bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6513: 3,3'-diindolylmethane enhances tumor regression after radiation through protecting normal cells to modulate anti-tumor immunity
Authors: Chen Renxiang , Li Lijun , Lin Yun-Tien , Humayun Arslon , Fornace Albert J. , Li Heng-Hong 
Published: September 2020

Abstract
Preclinical and clinical data indicate that radiotherapy acts as an immune modifier, having both immunostimulatory and immunosuppressive effects on the tumor immune microenvironment (TIME). 3.3'-Diindolylmethane (DIM), the acid-catalyzed dimer of the bioactive indole found in cruciferous vegetables, has long been known for its anticancer properties and has been proposed for use as a cancer prevention agent. The current study characterizes how DIM influences TIME and tumor regression after fractionated radiation treatment using preclinical breast cancer models. We first compared tumor graft models using immune-competent and immune-deficient mouse strains to find out whether immune cells are required for DIM's effects. Tumor targeted radiation was done using narrow-beam radiation with shielding. Tumor regression was monitored after DIM and radiation combined treatment and radiation alone. Our results indicated that DIM enhanced tumor regression after radiation treatment in immune-competent but not immuno-deficient mice. Data from nCounter® PanCancer immune profiling panel showed DIM increased intratumoral immune cells including cytotoxic T cells, neutrophils and macrophages after radiation and enhanced immunological processes such as adhesion and antigen processing. Expression of several MHC Class II molecules and CD74, a gene encoding chaperone and transport cofactor that assists MHC II molecules folding and presenting, significantly increased in the combined treatment of radiation and DIM. The results showing that DIM treatment alone does not affect tumor growth suggested that DIM's radioprotective effect on non-tumoral cells, including stromal cells and immune cells, plays a critical role in promoting a microenvironment that favors anti-tumor immunity. Additional experiments showed that DIM protected normal cells from radiation-caused immediate injuries in vitro and in vivo. In summary, DIM's radioprotective effects on immune cells and other normal cells are important in promoting a TIME that favors anti-tumor immunity. As a result, DIM increases the efficacy of radiation treatment on tumor regression. This study supports the development of DIM as an adjunct agent for radiation treatment.
Citation Format: Renxiang Chen, Lijun Li, Yun-Tien Lin, Arslon Humayun, Albert J. Fornace Jr., Heng-Hong Li. 3,3'-diindolylmethane enhances tumor regression after radiation through protecting normal cells to modulate anti-tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6513.
Abstract 653: Enhancing therapies for MYC-overexpressing Non-Hodgkin's lymphoma: A role for MYC downregulation and new combination therapies
Authors: Psaras Alexandra Maria , Brooks Tracy Ann 
Published: September 2020

Abstract
Background: Non-Hodgkin's Lymphoma (NHL) is the fifth most common cancer in the United States. Up to 40% of NHL is diffuse large B-cell lymphoma (DLBCL); while only 3% of NHL is classified as mantle cell lymphoma, it is a particularly lethal disease. DLBCL and MCL patients that aberrantly express MYC, which occurs up to 20 and 50% of the time, respectively, have worse survival rates and a lack of sustained clinical response to the standard R-CHOP therapy. We sought to examine both the effect of MYC downregulation on the efficacy of standard of care drugs and enhanced anti-cancer activity with a novel NF-kB targeting steroid, in place of prednisone/prednisolone, and also under conditions of MYC modulation, in NHL cells.
Methods and Summary of Findings: The downregulation of MYC was achieved in two distinct manners: with siRNA and with our pioneered MYC G-quadruplex (G4)-stabilizing DNA interference (DNAi) oligonucleotide. This DNAi was optimized for stability, specificity, and in cell activity, from our previously work developing this approach (Hao, et al, NAR 2016). The optimization was done using EMSA, chemical (DMS) footprinting, cell viability assays, qPCR, and microscopy. The lead steroid compound, which is selective for NF-κB signaling inhibition over DNA binding and transcription effects, was more cytotoxic than prednisolone, as determined by cell viability assays in NHL cells. Moreover, its effects on cell growth were additive with doxorubicin, and the overall effect of both drugs on cytotoxicity were enhanced by MYC downregulation. The combination studies were also performed with prednisolone; effects on decreased cell viability were more notable with the novel steroid, as compared to prednisolone.
Conclusion: MYC-overexpressing NHL, particularly DLBCL and MCL, respond poorly to the standard R-CHOP therapy. The addition of a MYC-downregulating DNAi, a novel NF-kB targeting steroid, or both, have been noted to enhance the cytotoxic effects of standard drugs. Work is expanding to evaluate the utility of an updated R-CHOP regimen in order to enhance survival for patients with MYC-overexpressing NHL.
Citation Format: Alexandra Maria Psaras, Tracy Ann Brooks. Enhancing therapies for MYC-overexpressing Non-Hodgkin's lymphoma: A role for MYC downregulation and new combination therapies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 653.
Abstract 6541: Accounting for immune escape mechanisms in personalized and shared neoantigen cancer vaccine design
Authors: Myronov Alexander , Niemiec Iga , Gruba Katarzyna , Mazzocco Giovanni , Sanecka-Duin Anna , Skoczylas Piotr , Drwal Michał , Kaczmarczyk Jan , Stepniak Piotr 
Published: September 2020

Abstract
The purpose of this study is to evaluate the importance of immune escape mechanisms (IEMs) when designing cancer immunotherapeutic strategies.
Cancer IEMs induced by negative selective pressure on tumor cells can have dramatic effects on immunotherapy treatment outcome. IEMs occurring during cancer evolution have been shown to facilitate loss of mutation-associated neoantigens (Anagnostou et al. Cancer Discov 2017). These mechanisms include: Loss of Heterozygosity (LOH), underexpression of HLA genes and mutations in the neoantigen presentation machinery.
During cancer evolution, the initially arising clonal neoantigens may be shared across many patients, followed by predominantly subclonal private neoantigens. The propensity of shared neoantigens to be clonal makes them promising candidates for the development of off-the-shelf cancer vaccines.
In order to optimize patient treatment strategies and qualify patients for either shared or private neoantigen-directed therapy, it is crucial to correctly assess the indication-specific IEMs and neoantigen landscape in both hot and cold tumors.
We carry out an extensive analysis of tumor neoantigen landscape from different indications based on TCGA, on Parkhurst et al. Cancer Discov. 2019 and other available data for selected indications (including MEL, NSCLC, CRC, and GBM). Using bioinformatics methods we investigate IEMs and their potential effects on the plasticity of neoantigen repertoires including enrichment of immunogenic neoantigens within the predicted vaccine composition, computed per patient. Immunogenicity is assessed using advanced deep learning models for neoantigen presentation and functional T-cell response prediction (Mazzocco et al., poster presented at SITC 2019).
We present the results of the comparison between different cancer indications including CRC, MEL, NSCLC and GBM using TCGA patient data and GI-tract cancer patients with validated T-cell responses. We present the frequency of particular immune evasion events, pointing out the differences in the number and quality of immunogenic neoepitopes (both shared and private) under those conditions and provide summary statistics.
As a result, we draw conclusions for vaccine design strategies, which are informed by the investigation of immune evasion events and are tested on selected datasets including experimentally-validated neoantigen responses.
Citation Format: Alexander Myronov, Iga Niemiec, Katarzyna Gruba, Giovanni Mazzocco, Anna Sanecka-Duin, Piotr Skoczylas, Michał Drwal, Jan Kaczmarczyk, Piotr Stepniak. Accounting for immune escape mechanisms in personalized and shared neoantigen cancer vaccine design [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6541.
Abstract 6551: Novel leads from Prosopis juliflora (Sw.) arrest the growth of B16F10 melanoma cancer cells by inducing apoptosis and down regulating the cell proliferating signalling pathways
Authors: Gacche Raju Nivarti 
Published: September 2020

Abstract
The evolving drug resistance and cancer heterogeneity is limiting the efficacy of current chemotherapy drugs. In the present state of the art, natural product and drug discovery has remained a significant hope for the identification of novel leads against series anti-cancer drug targets. The major issue is to convert the traditional knowledge into clinical reality by applying omics approaches. As a part of our continues efforts in exploring the efficacy of Prosopis juliflora as possible resource for the management of cancer, we have carried out the efficacy of P. juliflora against melanoma cancer using B16F10 as a melanoma model. The rational in selecting the melanoma lies in its aggressive metastatic phenotype and resistance to present chemotherapy drugs. Prosopis juliflora leaves methanol extract (PJLME) was assessed for its anticancer activity against B16F10 skin melanoma cancer cell line. Series of in vitro and in vivo experiments demonstrated that PJLME is cytotoxic (IC5017ug/ml), inhibited the migration ability of cells, inhibited the colony formation, arrested cell cycle at G0-G1 phase, induced apoptosis by up regulating the pro-apoptic markers like Bax & Bad, along with successful cleavage of Caspase-9 and PARP-1 and down regulated the anti-apoptotic marker Bcl2. The PJLME also suppressed the expression of Akt, mTOR and ERK signalling pathways. The in vivo xenograft studies in BALB/c mice model demonstrated impressive activity against the melanoma cancer. As a part of understanding the possible mechanism of action, our studies indicate that, PJLME induces cell death via apoptosis mechanism and by down regulating the cell proliferation signalling pathways. The HPLC-MS analysis of PJLME indicates the diversity of compounds, few of them are known for their anticancer effects. Our studies unraveled the significance of PJLME as a novel natural source for the management of melanoma cancer.
Citation Format: Raju Nivarti Gacche. Novel leads from Prosopis juliflora (Sw.) arrest the growth of B16F10 melanoma cancer cells by inducing apoptosis and down regulating the cell proliferating signalling pathways [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6551.
Abstract 6553: Plant power: Plant isolate dibenzyl trisulfide induces death of triple-negative breast cancer cells derived from an African American patient
Authors: Wooten Jonathan , Araújo Cristina , Wauchope Shaniece , Aja Joyce , Mavingire Nicole , Delgoda Rupika , Brantley Eileen 
Published: September 2020

Abstract
Triple negative breast cancer (TNBC), characterized by tumors that lack estrogen receptor, progesterone receptor, and human epidermal growth receptor expression, represents one of the most aggressive subtypes of breast cancer. TNBC carries a poor prognosis due, in part, to a lack of clinically available targeted therapy. Novel therapeutic strategies to combat TNBC primarily involve the use of synthetic small molecules. However, the World Health Organization reports that there is increased use of natural remedies and traditional medicine to treat diseases. Our lab has investigated the chemotherapeutic and chemopreventive effects of a variety of plant isolates. Dibenzyl trisulfide (DTS) is derived from Petiveria alliacea, a perennial shrub that grows in tropical regions of the world. Previous investigations surrounding DTS are limited to anticancer actions in European American breast cancer cells. The purpose of this study was to evaluate the anticancer actions of DTS in CRL-2335 cells which are derived from an African American patient with TNBC. We found that DTS inhibited TNBC cell migration and proliferation using wound healing and colony forming assays. Furthermore, we found DTS induced apoptotic body formation and nuclear fragmentation using relief contrast and fluorescence microscopy respectively. Moreover, using the Annexin V/PI assay we found that DTS induced early apoptosis, which was partially attenuated in cells pretreated with pan-caspase inhibitor zVAD-fmk. Finally, quantitative polymerase chain reaction analyses revealed that DTS induced the expression of pro-apoptotic genes BAK1, LTA and GADD45A. Our data suggest that DTS effectively induces caspase-independent death of TNBC cells derived from an African American patient and represents a promising agent to treat more refractory forms of breast cancer.
Citation Format: Jonathan Wooten, Cristina Araújo, Shaniece Wauchope, Joyce Aja, Nicole Mavingire, Rupika Delgoda, Eileen Brantley. Plant power: Plant isolate dibenzyl trisulfide induces death of triple-negative breast cancer cells derived from an African American patient [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6553.
Abstract 6560: Sann-Jhong-Kuey-Jian-Tang could inhibit glioblastoma cells through increasing TNF-α, Fas, Bax but decreasing Bcl-2, Mcl-1 expression
Authors: Su Chin Cheng 
Published: September 2020

Abstract
Glioblastoma is a highly malignant brain tumor and poor response to current chemotherapeutic medicine (such as Temozolomide). Glioblastoma remains a challenging disease and there is a need to identify new treatments. Sann-Jhong-Kuey-Jian-Tang (SJKJT), a traditional Chinese medicine prescription, has been prescribed as complementary medicine for patients with solid tumors in Taiwan. However, the anticancer effects of SJKJT on human brain tumor have not yet been elucidated. The present study focused on the anticancer effects and molecular mechanisms of SJKJT in human Glioblastoma by using DBTRG cells. In the present study, we evaluated the cytotoxic effects of SJKJT on DBTRG cells by MTT assay. The protein expression levels of tumor necrosis factor-α (TNF-α), Fas, Fas-associated Death Domain (FADD), Caspase-8, Caspase-9, Caspase-3, Bcl-2-associated X protein (Bax), Bcl-2 and myeloid cell leukemia 1 protein (Mcl-1) in the DBTRG cells were measured by western blotting. The cell cycles were analyzed by fluorescence-activated cell sorting (FACS). The protein expression of caspase-3 in DBTRG cells was analyzed by immunocytochemical (ICC) method. The results revealed that SJKJT inhibit the proliferation of DBTRG cells in a time- and dose-dependent manner. The protein expression levels of TNF-α, Fas, FADD, Caspase-8, Caspase-9, Caspase-3, Bcl-2-associated X protein (Bax) increased in the DBTRG cells treated with SJKJT; however, the level of Bcl-2 and Mcl-1 were decreased. These results indicated that SJKJT can inhibit DBTRG cells through both extrinsic and intrinsic pathway. The use of traditional Chinese medicine prescription SJKJT may become a feasible therapy option. Further studies are warranted to elucidate its mechanisms of action.
Citation Format: Chin Cheng Su. Sann-Jhong-Kuey-Jian-Tang could inhibit glioblastoma cells through increasing TNF-α, Fas, Bax but decreasing Bcl-2, Mcl-1 expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6560.
Abstract 6569: Regulatory networks of liver carcinoma reveal sex specific patterns of gene regulation
Authors: Lopes-Ramos Camila M. , Kuijjer Marieke , Glass Kimberly , DeMeo Dawn , Quackenbush John 
Published: September 2020

Abstract
Despite pronounced sex differences in cancer incidence, severity, and response to treatment, most current approaches to clinical management, as well as therapeutics development and selection, are sex-independent. For most cancer types, including liver cancer, males have a higher risk of developing the disease and a lower survival rate than women. However, the molecular features that drive these sex differences are poorly understood. We inferred patient-specific regulatory networks of liver hepatocellular carcinoma using data from TCGA. By comparing the female and male networks, we found marked sex differences in transcriptional regulatory processes relevant to disease development, progression, and response to therapy. We found that oncogenes have significantly higher regulatory targeting in males, while tumor suppressor genes have significantly higher targeting in females. Many “hallmark” cancer pathways, including the HEDGEHOG, WNT, and TGF-β signaling pathways, were significantly more highly targeted in males, while drug metabolism and immune related pathways were enriched for genes highly targeted in females. We also evaluated sex-biased somatic mutation patterns using mutation and copy number alteration data in TCGA. By summarizing mutations found in genes into pathway mutation scores, we found sex-biased mutation profiles for many pathways, providing additional support for biological sex differences associated with WNT, NOTCH, TGF-β, and HEDGEHOG signaling pathways. Our analysis uncovered patterns of gene regulation that differentiate male and female liver cancer and may be associated with sex differences in prognosis and treatment response. These findings provide insight into the mechanisms that drive clinically observed sex differences and underscore the importance of considering sex as a factor influencing disease etiology and in developing and prescribing therapies. Our network approach can provide insights into why some therapies have differential effect in males and females, and suggest new ways to optimize drug response in each sex.
Citation Format: Camila M. Lopes-Ramos, Marieke Kuijjer, Kimberly Glass, Dawn DeMeo, John Quackenbush. Regulatory networks of liver carcinoma reveal sex specific patterns of gene regulation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6569.
Abstract 6576: DNA methylation reveals alternative promoter usage in genes critical to pediatric tumors
Authors: Williams Justin , Xu Beisi , Putnam Daniel , Chen Xiang 
Published: September 2020

Abstract
Transcriptional regulation is fundamental for cell identity and function, and it's deregulation is a defining feature for common diseases, including cancers. Besides directly modifying the canonical promoter activities, tumors frequently utilize alternative promoters to increase the isoform diversity, activate oncogenes when the canonical promoters are repressed, and to evade host immune attacks by immune-editing. However, fresh-tissue availability and technical challenges represent major obstacles in genomewide promoter activity assessment in patient tumors by ChIP-seq experiments. Here, we presented MethylToActivity (M2A), a deep-learning framework that reveals promoter activities (H3K4me3 and H3K27ac) from DNA methylation (DNAm) patterns, a relatively stable epigenetic regulatory mechanism that can be robustly and accurately profiled in various tissues, including retrospective tumor samples archived using the formalin-fixed paraffin-embedded (FFPE) method. Trained from a cohort of neuroblastomas (N = 6), we demonstrate that M2A 1) approaches the accuracies of ChIP-seq experiments in revealing promoter activities, 2) is generalizable to various pediatric and adult cancers, 3) captures changes of promoter activity associated with differentially methylated regions, and 4) faithfully recapitulates differential promoter usages among tumor subtypes. Importantly, M2A uncovers oncogenic activation of alternative promoters in genes critical for tumor survival while the canonical promoter remains inactive. These results substantiate that M2A is capable of accurately measuring promoter activities, which will be of great use not only to functionally interpret differential DNAm patterns, but to unveil alternative promoter usages in patient tumors, which will facilitate precision medicine by tailoring treatments based on both epigenetic deregulations and genetic variants.
Citation Format: Justin Williams, Beisi Xu, Daniel Putnam, Xiang Chen. DNA methylation reveals alternative promoter usage in genes critical to pediatric tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6576.
Abstract 6583: Systems scale characterization of malignant pleural mesothelioma to discover novel therapies
Authors: Wilferd Sierra F. , Hoang Chuong D. , Plaisier Christopher L. 
Published: September 2020

Abstract
We have built a platform integrating systems genetics and functional genomics for the discovery of therapies to eradicate residual microscopic tumor foci after surgical resection of the deadly cancer malignant pleural mesothelioma (MPM). Using our SYstems Genetics Network AnaLysis (SYGNAL) network inference pipeline we constructed a malignant pleural mesothelioma gene regulatory network to discover disease causing TFs and miRNAs regulatory interactions. We then overlaid the MPM gene regulatory network with significant hits from pooled CRISPR-Cas9 knock-out out growth functional genomics screens in low passage number MPM patient-derived cell lines. We then queried this integrated network to identify patient survival associated TFs and miRNAs that when knocked-down (siRNA) or over-expressed (miRNA mimic), respectively, are likely to have anti-proliferative effects in low passage number patient-derived cell lines. The perturbation of a majority of these TFs and miRNAs led to significantly lower proliferation in the patient-derived cell lines. Further, the expression of the regulator or its target genes should function as a biomarker(s) for whether therapy will be effective for a particular patient's tumor. We are currently working with our collaborator at the NCI to develop these siRNA and miRNAs into their existing miRNA mimic hydrogel delivery system and test them in orthotopic xenografts using the low passage number patient derived cell lines.
Citation Format: Sierra F. Wilferd, Chuong D. Hoang, Christopher L. Plaisier. Systems scale characterization of malignant pleural mesothelioma to discover novel therapies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6583.