bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1906: Relationship between neuroendocrine and immune gene expression in small cell lung cancer
Authors: Cai Ling , Liu Hongyu , Huang Fang , Fujimoto Junya , Girard Luc , Xie Yang , Minna John , Gazdar Adi 
Published: July 2021

Abstract
Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings provide a new framework to guide design of treatment regimens in SCLC.
Citation Format: Ling Cai, Hongyu Liu, Fang Huang, Junya Fujimoto, Luc Girard, Yang Xie, John Minna, Adi Gazdar. Relationship between neuroendocrine and immune gene expression in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1906.
Abstract 1916: Lymph node targeting double stranded CpG act effective adjuvant in cancer peptide vaccine
Authors: Nakagawa Takayuki , Onishi Motoyasu , Tofukuji Soichi , Omoto Shinya , Katayama Kazufumi , Kugimiya Akira , Nagira Morio , Ishii Ken J. 
Published: July 2021

Abstract
Background: Adjuvants can enhance immune responses of vaccinated antigen by inducing host innate immune responses. While cancer peptide vaccines were largely studied in recent years, effective cancer peptide vaccines have not been found yet so far because of their poor immunogenicity. Developing an effective vaccine adjuvant suitable for peptide antigen is a promising approach. CpG oligodeoxynucleotides(CpG) are a toll-like receptor 9 agonists and effectively elicit innate immune responses. In order to improve adjuvanticity of CpG, we designed a novel lymph-node targeting CpG, which is composed from a single stranded CpG and a modified complementary strand with amphiphilic chain.
Methods: S-540956 is a double stranded oligodeoxynucleotide composed from a single stranded phosphorothioate oligonucleotide and the complementary strand with amphiphilic chain at the 5' end. Accumulating capability to lymph nodes of fluorescent labeled S-540956 was analyzed by flow cytometer, IVIS imaging system, and 2-photon microscopy. Incorporation of S-540956 by antigen-presenting cells in lymph nodes was assessed by Image Stream® imaging cytometer. To test cellular immune responses, three types of MHC class-I epitope peptides were employed as antigenic peptides. Therapeutic effect of S-540956 adjuvanted HPV E7 peptide vaccine was evaluated in TC-1 tumor model.
Results:S-540956 exhibited higher accumulating capacity to lymph nodes in mice compared to a typical CpG adjuvant, ODN2006. Systemic proinflammatory cytokine responses were decreased by combining the complementary strand with amphiphilic chain. S-540956 was efficiently incorporated into plasmacytoid DCs and induced the expression of costimulatory molecules. Cellular immune responses induced by S-540956 adjuvanted peptide vaccine were significantly higher than ODN2006 adjuvanted peptide vaccine. And this enhanced adjuvant effect was observed also in protein vaccine. In TC-1 tumor model, therapeutically administered S-540956 adjuvanted HPV-E7 peptide vaccine lead to significant tumor shrinkage compared to ODN2006 adjuvanted peptide vaccine.
Conclusion: S-540956 acted as a potent adjuvant for peptide vaccine by inducing cellular immune responses effectively. Accumulating capacity to lymph nodes of S-540956 is a promising adjuvant for not only for peptide but for protein or other biologic antigens.
Citation Format: Takayuki Nakagawa, Motoyasu Onishi, Soichi Tofukuji, Shinya Omoto, Kazufumi Katayama, Akira Kugimiya, Morio Nagira, Ken J. Ishii. Lymph node targeting double stranded CpG act effective adjuvant in cancer peptide vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1916.
Abstract 1918: Coxsackievirus A11 elicits a potent oncolytic activity in human malignant pleural mesothelioma via ICAM-1 receptor
Authors: Okamura Koji , Inoue Hiroyuki , Ikematsu Yuki , Furukawa Rie , Ota Keiichi , Yoneshima Yasuto , Iwama Eiji , Tanaka Kentaro , Okamoto Isamu 
Published: July 2021

Abstract
Malignant pleural mesothelioma (MPM) is an aggressive solid cancer with dismal prognosis. Oncolytic virotherapy is a promising anticancer treatment that directly lyses tumor cells. Coxsackievirus A11 (CVA11) is an emerging oncolytic virus against solid cancers. Herein we tested whether CVA11 infection has an oncolytic activity in human MPM cell lines and identified its cognate receptor. We found that CVA11 infection shows a remarkable oncolytic activity in six of six human MPM cell lines. MPM cells having higher intercellular adhesion molecule-1 (ICAM-1) expression showed higher CVA11-induced cytotoxicity, and that identified ICAM-1 as its surface receptor because coinfection with neutralizing ICAM-1 antibody substantially abrogated CVA11-triggered cytotoxicity in MPM cells. In addition, we unraveled that the activations of both phosphoinositide 3-kinase/Akt and mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) signaling pathways partially but significantly contributed to the CVA11-triggered cytotoxicity of CVA11 as evidenced by treating with respective inhibitors. Taken together, our findings show a novel oncolytic virotherapy using CVA11 could be an alternative therapeutic modality for human MPM.
Citation Format: Koji Okamura, Hiroyuki Inoue, Yuki Ikematsu, Rie Furukawa, Keiichi Ota, Yasuto Yoneshima, Eiji Iwama, Kentaro Tanaka, Isamu Okamoto. Coxsackievirus A11 elicits a potent oncolytic activity in human malignant pleural mesothelioma via ICAM-1 receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1918.
Abstract 1921: Armed oncolytic myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors
Authors: Franco Lina S. , Mamola Joseph , Abdullahi Wazir , de Matos Ana , Abrantes Mario , Walker Benjamin S. , Tacner Zachary , Grigaitis Nicole , Kien Cassandra , McFadden Grant , Sharp Leslie L. 
Published: July 2021

Abstract
Oncolytic viruses (OV) selectively replicate in and lyse tumor cells and provide stimulation to the immune system, representing a promising therapeutic option in development to treat cancers that do not respond well to treatment with immune checkpoint inhibitors. Myxoma virus (MYXV) is a member of the Pox family of double stranded DNA viruses. The natural host of MYXV is a subset of rabbits and hares, but MYXV can infect cancer cell lines of humans and other species. The genome of MYXV is relatively large and is amenable to engineering for expression of transgenes making it an excellent oncolytic virus for introduction of immunomodulatory proteins. Oncolytic activity and transgene production capability were examined in multiple mouse cancer cell lines. In vivo efficacy following intratumoral and intravenous administration of armed myxoma virus, both alone and with immune checkpoint inhibitors is demonstrated. Immunomodulatory mechanisms of actions are investigated. Multi-armed myxoma represents a novel, engineerable, oncolytic virus with preclinical characteristics that warrant further investigation as an immunomodulatory cancer therapeutic.
Citation Format: Lina S. Franco, Joseph Mamola, Wazir Abdullahi, Ana de Matos, Mario Abrantes, Benjamin S. Walker, Zachary Tacner, Nicole Grigaitis, Cassandra Kien, Grant McFadden, Leslie L. Sharp. Armed oncolytic myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1921.
Abstract 1923: Modulation of apoptosis in glioblastoma U87-MG cancer cells by aqueous extract of Bryophyllum pinnatum
Authors: Ferrer Kristin , Li Joshua , Kordas Camille , Cha Jasmine , Han Sung Been , Seo Joon , Manrique Nathaly , Kang Min Seo , Jin Yi Shan , Choi Si Won , Hiramoto Ben , Smith Denise , Wong Brian Yuen 
Published: July 2021

Abstract
Bryophyllum pinnatum (BP) has been used in anthroposophic medicine to treat “hyperactivity diseases” such as tocolytic symptom and overactive bladder syndrome since the beginning of 20th century with no side effect. Its major secondary metabolites include bufadienolides, flavonoids, triterpenes, and steroids. BP has been widely used in tropical regions as traditional medicine. It is reported to have antioxidant, immunomodulatory, antidiabetic, anti-inflammatory, antihypertensive, wound healing, cytotoxic, and antitumor promoting activities. Glioblastoma is an aggressive and lethal tumor of the brain with few treatment options. In this study, the effects of aqueous extracts of BP on the induction and modulation of apoptosis in glioblastoma U87-MG cells were assessed using the green/red/blue fluorescent Apoptosis/Necrosis Detection Kit and the Human Apoptosis Antibody Array - Membrane (43 Targets) test by the Abcam cooperation. Our data revealed that 3-hours of 1 mg/mL and 2 mg/mL BP treatment induced statistically similar amounts of apoptosis observed as green apoptotic cells and red necrotic cells in U87-MG cells respectively (apoptotic cells = 86.0 ± 6%, necrotic cells = 14.0 ± 6.0% ; apoptotic cells = 85.0 ± 4.0% , necrotic cells = 14.5 ± 3.5%). The percent of apoptosis was not significantly different as compared to that of the positive control induced by 1µMol Staurosporine (94.5 ± 0.5%, 5.5 ± 0.5%); while significantly different from the negative control which had none apoptotic cells. Slightly less induction of apoptosis was obtained from 6-hours of 1 mg/mL and 2 mg/mL BP treatment with more necrotic cells (81.5 ± 2.5%, 18.5 ± 2.5%; 78.0 ± 3.0%, 21.5 ± 2.5% respectively). Modulation of various apoptosis markers such as up-regulation of Bax, p53, Caspase 3; and down-regulation of Bcl-2 and Bcl-w was also observed. These results suggest that BP contains phytochemicals which induce apoptosis in glioblastoma U87-MG cells by modulating these apoptotic pathway markers. Further study of the specific modulation effects of BP on apoptosis is warranted to reveal its potential chemopreventive and therapeutic properties against glioblastoma and other cancers.
Citation Format: Kristin Ferrer, Joshua Li, Camille Kordas, Jasmine Cha, Sung Been Han, Joon Seo, Nathaly Manrique, Min Seo Kang, Yi Shan Jin, Si Won Choi, Ben Hiramoto, Denise Smith, Brian Yuen Wong. Modulation of apoptosis in glioblastoma U87-MG cancer cells by aqueous extract of Bryophyllum pinnatum [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1923.
Abstract 1925: Effect of Averrhoa carambola extract on the antineoplastic and apoptotic activities in mice
Authors: Hasan Md. Zahid , Siddika Ayesha 
Published: July 2021

Abstract
Medicinal plants play significant roles in the treatment of different diseases. Averrhoa carambola has important clinical values in the treatment of cancer. However, its antineoplastic and apoptotic activities are still obscure. In this study, we were aimed to investigate those potentials of Averrhoa carambola in mice. For this, first the powder, prepared from the leaf and flower of Averrhoa carambola, were suspended with methanol to yield methanol extract of leaf and flower. Antineoplastic effect of leaf (25 and 50 mg/kg) against Ehrlich Ascites Carcinoma (EAC) was assessed by evaluating the viable tumor cell count, survival time, body weight and hematological parameters of EAC cell bearing mice. The result showed that the treatment with leaf significantly (p&lt;0.05) decreased viable EAC cells and body weight gain thereby increasing the life span of EAC bearing mice and also revive the altered hematological (Hb, total RBC and WBC) parameters compare to those with normal values. Fluorescence microscopic view of 4,6-diamino-2-phenylindole (DAPI) staining demonstrated that leaf induced the alterations (i.e., nuclear condensation, fragmentation, membrane blabbing and apoptosis of cells) in the morphology of EAC cells. And, the quantitative analysis of p53 mRNA level by RT-PCR showed that p53 gene expression in leaf treated EAC cell was upregulated in respect to untreated control. These findings indicate that the induction of apoptosis in leaf-treated EAC cell was probably mediated through p53-dependent pathway. From this study, it can be concluded that the leaf of Averrhoa carambola exhibited potent antineoplastic and apoptotic activities that might be a potential agent for prevention of cancer in mice.
Citation Format: Md. Zahid Hasan, Ayesha Siddika. Effect of Averrhoa carambola extract on the antineoplastic and apoptotic activities in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1925.
Abstract 1927: Cancer cells induce apoptosis in hepatocytes as one of the mechanisms to displace hepatocytes in vessel co-opted colorectal cancer liver metastases
Authors: Rada Miran , Tsamchoe Migmar , Kapelanski-Lamoureux Audrey , Bloom Jessica , Petrillo Stephanie , Tabariès Sébastien , Kim Diane H. , Younan Peter , Gregorieff Alex , Siegel Peter , Lazaris Anthoula , Metrakos Peter 
Published: July 2021

Abstract
Vessel co-option in colorectal cancer liver metastases (CRCLM) has been recognized as one of the mechanistic pathways of resistance against anti-angiogenic therapy. The cancer cells are highly motile in co-opted lesions, which move toward and along the pre-existing sinusoidal vessels and hijack them to gain access to nutrient. The movement of cancer cells is accompanied by displacement of the hepatocytes. However, the molecular mechanisms underlying this displacement are unclear yet. To examine whether apoptosis involved in hepatocytes displacement by cancer cells in co-opted lesions, we performed immunohistochemical staining for pro-apoptotic markers, such as cleaved caspase-3 and cleaved PARP-1. We observed overexpression of pro-apoptotic markers in liver parenchyma of co-opted lesions compared to angiogenic lesions, specifically the hepatocytes that are in close proximity to the cancer cells. In vitro, we found that culturing hepatocytes with either colorectal cancer cells or conditioned media of co-opted CRCLM organoids induces apoptosis. Importantly, our results also suggested proprotein convertase subtilisin/kexin type 9 (PCSK-9 or PC-9) as a potential mediator of cancer cells-driven hepatocytes apoptosis. Altogether, these results confirm that cancer cells exploit apoptosis to establish vessel co-option in CRCLM.
Citation Format: Miran Rada, Migmar Tsamchoe, Audrey Kapelanski-Lamoureux, Jessica Bloom, Stephanie Petrillo, Sébastien Tabariès, Diane H. Kim, Peter Younan, Alex Gregorieff, Peter Siegel, Anthoula Lazaris, Peter Metrakos. Cancer cells induce apoptosis in hepatocytes as one of the mechanisms to displace hepatocytes in vessel co-opted colorectal cancer liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1927.
Abstract 1933: Improved DAMP assays for the in vitro assessment of immunogenic cell death
Authors: Niles Andrew L. , Kupcho Kevin R. , Lazar Dan F. , Cali James J. 
Published: July 2021

Abstract
The extracellular levels of damage-associated molecular patterns (DAMPs) released during immunogenic cell death (ICD) are positively correlated with the magnitude and efficacy of the resulting in vivo immune response. Therefore, extracellular ATP (eATP) and high mobility group box 1 (HMGB1) have been identified as key biomarkers for their predictive capacity during in vitro ICD screening activities. Current methods for identifying eATP and HMGB1 inducers are laborious, costly, and hampered by poor throughput. To overcome these challenges, we developed easy-to-use, homogeneous, bioluminescent assays that measure dose-dependent release of these immunostimulatory agents directly in cell culture. The eATP assay utilizes an optimized ATP detection chemistry that can be employed directly to assess live-cell kinetic responses for up to 24 h, with even longer exposures supported by a staggered reagent addition approach. The HMGB1 assay measures the protein's concentration at exposure endpoint in the same sample well using complementary luciferase fragment-labelled monoclonal antibodies. We tested the utility of the assays using U20S, Jurkat and U937 cells dosed with serial dilutions of known ICD inducers (doxorubicin, idarubicin, mitoxantrone, and bortezomib). The resulting data suggest the potency of eATP and HMGB1 release is dependent upon cell model and agent but can be reproducibly and robustly measured in 96 and 384 well environments. Further, the eATP assay produced remarkable early dose-dependent response resolution whereas the HMGB1 data provided a confirmatory post-mortem ICD parameter. This new ICD biomarker detection workflow may help to efficiently define and rank-order the capacity of new chemical entities to induce apoptosis and immunogenic cell death.
Citation Format: Andrew L. Niles, Kevin R. Kupcho, Dan F. Lazar, James J. Cali. Improved DAMP assays for the in vitro assessment of immunogenic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1933.
Abstract 1940: Autophagy mediates leptin induced migration and erk activation in breast cancer cells
Authors: Miranda Alin García , Alcalá Karen A. Solano , Alvarado José B. Montes , Leyva Julio Reyes , Maycotte Paola , Saucedo Eduardo Castañeda 
Published: July 2021

Abstract
Autophagy is an intracellular recycling process active in eukaryotic cells which involves the formation of an autophagosome that delivers cytoplasmic components to the lysosome for degradation. This process occurs at low rates under basal conditions, but it can be induced by diverse stress conditions such as starvation, hypoxia or metabolic disorders. Autophagic flux can also be enhanced in response to hormones, including leptin. Leptin is considered a pro-tumorigenic protein whose circulating levels have been related to a bad prognosis in obese breast cancer patients. It has been recently demonstrated that leptin can induce autophagy in cancer cell lines from different tissues, suggesting that autophagy could modulate the pro-tumorigenic effects associated with leptin. In this study, the role of autophagy in leptin-induced proliferation, migration, apoptosis and ERK phosphorylation in breast cancer cell lines was evaluated.
Methods: MCF7 estrogen receptor positive and MDA-MB-231 triple negative breast cancer cell lines were used. MCF7 and MDA-MB-231 cell lines were stimulated with 400 and 50 ng/ml of leptin, respectively. Autophagy was assessed by LC3-II and p62 protein levels by western blot, and autophagosome formation by fluorescence microscopy. Proliferation and migration were assessed by real-time microscopy in an IncuCyte analyzer; and cell death was evaluated by fluorescence analysis of caspase activity. Changes in ERK phosphorylation were measure by western blot.
Results: Leptin increased autophagy in MCF7 cells but not in triple negative MDA-MB-231 cells. In MCF7 cells, autophagy inhibition reduced leptin-induced cell proliferation, changes associated to a mesenchymal morphology, cell migration, and ERK activation. In MDA-MB-231 cells, autophagy inhibition reduced proliferation and increased apoptosis independently of leptin treatment. In both cell lines, leptin-induced migration and ERK phosphorylation were reduced by the inhibition of autophagy.
Conclusion: Autophagy was important for increased cancer cell migration induced by leptin and for the maintenance of ERK phosphorylation. Our data suggest a potential use for the inhibition of autophagy in breast cancer associated with obesity.
Citation Format: Alin García Miranda, Karen A. Solano Alcalá, José B. Montes Alvarado, Julio Reyes Leyva, Paola Maycotte, Eduardo Castañeda Saucedo. Autophagy mediates leptin induced migration and erk activation in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1940.
Abstract 1941: The regulation of ATG9A-mediated autophagy by an ULK1-independent ATG13 complex
Authors: Poole Daniel , Kananngara Ashari , Weerasekara Vajira , McEwan Colten , Thornock Alexandra , Lazaro Misael , Youngs Joshua , Andersen Joshua 
Published: July 2021

Abstract
Cancer cells rely on autophagy for survival during periods of nutrient stress or chemotherapy. The activation of autophagy in cancer is thought to be regulated by AMPK-dependent activation of the ULK1 complex, consisting of FIP200, ATG13, ATG101, and ULK1. However, the regulation and dynamic cooperation of these proteins to govern autophagy is not completely understood. Our preliminary data suggest that ATG13 and ATG101 exist in an ULK1-independent complex that plays a key role in the regulation of autophagy. In an effort to identify the function of this ULK1-independent ATG13 complex, we discovered that an ULK1 binding-deficient mutant of ATG13 interacts with ATG9A, an apical regulator of autophagy. Using a split-venus approach coupled with confocal imaging, we found that ATG13, ATG101 and ATG9A interact together at sites of autophagosome assembly. This interaction between ATG13 and ATG9A is unaffected by deletion of ULK1 or the canonical ULK1 complex protein, FIP200. Furthermore, we found that CRISPR/Cas9-mediated deletion of ATG13 led to an aberrant accumulation of ATG9A puncta that colocalize with p62/SQSTM1. Importantly, this accumulation of ATG9A in ATG13 KO cells was rescued by expression of the ULK1 binding-deficient mutant of ATG13. Taken together, these data suggest that ATG9A interacts with ATG13 and ULK1 separately, and that ATG101 is part of an ULK1-independent ATG13 complex that controls the trafficking of ATG9A to p62 puncta. We are currently developing approaches to selectively isolate, identify, and characterize additional interacting partners of the ULK1-independent ATG13-ATG101 complex, which will give us new insight into the regulation and broader function of this complex in autophagy.
Citation Format: Daniel Poole, Ashari Kananngara, Vajira Weerasekara, Colten McEwan, Alexandra Thornock, Misael Lazaro, Joshua Youngs, Joshua Andersen. The regulation of ATG9A-mediated autophagy by an ULK1-independent ATG13 complex [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1941.