bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5810: microRNAs targeting EMT transcription factors may be associated to lymph node metastasis in breast cancer tumors
Authors: Pérez-Moreno Elisa , Valarezo Gabriela , Zavala Valentina , Fernández Wanda , Carvallo Pilar 
Published: July 2017

Abstract
Breast cancer is the leading cause of cancer-associated deaths in women. Lymph node near to the primary breast tumor have a high chance of developing a secondary tumor, representing one of the first signs of metastasis in breast cancer. Metastasis is promoted by epithelial-mesenchymal transition (EMT), process leaded by the transcription factors SNAIL, SLUG, ZEB and TWIST. MicroRNAs are small non-coding RNAs, whose expression has been demonstrated to be altered in different cancer types. Because of their ability to regulate large sets of genes involved in cancer growth and metastasis, microRNAs have emerged as candidate molecular biomarkers and novel therapeutic targets. The aim of this study is to identify microRNAs differentially expressed in breast tumors in relation to EMT-transcription factor expression and lymph node metastasis, and that are involved in epithelial-mesenchymal transition. For this purpose, we used microRNA microarray data from 50 fresh frozen breast tumors with different tumor grades (1 to 3), 28 from patients with lymph node metastasis. Microarray data analysis using RankProd (R package) revealed approximately 40 microRNAS down-regulated in breast tumors with expression of EMT-transcription factors (p&lt;0.05). Several of the identified microRNAs have been previously described to regulate early steps of metastasis in different cancer types, like members of the miR-200 family (miR-200c and miR-141), miR-205 and miR-30a. In addition we found other microRNAs not previously associated to metastasis. Our results suggest that down regulation of specific microRNAs, and up regulation of their targets, may induce a metastatic behavior of tumor cells of the primary breast tumors, promoting invasion and colonization of the lymph nodes. In this sense, the changes in the expression of microRNAs may serve as biomarkers of breast cancer prognosis in patients.
Citation Format: Elisa Pérez-Moreno, Gabriela Valarezo, Valentina Zavala, Wanda Fernández, Pilar Carvallo. microRNAs targeting EMT transcription factors may be associated to lymph node metastasis in breast cancer tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5810. doi:10.1158/1538-7445.AM2017-5810
Abstract 5848: Fucoidan adminstration attenuates radiation pneumonitis and fibrosis through reducing inflammatory cytokine expression in lung tissue
Authors: Wu Szu-Yuan 
Published: July 2017

Abstract
Purpose: There is no well-known compound to prevent radiation pneumonitis (RP) or prophylactically use to attenuate the toxicity of RP. RP is one of major complications in chest part irradiation and limitations of radiation dose. Fucoidan is a sulfated polysaccharide found mainly in various species of brown algae and brown seaweed. Recent studies have demonstrated its anti-inflammation effect. Since RP is an radiation induced inflammatory and fibrosis related complication, we investigated the effect of fucoidan adminstration on radiation pneumonitis and fibrosis.
Materials and Methods: In this study, we compared the pneumonitis and fibrosis in lung tissue specimen between the lungs irradiated (10Gy/one shot) C57BL/6 mice with or without Fucoidan adminstration (200mg/kg /day, oral gavage for 14 days).
Results: The results demonstrated that fucoidan adminstration attenuates pneumonitis and fibrosis in lung tissue. We found the accumulation of neutrophils in irradiated lung tissue was decreased, and the radiation induced Masson trichrome staining fibrosis was decreased. We also investigate the inflammatory -cytokine profiles in the irradiated lung tissue by protein array. The results revealed that fucoidan adminstration changes the inflammatory -cytokine expression pattern in in the irradiated lung tissue.
Conclusions: This study demonstrated that inflammatory -cytokine expression after whole lung irradiation is correlated with neutrophil accumulation and radiation induced fibrosis. Interestingly, Fucoidan adminstration changes the inflammatory -cytokine expression pattern which may lead to attenuates radiation pneumonitis and fibrosis. It is potential to be a therapeutic molecular to attenuate or prevent radiation pneumonitis.
Note: This abstract was not presented at the meeting.
Citation Format: Szu-Yuan Wu. Fucoidan adminstration attenuates radiation pneumonitis and fibrosis through reducing inflammatory cytokine expression in lung tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5848. doi:10.1158/1538-7445.AM2017-5848
Abstract 5856: Molecular mechanism underlying breast cancer cell radioresistance: role of radiation-induced NF-KB self-sustenance
Authors: Yu Hui , Aravindan Natarajan , Xu Ji , Natarajan Mohan 
Published: July 2017

Abstract
Understanding the mechanism of breast cancer cell radioresistance and the associated selection pressure, tumor recurrence, would help us to develop molecular interventions and achieve disease/progression-free survival in patients with cancer. In the present study, we investigated the molecular mechanisms prompted in breast cancer cells in response to clinical radiation and the associated coordination of intra- and inter-cellular signaling that orchestrate radioresistance and tumor relapse/recurrence. Our findings showed that clinical doses of radiation increase NF-κB transcription and DNA-binding activity. Further, radiation exposure resulted in de novo TNF-α synthesis and secretion. An NF-κB gene manipulation approach revealed that NF-κB triggered NF-κB-mediated TNF-α transcriptional activity. NF-κB DNA binding kinetic analysis demonstrated both sustained and dual phase NF-κB activation with radiation. Radiation prompted NF-κB-dependent synthesis/secretion of TNF-α, a requisite for the second phase of NF-κB activation and maintenance. Radiation-associated NF-κB-dependent secretion of TNF-α from irradiated cells also activated NF-κB in the non-irradiated, non-targeted bystander cells. Together, these findings demonstrated that radiation-triggered NF-κB-dependent TNFα secretion is critical for self-sustenance of NF-κB (through autocrine positive feedback signaling) and for coordinating bystander response (through intercellular signaling: de novo activation of NF-κB in bystander cells) after radiation exposure. Further, the data suggest that this NF-κB→TNF-α→NF-κB feedback-dependent self-sustenance of NF-κB could drive the selection pressure (proliferation, clonal expansion) of surviving breast cancer cells and subsequent tumor relapse/recurrence.
Note: This abstract was not presented at the meeting.
Citation Format: Hui Yu, Natarajan Aravindan, Ji Xu, Mohan Natarajan. Molecular mechanism underlying breast cancer cell radioresistance: role of radiation-induced NF-KB self-sustenance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5856. doi:10.1158/1538-7445.AM2017-5856
Abstract 5876: Osimertinib (AZD9291), a mutant-selective EGFR inhibitor, reverses ABCB1-mediated drug resistance in cancer cells
Authors: Zhang Xiao-Yu , Lei Zi-Ning , Zhang Yun-Kai , Wang Yi-Jun , Gupta Pranav , Zeng Leli , Xu Megan , Wang Xiu-Qi , Yang Dong-Hua , Chen Zhe-Sheng 
Published: July 2017

Abstract
In recent years, tyrosine kinase inhibitors (TKIs) have been shown capable of inhibiting the ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR). In this study, we determine whether osimertinib, a novel selective, irreversible EGFR (epidermal growth factor receptor) TKI inhibitor, could reverse ABC transporter-mediated MDR. The results showed that at non-toxic concentrations, osimertinib significantly sensitized both ABCB1-transfected and drug-selected cell lines to substrate anticancer drugs colchicine, paclitaxel, and vincristine. Osimertinib significantly increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells by blocking the efflux function of ABCB1 transporter. In contrast, no significant alteration in the expression levels and localization pattern of ABCB1 was observed when ABCB1 overexpressing cells were exposed to 0.3μM osimertinib for 72 h. In addition, ATPase assay showed osimertinib stimulated ABCB1 ATPase activity. Molecular docking and molecular dynamic simulations showed osimertinib has strong and stable interactions at transmembrane domain of human homology ABCB1. Taken together, our findings suggest that osimertinib, a clinically approved third-generation EGFR TKI, can reverse ABCB1-mediated MDR, which supports the combination therapy with osimertinib and ABCB1 substrates may potentially be a novel therapeutic treatment in ABCB1-positive drug resistant cancers.
Citation Format: Xiao-Yu Zhang, Zi-Ning Lei, Yun-Kai Zhang, Yi-Jun Wang, Pranav Gupta, Leli Zeng, Megan Xu, Xiu-Qi Wang, Dong-Hua Yang, Zhe-Sheng Chen. Osimertinib (AZD9291), a mutant-selective EGFR inhibitor, reverses ABCB1-mediated drug resistance in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5876. doi:10.1158/1538-7445.AM2017-5876
Abstract 5910: Influence of 3D- cultured prostate cancer and stromal cells on drug response
Authors: Gales Dominique N. , Miller Sonni , Samuel Temesgen , Yates Clatyon 
Published: July 2017

Abstract
Background: Response to chemotherapeutic drugs presents a significant challenge to effective treatment of advanced prostate cancer. Exploration of therapeutic response has focused largely on the tumor cell. However, evidence suggests mechanisms that involve the tumor microenvironment mediate response to therapeutics. Therefore, it is imperative to mimic the in vivo tumor microenvironment, to bridge the gap between in vitro studies and the development of therapeutics. The concept of three-dimensional (3D) cell culture and co-culture of multiple cell types is critical to predict therapeutic efficacy and outcome. Thus, these studies sought to determine the distinct responses to anti-cancer drugs in 3D cell spheroids.
Methods: In this study, we utilized metastatic prostate cancer cells (PC3) and fluorescently labeled prostate bone stromal cell line (HS27a) to generate tumor spheroids. Tumor spheroid viability was measured at 72 and 120 h using the CellTiter-Glo 3D assay after treatment with three common anti-cancer drugs, Docetaxel (4ηM), Enzalutamide (30μM), and Bicalutamide (30μM).Treatments were compared with spheroids originated from HS27a and PC3 cells alone and in co-culture. The cell viability percentage was normalized using the untreated cells as 100% cell survival.
Results: Spheroid formation increased resistance to Docetaxel, Enzalutamide, and Bicalutamide. However, PC3 spheroid cells was significantly higher compared to HS27a and co-culture spheroids. For all three spheroids, as the size of the spheroids increase, cellular resistance to anti-cancer and hormone drugs increased.
Conclusion: The findings in this study demonstrated that the use for 3D-cell cultures influence many aspects of PCa behavior including, proliferation rates, and response to chemotherapeutics.
Note: This abstract was not presented at the meeting.
Citation Format: Dominique N. Gales, Sonni Miller, Temesgen Samuel, Clatyon Yates. Influence of 3D- cultured prostate cancer and stromal cells on drug response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5910. doi:10.1158/1538-7445.AM2017-5910
Abstract 5911: Omentin drives metabolic shift in ovarian cancer cells in the omental tumor microenvironment
Authors: Yeung Chi Lam Au , Achreja Abhinav , Zhao Hongyun , Yeung Tsz-Lun , Schmandt Rosemarie , Yip Daniel K. , Lu Karen H. , Nagrath Deepak , Mok Samuel C. 
Published: July 2017

Abstract
Advanced stage high grade serous ovarian cancer (HGSC) metastasizes preferentially to the omentum, which is a well-vascularized fold of peritoneal tissue and is a major site of adipose tissue accumulation. The mechanisms by which omental adipose tissue interact with ovarian cancer cells and promotes tumor growth and disease progression are not entirely clear. We previously showed that a novel adipokine called omentin (Intestinal Lactoferrin Receptor ITLN1) produced by the omental adipose tissue was significantly down-regulated in patients with HGSC compared with those in BMI matched healthy individuals, and omentin suppressed ovarian cancer cell growth only in the presence of adipocytes in vitro. Since we and others demonstrated that omentin induced insulin-dependent glucose uptake exclusively in adipocytes, we therefore hypothesized that omentin may suppress ovarian cancer growth via driving metabolic shift in ovarian cancer cells in the omental microenvironment. Using a cancer cell/adipocyte-co-culture model, we demonstrated that omentin reduced both glucose uptake and lactate secretion in ovarian cancer cells when they were co-cultured with adipocytes but not with other stromal cell types, suggesting that omentin-induced glucose uptake in adipocytes may deplete the surrounding glucose that fuels the glucose-addicted ovarian cancer cells in the omental microenvironment and thus drive metabolic shift in ovarian cancer cells. To delineate the underlying mechanism by which omentin induced glucose uptake in adipocytes, expression levels of the adipocyte-specific glucose transporter GLUT4 induced by omentin in adipocytes and the effect of GLUT4 silencing in adipocytes using GLUT4 specific siRNAs on ovarian cancer growth were examined. The results showed that omentin up-regulated GLUT4 in adipocytes and GLUT4 silencing in adipocytes abrogated the effects of omentin on glucose uptake in adipocytes and ovarian cancer cell growth in the co-culture model. Taken together, this study shows that omentin plays an important role in driving metabolic shift in ovarian cancer cells in the omental microenvironment. Therapeutic strategies based on up-regulating omentin in ovarian cancer patients may inhibit ovarian cancer progression and improve patient survival rates.
Note: This abstract was not presented at the meeting.
Citation Format: Chi Lam Au Yeung, Abhinav Achreja, Hongyun Zhao, Tsz-Lun Yeung, Rosemarie Schmandt, Daniel K. Yip, Karen H. Lu, Deepak Nagrath, Samuel C. Mok. Omentin drives metabolic shift in ovarian cancer cells in the omental tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5911. doi:10.1158/1538-7445.AM2017-5911
Abstract 5942: Collagen proly-hydroxylase regulates breast cancer progression and chemoresistance
Authors: Xiong Gaofeng , Xu Ren 
Published: July 2017

Abstract
Collagen prolyl hydroxylation (P4H), an enzyme hydroxylating proline residues in -X-Pro-Gly- sequences, is a potential therapeutic target for the disorders associated with increased collagen deposition. Upregulation of collagen prolyl-4-hydroxylase in cancer cells is required for breast cancer promotion. P4HA1 mRNA levels were significantly upregulated in triple-negative breast cancer (TNBC) compared to other cancer subtypes. Increased mRNA levels of P4HA1 correlated with poor clinical outcome in breast cancer patients. Silencing P4HA1 expression or treatment with the P4HA inhibitor significantly inhibited cell proliferation and suppressed aggressive phenotypes of breast cancer cells in 3D culture, accompanied by reduced deposition of collagen. We found that activation of the P4HA1 in TNBC cells enhanced cancer cell stemness. We also found that knockdown of P4HA1 inhibited mammary tumor growth and metastasis to lungs in xenograft models. Inhibition of P4HA1 activity with the P4H inhibitor sensitized TNBC to the docetaxel treatment in the patient-derived organoid (PDO) and xenograft models. Therefore, these results suggest the crucial role of P4HA1 in breast cancer progression and that targeting collagen P4H is a promising strategy to inhibit tumor progression and to sensitize TNBC to chemotherapy.
Citation Format: Gaofeng Xiong, Ren Xu. Collagen proly-hydroxylase regulates breast cancer progression and chemoresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5942. doi:10.1158/1538-7445.AM2017-5942
Abstract 5946: Universal consent for biospecimens: A novel electronic/video consent
Authors: Naeim Arash , Wenger Neil , Petruse Antonia , Sanchez Liliana , Sharif Azita , Dry Sarah 
Published: July 2017

Abstract
Background: Developing innovative, efficient and institutionally scalable bio-specimen consent for remnant tissue that meets the NIH consent guidelines for genomic and molecular analysis is essential for precision medicine efforts in cancer. Solutions in this arena need to satisfy the needs of patients, researchers, ethicists, IRB and compliance leadership, while fitting as seamlessly as possible into existing clinical workflows.
Methods: UCLA developed a video-application kiosk-based approach for providing universal consent to repurpose clinical remnant bio-specimen for research. The process was designed to be self-service, comprehensive yet fast (mean shorter than 5 minute for completion). The consent additionally asked the patient if they were willing to be contacted directly for future research projects. This approach was piloted with 474 patients who were coming in for routine services in laboratory medicine, radiology, oncology, and hospital admissions. Of the pilot population, 175 individuals had targeted surveys to evaluate drivers for opting-in or opting-out of the consent for allowing the collection and use of their remnant tissue for research. The cognitive survey was online and presented immediately after the consent process was completed.
Results: The opt-in rate for the pilot was 90.7%, and 56% agreed to direct contact for future research. Only 7% needed help navigating the online consent process. Of the subgroup of pilot population who completed the targeted survey, there was no difference between individuals who opted in and out regarding ease of use, of the consent application with about 75% stating it provided mostly or very useful information, 90% stating it was mostly or very easy to understand, and 85% stating they trusted the information. However, there were significant differences between those that opted-in and opted-out in their beliefs concerning usefulness of tissue, trusting researchers, importance of contributing to science and privacy risk with those opting in strongly supporting these beliefs (&gt;90%) compared to those that opted out (&lt;40%), p&lt;0.001.
Conclusions: Video-application approach for allowing individuals to consent for remnant specimens to be collected and used for research, including cancer research, can be efficient, patient-centric and meet the NIH requirements. This method could increase the availability of blood and tissue for cancer research and should be tested for scalability as an enterprise solution.
Citation Format: Arash Naeim, Neil Wenger, Antonia Petruse, Liliana Sanchez, Azita Sharif, Sarah Dry. Universal consent for biospecimens: A novel electronic/video consent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5946. doi:10.1158/1538-7445.AM2017-5946
Abstract 646: Targeting MHC class I molecules and immune checkpoints as key immune evasion strategies in EBV-associated nasopharyngeal carcinoma
Authors: Siu Sharie Pui-Kei , To Ka Fai , Chung Grace Tin-Yun , Lui Vivian W.Y. , Li Yvonne Y. , Hammerman Peter S. , Lo Kwok Wai 
Published: July 2017

Abstract
Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer that is consistently associated with intensive lymphocytes infiltration and Epstein-Barr virus infection. This study aims at elucidating the mechanism contributing to immune evasion in NPC. During NPC tumorigenesis, multiple intrinsic mechanisms are acquired to escape cellular immune response for the tumor and viral antigens. By genome sequencing, somatic alterations of multiple MHC class I genes including NLRC5, HLA-A, HLA-B, HLA-C and B2M were detected in 30% of primary NPC. Significant correlation of MHC class I gene alterations and poor survival rate in the patients was also shown. The finding suggested that the deficiency of antigen presentation mechanism represents a common strategy for immune evasion in NPC and favors rapid tumor progression. Losses of HLA-A, HLA-B and NLRC5 expression were validated in a panel of NPC tumor lines and selected primary tumors. The role of NLRC5 as key transcription regulator of HLA-A and HLA-B expression was demonstrated in the nasopharyngeal epithelial cells. To further evaluate the mechanisms contributed to immune evasion in NPC, we have elucidated immunosuppressive molecules involved in immune surveillance in Epstein Barr Virus (EBV)-associated NPC and its association with EBV-encoded LMP1 in an independent cohort of primary NPCs. By immunohistochemistry, the expression of EBV-encoded LMP1, MHC class I genes and various immunosuppressive molecules including PDL1, PDL2 and IDO1 was examined in 98 primary tumors. PDL1 and PDL2 were found to be over-expressed in 50% and 33.7% of NPC cases while IDO1 was found to be expressed in 28.8% of cases. Primary NPC cases expressing either PDL1 or PDL2 accounted for 64.3%. A significant association between LMP1 and PDL1 and PDL2 expression was also found. The correlation of PDL1, PDL2 and/or MHC class I molecule expression with the outcome of the patients was determined. The high incidence of MHC class I deficiencies and PDL1/PDL2 overexpression imply that EBV-associated NPC escape from the host immune response by targeting both antigen presentation mechanisms and immune checkpoints. Our findings also suggested that the expression of MHC class I molecules and PDL1/PDL2 is a potential biomarker for immunotherapy in NPC patients.
Citation Format: Sharie Pui-Kei Siu, Ka Fai To, Grace Tin-Yun Chung, Vivian W.Y. Lui, Yvonne Y. Li, Peter S. Hammerman, Kwok Wai Lo. Targeting MHC class I molecules and immune checkpoints as key immune evasion strategies in EBV-associated nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 646. doi:10.1158/1538-7445.AM2017-646