bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4310: SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway
Authors: Choi Yu-Jeong , Kim Myeong-Sun , Kang Soo-Yeon , Lee Kangwook , Ku Jin Mo , Hong Se Hyang , Kim Hyo In , Cheon Chunhoo , Ko Youme , Wen Huang Ching , Sasaki Yui , Kang Sohyeon , Kim Tai Young , Kim Ji Hye , Shin Yong Cheol , Ko Seong-Gyu 
Published: July 2017

Abstract
Herbal medicines have been used in cancer treatment, with many exhibiting favorable side effect and toxicity profiles compared with conventional chemotherapeutic agents. SH003 is a novel extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes Kirilowii Maximowicz combined at a 1:1:1 ratio that impairs the growth of breast cancer cells. Our data demonstrate that SH003 induced apoptosis in DU145 prostate cancer cells by inhibiting ERK signaling. SH003 induced apoptosis of prostate cancer cells in dose-dependent manner, which was independent of androgen dependency. SH003 also increased intracellular ROS levels but this is not associated with its pro-apoptotic effects. SH003 inhibited phosphorylation of Ras/Raf1/MEK/ERK/p90RSK in androgen-independent DU145 cells, but not androgen-dependent LNCaP and PC-3 cells. Moreover, ERK2 overexpression rescued SH003-induced apoptosis in DU145 cells. Thus, our data conclude that SH003 induces apoptotic cell death of DU145 prostate cancer cells by inhibiting ERK-mediated pathway.
Citation Format: Yu-Jeong Choi, Myeong-Sun Kim, Soo-Yeon Kang, Kangwook Lee, Jin Mo Ku, Se Hyang Hong, Hyo In Kim, Chunhoo Cheon, Youme Ko, Huang Ching Wen, Yui Sasaki, Sohyeon Kang, Tai Young Kim, Ji Hye Kim, Yong Cheol Shin, Seong-Gyu Ko. SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway [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 4310. doi:10.1158/1538-7445.AM2017-4310
Abstract 4318: Role of Bcl-2 in hematological cancer formation
Authors: Fortier Abigail V. , Koh Ally , Stanovski Lisa , Kepner Alisa , Jain Supriya , Ul-Islam Misha , Walter Ellie , Boise Lawrence 
Published: July 2017

Abstract
B cell leukemia/lymphoma 2 (BCL-2) is a 26 kilodalton, amphipathic, anti-apoptotic protein located on the outer mitochondrial membrane. BCL-2 interacts with other anti-apoptotic and pro-apoptotic factors in order to regulate apoptosis. If a structural change occurs on the BCL-2 gene, overexpression of the BCL-2 protein can result. This causes a change in the ratio of BCL-2 to its BCL-2 Homologous 3 (BH3) ligands, preventing the release of the apoptotic signal. The primary change associated with BCL-2 overexpression in lymphomas is a t(14;18) chromosomal translocation, which causes an increase in BCL-2 transcription. The upregulation of the oncogene allows for the survival of the mutated B cells by raising the apoptotic threshold, which then dislodges regular lymphocytes in the bone marrow or lymph nodes. Lack of cell death due to overexpression of BCL-2 has been linked to hematological malignancies, specifically lymphomas and myelomas. Both B-lymphocytic cancers can result from alterations of the immunoglobulin heavy chain locus on chromosome 14. While BCL2 translocation can cause Follicular Lymphoma, BCL2 over-expression is observed in many other tumor types and likely contributes to cancer progression and drug resistance in these tumors. Treatments to inhibit BCL-2 include attempts at activation and overexpression of the pro apoptotic BH3 proteins, BCL-2 Associated X Protein (BAX) and BCL-2 Associated K protein (BAK), and creation of BH3 mimetics. Indeed, the FDA approved the BCL2 inhibitor Venetoclax (ABT-199) earlier this year for the treatment of Chronic Lymphocytic Leukemia. These treatments could help cause cancer cell death by binding to targeted anti-apoptotic proteins and causing the signal for apoptosis to be released. This could neutralize the cancerous effects of the BCL-2 oncogene upregulation. Walton High School SMART (Students Modeling A Research Topic) Team used the computer program JMOL to create a 3D printed model of BCL-2 and composed a review poster of our secondary research to investigate and demonstrate the relationship between the structure and function of this molecule.
Citation Format: Abigail V. Fortier, Ally Koh, Lisa Stanovski, Alisa Kepner, Supriya Jain, Misha Ul-Islam, Ellie Walter, Lawrence Boise. Role of Bcl-2 in hematological cancer formation [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 4318. doi:10.1158/1538-7445.AM2017-4318
Abstract 4323: Metabolic reprogramming in acute myeloid leukemia cells by mesenchymal stromal cell-derived exosomes induces chemoresistance
Authors: Zhao Hongyun , Achreja Abhinav , Zhu Ziwen , Rawi Ahmed N. , Konopleva Marina , Andreeff Michael , Nagrath Deepak 
Published: July 2017

Abstract
Mesenchymal stromal cells play an important role in acute myeloid leukemia (AML) development. Altered cellular metabolism supports AML cells' survival in multiple aspects, such as drug resistance. Here, we demonstrate the role of MSC-derived exosomes in metabolic regulation of AML cells, and put forward a combinatorial strategy to sensitize AML cells to chemodrugs. Exosomes secreted by MSCs can reprogram the metabolic machinery following their internalization by AML cells. Through 13C tracing experiments and flux analysis, we elucidate that MSC-derived exosomes enhance oxidative phosphorylation and glutamine's entry into TCA cycle, which replenish the pool of carbon sources in mitochondria. Further, our work shows that inhibiting the interactions between MSCs and AML cells by targeting the metabolic regulation exerted by MSC-derived exosomes sensitizes AML cells to chemodrugs. Taken together, our work reveals a novel role of the TME in regulating the metabolic adaptation in AML cells and uncovers the improved strategy for AML therapy.
Citation Format: Hongyun Zhao, Abhinav Achreja, Ziwen Zhu, Ahmed N. Rawi, Marina Konopleva, Michael Andreeff, Deepak Nagrath. Metabolic reprogramming in acute myeloid leukemia cells by mesenchymal stromal cell-derived exosomes induces 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 4323. doi:10.1158/1538-7445.AM2017-4323
Abstract 4324: Estrogen promotes proliferation and apoptosis of endometrial carcinoma cell lines Ishikawa and HEC1A via endometrial stromal cells
Authors: Tao Xiang , Wu Jian , Yu Yinhua 
Published: July 2017

Abstract
Endometrial carcinoma is the leading malignancies of women in Western countries and the second leading cancer of female in China. As endometrial stromal cells (ESCs) are sharply decreased in endometrial carcinoma (EC) compared to normal endometrium, it is interested to explore the roll of ESCs in the tumorigenesis of endometrium. Unopposed estrogen is considered as the etiology of endometrioid carcinoma, but the underlying mechanism is needed to further explore. This study is to determine the biological effects of primary cultured ESCs on two endometrial cancer cell lines-Ishikawa and HEC1A. ESCs from normal, atypical hyperplastic and malignant endometrial specimens were collected, validated by immunohistochemistry and cultured in vitro, which were maintained in a medium containing 10 nM estradiol (E2) for three months to simulate the unopposed estrogen stimulation of EC patients. Microarray were performed to detect the alteration of gene expression, which were then confirmed by real time RT-PCR. Co-culture of ESC and EC cell lines were performed by Transwell plate. Cell proliferation was analyzed by CCK8 assay. Apoptosis was analyzed by flow cytometry based on PI/Anexin V staining. Our results showed E2 promoted the proliferation of three types of ESCs. E2 has no direct effect on cancer cell lines Ishikawa and HEC1A, but when they co-cultured with ESCs, which were stimulated by E2, the proliferation of cancer cells was promoted by all three type of ESCs. Moor interestedly, we found that the much obvious promoted effects were occurred by the ESCs that extracted from malignant samples. Estrogen could also reduce the apoptosis of both cancer cell lines when co-culturing with ESCs from normal specimen. Gene microarray and real time RT-PCR indicated that collagen 9 were up-regulated 2.3 times when ESCs cells treated by E2. In conclusion, Estrogen altered the microenvironment of stromal cells, which could lead to the proliferation of endometrial carcinoma cells via paracrine function. The alteration of collagen synthesis by ESCs might contribute to this communication between the epithelial and mesenchymal cells.
Citation Format: Xiang Tao, Jian Wu, Yinhua Yu. Estrogen promotes proliferation and apoptosis of endometrial carcinoma cell lines Ishikawa and HEC1A via endometrial stromal 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 4324. doi:10.1158/1538-7445.AM2017-4324
Abstract 4339: Single cell RNA sequencing dissects cellular growth factor dependencies and oncogenic driver effects in an organoid model of gastric cancer
Authors: Chen Jiamin , Andor Noemi , Grimes Susan M. , Lau Billy , Ji Hanlee P. 
Published: July 2017

Abstract
Gastric cancer is a lethal malignancy with few therapeutic options. Gastric tumors rely on complex intercellular signaling “crosstalk” that enables tumor development, metastasis, and therapeutic resistance. To recapitulate the intercellular communications among various cell populations that exist in vivo, we are using a three-dimensional culture system to grow and manipulate mouse gastric tissue in vitro, otherwise referred to as organoids. Importantly, this organoid model contains epithelium with its endogenous mesenchymal niche and does not require exogenous Wnt stimulation. To systematically analyze the distinct cellular lineages and their interactions, we applied a massively-scaled single cell RNA-Seq platform to sequence thousands of individual cells from organoid cultures. With PCA and t-SNE analysis of the high-dimensional data generated from single cell RNA-seq, we characterized two major cell types, i.e. epithelial and mesenchymal cells. Leverage the information from single cell transcriptome profiles, we identified specific niche factors of the Wnt signaling pathways that are activated in different stomach cell lineages. These results suggest that the mesenchymal cell populations provide a potential source of the R-spondin, a Wnt agonist, that sustains the growth of epithelium. Furthermore, we compared cell populations from Cdh1-/-/Trp53-/- and Trp53-/-organoids, and characterized changes on the transcriptome profiles due to the loss of Cdh1, an early oncogenic event in diffuse gastric cancer development. Overall, using organoid model and high-throughput single cell RNA-Seq provides a novel approach to study early tumor transformation and critical cancer-stroma interactions.
Citation Format: Jiamin Chen, Noemi Andor, Susan M. Grimes, Billy Lau, Hanlee P. Ji. Single cell RNA sequencing dissects cellular growth factor dependencies and oncogenic driver effects in an organoid model of gastric cancer [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 4339. doi:10.1158/1538-7445.AM2017-4339
Abstract 434: Characterizing the role of serine metabolism in pediatric sarcomas
Authors: Issaq Sameer , Kidner Ria , Rohde Jason , Boxer Matthew , Helman Lee 
Published: July 2017

Abstract
Sarcomas represent a diverse group of malignancies with unique molecular and pathological characteristics. In order to improve sarcoma treatment, a better understanding of the alterations associated with specific sarcoma subtypes is critically important. Renewed interest in the altered metabolic properties of cancer cells has led to an exploration of targeting metabolic dependencies as a novel therapeutic strategy. Metabolism of the amino acid serine is frequently altered in cancer, supporting a number of critical biological processes, including protein, lipid, and nucleotide synthesis, and redox balance. The first, rate-limiting step in the serine synthesis pathway is catalyzed by the enzyme 3-phosphoglycerate dehydrogenase (PHGDH), which is overexpressed in several cancers. Previous work has shown that PHGDH loss or inhibition is selectively toxic to cancer cells with high PHGDH expression or increased flux through the serine synthesis pathway. In this study, we have characterized the dependency of pediatric sarcomas on serine metabolism by examining expression of PHGDH in Ewing sarcoma and rhabdomyosarcoma cell lines, and evaluating the effects of PHGDH inhibition and serine deprivation on cellular proliferation and bioenergetic properties. We show that PHGDH is highly expressed in pediatric sarcoma cell lines, and that PHGDH knockdown resulted in decreased proliferation, especially under conditions of serine limitation. Moreover, pharmacological inhibition of PHGDH resulted in a dose-dependent decrease in proliferation and mitochondrial bioenergetic function. Furthermore, individual sarcoma cell lines were differentially sensitive to serine deprivation, indicating that some sarcoma cells may depend on extracellular serine in addition to de novo serine synthesis. Our findings suggest that the dependency of pediatric sarcomas on serine metabolism should be further investigated in order to identify vulnerabilities that could be targeted for potential therapeutic benefit.
Citation Format: Sameer Issaq, Ria Kidner, Jason Rohde, Matthew Boxer, Lee Helman. Characterizing the role of serine metabolism in pediatric sarcomas [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 434. doi:10.1158/1538-7445.AM2017-434
Abstract 4349: Adverse & anticancer activities of 5-azaCdR & DNA methyltransferase (DNMT) isoform specific inhibitors: therapeutic implications
Authors: Cheishvili David , Szyf Moshe 
Published: July 2017

Abstract
Activation of methylated and silenced promoters of genes that suppress tumorigenesis has been the rationale behind the clinical use of DNMT family inhibitor 5aza for treating cancer. However, the adverse effects of general DNA methylation inhibition on tumors through activation of tumor promoting and prometastatic genes as well adverse effects on normal cells have not been comprehensively assessed, nor is it known which particular DNMT is responsible for regulating these adverse effects. A related critical question is whether such potential toxicity could be reduced by targeting a specific isoform of DNMT. We, therefore, performed a comprehensive molecular characterization of the effects of the pan DNMT inhibitor 5aza and isoform-specific inhibition of DNMT1, DNMT3a and DNMT3b by shRNA on cell growth and invasiveness, the methylome and transcriptome of the breast, liver and lung cancer cells as well as their normal primary cell counterparts. Our results suggest that 5aza causes general DNA methylation inhibition both as far as genomic features as well as the genes that are affected. This results in activation of genes involved in promoting cancer and metastasis in both cancer and normal cells. 5aza also induces rampant activation of retroviral elements and ectopic transcription initiation in gene bodies and intergenic regions. Second, isoform-specific exhibit a more limited and specific profile of activity on promoter methylation and gene expression. Third, the adverse profile of 5aza corresponds to the effects of specific inhibition of DNMT3a suggesting that the adverse effects of 5aza are partly mediated through inhibition of DNMT3a. Fourth, specific inhibition of DNMT1 results in an enriched inhibition of DNA methylation in promoters and inhibition of growth without triggering activation of tumor suppressor genes and a more favorable molecular footprint on cancer cells. Our data provide a comprehensive assessment of the impact of DNA methylation inhibition on normal and cancer cells and points to the potential adverse effects of such an approach. However, since the different DNMTs have a different molecular footprint, these adverse effects might be inhibited using isoform-specific DNMT inhibitors. Our data needs to be considered for further clinical development of DNMT inhibitors.
Note: This abstract was not presented at the meeting.
Citation Format: David Cheishvili, Moshe Szyf. Adverse & anticancer activities of 5-azaCdR & DNA methyltransferase (DNMT) isoform specific inhibitors: therapeutic implications [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 4349. doi:10.1158/1538-7445.AM2017-4349
Abstract 4357: ESRP1 overexpression and its role in ovarian cancer
Authors: Kwon Mi Jeong 
Published: July 2017

Abstract
Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) are RNA binding proteins which are recently known to be involved in tumor progression via regulation of alternative splicing of cancer-associated genes. However, their expression and clinical significance in ovarian cancer remain unclear. Here, we found that ESRP1 and ESRP2 gene expression is upregulated in ovarian cancer cells compared with immortalized ovarian surface epithelial (IOSE) cells and their overexpression at protein level was also confirmed in ovarian cancer tissues. Consistent with TCGA data of ESRP1 gene amplification, higher ESRP1 gene copy number was observed in ovarian cancer cells compared with IOSE cells, whereas there was little correlation between gene copy number and gene expression in ovarian cancer cells. Importantly, their gene expression was inversely correlated with DNA methylation in ovarian cancer cells and ESRP2 overexpression in ovarian cancer was significantly associated with DNA hypomethylation (P= 0.036). Of note, TCGA data analysis showed that high ESRP1 gene expression is significantly associated with shorter 5-year survival of patients with ovarian cancer. Ectopic expression of ESRP1 in ESRP1 low-expressing mesenchymal type ovarian cancer cells increased cell proliferation, whereas it suppresses cell migration. Furthermore, our results revealed that the effect of ESRP1 overexpression on cell proliferation and migration is related to activation of the Akt/CyclinD pathway and increased of E-cadherin expression. In conclusion, our findings suggest that ESRP1 overexpression is associated with poor outcome of patients and ESRP1 may play a cancer-promoting role in ovarian cancer.
Citation Format: Mi Jeong Kwon. ESRP1 overexpression and its role in ovarian cancer [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 4357. doi:10.1158/1538-7445.AM2017-4357
Abstract 4361: An integrated genome-wide methylation analysis with gene expression in normal breast tissues identifies differentially methylated CpG loci associated with obesity
Authors: Weng Daniel Y. , Song Min-Ae , Brasky Theodore M. , Marian Catalin , Lan Renny S. , Llanos Adana A. , Spear Scott L. , Kallakury Bhaskar V. , Freudenheim Jo L. , Shields Peter G. 
Published: July 2017

Abstract
Introduction: Obesity is a risk factor for breast cancer, but the underlying mechanisms for this are only partially understood, and there has been only limited study of breast tissues molecularly before cancer develops.
Methods: Breast tissues from healthy women undergoing reduction mammoplasty and epidemiologic interviews (n=121) were profiled for the whole genome transcriptome (Affymetrix Human Transcriptome Arrays) and genome-wide DNA methylation (Infinium HumanMethylation 450 BeadChip array).
Results: After adjusting for confounding by age and race, 12,210 CpG dinucleotides with altered methylation levels correlated with body mass index (BMI) (10,808 positive correlations and1,402 negative correlations, FDR&lt;0.05). Among them 4,170 BMI-associated hypermethylated CpG dinucleotides (-1.5 kb from transcription start site, 1st Exon, and 5’UTR) and 443 BMI-associated hypomethylated CpG dinucleotides were located in promoter regions. By integrating DNA methylation and mRNA expression data, we identified 310 methylated genes that correlated with gene expression (FDR&lt;0.05). Of these, 242 genes had higher methylation status showing concurrent down-regulation in obese women, and 68 genes had lower methylation status showing concurrent up-regulation in obese women. Among the affected genes involved in diseases and disorders for inflammatory response, hereditary disorder, and immunological disease.
Conclusions: This study provides evidence that obesity epigenetically deregulates genes potentially involved in breast cancer that have functional relationships to gene expression.
Citation Format: Daniel Y. Weng, Min-Ae Song, Theodore M. Brasky, Catalin Marian, Renny S. Lan, Adana A. Llanos, Scott L. Spear, Bhaskar V. Kallakury, Jo L. Freudenheim, Peter G. Shields. An integrated genome-wide methylation analysis with gene expression in normal breast tissues identifies differentially methylated CpG loci associated with obesity [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 4361. doi:10.1158/1538-7445.AM2017-4361