expression and function and we have demonstrated that these TCR-redirected T cells significantly enhanced survival and reduced tumour growth in a NOD/SCID xenograft mouse model of colorectal cancer.
Citation Format: Else M. Inderberg-Suso, Sebastien Wälchli, Marit R. Myhre, Mengyu Wang, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack. T cell therapy targeting a neoantigen reduces in vivo tumour growth. [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 3146. doi:10.1158/1538-7445.AM2015-3146
Abstract 3151: T cells engineered to express a chimeric antigen receptor targeting chondroitin sulfate proteoglycan 4 (CSPG4) specifically kill medulloblastoma and produce inflammatory cytokines
Authors: Rota Christopher M. , Tschernia Nicholas , Feldman Steven , Mackall Crystal , Lee Daniel W. 
Published: August 2015

Abstract
Human T-cells expressing chimeric antigen receptors (CARs) recognizing common cancer antigens have shown great promise in the clinic with the potential for significant anti-tumor responses. CSPG4 is a chondroitin sulfate proteoglycan previously shown to be overexpressed in melanoma and breast cancer, as well as glioblastoma stem cells. CARs directed against CSPG4 have recently shown promising pre-clinical efficacy against these tumors. We evaluated the feasibility of targeting CSPG4 using CAR T cell therapy in medulloblastoma and neuroblastoma. Response to standard therapies for advanced neuroblastoma and medulloblastoma is poor and carries significant toxicities, which may be ameliorated by immunotherapy. We found that multiple medulloblastoma and neuroblastoma cell lines (DAOY, D283 Med, D425 Med, UW-228, and SKNAS) express CSPG4 at high levels, as does 143b osteosarcoma as a positive control. By contrast, CSPG4 in normal tissue is expressed only on pericytes and in low levels on small bowel as previously assessed by protein array [Beard et al, J Immunother Cancer 2014]. To evaluate therapeutic efficacy, a second generation CAR with a CD3ζ signaling domain and CD28 co-stimulatory domain containing the TP41.2 anti-CSPG4 scFv was transduced using a γ-retrovirus into T cells. CAR T cells were found to specifically kill 20% of DAOY, 50% of D283 Med, and 50% of 143b cancer cells at a 20:1 effector-to-target ratio in a 4-hour chromium release cytotoxicity assay, while not affecting CSPG4 negative control SY5Y (neuroblastoma) and DND41 (T cell leukemia) cells. Both CD4 and CD8 CAR T cells were also shown to produce IFNγ after exposure to 143b cells. Cytokine production in response to other CSPG4+ lines is ongoing as are cytotoxicity studies with neuroblastomas. For our in vivo model, we have begun to evaluate the efficacy of CAR T cells delivered either intravenously or via intratumoral injection against DAOY and D283 Med cells that have been orthotopically implanted in the cerebellum of immunodeficient NOD/SCID/IL2Rγ-/- mice. These results, if successful, will inform the development of a new clinical protocol for the treatment of children and young adults with medulloblastoma and neuroblastoma.
Citation Format: Christopher M. Rota, Nicholas Tschernia, Steven Feldman, Crystal Mackall, Daniel W. Lee. T cells engineered to express a chimeric antigen receptor targeting chondroitin sulfate proteoglycan 4 (CSPG4) specifically kill medulloblastoma and produce inflammatory cytokines. [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 3151. doi:10.1158/1538-7445.AM2015-3151
Abstract 3169: Influence of systemic and local immune response on overall survival after hepatic resection of colorectal liver metastasis
Authors: Hamada Takeomi , Hidenobu Ishizaki , Haruyama Yukihiro , Hamada Rouko , Yano Koichi , Otani Kazuhiro , Fujii Yoshiro , Kondo Kazuhiro , Kataoka Hiroaki 
Published: August 2015

Abstract
Background: Colorectal cancer progression is dependent on complex interactions between the tumor and the host. Tumor infiltrating lymphocytes (TIL) have been reported as a prognostic factor in colorectal cancer. The aim of this study was to assess the prognostic value of pre-operative systemic immune biomarkers and TIL in patients with resectable colorectal liver metastases (CLM).
Methods: Clinicopathological data were reviewed for patients (n = 31) underwent hepatic resections for CLM between 2000 and 2008. Prognostic variables are factors of the primary lesion, factors of the metastatic lesion, and factors of host inflammatory biomarkers measured from routine pre-operative blood tests (modified Glasgow Prognostic Score and neutrophil to lymphocyte ratio (NLR)). Univariate and multivariate analyses for prognostic factors were performed. To evaluate the local immune responses for resected metastatic lesion, immunohistochemical analysis was performed. The immune subsets were CD8+ T cells, CD45RO+ T cells, Fork head box p3+ (FOXP3+) T cells, and CD66b+ neutrophils.
Results: The number of metastases ≥ 4, extrahepatic metastasis, adjuvant chemotherapy, and raised NLR &gt; 4.1 were correlated with cancer-specific survival in univariate analysis. On multivariate analysis, the number of metastases ≥ 4, adjuvant chemotherapy, and elevated NLR remained independent prognostic indicators (metastases ≥ 4: HR = 0.09, CI = 0.01-0.56, p = 0.0102, adjuvant chemotherapy: HR = 0.08, CI = 0.01-0.39, p = 0.0025, NLR: HR = 0.11, CI = 0.01-0.99, p = 0.0494). Accumulation of CD45RO+ T cells and FOXP3+ T cells in the metasatic tumors were significantly associated with favorable survival in patients with resectable CLM (P = 0.02 and 0.04, respectively).
Conclusions: The results of the present study show that the NLR has prognostic value in patients who conduct a hepatic resection for CLM. Moreover, accumulation of CD45RO+ T cells and FOXP3+ T cells in metastatic lesions are independent favorable prognostic factor. Based on the present results and previously literature, systemic immune response including NLR and local immune response may be promising as prognostic factor of patients with resectable CLM.
Citation Format: Takeomi Hamada, Ishizaki Hidenobu, Yukihiro Haruyama, Rouko Hamada, Koichi Yano, Kazuhiro Otani, Yoshiro Fujii, Kazuhiro Kondo, Hiroaki Kataoka. Influence of systemic and local immune response on overall survival after hepatic resection of colorectal liver 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 3169. doi:10.1158/1538-7445.AM2015-3169
Abstract 3198: The impact of aerobic exercise on oxygenation and vascularity in breast cancer models
Authors: Wiggins Jennifer M. , Lee Jennifer A. , Rice Lori , Siemann Dietmar 
Published: August 2015

Abstract
Background: Intratumoral hypoxia (pO2 &lt;10mmHg) is associated with aggressive tumor progression and poor patient outcome. It is often found in solid tumors, and can constitute a major obstacle to anticancer therapy. The primary cause of abnormal oxygen tensions in tumors is the aberrant tumor vasculature, characterized by tortuous, leaky and immature vessels. A number of intervention strategies designed to overcome tumor hypoxia have been investigated including high oxygen content breathing and the use of bioreductive prodrugs, but these have had only moderate success in the clinic.
Purpose: The goal of the present investigations was to determine whether aerobic exercise could be applied as a means to improve tumor physiology and decrease tumor hypoxia in breast cancer models.
Methods: The effects of single and repeated bouts of moderate intensity exercise (treadmill running) were studied in mice bearing syngeneic murine mammary carcinoma models (EMT6 and 4T1). The exercise intensities were determined by measuring the anaerobic threshold, which is reflected by the steady rise in blood lactate during an exercise bout. Mice were orthotopically injected with tumor cells and once the tumors reached a size of 250 mm3, the mice were exposed to either a single bout of exercise or daily exercise bouts performed for 5 consecutive days. Controls for each treatment consisted of sedentary mice exposed to a stationary treadmill for the equivalent amount of time. Following cessation of each exercise regime tumors were harvested, sectioned and evaluated by immunofluorescence. Vessel density (MECA-32), blood perfusion (Hoechst-33342) and hypoxia (EF5) were quantified and significance was established at p&lt;0.05.
Results: Preliminary data indicate that even a single exercise bout may begin to demonstrate improvements in blood vessel perfusion and tumor oxygenation. Importantly, after 5 daily bouts of exercise, there was a significant increase in the number of patent vessels and improvement in oxygenation in the tumors of exercising mice compared to those of sedentary controls.
Conclusion: The results indicate that moderate aerobic exercise can improve the oxygenation status of solid tumors. These findings suggest that such a non-toxic intervention may have potential utility in overcoming hypoxia-associated treatment resistance in cancer patients and improve patient outcome.
Citation Format: Jennifer M. Wiggins, Jennifer A. Lee, Lori Rice, Dietmar Siemann. The impact of aerobic exercise on oxygenation and vascularity in breast cancer models. [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 3198. doi:10.1158/1538-7445.AM2015-3198
Abstract 3214: Genome-wide analysis of stroma-tumor crosstalk pathways in lung cancer: therapeutic implications
Authors: Choi Hyejin , Shen Jianting , Durrans Anna , El Rayes Tina , Fischer Kari , Gao Dingcheng , Wong Steve , Altorki Nasser , Mittal Vivek 
Published: August 2015

Abstract
We have systematically dissected the microenvironmental hetereogeneity of lung adenocarcinomas, and provide cellular and molecular landscapes that contribute to carcinogenesis. RNA deep sequencing analysis of individually sorted stromal and tumor epithelial compartments from fresh clinical specimens and a mouse model of KrasG12D; p53-/- tumors identified cell type-specific differentially regulated genes, indicative of tumor “activated/reprogrammed” stroma. We developed a computational crosstalk discovery algorithm to model crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks, and identified novel tumor-stroma paracrine and tumor autocrine crosstalk signaling pathways in the lung cancer microenvironment. We have explored the mechanistic basis of selected crosstalk pathways including HGF-MET, IL6-Stat3, Tsp-1-CD36, MMP14-HB-EGF in conferring lung adenocarcinoma progression and in mediating therapeutic resistance, and have used both genetic and pharmacological approaches to block these pathways. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions, and may complement conventional anti-cancer treatments.
Citation Format: Hyejin Choi, Jianting Shen, Anna Durrans, Tina El Rayes, Kari Fischer, Dingcheng Gao, Steve Wong, Nasser Altorki, Vivek Mittal. Genome-wide analysis of stroma-tumor crosstalk pathways in lung cancer: therapeutic implications. [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 3214. doi:10.1158/1538-7445.AM2015-3214
Abstract 3230: Human stem cell-based model of MYCN-driven neuroblastoma
Authors: Huang Miller , McHenry Lauren K. , Miller Matthew L. , Kim Grace E. , Moriarity Branden S. , Miyaoka Yuichiro , Bronner Marianne E. , Largaespada David A. , Conklin Bruce R. , Ji Hanlee P. , Maris John M. , Matthay Katherine K. , Weiss William A. 
Published: August 2015

Abstract
Neuroblastoma (NB), a disease of neural crest (NC) origin, is the most common extracranial solid tumor in childhood. High-risk NB patients represent the subgroup with the worst prognosis and frequently harbor amplification of MYCN. Due to its biochemical structure as a transcription factor, MYCN has been difficult to target directly with small molecules. Alternatively, identification of cooperating partners of MYCN-induced tumorigenesis can reveal a more therapeutically viable target, such as anaplastic lymphoma kinase (ALK). While genetically engineered mouse models (GEMMs) of NB driven by MYCN and ALK exist, recent studies have found significant differences between mouse models of disease and the human tumors they are intended to represent. In support of this, mouse and human NC cells differ in development and marker expression, and the genetic requirement for transformation of human cells has been shown to be more complex than mouse cells, suggesting that a human cell-based NB model would be more relevant. To develop a human cell-based model of NB, we started with a normal human induced pluripotent stem (iPS) cell line derived integration-free from a healthy adult and transduced empty vector, ALK F1174L (active mutant), doxycycline-inducible MYCN (DOX-MYCN), or ALK F1174L/DOX-MYCN. These iPS cells were differentiated towards NC cells and subsequently implanted orthotopically into renal capsules of mice fed on dox chow. Within 3 months, 60% of mice developed tumors with ALK F1174L/DOX-MYCN, 10% with DOX-MYCN, and 0% with both empty vector and ALK F1174L alone. Tumors were transplantable and demonstrated histologic characteristics consistent with NB, including morphology and expression markers. Thus, we are demonstrating the first, to our knowledge, human stem cell-based model of NB. We are using this system to further investigate similarities and differences with GEMMs of NB, test and establish novel candidate drivers of NB, and evaluate potential therapeutic options.
Citation Format: Miller Huang, Lauren K. McHenry, Matthew L. Miller, Grace E. Kim, Branden S. Moriarity, Yuichiro Miyaoka, Marianne E. Bronner, David A. Largaespada, Bruce R. Conklin, Hanlee P. Ji, John M. Maris, Katherine K. Matthay, William A. Weiss. Human stem cell-based model of MYCN-driven 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 3230. doi:10.1158/1538-7445.AM2015-3230