tbuckley/cabot-search huggingface dataset:
Abstract 2439: Establishment of six human colorectal cancer cell lines: identification of genes that have metastatic potential
Authors: Soon-Chan Kim, Chang-Won Hong, Sang-Geun Jang, Seung-Yong Jeong, Jae-Gahb Park, Ja-Lok Ku
Journal: Cancer Research (2017)

Abstract A number of genes have been studied in accordance with their metastatic potential. Nevertheless, widely used metastatic colorectal cancer cell lines such as SW-620 or IS3 only show the influence of metastatic genes within limited mutational landscape. Here, three pairs of primary CRC (SNU-2335A, SNU-2335D, SNU-2404A, SNU-2404B, SNU-2414A, and SNU-2414B) and corresponding metastasis cell lines were established and analyzed by whole exome sequencing and microarray. Three pairs of primary CRC (SNU-2335A, SNU-2404A, and SNU-2414A) and corresponding matched metastasis cell lines (SNU-2335D, SNU-2404B, and SNU-2414B) were analyzed for gene expression by microarray and whole exome sequencing. Selected target genes from microarray were analyzed again by real-time PCR in order to confirm the mRNA expression level in the paired CRC cell lines. The genes selected for examination were calponin 3, acidic (CNN3); sorbin and SH3 domain containing 1(SORBS1); epithelial stromal interaction 1 (EPSTI1); bone marrow stromal cell antigen 2(BST2); kelch-like 5 (KLHL5); trypsinogen C (TRY6); and synaptotagmin-like 5 (SYTL5). We calculated the intersection of all three metastatic CRC cell lines. Five genes (BST2, SORBS1, CNN3, EPSTI1, and KLHL5) were up-regulated in metastatic cell lines compared to primary cell lines. Two genes (TRY6 and SYTL5) were down-regulated in metastatic cell lines compared to primary cell lines. Then, we ranked 15 genes that were up-regulated and 15 genes that were down-regulated in omental metastasis regardless of the 2-folds threshold. Of the 30 genes that were differently expressed, we selected three genes (CNN3, SORBS1, and TRY6) that showed the highest fold changes and are found in 2-fold change analysis. We identified 7 genes that were differently expressed in metastatic CRC cell lines compared to primary CRC cell lines. These genes may serve as diagnostic markers and therapeutic targets for patients with metastatic CRC. Note: This abstract was not presented at the meeting. Citation Format: Soon-Chan Kim, Chang-Won Hong, Sang-Geun Jang, Seung-Yong Jeong, Jae-Gahb Park, Ja-Lok Ku. Establishment of six human colorectal cancer cell lines: identification of genes that have metastatic potential [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 2439. doi:10.1158/1538-7445.AM2017-2439
Abstract 4915: Alcohol-induced reprogramming of tumor plasticity is mediated via suppression of CCN5 signaling in breast cancer cells
Authors: Inamul Haque, Arvind Subramanian, Vijayalaxmi Gupta, Sandipto Sarkar, Snigdha Banerjee, Sushanta K. Banerjee
Journal: Cancer Research (2017)

Abstract Background and Objective: The epidemiological and experimental studies suggest that alcohol consumption is associated with increased risk for breast cancer development and metastasis. However, the mechanisms of alcohol-induced breast cancer progression and metastasis remain unknown. In this study, we examined the roles of CCN5, a tumor suppressor gene in alcohol induced breast cancer cell migration/invasion, epithelial to mesenchymal transition (EMT) and stemness. Methods: Estrogen receptor-positive (ER+) human breast cancer cell line MCF-7 and immortalized normal human epithelial breast cell line MCF-12A were treated with ethanol at various concentrations in the presence and absence of human recombinant human CCN5 protein (hrCCN5) . Invasive/migratory ability of treated and untreated cells was measured by Boyden chamber assays. The mRNA and protein expression level of CCN5 was determined by real-time qRT-PCR and Western blot. EMT and stemness markers were evaluated by Western blot. Single-cell suspensions from pre-treated cells were re-suspended at a density of 500 cells/ml mammocult media in ultralow attachment dishes. Number as well as the size of the mammosphere in specified experimental set-up was monitored and recorded alternate day for 8-10 days. Results: The studies demonstrated that alcohol promotes significantly the invasive/migratory ability and EMT phenotypes of breast cancer cells through the suppression of CCN5. Interestingly, hrCCN5 protein treatment suppresses the effect of alcohol and reprograms MET (mesenchymal to epithelial transition). In addition, alcohol-induced mammosphere formation efficiency is also suppressed by hrCCN5 protein-treatment. Conclusions: Our findings suggest that the CCN5 signaling plays a preventive role in alcohol-induced reprogramming of tumor plasticity in breast cancer cells. Citation Format: Inamul Haque, Arvind Subramanian, Vijayalaxmi Gupta, Sandipto Sarkar, Snigdha Banerjee, Sushanta K. Banerjee. Alcohol-induced reprogramming of tumor plasticity is mediated via suppression of CCN5 signaling in breast cancer 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 4915. doi:10.1158/1538-7445.AM2017-4915
Abstract 3866: Investigating the role of class I HDACs in Ewing sarcoma pathology
Authors: Kristina von Heyking, Tim Hensel, Julia Singer, Oxana Schmidt, Stefan Burdach, Günther H. Richter
Journal: Cancer Research (2017)

Abstract Introduction: Recent evidence demonstrated that a low mutation rate seems a general feature of pediatric cancers. Ewing sarcoma (ES) is defined by balanced chromosomal EWS/ETS translocations, which give rise to oncogenic chimeric proteins (EWS-ETS). Other contributing somatic mutations involved in disease development have only been observed at low frequency. Thus, cancer in children is not solely a genetic disease and can neither be understood nor cured presumably without epigenetics. Previously, we identified the histone methyl-transferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the enzymatic subunit of the polycomb PRC2 complex, to be over-expressed in ES. RNA interference of EZH2 suppressed tumor development and metastasis in vivo and microarray analysis of EZH2 knock down revealed an EZH2-maintained, undifferentiated, reversible phenotype in ES. Experimental procedures: The role of class I histone deacetylases (HDACs) was determined using different potent inhibitors like Trichostatin A (TSA), Romidepsin (FK22), Entinostat (MS-275) and PCI-34051 as well as a CRISPR/Cas9 approach to knock out specific HDACs. To analyze resulting changes qRT-PCR, Western Blotting, proliferation, apoptosis and invasion assays as well as immunofluorescence experiments were deployed. Results: Interestingly, the effects of gene silencing after RNA interference of EZH2 could be mimicked by treatment of ES with TSA or MS-275. Microarray analysis revealed that treatment with MS-275 or TSA resulted in the induction of a similar pattern of differentiation genes as was previously observed after EZH2 blockade and seems to be dependent on histone deacetylase (HDAC) activity. Furthermore, in proliferation assays ES were more susceptible to treatment with HDAC inhibitors than other small round blue cell tumors such as neuroblastoma or pediatric cALL cells. Treatment of enzymatic inhibitors blocking EZH2 activity could not mimic the results observed after EZH2 RNA interference indicating that EZH2-containing PRC2 complexes may serve as a building block of class I HDAC activity in ES. Conclusion: Class I HDACs seem to be important mediators of the pathognomonic EWS-ETS-mediated transcription program in ES and thus interesting new treatment opportunities for this malignant disease. Citation Format: Kristina von Heyking, Tim Hensel, Julia Singer, Oxana Schmidt, Stefan Burdach, Günther H. Richter. Investigating the role of class I HDACs in Ewing sarcoma pathology [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 3866. doi:10.1158/1538-7445.AM2017-3866
Abstract 5421: Differential expression of lysosomal acid lipase (LAL) between benign and malignant tissues among human organs
Authors: Mohamed EI Gassim, Jinghe Mao, Tangen Ma, Xinchun Zhou
Journal: Cancer Research (2017)

Abstract Background: Lysosomal acid lipase (LAL), a lysosomal enzyme is able to degrade cholesteryl esters to free fatty acids and cholesterol. The information on the association of LAL with malignancies is limited. This study is to determine the difference in expression level of LAL between benign and malignant tissues among human organs. Method: Immunohistochemistry (IHC) for human LAL was performed on A tissue microarray (TMA) containing 360 benign and malignant tissues from 36 human organs. The expression level of LAL was represented by an IHC score calculated by multiplying area score (0-3) with intensity score (0-3), ranged from 0 to 9. Student’s t-test was used to compare the mean IHC score between benign and malignant tissues in same organs. Results: Eighteen out of 36 human organs have IHC stains on both benign and malignant tissues. As shown in Table 1, LAL expression level was higher in malignancy than in benign tissues in 9 organs. The difference in LAL expression level was significantly (or nearly lower in malignant tissues of adrenal gland, stomach, liver, testis and kidney. Conclusion: The expression level of LAL varies among human organs. As compared with elevation of LAL expression level, decreased expression level of LAL in malignancies could be of more significance. Table 1Difference in expression level of LALOrganmalignantBenignpM/BnMeanSEnMeanSEvalueRatioAdrenal Gland31.670.73560.950.02-1.36Stomach131.170.4583.130.820.035-2.7Liver131.350.3483.560.490.001-2.6Larynx80.250.0940.630.380.22-2.5Testis41.630.4743.750.750.054-2.3Uterus131.620.4272.570.970.302-1.6Kidney122.920.3134.50.870.051-1.5Prostate152.970.51441.22.389-1.3Urinary Bladder110.680.1750.70.30.9561Cervix41.630.4751.250.560.6361.3Colon162.340.3991.50.280.1451.6Esophagus41.630.992100.6951.6Ovary43.631.0741.940.930.2781.9Skin83.591.3251.850.720.3491.9Breast142.860.5861.380.550.1392.1Pancreas101.80.5590.830.140.1262.2Brain32.170.4450.80.560.144`2.7Lung81.970.7450.600.290.193.3 Citation Format: Mohamed EI Gassim, Jinghe Mao, Tangen Ma, Xinchun Zhou. Differential expression of lysosomal acid lipase (LAL) between benign and malignant tissues among human organs [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 5421. doi:10.1158/1538-7445.AM2017-5421
Abstract 220: Proteomic identification of therapeutics targets for Enzalutamide resistance in Castration Resistant Prostate Cancer
Authors: Lauriane VELOT, Dominique Levesque, François-Michel Boisvert, Nicolas Bisson, Frédéric Pouliot
Journal: Cancer Research (2017)

Abstract Prostate cancer (PC) is the most frequently diagnosed cancer in Canadian men and is the 3rd cause of cancer mortality. The Androgen Receptor (AR) is activated by androgens (e.g. testosterone), which leads to prostatic cell proliferation. The primary treatment for advanced PC is androgen-deprivation therapy, which is achieved via surgical or chemical castration. Nevertheless, most PC will become castration-resistant (CRPC). Although new anti-androgens (e.g. Enzalutamide) were developed to improve patients’ survival, their efficacy is still very limited and most CRPC patients will die from the disease within a few years. We postulate that by gaining insights into AR signalling networks in the context of CRPC, we could better direct patients towards the best-suited therapy and propose new therapeutic targets. To this aim, we took advantage of an innovative proteomics approach, namely proximity-labeling (BioID), to characterize global AR signalling networks in hormone-dependant LAPC4 cells. We identified 45 AR-associated proteins in non-stimulated cells, 35 of which were not previously reported. Upon androgenic stimulation, the AR signalling network increased to 320 proteins, including 278 (253 were novel) that were restricted to androgen-stimulated cells. Enzalutamide treatment resulted in a loss of 259 proteins from the network when compared to stimulated cells. As expected, this reproduced quite faithfully the status of non-stimulated LAPC4 cells. Interestingly, we identified 4 proteins in the AR network specifically after Enzalutamide treatment. These are interesting targets that may be relevant for the acquisition or the prediction of Enzalutamide resistance. Hence, they could become in time alternative therapeutic targets for CRPC treatment, to be used when Enzalutamide fails. Citation Format: Lauriane VELOT, Dominique Levesque, François-Michel Boisvert, Nicolas Bisson, Frédéric Pouliot. Proteomic identification of therapeutics targets for Enzalutamide resistance in Castration Resistant 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 220. doi:10.1158/1538-7445.AM2017-220
Abstract 4628: Selection of Smad2 for TGF-β to suppress dendritic cells by STAT3/c-Ski-induced repression of Smad3
Authors: Jeong-Hwan Yoon, Eunjin Bae, Katsuko Sudo, Masakatsu Takanashi, Jin Soo Han, Seok Hee Park, Michael Weinstein, Susumu Nakae, Tadashi Yamashita, In-Kyu Lee, Ji Hyeon Ju, Takayuki Sumida, Masahiko Kuroda, Keiji Miyazawa, Mitsuyasu Kato, Mizuko Mamura
Journal: Cancer Research (2017)

Abstract The mechanisms how Smad-mediated transforming growth factor-β (TGF-β) signalling regulates dendritic cells (DCs) remain largely unknown, despite its crucial regulatory roles in the differentiation and activation of DCs. Here, we show that STAT3/c-Ski-induced downregulation of Smad3 during differentiation selects Smad2 as the specific TGF-β receptor-regulated Smad (R-Smad) to suppress the immunogenicity of DCs. Smad3 transcribed by unphosphorylated Smad2/3 prevented the progenitor cells from DC differentiation with repression of Flt3, IRF4 and STAT3. Repression of Smad3 by synergy of phosphorylated STAT3 and c-Ski was essential for DC differentiation. TGF-β suppressed DC activation via Smad2, hence DC-specific Smad2 deletion enhanced anti-lymphoma effector functions of cytotoxic T lymphocytes (CTLs) and type 1 helper T (Th1) cells in a mouse EL4 lymphoma model. Our findings reveal stepwise regulatory roles of R-Smads in DC regulation: Smad3 inhibits differentiation and Smad2 suppresses immunogenicity. Citation Format: Jeong-Hwan Yoon, Eunjin Bae, Katsuko Sudo, Masakatsu Takanashi, Jin Soo Han, Seok Hee Park, Michael Weinstein, Susumu Nakae, Tadashi Yamashita, In-Kyu Lee, Ji Hyeon Ju, Takayuki Sumida, Masahiko Kuroda, Keiji Miyazawa, Mitsuyasu Kato, Mizuko Mamura. Selection of Smad2 for TGF-β to suppress dendritic cells by STAT3/c-Ski-induced repression of Smad3 [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 4628. doi:10.1158/1538-7445.AM2017-4628
Ventilatory practices and adjunctive therapies in children with ARDS: a prospective observational study
Authors: Eliane Roseli Barreira, Shieh Huei Hsin, A. S. Suzuki, N. V. Degaspare, P. O. Cavalheiro, G. O. C. Munoz, J. A. D. S. Martines, C. Lane, W. B. Carvalho, Alfredo Elias Gilio, A. R. Precioso
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Apresentado no American Thoracic Society International Conference; San Diego, 2014 May 16-21.
Abstract 231: Improving Physical and Mental Health Through a Community-based, Multi-disciplinary Obesity Reduction Program Promoting Social Support and Adherence
Authors: Mark Lemstra
Journal: Circulation Research (2016)

Background: The Healthy Weights Initiative is a community-based, multi-disciplinary obesity reduction program that was developed after 153 community consultations and is delivered for free to obese adults. Social support was an important component and strongly promoted in the program. Each participant was asked to attend with “buddy” and to complete a social support contract. Methods: The initial 12 weeks of the program offered 60 group exercise sessions, 12 group cognitive therapy sessions, and 12 group dietary sessions with licensed professionals. During the second 12 week period, maintenance therapy includes 12 group exercise sessions. Results: Altogether, 234 people have completed the program (79.1%). Mean objective reductions included 12.6 lbs of body fat, 3.1 inches form the waist, 2.6 inches from the hips, blood cholesterol by 0.3 mmol/L, systolic blood pressure by 5.2 mmHg and diastolic by 2.5 mmHg. Depressed mood prevalence decreased from 45.7% to 11.7%; 84.5% of those who completed the program had improvements in health-related quality of life (HRQL), and significant increases in mean scores on eight dimensions of health were also observed (such as physical functioning, which increased by 15.5%). Using binary logistic regression, independent risk factors for not completing the program (no social support contract and lower education); not improving depressed mood after completion of the program (low general health); and not improving HRQL after completion of the program (smoking and no buddy in program) were determined. Conclusion: Comprehensive obesity reduction programs can be effective when there is extensive consultation at the community level and social support at the individual level. Successful obesity reduction programs can have important cardiovascular health implications by reducing blood pressure, blood cholesterol, and improving cardiovascular fitness.
Abstract 5046: Exposure-efficacy (OS) analysis of tremelimumab in unresectable malignant mesothelioma
Authors: Paul Baverel, Lorin Roskos, Manasa Tatipalli, Nancy Lee, Paul Stockman, Maria Taboada, Paolo Vicini, Kevin Horgan, Rajesh Narwal
Journal: Cancer Research (2017)

Abstract Purpose: Tremelimumab is a fully human anti-CTLA-4 IgG2 monoclonal antibody that enhances human T-cell activation. Tremelimumab was evaluated in a Phase IIb (DETERMINE), randomised, double-blind, placebo-controlled study in patients with unresectable pleural or peritoneal malignant mesothelioma, randomised (2:1) to receive either tremelimumab (10 mg/kg, seven doses Q4W followed by Q12W) or placebo. The study demonstrated no clinically meaningful differences in overall survival (OS). The primary objectives of this analysis were to evaluate the relationship of exposure with OS, and the impact of potential confounders. Methods: A population PK model was developed to estimate and derive PK exposure metrics (area under the curve at steady state [AUCss] or clearance [CL]) for exposure-OS analysis. Impact of potential confounders was evaluated using graphical and exploratory approaches. Factors including body weight, age, gender, race, ECOG status, anatomical site (pleural or peritoneal), line of therapy, EORTC status, tumour histology, baseline tumour size, LDH, and CRP were evaluated. The analyses were performed using NONMEM 7.2 and R software. Results: The population PK included 376 patients and 1328 post-first dose PK concentrations. PK was consistent with previous knowledge and low incidence of anti-drug antibodies was observed. A 2-compartment linear PK model adequately described the data. Tremelimumab CL and volume of distribution (V1) were 310 mL/day and 3.85 L, with moderate variability of ~38% and ~32%, respectively. There was an apparent exposure-OS relation when stratified by AUCss. However, at least 3 factors (gender, CRP, and baseline tumour size) were statistically significant PK predictors (p&amp;lt;0.05 on CL) indicating multi-dimensional confounding effect. Higher baseline tumor size, higher CRP levels and males were associated with lower PK exposure of tremelimumab. Conclusions: The observed apparent exposure-OS relationship is the result of imbalance in prognostic factors impacting OS rather than a true association of exposure with efficacy. Citation Format: Paul Baverel, Lorin Roskos, Manasa Tatipalli, Nancy Lee, Paul Stockman, Maria Taboada, Paolo Vicini, Kevin Horgan, Rajesh Narwal. Exposure-efficacy (OS) analysis of tremelimumab in unresectable malignant mesothelioma [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 5046. doi:10.1158/1538-7445.AM2017-5046
The KMT1A-GATA3-STAT3 Circuit Is a Novel Self-Renewal Signaling of Human Bladder Cancer Stem Cells
Authors: Zhao Yang, Luyun He, Kaisu Lin, Yun Zhang, Aihua Deng, Yong Liang, Chong Li, Tingyi Wen
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Bladder cancer is one of the most common urinary malignancies worldwide characterized by a high rate of recurrence and no targeted therapy method. Bladder cancer stem cells (BCSCs) play a crucial role in tumor initiation, metastasis, and drug resistance. However, the regulatory signaling and self-renewal mechanisms of BCSCs remain largely unknown. Here, we identified a novel signal, the KMT1A-GATA3-STAT3 circuit, which promoted the self-renewal and tumorigenicity of human BCSCs. Experimental Design: In a discovery step, human BCSCs and bladder cancer non-stem cells (BCNSCs) isolated from primary bladder cancer samples #1 and #2, and the bladder cancer cell line EJ were analyzed by transcriptome microarray. In a validation step, 10 paired bladder cancer and normal tissues, different tumor cell lines, the public microarray datasets of human bladder cancer, and The Cancer Genome Atlas database were applied for the verification of gene expression. Results: KMT1A was highly expressed and responsible for the increase of tri-methylating lysine 9 of histone H3 (H3K9me3) modification in BCSCs compared with either BCNSCs or normal bladder tissue. GATA3 bound to the -1710∼-1530 region of STAT3 promoter and repressed its transcription. H3K9me3 modification on the -1351∼-1172bp region of the GATA3 promoter mediated by KMT1A repressed the transcription of GATA3 and upregulated the expression of STAT3. In addition, the activated STAT3 triggered self-renewal of BCSCs. Furthermore, depletion of KMT1A or STAT3 abrogated the formation of BCSC tumorspheres and xenograft tumors. Conclusions: KMT1A positively regulated the self-renewal and tumorigenicity of human BCSCs via KMT1A-GATA3-STAT3 circuit, in which KMT1A could be a promising target for bladder cancer therapy. Clin Cancer Res; 23(21); 6673–85. ©2017 AACR.
18F-FDG PET/CT Findings Following Repeated Intramuscular Injections of “Site Enhancement Oil” in the Upper Extremities
Authors: Danijela Dejanović, Annika Loft
Journal: Clinical Nuclear Medicine (2017)

We present the findings on 18F-FDG PET/CT in a 50-year-old man known to self-administer intramuscular injections with site enhancement oil in the upper extremities. PET images show diffuse pathological high FDG uptake in soft tissue of the upper arms and in scanned portions of the forearms. On the CT images, the muscles in the upper arm are swollen with a moth-eaten appearance and surrounding edema. Interspersed in the muscle tissue are several “cystic” lesions interpreted as oil deposits termed oleomas.