tbuckley/cabot-search huggingface dataset:
Abstract 3930: Inhibition of the Malate-aspartate Shuttle Abolishes Cardioprotection by Postconditioning in Rat Hearts
Authors: Bo Løfgren, Rebekka Thomsen, Nicolaj Brejnholt Støttrup, Steen Buus Kristiansen, Hans Erik Bøtker, Torsten Toftegaard Nielsen
Journal: Circulation (2009)

Objective:  To investigate the importance of the malate-aspartate shuttle (MAS) for cardioprotection by ischemic postconditioning (iPCON). Furthermore, we studied whether postconditioning (iPCON) modulates metabolism of L-glutamate, a key metabolite of the MAS.   Methods:  Isolated rat hearts were perfused with glucose and subjected to 40 min of global ischemia followed by 120 min reperfusion. iPCON was induced by 6 cycles of 10 sec reperfusion/10 sec ischemia. To inhibit the MAS the amino acid transaminase inhibitor aminooxyacetate (AOA: 0.025 mM) was administered during reperfusion. Hearts were allocated to 4 groups:  Control;  iPCON;  Control + AOA and  iPCON + AOA (N=10 in each group) and infarct size and hemodynamic recovery were evaluated.  Coronary effluent, microdialysis and myocardial tissue were collected for metabolic measurements.   Results : iPCON significantly reduced infarct size when compared to control. Inhibition of the MAS by AOA abolished the infarct reducing effect by postconditioning (Figure 1A). Myocardial release of glutamate was significantly decreased during iPCON (P   Conclusion:  Activity of the malate-aspartate shuttle is crucial for cardioprotection by iPCON. The mechanisms underlying iPCON includes myocardial glutamate metabolism.
Abstract 2543: The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma stem cells
Authors: Wei Jiang, Shlomit Brodie, Simona Cazacu, Cunli Xiang, Laila Poisson, Steve Kalkanis, Doron Ginsberg, Chaya Brodie
Journal: Cancer Research (2017)

Abstract Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), the median survival of 12-14 months has not changed significantly. Therefore, there is an imperative need to identify molecular mechanisms that play a role in patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM with poor prognosis, in GBM specimens derived from short-term survivors and in glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell proliferation and arrested the cells in the G1\S phase of the cell cycle in various cancer cell lines. In addition, silencing of TALNEC2 decreased the self-renewal and mesenchymal transformation of GSCs, increased sensitivity of these cells to radiation and prolonged survival of mice bearing GSC-derived xenografts. Using miRNA array analysis, we identified specific miRNAs that were altered in the silenced cells that were associated with cell-cycle progression, proliferation and mesenchymal transformation. Two of the downregulated miRNAs, miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM and in tumors from patients of short-term survival. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM. Citation Format: Wei Jiang, Shlomit Brodie, Simona Cazacu, Cunli Xiang, Laila Poisson, Steve Kalkanis, Doron Ginsberg, Chaya Brodie. The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the stemness and radiation response of glioma 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 2543. doi:10.1158/1538-7445.AM2017-2543
Induction of Leukemia in Mice by Methylcholanthrene and X-Rays&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: D. P. McEndy, Mary C. Boon, Jacob Furth
Journal: JNCI Journal of the National Cancer Institute (1942)

Induction of Leukemia in Mice by Methylcholanthrene and X-Rays Get access D. P. McEndy, D. P. McEndy resident in pathology Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary C. Boon, Mary C. Boon research assistant Search for other works by this author on: Oxford Academic PubMed Google Scholar Jacob Furth Jacob Furth associate professor of pathology Cornell University Medical College and New York Hospital, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 3, December 1942, Pages 227–247, https://doi.org/10.1093/jnci/3.3.227 Published: 01 December 1942
3D Cell Printed Tissue Analogues: A New Platform for Theranostics
Authors: Yeong-Jin Choi, Hee-Gyeong Yi, Seok-Won Kim, Dong-Woo Cho
Journal: Theranostics (2017)

Stem cell theranostics has received much attention for noninvasively monitoring and tracing transplanted therapeutic stem cells through imaging agents and imaging modalities. Despite the excellent regenerative capability of stem cells, their efficacy has been limited due to low cellular retention, low survival rate, and low engraftment after implantation. Three-dimensional (3D) cell printing provides stem cells with the similar architecture and microenvironment of the native tissue and facilitates the generation of a 3D tissue-like construct that exhibits remarkable regenerative capacity and functionality as well as enhanced cell viability. Thus, 3D cell printing can overcome the current concerns of stem cell therapy by delivering the 3D construct to the damaged site. Despite the advantages of 3D cell printing, the
Abstract 919: Identification of stem cells in stomach corpus and antrum
Authors: Junichi Matsuo, Akihiro Yamamura, Khay Guan Yeoh, Motomi Osato, Yoshiaki Ito
Journal: Cancer Research (2017)

Abstract Gastric cancer is still relatively poorly understood, because of the lack of knowledge on stem cells in stomach. By radio-labeling experiments and electron microscopy, rapidly proliferating stem cells have been suggested in isthmus of both corpus (which is just below pit cell zone) and antrum (which is a quarter above the base) (1). In addition, there have been reports indicating the proliferation capacity under certain conditions in a subset of chief cells present at the base in corpus (2). We reported earlier that 270 bp Runx1 enhancer element (termed aR1) that drives the expression of Runx1 in hematopoietic stem cells (3). We found that eR1 also marks the cells in these three locations of stomach (4). In antrum, the stem cell marker, Lgr5, has been reported to mark the cells at the base of antrum but not in corpus (5). eR1+ and Lgr5+ stem cell in antrum appears to be different. It will be interesting to find out the difference between these two types of stem cells. Transgenic mouse was generated that harbors eR1 linked to heterologous promoter and Cre recombinase (eR1-CreERT2). By treating the mouse with tamoxifen, we showed lineage tracing from eR1+ cells in the isthmus of both corpus and antrum that replenish entire glands. We expressed K-rasG12D in eR1+ cells in isthmus and observed antralization of corpus epithelium that is similar to precancerous lesion in human stomach after H pylori infection. On the other hand, eR1+ chief cells rarely multiply. However, they robustly proliferate after tissue damage or oncogene expression. When K-rasG12D is activated in eR1+ chief cells, they show retrodifferentiation to show SPEM (spasmolytic polypeptide expressing metaplasia) phenotype. eR1+ chief cells appear to be reserve stem cells that can replace cells after tissue damage. We now have capability to activate or inactivate genes of interest in the stomach stem cells. We are examining stepwise carcinogenesis in stomach. From eR1+ cells in isthmus of both corpus and antrum, we are generating organoids. We will describe interesting difference in the properties of organoids generated from eR1+ cells from corpus and those from antrum. &amp;lt;Reference&amp;gt; (1) Karam and Leblond., The Anatomical Record 1993; 236: 259-273. (2) Goldenring et al., Gastroenterology 2011; 138: 2207-2210. (3) Ng et al., Stem Cells 2010; 28: 1869-81. (4) Matsuo et al., Gastroenterology 2016; PMID: 27670082. (5) Barker et al., Cell Stem Cell 2010; 6: 25-36. Citation Format: Junichi Matsuo, Akihiro Yamamura, Khay Guan Yeoh, Motomi Osato, Yoshiaki Ito. Identification of stem cells in stomach corpus and antrum [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 919. doi:10.1158/1538-7445.AM2017-919
Abstract 5055: Multiplatform metabolomics analysis of growth arrest in pancreatic tumor xenografts
Authors: Irving W. Wainer, Danuta Dudzik, Michel Bernier, Coral Barbas
Journal: Cancer Research (2017)

Abstract R,S-4-Methoxy-1-naphthylfenoterol, MNF, inhibits the G protein-coupled receptor GPR55. In this study, we determine the effect of MNF on human PANC-1 pancreatic tumor growth in mice and apply multiplatform metabolomics analysis to identify pathways associated with growth arrest. Methods: Female Balb/c nude mice, 6-8 weeks old, 18-20g, were inoculated subcutaneously with 5 x 106 PANC-1 cells. On Day 8, mice were placed in groups of 10 using random block design based upon tumor volume. Mice received daily ip injections of vehicle or 40mgxkg-1 MNF 5 days/week for 3 treatment cycles. Mice were monitored daily and tumor volumes measured at beginning and end of each dosing cycle. On Day 33, mice were euthanized, and plasma samples and tumors collected. Tumor tissue was homogenized, extracted and analyzed using liquid chromatography-QTOF-MS, capillary electrophoresis-TOF-MS and gas chromatography-EI-Q-MS. Differences between groups were evaluated by unpaired t-test or Mann−Whitney test with post hoc Benjamini-Hochberg correction. Statistical significance was set at P≤0.05. Compound identification was accomplished using online databases and in-house standards Results Tumor volume increased in vehicle-treated mice by ~700%, 142 ± 8 mm3 to 957 ± 79 mm3 and only ~250% in MNF-treated mice, 143 ± 8 mm3 to 259 ± 27 mm3. On Day 33, MNF was not detected in plasma but accumulated in tumor tissues, 43.9 ± 32.7 ng/g. Plasma L-lactate levels were reduced from 3.29 ± 0.66 mmol/L το 2.81 ± 0.60 mmol/L, P≤0.001. Differences in tumor tissue metabolome were observed with MNF compared to vehicle, which was reflected by significant, P≤0.05, changes in relative metabolite signals. MNF treatment was accompanied by the disruption of pyrimidine nucleotide biosynthesis at uridine 5'-monophosphate, UMP, and increased UMP degradation. Moreover, the +237% increase in ophthalmic acid and +95% increase in its precursor 2-aminobutyrate indicate higher oxidative stress and the +51% increase in 2-hydroxyproline suggest greater HFI-1α proteolysis upon MNF treatment. Conclusions These results are consistent with our previous observations in PANC-1 cells showing that GPR55 inhibition attenuates activation of the EGFR-MEK-ERK, Wnt-β-catenin and PI3K/AKT pathways resulting in lower cyclin D1 expression and halting the cell cycle in G1. The reduction in HIF-1α expression and glycolytic flux in MNF-treated PANC-1 cells is in line with the decline in L-lactate plasma levels in MNF-treated mice. The data from this study indicate that MNF may be useful in the treatment of pancreatic cancer. Citation Format: Irving W. Wainer, Danuta Dudzik, Michel Bernier, Coral Barbas. Multiplatform metabolomics analysis of growth arrest in pancreatic tumor xenografts [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 5055. doi:10.1158/1538-7445.AM2017-5055
Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18
Authors: Ying Lai, Ucheor B. Choi, Jeremy Leitz, Hong Jun Rhee, Choongku Lee, Bekir Altas, Minglei Zhao, Richard A. Pfuetzner, Austin L. Wang, Nils Brose, JeongSeop Rhee, Axel T. Brunger
Journal: Neuron (2017)
Lack of a pulmonary vein causing unilateral interlobular septal thickening
Authors: Hanping Wang, Li Zhang, Wei Liu, Kai-Feng Xu, Juhong Shi
Journal: Thorax (2017)

A 24-year-old woman presented with an 8-year history of chest tightness and shortness of breath during intense exercise. Physical examination showed decreased expansion of the right rib cage and respiratory sounds in the right lung were quiet. A routine examination was unremarkable. There were no systemic symptoms, including fever, skin rash and arthralgia. The erythrocyte sedimentation rate and high sensitivity C-reactive protein levels were normal. Autoantibodies, including antinuclear antibodies, antiextractable nuclear antigen antibodies and antineutrophil cytoplasmic antibodies, were negative.

Chest high-resolution CT showed a low right lung volume, markedly thickened interlobular septae (mainly in the right lower lung) and some ground-glass opacity, showing a wedge-shaped area of consolidation (figure 1A). Bronchoscopy showed submucosal varices of the right bronchial tree, with markedly increased surface secretions and mucosal hypertrophy (figure 2). Echocardiography showed normal inner atrial and ventricular diameters. Additionally, ostia of the right superior pulmonary vein were unclear, and pulmonary arterial systolic pressure was normal. CT pulmonary angiography …
Abstract 5516: Regulation of TFPI-2 in the progression of ovarian cancer
Authors: Jacqueline Fry, Sumie Kato, Lorena Abarzua, Pamela Gonzalez, Carolina Ramirez, Elisa Cumsille, Erasmo Bravo, Raimundo Correa, Juan E. Leiva, Cesar Paredes, Juan C. Roa, Carolina Ibañez, Mauricio Cuello, Gareth I. Owen, Maria L. Bravo
Journal: Cancer Research (2017)

Abstract Ovarian cancer metastasis occurs when malignant cells migrate from the primary tumor into the ascitic fluid and form a secondary tumor in the peritoneal cavity. The cells responsible for this process, Metastases Initiating Cells (MICs), suffer a series of changes in protein expression, with increased Epithelial Mesenquimal Transition and stem cell markers having been reported. Tissue Factor Pathway Inibitor-2 (TFPI-2) is a serine proteinase inhibitor and potential tumor suppressor gene, whose reduction is correlated with more metastases and poor prognosis. As the exact stage of TFPI-2 loss is still unknown, the purpose of our study was to determine TFPI-2 during ovarian cancer progression. Protein and RNA levels were assessed in primary tumor and metastatic tissue from papillary serous carcinoma by immunohistochemistry and qPCR, respectively. TFPI-2 RNA and protein levels were analyzed in cancer cell lines and primary cultured cancer cells isolated from ascitic fluid of advanced ovarian cancer patients and in cancer spheres derived from these cultures. Epigenetic changes of 3 CpG were analized by bisulfite and pirosequencing technique in ovarian cancer cell lines and in cancer spheres derived from these cultures. We report that significantly decreased TFPI-2 protein levels in metastatic tissue compared to the primary tumor, a result confirmed in matched primary and metastatic lesions from the same ovarian cancer patients. Furthermore, cancer spheres (representing potential MICs) displayed significantly lower levels of TFPI-2 than corresponding cell line and some primary cultured cancer cells. The cancer spheres showed a modest increase in methylation percentage in three specific CpG sites within the TFPI-2 promoter. Our results suggest that TFPI-2 loss plays a role in the cancer cell escape from the primary tumor. Future studies will determine the mechanism and the biological consequences of the progressive loss of TFPI-2 in cancer. Funding: FONDECYT 11140657, 1160800, 1140970, 3140335, 3150028, CORFO L2 13IDL2-18608, IMII-P09/016-F, CONICYT-FONDAP 15130011, BMRC 13CTI21526-P6 Citation Format: Jacqueline Fry, Sumie Kato, Lorena Abarzua, Pamela Gonzalez, Carolina Ramirez, Elisa Cumsille, Erasmo Bravo, Raimundo Correa, Juan E. Leiva, Cesar Paredes, Juan C. Roa, Carolina Ibañez, Mauricio Cuello, Gareth I. Owen, Maria L. Bravo. Regulation of TFPI-2 in the progression of 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 5516. doi:10.1158/1538-7445.AM2017-5516
Abstract 462: The role of miR-24 as a race-related genetic factor in prostate cancer
Authors: Yutaka Hashimoto, Marisa Shiina, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Varahram Shahryari, Priyanka Kulkarni, Pritha Dasgupta, Yozo Mitsui, Mitsuho Sumida, Guoren Deng, Laura Tabatabai, Deepak Kumar, Rajvir Dahiya
Journal: Cancer Research (2017)

Abstract The incidence of prostate cancer (PCa) among African-Americans (AfA) is significantly higher than Caucasian-Americans (CaA) but the genetic basis for this disparity is not known. To address this problem, we analyzed miRNA expression in AfA (n=81) and CaA (n=51) PCa patients. Here, we found that miR-24 is differentially expressed in AfA and CaA PCa patients and attempt to clarify its role in AfA patients. Also, the public sequencing data of the miR-24 promoter confirmed that it was highly methylated and down-regulated in PCa patients. Utilizing a VAMCSF and NDRI patient cohorts, we discovered that miR-24 expression was linked to a racial difference between AfA/CaA PCa patients. Interestingly, miR-24 was restored after treatment of PCa cells with 5Aza-CdR in an AfA cell line (MDA-PCa-2b), while restoration of miR-24 was not observed in CaA cells, DU-145. Ectopic expression of miR-24 showed decreased growth and induced apoptosis, though the effect was less in the CaA cell line compared to the AfA cell line. Finally, we found unique changes in biological pathways and processes associated with miR-24 transfected AfA cells by quantitative PCR-based gene expression array. Evaluation of the altered pathways showed that AR, PDPK1, IGF1, and IGFBP5 were markedly decreased in the AfA derived cell line compared with CaA cells, and there was a reciprocal regulatory relationship of miR-24/target expression in prostate cancer patients. These results demonstrate that miR-24 may be a central regulator of key events that contribute to race-related tumorigenesis and has potential to be a therapeutic agent for PCa treatment. Citation Format: Yutaka Hashimoto, Marisa Shiina, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Varahram Shahryari, Priyanka Kulkarni, Pritha Dasgupta, Yozo Mitsui, Mitsuho Sumida, Guoren Deng, Laura Tabatabai, Deepak Kumar, Rajvir Dahiya. The role of miR-24 as a race-related genetic factor in prostate 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 462. doi:10.1158/1538-7445.AM2017-462
Congenital Heart Disease in Adults
Authors: M. Elizabeth Brickner, L. David Hillis, Richard A. Lange
Journal: New England Journal of Medicine (2000)

Cyanotic ConditionsPatients with cyanotic congenital heart disease have arterial oxygen desaturation resulting from the shunting of systemic venous blood to the arterial circulation. The magnitude of shunting determines the severity of desaturation. Most children with cyanotic heart disease do not survive to adulthood without surgical intervention. In adults, the most common causes of cyanotic congenital heart disease are tetralogy of Fallot61 and Eisenmenger's syndrome.Tetralogy of FallotTetralogy of Fallot, the most common cyanotic congenital heart defect after infancy, is characterized by a large ventricular septal defect, an aorta that overrides the left and right ventricles, obstruction of the . . .
Abstract SY21-03: Cancer evolution as a therapeutic target
Authors: Alberto Bardelli
Journal: Cancer Research (2017)

Abstract When metastatic cancers are challenged with targeted agents, almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near-certainty of disease recurrence following treatment with targeted agents? Addressing this question means considering as a target not “only” individual oncogenes but also the evolving nature of human tumors. We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumor’s evolution, the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars. To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells; that is to say, therapies must adapt to tumor evolution. One possibility is to anticipate the changes the tumors will make. For example, by knowing in advance how CRC cells overcome resistance to EGFR blockade, we devised further rounds of therapy. Another approach is to unleash the ability of the immune system to recognize drug-resistant cells. We tested this possibility in syngeneic mouse models of CRC sensitive to targeted therapies. Our findings indicate that manipulation of the mutational loads can trigger prolonged therapeutic responses that are not observed when cancer cells are challenged with targeted drugs alone. We postulate that rationally combined targeted therapies and immunotherapies can restrain tumor evolution and can limit the emergence of drug resistance, thus leading to long-term responses. Citation Format: Alberto Bardelli. Cancer evolution as a therapeutic target [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 SY21-03. doi:10.1158/1538-7445.AM2017-SY21-03