bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1319: Edge-based integration of multi-omics data gives more accurate prognostic prediction in pancreatic cancer
Authors: Sun Yidi , Li Chen , Zeng Rong 
Published: August 2018

Abstract
Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, and predicted to be the second within a decade. Five-year survival of PC is less than 5% with a median survival just a couple of months. Therefore, a better understanding of the molecular pathology of PC is an urgent need to achieve advances in clinical treatment for patients. Genomic analyses previously have revealed heterogeneous landscapes of mutation, copy number variation, structural variation and gene expression in pancreatic cancer. While clinical evidence for this proposition is limited and the signaling and biological effects of genomic variations are not routinely determined in human tumors even though they are rationally considered to be drug targets. Luckily, with recent advances in mass spectrometry (MS), comprehensive proteomic and lipidomics analyses provide a potentially valuable approach to validate genomic findings and discover targeted treatments for pancreatic cancer patients.
We generated high-throughput proteomic and lipidomic data for pancreatic cancer patients aged from 40 to 80 years old with matched normal samples using TMT-labeling quantitative proteomic method and target lipidomic method. We found promising protein and lipid biomarkers closely related with the clinical outcome of pancreatic cancer patients. Taking signaling and biologically pathways into consideration, we used an edge-based method to distinguish prognostics, where edge features were constructed based on the correlation between each pair of molecules. We then performed feature selection and prognostic classification for both the original expression dataset and the transformed edge dataset and found the edge-based features can give a more accuracy for prognostic prediction, suggesting the promising role of protein and lipid edge biomarkers for clinical utility in pancreatic cancer.
Our preliminary results highlight the usefulness of edge-based integration of proteomics and lipidomics data. To explain the mechanisms in the development of pancreatic cancer, we are going to integrate genomic variations from whole genome sequencing (WGS) into our current progress for further analysis. In conclusion, this initial work demonstrated a strategy that may enable more accurate prediction of the survival of pancreatic cancer by integrating multi-omics data from genomics, proteomics and lipidomics. In principle, we anticipate the declaration of possible mechanisms enabling the treatment of pancreatic cancer patients in the near future.
Citation Format: Yidi Sun, Chen Li, Rong Zeng. Edge-based integration of multi-omics data gives more accurate prognostic prediction in pancreatic cancer [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 1319.
Abstract 1321: Mutational landscape of adherens junctions in skin cutaneous melanoma
Authors: Korla Praveen Kumar , Gracilla Daniel Esguerra , Kuo Brian Yu-Ting , Sheu Jim Jinn-Chyuan 
Published: August 2018

Abstract
Cadherin proteins regulate cell-cell contact through calcium-dependent manner, thus play pivotal roles in morphogenetic and differentiation processes during tissue development. Reprograming in cadherin profiles contributes to epithelial-mesenchymal transition (EMT), leading to disorganized lining of epithelial tissues and cancer metastasis. To elucidate genetic impacts of classical cadherins on melanoma development, mutation profiles were analyzed using data from the TCGA databank. Among 20 classical cadherins, CDH6 showed the highest mutation frequency (11.3 %), and most of which were G to A or C to T nucleotide substitutions, a signature for UV-caused DNA damage. Two groups of unique hotspots were found on the fifth cadherin domain (D5) (S524L and S526F) and cytoplasmic cadherin domain (CDH-C) (E662K and E722K), respectively. Protein interactome and expression co-occurrence analyses placed CDH6 at the center of core cadherin network and showed strong heterophilic interactions of CDH6 with CDH4, CDH9, and CDH12. Multiple sequence alignment indicated the involvement of those hotspots in the conserved regions, which are responsible for heterophilic interaction on D5 or catenin (alpha, beta, and gamma) binding on CDH-C. Molecular modeling defined alterations in protein structures of the D5 and CDH-C domains caused by the hotspot mutations, which may influence cell-cell contact and the down-stream signaling. In sum, our data suggest CDH6 as the key player to modulate adherens junctions during the development of melanoma.
Citation Format: Praveen Kumar Korla, Daniel Esguerra Gracilla, Brian Yu-Ting Kuo, Jim Jinn-Chyuan Sheu. Mutational landscape of adherens junctions in skin cutaneous melanoma [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 1321.
Abstract 1336: Autophagy inhibition reverses EMT and reduces 3D growth of pancreatic adenocarcinoma cells in vitro and in vivo
Authors: Pearce Jane B. , O'Flanagan Ciara H. , Hursting Stephen D. 
Published: August 2018

Abstract
Pancreatic cancer is the 4th most fatal cancer in US men and women, with 5-year survival rates under 5%. Obesity is one risk factor known to increase pancreatic cancer risk by facilitating tumorigenesis and metabolic processes associated with pancreatic tumor growth and progression. Autophagy is the catabolic process of recycling cellular organelles to provide energy to the cell and is often induced when cells become stressed. Autophagy plays a critical role in cancer growth and metastasis, and in many cancers autophagy inhibition decreases the size of tumors in in vivo models. Our current studies investigate the link between the autophagy inhibition and the invasiveness of pancreatic cancer. To understand the role of autophagy on invasion, EMT and 3D growth in pancreatic cancer, Kras-driven Panc02 mouse pancreatic cancer cells were transduced using CRISPR/Cas9 to cleave the gene encoding autophagy related protein 5 (Atg5). Atg5 deletion resulted in striking morphological alterations, including a more epithelial-like appearance. In addition, Atg5 deletion resulted in increased expression of the epithelial marker E-Cadherin, concurrent with decreased expression of mesenchymal markers N-Cadherin and Snail. Furthermore, Atg5 deletion resulted in significant decreased invasiveness and ability to form colonies under anchorage-independent conditions, with no significant difference in 2D cell growth. Orthotopic, intrapancreatic injection of these cells into C57BL/6 mice resulted in reduced tumor take and growth. Taken together, these results for the first time show that autophagy inhibition results in reduced EMT and 3D growth in pancreatic adenocarcinoma and highlight autophagy's role in pancreatic adenocarcinoma progression.
Citation Format: Jane B. Pearce, Ciara H. O'Flanagan, Stephen D. Hursting. Autophagy inhibition reverses EMT and reduces 3D growth of pancreatic adenocarcinoma cells in vitro and in vivo [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 1336.
Abstract 134: Dysbiosis of gut microbiota in chronic stressed patients with endometriosis
Authors: Xu Jing , Kang Yu , Yu Yinhua 
Published: August 2018

Abstract
Although endometriosis is a benign disease, it has malignant characters such as invasion and migration. Besides, there is an endometrial type of ovarian cancer, which means endometriosis is similar to malignant disease at some extent. Existing researches showed that patients with endometriosis often have high level of chronic stress. Furthermore, chronic stress can promote the growth of endometriosis by activating the β-adrenergic signaling pathway. Gut microbiota is reported to be related to the stress level through the gut-brain axis. So we wonder whether gut microbiota is associated with chronic stress level in endometriosis patients, which may provide a new clinical intervention method to improve prognosis. We grouped the endometriosis patients into stress group and control group with GAD-7 and PHQ-9 questionnaires and collected patients' fecal and tissues samples. Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method and we performed Immunohistochemistry (IHC) to detect the activation of inflammatory pathways in endometriosis tissues. We found that in patients with endometriosis, dysbiosis of gut microbiota is associated with patients' stress levels and Paraprevotella, Odoribacter, Veillonell and Ruminococcus show significant differences with reduced levels in chronic stressed endometriosis patients group, which represents a disease-specific change of gut microbiota on the genus level. Besides, compared to the control group, the expression level of inflammatory cytokines, NF-κB p65 and COX-2, increased in the chronic stressed patients group, which means that dysbiosis of gut microbiota may active the inflammatory pathway of gut-brain axis. In conclusion, we found new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis, which can be a new examination target of chronic stress level and may provide an adjuvant therapy method for clinical psychological intervention, reducing the stress level and improving the prognosis of endometriosis patients.
Citation Format: Jing Xu, Yu Kang, Yinhua Yu. Dysbiosis of gut microbiota in chronic stressed patients with endometriosis [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 134.
Abstract 1340: Assessing autophagic flux in cell culture models with a novel plate-based assay
Authors: Lazar Dan F. , Kessens Ryan W. , Gillette Amani A. , Butler Braeden L. , Eggers Christopher T. , Binkowski Brock F. , Vidugiris Gediminas , Slater Michael R. , Ma Dongping , Cali James J. 
Published: August 2018

Abstract
The importance of autophagy in normal cell health and diseased states, including cancer, immunology and inflammation, has become quite clear. Given the growing interest in screening for autophagy modulators, we have developed a homogeneous plate-based assay to measure autophagic flux in cell culture models using NanoLuc® Binary Technology (NanoBiT™). LC3B (Atg8) protein was tagged on its N-terminus with an 11 amino acid peptide, (HiBiT), as well as an intervening “spacer” sequence. When expressed at low-to-moderate levels in mammalian cell lines, this LC3-based reporter is subject to degradation by the autophagic pathway. Changes in reporter levels following cell treatment are determined by addition of a lytic reagent containing Large BiT (LgBiT), which rapidly associates with HiBiT to produce a bright, luciferase activity in the presence of added substrate. In stable U2OS reporter cells, mTORC inhibitor treatment decreased assay signal by 25% (rapamycin) to 60% (PP242, AZD8055), consistent with compound stimulation of autophagic flux and degradation of the autophagy reporter. In contrast, treatment with autophagy inhibitors (bafilomycin A1, chloroquine) produced a 70-80% increase in assay signal, consistent with accumulation of autophagy reporter following blockade of basal autophagy. Similar results were obtained in HEK293 cells stably expressing the reporter, as well as in cells in which autophagy reporter was transiently expressed via simple, one-step transduction with BacMam viral particles. Mechanism of action of autophagy modulators was confirmed through blockade of effects by 50nM bafilomycin A1 cotreatment. Multiplex with a cell necrosis detection agent allowed for same-well determination of cytotoxic effects that might undermine analysis of a compound's discrete effects on autophagic flux. When assayed in 384-well plates with automation, U2OS and HEK293 autophagy reporter cells produced Z' values of 0.6-0.7 in response to autophagy induction (PP242), and Z' values of 0.7-0.8 by subsequent blockade of autophagy (PP242 + bafilomycin A1). Therefore, using this novel plate-based assay system for the determination of autophagic flux, it is possible to screen test agents and quantitatively assess their effects in cell culture models.
Citation Format: Dan F. Lazar, Ryan W. Kessens, Amani A. Gillette, Braeden L. Butler, Christopher T. Eggers, Brock F. Binkowski, Gediminas Vidugiris, Michael R. Slater, Dongping Ma, James J. Cali. Assessing autophagic flux in cell culture models with a novel plate-based assay [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 1340.
Abstract 1346: Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma
Authors: Yuhaiyang Yuhaiyang Yuhaiyang 
Published: August 2018

Abstract
Lycorine is a multi-functional bioactive compound, and it possesses potential anti-cancer activities. However, little is known about the underlying mechanism. In this research we have found that lycorine significantly induces the apoptotic and autophagic capacities of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Treatment with specific autophagy inhibitor (3-methyladenine/Bafilomycin A1) or knockdown of LC-3B/Atg5 by siRNA drastically enhances the apoptotic cell death effect by facilitating the switch from autophagy to apoptosis. Molecular validation mechanistically demonstrates that lycorine-induced apoptosis and autophagy in HCC cells is associated with decreased protein levels of tongue cancer resistance-associated protein 1 (TCRP1), and we further find that inhibition of TCRP1 decreases phosphorylation level of Akt and represses Akt/mTOR signaling. Finally, lycorine-induced apoptosis and autophagy suppress the growth of xenograft hepatocellular tumors without remarkable toxicity. Our results elucidate a novel molecular mechanism whereby lycorine promotes apoptosis and autophagy through TCRP1/Akt/mTOR pathway in HCC. Our results reveal that lycorine might be a potential therapeutic agent for the treatment of HCC.
Citation Format: Yuhaiyang Yuhaiyang Yuhaiyang. Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma [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 1346.
Abstract 1349: Functional and mechanistic characterization of PRMT6 regulated autophagy in hepatocellular carcinoma
Authors: Che Noélia , Tong Man , Ng Kai Yu , Kau Phillis WF , Guan Xin Yuan , Huen Michael SY , Ma Stephanie 
Published: August 2018

Abstract
Hepatocellular carcinoma (HCC) is a major health burden worldwide. Tumor recurrence and therapy resistance represent major obstacles in the treatment of the disease, with their mechanism of action largely uncharacterized. Autophagy is a critical survival factor for cancer cells, whereby it maintains cellular homeostasis including degradation of damaged organelles and unwanted proteins as well as the support of cellular biosynthesis in response to environmental stress, preventing cells from undergoing apoptosis. Our group has recently reported on the regulatory role of protein arginine methyltransferase 6 (PRMT6) down-regulation in maintenance of HCC, particularly potentiating resistance to sorafenib and chemotherapy. By tandem affinity purification/mass spectrometry analysis of cells with PRMT6 stably overexpressed, we identified a number of autophagy related proteins as potential interacting partners of PRMT6, suggesting a possible role of PRMT6 in modulating autophagy in HCC. Treatment of HCC cells with stress induced conditions, including sorafenib, nutrient deprivation and hypoxic condition, resulted in a marked reduction of PRMT6 expression, concomitant with elevated levels of LC3BII. Further, under these various stimuli, knockdown of PRMT6 in HCC cells would also result in enhanced expression of LC3BII, accumulation of GFP-LC3B positive puncta staining as well as an increase in autophagosome formation. Consistently, treatment of HCC cells with PRMT6 overexpressed would leading to an opposing effect. Further studies by immunoprecipitation analysis validated PRMT6 to physically interact with AMBRA1 (activating molecule in BECN1-regulated autophagy protein 1), a well-known autophagy initiative component, which takes part in autophagy vesicle nucleation, a critical step for autophagic initiation. Our findings suggest PRMT6 down-regulation in HCC tumors to promote tumorigenicity through autophagic flux de-regulation. Targeting the mechanisms of stress response may provide novel therapeutic insights for the disease.
Citation Format: Noélia Che, Man Tong, Kai Yu Ng, Phillis WF Kau, Xin Yuan Guan, Michael SY Huen, Stephanie Ma. Functional and mechanistic characterization of PRMT6 regulated autophagy in hepatocellular carcinoma [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 1349.
Abstract 1351: Inhibition of autophagy enhances dihydroartemisinin (DHA)-induced cytotoxicity through DR5 upregulation
Authors: Mei-Chuan Chen 
Published: August 2018

Abstract
Artemisinin (Qinghaosu) comes originally from Qinghao has been used against Plasmodium falciparum malaria for a long time. Dihydroartemisinin, an analogue of artemisinin, is also be listed by WHO to exhibit antimalarial and anticancer properties.
In our study, DHA exhibits antiproliferative activity in several solid tumors, especially against colorectal cancer (CRC) HCT116 cells. Our current results show DHA suppresses cell proliferation and induces caspase-dependent apoptosis without inducing necrosis-like cell death in HCT116 cells. In addition, DHA interferes autophagy pathway by upregulating of LC3 II formation in HCT116 cells. Inhibition of autophagy with either autophagy inhibitor 3-methyladenine (3MA) or KD of ATG5 potentiated DHA-induced cell death. We found DHA increased expression level of DR5 while had no effect on DR4 expression level on surface of tumor cells. Further, cell-surface DR5 expression was significantly elevated in DHA-treated ATG5-KD cells. These findings suggest that inhibition of the autophagy enhances DHA-induced cytotoxicity through DR5 upregulation.
Key words: Apooptsis, DR5 (Death Receptor 5), autophagy, colorectal cancer
Citation Format: Chen Mei-Chuan. Inhibition of autophagy enhances dihydroartemisinin (DHA)-induced cytotoxicity through DR5 upregulation [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 1351.
Abstract 1363: Regulation of BRCA1 by SIRT2
Authors: Minten Elizabeth , Zhang Hui , Li Chunyang , Head PamelaSara , Yu David 
Published: August 2018

Abstract
In our everyday lives, we are constantly being exposed to DNA damaging agents, both from internal and external sources. The most deleterious type of DNA damage a cell can suffer is the DNA double-stranded break (DSB). Breast Cancer 1 (BRCA1) is a protein necessary for the proper repair of resultant DNA DSBs through the homologous recombination (HR) pathway. Defects in BRCA1 have been linked to different types of cancer in both men and women, including breast, ovarian, and pancreatic cancer. However, the regulation of BRCA1 is not yet well understood, and in many cases, how defects in this pathway lead to an increased risk of developing cancer is also unknown, making preventative care and treatment of resulting cancers more difficult. Our lab has discovered that SIRT2, a histone deacetylase and putative human tumor suppressor, plays a crucial role in the DNA damage response (DDR) and repair of DNA DSBs. We have shown that depletion of SIRT2 impairs HR and increases cell sensitivity to IR in a deacetylase-dependent manner. A mass spectrometry analysis showed SIRT2 interacts with a number of proteins involved in DDR, including BRCA1. We validated the interaction between SIRT2 and BRCA1 and also found SIRT2 deacetylates BRCA1 both in vitro and in cells. Depletion of SIRT2 and subsequent deacetylation of BRCA1 decreases BRCA1 protein levels in cells and thus impairs HR. Our results show SIRT2 is a novel regulator of BRCA1 and is critical for the repair of DNA DSBs through HR. These findings provide insight into how dysregulation of SIRT2 or BRCA1 can result in genomic instability and lead to the development of cancer.
Citation Format: Elizabeth Minten, Hui Zhang, Chunyang Li, PamelaSara Head, David Yu. Regulation of BRCA1 by SIRT2 [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 1363.