bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3616: Potential therapeutic use of Estrogen Receptor β agonist in the prevention and progression of breast cancer using HER-2/neu mouse model
Authors: Ramasamy Kumaraguruparan , Samayoa Cathy , Krishnegowda Naveen K. , Vadlamudi Ratna K. , Tekmal Rajeshwar R. 
Published: July 2017

Abstract
Breast cancer is the most common cancer among women worldwide. Hormone-mediated therapy to treat estrogen receptor alpha (ERα) positive breast cancers include the use of ER antagonist, Tamoxifen, aromatase inhibitors and other compounds that degrade ERα. Unlike ERα, ERβ has been shown to have tumor-suppressive function in various cancers, including breast cancer. Recent studies have identified, synthesized, and tested the clinical safety of ERβ-selective agonists. Given the tumor-suppressive properties of ERβ, it may be possible to use these compounds to induce or activate the ERβ and test their role in the chemoprevention and blocking the progression of breast cancer. We have investigated the therapeutic utility of ERβ agonists in the prevention and progression of breast cancer using MMTV-HER2/neu mice transgenic mouse model. MMTV-HER2/neu mice develop premalignant lesions at 4-5 months, and tumors starting at month 7 due to overexpression of the HER2/neu proto-oncogene. MMTV-HER2/neu mice were treated with an ERβ agonist, LY500307 examined the prevention and progression of mammary cancers in these mice. When compared to controls, ERβ agonist-treated mice exhibited a significant decrease in the development of preneoplastic changes. Differential gene expression analysis revealed a significant change in the expression of a number of genes in response to LY500307 treatment. Pathway analysis identified an enrichment for chemokines signaling pathways, particularly TNF, in blocking the development of preneoplastic changes resulting from treatment with ERβ agonists. Our studies also show a decrease in the formation of mammary tumors in HER-2/neu mice with preexisting preneoplastic changes when treated with LY500307. This study suggests that ERβ agonist treatment may be a valuable therapeutic option for the prevention in women at increased risk of breast cancer and in blocking the progression of hormone receptor positive breast tumors.
Citation Format: Kumaraguruparan Ramasamy, Cathy Samayoa, Naveen K. Krishnegowda, Ratna K. Vadlamudi, Rajeshwar R. Tekmal. Potential therapeutic use of Estrogen Receptor β agonist in the prevention and progression of breast cancer using HER-2/neu mouse 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 3616. doi:10.1158/1538-7445.AM2017-3616
Abstract 3671: Anti-PD-1 treatment may potentiate the radiation-induced lung injury
Authors: Xue Jianxin , Du Shisuo , Lu You , Dicker Adam , Lu Bo 
Published: July 2017

Abstract
Purpose: Combination of radiation therapy and anti-PD1 immunotherapy has been investigated both in the lab and in the clinic. Pneumonitis is a rare but potentially fatal toxicity of ant-programmed death-1 (PD-1) monoclonal antibodies (mAbs). The purpose of our study is to address whether anti-PD-1 mAbs will potentiate radiation-induced lung toxicity and mortality in a murine model using Small Animal Radiation Research Platform (SARRP) for lung-targeting irradiation (IR).
Methods: Both lungs of male C57bl/6 mice were targeted for 20Gy using the SARRP. Mice were stratified into 4 treatment groups receiving IgG, anti-PD1, IR + IgG, or IR + anti-PD1. IgG or anti-PD-1 mAbs administrated via i.p. injection, with a dosage of 10mg/kg, twice per week for five doses. Acute lung injury was assessed by H&E staining and flow cytometry to measure CD4 or CD8 positive T lymphocytes. A duplicate study (n=10) was performed to determine long-term survival following lung irradiation.
Results: 30 days following lung irradiation, lung tissues exhibited abnormal alveoli, with exudates and inflammatory cells in the alveolar septa (H&E staining). The extent of these changes was more prominent in IR+anti-PD-1 group. Moreover, there were significantly (2.1 fold increase; p&lt;0.05) more CD8+ cytotoxic T lymphocytes, rather than CD4+ cells lymphocytes, in the irradiated lung tissues in the group of IR+anti-PD1 compared to that of IR+IgG. Up to 120 days post IR, 90% mice survived in the group of IR+IgG while 70% mice survived in the IR+anti-PD-1 group (p=0.657).
Conclusions: Anti-PD-1 mAbs potentiates the radiation-induced pneumonitis, likely mediated by increased CD8+ cytotoxic T lymphocytes. Anti-PD-1 mAbs may increase the radiation-related mortality although it was not statistically significance at the day 120 following IR. Care should be taken for excessive lung toxicities in ongoing clinical trials of combining thoracic RT and anti-PD1 therapy. We will collaborate with NRG to further investigate clinical lung toxicities from combining thoracic radiotherapy with Nivo in the ongoing RTOG 3505 though analyzing the collected biospecimens.
Note: This abstract was not presented at the meeting.
Citation Format: Jianxin Xue, Shisuo Du, You Lu, Adam Dicker, Bo Lu. Anti-PD-1 treatment may potentiate the radiation-induced lung injury [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 3671. doi:10.1158/1538-7445.AM2017-3671
Abstract 3674: Local irradiation promotes antitumor immunity and abscopal effect of antigen-specific immunotherapy by enhancing dendritic cell maturation
Authors: Chang Ming-Cheng , Cheng Jason Chia-Hsien , Chiang Ying-Cheng 
Published: July 2017

Abstract
Background: Ionizing radiation therapy (RT) is a well-established method to eradicate locally advanced tumors. Whether or no local RT can enhance the potency of an antigen-specific DNA vaccine and the possible underlying mechanism were evaluated.
Materials and Methods: The number of E7-specific CD8+ cytotoxic T cell precursors and anti-E7 Abs from Tumor-bearing mice treated with local RT (6Gy twice per week) and the CTGF/E7 DNA vaccine were evaluated. Abscopal effects were also monitored. HMGB-1and DC maturation from local irradiation were analyzed by flow cytometry. The ratio of effector-to-suppressor cells in the tumor microenvironment was also investigated.
Results: Tumor-bearing mice treated with local RT (6Gy twice per week) and the CTGF/E7 DNA vaccine exhibited a dramatic increase in the number of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, a significant reduction of tumor size, and longer survival. The combination of local RT and the CTGF/E7 vaccine also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. Local irradiation can induce the expression of HMGB-1 in apoptotic tumor cells and stimulate DC maturation, which results in inducing antigen-specific immune responses. In addition, local irradiation, although inducing Treg cells, can eventually increase a higher ratio of effector-to-suppressor cells in the tumor microenvironment.
Conclusions: Local irradiation can enhance the antigen-specific immunity and antitumor effects on local and distant metastatic tumors generated by an antigen-specific DNA vaccine. Irradiation combined with antigen-specific immunotherapy is a potential new strategy for cancer therapy.
Citation Format: Ming-Cheng Chang, Jason Chia-Hsien Cheng, Ying-Cheng Chiang. Local irradiation promotes antitumor immunity and abscopal effect of antigen-specific immunotherapy by enhancing dendritic cell maturation [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 3674. doi:10.1158/1538-7445.AM2017-3674
Abstract 3703: A genomic characterization of testicular germ cell tumor immune microenvironment
Authors: Hollern Daniel P. , Hoadley Katie , Vincent Benjamin , Perou Charles M. , Group TCGA Testicular Germ Cell Tumor Analysis Working 
Published: July 2017

Abstract
Testicular germ cell tumors (TGCT) are a histologically diverse set of tumors and the most common cancer type in young men. As part of the TCGA effort, we analyzed tumors from 133 patients including 4 patients with asynchronous double primary TGCTs (137 primary tumors) by histopathologic, genomic, epigenomic, transcriptomic, and proteomic methods. We noted molecular signatures of various immune cells were greater in seminomas than other histologies. Specifically, we find seminomas show elevation of expression signatures for B-Cells, Cytotoxic T-Cells, Th17 Cells, and T-regulatory cells. This increase in immune cells were accompanied by high expression of specific cytokines and key immune checkpoint molecules such as CTLA4, LAG3, and PD-L1. Strong positive correlations were identified between immune cell signatures and increases in T-Cell and B-Cell receptor diversity measures. Interestingly, increases in receptor diversity also showed strong positive associations to gene expression signatures for anti-tumor immune responses. This indicates that anti-tumor immune responses in seminomas may be polyclonal. We found no evidence for relationships between immune cells and mutation load, neoantigen load, or detected viruses. We do observe that seminomas have significantly high expression of the testis specific antigens, yet the contribution of these antigens to the immune response did not show strong or uniform statistical indications. Instead, the strongest association between expanded immune cells populations in seminomas were the presence of activating mutations in KIT accompanied by elevation of gene expression of signatures associated with KIT and expression of MHC class I and II genes. Together, these data describe the immune microenvironment of seminomas and suggest alterations and events in the kit pathway as being critical to the nature of the immune microenvironment in seminomas.
Citation Format: Daniel P. Hollern, Katie Hoadley, Benjamin Vincent, Charles M. Perou, TCGA Testicular Germ Cell Tumor Analysis Working Group. A genomic characterization of testicular germ cell tumor immune microenvironment [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 3703. doi:10.1158/1538-7445.AM2017-3703
Abstract 3708: RAS-MAPK signal is required for enhanced PD-L1 expression in human lung cancers
Authors: Sumimoto Hidetoshi , Takano Atsushi , Teramoto Koji , Daigo Yataro 
Published: July 2017

Abstract
Ectopic programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancers (NSCLCs) is related to immune evasion by cancer, and it is a molecular target of immune checkpoint therapies. Since the precise mechanisms responsible for ectopic PD-L1 expression remains obscure, we analyzed the molecular mechanisms of ectopic PD-L1 expression in human lung cancers, focusing on the MAPK signal. Because we found a higher frequency of EGFR/KRAS mutations in NSCLC cell lines with high PD-L1 expression (p &lt; 0.001), we evaluated the relationships between downstream signals and PD-L1 expression, particularly in three KRAS-mutant adenocarcinoma cell lines. The MEK inhibitor U0126 (20 μM) significantly decreased the surface PD-L1 levels by 50-60% compared with dimethyl sulfoxide (p &lt; 0.0001). Phorbol 12-myristate 13-acetate stimulation (100 nM, 15 min) increased (p &lt; 0.05) and two ERK2 siRNAs as well as KRAS siRNAs decreased (p &lt; 0.05) PD-L1 expression. Post-transcriptional mechanism by miR-200s appears not to be in general under the downstream of MAPK in the PD-L1 expression. The transcriptional activity of the potential AP-1 site (+4785 to +5056 from the transcription start site) in the PD-L1 gene was demonstrated by luciferase assays, which was inhibited by U0126. The chromatin immunoprecipitation assay demonstrated the binding of cJUN to the AP-1 site. Two STAT3 siRNAs decreased PD-L1 expression by 10-32% in two of the three KRAS-mutant lung adenocarcinoma cell lines (p &lt; 0.05), while the PI3K inhibitor LY294002 (40 μM) did not change the expression level. Supervised cluster analysis and gene set enrichment analysis between the PD-L1-high and -low NSCLCs revealed a correlation between PD-L1 expression and genes/pathways related to cell motility/adhesion. These results indicate that MAPK signaling is the dominant downstream signal responsible for ectopic PD-L1 expression at a transcriptional level, in which STAT3 is also involved to some extent. Furthermore, MAPK signaling may control the expression of PD-L1 and several genes related to enhanced cell motility. Our findings suggest that MAPK is important for determining PD-L1 expression, which could be useful for targeted therapies against lung cancers.
Citation Format: Hidetoshi Sumimoto, Atsushi Takano, Koji Teramoto, Yataro Daigo. RAS-MAPK signal is required for enhanced PD-L1 expression in human lung cancers [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 3708. doi:10.1158/1538-7445.AM2017-3708
Abstract 371: Developing small molecule therapeutics to target AKT signaling in non-small cell lung cancer
Authors: Chandrasekaran Balaji , Pal Deeksha , Kolluru Venkatesh , Ramisetti Srinivasa R. , Sharma Arun K. , Ankem Murali , Damodaran Chendil 
Published: July 2017

Abstract
Lung cancer remains a leading public health problem which is evidenced by its increasing death rate. Platinum-based chemotherapy is the first-line of treatment for patients in advanced stages of non-small cell lung cancer (NSCLC), however the success rates are not quite impressive. Hence, developing individualized treatment strategies for metastatic lung cancer gains momentum, such as Tyrosine kinase inhibitors erlotinib and gefitinib, or ALK inhibitors ceritinib and alectinib are commonly used in the clinic. Recent reports suggest that pAKT(ser473) is highly expressed in NSCLC and higher nuclear expression of pAKT correlated with poor prognosis and an independent prognostic marker for survival. Our lab is interested to develop novel small molecules which specifically inhibit AKT signaling in NSCLC. Structure-activity relationship (SAR) studies in our laboratory have recently ideintifed one such compound, AKS-407, that effectively inhibited cell growth at nanomolar concentration in NSCLC cell lines (A549 and H460; 250nM). Molecular studies revealed AKS-407 inhibited AKT signaling by down regulating pAKT(ser473) expression and downstream events including NFκB activation, BCl-2 expression in both the cell lines. As signaling through AKT regulates epithelial-mesenchymal transition (EMT) in NSCLC, we determined the effect of AKS-407 on EMT phenotype on NSCLC cells. Treatment of AKS-407 inhibited the mesenchymal markers includes snail, MMP9, N-cadherin, β-catenin and vimentin expression that resulted in blocking invasion and migration of A549 and H-460 cells. These results suggest AKS-407 to be a promising small molecule targeting AKT signaling pathway which remains an important target for the development of effective treatment of metastatic NSCLC. Validating in-vivo efficacy of this potential drug candidate would further support our overall goal of the study.
Citation Format: Balaji Chandrasekaran, Deeksha Pal, Venkatesh Kolluru, Srinivasa R. Ramisetti, Arun K. Sharma, Murali Ankem, Chendil Damodaran. Developing small molecule therapeutics to target AKT signaling in non-small cell lung 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 371. doi:10.1158/1538-7445.AM2017-371
Abstract 3742: Exposure burden for patients during an experimental study using a dual-energy contrast-enhanced spectral mammography
Authors: Rawojc Kamila , Kisielewicz Kamil , Dziecichowicz Anna , Tomaszuk Monika , Cepiga Anna , Anna Jankowska , Izabela Cieśla , Dominika Najberg , Elzbieta Luczynska , Kieltyka Bartosz 
Published: July 2017

Abstract
Mammography provides early micro-calcification recognition, that is important for further breast cancer (BC) diagnosis. Imaging choice for BC detection is X-ray mammography (MG) with the use of high-resolution digital modality combined with iodinated contrast agents. However, a conventional MG has some sensitivity limitations, especially in patients with densely treated breasts. Moreover, MG contributes radiation risk for BC that is correlated with an exposure to ionizing radiation. Patients, for whom MG study does not give a clear interpretation are often further diagnosed by contrast-enhanced breast MRI, the most sensitive BC detection technique. Alternatively, it is limited by higher costs, lower availability and increased false positives. Dual-energy contrast-enhanced spectral mammography (CESM) is a new method applied in BC that enables accurate detection of malignant breast lesions similar to breast MRI. The aim of this study was to compare the usefulness of CESM versus MG in BC detection. Additionally, doses given to the BC patients during imaging were compared. In this study, 250 consecutive women (144 MG vs. 105 CESM), that were screened using mammography between 2011 and 2014 were retrospectively enrolled in the study. The comparison of entrance surface air kerma and mean glandular dose values for both options were recorded, respectively and analyzed using different statistical and retrospective approach. Results of presented study showed that CESM might be a new diagnostic tool allowing an accurate detection of BC lesions, giving results similar to those received from magnetic resonance imaging. A good agreement found between sensitivity of the method and tumour diameters measurements based on CESM, supports this tool as a potential replacement for breast MRI in the preoperative evaluation of BC patients. However, a radiation burden for patients might be significantly higher than that for a standard full-field digital mammography procedure. In summary, each method has its own benefits with respect to specific applications that are further discussed in the study.
Citation Format: Kamila Rawojc, Kamil Kisielewicz, Anna Dziecichowicz, Monika Tomaszuk, Anna Cepiga, Jankowska Anna, Cieśla Izabela, Najberg Dominika, Luczynska Elzbieta, Bartosz Kieltyka. Exposure burden for patients during an experimental study using a dual-energy contrast-enhanced spectral mammography [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 3742. doi:10.1158/1538-7445.AM2017-3742
Abstract 3761: Specific and dynamic tumor antigen-specific immune responses were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy
Authors: Han Yanyan , Wu Ye , Yang Chou , Huang Jing , Guo Yabing , Liu Li , Chen Ping , Wu Dongyun , Liu Junyun , Li Jin , Zhou Xiangjun , Hou Jinlin 
Published: July 2017

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus (HBV) infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs). DCs were loaded with a peptide pool of multiple HCC-related tumor antigens, and T cells were stimulated by these DCs. Thirteen patients with HCC received repeated MASCT after tumor resection during which their immune responses were examined. After three courses of MASCT, the frequency of regulatory T cells in the patients’ PBMCs significantly decreased (p &lt; 0.001), while the antigen peptide pool-triggered T cell proliferation (p &lt; 0.001) and IFNγ production (p = 0.001) were significantly enhanced. The specific T cell responses against each antigen in the pool were detected in eleven patients, but with individualized distinct patterns. The most immunogenic TAAs for HCC are survivin, CCND1, and RGS5. Moreover, the antigen-specific immune responses observed in tumor-free patients’ PBMCs were significantly stronger than that in the patients with recurrence (p = 0.037).
Conclusion: Our study demonstrates that MASCT is well-tolerated by patients with HCC and elicits strong and dynamic immune responses specifically against multiple tumor associated antigens, which may correlate with clinical outcomes.
Citation Format: Yanyan Han, Ye Wu, Chou Yang, Jing Huang, Yabing Guo, Li Liu, Ping Chen, Dongyun Wu, Junyun Liu, Jin Li, Xiangjun Zhou, Jinlin Hou. Specific and dynamic tumor antigen-specific immune responses were elicited in patients with hepatocellular carcinoma after cell-based immunotherapy [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 3761. doi:10.1158/1538-7445.AM2017-3761