tbuckley/cabot-search huggingface dataset:
Abstract 846: A novel high-throughput 3D screening system for EMT inhibitors
Authors: Kazuya Arai, M Mamunur Rahman, Manabu Itoh, Norio Masuda, Takanori Eguchi, Tetsuya Nakatsura, Stuart K. Calderwood
Journal: Cancer Research (2017)

Abstract EMT (epithelial-mesenchymal transition) is a significant event in tumor metastasis and malignancy. Therefore, inhibition of EMT is considered to enable controlling of malignant transformation. In this study, we introduce an innovative three-dimensional (3D) high-throughput (HTS) system that leads to an identification of EMT inhibitors. At first, we established 3D-HTS EMT model with NanoCulture Plate (NCP) that provided a gel-free micro-patterned scaffold for cells forming spheroids naturally. In the NCP-based 3D cell culture system, A549 lung cancer cells migrated, gathered, and then formed multiple spheroids within 7 days. Live cell imaging experiments showed that an established EMT-inducer TGF-β promoted peripheral cells around the core of spheroids to acquire mesenchymal spindle shapes, loss of intercellular adhesion, and migration from the spheroids. Along with such morphological change, EMT-related gene expression signatures were altered, particularly alteration of mRNA levels of ECAD/CDH1, NCAD/CDH2, VIM and ZEB1/TCF8. These EMT-related phenotypic changes were blocked by SB431542, a TGF-βreceptor I (TGFβR1) inhibitor. Inside of the spheroids were highly hypoxic; in contrast, spheroid derived peripheral migrating cells were normoxic, revealed by visualization and quantification using Hypoxia Probe. Thus, TGF-β-triggered EMT caused spheroid hypoplasia and loss of hypoxia. Spheroid EMT inhibitory (SEMTIN) activity of SB431542 was calculated from fluorescence intensities of the Hypoxia Probe, and then was utilized in a drug screening of EMT-inhibitory small molecule compounds. In a pilot screening, 9 of 1,330 compounds were above the thresholds of the SEMTIN activity and cell viability. Finally, two compounds SB-525334 and SU9516 showed SEMTIN activities in a dose dependent manner. SB-525334 was a known TGFβR1 inhibitor. SU9516 was a cyclin-dependent kinase 2 (CDK2) inhibitor, which we showed also had an EMT-inhibitory activity. Taken together, it was shown that this 3D NCP-based HTS system was useful for screening of EMT-regulatory drugs. Citation Format: Kazuya Arai, M Mamunur Rahman, Manabu Itoh, Norio Masuda, Takanori Eguchi, Tetsuya Nakatsura, Stuart K. Calderwood. A novel high-throughput 3D screening system for EMT inhibitors [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 846. doi:10.1158/1538-7445.AM2017-846
Abstract 3416: Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database
Authors: Masayoshi Higashiguchi, Izumi Nagatomo, Takashi Kijima, Osamu Morimura, Kotaro Miyake, Toshiyuki Minami, Shohei Koyama, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
Journal: Cancer Research (2017)

Abstract Identification of somatic mutations that contribute to cancer development leads not only to more precise understanding of cancer pathogenesis, but also development of novel molecular targeted therapies. Analyses of cancer genomes using high-throughput sequencing technology are currently conducted as international collaborative research projects, and the results of those analyses are deposited in public databases, allowing everyone in the world to access to these data. To identify a somatic mutation that plays an important role in cancer pathogenesis, we counted the occurrences of each somatic mutation found in the TCGA lung adenocarcinoma dataset and became interested in the CHK2 K373E mutation (c1117A&amp;gt;G), which was present in 31 of 542 patients. The K373E mutation impaired CHK2 autophosphorylation at Thr383 and Ser516. In vitro kinase assay revealed that the K373E mutation markedly attenuates CHK2 kinase activity. Growth curves showed that wild-type CHK2 substantially suppressed cell proliferation, but this effect was lost in the K373E mutant in HCT-15 harboring tetracycline-inducible CHK2. Clonogenic assays revealed that wild-type CHK2 promoted survival after ionizing radiation and this pro-survival function was impaired in K373E CHK2. The results of western blotting and RT-PCR suggested that the p53-independent induction of p21 by CHK2 might underlie these effects. Therefore, we identified a somatic mutation that contributes to cancer pathogenesis, using information in a public database. This kind of attempt is expected to lead to discovering new 'driver' mutations in the future. Citation Format: Masayoshi Higashiguchi, Izumi Nagatomo, Takashi Kijima, Osamu Morimura, Kotaro Miyake, Toshiyuki Minami, Shohei Koyama, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh. Clarifying the biological significance of the CHK2 K373E somatic mutation discovered in The Cancer Genome Atlas database [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 3416. doi:10.1158/1538-7445.AM2017-3416
Abstract 1279: A polymorphism of VEGF -2489C/T is associated with prostate cancer susceptibility in Mexicans
Authors: Abril Martínez-Rizo, Xavi Casillas-Rangel, Hilda Andrade-Madrid, Veronica Benites-Godinez, Nallhely Rodríguez-Ocampo
Journal: Cancer Research (2017)

Abstract Introduction: Prostate cancer (CaP) encompasses a range of malignant prostate tissue dysplasias that primarily affects men over 50 years, is the second leading cause of cancer mortality in males. VEGF expression is associated with tumor progression and metastasis in patients with CaP. The SNP -1154 G/A is associated with the severity of CaP populations in Tunisia and the United Kingdom while -634 G/C alone has been associated in Tunisian population. It is unknown whether these polymorphisms could serve as biomarkers in the Mexican population. Aim: To associate VEGF polymorphisms -1154 G/A and - 634 G/C with the severity of prostate cancer in patients of western Mexico. Materials and methods: The gDNA was analyzed a total of 525 men of whom 301 are presented HBP and 224 patients with clinical diagnosis of prostate cancer. For association with severity they were subclassified into high (≥7) and low grade (≤6) following the Gleason scale. Genotyping was performed by Real Time PCR using TaqMan probes system. Results. When we compare the allelic frequencies in the control group, they are in Hardy-Weinberg equilibrium. However, no significant association of the disease with polymorphisms or severity or progression was found. Conclusions: There is no association between prostate cancer and genetic polymorphisms at -634 and -1154 position of the promoter region of VEGF. Note: This abstract was not presented at the meeting. Citation Format: Abril Martínez-Rizo, Xavi Casillas-Rangel, Cuerpo Académico Investigación Bioquímica (UAN-CA-266), Hilda Andrade-Madrid, Veronica Benites-Godinez, Nallhely Rodríguez-Ocampo. A polymorphism of VEGF -2489C/T is associated with prostate cancer susceptibility in Mexicans [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 1279. doi:10.1158/1538-7445.AM2017-1279
Abstract 4444: MicroRNA hsa-miR-145 expression in hepatocellular carcinoma correlates with patient survival
Authors: Go Nakajima, Kazuhiko Hayashi
Journal: Cancer Research (2017)

Abstract Aim: MicroRNAs (miRNAs) are known as one of the regulator of gene expression at a post-transcriptional level. Previous study from our group identified forty nine miRNAs that are expressed differentially by comparing 26 pair samples of hepatocellular carcinoma (HCC) tumor tissue and non-tumor liver tissue using next-generation sequencer system, and hsa-miR-145, one of the candidate miRNA was chosen for this validation study. The expression of hsa-miR-145 in validation set HCC samples were measured by real-time PCR, and were examined the correlation between the miRNA expression and clinical data. Patients and Methods: Forty-four patients diagnosed as HCC had undergone surgical removal from 1991 to 1997 at the Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Japan. The formalin-fixed paraffin embedded samples were prepared using the standard protocol. The paraffin blocks were cut into 10 micrometer sections, and the tumor and its adjacent non-tumor liver tissue were collected using laser-captured microdissection and total RNA including miRNA fraction were isolated. After synthesized cDNA using miRNA specific primer, real-time PCR was performed using miRNA specific primer/probe. Results: The expression level of hsa-miR-145 was down-regulated in tumor compared to non-tumor liver tissue (P=0.0004). The patients were divided into two groups, higher/lower expression, the group of the higher hsa-miR-145 expression was significantly longer overall survival time compared to the lower expression group (P=0.0378). Conclusion: The hsa-miR-145 may be potential prognostic factor for HCC patients. Citation Format: Go Nakajima, Kazuhiko Hayashi. MicroRNA hsa-miR-145 expression in hepatocellular carcinoma correlates with patient survival [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 4444. doi:10.1158/1538-7445.AM2017-4444
Abstract 2516: Pokemon functions as a metabolic oncoprotein integrating glucose &amp; lipid metabolism in hepatocellular carcinoma
Authors: Yibao Jin, Shangfu Li, Deliang Cao, Dan Gao, Hongxia Liu, Feng Liu, Tiejie Wang, Yuyang Jiang
Journal: Cancer Research (2017)

Abstract Pokemon (also known as FBI-1 or LRF) is a proto-oncogene encoded by ZBTB7A gene. It functions as a transcription factor, playing important roles in embryonic development, cell differentiation and neoplasia. Pokemon is abnormally expressed in hepatocellular carcinoma (HCC) and may contribute to the metabolic homeostasis of HCC cells, but the mechanism of action remains to be fully understood. This study demonstrated that Pokemon may integrate glycolysis and lipid metabolism in hepatocellular carcinogenesis. Our data showed that Pokemon was upregulated in HCC cell lines and clinical samples. Ectopic expression of Pokemon stimulated HCC cell growth and proliferation in culture and tumorigenesis in nude mice. Lipid metabolomic analysis by LC/MS exhibited that in HCC cells lipogenesis was positively correlated with Pokemon expression levels, and targeted expression of Pokemon in HCC cells promoted the flux of radiolabeled glucose to lipids, including membrane phospholipids, through the aerobic glycolysis-acetyl-CoA metabolic stream. Mechanistic studies revealed that Pokemon stimulated glycolysis through activation of PKA and its mediated Raf/c-Myc pathway. In the tested HCC cells, Pokemon activated fatty acid synthase (FASN) and suppressed AMPK, an inhibitor of acetyl-CoA carboxylase α (ACC-α), stimulating fatty acid and lipid synthesis. Together our results suggest that Pokemon correlates glycolysis and lipid synthesis and thus promotes lipogenesis and hepatocellular tumorigenesis. Note: This abstract was not presented at the meeting. Citation Format: Yibao Jin, Shangfu Li, Deliang Cao, Dan Gao, Hongxia Liu, Feng Liu, Tiejie Wang, Yuyang Jiang. Pokemon functions as a metabolic oncoprotein integrating glucose &amp; lipid metabolism 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 2516. doi:10.1158/1538-7445.AM2017-2516
Abstract 4225: Disparities in cervical cancer screening participation: a comparison of Russian, Somali and Kurdish immigrants with the Finnish general population
Authors: Esther E. Idehen, Päivikki Koponen, Tommi Harkanen, Tellervo Korhonen
Journal: Cancer Research (2017)

Abstract Background: Cervical cancer screening through Pap test has been shown as an effective preventive measure for early detection of precancerous in the cervix. Finland offers mass Pap test screening to all eligible women. Knowledge about disparities in the screening participation among immigrants compared with the Finnish general population is limited. Objectives: (1) To compare Pap test screening participation in the past five years among Russian, Somali and Kurdish immigrants living in Finland with the Finnish general female population; (2) to examine if the observed disparities remain similar when adjusted for socio- demographic and health-related confounding factors. Methods: Data from the Finnish Migrant Health and Well-being Study and Finnish Health 2011 Survey were used. Random samples of persons living in six cities in Finland were drawn from the national population registry. Data of self-reported cervical screening participation (Pap test) among women aged 29-60 were available from the women of Russian (n=257), Somali (n=113), Kurdish (n=167) origin and the general population (n= 436). Logistic regression was used for statistical analysis. Results: The age-adjusted Pap test participation rates were 79% among the Russian, 41% among the Kurdish, and 64% among the Somali, compared to 94% among the Finnish general population. After adjusting for age, socio - demographic, and health-related confounders, the immigrants had significantly lower likelihood for screening compared with the Finnish reference group (Russian Odds Ratio[OR] 0.33, 95% confidence interval [CI] 0.19-0.58; Somali [OR]0.08, [CI] 0.03-0.19; Kurdish [OR] 0.17 [CI]0.08-0.34). Conclusions: Initial results demonstrate significantly lower likelihood for Pap test screening among the immigrant groups compared with the Finnish general population. Note: This abstract was not presented at the meeting. Citation Format: Esther E. Idehen, Päivikki Koponen, Tommi Harkanen, Tellervo Korhonen. Disparities in cervical cancer screening participation: a comparison of Russian, Somali and Kurdish immigrants with the Finnish general population [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 4225. doi:10.1158/1538-7445.AM2017-4225
Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells
Authors: Yulong Gao, Fernando Souza-Fonseca-Guimaraes, Tobias Bald, Susanna S Ng, Arabella Young, Shin Foong Ngiow, Jai Rautela, Jasmin Straube, Nic Waddell, Stephen J Blake, Juming Yan, Laurent Bartholin, Jason S Lee, Eric Vivier, Kazuyoshi Takeda, Meriem Messaoudene, Laurence Zitvogel, Michele W L Teng, Gabrielle T Belz, Christian R Engwerda, Nicholas D Huntington, Kyohei Nakamura, Michael Hölzel, Mark J Smyth
Journal: Nature Immunology (2017)
Abstract SY23-01: KSHV: Immune evasion and oncogenesis
Authors: Blossom A. Damania
Journal: Cancer Research (2017)

Abstract Infection of cells with oncogenic DNA viruses, including herpesviruses, triggers innate immune responses mediated by DNA sensors. Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor that upon activation produces the cyclic dinucleotide cGAMP, which binds and activates Stimulator of Interferon Genes (STING), leading to interferon production and an antiviral response. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked to several human malignancies including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). We have found that KSHV infection activates the cGAS-STING pathway and that cGAS and STING also play an important role in regulating KSHV reactivation from latency. Furthermore, we have identified several KSHV viral proteins that inhibit the cGAS-STING pathway. It appears that modulation of this pathway is important for viral transmission and the lifelong persistence of oncogenic herpesviruses in the human population. Citation Format: Blossom A. Damania. KSHV: Immune evasion and oncogenesis [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 SY23-01. doi:10.1158/1538-7445.AM2017-SY23-01
Détection des adénomes lors de coloscopies réalisées avec instillation d’eau bleutée: un essai randomisé
Journal: Endoscopy (2017)

L’amélioration de notre taux de détection d’adénomes (TDA, pourcentage de patient avec au moins un adénome/adénocarcinome) voire maintenant de notre nombre moyen d’adénomes/adénocarcinomes par patient (MAP), indicateurs qualité en endoscopie, est un élément crucial pour la prévention du cancer colo-rectal par coloscopie.
Abstract 3242: Synthetic analogs of curcumin as modulators of multidrug resistance-linked ABC transporters
Authors: Megumi Obara, Shinobu Ohnuma, Eduardo E. Chufan, Masaharu Ishida, Katsuyoshi Kudoh, Norihiko Sugisawa, Hideo Ohtsuka, Takeshi Naitoh, Hiroyuki Shibata, Yoshiharu Iwabuchi, Suresh V. Ambudkar, Michiaki Unno
Journal: Cancer Research (2017)

Abstract Cancer patients often develop resistance to anticancer drugs. ATP-binding cassette (ABC) transporter-mediated drug efflux is one of the mechanisms responsible for development of resistance to anticancer drugs. The present study investigates the use of curcumin, a natural product and a dietary constituent of turmeric, which inhibits the function of three ABC drug transporters including ABCB1, ABCC1 and ABCG2. However, limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinic. We focused on curcumin analogs that were synthesized at Tohoku University and have been shown to exhibit higher bioavailability than natural curcumin to test whether the synthetic analogs also inhibit the function of ABC drug transporters. To investigate this, KB-V1 and K562/BCRP cell lines overexpressing ABCB1 and ABCG2 were used for the experiments. For these studies, we screened nineteen synthetic analogs of curcumin for their effect on the transport function of ABCB1 and ABCG2 by flow cytometry. Four curcumin analogs, GO-Y030, GO-Y078, GO-Y168 and GO-Y172 inhibited efflux of mitoxantrone mediated by ABCG2 and sensitized ABCG2-expressing K562 leukemic cells to the anticancer drug, SN-38 in cell toxicity assays. Some of the curcumin analogs (GO-Y030, GO-Y078, GO-Y172) stimulated ATPase activity of ABCG2 at nanomolar concentrations (EC50 = 480 ± 0.06, 790 ± 0.10, 930 ± 0.12 nM). In addition, GO-Y030, GO-Y078, GO-Y168, GO-Y172 analogs also inhibited photolabeling of ABCG2 in MCF-7-FL plasma membranes with iodoarylazidoprazosin, which is transported by this transporter. These data demonstrate that similar to curcumin, synthetic curcumin analogs also interact at the drug-binding pocket of ABCG2. In aggregate, these results suggest that non-toxic synthetic curcumin analogs with increased bioavailability may be useful to reverse ABCG2-mediated resistance to anticancer agents. Citation Format: Megumi Obara, Shinobu Ohnuma, Eduardo E. Chufan, Masaharu Ishida, Katsuyoshi Kudoh, Norihiko Sugisawa, Hideo Ohtsuka, Takeshi Naitoh, Hiroyuki Shibata, Yoshiharu Iwabuchi, Suresh V. Ambudkar, Michiaki Unno. Synthetic analogs of curcumin as modulators of multidrug resistance-linked ABC transporters [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 3242. doi:10.1158/1538-7445.AM2017-3242
Abstract 3373: The use of long-read sequencing to determine the structure of the Her2 amplicon in breast cancer
Authors: Jeffrey Rosenfeld, Sara Goodwin, Shridar Ganesan
Journal: Cancer Research (2017)

Abstract HER2 amplification is present in ~15% of breast cancers, and is present in small subsets of other cancer types including gastric and lung cancers. Therapy targeting HER2 is now routinely used in treatment of HER2-amplificed breast cancer and has changed the natural history of this disease. The region of chromosome 17q12 containing Her2 contains many genes, and little is known about the actual genomic alterations that underlie the amplification event. While it is known that parts of the amplicon exist in multiple copies in a tumor, the exact structure of the duplicated region is not known and their relative orientation and positions in the genome is not clear. There is the potential for rearrangements between the genes and for different segments of the amplicon to exist and varied copy numbers. There is no clear way to assemble the complete structure of this region using short reads, as they cannot resolve repetitive regions and identify junction reads. Long read sequencing has the potential to overcome these limitations, however the sequencing depth is limited and difficult to apply to large genomes. To apply long read sequencing to a limited part of the cancer genome, we have used Nimblegen target enrichment coupled with Oxford Nanopore and Pacific Bioscience sequencing in an attempt to sequence and assemble the Her2 amplicon. The error rate of the sequencers are not of concern since we are not looking at base-pair level variation. Instead, our need is for long reads that can span the gene boundaries and repetitive elements to give complete structure of the amplicon. Nimblegen custom capture probes were designed for the 2mb chromosomal region containing Her2. DNA was extracted from 3 breast cancer cell lines and enriched using the Nimblegen kit. This DNA was then sequenced with long reads on the MinIon and the PacBio to allow for complete assembly of the region. The DNA was assembled to determine the structure of the HER2 amplicon in each cell line. These results may give new insight into the molecular events that led to formation of the HER2 amplicon. Citation Format: Jeffrey Rosenfeld, Sara Goodwin, Shridar Ganesan. The use of long-read sequencing to determine the structure of the Her2 amplicon in breast 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 3373. doi:10.1158/1538-7445.AM2017-3373