bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3136: Comprehensive profiling the immune-status of a broad range of in vivo syngeneic models
Authors: Huang Jingqi , Hu Shipzong , Li Wentao 
Published: August 2018

Abstract
Latterly with approval of PD-1, PD-L1 antibodies in clinical oncology, immunotherapy has gain recognition for cancer treatment for changing the way by joining chemotherapy, radiation and surgery. This type of cancer treatment aims to produce greater effectiveness with less toxicity than cancer chemotherapy and mainly acts by boosting the body's natural defenses to fight the cancer. It uses substances made by the body or laboratory agent to improve or restore the function of immune system. Therefore, understood the nature immune status and micro environment of in vivo tumor models is very important to assist exploring immunotherapy. As a results, nearly 40 tumor cell lines over a broad range of tumor type as well as corresponding in vivo syngeneic models were intensively studied on its immune status under two conditions when tumor volume were 100 mm3 and 500 to 600mm3 . The effort has been focus on the immune status including T cell status and levels of immune-suppression via FACS analysis of the population of CD4+, CD8+, Treg, MDSC, macrophage and DC cells. Furthermore, not only population of immune cells but also the expressions of immune related gene were analyzed by RE-PCR which are the genes related regulatory of T cells i.e., CD4, Foxp3, GITR; gene of tumor associated macrophage CSF1R, CD68, CX3CR1, ITGAM, CD163, MARC1; gene of co-stimulator receptors of T cells ICOS, CD137(Tnfrsf9), OX40(Tnfrsf4); co-inhibitory receptors of T cell BTLA, HAVCR2, CTLA4, LAG3, CD28, PDCD1; and gene of co-inhibitory ligands of tumor cells CD274, CD137L(Tnfsf9), PDCD1LG2, HVEM(Tnfsf14), OX40L(Tnfsf4). The profiling data illustrated, indeed, the expression of PD-L1 is different on different tumor cells; the immune status certainly pending on the tumor type but also related to the tumor progression. The bigger tumor size the higher level of expression of immune suppression which deterring the immune cell ability to conquer cancer. We believe that this profiling data will help many scientists to properly select correct model to support R&D and to better understand how immune therapeutically agent acts in the immune system. With this comprehensive research data, we're now at a point where this information has started to become translated into treatment possibilities for cancer patients.
Citation Format: Jingqi Huang, Shipzong Hu, Wentao Li. Comprehensive profiling the immune-status of a broad range of in vivo syngeneic 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 3136.
Abstract 3148: p140Cap affects breast cancer features through the regulation of the tumor microenvironment composition
Authors: Salemme Vincenzo 
Published: August 2018

Abstract
Increasing data indicate the key role of the tumor microenvironment in cancer progression, metastasis formation and treatment sensitivity, where the tumor stroma and the immune infiltrate strongly influence tumor features. Our recent studies indicate that the adaptor protein p140Cap is highly expressed in about 50% of ERBB2-amplified breast cancer patients. Its expression correlates with increased patient survival and decreased probability to develop metastasis. Causally, p140Cap negatively regulates breast tumor properties both in vitro and in the NeuT preclinical mouse model. In this study, we observed an indirect influence of p140Cap-expression on tumor immune infiltrate composition of a syngeneic ERBB2+ breast cancer model. p140Cap tumor cells and tumors show reduced level of G-CSF mRNA and protein. Accordingly, we observed a reduced mobilization of G-CSF-dependent myeloid-derived suppressor cells (MDSCs- CD11b+Ly6G+Ly6Clo) from bone marrow and a decreased level of MDSCs in tumor, blood and spleen of mice orthotopically injected with p140Cap tumor cells, compared to controls. This “less” immune suppressive microenvironment associated to p140Cap-expression, was also confirmed by an increase in CD8+, M1 macrophages and Natural Killer lymphocytes concomitant with a decrease in M2 macrophages and FoxP3 regulatory T cells. Interestingly, the expression of p140Cap in cells and tumors significantly reduce the fraction of cancer stem cells and their sphere and tumor initiation frequency, by modulating their proliferative potential. Since that the tumor initiating cell exhibit an enhanced G-CSF production, these data suggest that p140Cap, by regulating the cancer stem cell compartment, limits ERBB2 tumor aggressiveness by creating a tumor microenvironment less favorable to tumor progression.
Citation Format: Vincenzo Salemme. p140Cap affects breast cancer features through the regulation of the tumor microenvironment composition [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 3148.
Abstract 3150: Serglycin promotes cell migration mediated through the interaction of its GAG moiety with CD44
Authors: Chen Joanne Jeou-Yuan , Guo Jing-You , Chiu Chu-Hsuan , Wang Mei-June 
Published: August 2018

Abstract
Tumor microenvironment (TME) plays an important role in cancer progression. We have recently shown that serglycin (SRGN), a chondroitin sulfate proteoglycan (CSPG), is overexpressed in primary non-small cell lung cancers (NSCLCs), by carcinoma as well as stromal cells, and that the secreted SRGN can bind to CD44 and promotes NSCLC aggressiveness (Oncogene 36:2457, 2007). In this study, we further examined the molecular mechanisms underlying SRGN-elicited cell migration. By gain- and loss-of-function studies, we first showed that SRGN promoted cell migration in a CD44-dependent manner. SRGN promoted SRC activation, leading to increased phosphorylation of paxillin (PAX) at Y118 as well as reduced PAX/FAK complex formation, suggesting that SRGN promotes cell migration through facilitating focal adhesion turnover. In support, knockdown of SRC or treatment of cells with PP2, a SRC family inhibitor, abolished SRGN-elicited migratory activity. In addition, we showed that SRGN induced actin cytoskeleton reorganization and promoted lamellipodia and filopodia formation at the leading edge, facilitating a directional movement during wound closure in NSCLC cells. In consistence, increased levels of activated RAC1, which is required for lamellipodia formation, and CDC42, which is required for filopodia formation, were detected. We further examined the role of CS modification in SRGN-mediated function. We generated the SRGN(S/A) mutant in which the eight serine residues involved in GAG modification were converted to alanine, and showed that SRGN(S/A) mutant not only failed to induce the phosphorylation of SRC and paxillin, but also failed to promote cell migration. In consistence, pre-treatment of SRGN-containing conditional medium with Chondroitinase ABC also suppressed SRGN-elicited cell migration. Taken together, our data demonstrated that SRGN interacts with CD44 through its GAG modifications, leading to increased cell migration by promoting FA turnover and cytoskeleton reorganization.
Citation Format: Joanne Jeou-Yuan Chen, Jing-You Guo, Chu-Hsuan Chiu, Mei-June Wang. Serglycin promotes cell migration mediated through the interaction of its GAG moiety with CD44 [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 3150.
Abstract 3155: Loss of YAP1 dysregulates RhoA signaling and promotes cell invasion
Authors: Hendrick Natalie M. , Iwanicki Marcin P. , Li Carman Man-Chung , Bui Duyen Amy , Selfors Laura M. , Brugge Joan S. 
Published: August 2018

Abstract
While Hippo pathway signaling undoubtedly plays an important role in cancer, the role of its effector YAP1 as an oncogene or tumor suppressor is context dependent. The precise conditions that support the tumor-promoting or tumor-suppressing roles of YAP1 remain largely undefined. While YAP1 can drive oncogenic programs through its nuclear function as a transcriptional coactivator of TEAD and other transcription factors, previous findings from our lab and others suggest that loss of YAP1 function can also have tumor promoting consequences. One well-characterized role of YAP1 is that of a nuclear relay of signals triggered by mechanical forces that lead to activation of Rho GTPases. Our new studies using a combination of genetic, biochemical, and microscopy techniques provide evidence that YAP1 is not only activated by Rho, but can also regulate Rho activation and the actin cytoskeleton. Knockdown of YAP1 in MCF10A immortalized mammary epithelial cells resulted in increased lamellipodia formation in culture as seen by time-lapse microscopy, and increased protrusive, invasive activity in 3D Matrigel culture. YAP1 knockdown also induced a scattering phenotype, characterized by cell dissociation from the leading edge of a wounded monolayer. While E-cadherin protein levels were unaffected by YAP1 knockdown, adherens junction maturation at cell-cell junctions was compromised. These morphological alterations were associated with decreased levels of active RhoA, as well as a decrease in downstream myosin light chain phosphorylation. Our results indicate loss of YAP1 decreases active RhoA, leading to reduced cell-cell adhesion and increased protrusive cellular behavior. Our findings raise the possibility that YAP1 is not only a Rho-sensor, but also mediates a feedforward regulatory loop to maintain Rho-regulated cytoskeletal structures, and that loss of YAP1 through genetic deletion in tumor cells could promote invasive behavior.
Citation Format: Natalie M. Hendrick, Marcin P. Iwanicki, Carman Man-Chung Li, Duyen Amy Bui, Laura M. Selfors, Joan S. Brugge. Loss of YAP1 dysregulates RhoA signaling and promotes cell invasion [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 3155.
Abstract 3160: The actin-binding protein Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization
Authors: Wang Xiaoze , Enomoto Atsushi , Weng Liang , Haga Hisashi , Ishida Sumire , Takahashi Masahide 
Published: August 2018

Abstract
Pathological observations show that cancer cells frequently invade the surrounding stroma in collective groups rather than through single cell migration. The identification of genes and proteins that are specifically involved in the collective behavior of cancer cells has thus far been limited. Here, we studied the role of the actin-binding protein Girdin in collective cancer cell migration. This protein is a specific regulator of collective migration of neuroblasts born in the subventricular zone of the postnatal and adult brains and participates in the progression of cancer. We found that Girdin was essential for the collective migration of the skin cancer cell line A431 on collagen gels as well as their fibroblast-led collective invasion in an organotypic culture model. We provide evidence that Girdin binds to β-catenin that plays important roles in the Wnt signaling pathway and in E-cadherin-mediated cell-cell adhesion. Girdin-depleted cells displayed scattering and impaired E-cadherin-specific cell-cell adhesion. Importantly, Girdin depletion led to impaired cytoskeletal association of the β-catenin complex, which was accompanied by changes in the supracellular actin cytoskeletal organization of cancer cell cohorts on collagen gels. Although the underlying mechanism is unclear, this observation is consistent with the established role of the actin cytoskeletal system and cell-cell adhesion in the collective behavior of cells.
Citation Format: Xiaoze Wang, Atsushi Enomoto, Liang Weng, Hisashi Haga, Sumire Ishida, Masahide Takahashi. The actin-binding protein Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization [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 3160.
Abstract 3161: The macrolide toxin mycalolide B disrupts actin-driven invasion and metastasis of HER2-positive cancers
Authors: Nersesian Sarah , Williams Rodette , Evans Dr. Andrew , Allingham Dr. John , Craig Dr. Andrew 
Published: August 2018

Abstract
HER2 is a driver and clinical target in cancers afflicting women. HER2-positive (HER2+) cancers have high rates of metastasis and lower overall survival rates compared to other cancer subtypes. The goal of this study is to test the vulnerability of HER2+ cancer cells and tumors to disruption of their actin cytoskeleton using the marine macrolide toxin mycalolide B (Myc B), as these cells are highly dependent on rapid actin polymerization and remodeling for migration and invasion into new sites of tumor growth. The effects of Myc B treatment on HER2+ breast (HCC1954) and ovarian (SKOV3) cancer cell lines were profiled in assays of cell viability, motility, and invasion. Treatments of Myc B alone or in combination with Trastuzumab were also performed in HER2+ tumor xenograft assays. Myc B showed potent growth suppressive and cytotoxic effects on HER2+ cancer cells at doses in the 70-100 nM range. At sub-lethal doses, Myc B caused a rapid loss of leading edge protrusions, and sustained defects in HER2+ cancer cell motility and invasion. HER2 internalization and killing of HER2+ cancer cells by Trastuzumab-emtansine was not compromised with Myc B treatment. In a HER2+ tumor xenograft model, Myc B treatment alone, or in combination with Trastuzumab, led to significant reductions in tumor growth and metastasis. Together, these findings identify a major vulnerability in metastasis-initiating HER2+ cancer cells to the actin toxin Myc B, and provide a rationale to exploit this vulnerability with the development of new therapeutics targeting actin.
Citation Format: Sarah Nersesian, Rodette Williams, Dr. Andrew Evans, Dr. John Allingham, Dr. Andrew Craig. The macrolide toxin mycalolide B disrupts actin-driven invasion and metastasis of HER2-positive cancers [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 3161.
Abstract 3171: Vangl2 regulates cancer stem cell self-renewal and growth in rhabdomyosarcoma
Authors: Hayes Madeline , McCarthy Karin , Jin Alexander , Iyer Sowmya , Garcia Sara , Oliveira Mariana L. , Sindiri Sivasish , Gryder Berkley , Motala Zainab , Nielsen G Petur , Borg Jean-Paul , Rijn Matt van de , Malkin David , Khan Javed , Ignatius Myron , Langenau David M. 
Published: August 2018

Abstract
Growth and relapse are driven by cancer stem cells (CSCs) in a subset of tumors, yet mechanisms driving cancer cell fate choices, maintenance and self-renewal are not fully understood. Here, we show that Van Gogh-like 2 (Vangl2), a core regulator of the non-canonical Wnt/planar cell polarity pathway (Wnt/PCP), regulates CSCs self-renewal in human rhabdomyosarcoma (RMS) – a common pediatric cancer of muscle. Wnt/PCP signaling is essential during development and recent work has linked this pathway to cancer growth, invasion and metastasis. However, roles for Vangl2 in regulating tumor self-renewal have not been previously described. Here, we show that VANGL2 is expressed in a majority of human RMS, specifically within early mononuclear progenitor-like cells. VANGL2 depletion inhibited proliferation, reduced self-renewal, and induced differentiation of human RMS. VANGL2 was also required for continued tumor growth and maintenance following engraftment of human RMS using mouse xenografts. Using a zebrafish model of embryonal rhabdomyosarcoma (ERMS) and limiting dilution cell transplantation approaches, we identified that Vangl2 expression enriches for CSCs in vivo and when transgenically expressed, at high levels elevates cancer stem cell number by 9-fold. Mechanistic studies revealed a role for RhoA downstream of Vangl2 in regulating maintenance of stem cell programs in human RMS. Our studies offer novel opportunities to isolate and characterize RMS cancer stem cells in vivo, and identify potential therapeutic targets for patient treatment.
Citation Format: Madeline Hayes, Karin McCarthy, Alexander Jin, Sowmya Iyer, Sara Garcia, Mariana L. Oliveira, Sivasish Sindiri, Berkley Gryder, Zainab Motala, G Petur Nielsen, Jean-Paul Borg, Matt van de Rijn, David Malkin, Javed Khan, Myron Ignatius, David M. Langenau. Vangl2 regulates cancer stem cell self-renewal and growth in rhabdomyosarcoma [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 3171.
Abstract 3197: Beta-Apopicropodophyllin, a derivative of podophyllotoxin, has a function as anticancer drug and radiosenstizer against non-small cell lung cancer cells
Authors: Kim Ju Yeon , Cho Jeong Hyun , Hwang Sang-Gu , Song Jie-Young , Lee EunAh , Um Hong-Duck , Park Jong Kuk 
Published: August 2018

Abstract
We have synthesized new 32 derivatives of podophyllotoxin and screened candidate showed anti-cancer effect. Among these derivatives, we found beta-Apopicropodophyllin (APP) is candidate derivative inducing cell death against non-small cell lung cancer (NSCLC) cell lines: A549, NCI-1299 and NCI-460 (IC50 values =16.9, 13.1 and 17.1 nM, respectively). We also analyzed MOA (mode of action) of APP and found APP induced cell death via various mechanisms. Firstly, APP inhibits the polymerization of microtubule and induces G2/M phase arrest as well as DNA damage. APP treatment induces expressions of mitosis-related proteins, phospho-ATM, γ-H2AX and p21. Next, the intrinsic and extrinsic apoptotic pathways by APP are activated as shown in the activations of caspase-3, -8 and -9. APP also induces pro-apoptotic ER stress signaling pathway as indicated by elevated expression levels of BiP, phospo-eIF2α, CHOP and ATF4. Additionally, APP also showed radiosensitizer function. Combination of APP and gamma-ionizing radiation (IR) enhanced apoptotic cell death of NSCLC cell via amplification of ER stress. Taken together, these results implied APP might be a potent anti-cancer drug candidate inducing microtubule disruption, DNA damage, cell cycle arrest and ER stress.
Citation Format: Ju Yeon Kim, Jeong Hyun Cho, Sang-Gu Hwang, Jie-Young Song, EunAh Lee, Hong-Duck Um, Jong Kuk Park. Beta-Apopicropodophyllin, a derivative of podophyllotoxin, has a function as anticancer drug and radiosenstizer against non-small cell lung 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 3197.
Abstract 3201: A theranostic approach using photodynamic therapy to efficiently kill neuroblastoma cancer cells through induction of apoptosis
Authors: Davids Lester M. , Schwar Anja , Lang Dirk 
Published: August 2018

Abstract
Neuroblastoma is an extra-cranial tumour of childhood and arises from the sympatho-adrenal lineage of the neural crest tissue. Despite advances in treatment strategies, significant complications in curing this cancer remain. Furthermore, severe consequential effects on patient health have been associated with chemotherapy and/or radiation. Photodynamic therapy (PDT) with the photosensitiser hypericin (HYP) presents an attractive and efficient adjunctive therapy alternative for this aggressive cancer. HYP, an extract from Hypericum perforatum (St John's Wort) species, has a high quantum yield following photo-activation and a low dark toxicity and genotoxiciy. This study tests the anti-cancer efficacy of HYP-PDT in SK-N-SH neuroblastoma cells using an in vitro tissue culture model. Results show through detailed uptake kinetics that HYP is absorbed effectively by SK-N-SH cells after 6 hours of incubation and live fluorescent confocal microscopy revealed primary localisation of HYP to lysosomes and mitochondria. Through cell viability assays it was determined that 2, 3 and 4μM HYP-PDT resulted in 45.6±5.1% cell death within 24 hours of treatment. Additionally, 24 hours post 0.25μM and 2μM HYP-PDT, we observed distinct morphological changes in SK-N-SH cells using phase contrast microscopy, and determined a high apoptotic mode of cell death using Fluorescent Activated Cell Sorting (FACS). These results demonstrate that HYP-PDT is effective in killing neuroblastoma cells and that the mode of cell death is apoptotic in nature. This study is ongoing with further investigation into the signalling underlying this photo-toxicity with particular emphasis on cell death resistance mechanisms in neuroblastoma cells.
Citation Format: Lester M. Davids, Anja Schwar, Dirk Lang. A theranostic approach using photodynamic therapy to efficiently kill neuroblastoma cancer cells through induction of apoptosis [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 3201.
Abstract 3207: CXCR4 endows radioresistance in non-small cell lung cancer cells through STAT3-mediated Slug expression
Authors: Lee Dae-Hee , Kim Jeong-Yub , Kim Hee-Jin , Park Myung-Jin 
Published: August 2018

Abstract
Lung Cancer is one of the most common causes of cancer-related mortality worldwide, despite of significant advance of treatment strategies including chemotherapy and radiotherapy. Although chemotherapy is the first choice for treatment of non-small cell lung cancer cells (NSCLCs) except surgery, radiotherapy is primary treatment modality for patients with unresectable NSCLC on its own or with another treatment like chemotherapy. CXCR4 is chemokine (C-X-C motif) receptor 4 whose ligand is Stromal-derived-factor-1 (SDF1a), so-called CXCL12. According to the current reports, CXCR4 is widely expressed by malignant tumor and crucial for tumor growth, vascularization, metastasis, cell migration and related to poor prognosis. Here, we show that CXCR4 signaling confers resistance to ionizing radiation (IR) in NSCLCs. Drug-resistant A549/GR cells with enhanced CXCR4 expression exhibited high colony forming ability after IR compared with A549 cells. Transfection of siRNA against CXCR4 or treatment of pharmacological inhibitor (AMD3100) sensitized these cells to IR. Reversely, overexpression of CXCR4 in A549 and H460 enhanced clonogenic survival after IR. IR stimulated CXCR4 expression and CXCR4-mediated STAT3 phosphorylation in NSCLCs. Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the colony forming ability, indicating that CXCR4-mediated STAT3 signaling is important for IR resistance in NSCLC cells. CXCR4/STAT3 signaling upregulated the expression of Slug and down-regulation of Slug with siRNA increased IR sensitivity in NSCLCs. Taken together, our data suggest that CXCR4/STAT3/Slug axis is crucial for IR resistance of NSCLCs and is able to be considered as a therapeutic target for enhancing IR sensitivity of this devastating cancer.
Citation Format: Dae-Hee Lee, Jeong-Yub Kim, Hee-Jin Kim, Myung-Jin Park. CXCR4 endows radioresistance in non-small cell lung cancer cells through STAT3-mediated Slug expression [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 3207.