tbuckley/cabot-search huggingface dataset:
Conflicts of Interest in Dermatology Patient Advocacy Organizations—Reply
Authors: Sean Singer, David G. Li, Arash Mostaghimi
Journal: JAMA Dermatology (2019)

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Flow cytometry for molecular profiling of solid tumors (breast, colon and ovary cancer)
Authors: Rafael Nunez, John Magenau, Sergio Zamorano, Antonella Lostumbo, Divyesh Mehta
Journal: Cancer Research (2006)

1978  Methods of determining prognosis in breast, ovary, and colon cancer includes detection of molecular markers such as the estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu. These markers are routinely assessed via immunohistochemistry (IHC) and Fluorescent In-situ hybridization (FISH). Flow cytometry (FC) has not yet been established for routine detection of these markers in tumors. We performed FC on cells from fourteen ovary, five breast, and four colon cancer tumors. FC was used to detect the presence of ER, PR, HER-2/neu, Epidermal Growth Factor Receptor (EGFR), E-cadherin, RAS, ERK and TUJ1. Cells obtained directly from tumoral tissue were simultaneous analysized by cell cycle stage (G0, G2M, and > G2M) and presence of antigenic markers. In ovarian tumors, 7 of 14 samples demonstrated >50% of cells with her-2/neu expression in aneuploid fractions (>G2M), 9 of 14 in G2M phase, and only 2 of 14 in G0 phase. With respect to ER, 7 of 14 ovarian tumors exhibited >19% of cells in G2M and >G2M fractions, while only 1 of 14 samples had >19% at G0. The PR receptor was expressed in >19 % of cells in 8 of 14 (>G2M), 7 of 14 (G2M), and 2 of 14 (G0). In breast tumors, 4 of 5 tumors demonstrated >50% expression of HER-2/neu in G2M and >G2M cell phases, and only 2 of 5 demonstrated >50% her2neu expression in G0. Three of five tumors had >19% cellular expression of ER in the >G2M and G2M phases, while only one had >19% in G0. With PR, 3 of 5 breast tumors had >19% cellular expression in G0, G2M, and >G2M phases. In colon tumors, 2 of 4 had >50% cellular expression of her2neu in >G2M fractions, 4 of 4 in G2M, and only 1 of 4 in G0. Interestingly, cell fractions containing G2M and > G2M DNA had > 50% cellular expression for RAS and ERK in 2 of 4 colon tumors (Figure). No colon tumors expressed RAS and ERK significantly in G0 cells. We found that ER, PR, and HER-2/neu marker expression were consistent with established patterns. Additionally, these data point to specific expression patterns that are associated with the cell cycle stage. In particular, we note high expression of Her-2/nue, ER, and PR in aneuploid (>G2M) cells. These results suggest that patterns of expression can be assessed in tumor tissues using FC, and the potential for broad application to all solid tumors.
Abstract 3022: Dissecting rapamycin resistance in a Tsc2-null rat leiomyoma cell line developed in a murine xenograft
Authors: Natalia Filippidou, Mathildi Valianou, Daniel L. Johnson, John J. Bissler, Aristotelis Astrinidis
Journal: Cancer Research (2019)

Abstract Despite the identification of mTOR hyperactivation as the main biochemical defect downstream of TSC1/TSC2 inactivation in Lymphangioleiomyomatosis (LAM) and Tuberous Sclerosis Complex (TSC), and the approval of rapamycin and rapalogs for the treatment of the related lesions, these drugs are cytostatic and continued treatment is required for clinical benefit. The latter raises the possibility of acquired drug resistance over long-term use. To explore the mechanisms leading to rapamycin resistance in LAM/TSC, we xenografted SCID mice with ELT3 cells (Tsc2-null derived from an Eker rat uterine leiomyoma), explanted a tumor that was not responsive to rapamycin, and generated cell line ELT3-245. The cell growth of ELT3-245 is not inhibited by rapamycin in vitro. SCID mice inoculated with ELT3-245 form palpable tumors significantly faster, compared to ELT3 cells, respond very poorly to rapamycin at the initial stages of treatment, but soon become non-responsive. In addition, these cells form macroscopically visible metastases to the lungs of ELT3-245 tumor-bearing mice. We performed global gene expression profiling, comparing ELT3-245 to ELT3 cells, and found that the rapamycin-resistant cells have decreased expression of genes associated with epithelial cells and increased expression of genes associated with mesenchymal-like characteristics. Relative gene expression of Myc, Egfr, Akt2, Jun, and Ocln were assessed by RT-qPCR in ELT3 vs ELT3-245 after 24h of treatment with 20 nM rapamycin or DMSO. Important discrepancies include a 2.8-fold increased expression of Egfr under rapamycin treatment in ELT3 cells but not in ELT3-245; however, ELT3-245 had a 15-fold higher expression of Egfr prior to treatment, compared to ELT3. In addition, ELT3-245 cells strikingly increase expression of Myc when challenged with rapamycin, compared to ELT3. Similarly, Akt2 is increased considerably under rapamycin treatment in ELT3-245 and is already higher prior to treatment compared to ELT3. Finally, Ocln expression was at least 100-fold reduced in ELT3-245, compared to ELT3, both under rapamycin treatment and no-treatment conditions. These results suggest that Myc, Egfr, Akt2, and Ocln are among the genes highly relevant to acquired rapamycin resistance in this Tsc2-null rat leiomyoma cell line and point toward the pathways that need to be interfered with in order to overcome it. Citation Format: Natalia Filippidou, Mathildi Valianou, Daniel L. Johnson, John J. Bissler, Aristotelis Astrinidis. Dissecting rapamycin resistance in a Tsc2-null rat leiomyoma cell line developed in a murine xenograft [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3022.
Bacterial Metabolism and Antibiotic Efficacy
Authors: Jonathan M. Stokes, Allison J. Lopatkin, Michael A. Lobritz, James J. Collins
Journal: Cell Metabolism (2019)

Antibiotics target energy-consuming processes. As such, perturbations to bacterial metabolic homeostasis are significant consequences of treatment. Here, we describe three postulates that collectively define antibiotic efficacy in the context of bacterial metabolism: (1) antibiotics alter the metabolic state of bacteria, which contributes to the resulting death or stasis; (2) the metabolic state of bacteria influences their susceptibility to antibiotics; and (3) antibiotic efficacy can be enhanced by altering the metabolic state of bacteria. Altogether, we aim to emphasize the close relationship between bacterial metabolism and antibiotic efficacy as well as propose areas of exploration to develop novel antibiotics that optimally exploit bacterial metabolic networks.
Abstract 2586: Therapeutic potential of the topical treatment of <i>miR-634</i> ointment for cutaneous squamous cell carcinoma
Authors: Jun Inoue, Kentaro Gokita, Masahiro Kishikawa, Hidetoshi Hamamoto, Katsunori Kobayashi, Kyoko Fujiwara, Takahiro Asakage, Kazuyuki Kojima, Johji Inazawa
Journal: Cancer Research (2019)

Abstract Cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancers. Surgery represents the gold standard for CSCC treatment, however it is needed to develop the noninvasive and effective treatments as the nonsurgical options for CSCC patients whose conditions are not suitable for or who refuse operation. On the other hand, microRNAs (miRs) are endogenous small non-coding RNAs negatively regulate gene expression by interfering with the translation or stability of target transcripts. Some tumor-suppressive miRs can target multiple cancer-promoting genes concurrently and may be useful as a therapeutic agent for cancer therapy. We have previously found that overexpression of miR-634 activated the mitochondrial apoptotic pathway by directly targeting genes associated with cytoprotective processes, including mitochondrial homeostasis, anti-apoptosis, antioxidant ability, and autophagy, in various cancer cells. The development of drug delivery system (DDS) is critical for the implementation of miR-based therapeutics. While topical pharmacotherapy represents a nonsurgical option to consider in CSCC, we validated the therapeutic potential of topical treatment of miR-634 ointment in mice model of CSCC. In xenograft tumors of A431 cells, a human epidermoid carcinoma cell line, in mice the topical treatment of ointment incorporated double-strand miR-634 mimics significantly reduced tumor growth. Furthermore, the topical treatment of miR-634-ointment also inhibited tumor growth in carcinogen-induced mouse skin papilloma model. Taken together, these findings suggest that topical treatment of miR-634-ointment may be useful as a noninvasive and effective treatments for CSCC. Citation Format: Jun Inoue, Kentaro Gokita, Masahiro Kishikawa, Hidetoshi Hamamoto, Katsunori Kobayashi, Kyoko Fujiwara, Takahiro Asakage, Kazuyuki Kojima, Johji Inazawa. Therapeutic potential of the topical treatment of miR-634 ointment for cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2586.
Abstract 4280: The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells
Authors: NAN YAO, Haiyan Sun, Maohua Huang, Wencai Ye, SiBao Chen, Dong-Mei Zhang
Journal: Cancer Research (2019)

Abstract Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging evidence has demonstrated the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition may be a promising strategy for conquering drug resistance in liver cancer cells. Methods: HepG2/ADM cells were treated with ADCX in the presence or absence of relevant inhibitors, apoptosis was measured by flow-cytometry and expression of autophagy and apoptosis related proteins was detected by western blotting. Confocal microscope was used for GFP-LC3 assay, tandem mRFP-GFP-LC3 assay, DQ-BSA method and colocalization of GFP-LC3 and LAMP1. Celluar ultrastructure was observed by transmission electronic microscopy. Results: ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae Rhizoma (Shengma), inhibited autophagic degradation by impairing the maturation of lysosomal cathepsins in multidrug resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition. Interestingly, Akt was over-activated by ADCX treatment, which was associated with impairment of cathepsin maturation. Moreover, impairing autophagic degradation promoted ADCX-induced apoptotic cell death in HepG2/ADM cells. Conclusions: Our study indicates that impairing autophagic degradation may be an effective approach for overcoming resistance and also suggests a novel role for Akt in autophagic degradation. Citation Format: NAN YAO, Haiyan Sun, Maohua Huang, Wencai Ye, SiBao Chen, Dong-Mei Zhang. The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4280.
Abstract 2416: Vitamin D concentration and the risks of Barrett’s esophagus and esophageal adenocarcinoma: A Mendelian randomization study
Authors: Jing Dong, Aaron Thrift
Journal: Cancer Research (2019)

Abstract Background Epidemiological studies on circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risks of esophageal adenocarcinoma (EAC) have shown conflicting results. Here we conducted a Mendelian randomization (MR) study to determine the associations between circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risks of EAC and its precursor, Barrett’s esophagus (BE). Methods We conducted a MR study using a two-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs) (rs3755967, rs10741657, rs12785878, rs10745742, rs8018720 and rs17216707) associated with circulating 25(OH)D concentrations were used as instrumental variables. Data from 6,167 BE patients, 4,112 EAC patients and 17,159 control participants were from studies participating in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. Results Overall, we found no evidence for an association between genetically estimated 25(OH)D concentrations and the risk of BE or EAC. The odds ratio (OR) per standard deviation unit increase in genetically estimated 25(OH)D concentrations for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% confidence interval, CI, 0.77-1.92; P = 0.41). The OR for EAC risk estimated by combining the individual SNP association using inverse variance weighting was 0.68 (95% CI, 0.39-1.19; P = 0.18). Conclusions This Mendelian randomization study found that genetically estimated low 25(OH)D concentrations were not associated with increased risks of BE or EAC. Citation Format: Jing Dong, Aaron Thrift. Vitamin D concentration and the risks of Barrett’s esophagus and esophageal adenocarcinoma: A Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2416.
Abstract 14284: A Clinical Risk Score Predicting Heart Failure and Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer
Authors: Ghideon Ezaz, Jessica P Long, Cary P Gross, Jersey Chen
Journal: Circulation (2013)

Introduction: Adjuvant trastuzumab improves survival for HER2+ breast cancers. However, trastuzumab, independently and in combination with anthracyclines, increases the risk of heart failure and/or...
Abstract 15584: A Novel and Orally Available Lecithin Cholesterol Acyltransferase Activator Prevents the Progression of Plaque Accumulation in an Atherosclerosis Mouse Model
Authors: Keisuke Yamada, Mina Delawary, Hideki Kobayashi, Toshio Kaneko, Akiko Watanabe, Shinji Shimizu, Atsuhiro Sugidachi
Journal: Circulation (2017)

Introduction: As a novel therapeutic strategy for lowering the risk of cardiovascular diseases, HDL functionality has been focused on. Lecithin cholesterol acyltransferase (LCAT) is a plasma enzyme...
Abstract 10160: In Hypertrophic Cardiomyopathy the Presence of Edema is Associated With a More Advanced Stage of Disease
Authors: Frank Gommans, Etienne Cramer, Jeannette Bakker, Michael A Fouraux, Michelle Michels, Folkert J ten Cate, Freek W Verheugt, Marc A Brouwer, Marcel J Kofflard
Journal: Circulation (2013)

Introduction: Recurrent episodes of ischemia are generally considered to be a key factor in the development of fibrosis in the majority of patients with hypertrophic cardiomyopathy (HCM). As fibros...
Abstract P160: Weight Management Program Characteristics: Keeping Patients Engaged Through Group Activities
Authors: Laura A Graham, Joshua Richman, Emily B Levitan
Journal: Circulation (2017)

Introduction: Weight management programs must be effective at engaging patients in order to be successful. However, few studies have examined program characteristics associated with better patient engagement. Hypothesis: The objective of this study was to assess patient engagement on a facility-level in the nation’s largest population-based weight management program (MOVE!). Methods: Facility-level data were collected from the Veterans Health Administration (VHA) Support Services Center. Patient engagement was measured as the average number of MOVE! visits per patient per year (VPY). Bivariate statistics were examined and multivariate-adjusted generalized linear models were used to examine factors associated with VPY. Results: We identified 140 VHA hospitals enrolled in MOVE! between 2008-2013 representing a nationwide sample of 462,132 patients with over 3 million visits. The 140 hospitals were distributed across the nation and represented a population that was 15% female, 72% white, and 34% rural. In 2008, 96% of MOVE! programs offered group counseling, 53% offered weight loss medications, and 26% offered bariatric surgery. The average facility VPY was 5.3 (SD 2.9) and increased from 4.9 (SD 3.9) in 2008 to 6.3 (SD 2.8) in 2013 (p&lt;.01). Factors associated with higher facility VPY were more administrative staff support (p&lt;.01), group counseling (5.3 vs. 3.3, p=0.01), and higher proportions of group counseling sessions among all MOVE! visits at a facility (p&lt;.01). In adjusted analyses, facilities offering group counseling reported 1.8 more VPY than facilities without group counseling (p=0.01, Figure). Offering weight loss medications (p=0.76) and bariatric surgery (p=0.57) had no effect on engagement. Conclusions: Our study demonstrates that weight loss programs offering group counseling may be more effective at engaging patients in the intervention. These findings identify potential areas for improving utilization of weight management programs.
Abstract 1788: Targeting ornithine decarboxylase down-regulates multiple pathways involved in precancerous lesion formation of esophageal squamous cell cancer
Authors: Yifei Xie, Qiong Wu, Jimin Zhao, Kangdong Liu
Journal: Cancer Research (2019)

Abstract Precancerous lesion of esophageal squamous cell cancer (ESCC) owns the characteristic of bidirectional instability, which can develop to cancer or reverse to normal epithelium by appropriate interference. Therefore, the feature of precancerous lesion provides possibility for ESCC chemoprevention. In the current study, we found that ornithine decarboxylase (ODC) protein level is higher in esophageal precancerous lesions compared with normal esophageal epithelium. Knocking down ODC suppresses cell proliferation and clone formation of ESCC. Moreover, difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, decreases N-nitrosomethylbenzylamine (NMBA)-induced rats’ esophageal precancerous lesions. Further molecular study indicated that ODC down-regulates p38, ERK in the MAP kinase pathway and AKT/mTOR/p70S6K pathway, which are involved in the carcinogenesis process. Overall, our results indicate that ODC may be a potential target for ESCC chemoprevention. Citation Format: Yifei Xie, Qiong Wu, Jimin Zhao, Kangdong Liu. Targeting ornithine decarboxylase down-regulates multiple pathways involved in precancerous lesion formation of esophageal squamous cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1788.
Enasidenib Monotherapy Is Effective and Well-Tolerated in Patients with Previously Untreated Mutant- <i>IDH2</i> (m <i>IDH2</i>) Acute Myeloid Leukemia (AML)
Authors: Daniel A. Pollyea, Martin S. Tallman, Stephane De Botton, Courtney D. DiNardo, Hagop M. Kantarjian, Robert H. Collins, Anthony S. Stein, Qiang Xu, Alessandra Tosolini, Ira Gupta, Samuel V. Agresta, Eytan M. Stein
Journal: Blood (2017)
Abstract 2157: Eliminating Edge Effect in 96-Well Plates by Controlling Thermal Conditions during Cell Plating
Authors: Shannon Darou, Alicia Henn, Kersti Alm, Allayna M. Frank, Randy Yerden
Journal: Cancer Research (2019)

Abstract The traditional approach to avoiding the increased variability in 96-well plate edge wells has been to avoid using them. This results in a 37% loss in usable assay space, increasing time and materials needed for cell-based assays. Approaches to reducing this “edge effect” have included reducing plate evaporation during long-term incubation. However, we have preliminary data that plating cells at a constant 37 degrees C dramatically reduces edge effect. We have previously showed that in plates filled at room temp (RT), the cells in edge and corner wells experienced the most directional cell rolling during cell settling, preventing random cell deposition. In contrast, cells plated at 37 degrees C settled randomly in edge wells with less or no directional rolling. Here, we extend these findings with studies of well-specific cell settling patterns associated with plate-wide thermal changes after cell plating. Our null hypothesis was that intra-well thermal currents as plates warm to 37 degrees C from RT do not disrupt random cell deposition during settling. A549 human lung carcinoma cells were plated in warmed medium in either traditional uncontrolled RT conditions or in an Xvivo System under completely controllable conditions. In this closed chamber, everything (chamber floor, atmosphere, the pipettor, tips, fluids, gloves, and plate) was at the same temp as the incubator, where cells typically settle in the wells after plating. We used the PHI HoloMonitor M4 microscope to record holographic time-lapse images of cells settling and adhering to the well floor. Crystal violet staining was used to assess cell deposition patterns. We found that not only did constant temp conditions change well-specific cell settling patterns, but when plate-wide thermal changes were inverted, by plating cells at 37 degrees C and letting them settle at RT, we were able to alter well-specific cell rolling and cell settling patterns. We concluded that it is thermal changes that drive edge well variability and that constant temperature control during cell plating can reduce or eliminate edge effect. Plating cells under full-time control of conditions could have a tremendous impact on cell-based drug discovery and pre-clinical testing by allowing full use of 96-well plates. This could reduce assay time and materials as well as improve assay reproducibility. Citation Format: Shannon Darou, Alicia Henn, Kersti Alm, Allayna M. Frank, Randy Yerden. Eliminating Edge Effect in 96-Well Plates by Controlling Thermal Conditions during Cell Plating [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2157.