bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4198: 2-Hydroxymelatonin shows antitumor activity against human colorectal cancer cells
Authors: Yang Yi , Zhou Rui , Park So-Yeon , Kim Kyung Keun , Kim Hangun 
Published: August 2018

Abstract
2-Hydroxymelatonin is a predominant hydroxylated melatonin metabolite in plants. To investigate whether it has potent cytotoxic effects on colorectal cancer cells, four colorectal cancer cell lines, Caco2, HCT116, DLD1, and CT26, were treated with 2-hydroxymelatonin and melatonin. 2-Hydroxymelatonin had a much lower IC50 value than melatonin in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic effect of 2-hydroxymelatonin was much stronger than that of melatonin at high concentrations (1000 or 2000 μM) in HCT116, DLD1, and CT26 cells, but only at intermediate concentrations (250 or 500 μM) in Caco2 cells. The cytotoxicity of 2-hydroxymelatonin was induced through activation of the apoptotic signaling pathway, as confirmed by Hoechst staining and Annexin V-FITC/propidium iodide double labeling of cells treated with a lethal dose (1 mM). However, sub-lethal doses of 2-hydroxymelatonin inhibited the invasive ability of Caco2 cells. Epithelial-mesenchymal transition (EMT) markers were significantly regulated by 2-hydroxymelatonin. Overall, the anti-cancer activity of 2-hydroxymelatonin is more potent than that of melatonin. Taken together, 2-hydroxymelatonin exhibits potent anti-cancer activity against human colorectal cancer cells via induction of apoptosis and inhibition of EMT.
Citation Format: Yi Yang, Rui Zhou, So-Yeon Park, Kyung Keun Kim, Hangun Kim. 2-Hydroxymelatonin shows antitumor activity against human colorectal 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 4198.
Abstract 4201: Dp44mT, an iron chelator, suppresses cell growth and invasion by inducing N-myc downstream-regulated gene 1 and inhibiting Wnt/β-catenin signaling in human glioma cells
Authors: Luo Peng , Zhang Ye , Jiang Yang , Xu Ying , Jing Zhitao 
Published: August 2018

Abstract
The iron-chelating agent di-2-pyridylketone 4, 4-dimethyl-3-thiosemicarbazone (Dp44mT) can inhibit cell growth and invasion in some human cancers. However, the precise molecular mechanisms involved remain obscure in the context of glioma. Recent evidence suggests that N-myc downstream-regulated gene (NDRG)1 has an oncogenic role function. In the present study, we investigated whether Dp44mT regulates the NDRG1 expression and thereby inhibits glioma cell growth and invasion. We found that Dp44mT inhibited glioma proliferation and invasion in vitro, and reduced average tumor size and wet weight in a xenograft model. Dp44mT overexpression increased NDRG1 expression; NDRG1 silencing stimulated cell growth and invasion and triggered epithelial-to-mesenchymal transition (EMT). We also found that Dp44mT exerts its anti-tumor activity via inhibition of Wnt/β-catenin signaling. Taken together, these findings suggest that the iron chelator Dp44mT inhibits glioma development and progression both in vitro and in vivo by inducing the expression of NDRG1 and suppressing Wnt/β-catenin signaling. Thus, targeting NDRG1 with Dp44mT can be an effective treatment for glioma.
Citation Format: Peng Luo, Ye Zhang, Yang Jiang, Ying Xu, Zhitao Jing. Dp44mT, an iron chelator, suppresses cell growth and invasion by inducing N-myc downstream-regulated gene 1 and inhibiting Wnt/β-catenin signaling in human glioma 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 4201.
Abstract 4244: Hookah pipe awareness and perceived harmfulness: Prevalence, correlates, and association with smoking cessation outcomes
Authors: Mohammed Kahee A. , Schoen Martin W. , Osazuwa-Peters Nosayaba , Subramaniam Divya S. , Arnold Lauren D. , Hinyard Leslie , Burroughs Thomas E. 
Published: August 2018

Abstract
Introduction: Hookah smoking is becoming an increasingly popular choice of tobacco use and is remarkably common among young adults in the United States. This study aimed to evaluate the prevalence and correlates of hookah awareness and perceived harmfulness among US adults and to examine its association with cigarette smoking quit intention and attempt. Methods: Data from the Health Information National Trends Survey 2013 to 2017 were analyzed. The sample included 6,711 adults aged ≥ 18 years. Weighted multivariable logistic regression analyses were performed and adjusted for age, gender, race/ethnicity, education, household income, region, and cigarette smoking status. Results: Overall, 78% of US adults were aware of hookah. Of these, 72% believed hookah pipes were equally harmful as cigarettes, whereas 17.6% believed otherwise. Those who were aware of hookah were less likely to be older (aOR=0.12, 95% CI=0.09 - 0.16), Black (aOR=0.56, 95% CI=0.43 - 0.72) and Hispanic (aOR=0.61, 95% CI=0.48 - 0.79), and lesser-educated (aOR=0.40, 95% CI=0.29 - 0.54) adults. Compared to never smokers, former smokers were 64% (95% CI=1.37 - 1.96) more likely to be aware of hookah. Among those aware of hookah, older (aOR=0.49, 95% CI=0.37 - 0.65), Black (aOR=0.73; 95% CI=0.58 - 0.97), and lesser-educated (aOR=0.69; 95% CI=0.48 - 0.95) were less likely to perceive hookah as less harmful than cigarettes. Those who perceived hookah to be just as harmful as cigarettes were less likely to try to quit cigarette smoking in the past year (aOR=0.49, 95% CI=0.25 - 0.93). Those who perceived hookah to be less harmful than cigarettes were more likely to consider quitting cigarette smoking in the next 6 months (aOR=2.86, 95% CI=1.29 - 6.33). Conclusions: Young, White, and college graduate adults are more likely to believe that hookah smoking is less harmful that cigarettes. These disparities can be used to target behavioral interventions aimed at increasing individuals' perceived risk, knowledge, and perceived harmfulness of hookah smoking.
Citation Format: Kahee A. Mohammed, Martin W. Schoen, Nosayaba Osazuwa-Peters, Divya S. Subramaniam, Lauren D. Arnold, Leslie Hinyard, Thomas E. Burroughs. Hookah pipe awareness and perceived harmfulness: Prevalence, correlates, and association with smoking cessation outcomes [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 4244.
Abstract 4252: Antihypertensive medication use and ovarian cancer survival
Authors: Huang Tianyi , Sood Anil K. , Tworoger Shelley S. 
Published: August 2018

Abstract
Background: Both experimental and clinical studies suggest that beta-blockers, a common antihypertensive agent, may reduce ovarian tumor aggressiveness, inhibit angiogenesis and metastasis, and improve survival. However, no study has considered the potential role of other antihypertensive medications in conjunction with beta-blockers in ovarian cancer survival. Methods: We evaluated the associations of pre-diagnostic (n=899) and post-diagnostic (n=683) use of individual antihypertensive medications with ovarian cancer survival in the Nurses' Health Study (NHS; diagnosed between 1994-2012) and NHSII (diagnosed between 2001-2013), with at least 4 years of follow-up for death. Cox proportional hazards models were used to estimate hazard ratios (HR) for ovarian cancer mortality according to antihypertensive medication use. Results: In analyses of individual drugs adjusted for age, BMI and tumor characteristics, pre-diagnostic use of calcium-channel blockers (CCB) was associated with higher ovarian cancer mortality (HR: 1.52; 95% CI: 1.15, 2.00), whereas lower mortality was observed for post-diagnostic use of beta-blockers (HR: 0.76; 95% CI: 0.58, 1.01) and angiotensin-converting enzyme (ACE) inhibitors (HR: 0.64; 95% CI: 0.44, 0.93). While hypertension itself was not associated with ovarian cancer mortality (HR: 0.99; 95% CI: 0.83, 1.17), the associations between antihypertensive medications and ovarian cancer mortality were suggestively stronger among women with history of hypertension. Conclusion: Our findings suggest that post-diagnosis use of beta-blockers and ACE inhibitors is associated with lower ovarian cancer mortality and pre-diagnosis use of CCBs may be associated with higher mortality. These results warrant further investigation, and ongoing work is exploring whether the observed associations may be explained by changes in antihypertensive medication prescription after ovarian cancer diagnosis or changes in overall prescription patterns over time.
Citation Format: Tianyi Huang, Anil K. Sood, Shelley S. Tworoger. Antihypertensive medication use and ovarian cancer survival [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 4252.
Abstract 4277: Modeling selectin-coated microprobe adhesion to selectin ligands heterogeneously expressed on cancer tissues
Authors: Martin Eric , Goetz Douglas , Burdick Monica 
Published: August 2018

Abstract
The transition to an era of functional glycomics has created a need for the development of novel techniques to assess complex glycoconjugate cellular adhesion molecules (e.g., selectin ligands) that may be involved in capturing and mediating the adhesion circulating tumor cells to distant sites. Cell line, knockout, and selectin antagonist evidence suggests that selectin/selectin-ligand interactions are involved in metastasis. However, identification and characterization of functional selectin ligand expression on cancer tissue (i.e., CTC origin site) remains challenging due to the inherent heterogeneity of tissues magnified by the "catch-slip" and stochastic nature of selectin/selectin-ligand bonds. We have developed a flow-based assay known as dynamic biochemical tissue analysis (DBTA) that involves the perfusion of selectin-coated microprobes over tissues at physiologic wall shear rates. Using DBTA, the expression of functional selectin ligands has been detected (i.e., specific binding and rolling of selectin-coated microprobes) on tissue from multiple solid tumors at primary and metastatic sites. Although DBTA provides evidence that multiple types of cancer can express complicated glycoconjugate structures (selectin ligands) that are able to bind to selectins in a shear-dependent manner, the challenge of the assay is in the analysis of the large amounts of image sequence data generated. This analysis is further complicated by the dynamic behavior of selectin-coated microprobe adhesion to selectin ligands expressed on a heterogeneous cancer tissue surface. To extract the biophysical underpinnings towards the development of this prospective in vitro diagnostic, a mathematical model was devised to refine the design space of this flow assay. The model is semi-empirical and consists of a coupled set of stochastic, 4D partial differential equations that account for the transport of probes to the tissue surface as well as the dynamics of probe adsorption to a heterogeneous tissue surface. Empirical data were obtained by processing image sequences with machine-learning, template-matching algorithms to conduct image segmentation, followed by probe tracking over time using a program written in Python. The empirical data displayed a stochastic adsorption profile and showed agreement with the model equations that were solved numerically using a finite difference scheme written in C++. Altogether, this approach is able to successfully bridge the gap between the seemingly random rolling interactions observed in the flow assay and the underlying physical mechanisms.
Citation Format: Eric Martin, Douglas Goetz, Monica Burdick. Modeling selectin-coated microprobe adhesion to selectin ligands heterogeneously expressed on cancer tissues [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 4277.
Abstract 4279: The genomic profile investigation of metastatic triple-negative breast cancer for precision medicine achievement
Authors: Jang Wooyeong , Kim Jihyun , Yang Hanna , Kwon Youngmee , Lee Keun Seok , Sim Sung Hoon , Kong Sun-Young , An Kyounghee , Park In Hae , Park Charny 
Published: August 2018

Abstract
Objective: The molecular profile of primary breast cancer has been studied associated with drug responses. Metastatic triple-negative breast cancer (mTNBC) is heterogeneous disease and there is no effective therapeutic target. We investigated the genomic profiles of mTNBC to find potential drug targets.
Methods: Metastatic breast cancer samples were collected for genomic analysis (fresh tissue, n=17; FFPE, n=28). We conducted both whole-exome sequencing and RNA-seq for these samples and validated genomic variants by Sanger sequencing. We built up pipelines for somatic mutation, copy number alteration, mRNA expression, and fusion gene analysis. Precise somatic mutations were additionally filtered out for FFPE without matched normal. In addition, we investigated the differences of genomic profiles of mTNBC with those of primary breast cancer from TCGA data.
Results: Most of somatic mutation profiles of mTNBC were similar with those of primary cancer. However, there were some specific alterations that were not found in primary tumor. TP53 (&gt;40 %) was concordantly discovered with primary TNBC, but KDM6A (&gt;20 %) was highly recurrent than other breast datasets. We ascertained the diversity of immune cell activity from mRNA expression analysis, and additional pathways also represented the variance within our mTNBC population, which was differentiated from those of primary breast cancer. In addition, we found two novel FGFR1/2 fusion in two cases and validated it by RT-PCR and Western blot.
Conclusion: We found specific genomic profiles of mTNBC that were distinct from those of primary tumor. Novel structural variants discovered in our dataset could be potential therapeutic targets for mTNBC patients.
Citation Format: Wooyeong Jang, Jihyun Kim, Hanna Yang, Youngmee Kwon, Keun Seok Lee, Sung Hoon Sim, Sun-Young Kong, Kyounghee An, In Hae Park, Charny Park. The genomic profile investigation of metastatic triple-negative breast cancer for precision medicine achievement [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 4279.
Abstract 4288: The cell cycle gene regulatory DREAM complex is disrupted by oncogenic B-Myb
Authors: Iness Audra N. , Ananthapadmanabhan Varsha , Sesay Fatmata , Dozmorov Mikhail , Litovchick Larisa 
Published: August 2018

Abstract
The oncogene MYBL2 (encoding B-Myb) is a poor prognostic biomarker in many cancers. B-Myb interacts with the MuvB core of five proteins (LIN9, LIN37, LIN52, LIN53/RBBP4, and LIN54) to form the MMB (Myb-MuvB) complex and promotes expression of late cell cycle genes necessary for progression through mitosis. Both MYBL2 amplification and over-expression are associated with deregulation of the cell cycle and increased cell proliferation. Alternatively, by interacting with E2F4-DP1 and p130/p107, the MuvB core becomes part of the DREAM complex (DP, RB-like, E2F, and MuvB). The DREAM complex opposes MMB by globally repressing cell cycle genes in G0/G1, maintaining the cell in a quiescent state. However, the specific mechanism by which B-Myb alters the cell cycle is not well understood. Herein, we show that B-Myb disrupts the DREAM complex by sequestration and stabilization of LIN52. Analysis of The Cancer Genome Atlas data revealed significant upregulation of DREAM and MMB target genes in breast and ovarian cancer with MYBL2 gain. Given that most of the DREAM target genes are not directly regulated by B-Myb, we investigated the effects of B-Myb on DREAM formation. We found that depletion of B-Myb results in increased DREAM formation in cancer cell lines, while its overexpression inhibits DREAM formation in non-transformed cells. Since the MuvB core subunit LIN52 is essential for assembly of both the DREAM and MMB complexes, we tested whether B-Myb disrupts DREAM by sequestering LIN52. Overexpression of LIN52 did not increase either DREAM or MMB formation, but instead increased the turnover rate of the endogenous LIN52 protein. Interestingly, co-expression of B-Myb increased the expression of both endogenous and overexpressed LIN52 while knockdown of B-Myb had an opposite effect. We found that regulation of LIN52 occurs at the protein level, and that activity of DYRK1A kinase, the enzyme that triggers DREAM complex formation by phosphorylating LIN52, is required for this regulation. These findings are the first to implicate B-Myb in the disassembly of the DREAM complex and offer further mechanistic insights for cancers with MYBL2 amplification. We conclude that B-Myb's oncogenic effects are not only secondary to increased mitotic gene expression by the MMB complex, but also broad disruption of cell cycle gene regulatory programs through compromised DREAM formation.
Citation Format: Audra N. Iness, Varsha Ananthapadmanabhan, Fatmata Sesay, Mikhail Dozmorov, Larisa Litovchick. The cell cycle gene regulatory DREAM complex is disrupted by oncogenic B-Myb [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 4288.
Abstract 4289: Involvement of the miR-6883 family and the circadian rhythm gene PER1 in the DNA damage response (DDR) and chemosensitivity
Authors: Lulla Amriti R. , Lev Avital , Slifker Michael , Dicker David T. , El-Deiry Wafik S. 
Published: August 2018

Abstract
PER1 is a circadian clock protein known to play a role in the cell cycle by directly regulating levels of Wee1 and indirectly influencing levels of Cdc2 and Cyclin B1. PER1 interaction with CHK2 promotes apoptosis in response to DNA damaging agents and loss of PER1 promotes chemoresistance. Expression of PER1 is found to be lost in most CRC tumors and restoring it sensitizes CRC cell lines to DNA damaging chemotherapeutic agents. However, the regulation of PER1 and its mechanism of repression in CRC remains unknown. We recently discovered and characterized miR-6883-5p, which is an intronic miRNA in the PER1 gene. Since PER1 is lost in most CRC it is suggested that the expression of miR-6883-5p is also lost. We showed that restoring the expression of miR-6883-5p via mimics induces G1-arrest and subsequent cell death in CRC cell lines. Similar to the overexpression of PER1, expression of miR-6883-5p with mimics increased the sensitivity of CRC cell lines to chemotherapeutic agents such as irinotecan and 5-FU. miR-6883-5p is a direct negative regulator of CDK4 and CDK6 and the downstream G1-S transition via RB. Our ongoing studies are characterizing molecular targets of miR-6883-5p and its role in the DNA damage response (DDR). FOXM1 is a downstream effector of CDK4 that plays a role in the DDR. Downregulation of FOXM1 sensitizes cells to DNA damage and restores chemosensitivity. We are further evaluating the direct effects of miR-6883-5p on FOXM1. FOXM1 is a member of the forkhead box (FOX) transcription factor family, expressed exclusively in proliferating cells. Its upregulation in different tumor types, including CRC promotes cell proliferation, EMT and chemoresistance. Interestingly, FOXM1 is also a repressor of the clock gene CRY2. Here, we hypothesize that miR-6883-5p mediated targeting of FOXM1 is crucial for the DDR, and, further, like CRY2, FOXM1 might have a role in regulating PER1 and thus miR-6883-5p endogenous levels. We report that miR-6883-5p levels are increased following exposure of tumor cells to chemotherapeutic agents that cause DNA damage. We are further elucidating the role of FOXM1 in the induction of miR-6883-5p under the DDR, and propose that induction of miR-6883-5p may provide a novel mechanism for tumor growth arrest in chemotherapy-exposed cells.
Citation Format: Amriti R. Lulla, Avital Lev, Michael Slifker, David T. Dicker, Wafik S. El-Deiry. Involvement of the miR-6883 family and the circadian rhythm gene PER1 in the DNA damage response (DDR) and chemosensitivity [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 4289.
Abstract 4294: SUMOylation promotes nuclear import and stabilization of polo-like kinase 1 to support its mitotic function
Authors: Wen Donghua , Wu Jianguo , Wang Lei , Fu Zheng 
Published: August 2018

Abstract
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the regulatory pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report for the first time that a novel PTM, SUMOylation, plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1, upon initial phosphorylation and activation by CDK1/cyclin B. By in vivo and in vitro SUMOylation assays, PLK1 was identified as a physiologically relevant SUMO-targeted protein, preferentially modified by SUMO-1. We further showed that K492 on PLK1 was the lysine residue essential for SUMOylation. SUMOylation not only led to PLK1's nuclear import, but also significantly increased its protein stability by preventing the recruitment of APC/Ccdh1, the ubiquitin E3-ligase of PLK1. Resembling Ubc9 deficiency, cells expressing PLK1-K492R mutant exhibited mitotic aberrations characterized by prolonged mitotic progression, and misaligned and/or mis-segregated chromosomes, which could be rescued by reintroducing SUMOylation modification to PLK1. Collectively, our findings suggest that SUMOylation is another important regulatory mechanism governing PLK1's mitotic function to ensure normal mitotic progression and genomic integrity.
Citation Format: Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu. SUMOylation promotes nuclear import and stabilization of polo-like kinase 1 to support its mitotic function [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 4294.