bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4431: Cytotoxic effects of the Jamaican yam tuber in hormone-sensitive cancers and its potential use in green nanotechnology formulation
Authors: Wright Sasha-gay A. 
Published: August 2019

Abstract
Historically, plant materials have been widely explored for their anti-proliferative effects against a variety of cancer cells, with many of them proving to be very effective. Additionally, their efficacy has been seen in the specific field of targeted cancer therapy. The use of plants for therapeutic purposes in place of or with traditional medicine is collectively referred to as complementary and alternative medicine (C.A.M). Several Jamaican Yam species have shown to be useful as C.A.M in the treatment of certain medical conditions such as diabetes, hypercholesterolemia and cancer. Hormone-sensitive cancers such as breast and prostate cancer are the most frequently diagnosed malignancy and when combined, is the leading cause of cancer related deaths among the Jamaican populace. These statistics unfortunately, are also reflected in the wider Caribbean region. Currently treatment involves: surgery, radiation and androgen deprivation therapy; however, there are some cases in which mutation causes further growth of the cancer cells regardless of treatment. As such, there still remains a dire need of a more effective and lasting therapy. The aim of this study was to assess the antiproliferative effects of yam material and to also deduce a possible mechanism of action in an effort to formulate a means of targeted therapy. The results showed that an alcoholic extract of the Jamaican yam tuber (Dioscorea spp.) demonstrated anti-proliferative effects in androgen insensitive prostate cancer cell lines (IC50 of 18 ppm, 95% C.I. 24-33ppm) and invasive breast cancer cell lines (IC 50 of 28 ppm, 95% C.I 36-54ppm). Western blot assays also indicated that cell death was possibly induced through the cell cycle regulatory protein, cyclin D. The antiproliferative effects and purported mechanism of action of the yam extract against some hormone-sensitive cancer cells makes it an ideal alternative for the formulation of green nanotechnology for targeted therapy.
Note: This abstract was not presented at the meeting.
Citation Format: Sasha-gay A. Wright. Cytotoxic effects of the Jamaican yam tuber in hormone-sensitive cancers and its potential use in green nanotechnology formulation [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 4431.
Abstract 4432: Multi-omics profiling establishes the polypharmacology of FDA Approved CDK4/6 inhibitors and its impact on drug response
Authors: Mills Caitlin E. , Hafner Marc A. , Subramanian Kartik , Chen Chen , Chung Mirra , Boswell Sarah A. , Everley Robert A. , Liu Changchang , Walmsley Charlotte S. , Juric Dejan , Sorger Peter K. 
Published: August 2019

Abstract
FDA approval of multiple drugs with different chemical structures against the same protein target raises the question whether such drugs have sufficiently similar mechanisms of action to be considered functionally equivalent. We compare three recently approved inhibitors of the cyclin-dependent kinases CDK4/6 - palbociclib, ribociclib, and abemaciclib - that have become highly promising therapies for the treatment of breast cancer and potentially other solid tumors. All three drugs have the same nominal targets but differ in selectivity. In humans, abemaciclib uniquely appears to exhibit single-agent activity and has a distinct toxicity profile. We systematically profile targets and activities of these CDK4/6 inhibitors using biochemical assays, mRNA profiling, mass spectrometry-based phospho-proteomics, GR-based dose-response assays, and mouse xenografts. We find that the three drugs differ at a cellular level and that abemaciclib has targets and activities not shared by palbociclib or ribociclib including: induction of cell death (even in pRb-deficient cells), arrest in the G2 phase of the cell cycle, reduced drug adaptation, and unique transcriptional effects in vitro and in vivo. These activities appear to arise from inhibition of CDKs other than CDK4/6 including CDK2/Cyclin A/E and CDK1/Cyclin B. We propose that inhibition of these kinases by abemaciclib target known mechanisms of resistance to CDK4/6 inhibition and thus elicit a response in cell lines that are resistant to palbociclib or ribociclib.
Citation Format: Caitlin E. Mills, Marc A. Hafner, Kartik Subramanian, Chen Chen, Mirra Chung, Sarah A. Boswell, Robert A. Everley, Changchang Liu, Charlotte S. Walmsley, Dejan Juric, Peter K. Sorger. Multi-omics profiling establishes the polypharmacology of FDA Approved CDK4/6 inhibitors and its impact on drug response [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 4432.
Abstract 4437: Effects of atypical protein Kinase c inhibitor (DNDA) on lung cancer proliferation and migration by PKC-ι/FAK ubiquination through the Cbl-b pathway
Authors: Bommareddy Raja Reddy , Patel Rekha , Duncan Mildred Acevedo 
Published: August 2019

Abstract
Lung cancer is the second most common cancer and it is the leading cause of cancer death in both men and women. PKC isozymes play an important role in the development and progression of many cancers by regulating the cell cycle, survival, apoptosis, cell motility and malignant transformation. Our focus is to study the role of atypical PKCs (aPKC) in cell proliferation and migration in lung cancer cell lines. We used a novel non-specific inhibitor of aPKC namely DNDA (3,4-amino-2,7napthalenedisulfonic acid). Our hypothesis is that DNDA inhibits cell proliferation and migration of lung cancer cells. Our data from cell viability and flow cytometry showed significant reduction in cell proliferation and induction of apoptosis with DNDA (10µM) in A549 and H1299 lung cancer cells. Additionally, DNDA showed no toxic effect on BEAS-2B normal lung cells. Elevated levels of Focal Adhesion kinase (FAK) are implicated in the progression of cancer and plays a vital role in the invasion and migration of cancer cells. Western blot results showed that the phosphorylation of PKC-ι and phosphorylation of FAK were decreased in A549 lung cancer cells upon DNDA treatment. Moreover, there was no significant reduction in phosphorylation of FAK in H1299 lung cancer cells upon treatment with DNDA. Immunoprecipitation (IP) data revealed an association of PKC-ι with FAK and FAK with Cbl-b. Ubitest results suggests that PKC-ι regulates the cleavage of FAK through its ubiquination by cbl-b and thus inhibits the migration of A549 lung cancer cells which was evident from scratch assay. Our data indicates that DNDA might inhibit the migration of A549 lung cancer cells by PKC-ι/FAK ubiquination via Cbl-b.
Citation Format: Raja Reddy Bommareddy, Rekha Patel, Mildred Acevedo Duncan. Effects of atypical protein Kinase c inhibitor (DNDA) on lung cancer proliferation and migration by PKC-ι/FAK ubiquination through the Cbl-b pathway [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 4437.
Abstract 4441: Discovery of potent and selective inhibitors of USP7 with anti-tumor activity in vitro and in vivo
Authors: Ohol Yamini M. , Sun Michael , Leger Paul , Hu Dennis , Biannic Berenger , Rana Payal , Cho Cynthia , Jacobson Scott , Wong Steve , Sanchez Jerick , Han Xinping , Young Kyle , Okano Akinori , Maung Jack , Cutler Gene , Shah Nick , Adusumilli Lavanya , Kaveri Deepika , Talay Oezcan , Pookot Deepa , Abraham Betty , Bradford Delia , Kozon Nathan , Colas Christophe , Kim Andrea , Schwarz Jacob , Wustrow David , Brockstedt Dirk , Kassner Paul 
Published: August 2019

Abstract
USP7 is a deubiquitinase that regulates the levels of multiple downstream targets with roles in cancer progression and immune response. Inhibitors of USP7 may thus decrease oncogene function, increase tumor suppressor function, enhance immune function and sensitize tumor cells to DNA damaging agents. We have discovered a novel chemical series that potently and selectively inhibits USP7 in biochemical and cellular assays. Our inhibitors reduce the viability of multiple p53-wild type cell lines, including several blood cancer and MYCN-amplified neuroblastoma cell lines, as well as a subset of p53-mutant tumor cell lines in vitro. Further, oral administration of our USP7 inhibitors inhibits MM.1S (multiple myeloma; p53-wild type) and H526 (small cell lung cancer; p53-mutant) tumor growth in vivo. Our work confirms that USP7 is a pharmacologically tractable target and future studies will aim to further understand the mechanism of action of USP7 inhibitors in p53-mutant cancers.
Citation Format: Yamini M. Ohol, Michael Sun, Paul Leger, Dennis Hu, Berenger Biannic, Payal Rana, Cynthia Cho, Scott Jacobson, Steve Wong, Jerick Sanchez, Xinping Han, Kyle Young, Akinori Okano, Jack Maung, Gene Cutler, Nick Shah, Lavanya Adusumilli, Deepika Kaveri, Oezcan Talay, Deepa Pookot, Betty Abraham, Delia Bradford, Nathan Kozon, Christophe Colas, Andrea Kim, Jacob Schwarz, David Wustrow, Dirk Brockstedt, Paul Kassner. Discovery of potent and selective inhibitors of USP7 with anti-tumor activity 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 4441.
Abstract 4498: O GlcNAcylation of SOX2 regulates its tumor initiation properties in pancreatic cancer
Authors: Sharma Nikita S. , Gupta Vineet K. , Dauer Patricia , Hadad Roey , kesh Kousik K. , Dudeja Vikas , Saluja Ashok , Banerjee Sulagna 
Published: August 2019

Abstract
Background: Pancreatic Cancer is an extremely aggressive disease with a bad outcome owing to its late detection, high rate of metastasis and self-renewal post-surgical and chemotherapeutic intervention. In cancer the balance between differentiation and self-renewal is tightly regulated by SOX2. Over expression of SOX2, as in pancreatic cancer, can tilt the balance towards self-renewal and thus increase the population of these undifferentiated “stem cells”.
Methods: A CRISPR based OGT knockout kit was purchased from Origene and a knockout cell line was generated with S2VP10 cells. For the tumor initiation studies OGTi (OGT knockout cells) were implanted subcutaneously at a limiting dilution from 500,000 cells to 500 cells. Site directed mutagenesis was performed using theQuick-change Lightning from Agilent.
Results: In the current study we show for the first time that SOX2 undergoes a type of post translational modification known as O GlcNAcylation. We also show for the first time that in humans this modification happens at Serine 246 and mutating this particular site via a side directed mutagenesis leads to a loss of O GlcNAcylation of SOX2.O GlcNAc modification of SOX2 further leads to its activation which then leads to its stabilization in the nucleus. A CRISPR-OGT knockout in pancreatic cancer cell line S2VP10 resulted in a delayed tumor initiation. We further showed that mutation of this site (S246A) prevents the modification of Sox2 and its downstream activity. Our study also demonstrated that targeting OGT in vivo with a small molecule inhibitor OSMI, results in decreased tumor burden, delayed tumor progression and a decreased expression of SOX2 in pancreatic cancer cells.
Conclusion: Our study highlights for the first time that the O-GlcNAc transferase dependent SOX2 glycosylation has a profound effect on the transcriptional activity of SOX2 and is instrumental in determining self-renewal in pancreatic cancer which can be targeted therapeutically.
Citation Format: Nikita S. Sharma, Vineet K. Gupta, Patricia Dauer, Roey Hadad, Kousik K. kesh, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee. O GlcNAcylation of SOX2 regulates its tumor initiation properties in pancreatic cancer [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 4498.
Abstract 4500: Mechanisms of tumor-associated myeloid cells in modulating host immune microenvironment and metastatic progression
Authors: Ishii Hiroki , Hollander Christine , Greten Tim , Yang Li 
Published: August 2019

Abstract
The immune checkpoint inhibitor blockade takes advantage of the specific receptor-ligand interactions between immune and tumor cells. However, the immunosuppressive microenvironment has been largely ignored, which likely contribute to low efficacy and resistance in immune therapies. Our studies demonstrate that TGF-β signaling in tumor-associated myeloid cells isessential in systemic immune suppression and metastatic progression. Using mouse models of breast cancer metastasis, we further uncover that miR130a and 145 are critical in regulating TGF-β signaling in myeloid cells. miR130a and 145 are down-regulated in these myeloid cells, leading to increased TGF-β RII. Ectopic expression of miR-130a and miR-145 in the myeloid cells decrease tumor metastasis. This is mediated through a downregulation of type 2 cytokines in myeloid cells and an increase in IFNgamma-producing cytotoxic CD8 T lymphocytes. Lastly, miR-130a and miR-145 mimics improve systemic anti-tumor immunity and inhibit metastasis in preclinical mouse models. Another important mechanism in myeloid-mediated immune suppression involves a decreased expression of Lamin A/C, nuclear lamina proteins that prominently interact with heterochromatin. Lamin A/C knockout in myeloid cells leads to H3K4me3-mediated upregulation of Gfi1 and C/EBPϵ,critical transcription factors responsible for granulocytic lineage differentiation. In addition, loss of Lamin A/C attenuates antigen-presentation and compromises host anti-tumor immunity. These mechanistic understandings provide options to reprogram tumor-associated myeloid cells by altering the cytokine milieu and metastatic microenvironment, thus enhancing host antitumor immunity.
Citation Format: Hiroki Ishii, Christine Hollander, Tim Greten, Li Yang. Mechanisms of tumor-associated myeloid cells in modulating host immune microenvironment and metastatic progression [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 4500.
Abstract 4516: Suppression of metastasis by inhibiting nanoscale physical communication of cancer cell and the endothelium
Authors: Dash Chinmayee , Saha Tanmoy , Khiste Sachin , Sengupta Shiladitya 
Published: August 2019

Abstract
The progression of metastasis proceeds through the physical communication of cancer cells with the endothelium via tunneling nanotubes (TNTs). Restriction on the cancer cell and the endothelium communication by inhibiting TNT formation can lead to breakthrough advancement in the treatment of metastasis. However, the mechanistic interpretation about the formation of TNTs between the cancer cells and the endothelium has been poorly defined in literature. Our study integrates the investigation of mechanism behind the TNT formation and introduction of a pharmacological inhibitor for TNT formation.
The nanobridges are primarily composed of cytoskeletal elements such as actin and tubulin, which originates from the energy dependent remodeling of membrane cytoskeletal elements. Here, we propose that the members of Rho-family of GTPases, Cdc42, Ral and Rac along with exocyst complex, are involved in the actin polymerization based on their localization to the nanobridges between the metastatic cancer cells and the endothelium. A significant decrease in mitochondrial transfer and TNT formation has been observed when the inhibitor for Cdc42/Rac1 GTPase inhibitor (ML141), and a geranylgeranyltransferase 1 inhibitor (L-778,123) has been employed in the co-culture. The amount of mitochondrial transfer was evaluated with flow cytometry and the number of TNT formation was counted from imaging, which in case of inhibitors was highly reduced. Simultaneously the involvement of exocyst complex was confirmed through imaging. The proteins involved in the exocyst complex co-localize with the nanotubes and was further validated by siRNA-based knock down study. The nanotubular pathways are the primary mode of communication between cancer cell and endothelium, which leads to the conversion of healthy endothelium to a pathological one. Hindering the TNT mediated communication via pharmacological inhibitors can reduce the chance of metastasis.
Conclusion: Investigation of molecular mechanism behind the TNT formation and employing innovative ways to have restriction over that can be a potential next generation therapeutic module for controlling metastasis.
Reference: Connor Y, Tekleab S, Nandakumar S, Walls C, Tekleab Y, Reiberger T, Husain A, Gadish O, Sabbisetti V, Kaushik S, Sehrawat S, Kulkarni A, Dvorak H, Zetter B, Jain RK, Edelman E, Sengupta S. Physical nanoscale conduits-mediated communication between tumor cells and endothelium enables a metastatic hijack. Nature Communications (2015) 6:8671.
Citation Format: Chinmayee Dash, Tanmoy Saha, Sachin Khiste, Shiladitya Sengupta. Suppression of metastasis by inhibiting nanoscale physical communication of cancer cell and the endothelium [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 4516.
Abstract 453: A circulating tumor cell assay for dynamic assessment of drug sensitivity in metastatic castration-resistant prostate cancer
Authors: Teng Pai-Chi , Jan Yu Jen , Yoon Junhee , Chen Jie-Fu , Chen Pin-Jung , Yao Nu , Cheng Shirley , Lozano Amber , Freeman Michael R. , You Sungyong , Tseng Hsian-Rong , Posadas Edwin M. 
Published: August 2019

Abstract
Background: Tissue-based gene signatures can predict clinical behavior in prostate cancer (PC). Our objective was to extend their application to circulating tumor cells (CTCs) and to show that changes in the signature were associated with changes in clinical behavior.
Methods: Our approach combined the Thermoresponsive(TR)-NanoVelcro CTC purification system with the Nanostring nCounter system for cellular purification and transcriptomic analysis. The Prostate Cancer Classification System (PCS) panel was modified for use in CTCs. We selected 31 blood samples from 23 PC patients receiving androgen receptor signaling inhibitors (ARSI) and measured the PCS1 Z score (probability). These findings were compared with clinical outcome data (responsiveness/resistance).
Results: A modified, 16-gene PCS1 signature was established and validated through a rigorous bioinformatics process. We performed analytical validation of our combined CTC-RNA system to ensure reproducibility and specificity. In patient bloods, ARSI-resistant samples (ARSI-R, n=14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n=17) (Rank-sum test, P=0.003). The analyzed bloods contained samples from 8 patients who developed resistance to an ARSI allowing for dynamic measurement of gene expression. Our analysis found that the PCS1 Z score increased at the time that ARSI-resistance emerged (Pairwise T-test, P=0.016).
Conclusions:Using this new methodology, contemporary, clinically-relevant gene signatures such as PCS could be measured non-invasively in CTCs. These findings can be used to relate gene expression to clinical drug response. This approach also allowed for measurement of dynamic variations of gene expression in individual patients over time that correlated to ARSI sensitivity.
Citation Format: Pai-Chi Teng, Yu Jen Jan, Junhee Yoon, Jie-Fu Chen, Pin-Jung Chen, Nu Yao, Shirley Cheng, Amber Lozano, Michael R. Freeman, Sungyong You, Hsian-Rong Tseng, Edwin M. Posadas. A circulating tumor cell assay for dynamic assessment of drug sensitivity in metastatic castration-resistant prostate cancer [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 453.
Abstract 4534: Label free molecular imaging of tumor sections for two and three dimensional tissue classification and pathway mapping
Authors: Jones Emrys A. , Gurung Dipa , Henderson Fiona , Gentry Matthew , McDougall Danielle , Shanneik Yasmin , Langridge James , McMahon Adam , Takats Zoltan 
Published: August 2019

Abstract
Mass spectrometry imaging allows for the presence and abundance of a wide range of bio-molecules to be measured directly from tissue sections without the use of labels or tags. This results in the ability to compare the spatial distribution of hundreds of metabolites, lipids, peptides, and proteins within the same section in a single experiment. Desorption electrospray ionization (DESI) mass spectrometry imaging can differentiate and classify tissue types, and associated disease states, by measuring the unique characteristic molecular fingerprints of the tissues1,2. Furthermore, using histologically annotated databases of molecular profiles, unknown tissues can be classified using the mass spectrometry output coupled to machine learning approaches. A major benefit of DESI is that the analyzed sections are left largely unchanged by the process; the sections can subsequently be stained and the results validated by immunohistochemistry or conventional H&E approaches. During DESI fingerprinting analyses, a full mass spectrum on a cell by cell resolution of 20-50µm pixel size is collected. Chemical changes on very small scales can be distinguished and explored, allowing the chemistry of tumor margins and interface zones to be understood through mapping results onto metabolic pathways. As the data in a DESI experiment is collected and stored, multiple interrogations of the data are possible; as new discoveries are made, previously collected data can be retrospectively mined for additional insights. In this study, the three-dimensional chemical heterogeneity of drug dosed spheroids and tumor xenografts was measured with DESI and compared with MRI and PET imaging modalities and with FT-IR spectroscopic techniques. We demonstrate the power of this multi-analytical approach in glioma models and in colorectal and prostrate tumor samples to uncover metabolic and lipidomic changes during disease progression and to reveal the inherent heterogeneity within a tumor. 1. 1. Calligaris, D.Caragacianu, D.Liu, et al; PNAS, 2014, 111, 15185-151892. Guenther, S., Muirhead, L.J., et al, Cancer Res, 2015, 75, 1828-1837
Citation Format: Emrys A. Jones, Dipa Gurung, Fiona Henderson, Matthew Gentry, Danielle McDougall, Yasmin Shanneik, James Langridge, Adam McMahon, Zoltan Takats. Label free molecular imaging of tumor sections for two and three dimensional tissue classification and pathway mapping [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 4534.