bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 692: Treating spinal cord metastases with tumor treating fields
Authors: Yesharim Ofir , Naveh Ariel , Bomzon Ze'ev 
Published: August 2019

Abstract
Introduction: Tumor Treating Fields (TTFields) is an anti-mitotic technology utilizing low-intensity (1-3 V/cm) electric fields within the medium frequency range (100-300 kHz) to treat solid tumors. TTFields are currently approved for the treatment of Glioblastoma (GBM). Some cancer types, such as breast cancer, lung cancer, and melanoma, frequently result in metastases to the spinal cord. Transducer array positioning used to treat abdominopelvic diseases (e.g. pancreatic cancer), in which one pair of arrays are placed on the anterior and posterior of the patient, and another pair of arrays placed on the lateral aspects of the patient have been shown to be inefficient for treating the spinal cord because the clinical threshold for field intensity of 1V/cm is not reached in the spine when these layouts. The structure of the spine, in which a relatively resistive bone structure encapsulates a highly conductive layer of fluid (cerebrospinal fluid), shunts the current delivered across the body by the arrays away from the spine, reducing the field within the spine to below the therapeutic threshold. To overcome this limitation, a new approach of array placement on the body is needed. Here we present a simulation-based study designed to identify array layouts that effectively deliver TTFields to the spine.
Methods: To simulate delivery of TTFields to the spine, we used a human male 34 years old realistic computerized model (DUKE v3.1 by ITI’S, Zurich). In order to generate TTFields, an alternating current with current density of 200mA/disk with a frequency of 150 kHz was imposed on the outer surfaces of the disks of each pair of arrays. The simulations were performed using ZMT's Sim4Life v4.0 electro-quasi-static solver.
Results: One of the array layouts tested was placement of a pair of arrays on the back of the patient. One array is placed above the target region in the spine to which treatment would be delivered, and the other array is placed below the region. With this configuration, a high electric field is induced within the spinal cord and surrounding CSF. Mean field intensity within the spine and nerves in between vertebrae T8-T9 at the top, and L3-L4 at the bottom were calculated at a value of 1.77 V/cm. It is important to note that the electric field is oriented along the spine in this instance (a vertical field). In general, the whole spine could be treated by placing one array on the neck, and one at the bottom of the spine.
Conclusions: Placing two transducer arrays on the patient’s back allows single-direction treatment of the spinal cord and nerves. Further work should be conducted to find an effective treatment in the perpendicular direction.
Citation Format: Ofir Yesharim, Ariel Naveh, Ze'ev Bomzon. Treating spinal cord metastases with tumor treating fields [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 692.
Abstract 695: Using PSA dynamics to predict patient-specific responses to intermittent androgen deprivation
Authors: Brady Renee , Enderling Heiko 
Published: August 2019

Abstract
Intermittent androgen deprivation therapy (IADT) is an attractive treatment approach for biochemically recurrent prostate cancer, whereby cycling treatment on and off has been shown to limit toxicities and reduce cumulative dose. While IADT has been shown to delay the development of treatment resistance, underlying mechanisms and actionable biomarkers are required to accurately predict when resistance will emerge and how to maximally delay time to progression. We developed a quantitative framework to simulate the enrichment of prostate cancer stem cell dynamics during treatment as a plausible mechanism of resistance evolution. Using simulated dynamics of cancer stem cells and non-stem cancer cells we derive longitudinal blood serum prostate-specific antigen (PSA) concentrations that were calibrated to and validated with data of 86 patients undergoing multiple cycles of IADT. Model analysis suggests that cancer stem cell proliferation patterns correlate with PSA dynamics and patient outcomes. Learning these dynamics adaptively from the earlier treatment cycles in individual patients can predict the evolution of resistance in subsequent IADT cycles with a predictive power of 80%, which warrants prospective evaluation in a clinical setting.
Citation Format: Renee Brady, Heiko Enderling. Using PSA dynamics to predict patient-specific responses to intermittent androgen deprivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 695.
Abstract 71: NEDD8-activating enzyme inhibitor MLN4924 reduces cell viability and induces apoptosis in chemoresistant cancer stem-like cells of human urothelial carcinomas in vitro and in vivo
Authors: Liao Shih-Ming , Hsu Fu-Shun , Yang Shao-Ping , Chang Yu-Wei , Chow Po-Ming , Pu Yeong-Shiau , Tsai Yu-Chieh , Kuo Kuan-Lin , Huang Kuo-How 
Published: August 2019

Abstract
Emerging evidence indicates that cancer stem cells (CSCs) may play a crucial role in cancer tumorigenesis, metastasis, and drug resistance. To develop treatment to inhibit CSCs provides promising target for cancer therapy. In this study, we identified a subpopulation of chemoresistant cancer stem-like cells of UCs (T24/R) after chemotherapeutic drug selection from T24, a bladder UC cell line. The T24/R cells displayed stemness markers (SOX2, Nanog, and Kruppel-like factor 4), high tumorigenicity in vivo, and enhanced invasion ability because of their epithelial-mesenchymal transition (EMT) properties. A neddylation inhibitor, MLN4924, efficiently inhibited viability and migration as well as induced apoptosis in the T24/R cells with concomitant suppression of stemness and EMT markers. Our findings suggest that MLN4924 effeiciently suppressed chemoresistant cancer stem-like UC cells and was a promising agent to conquer drug resistance in human bladder UCs.
Citation Format: Shih-Ming Liao, Fu-Shun Hsu, Shao-Ping Yang, Yu-Wei Chang, Po-Ming Chow, Yeong-Shiau Pu, Yu-Chieh Tsai, Kuan-Lin Kuo, Kuo-How Huang. NEDD8-activating enzyme inhibitor MLN4924 reduces cell viability and induces apoptosis in chemoresistant cancer stem-like cells of human urothelial carcinomas in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 71.
Abstract 712: Down-regulation and nuclear localization of survivin by sodium butyrate induces caspase-dependent apoptosis in human oral mucoepidermoid carcinoma
Authors: Ahn Chi Hyun , Cho Sung-Dae 
Published: August 2019

Abstract
Sodium butyrate (NaBu) is a histone deacetylase inhibitor that possess an apoptotic ability. However, the molecular mechanism by which NaBu induces apoptosis in human oral mucoepidermoid carcinoma (MEC), a type of salivary gland tumor, remains unclear. The anticancer effects of NaBu and its related molecular mechanisms were determined by trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole staining, live/dead assay, human apoptosis array, RT-PCR, western blotting, immunocytochemistry, preparation of nuclear fractions, and nude mice tumor xenograft. In this study, we found that NaBu inhibited growth and induced apoptosis in the human oral MEC cell lines MC3 and YD15 with the acetylation of histone proteins H2A and H3. NaBu apparently down-regulated survivin protein, as evidenced by the results of the human apoptosis antibody array, and modulated it at the post-translational process. Interestingly, NaBu caused nuclear translocation of survivin protein in both cell lines. NaBu also resulted in decreased expression levels of Bcl-xL mRNA and protein, leading to induction of caspase-dependent apoptosis in human oral MEC cell lines. In addition, NaBu administration inhibited tumor growth in vivo at a dosage of 500 mg/kg/day, but it did not cause any hepatic or renal toxicity. This study provides new insights into the molecular mechanism of apoptotic actions by NaBu in human oral MEC and the basis of its clinical application for the treatment of human oral MEC.
Citation Format: Chi Hyun Ahn, Sung-Dae Cho. Down-regulation and nuclear localization of survivin by sodium butyrate induces caspase-dependent apoptosis in human oral mucoepidermoid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 712.
Abstract 717: Erianin induces autophagy-dependent apoptosis in oral cancer cells
Authors: Lin Chiao-Wen , Yang Shun-Fa 
Published: August 2019

Abstract
Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide. It has a very poor prognosis with 5-year over survival rate of only 50%. Thus, it is important to identify effective therapeutic interventions against oral cancer. The present study was designed to evaluate the effect of erianin, a natural bibenzyl compound found in a traditional Chinese orchid Dendrobium chrysotoxum, on human oral cancer cell proliferation. Results of the study revealed that treatment with erianin significantly reduced the viability of different OSCC cell lines. Erianin exerted its cytotoxic effect by inducing cell cycle arrest at G2/M phase and caspase-dependent apoptotic pathways. Both intrinsic and extrinsic pathways were found to be involved in erianin-mediated cell death. In addition, treatment with erianin also increased autophagy in OSCC cells. With further analysis, it was found that erianin induced both apoptosis and autophagy by regulating MAPK signaling pathways. Taken together, our study indicates that erianin plays an important role in reducing oral cancer cell viability, and thus, can be considered as a potential anticancer agent.
Citation Format: Chiao-Wen Lin, Shun-Fa Yang. Erianin induces autophagy-dependent apoptosis in oral cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 717.
Abstract 722: Epigenetic regulation of the Birc5 promoter explains mechanism of action of YM-155 in synovial sarcoma
Authors: Mika Aleksander , Luelling Sarah , Pavek Adriene , Parkinson Neil , Heyneman Alexandra , Barrott Jared J. 
Published: August 2019

Abstract
YM-155 is an anti-cancer therapy that has advanced into 11 different human clinical trials to treat various cancers. This apoptosis-inducing therapy indirectly affects the protein levels of Survivin (Gene: Birc5), but the molecular underpinnings of the mechanism remain largely unknown. Synovial sarcoma is another cancer with high protein expression of Survivin. We investigated whether YM-155 would be a viable therapeutic option to treat synovial sarcoma. We, therefore, applied YM-155 therapy to human synovial sarcoma cell lines and a genetically engineered mouse model of synovial sarcoma. We discovered that YM-155 exhibited nanomolar potency against human synovial sarcoma cell lines and the treated mice with synovial sarcoma demonstrated a 50% reduction in tumor volume compared to control treated mice. We further investigated the mechanism of action of YM-155 by looking at the change of modifications of the histone tails that were near the Birc5 promoter. Using chomatin immunoprecipitation (ChIP) we discovered that the histone epigenetic marks of H3K27 for the Birc5 promoter changed upon YM-155 treatment. H3K27me3 increased whereas the H3K27ac decreased, highlighting the decrease of the protein Survivin occurs through epigenetic silencing of the gene’s promoter. The treatment of YM-155 was accompanied by an increase in NFkB protein expression, which indicates an attempt of the cell to initiate a positive feedback due to the decrease in Survivin expression. This combination of molecular events eventually resulted in Caspace 3/7/8 upregulation and death of the sarcoma cells.
Citation Format: Aleksander Mika, Sarah Luelling, Adriene Pavek, Neil Parkinson, Alexandra Heyneman, Jared J. Barrott. Epigenetic regulation of the Birc5 promoter explains mechanism of action of YM-155 in synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 722.
Abstract 725: Anticancer effect and mechanism of exosomes mediated microRNA let-7b in breast cancer cells
Authors: Biantiao Xu 
Published: August 2019

Abstract
Exosome is referred as membrane-bound nano-vesicles secreted by various mammalian cells. It can be found in different body fluids, such as plasma, saliva, urine, latex, cerebrospinal fluid, ascites, and cell supernatant, which contains a large number of proteins, miRNAs, mRNAs, lipids, nucleic acids, peptides and other substances. Exosome plays a pivotal role in the information transmission signals between cells and the diagnosis and prognosis of diseases as well as drug evaluation. It has become an emerging field in cancer research recently. Therefore, we separated exosomes from human kidney embryo cell (HEK-293) by ultra high speed centrifugation. To identify exosomes from their surface specific proteins by Western blotting analysis. We found enrichment of exosome markers CD63 and TSG101 without Calnexin protein in the exosoms so confirmed that exosome was successfully isolated. Then, we transfered mRNA let-7b into the exosomes by electric transfection further evaluated the effects of cytotoxicity and apoptosis induction on human breast cancer MCF-7 cells by CCK 8 assay Hochest 33342-PI and AnnexinV-PI dual staining analysis, respectively. The results showed that exosome mediated microRNA let-7b exhibited significant anticancer activity and apoptosis induction in a concentration-dependent manner in MCF-7 cells. Moreover, exosome mediated let-7b significantly up-regulated the expression levels of apoptosis related proteins casepase 3, casepase 9, and PARP determined by Western blotting analysis. Our results indicate that the exosomes mediated microRNA such as let-7b can effectively inhibit cell growth and induce apoptosis against breast cancer cells and it may be developed as a novel anticancer agent in the treatment of cancer clinically.
Citation Format: Xu Biantiao. Anticancer effect and mechanism of exosomes mediated microRNA let-7b in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 725.
Abstract 737: NF-κB pathway activation by clonal mutations contributes to the recurrence of nasopharyngeal carcinoma
Authors: You Rui , Liu You-Ping , Chen Ming-Yuan 
Published: August 2019

Abstract
Objectives: Identification and characterization of the genomic features that potentially drive NPC recurrence.
Methods: We performed whole-genome/whole-exome sequencing of fresh tumors and corresponding blood samples from 55 rNPC and 44 pNPC patients. Additionally, previously published pNPC exome data were integrated for analysis. Immunohistochemistry and histologic analyses were performed to identify novel biomarkers among the differential mutational events between pNPC and rNPC in independent cohorts of 148 rNPC and 237 pNPC samples with complete clinical follow-up.
Results: rNPC and pNPC tissues had similar mutational burdens; however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD and NFKBIA were all clonal in rNPC; however, 55.6-57.9% of them were clonal in pNPC (P &lt; 0.05). In general, the number of clonal mutations in NF-κB pathway-associated genes was significantly higher in rNPC than in pNPC (P &lt; 0.05). Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with local regional relapse than in those without relapse (P = 0.006). Further, in both the pNPC training and validation cohorts, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival (LRRFS) in pNPC. Accordingly, concurrent chemotherapy for patients with high nuclear NF-κB reduced the rate of locoregional relapse. Lastly, we functionally validated that inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in NPC cells, strongly supporting our in vivo results.
Conclusion: NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting LRRFS and suggesting treatment for pNPC patients. Finally, blocking NF-κB activity may be a novel and effective therapeutic modality for treating NPC.
Citation Format: Rui You, You-Ping Liu, Ming-Yuan Chen. NF-κB pathway activation by clonal mutations contributes to the recurrence of nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 737.
Abstract 74: Heterogeneity response to afatinib in gastric cancer patient with uncommon EGFR mutations
Authors: Liu Qin , Wei Jia , Yang Yang , Wang Yue , Liu Baorui , Shao Yang 
Published: August 2019

Abstract
Introduction: Gastric cancer is the third leading cause of cancer mortality worldwide. Gatric cancer based on driver gene mutation detection may benefit patients by facilitating molecular targeted drugs development and improving survival in gastric cancer patients. On the other hand, the complex and heterogeneous molecular mechanisms of gastric cancer also plays an essential role in the drug resistance.
Methods: Whole exome sequencing (WES) was performed, revealing uncommon EGFR ex21 L861Q and ex18 G719S mutation of formalin-fixed paraffin-embedded sections from primary tumor and different metastatic lesions in a gastric cancer patient. The periodic circulating tumor DNA (ctDNA) was also determined by next generation sequencing (NGS). Stable gastric cancer cell and NIH-3T3 cell lines harboring the mutations were established to investigate the effect and mechanisms.
Results: Tumors with compond EGFR L861Q/G719S mutations and EGFR gene amplfication are sensitive to afatinib, which caused tumor progression in short time. However, the lung metastatic lesion, which lacked EGFR gene amplification demonstrated primary resistance to afatinib. A dramatic increase of MET gene copy number may collectively related to the patient’s rapid progression. Periodic mutation profiling of patient’s ctDNA by NGS correspondingly revealed compond EGFR L861Q/G719S mutations, and a consitent increase of MET gene amplification. In in vitro studies, afatinib treatment reduced proliferation and inhibited EGFR phosphorylation in L861Q/G719S and L861Q mutant cells.
Conclusions: Afatinib may be a beneficial therapeutic option for a subset of gastric cancer patients with rare EGFR mutations in their tumors. Our results also illustrated the great potential of ctDNA profiling for treatment decision-making to patients with gastric cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Qin Liu, Jia Wei, Yang Yang, Yue Wang, Baorui Liu, Yang Shao. Heterogeneity response to afatinib in gastric cancer patient with uncommon EGFR mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 74.
Abstract 743: Fusion gene identification from common cancer cell lines and comparison to primary tumors
Authors: Vellichirammal Neetha Nanoth , Albahrani Abrar , Banwait Jasjit K. , Li You , Guda Babu 
Published: August 2019

Abstract
Fusion transcripts, frequently observed in cancer, contribute to oncogenicity by either altering the expression of tumor suppressors/proto-oncogenes or modifying the original function of a protein resulting in an abnormal chimeric protein that stimulates tumorigenesis. Cancer cell lines, extensively used as in-vitro molecular models to study biological processes related to cancer, often do not represent the genomic profiles of primary tumors. To examine the true representation of the cancer cell lines, we examined fusions in tumor- derived cancer cell lines from 20 cancer types in the Cancer Cell Line Encyclopedia (CCLE) and compared them to fusions present in the primary tumors from the TCGA (The Cancer Genome Atlas). ChimeRScope, an alignment-free algorithm developed by our group, was used to screen fusion genes using level 1 paired-end RNA sequencing read data from CCLE and TCGA (GDC data portal). A total of 8,883 primary tumor samples, 730 normal samples spanning 33 cancer types from TCGA, and 802 common laboratory cell lines from CCLE were analyzed in this study. The pool of recurrent fusions identified from CCLE was vastly different from those identified in primary tumors with merely 2% of an overlap. Canonical fusions were found to be more common than non-canonical fusions (fusions containing genes in antisense strand) between TCGA and CCLE. Hierarchical clustering analysis of both canonical and non-canonical recurrent fusions in CCLE and TCGA clustered the primary tumors and cell lines into separate clusters, revealing that fusions in cell lines are vastly different from primary tumors. However, canonical and non-canonical fusion profiles of endometrial cancer cell lines were very similar to female primary tumors (ovarian and breast) and thyroid cancer cell lines were similar to bladder cancer in TCGA. The results from this study indicate that the recurrent fusions in common cancer cell lines harbor fusions that are significantly different from primary tumors.
Citation Format: Neetha Nanoth Vellichirammal, Abrar Albahrani, Jasjit K. Banwait, You Li, Babu Guda. Fusion gene identification from common cancer cell lines and comparison to primary tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 743.