bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4512: Doublecortin-like kinase 1 (DCLK1) correlates with Notch pathway signaling, controls metastatic characteristics in head and neck cancer
Authors: Broner Esther Channah , Subbannayya Tejaswini , Advani Jayshree , Zhavoronkov Alex , Artemov Artem , Ozerov Ivan , Sloma Ido , Gowda Harsha , Sidransky David , Izumchenko Eugene , Chatterjee Aditi 
Published: August 2018

Abstract
Despite advancements in the field, the 5 year survival rate of Head and Neck Squamous Cell Carcinoma (HNSCC) still hovers at 60%. In a quest for novel therapy targets for this disease, we performed an extensive and comprehensive quantitative phosphoproteomics scan on 10 HNSCC patient derived xenografts (PDXs) in order to find dysregulated phosphoproteins. DCLK1 is hyperphosphorylated but not over expressed in most of the HNSCC derived PDXs. DCLK1 has been shown to regulate epithelial-to-mesenchymal transition (EMT) as well as serving as a cancer stem cell marker in colon and pancreas cancer. DCLK1 is also associated with bad prognosis in colon, renal and oropharyngeal cancers. We performed a comprehensive transcriptome-based computational analysis on hundreds of HNSCC patients from TCGA and GEO databases. While our results confirm the role of DCLK1 in regulating EMT and focal adhesion kinase (FAK) mediated integrin signaling, we found that high DCLK1 expression also correlates with NOTCH pathway signaling signatures in HNSCC. We have selected 5 cell HNSCC cell lines (JHU-011, JHU-022, JHU-029, FaDu and Cal29) that express DCLK1, and inhibited DCLK1 with LRRK2-in1 inhibitor and siRNA. DCLK1 inhibition resulted in substantially decreased proliferation, migration, and colony formation. Furthermore, these effects paralleled downregulation NOTCH1 signaling in all cell lines tested. Overall, our results demonstrate the novel role of DCLK1 in regulating the NOTCH signaling network and suggest its potential as a therapeutic target in HNSCC.
Citation Format: Esther Channah Broner, Tejaswini Subbannayya, Jayshree Advani, Alex Zhavoronkov, Artem Artemov, Ivan Ozerov, Ido Sloma, Harsha Gowda, David Sidransky, Eugene Izumchenko, Aditi Chatterjee. Doublecortin-like kinase 1 (DCLK1) correlates with Notch pathway signaling, controls metastatic characteristics in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4512.
Abstract 4519: Preliminary data of a stool test for lung cancer from a prospective study
Authors: Tobi Martin , Tobi Yosef Y. , Antaki Fadi , Rambus MaryAnn , Lawson Michael 
Published: August 2018

Abstract
Lung cancer is the biggest cancer killer Worldwide with a limited prognosis despite personalized treatment regimens. Low-dose CT scanning as a means to early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need to be developed that offer both timely diagnosis and predict prognosis. Methods: In the course of stool testing in a large scale testing of patients at increased risk of CRC we were able to ascertain 55 patients documented to have prospectively been diagnosed with lung cancer. Stool and colonic effluents were tested for anti-adenoma antibody (Adnab-9) reactivity by ELISA and Western blot. Survival data were obtained where available. Results: Of 55 cancers 40% were squamous (SSC), 23.7 were adenocarcinoma, 14.6 small, 12.7 large cell and 9% were designated NSCLC. 49.1% of the lung cancer patients had adnab-9 testing. Overall 53.6% (14 of 26) had positive testing compared to 2 of 11 controls (18.2%) which bordered on significance (OR5(CI1-29)). Cancers with higher lethality were more likely to test positive (67% for both small and large cell lung cancers, 50% SCC and adenocarcinoma, 33% NSCLC). In the larger groups overall survival was worse in those testing positive (474 versus 844 days in SCC and 54 versus 749 days in adenocarcinoma patients). Most importantly the time from a positive test to the clinical diagnosis ranged from 2.72 years for small cell, 3.13 for adenocarcinoma, 5.07 for NSCLC, 6.07 for SSC, and 6.24 for large cell cancer). In excluded cases where lung cancer was believed to be metastatic 75% of cancers were positive. Conclusions: At a projected real world sensitivity of 0.53 and specificity of 0.82 and the ability to predate diagnosis by up to 4.7 years overall, this test could help direct lung cancer screening. In addition, the Adnab-9 testing selectively detects worse tumor types (67%) and those with worse prognosis amongst the more common, favorable phenotypes thus making early diagnosis possible in those patients who stand to benefit most from this strategy. Metastatic lung cancer also detected by the test should be identified by the follow-up imaging studies and therefore would not be considered to be a major pitfall.
Citation Format: Martin Tobi, Yosef Y. Tobi, Fadi Antaki, MaryAnn Rambus, Michael Lawson. Preliminary data of a stool test for lung cancer from a prospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4519.
Abstract 4566: PD-L1 and B7-H3 expression in serous carcinoma of endometrium
Authors: Nishimura Masato , Mineda Ayuka , Abe Akiko , Irahara Minoru 
Published: August 2018

Abstract
Endometrial cancer keeps increasing in Japan explosively. In endometrial cancer, the prognosis of serous carcinoma is very poor, because of early progression to abdominal cavity. Remedy for endometrial cancer is limited, so new therapy has been required for a long time. Immunotherapy is very promising in various cancers recently. PD-L1 (programmed cell death ligand 1) and B7-H3 are factors of immunoresponse between cancer cells and lymphcyte. Purpose: The purpose of this study is to investing the expression of PD-L1 and B7-H3, moreover, relationship with clinicopathological factors in serous carcinoma of endometrium. We immunohistochemically evaluated PD-L1 and B7-H3 expression in 21 serous carcinoma. The result was graded as positive in case stained more than 10% area. Result: 2/21(9.5%) for PD-L1 and 10/21(47.6%) for B7-H3 were positive. There was no correlation with tumor diameter, lymphnode metastasis, advanced stage and recurrence in PD-L1, however, B7-H3 expression had trend node metastasis, 3/10 in positive cases vs 0/11 in negative cases (p=0.05). In 4 recurrent cases treated with taxane and carboplatin as second line therapy, one case with B7-H3 negative got complete remission, however 3 cases with B7-H3 positive got partial improvement once, but finally got progression. Conclusion: PD-L1 expression was limited in serous carcinoma, so immunotherapy targeted for PD-1 and PD-L1 may be limited. The expression of B7-H3 is related to chemotherapy resistance. B7-H3 may be a biomarker for chemotherapy and target of new immunotherapy for serous carcinoma of endometrium.
Citation Format: Masato Nishimura, Ayuka Mineda, Akiko Abe, Minoru Irahara. PD-L1 and B7-H3 expression in serous carcinoma of endometrium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4566.
Abstract 4664: Enzymatically-responsive tumor-targeted mesoporous silica nanoparticle for identification of pancreatic cancer
Authors: Nairon Kylie , Samykutty Abhilash , McNally Molly W. , Mishra Girish , Grizzle William E. , McNally Lacey R. 
Published: August 2018

Abstract
Purpose: Pancreatic cancer remains an unsolved health issue, with its rapid progression and resistance to modern therapy leading to poor prognoses for most patients. The prevalence of metastasis in pancreatic cancer makes complete tumor location and removal rare, and those who do have resectable disease have only a 20% 5-year survival rate. In recent years, nanoparticles have been explored as targeted delivery agents for chemotherapeutic drugs and imaging dyes, however few have achieved clinical success due to overestimation of biological phenomena and reliance on passive targeting systems. In this work, an enzyme-responsive nanoparticle has been developed for increased active pancreatic tumor targeting and specific release at biologically-significant enzyme concentrations.
Methods: Mesoporous silica nanoparticles were formed using a scaffold of hexadecyltrimethylammonium bromide (CTAB) at 80°C. The scaffold was removed to form wormhole-like pores using a series of dialysis procedures. Transmission electron microscopy (TEM) confirmed the 35 nm diameter and porous structure of the particles. The particles were then loaded with IR780 dye, and surfaces were functionalized with (3-aminopropyl) triethoxysilane (APTES). The loaded particles were then encapsulated with a combination of Type A and Type B gelatin, followed by a stabilizing polyvinylpyrrolidone (PVP) layer. Dynamic light scattering (DLS) and zeta potential were used to confirm coating. Coated particle samples were exposed to collagenase type IV (MMP-9) enzyme to test encapsulation efficiency and enzyme sensitivity. Enzyme-treated and intact samples were transferred to tissue phantoms, and Multispectral optoacoustic tomography (MSOT) was used for comparative analysis.
Results: TEM confirmed the formation of stable 35 nm silica nanoparticles with a wormhole-like pore structure. Zeta potential decrease from 55 mV to 5 mV and DLS particle diameter increase from 35 nm to 334.5 nm indicated binding of gelatin and PVP to particle surfaces. MSOT imaging showed 10 X increased signals from untreated nanoparticles as compared to enzyme-treated nanoparticles, indicating that dye molecules remained inside the pores of coated particles and were released when exposed to MMP-9.
Conclusion: Gelatin/PVP-coated mesoporous silica nanoparticles encapsulated dye and demonstrated MMP-9 activated dye release at biologically-relevant enzyme concentrations.
Citation Format: Kylie Nairon, Abhilash Samykutty, Molly W. McNally, Girish Mishra, William E. Grizzle, Lacey R. McNally. Enzymatically-responsive tumor-targeted mesoporous silica nanoparticle for identification of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4664.
Abstract 4671: Rapid, no-wash measurement of immune checkpoint molecules expression induced by interaction with peripheral blood mononuclear cells in breast and cervical cancer cell models
Authors: Hinterneder Jeanine M. , Carlstrom Jen , Carlson Adam , Nida Dawn 
Published: August 2018

Abstract
The purpose of this study was to examine the pathways involved in the induction of immune checkpoint molecules in basal breast and cervical cancer cell lines by measuring classical biomarker expression using AlphaLISA no-wash homogeneous assays. Programmed cell death-ligand 1 (PD-L1) expression increases with tumor severity in basal-like breast cancer and is enhanced in intraepithelial neoplasia and cervical cancers. Basal-breast tumors can adapt to lymphocytic infiltration by responding to heightened concentrations of interferon gamma (IFN-y) secreted by Type 1 helper T cells with upregulation of PD-L1 protein allowing the tumors to evade immune targeting and reduce the immune response. We show here that human peripheral blood mononuclear cells (PBMCs) secrete IFN-y and other cytokines in response to stimulation with CD3/CD38 Dynabeads. We then examined modulation in expression of immune checkpoint molecules (PD-L1 and others) in HCC38 (basal breast cancer-derived) and HeLa (cervical cancer) cells in response to co-culturing with activated PBMCs, treatment with conditioned media collected from activated PBMCs, and direct treatment with recombinant IFN-y. As expected, IFN-y treatment induced dose-dependent upregulation of PD-L1 protein expression in both HCC38 and HeLa cell lines, whereas the effects of conditioned media and direct co-culturing with PBMCs resulted in more complex effects which are discussed. To determine if tumor cytoarchitecture influences responsiveness to the PBMCs, biomarker expression was measured from cultures grown in both traditional adherent monolayers and in 3D spheroid cultures using Ultra-Low Attachment (ULA) microplates. Cellular health and proliferation was assessed by measuring ATP concentration with ATPlite luminescence assays and cellular imaging with viability dyes. The upregulation of PD-L1 expression was observed to be largely independent of cellular proliferation and is further shown to be dependent on signaling through the JAK/STAT pathway by probing with AlphaLISA SureFire phosphorylation
assays. These data illustrate and address some of the challenges in developing a biologically relevant culture system for examining the complex mechanisms involved in tumor evasion of the innate immune response.
Citation Format: Jeanine M. Hinterneder, Jen Carlstrom, Adam Carlson, Dawn Nida. Rapid, no-wash measurement of immune checkpoint molecules expression induced by interaction with peripheral blood mononuclear cells in breast and cervical cancer cell models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4671.
Abstract 4748: Snail1 regulates the tumor-infiltrating regulatory T cell population in breast cancer through Pglyrp3
Authors: Chen Dongjiang , Sebastian Mathew , Le Son , Thomas Nagheme , Tran David D. 
Published: August 2018

Abstract
Breast cancer is the second-leading cause of cancer deaths in women. Nearly 30% of breast cancer patients developed recurrent and/or metastatic disease despite several effective receptor-targeting treatments. Although immunotherapy, especially immune checkpoint inhibitors, has proven to be efficacious against many cancers, they have shown more limited activities against poorly immunogenic cancers such as breast cancer. The cause of this relative resistance to immunotherapy is unclear but is thought to be due in part to an enrichment of inhibitory immune cells such as regulatory T cells (Tregs) in the tumor microenvironment (TME). Therefore there is an urgent need to have a better understanding of the underlying genetic and epigenetic determinants of immunotherapeutic resistance in breast cancer to develop methods to overcome it. To that end, using a computational algorithm that we have recently developed, we have discovered a novel gene regulatory subnetwork downstream of the master epithelial mesenchymal transition (EMT) regulator Snail1 in mouse models of human breast cancer. In advanced breast cancer, Snail1 is thought to initiate the epithelial mesenchymal transition (EMT) to promote local invasion and metastatic spread, while also maintaining tumor-initiating cells. On the contrary, this new Snail1-induced subnetwork operates independently of and possibly in place of its EMT function during early tumorigenic changes, when it is required to maintain a powerful tissue surveillance program to curtail transformed cells' ability to progress to advanced cancer. Breast-restricted deletion of Snail1 early in the course of tumorigenesis of several mouse models of breast cancer results in accelerated growth of the primary tumor in an immunocompetent TME, while in an immunosuppressed TME lack of Snail1 significantly reduced growth. We found that Snail1 suppressed regulatory T cells likely by tumor-associated cytokine production, possibly through several key nodes including Hmga2 and Pglyrp3, to promote immune surveillance and clearance of cancer cells. Ongoing experiments are aimed at validating the criticality of this new pathway as individual nodes and as a whole and to evaluate its utility as a novel therapeutic target to improve breast cancer's response to immunotherapy.
Citation Format: Dongjiang Chen, Mathew Sebastian, Son Le, Nagheme Thomas, David D. Tran. Snail1 regulates the tumor-infiltrating regulatory T cell population in breast cancer through Pglyrp3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4748.
Abstract 4924: Evaluation of the efficacy of curcumin and Y15 in platinum resistant ovarian cancer cells
Authors: Levy Arkene S. , Rathinavelu Appu , Coelho Nicole , Ramnot Amanda , Kanagasabai Thanigaivelan , Bracho Olena , Smith Robert 
Published: August 2018

Abstract
Curcumin, a compound derived from turmeric (Curcuma longa), inhibits the proliferation of multiple cancer cell types, including ovarian, pulmonary, brain, and breast through various mechanisms. In advanced ovarian cancer, focal adhesion kinase (FAK), a tyrosine kinase, is overexpressed and contributes to platinum resistance. The compound Y15 (1, 2, 4, 5-benzene tetra amine tetrahydrochloride) inhibits FAK phosphorylation and subsequent activation. Therefore, in the present study we evaluated the combined cytotoxic efficacy of Curcumin and Y15 in platinum resistant OVCAR3 ovarian cancer cells. Cells were initially treated with concentrations of Y15 (10-100 μM), and curcumin (0-20µM) to determine IC10 values. Cells were subsequently treated with Y15 (20 μM) and curcumin (5 µM) alone and in combination. The cytotoxic profile of each treatment was assessed using the MTT assay. DNA fragmentation and poly ADP ribose polymerase (PARP) cleavage assays were performed to evaluate the mechanism of cell death. We further evaluated the expression of total FAK, phosphorylated FAK, p53, p21, and BAX in response to treatments using western blot. Y15 significantly increased the cytotoxic efficacy of curcumin when compared to the curcumin only treatment. Cell death by apoptosis was confirmed by PARP cleavage and the presence of DNA fragments in Y15, curcumin, and curcumin plus Y15 treatment groups. The curcumin plus Y15 combination significantly downregulated the expression of phosphorylated FAK when compared to the individual treatments and control. Reduced FAK phosphorylation also correlated with increased expression of P53, P21 and BAX in curcumin and Y15 treatment groups. These results indicate that Y15 significantly enhances the cytotoxic profile of curcumin in platinum resistant OVCAR-3 cells. This study is the first to report a FAK dependent cytotoxic mechanism of curcumin in ovarian cancer and in further work we will evaluate the signaling pathways involved.
Citation Format: Arkene S. Levy, Appu Rathinavelu, Nicole Coelho, Amanda Ramnot, Thanigaivelan Kanagasabai, Olena Bracho, Robert Smith. Evaluation of the efficacy of curcumin and Y15 in platinum resistant ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4924.
Abstract 5004: Profiling the extracellular matrix landscape of tumor microenvironments using proteomics
Authors: Naba Alexandra , Clauser Karl R. , Carr Steven A. , Hynes Richard O. 
Published: August 2018

Abstract
"Your cancer has spread" remains for most cancer patients synonymous with a death sentence. Indeed, the majority of cancer deaths are due to metastases: the dissemination of tumor cells from a primary tumor to distant vital organs. As of today, we do not have efficient treatments to stabilize or cure most metastatic cancers, and for patients diagnosed early, i.e., before metastases are detectable, we do not have reliable markers to predict whether their tumors will remain indolent or will become deadly. Tumor progression critically depends on a locally permissive microenvironment, including a unique tumor-associated extracellular matrix (ECM). The ECM is a complex meshwork of proteins providing architectural support to cells and conferring biomechanical properties to tissues. ECM-derived biochemical signals transduced by cell-surface receptors, such as the integrins, regulate cellular functions such as proliferation and survival, adhesion, and migration, all essential for metastasis. Importantly, clinicians have observed that more aggressive tumors present a higher ECM content. Thus, to fully understand how tumors progress and disseminate, it is essential to study the tumor ECM. To do so, we have developed a pipeline combining bioinformatics and proteomics to comprehensively characterize the ECM composition, or "matrisome," of tissues and tumors. Using this pipeline, we demonstrated that the composition of the ECM varies i) between normal tissues and tumors, ii) between poorly and highly metastatic primary tumors, and iii) between primary tumors and derived metastases. Here we present for the first time "The Tumor ECM Atlas," a compendium of ECM proteins identified by proteomics in the microenvironment of 10+ types of primary tumors and derived metastases, including breast, colorectal and lung cancers, insulinomas and multiple myelomas, which revealed the presence of a unique subset of cancer-specific and cancer type-specific ECM proteins. We believe that this atlas is a powerful tool to formulate novel hypotheses on the roles of the ECM in tumor progression and metastasis. In addition, we propose that the ECM is an underexplored reservoir of potential diagnostic and prognostic markers and therapeutic targets, and that its exploration using proteomics will pave the way for the development of novel approaches to better care for cancer patients.
Citation Format: Alexandra Naba, Karl R. Clauser, Steven A. Carr, Richard O. Hynes. Profiling the extracellular matrix landscape of tumor microenvironments using proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5004.