tbuckley/cabot-search huggingface dataset:
Abstract 4906: Sphingolipid regulates pro-inflammatory cytokines to subdue the neoplastic lesions in hepatocellular carcinoma
Authors: Nabanita Chatterjee, Krishna Das Saha
Journal: Cancer Research (2017)

Abstract Hepatocellular carcinoma (HCC), is the most leading cause of cancer-related death in all over the world (seems to more than 80% of death cases). It is frequently linked with continuous hepatocytes death, inflammatory cell infiltration, and compensatory liver regeneration with higher angiogenic rate. Considering the different signalling process during this tumorogenesis with the involvement of new ‘lead’ identification of different sources, desire to be less toxic and higher bioavailability. The use of live, attenuated or genetically compensated microbes or its cellular component(s) or metabolites has begun to emerge as a potential new approach in medicinal research to deliver bioactive entities. Thus, advancing our knowledge of such microbes-mediated therapy may suggest new avenues for therapeutic intervention in many fatal diseases. Lipid (LSPL-1) isolated from Leishmania donovani could induce apoptosis in human HepG2 (Hepatocellular carcinoma cell, human) cells, as characterized by phosphatydylserine serine exposure, DNA fragmentation, alteration of BaX/Bcl2 ratio with loss of mitochondrial membrane potential and cytochrome C release, activation of series of caspases and cleaved PARP. LSPL-1 also modulates the various transcription factors like NF-kb65, p53 through regulation of cell proliferation exerted the death cause. Moreover this study also focused that the LSPL-1 effectively suppressed diethylnitrosamine (DEN) induced liver inflammation and hyperplasia in murine also decline in lipid peroxidation and increase in enzymic antioxidants (SOD, CAT, GPx, GR and GST) status with improvement of their survival rate. It reduced the elevated level of cytokines including tumor necrosis factors, interleukins, interferon (alpha and gamma), and transforming growth factors in hepatocytes from liver fibrosis bearing mice. As evident from immunochemical analysis, inflamed hepatocytes and liver tissue may up regulated the various growth factors including EGF, HGF, endothline-1 regulation with promoting angiogenic activity via modulation of CD34, VEGF, HIF-1α expression and alteration of these changes were balanced by LSPL-1. So taken together, these finding indicated that, LSPL-1 may induce apoptosis and in hyper proliferating cancer cells via altering cytokines level with tumour growth regulation in carcinogen exposed rodent system. Note: This abstract was not presented at the meeting. Citation Format: Nabanita Chatterjee, Krishna Das Saha. Sphingolipid regulates pro-inflammatory cytokines to subdue the neoplastic lesions in hepatocellular carcinoma [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 4906. doi:10.1158/1538-7445.AM2017-4906
Gabapentin and Pregabalin for Pain — Is Increased Prescribing a Cause for Concern?
Authors: Christopher W. Goodman, Allan S. Brett
Journal: New England Journal of Medicine (2017)

Recent guidelines from the CDC recommend gabapentinoids as first-line agents for neuropathic pain. But some clinicians may be prescribing these medications excessively for various types of acute, subacute, and chronic noncancer pain in an attempt to avoid opioids.
Abstract 5288: Perception of barriers and facilitators to hepatitis B virus screening, vaccination, and treatment care among Asian American physicians
Authors: Patricia Estrella, Ming Chin Yeh, Yin Tan, Carolyn Y. Fang, Sarit A. Golub, Grace X. Ma
Journal: Cancer Research (2017)

Abstract Objective: To examine practices and factors affecting Hepatitis B Virus (HBV) screening, vaccination, and treatment among Asian-American physicians in New York City. Methods: Members of the Chinese American Independent Practice Association (CAIPA) will be recruited to participate in a comprehensive survey, developed based on prior research, to assess physicians’ practice in HBV screening, vaccination and treatment. This study will also examinebarriers/facilitators toward HBV prevention and treatment in knowledge, familiarity or awareness of guidelines, perception, attitude/behaviors, self-efficacy, motivation, patient factors, cultural, and environmental factors. A bivariate analysis and multivariate regressions will be conducted to evaluate factors that predict study outcomes. Results: We hypothesize that Asian American physicians are more likely to screen for HBV, but are experiencing many barriers unique to the Asian American physicians that are leading them improperly perceive certain patients not at risk for HBV infection. Furthermore, we anticipate finding significant key barriers and facilitators among Asian American physicians for HBV screening and vaccination and treatment towards Asian patients. Preliminary findings will be presented at the conference. Conclusions &amp; Implications: Asian/Pacific Islanders (APIs) are disproportionally affected by chronic hepatitis B. Therefore, identifying chronically infected persons and linking them to care is crucial. As a result of the reverence of the doctors, a cultural norm prevalence within the Asian community, physicians are uniquely positioned to improve HBV screening and vaccination rates and if necessary, recommend linkage to care. This study will fill in an important gap in creating a culturally-relevant, physician-focused intervention to improve HBV care and reduce the burden of HBV infection within the Asian community. Citation Format: Patricia Estrella, Ming Chin Yeh, Yin Tan, Carolyn Y. Fang, Sarit A. Golub, Grace X. Ma. Perception of barriers and facilitators to hepatitis B virus screening, vaccination, and treatment care among Asian American physicians [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 5288. doi:10.1158/1538-7445.AM2017-5288
Abstract 202: Comprehensive spatial mapping by MALDI imaging mass spectrometry of the N-glycan tissue glycome and database generation for eighteen tumor types
Authors: Richard R. Drake, Kacey Talbot, Kim Norris-Caneda, Evelyn Bruner, Peggi M. Angel
Journal: Cancer Research (2017)

Abstract Glycoproteins account for approximately 80% of the proteins located at the cell surface and in the extracellular environment, and serve as binding ligands for cell adhesion, extracellular matrix molecules, signaling receptors, immune cells, lectins and pathogens. Alterations and changes in cell surface glycosylation during tumorigenesis are well documented, including the major N-linked glycan class of glycosylated proteins. We have recently developed a MALDI imaging mass spectrometry (MALDI-IMS) method to spatially profile N-linked glycans in frozen and formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMAs). In order to facilitate method development and maximize glycome determinations for many cancer types, we have generated two custom TMAs comprised of multiple tissue core pairs of non-tumor and tumor regions representing eighteen different tumor types (pancreatic, colon, prostate, breast, lung, melanoma, sarcoma, head/neck, kidney, liver, glioma, ovarian, thyroid, uterine, cervical, testicular, gastric, bladder). Tissues are incubated with a molecular coating of peptide N-glycosidase, and released N-glycans are detected directly using MALDI-FTICR imaging, linked directly with tissue histopathology. The method is able to simultaneously identify and distinguish 50 or more components of the N-glycome on a single slide. The approach allows comparison of the similarities and differences in N-glycome compositions across each tumor tissue type, as well determine the relative abundance of each individual glycan across all tumor types. For example, an increase in high mannose glycans is common to many tumor types. From the TMA data, this glycan class is consistently elevated for colon, prostate, lung, breast and bladder cancers, while the other tumor types are variable. Differences in branching complexity, bisecting N-acetylglucs0amine, and the degree of fucosylation and sialylation are also readily evaluable. Additionally, data from each of the TMA core pairs is being compared systematically to the N-glycans detected in the source FFPE blocks. The goal is to generate an extensible reference database of expected N-glycans for each tumor tissue type. This will also provide a framework to expand to other classes of glycans, and complementary glycan data generated by other methods on the same TMA cores. Citation Format: Richard R. Drake, Kacey Talbot, Kim Norris-Caneda, Evelyn Bruner, Peggi M. Angel. Comprehensive spatial mapping by MALDI imaging mass spectrometry of the N-glycan tissue glycome and database generation for eighteen tumor types [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 202. doi:10.1158/1538-7445.AM2017-202
Abstract 485: Epigentic silencing of miR-142-3p promotes metastasis by targeting ZEB2 in NPC
Authors: Yingqin Li, Na Liu, Jun Ma
Journal: Cancer Research (2017)

Abstract Metastasis is the major cause of cancer-related death in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms governing metastasis remain poorly understood in NPC. Here, we demonstrated that miR-142-3p was downregulated and significantly suppressed NPC cell migration, invasion in vitro and in vivo. We identified zinc finger E-box binding homeobox 2 (ZEB2) as a direct target of miR-142-3p, and its overexpression rescued the inhibitory effects of miR-142-3p in NPC. Importantly, miR-142-3p downregulation was associated with DNA methylation within the miR-142 locus. Enhancer of zeste homologue 2 (EZH2) suppressed miR-142 methylation and miR-142-3p expression. Systemic reversal of miR-142 silencing suppressed lung metastasis of NPC cells. Furthermore, miR-142 hypermethylation was associated with poor metastasis-free survival. This study demonstrates a suppressive role of miR-142-3p in metastasis and uncovers an epigenetic mechanism for miR-142-3p silencing in NPC, suggesting a potential prognostic factor and therapeutic target to combat metastasis in NPC. Note: This abstract was not presented at the meeting. Citation Format: Yingqin Li, Na Liu, Jun Ma. Epigentic silencing of miR-142-3p promotes metastasis by targeting ZEB2 in NPC [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 485. doi:10.1158/1538-7445.AM2017-485
A common intronic variant of PARP1 confers melanoma risk and mediates melanocyte growth via regulation of MITF
Authors: Jiyeon Choi, Mai Xu, Matthew M Makowski, Tongwu Zhang, Matthew H Law, Michael A Kovacs, Anton Granzhan, Wendy J Kim, Hemang Parikh, Michael Gartside, Jeffrey M Trent, Marie-Paule Teulade-Fichou, Mark M Iles, Julia A Newton-Bishop, D Timothy Bishop, Stuart MacGregor, Nicholas K Hayward, Michiel Vermeulen, Kevin M Brown
Journal: Nature Genetics (2017)
Abstract 3905: Development of anticancer aptamers targeting cancer stem cells
Authors: Yuh-Ling Chen, I-Shan Hsieh, Keng-Fu Hsu, Tse-Ming Hong
Journal: Cancer Research (2017)

Abstract Background: Cancer stem cells (CSC), also called tumor initiating cells (TIC), are a small population of cancer cells within a tumor that drive the tumor initiation, metastasis, and resistance to chemotherapeutic drugs. An effective cancer stem cell targeting strategy by oligonucleotide-based approaches such as aptamers in diagnosis and treatment are urgently needed. In this study, we aimed to develop an effective aptamer-based biomarker for CSCs in cancer detection and therapy. Material and methods: E-cadherin-null lung cancer cells, shEcad-A549, was confirmed with stemness properties and used as targeting cells. The isolation of DNA aptamers binding to CSCs was by using a Cell-SELEX (systematic evolution of ligands by exponential enrichment). By combining the aptamer-pull-down approach with proteomics, we identified the potential binding proteins of CSC-aptamer. Flow cytometry, gene silencing and lung cancer xenograft models were used to explore the functions of CSC-aptamer and its targeted protein in lung cancer formation. Results: The aptamer AP-9R was identified to bind lung CSCs with high affinity and specificity. AP-9R reduced lung cancer cell stemness and migration but no apparent cytotoxicity. By using proteomic approaches, the target protein of AP-9R in non-small cell lung cancer was further identified and characterized its important role in cancer stemness. For CSCs detection, we developed AP-9R conjugated beads and confirmed their effective captured rate of lung CSCs in vitro. Moreover, administration of AP-9R significantly reduced lung tumor growth in the xenograft model. Conclusions: Our data are moving closer to understand the significance of cancer stem cells during cancer progression and demonstrate that aptamer-based therapies will be useful as therapeutic and diagnostic agents for lung cancer. Citation Format: Yuh-Ling Chen, I-Shan Hsieh, Keng-Fu Hsu, Tse-Ming Hong. Development of anticancer aptamers targeting cancer stem 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 3905. doi:10.1158/1538-7445.AM2017-3905
Abstract 2116: Combining the power of different profiling approaches to better understand the activity of kinase inhibitor drugs
Authors: Alastair J. King, Jesse J. Parry, Samantha C. Burkart, Lee R. Cavedine, Alyssa M. Cracchiolo, Brogan A. Epkins, Steven M. Garner, Timothy J. Sindelar, Charles R. Wageman, Stephen P. Davies, Andrew Plater, Anna M. Woodward, Usha Warrior
Journal: Cancer Research (2017)

Abstract Profiling of inhibitors for eventual therapeutic use is an essential part of drug discovery and development. Evaluating the in vitro potency of kinase inhibitors in a wide panel of enzyme assays is critical, not only to guiding SAR knowledge for improving drug design, but also for assessing selectivity, which has long-reaching consequences for both biological activity and safety. Evaluation of the same inhibitors in cellular models yields information on the activity of these inhibitors in a more physiologically relevant environment. However, while some selective kinase inhibitors show predictably selective profiles in cell proliferation assays, others do not. Thus, the biological context in which a kinase inhibitor functions, and the signaling networks influenced by inhibition of both the desired target and off-target activities, help to define how that inhibitor will work in a cellular setting and, ultimately, in a therapeutic application. We demonstrate the power of profiling several well-known kinase inhibitors in complementary panel assays, to predict behavior that has implications for clinical activity. The in vitro profiles of selective (trametinib, vemurafenib) and less selective (dasatinib, sorafenib) kinase inhibitors are shown and compared. With careful evaluation of their in vitro enzyme activity profiles in Eurofins’ KinaseProfiler™ panel, cellular response profiles in OncoPanel™, and predictive biomarker identification by univariate genomic analysis, a fuller picture of these inhibitors’ biological activity can be generated, and may be applied to predicting the therapeutic potential of such inhibitors. While, in some cases, clinical response is seen as expected, this kind of comprehensive analysis opens up the possibility for expanding clinical utility of an asset by potential repurposing for other indications. Collectively, this demonstrates not only the need to understand an inhibitor’s fundamental activity(ies) at its designated target(s), but also the importance of considering cellular context, when assessing its maximum potential clinical utility. Citation Format: Alastair J. King, Jesse J. Parry, Samantha C. Burkart, Lee R. Cavedine, Alyssa M. Cracchiolo, Brogan A. Epkins, Steven M. Garner, Timothy J. Sindelar, Charles R. Wageman, Stephen P. Davies, Andrew Plater, Anna M. Woodward, Usha Warrior. Combining the power of different profiling approaches to better understand the activity of kinase inhibitor drugs [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 2116. doi:10.1158/1538-7445.AM2017-2116
Endotoxin and Traumatic Shock
Authors: Charles C. Berdjis
Journal: JAMA (1968)

From previous experiments and this report, it appears that the capillaries and small blood vessels are the most sensitive organs in shock situations. The early histologic changes detected by electron microscopy and reported here confirm this observation. This finding also helps to distinguish experimentally between the two phases of shock. The vesiculation, intracapillary fibrin formation, disseminated thrombi, and associated metabolic disturbances are considered to be the initiators of irreversible shock. The cardiovascular management, therefore, occupies the utmost important place in this complex syndrome.
Abstract P061: The Possible Apoptosis Pathways Involved in Mechanical Trauma-Induced Secondary Heart Injury
Authors: Zi Yan, Li Guo, Yongjin Wen, Chengzhang Cao, Jie Wang, Yan Zhang, Yong Guo, Feng Liang
Journal: Circulation Research (2011)

Background: Trauma induces not only primary heart injury but also secondary heart injury. Our previous study has demonstrated that mechanical trauma could cause cardiomyocyte apoptosis which contributes to posttraumatic secondary cardiac dysfunction. The aim of the present study was to elaborate the potential mechanism involved in secondary post-traumatic cardiac dysfunction. Methods: Male adult rats were subjected to Noble-Collip drum with a total of 200 revolutions at a rate of 40 rpm. The activities of cardiomyocyte Caspase 3, 8, 9, 12 were detected respectively by Fluorometric assays. The cardiac function in vitro was determined using a Langendorff isolated heart perfusion system. Results: No direct mechanical traumatic injury was observed in the heart immediately after trauma. (1)Compared with the sham group, myocardial Caspase-3 activity in the traumatized rats significantly increased 6h after trauma (51±4 vs. 16±2, P &lt;0.01). 12h after trauma myocardial Caspase-3 activity reached the peak (69±4 vs. Sham, P &lt;0.01), which still remained at high level (46±3 vs. Sham, P &lt;0.01) 24h after trauma. (2) Administration of Z-VAD-FMK, a broad-spectrum caspase inhibitor, could reverse post-traumatic cardiac dysfunction evidenced by increased +dP/dt max [(4111±189) mmHg/sec, vs. sham (3414±208) mmHg/sec, P &lt;0.01], and decreased -dP/dt max [(-4997±351) mmHg/sec, vs. sham group (-3301±458) mmHg/sec, P &lt;0.01] 24h after trauma. (3) Compared with the sham group, myocardial Caspase-12 activity significantly increased 3h after trauma (66±8 vs. 27±10, P &lt;0.01). 6h after trauma Caspase-12 activity reached the peak (89±16, P &lt;0.01 vs. Sham) , but 12h after trauma it decreased ( P &gt;0.05 vs. Sham). Both myocardial Caspase-8 activity and Caspase-9 activity markedly increased 24h after trauma (2312±648 vs. 1449±296, P &lt;0.01 vs. Sham; 875±460 vs. 470±222, P &lt;0.01 vs. Sham, respectively). Conclusion: Caspase-dependent apoptotic pathway played an important role in post-traumatic secondary cardiac dysfunction. Moreover, in the early period of trauma, cardiomyocyte apoptosis was induced by activation the Caspase-12, an endoplasmic reticulum (ER)-specific caspase, following by activation of Caspase-8 (extrinsic pathway) and Caspase-9 (intrinsic pathway).
Harnessing CXCR4 antagonists in stem cell mobilization, HIV infection, ischemic diseases, and oncology
Authors: Lun Kelvin Tsou, Ying‐Huey Huang, Jen‐Shin Song, Yi‐Yu Ke, Jing‐Kai Huang, Kak‐Shan Shia
Journal: Medicinal Research Reviews (2017)

Abstract CXCR4 antagonists (e.g., Plerixafor TM ) have been successfully validated as stem cell mobilizers for peripheral blood stem cell transplantation. Applications of the CXCR4 antagonists have heralded the era of cell‐based therapy and opened a potential therapeutic horizon for many unmet medical needs such as kidney injury, ischemic stroke, cancer, and myocardial infarction. In this review, we first introduce the central role of CXCR4 in diverse cellular signaling pathways and discuss its involvement in several disease progressions. We then highlight the molecular design and optimization strategies for targeting CXCR4 from a large number of case studies, concluding that polyamines are the preferred CXCR4‐binding ligands compared to other structural options, presumably by mimicking the highly positively charged natural ligand CXCL12. These results could be further justified with computer‐aided docking into the CXCR4 crystal structure wherein both major and minor subpockets of the binding cavity are considered functionally important. Finally, from the clinical point of view, CXCR4 antagonists could mobilize hematopoietic stem/progenitor cells with long‐term repopulating capacity to the peripheral blood, promising to replace surgically obtained bone marrow cells as a preferred source for stem cell transplantation.
Abstract 5113: Usnic acid, lichen secondary metabolite, inhibits glioblastoma progression through the reduction of epithelial-mesenchymal transition and glioma stemness factors
Authors: Kyung-Hwa Lee, Se-Jeong Oh, Shin Jung, Kyung-Keun Kim, Jae-Hyuk Lee, Kyung-Sub Moon
Journal: Cancer Research (2017)

Abstract Background: Usnic acid (UA), an active compound mainly found in lichens, has shown some anti-tumoral activities for lung and breast cancers. The therapeutic role of UA in glioblastoma (GM) have not yet been determined, nor has the definitive relationships of UA with EMT and cancer stem cells. Methods: We tested the anti-tumoral activities of UA against glioblastoma (GM) progression and further investigated the mechanistic link with epithelial-mesenchymal transition (EMT) and cancer stemness factors. The targeting and anti-tumor effect of UA was also checked in orthotopic mouse glioma model. Results: In vitro assay, we found that UA increased apoptotic cell death and inhibited the invasion/migration of GM cells. Sphere and colony forming abilities were also decreased in treated GM cells. UA decreased the expression of the EMT markers (N-cadherin, ZEB1, ZEB2, SNAIL and SLUG) and the cancer stemness markers (CD133, ALDH1 and CD44). In orthotopic mouse glioma models, UA localized in GBM and significantly decreased tumor growth and progression to lead longer survival. Conclusion: Taken together, these findings showed that UA prevent GBM invasiveness and progression, through the down-regulation of EMT and cancer stemness markers. Citation Format: Kyung-Hwa Lee, Se-Jeong Oh, Shin Jung, Kyung-Keun Kim, Jae-Hyuk Lee, Kyung-Sub Moon. Usnic acid, lichen secondary metabolite, inhibits glioblastoma progression through the reduction of epithelial-mesenchymal transition and glioma stemness factors [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 5113. doi:10.1158/1538-7445.AM2017-5113