bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1161: Interaction between doxorubicin and amniotic membrane stem cells on the canine inflammatory mammary cancer cell line IPC-366
Authors: Borghesi Jessica , Caceres Sara , Mario Lara C. , Hayashi Rafael Gonçalves , Peña Laura , Alonso-Diez Angela , Illera Maria J. , Silvan Gema , Miglino Maria A. , Carreira Ana C. Oliveira , Favaron Phelipe Oliveira , Illera Juan C. 
Published: August 2018

Abstract
The aim of this study was to evaluate the efficiency of doxorubicin, canine amniotic membrane stem cells (AMC) and the association between them in the triple-negative canine inflammatory mammary cancer cell line IPC-366. Experiments were carried out for 72 hours in 4 groups: IPC-366 untreated cells; cells treated with 10mg/mL of doxorubicin; coculture IPC-366 cells with 105 AMC; and cells treated with doxorubicin+AMC. MTT assays were performed for evaluating proliferation; flow cytometry to analyze hormonal and angiogenesis markers, and anti-inflammatory cytokines; and EIA techniques were used to evaluate secretion of steroid hormones (progesterone (P4); dehydroepiandrosterone (DHEA); androtenedione (A4); 17β-estradiol (E2); estrone sulphate (SO4E1)) in cell culture media. Results showed that cells treated with 10 mg/mL of doxorubicin resulted in a reduction of 71.64% on cell proliferation at 72h of treatment. A reduction in the expression of VEGF and PCNA-3 was observed by flow cyotmetry in treated cells compared to control cells. Differences on IL-10 were found within groups: treatment with doxorubicin resulted in a reduction on IL-10 expression although in AMC group expression remained similar to control group. Estrogen intracellular levels were significantly increased in doxorubicin+AMC group (4.67% vs. 27.1%). Regarding steroid hormone secretion, in AMC treated group any differences in hormone levels were found compared to control group. P4 and E2 secretion resulted in an increase in doxorubicin-treated group although in doxorubicin+AMC group these levels decreased with respect to control group. DHEA secretion was significantly decreased in treated groups compared to control group. Interestingly, A4 and SO4E1 secretion levels showed a significant increase compared to control group. Collectively, these results suggest that combination of doxorubicin and AMC caused a synergy that alters the cancer cell's secretion hormone profile by accumulation of estrogens. These findings attempt to give an approach of the combination of well-known treatments and amniotic stem cells as a canine mammary tumors therapy.
Citation Format: Jessica Borghesi, Sara Caceres, Lara C. Mario, Rafael Gonçalves Hayashi, Laura Peña, Angela Alonso-Diez, Maria J. Illera, Gema Silvan, Maria A. Miglino, Ana C. Oliveira Carreira, Phelipe Oliveira Favaron, Juan C. Illera. Interaction between doxorubicin and amniotic membrane stem cells on the canine inflammatory mammary cancer cell line IPC-366 [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 1161.
Abstract 1163: Chemoprevention of testosterone-induced benign prostatic hyperplasia by hexane fraction from seeds of Annona muricata (soursop) in rats
Authors: Adaramoye Oluwatosin A. , Oladipo Taiwo D. , Akanni Olubukola O. , Owumi Solomon O. , Abiola Olusoji J. 
Published: August 2018

Abstract
Alternative medicine is an extensively recognized therapeutic approach for the management of several diseases. Annona muricata commonly called sour sop is traditionally used to manage an array of human diseases, especially cancer. In this study, we hypothesized that hexane fraction from seeds of Annona muricata (HFAM) will ameliorate testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) in rat model. Castration was performed via the scrotal route under ketamine anesthesia and BPH was induced through daily intraperitoneal injection of TP (3 mg/kg) for 4 weeks after castration. Rats were assigned into six groups of six animals each viz: non-castrated control, castrated control, castrated rats that received TP (BPH group), BPH + HFAM, BPH + HFAM + finasteride, BPH + finasteride. Results showed that BPH rats had 3.1 and 2.4 folds increase in prostatic and organo-somatic weight, respectively. Furthermore, BPH increased the activities of total acid and alkaline phosphatases by 62% and 53%, respectively, and levels of lipid peroxidation products by 48% in the prostate of rats. Also, BPH caused significant increase in the levels of inflammatory markers (Myeloperoxidase and total nitric oxide) in rats. In contrast, there were no significant differences in the activities of prostatic antioxidant enzymes in BPH group relative to others. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, Bcl2, beta-catenin, androgen and estrogen receptors proteins, while mild expression of p53 and Bax were observed. Interestingly, treatment of BPH rats with HFAM or HFAM + finasteride significantly attenuated inflammatory indices and induced apoptotic parameters. Overall, hexane fraction from seeds of Annona muricata may be used as a therapeutic agent for BPH via anti-inflammatory effect.
Citation Format: Oluwatosin A. Adaramoye, Taiwo D. Oladipo, Olubukola O. Akanni, Solomon O. Owumi, Olusoji J. Abiola. Chemoprevention of testosterone-induced benign prostatic hyperplasia by hexane fraction from seeds of Annona muricata (soursop) in rats [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 1163.
Abstract 1166: Identification of predictive markers for clinical efficacy of triple-negative breast cancer chemotherapy
Authors: Yun Jihui , Hur Saem , Kang Wonyoung , Na Deukchae , Chae Jeesoo , Kang Jinjoo , Kim Ju-Hee , Lee Jiwoo , Heo Woohang , Han Wonshik , Lee Charles , Noh Dong-Young , Moon Hyeong-Gon , Kim Jong-Il 
Published: August 2018

Abstract
Triple Negative Breast Cancer (TNBC) is uncommon type of invasive breast cancer accounting for about 10~20% of all breast cancers. TNBC is characterized by a lack of expression of estrogen receptors (ER), human epidermal growth factor receptor 2 (HER2) and progesterone receptors (PR). Due to this characteristic, common treatments including hormone therapy and drugs targeting these receptors are not effective against TNBC despite more aggressive clinical behavior when compared to other subtypes. Paclitaxel is one of the well-known chemotherapeutic agents used in treatment for patients with breast cancer. However, previous studies have reported that advanced breast cancer treated with paclitaxel often develop resistance to the paclitaxel. To understand molecular characteristics and mechanism associated with molecular adaption in cancer cell when treated with paclitaxel, we performed next generation sequencing (NGS) and in vivo experiment using patient derived xenograft (PDX) models. We established ten PDX models from two cases with TNBC each. Mice were divided into two group consisting of control (n=5) and paclitaxel treatment (n=5). We performed exome and transcriptome sequencing on three of five samples for each group. We didn't find significant differences between control and paclitaxel treatment groups in exome data. In transcriptome data, We identified 14 differentially expressed genes (DEGs) including members of CXCL gene family between control and paclitaxel treatment groups. Among these DEGs, 13 DEGs were up-regulated in paclitaxel treatment groups when compared to control group. We are conducting in vitro experiment for several genes among these 13 DEGs. Furthermore, we will perform transcriptome sequencing on PDX tumor samples of additional cases with TNBC for validation of the results so far achieved.
Citation Format: Jihui Yun, Saem Hur, Wonyoung Kang, Deukchae Na, Jeesoo Chae, Jinjoo Kang, Ju-Hee Kim, Jiwoo Lee, Woohang Heo, Wonshik Han, Charles Lee, Dong-Young Noh, Hyeong-Gon Moon, Jong-Il Kim. Identification of predictive markers for clinical efficacy of triple-negative breast cancer chemotherapy [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 1166.
Abstract 1169: Novel renal medullary carcinoma cell lines, UOK353 and UOK360, provide preclinical tools to identify new therapeutics
Authors: Wei Darmood , Yang Youfeng , Ricketts Christopher J. , Vocke Cathy D. , Ball Mark W. , Sourbier Carole , Wangsa Darawalee , Wangsa Danny , Guha Rajarshi , Zhang Xiaohu , Meltzer Paul , Reid Thomas , Thomas Craig J. , Merino Maria J. , Linehan W. Marston 
Published: August 2018

Abstract
Renal medullary carcinoma (RMC) is a rare and aggressive disease that predominantly afflicts individuals of African or Mediterranean descent with sickle cell trait. RMC comprises 1% of all renal cell carcinoma diagnoses, and the median overall survival for RMC patients is only 13 months. Patients are typically young (median age-22yo) and male (male:female ratio of 2:1). RMC was first characterized in 1995, and its hallmark SMARCB1 loss was identified in 2008. Due to the low incidence of RMC and the disease's aggressiveness, treatment decisions are often based on case reports. Thus, it is critical to develop preclinical models of RMC to both better understand the pathogenesis of this disease and identify an effective therapy. These RMC cell lines overexpress EZH2, relative to normal renal proximal tubule epithelium, thus making it an attractive druggable target. EZH2 inhibition in RMC tumor spheroids did not result in decreased viability. We have evaluated a potential clinical treatment (bortezomib) found in the literature and validate bortezomib's potency in vitro. Intriguingly, these cells lines not only lack NQO1, an antioxidant enzyme, but also the addition of N-acetyl cysteine, an antioxidant, has a protective effect against bortezomib. Together the data suggest that RMC are highly sensitive to oxidative stress. This evidence is consistent with case reports in the literature that found bortezomib treatment of RMC resulted in positive outcomes.
Citation Format: Darmood Wei, Youfeng Yang, Christopher J. Ricketts, Cathy D. Vocke, Mark W. Ball, Carole Sourbier, Darawalee Wangsa, Danny Wangsa, Rajarshi Guha, Xiaohu Zhang, Paul Meltzer, Thomas Reid, Craig J. Thomas, Maria J. Merino, W. Marston Linehan. Novel renal medullary carcinoma cell lines, UOK353 and UOK360, provide preclinical tools to identify new therapeutics [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 1169.
Abstract 117: Lysyl oxidase secreted by PTEN-deficient glioblastoma cells recruits macrophages and promotes malignant growth
Authors: Chen Peiwen , Wang Alan Y. , DePinho Ronald A. 
Published: August 2018

Abstract
Glioblastoma (GBM) is the most lethal form of brain cancer in adults. The median survival of GBM patients is only about one year after initial diagnosis. Genomic profiling has stratified GBM into various subgroups, which are driven by specific genetic alternations of core signaling pathways, including RTK/RAS/PI3K, P53 and RB pathways. Loss of PTEN, TP53 and CDKN2A tumor suppressors, and amplification of EGFR are frequently observed in GBM. However, targeted therapies, such as therapy against EGFR, have failed in the clinic, and no effective therapeutic drugs available to target tumor suppressors. The main reason for this failure is tumor-cell genetic heterogeneity, which induces aberrant activation of multiple signaling pathways. Stromal/immune cells in the tumor microenvironment (TME) are genetically stable, which not only play a pivotal role in GBM progression by affecting multiple cancer hallmarks, but can also be educated by cancer cells. However, whether and how the behavior and function of specific stromal/immune cells in the TME are regulated by cancer cell genetic alternations in GBM remain relatively undefined. Here, we show that PTEN deficiency in GBM specifically triggers immune response by promoting macrophage recruitment, while without affecting macroglia and other immune cells. Using unbiased transcriptome profiling, we identified that lysyl oxidase (LOX) is preferentially secreted by PTEN-deficient cancer cells, and is a potent macrophage chemoattractant. Transcriptome profiling following Gene Set Enrichment Analysis (GSEA) and functional validation demonstrated that activation of SRC and AKT signaling pathways drives LOX upregulation in PTEN-deficient cancer cells via the YAP1-TEAD complex. Upon the secretion from PTEN-deficient cancer cells, LOX can be uptaken by macrophages via integrin β1 signaling. Using the phospho-kinase antibody array, we identified PYK2 as the main downstream of LOX that is responsible for macrophage migration. Genetic and pharmacological inhibition of LOX in PTEN-deficient cancer cells does not affect tumor cell proliferation in vitro, but markedly inhibits macrophage density and tumor growth in vivo. Bioinformatics analysis in clinical samples demonstrated that PTEN-YAP1-LOX-integrin β1 axis is enriched in GBM patients with higher macrophage density, and that these patients show lower survival. Together, our findings highlight the significance of PTEN-YAP1-LOX-integrin β1 axis in macrophage infiltration in GBM, and demonstrate a possibility of improving GBM treatment by targeting this axis-mediated macrophage recruitment.
Citation Format: Peiwen Chen, Alan Y. Wang, Ronald A. DePinho. Lysyl oxidase secreted by PTEN-deficient glioblastoma cells recruits macrophages and promotes malignant growth [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 117.
Abstract 1170: NCI-H1975 L858R/T790M/C797S isogenic cell line for next-generation EGFR inhibitor screening
Authors: Hao Feng , He Feng , Zhang Wenna , Bai Zhaoshuai , Ning Jinying 
Published: August 2018

Abstract
Non-small-cell lung cancer (NSCLC) is the most common cause of cancer death. Over-activation of EGFR occurs in 13%~23% of NSCLC. The identification of EGFR as a cancer driver gene had led to rapid development of NSCLC targeted therapy, but the mutation of EGFR during treatment can cause drug resistance and cancer relapse. For example, T790M mutation causes resistance to the first generation of EGFR inhibitor Erlotinib and C797S mutation contributes to the resistance to the 3rd EGFR inhibitor AZD9291. There are several human cell lines for T790M mutation research, but there is not yet any primary human cancer cell line with C797S mutation. In the current study, a human isogenic EGFR C797S mutation cell line was generated through introducing nucleotide mutation into the EGFR gene in NCI-H1975 cell line using CRISRP technology, which originally bears L858R and T790M mutations of EGFR. First, the sgRNA sequence around the exon-20 of EGFR gene was screened using CRIPSR plasmid. Second, the donor plasmid with the homology arm containing exon-20 of EGFR and selecting marker was constructed and co-transfected into the parental cell line. Then, the NCI-H1975 C797S isogenic cell line was obtained and confirmed after screening over 100 single clones using the PCR method. The NCI-H1975 C797S isogenic cell line was resistant to AZD9291 but sensitive with EAI045 (the potential 4th generation EGFR inhibitor) combined with cetuximab. These data indicate that our NCI-H1975 L858R/T790M/C797S isogenic line is a useful model for next generation EGFR inhibitor study.
Citation Format: Feng Hao, Feng He, Wenna Zhang, Zhaoshuai Bai, Jinying Ning. NCI-H1975 L858R/T790M/C797S isogenic cell line for next-generation EGFR inhibitor screening [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 1170.
Abstract 1170A: Organoids: A new tool for the prediction of breast cancer patients' outcome
Authors: Roscigno Giuseppina , Cirella Assunta , Affinito Alessandra , Palma Francesco , Albero Maurizio , Messere Martina , Gelormini Martina , Cocca Lorenza , Thomas Renato , Condorelli Gerolama 
Published: August 2018

Abstract
Breast cancer is one of the leading causes of cancer mortality among women. The main causes of death are related to recurrence and metastasis. One major limitation in the breast cancer research field is that there are few in vitro models of breast cancer able to predict clinical patients' outcome. The main reason of this failure is that the present models do not take complexity or heterogeneity into account. Therefore, innovative models are now required to better represent tumor fidelity. To address this issue, we developed an in vitro 3D organoid culture system using primary human breast cancer tissue. Organoids are miniature forms of tissues that exhibit three-dimensional architecture and are able to maintain phenotypical properties cultured in a dish. Therefore, they could be used as models for diseases, including cancer. A major difficulty in the development of such models is to identify in vitro conditions that preserve the breast cancer phenotypes observed in vivo. For this reason, we isolated organoids from breast cancer patients and optimized the organoids growing conditions. We used a specialised medium and matrix (Cultrex Trevigen) required for supporting cell growth as it occurs in the human body. Then, we decided to test whether the obtained organoids could be used as an in vitro prediction tool. First, we performed immunofluorescence assay to assess the preservation of patient architecture (CK14, CK18 and E cadherin) and clinical phenotype (HER2, ER, PR). Then, we used an innovative chemotaxis assay in 3D collagen gels for analysing organoids cell invasion. It is based on a chamber in which a chemoattractant gradient is generated by diffusion through a porous membrane for mimicking blood microenvironment. Then we analysed the morphological changes after chemotherapeutics treatment to correlate the organoids response with patient tumor behaviour. Thus, organoids can be considered as a new tool for studying breast cancer and developing personalized medicine approaches for this disease.
Citation Format: Giuseppina Roscigno, Assunta Cirella, Alessandra Affinito, Francesco Palma, Maurizio Albero, Martina Messere, Martina Gelormini, Lorenza Cocca, Renato Thomas, Gerolama Condorelli. Organoids: A new tool for the prediction of breast cancer patients' outcome [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 1170A.
Abstract 118: Immuno-modulation of macrophages by ovarian cancer stem cells in an in vitro 3D spheroid platform
Authors: Raghavan Shreya , Mehta Geeta 
Published: August 2018

Abstract
The ascites microenvironment of ovarian cancers is enriched in ovarian cancer stem cells (OvCSCs) and macrophages (MPs). The immune system is complicit in the progression, chemoresistance and metastasis of ovarian cancer, yet little is known about the exact nature of interactions between OvCSCs and MPs, especially in the malignant ascites microenvironment. Here, we describe the use of the 3D in vitro hanging drop spheroid platform to study the reciprocal interactions between OvCSCs and MPs. Hetero-spheroids contained: i) monocyte-derived Macrophages (MP); and ii) OvCSCs (ALDH+ CD133+ OVCAR3). For immuno-modulation, we characterized MP polarization markers by flow cytometry and gene expression analysis. Using qPCR, we quantified changes in IL6, IL10, IL12, and Wnt7A, to understand signaling involved in OvCSC/MP hetero-spheroids. CD68 expression (~50%) was observed in OvCSC/MP hetero-spheroids, indicating the presence of MPs. OvCSCs drove higher CD206 expression in MPs (75%) when compared to unsorted ovarian cancer cells (OvCa; 40%). Even if MPs were pre-polarized to inflammatory M1 (HLA-DR+ CD206-), co-culture with OvCSCs reversed the M1 phenotype, and strongly induced CD206 expression. Pre-polarized M2 MPs resulted in 2-fold increase in ALDH+ cells in hetero-spheroids. Apart from CD206, MPs in hetero-spheroids also expressed iNOS, IFN-ϒ, and CD163. Gene expression analysis revealed increased immuno-suppressive IL10 in hetero-spheroids, with more IL10 in OvCSC/MP (3.5 fold) compared to OvCa/MP. OvCSC/MP and OvCa/MP spheroid also had consistently elevated (2-3 fold) increase in IL6 gene expression, consistent with the importance of the IL6/STAT3 axis in both cancer stem cell and macrophage signaling. Lastly, Wnt7A was significantly elevated in both differentiated MPs, and OvCSC/MP spheroids, indicating reciprocal trophic and immuno-suppressive signaling components at play. The 3D spheroid model can simulate biological interactions between OvCSCs and MPs within the malignant ascites. We describe that OvCSCs primarily polarize macrophages into a mixed phenotype that express both inflammatory and pro-tumoral markers. We believe that the putative involvement of Wnt7a in OvCSC/MP interactions drives this phenotype, and could have functional implications for tumorigenicity, response to chemotherapeutics and metastatic potential. This work was supported by the DOD OCRP W81XWH-13-1-0134, MIOCA, Rivkin Center for Ovarian Cancer and NIH T32DE00007057-41 and P30CA046592.
Citation Format: Shreya Raghavan, Geeta Mehta. Immuno-modulation of macrophages by ovarian cancer stem cells in an in vitro 3D spheroid platform [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 118.