bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1102: Time and spatial distribution of monocytic lineages in the process of carcinogen-induced oral cancer
Authors: Chen Chi Jui 
Published: August 2019

Abstract
Head and neck cancer (HNC) is the sixth among the top ten cancers in the world. Among this group of disease, oral cancer has been one of the top five killers in males for many years in Taiwan. Despite combined treatment, the prognosis for HNC patients is, in general, poor, which has strongly stimulated research on finding new strategies specific for HNC. To find a new treatment protocol for HNC, we examined the tumor microenvironment of a carcinogen (4-Nitroquinolone-1-oxide,4-NQO)-induced oral cancer. The immunohistochemical staining (IHC) results showed that this tumor has relative low density of vessels and high percentage of hypoxia around tumor edge. In addition, we found a layer of α-SMA positive cancer-associated fibroblast (CAF) in the junction of tumor and normal tissues. Further, we also found that a cluster of high density of CD68+ macrophages and Gr-1+ cells in this junction. To our surprise, very few tumor-associated macrophages (TAMs) could be identified in other tumor regions except this junction. In addition, the analysis of blood sample during tumor development found that the population of monocytic and granulocytic myeloid-derived suppressor cells (M-MDSCs and G-MDSCs) in the whole blood increases with the growth of the tumor, which has good correlation with the decrease of CD8+ and CD4+ T cells. The unique spatial distribution of myeloid cells in tumor tissue and consistent dynamic change of MDSC and T cells in the blood provides us an ideal tumor model for designing new strategies specific for HNC. We are currently using this tumor model to study the potential of combining immunotherapy with boron neutron capture therapy (BNCT) for HNC.
Citation Format: Chi Jui Chen. Time and spatial distribution of monocytic lineages in the process of carcinogen-induced oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1102.
Abstract 1105: Cisplatin treatment alters the preference of melanoma metastasis to liver associated with Ly6G positive cells
Authors: Chun-Hsiang Chang 
Published: August 2019

Abstract
This study examined the influence of cisplatin on host stroma and its consequence on metastasis using a metastatic melanoma tumor model. This preliminary result indicates that Gr-1+ cells could play important role on cisplatin treatment-directed liver metastasis. To further examine the role of Gr-1+ cells on this phenomena, Gr-1Ab was administered at day 16 after tumor inoculation. Results show that Gr-1Ab treatment could effectively decrease the Ly6G+ cells in both lung and liver and without significant reduced in lung-metastasis but, increased the metastasis in lung. To identify the effect of cisplatin treatment on B16-F0 melanoma metastasis, normal mice were treated with cisplatin prior to iv inject of B16-F0 melanoma cells. Cisplatin prevented treatment, similar to Gr-1 Ab therapy, decreased Ly6G+ cell in lung and liver tissue. And, it is minor difference of lung metastasis compare to Gr-1 Ab treatment, but more metastatic site than it. It demonstrates that cisplatin therapy induced liver-metastasis could associate with Ly6G+ cells. This study concludes that the cisplatin treatment could alter the preference of tumor metastasis, which is associated with the reduction of Ly6G+ cells It could be a potential target to enhance therapy efficiency.
Citation Format: Chang Chun-Hsiang. Cisplatin treatment alters the preference of melanoma metastasis to liver associated with Ly6G positive cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1105.
Abstract 1109: CPAP promotes HCC angiogenesis and metastasis via interacting with and enhancing STAT3 signaling
Authors: Chen Ruo Yu , Hung Liang-Yi 
Published: August 2019

Abstract
Centrosomal P4.1-associated protein (CPAP) is a centrosomal protein and can as a transcriptional coactivator of STAT5 and NF-κB in cancer. Our previous studies indicated that CPAP is overexpressed in tumor tissue and can increase TNFα-mediated NF-κB activation in HCC. Here, we demonstrated that overexpressed CPAP increases tumor growth, angiogenesis, as well as metastasis ex vivo and in vivo. We found that CPAP increases these malignant abilities of tumor cells are through IL-6/STAT3 signaling. We demonstrated that CPAP directly interacts with C-terminal domain of STAT3 to increase STAT3 activity. Overexpression of CPAP enhances IL-6/STAT3/IL-8-mediated angiogenesis and other metastatic genes expression such as CD44 and MCAM. These results indicated that CPAP leads to HCC malignancy and metastasis by increasing STAT3 activity through directly interaction. Clinically, CPAP positively correlates with IL-8 in HCC with vascular invasion; and also positively correlates with CD44 and MCAM in HCC tissues. In summary, our findings shed light on the importance of CPAP to act as a potential therapeutic target for inhibiting the IL-6/STAT3-mediated angiogenesis pathway and treating metastatic HCC.
Citation Format: Ruo Yu Chen, Liang-Yi Hung. CPAP promotes HCC angiogenesis and metastasis via interacting with and enhancing STAT3 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1109.
Abstract 1118: FOXQ1 stimulates WNT-signaling through transcriptional activation of WNT5B to promote the epithelial to mesenchymal transition
Authors: Mitchell Allison V. , Wu Guojun 
Published: August 2019

Abstract
Aberrant induction of the epithelial to mesenchymal transition (EMT) is an acknowledged mechanism of acquired metastatic competence and drug resistance in many epithelial cancer types. Both physiological and pathological forms of EMT are thought to occur through a network of transcription factors (TFs) that drive cell plasticity and the acquisition of stem-like traits. The forkhead box transcription factor, FOXQ1, is a potent driver of EMT. FOXQ1 has been shown to be specifically upregulated in the triple negative subtype of breast cancer (TNBC) where is it associated with worse clinical prognosis. However, the role of FOXQ1 within the EMT transcriptional network has not been extensively characterized. In this study, we employed chromatin immunoprecipitation and RNA sequencing in a human mammary luminal epithelial cell line with ectopic FOXQ1 (HMLE/FOXQ1), as a model of breast EMT. We identified FOXQ1 localization within the promoter regions of prominent EMT-TFs, including TWIST1, ZEB1, FOXC2 and SIX2. Further, FOXQ1 direct gene targets are enriched in signaling pathways previously associated with EMT, including the WNT-signaling pathway. Within the WNT pathway, the WNT5B signaling ligand was a direct target for transcriptional activation by FOXQ1. Gene expression analysis in a panel of breast cancer cell lines revealed both FOXQ1 and WNT5B are enriched in the basal B subtype of TNBC. FOXQ1 and WNT5B expression were also found to be upregulated and correlated downstream of TGFβ induced EMT. Disruption of WNT5B expression attenuated EMT-associated stem-like traits, including decreases in mammosphere formation and in the CD44+/CD24- population, and significantly reduced cell invasion. Analysis of breast cancer gene expression from the TCGA revealed that FOXQ1 and WNT5B expression are correlated across all breast samples (r=0.46) and differentially upregulated in ER- breast cancer. Additionally, both FOXQ1 and WNT5B expression were associated with worse recurrence-free survival. Our data supports that WNT5B is a critical FOXQ1 target for mediating EMT features and suggests that disrupting the FOXQ1-WNT5B axis could be a potential strategy to target the EMT cell population in TNBC patients.
Citation Format: Allison V. Mitchell, Guojun Wu. FOXQ1 stimulates WNT-signaling through transcriptional activation of WNT5B to promote the epithelial to mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1118.
Abstract 112: Patient derived models reveal impact of the tumor microenvironment on therapeutic response
Authors: Shafi Ayesha A. , Schiewer Matthew J. , Leeuw Renée de , Dylgjeri Emanuela , McCue Peter A. , Shah Neelima , Gomella Leonard , Lallas Costas , Trabulsi Edouard , Centerera Margaret , Hickey Theresa , Butler Lisa , Raj Ganesh , Tilley Wayne , Cukierman Edna , Knudsen Karen E. 
Published: August 2019

Abstract
Prostate cancer (PCa) is the most common non-cutanenous cancer and the second leading cause of cancer-related death in American men. Androgen receptor (AR) is a hormone-activated transcription factor that plays an important role in both the development and progression of PCa. Androgen deprivation therapy is a common first-line therapy for disseminated disease. However, virtually all tumors become resistant to such therapy and the tumor recurs. Thus, there is a vital need for the development of novel, more effective drugs. One major hurdle in this aspect is the lack of adequate preclinical models. Current models do not effectively recapitulate the heterogeneity and the microenvironment of human PCa tumors, significantly hindering the ability to accurately predict therapeutic response. Our collaborative group has utilized and characterized a method to culture patient tumors ex vivo, termed Patient Derived Explant (PDE). This approach maintains the integrity of the native tumor microenvironment, tumor tissue morphology, and molecular signaling. Importantly, our PDE model can be manipulated both chemically (drugs/compounds) and genetically (shRNA) in order to determine specific reactions and mechanisms of response on individual tumor growth. Furthermore, with this model we can quantitatively assess drug efficacy on numerous parameters (i.e. AR levels, Ki67 staining, apoptosis screening, and desmoplasmic indices). Data to be discussed will assess the variances in response to AR-directed therapeutics and underlying mechanisms of action, while also utilizing TME characteristics as a means to predict response to therapy. In addition, we can potentially identify clinically relevant subpopulations of patients and molecularly profile their cultured tissue to uncover new pathways for therapeutic intervention. Thus, the PDE model allows for a comprehensive evaluation of individual tumors in their native microenvironment to ultimately develop more effective therapies. This study will have transformative clinical impact discerning novel metrics for the inclusion of precision medicine for advanced PCa.
Citation Format: Ayesha A. Shafi, Matthew J. Schiewer, Renée de Leeuw, Emanuela Dylgjeri, Peter A. McCue, Neelima Shah, Leonard Gomella, Costas Lallas, Edouard Trabulsi, Margaret Centerera, Theresa Hickey, Lisa Butler, Ganesh Raj, Wayne Tilley, Edna Cukierman, Karen E. Knudsen. Patient derived models reveal impact of the tumor microenvironment on therapeutic response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 112.
Abstract 1122: CD44 as potential therapeutic target for medulloblastoma metastasis
Authors: Qi Dan , Wang Fengfei , Fonkem Ekokobe , Huang Jason H. , Wu Erxi 
Published: August 2019

Abstract
Medulloblastoma (MB) is a commonly diagnosed pediatric brain tumor that shows highly variable rates of morbidity and mortality. Metastasis is the leading cause of death in patients with MB, approximately 30% of MB patients have metastatic tumors right at diagnosis. Therefore, there is a critical need to dissect the molecular mechanisms that govern MB progression and metastasis. In our previous work, we found that DHA and VP16 synergistically inhibit MB cell proliferation and induce cell death accompanied with a marked reduction in the expression of CD44 standard form (CD44s). In this study, we show that MB cells express CD44s mainly and the elevated level of CD44s enhances MB cell invasion, suggesting that CD44s may play a crucial role in MB metastasis. In addition, we observed CD44s expression only in MB patients with metastasis using a small cohort of samples. Large database analysis show that MB patients with elevated levels of CD44 have poorer outcomes. Moreover, CD44 knockdown markedly reduces the expressions of transcription factor c-Myc and the platelet derived growth factor receptor (PDGFR) β, both are therapeutic targets for MB. Interestingly, PDGFRβ knockdown abolishes CD44s expression and downregulates the level of c-Myc. However, there is no expression change of CD44s and PDGFR β after the knockdown of c-Myc. These results indicate that the expression and function of CD44s could be critical to MB progression and metastasis, highlighting the potential therapeutic targets for MBs with metastasis.
Citation Format: Dan Qi, Fengfei Wang, Ekokobe Fonkem, Jason H. Huang, Erxi Wu. CD44 as potential therapeutic target for medulloblastoma metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1122.
Abstract 1124: S100A14 suppresses metastasis of nasopharyngeal carcinoma via inhibition of NF-kB signaling
Authors: Meng Dong-Fang , Qian Chao-Nan 
Published: August 2019

Abstract
Nasopharyngeal carcinoma (NPC) has a high incidence rate in southern China and Southeast Asia. Distant metastasis is the main reason for treatment failure. By analyzing our previously published whole genomic expression profiling data comparing low- versus high-metastasis NPC cells, we found that S100A14 expression was dramatically suppressed in high-metastasis cells. The reduced expression of S100A14 protein in the primary NPC collated with poorer overall survival of the NPC patients. Our preliminary experiments showed that S100A14 could inhibit the migratory and invasive abilities, as well as the epithelial-mesenchymal translation of NPC cells. RNA sequencing analyses found that NF-kB signaling pathway was the most dramatically influenced pathway by S100A14 with a negative relationship found between S100A14 and NF-kB signaling. We therefore propose a hypothesis that S100A14 inhibits NPC metastasis through inhibition of NF-kB signaling. In the proposed study, we will use a series of in vitro and in vivo approaches to clarify the inhibitory effects of S100A14 in terms of nuclear localization of P50 and P65, expression of IL-1beta, phosphorylation activation of the key molecules in NF-kB signaling pathway, as well as the in vivo metastasis of NPC cells. The accomplishment of the proposed study will reveal a novel mechanism of inhibiting NPC metastasis via inhibitory effects of S100A14 upon NF-kB signaling, which should be composed of drugable targets for metastasis prevention and treatment.
Citation Format: Dong-Fang Meng, Chao-Nan Qian. S100A14 suppresses metastasis of nasopharyngeal carcinoma via inhibition of NF-kB signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1124.
Abstract 1142: An activity-dependent proximity ligation platform for spatially resolved and multiplexed quantifications of active enzymes in single cells
Authors: Li Gang , Moellering Raymond E. 
Published: August 2019

Abstract
Integration of chemical probes into proteomic workflows enables the interrogation of protein activity, rather than abundance. Current methods limit the biological contexts that can be addressed due to sample homogenization, signal-averaging, and bias toward abundant proteins. To expand the application scope of chemical proteomics and explore the cellular heterogeneity on enzyme activities, we developed a new platform that integrates family-wide chemical probes with proximity-dependent oligonucleotide amplification and imaging to quantify enzyme activity in native contexts with high spatial and single cell resolution. Application of this method, activity-dependent proximity ligation (ADPL), to serine hydrolase and cysteine protease enzymes enables quantification of differential enzyme activity resulting from endogenous changes in localization and expression. In a competitive format, small molecule target engagement with endogenous proteins in live cells can be quantified. Retention of sample architecture enables interrogation of complex environments such as cellular co-culture and patient samples. We also successfully applied ADPL in xenograft tissue sample, exhibiting the application prospect in primary patient tissue. Additionally, implementation of barcoded antibody-oligo direct conjugation enabled multiplexed readout of active enzymes within and between enzyme families, providing the possibility of simultaneous biomarker detection. Together, this work supports ADPL should be amenable to diverse and multiplexed protein families to detect active enzymes at scale and resolution out of reach with current methods.
Citation Format: Gang Li, Raymond E. Moellering. An activity-dependent proximity ligation platform for spatially resolved and multiplexed quantifications of active enzymes in single cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1142.
Abstract 1144: Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET
Authors: Saleem Azeem , Helo Yusuf , Searle Graham , Dekaj Fatjon , Cook Jo , Win Zarni , Gunn Roger , Wells Paula 
Published: August 2019

Abstract
Integrin αvβ6 plays a key role in the fibrotic pathway by activation of Transforming Growth Factor β. Expression of αvβ6 integrin in alveolar epithelium increases after radiotherapy (RT) before onset of fibrosis and anti- αvβ6 therapy prevents fibrogenesis. Post-RT lung fibrosis, a major barrier to improved cure rate presents as progressive pulmonary injury. The utility of PET imaging with a αvβ6 integrin ligand was evaluated in patients with non-small cell lung cancer following pulmonary RT.
Subjects who had received pulmonary RT within 6 months were recruited. PET imaging of the lungs over 60 minutes was performed after administration of a fluorine-18 radiolabelled 20 amino acid αvβ6-specific peptide ligand, [18F]-FBAA20FMDV2 (IMAFIB; Cancer Research Technologies (CRT) patented). PET-CT scans were co-registered with the RT planning (RTP) scans and segmented to regions corresponding to RT doses of &gt; 40 Gy (excluding tumour), 25-40 Gy, 15-25 Gy, 8-15 Gy and &lt; 8 Gy. Time activity curves and the standardised uptake values (SUVs) were calculated and comparisons made between RT dose and PET uptake (SUV). Linear regression between SUV and RT dose was performed for each subject and normalised to an intercept of 1.
6 subjects (3M; 3 F) aged 51-75 years underwent an IMAFIB-PET scan between 6 -22 weeks after RT completion and mean IMAFIB radioactivity of 45.4 (range 8.9 – 122) MBq administered. 5 subjects received conformal external beam RT, while one subject received stereotactic RT (SBRT). A correlation between a higher PET uptake (SUV) and higher RT doses received by the lung was observed in all subjects with a significant relationship (p &lt; 0.05) in 3 of the 6 subjects (table). The averaged normalised SUV across all subjects increased monotonically with RT dose, between 1.05 ± 0.14 at 4 Gy and 1.58 ± 0.31 at 52 Gy.
Subject No.111216172021RT dose and fractionation55Gy in 5 fractions. SBRT64 Gy in 32 fractions45 Gy in 15 fractions50 Gy in 20 fractions64 Gy in 32 fractions64 Gy in 32 fractionsTime between completion of RT and PET scan (weeks)822136714Gradient of relationship between PET uptake and RT dose0.0290.0050.0100.0060.0030.008Intercept1.3050.5040.8370.3910.6910.469r20.8410.5390.8360.8790.3100.672p value0.0280.1580.0300.0180.1630.089
A relationship between IMAFIB PET uptake and RT dose is consistent with RT dose-related activation of αvβ6 integrin in the irradiated lung and to the induction of lung fibrosis in subjects receiving pulmonary RT.
Citation Format: Azeem Saleem, Yusuf Helo, Graham Searle, Fatjon Dekaj, Jo Cook, Zarni Win, Roger Gunn, Paula Wells. Imaging radiotherapy induced pulmonary fibrogenic changes with integrin-PET [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1144.
Abstract 1149: Systems pathology by Optra 30 color multiplex immunofluorescence automated whole slide imaging system integrated with image analysis
Authors: Gholap Abhi , Jadhav Anagha P. , Somwanshi Suraj , Kamble Gurunath , Doshi Isha , Huang Jiaoti 
Published: August 2019

Abstract
Background A paradigm shift from single marker immunohistochemistry (IHC) to multiplexing in molecular histopathology has helped better understand the cellular composition and heterogeneity of sub population of cells in tissues. Presently, one needs to manually exchange filters after each multiplex scan for capturing all fluorophores per staining round. This is very cumbersome and inefficient, as this process requires rescanning the same slide multiple times. Moreover, visual assessment and quantification of biomarkers is limited by inter and intra-observer variability. We hereby present an automated multispectral whole-slide imaging system integrated with image analysis for detection of upto 30-color multiplex assay with spectral unmixing and cell segmentation functionality.
Material and Methods
Multiplex IHC whole slide imaging Formalin Fixed Paraffin Embedded rat brain; indirect IHC stained sections with 10 antibodies using photostable fluorophores were obtained. The staining was based on antigenic integrity and antibody binding affinity. Optra's multispectral fluorescent whole slide scanning process was optimized to image sensitive antigens in early cycles and robust antigens in latter cycles. The fully automated fluorescence scanning system imaged weakly expressing biomarkers in the visible range (480-620 nm), highly expressing targets in the violet/blue (405-440 nm), far-red (650-680 nm) and NIR (700-800 nm) range across the entire usable light spectrum (350-800 nm).
ResultsWe could simultaneously detect up to 30 biomarkers within a single tissue section, using 12 staining-imaging-stripping cycles, with 10 antibodies screened per cycle. Software measures enabled separation of spectrally overlapping markers in the multiplex assay. A computer-controlled X-Y-Z stage used autofocusing at 20X/40X magnification. Integrated image analysis solution performed comprehensive evaluation of antigens of interest with accurate quantification of the target proteins based on parameters including but not limited to hue value/width, intensity threshold scoring, morphological characterization, pixel-count thresholding and color saturation.
Conclusion This proposed solution is efficient compared to the current imaging methods to tackle the aforementioned image acquisition and image analysis challenges associated with multiplexing assays.
Note: This abstract was not presented at the meeting.
Citation Format: Abhi Gholap, Anagha P. Jadhav, Suraj Somwanshi, Gurunath Kamble, Isha Doshi, Jiaoti Huang. Systems pathology by Optra 30 color multiplex immunofluorescence automated whole slide imaging system integrated with image analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1149.