tbuckley/cabot-search huggingface dataset:
Abstract #1789: Cellular activity of ABT-869 against colony-stimulating-factor-1 receptor (CSF-1R) in macrophage-like cell lines
Authors: jun guo, Yujia Dai, Mai Bui, Zehan Chen, Reuter David, Terry Magoc, Junling Li, Niru Soni, Patrick Marcotte, Eric Johnson, Daniel Albert, Michael Michaelides, Steven Davidsen, Keith Glaser
Journal: Cancer Research (2009)

ABT-869 is a potent inhibitor of the VEGFR and PDGFR families of receptor tyrosine kinases, including c-fms (CSF-1R). Colony-stimulating-factor-1 (CSF-1) signaling through CSF-1R is elevated in several diseases including many types of carcinoma. Most tumors contain an appreciable infiltrate of tumor associated macrophages (TAMs) that are polarized to the M2 phenotype associated with angiogenesis. CSF-1 (M-CSF) is a potent chemoattractant for macrophages and recruits macrophages into tumor tissues where they adopt this tumor promoting phenotype. Ablation of macrophages or neutralization of CSF-1 attenuates tumor growth and increases chemosenstivity of some tumors in vivo. Herein, we evaluated the selectivity of ABT-869 and four other small molecule VEGFR/PDGFR family inhibitors against CSF-1 signaling in various macrophage-like cell lines. ABT-869 potently inhibits the catalytic activity of the CSF-1R kinase in vitro (IC 50  = 5 nM) and more importantly human CSF-1R signaling in transfected NIH 3T3 cells (IC 50  = 24 nM; Guo, J. et al. (2006) Mol. Cancer Ther. 5: 787); however, demonstration of activity against endogenous CSF-1R has not been reported. The murine myeloid cell line M-NSF-60 was chosen as a model system to evaluate the effect of ABT-869 on endogenous CSF-1R signaling as this cell line is dependent on CSF-1 or IL-3 for growth. ABT-869 was found to potently inhibit the CSF-1-dependent growth of M-NFS-60 and RAW 264.7 cells, with IC 50  values of 30 and 50 nM, respectively. In contrast, ABT-869 weakly inhibited the IL-3-dependent growth of M-NFS-60 cells (IC 50  = 4,400 nM) and the CSF-1-independent (10% FBS) growth of RAW 264.7 cells (IC 50  = 8,600 nM), demonstrating selectivity for CSF-1 signaling in these cell lines. The four reference compounds (sorafenib, sunitinib, cediranib and axitinib) demonstrated little or no separation of effects on CSF-1 and IL-3 dependent growth in M-NSF-60 cells. Inhibition of CSF-1R signaling in vivo was demonstrated in a CSF-1 primed model of LPS-induced TNF\#945; release in mice. At doses of 3 to 25 mg/kg, orally, ABT-869 reduced the CSF-1 primed release of TNF\#945; to non-primed levels. These results demonstrate that ABT-869 has potent activity against CSF-1R signaling both in vitro and in vivo, and suggests that ABT-869 may have value in treating cancers where elevated levels of inflammatory TAMs drive tumor progression.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1789.
Non-invasive prenatal testing: public and doctors should be consulted, says BMA
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The BMA has the backing of doctors to lobby the government to undertake a consultation on the views of the public and medical profession on new non-invasive prenatal testing (NIPT) and whether limits should be set on its use.

Disability advocacy groups welcomed the passing of a motion at the BMA’s annual representative meeting in Brighton on 27 June which said that “the time is right” for a consultation on the matter.

The move increases the pressure on the government to undertake a proper consultation and ethical review of NIPT. Last year, an open letter1 signed by …
Abstract 2499: Identification of functional proteins interacting with NSD2 in multiple myeloma
Authors: Jing Yuan Chooi, Zhigang Xie, Hannah Lee-Foon Swa, Jayantha Gunaratne, Dennis Kappei, Wee Joo Chng
Journal: Cancer Research (2018)

Abstract Multiple myeloma (MM), characterized by the uncontrolled proliferation of malignant plasma cells, occurs mainly in the elderly population. Recurrent chromosomal translocations are central to the pathogenesis of MM, with t(4;14) being the second most common and associated with poor prognosis. The histone methyltransferase (HMTase) NSD2 is overexpressed in MM due to the t(4;14) translocation and has been suggested to play an important tumorigenic role in t(4;14) MM. However, the detailed molecular mechanism or signaling pathways describing how deregulation of NDS2 contributes to MM cell growth and survival are still uncertain. In this study, stable isotope labeling of amino acid in cell culture (SILAC)-based mass spectrometry analysis was used to determine NSD2-interacting proteins. Mass spectrometry analysis indicated that there were 75 proteins identified in the immunoprecipitation of NSD2 protein complexes. Gene ontology (GO) enrichment analysis showed that these proteins were enriched in processes related to chromatin organization, RNA processing and translation. Five high potential MMSET-interacting proteins from the most enriched functions were selected and verified by Immunoprecipitation and Western blot assays. The results indicated that there were interactions between NSD2 and SMARCA2, topoisomerase IIa, ADAR1, DDX5 and RPS6. In silico analysis with STRING database showed that SMARCA2 interacts with NSD2. SMARCA2 is the ATPase subunit of the SWI/SNF chromatin remodeling complex, which harnesses the energy from ATP to remodel the position of nucleosomes, making the DNA accessible during transcription, replication and DNA repair. Double immunofluorescence showed NSD2 and SMARCA2 co-localized in the cell nucleus. SMARCA2 was knocked down (KD) by shRNAs in t(4;14) MM cells. CellTiter-Glo Luminescent Cell Viability Assay (CTG assay) indicated that SMARCA2 KD by shRNA reduced t(4;14) MM cell growth. SMARCA2 KD also significantly inhibited the capacity to form colonies in t(4;14) MM cells on methylcellulose colony formation assay. Inhibiting SMARCA2 with active DNA-dependent ATPase A domain inhibitor (ADAADi) also reduced t(4;14) MM cell growth. In addition, SMARCA2 KD reduced cell cycle S phase. Western blot analysis showed downregulation of PRL3 and CCND1 protein level upon NSD2 or SMARCA2 KD. This study reveals a protein-protein interaction between NSD2 and SMARCA2. SMARCA2 KD showed SMARCA2 might be a novel therapeutic target for t(4;14) MM. Citation Format: Jing Yuan Chooi, Zhigang Xie, Hannah Lee-Foon Swa, Jayantha Gunaratne, Dennis Kappei, Wee Joo Chng. Identification of functional proteins interacting with NSD2 in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2499.
Reference equations for the 6-minute walk distance in healthy Portuguese subjects 18–70 years old
Authors: M.J. Oliveira, R. Marçôa, J. Moutinho, P. Oliveira, I. Ladeira, R. Lima, M. Guimarães
Journal: Pulmonology (2018)

Six-minute walk test (6MWT) is used for evaluating functional exercise capacity. To the best of our knowledge, there are no reference equations to predict six-minute walk distance (6MWD) for the Portuguese population. The aims of the present study were to measure anthropometric data and 6MWD in a sample of healthy Portuguese population, to establish reference equations to predict 6MWD and to compare our equations with those obtained by previously published studies. We conducted an observational prospective study. We consecutively recruited 158 healthy 18–70 years old subjects from Porto district, who performed two 6MWTs using a standardized protocol. The best 6MWD was used for further analysis. The mean 6MWD was 627.8 m (SD = 73.3 m). The variables that were significantly associated with the 6MWD were age, sex, BMI and ΔHR (Heart Rateat the end of the test − HRat rest). We found three explanatory models for 6MWD, the best with an explanatory power of 38%: 6MWD = 721.7 − 1.6 × Age − 4.0 × BMI + 0.9 × ΔHR + 58.4 × Sex. We verified that 6MWD decreased 1.6 m per year of age, and 4.0 m per unit of BMI and increased 0.892 m per beat per minute. Moreover, on average, males walk 58.4 m more than females (p < 0.001). Applying equations from other studies to our population resulted in an overestimation or underestimation of the 6MWD. The present study was the first to describe the 6MWD in healthy Portuguese people aged 18–70 years old and to propose predictive equations. These can contribute to improving the evaluation of Caucasian Mediterranean patients with diseases that affect their functional capacity.
Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
Authors: David Adams, Alejandra Gonzalez-Duarte, William D. O’Riordan, Chih-Chao Yang, Mitsuharu Ueda, Arnt V. Kristen, Ivailo Tournev, Hartmut H. Schmidt, Teresa Coelho, John L. Berk, Kon-Ping Lin, Giuseppe Vita, Shahram Attarian, Violaine Planté-Bordeneuve, Michelle M. Mezei, Josep M. Campistol, Juan Buades, Thomas H. Brannagan, Byoung J. Kim, Jeeyoung Oh, Yesim Parman, Yoshiki Sekijima, Philip N. Hawkins, Scott D. Solomon, Michael Polydefkis, Peter J. Dyck, Pritesh J. Gandhi, Sunita Goyal, Jihong Chen, Andrew L. Strahs, Saraswathy V. Nochur, Marianne T. Sweetser, Pushkal P. Garg, Akshay K. Vaishnaw, Jared A. Gollob, Ole B. Suhr
Journal: New England Journal of Medicine (2018)

Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.
Abstract 11474: Pro-Inflammatory Environment and Oxidized LDL Convert “Early” Endothelial Progenitor Cells Into Antigen Presenting Cells With Distinct Gene Expression Profiles
Authors: Maria Cristina Vinci, Luca Piacentini, Gian Luca Polvani, Gualtiero I Colombo, Maurizio Pesce
Journal: Circulation (2013)

Background:  We previously found that exposure to pro-inflammatory environment or oxidized-LDL (oxLDL), an atherogenic autoantigen, converts human peripheral blood-derived “early” endothelial progenitor cells (EPCs) into functional antigen presenting cells (APCs). In the present work we assessed whether exposure to the two distinct environments causes specific changes in gene expression potentially affecting their function as pro-atherogenic cells.   Methods and Results:  EPCs were derived by culturing mononuclear cells of human healthy donors into EGM-2 for 7 days. EPCs were primed for 3 days with GM-CSF and IL4 (10 ng/ml) in 10% FBS containing medium, followed by culture in 10% FBS, IL1β and TNFα (10ng/ml) [APC], or in 1% FBS and oxLDL (80ng/ml) [APCox] containing media. EPCs, APCs and APCox RNA (n=6) was hybridized onto HumanHT-12 v4 microarrays (Illumina). Data were pre-processed (VST and RSN) and genes were filtered-out when the 25th percentile of intensities had a  P -value detection level  P >0.01. The ANOVA F-test identified 2571 genes differentially expressed among groups with a significance level  P  vs.  EPCs, 902 were up- and 952 were down-regulated in oxAPCs  vs.  EPCs, and 590 were up- and 618 were down-regulated in oxAPCs  vs.  APCs. Gene Ontology set expression comparisons (LS/KS permutation test and Efron-Tibshirani’s GSA maxmean test;  P =0.005) were then performed to assess gene set expression changes related to specific functions. Results showed a significant increase in gene sets expression related to innate immunity, cytokine production/response and lymphocyte activation in APCs vs. EPCs (24 gene sets) and oxAPCs  vs.  EPCs (6 gene sets). A reduced immunomodulatory and cholesterol metabolism gene sets expression in oxAPCs vs. APCs (64 gene sets) was observed. Finally, 3 gene sets related to TNFalpha signaling were upregulated in oxAPCs.   Conclusions:  Conversion of human EPCs into APCs is associated to robust modifications in gene expression profile. This establishes the basis for a functional divergence of pro-angiogenic cells primed in an inflammatory  vs.  an atherogenic environment.
Unmet Survivorship Care Needs of Adolescent and Young Adult Cancer Survivors
Authors: Stacey Marjerrison, Ronald D. Barr
Journal: JAMA Network Open (2018)

Mette Vestergaard Jensen, MD; Kathrine Rugbjerg, PhD; Sofie de Fine Licht, PhD; Christoffer Johansen, DMSc; Kjeld Schmiegelow, DMSc; Klaus Kaae Andersen, PhD; Jeanette Falck Winther, DMSc
Moral Dilemmas for Physicians Treating Terminal Patients—Reply
Authors: Bernard E. Trappey
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Authors: Elena Bonazzoli, Federica Predolini, Emiliano Cocco, Stefania Bellone, Gary Altwerger, Gulden Menderes, Luca Zammataro, Anna Bianchi, Francesca Pettinella, Francesco Riccio, Chanhee Han, Ghanshyam Yadav, Salvatore Lopez, Aranzazu Manzano, Paola Manara, Natalia Buza, Pei Hui, Serena Wong, Babak Litkouhi, Elena Ratner, Dan-Arin Silasi, Gloria S. Huang, Masoud Azodi, Peter E. Schwartz, Joseph Schlessinger, Alessandro D. Santin
Journal: Clinical Cancer Research (2018)

Uterine serous carcinoma (USC) is a rare and aggressive variant of endometrial cancer. Whole-exome sequencing (WES) studies have recently reported c-Myc gene amplification in a large number of USCs, suggesting c-Myc as a potential therapeutic target. We investigated the activity of novel BET bromodomain inhibitors (GS-5829 and GS-626510, Gilead Sciences Inc.) and JQ1 against primary USC cultures and USC xenografts.
Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy
Authors: Jinyang Li, Katelyn T. Byrne, Fangxue Yan, Taiji Yamazoe, Zeyu Chen, Timour Baslan, Lee P. Richman, Jeffrey H. Lin, Yu H. Sun, Andrew J. Rech, David Balli, Ceire A. Hay, Yogev Sela, Allyson J. Merrell, Shannon M. Liudahl, Naomi Gordon, Robert J. Norgard, Salina Yuan, Sixiang Yu, Timothy Chao, Shuai Ye, T.S. Karin Eisinger-Mathason, Robert B. Faryabi, John W. Tobias, Scott W. Lowe, Lisa M. Coussens, E. John Wherry, Robert H. Vonderheide, Ben Z. Stanger
Journal: Immunity (2018)
Recommendations on Disease Management for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Clinical Practice Guideline Update
Authors: Naren Ramakrishna, Sarah Temin, Sarat Chandarlapaty, Jennie R. Crews, Nancy E. Davidson, Francisco J. Esteva, Sharon H. Giordano, Jeffrey J. Kirshner, Ian E. Krop, Jennifer Levinson, Shanu Modi, Debra A. Patt, Jane Perlmutter, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2018)

Purpose To update the formal expert consensus-based guideline recommendations for practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. In 2014, the American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts, and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment in a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging to screen for brain metastases, but rather should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. Additional information is available at www.asco.org/breast-cancer-guidelines .
Synthesizing retinal and neuronal images with generative adversarial nets
Authors: He Zhao, Huiqi Li, Sebastian Maurer-Stroh, Li Cheng
Journal: Medical Image Analysis (2018)

This paper aims at synthesizing multiple realistic-looking retinal (or neuronal) images from an unseen tubular structured annotation that contains the binary vessel (or neuronal) morphology. The generated phantoms are expected to preserve the same tubular structure, and resemble the visual appearance of the training images. Inspired by the recent progresses in generative adversarial nets (GANs) as well as image style transfer, our approach enjoys several advantages. It works well with a small training set with as few as 10 training examples, which is a common scenario in medical image analysis. Besides, it is capable of synthesizing diverse images from the same tubular structured annotation. Extensive experimental evaluations on various retinal fundus and neuronal imaging applications demonstrate the merits of the proposed approach.
Effect of Accelerated Infliximab Induction on Short- and Long-term Outcomes of Acute Severe Ulcerative Colitis: A Retrospective Multicenter Study and Meta-analysis
Authors: Niharika Nalagatla, Katherine Falloon, Gloria Tran, Nienke Z. Borren, Danny Avalos, Jay Luther, Francis Colizzo, John Garber, Hamed Khalili, Joanna Melia, Matthew Bohm, Ashwin N. Ananthakrishnan
Journal: Clinical Gastroenterology and Hepatology (2018)
Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma
Authors: Chun Jye Lim, Yun Hua Lee, Lu Pan, Liyun Lai, Camillus Chua, Martin Wasser, Tony Kiat Hon Lim, Joe Yeong, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian KP Goh, Alexander Chung, Mathias Heikenwälder, Irene OL Ng, Pierce Chow, Salvatore Albani, Valerie Chew
Journal: Gut (2018)

Background and aims Chronic inflammation induced by chronic hepatitis B virus (HBV) infection increases the risk of hepatocellular carcinoma (HCC). However, little is known about the immune landscape of HBV-related HCC and its influence on the design of effective cancer immunotherapeutics. Methods We interrogated the immune microenvironments of HBV-related HCC and non-viral-related HCC using immunohistochemistry and cytometry by time-of-flight (CyTOF). On identifying unique immune subsets enriched in HBV-related HCC, we further interrogated their phenotypes and functions using next-generation sequencing (NGS) and in vitro T-cell proliferation assays. Results In-depth interrogation of the immune landscapes showed that regulatory T cells (T REG ) and CD8 + resident memory T cells (T RM ) were enriched in HBV-related HCC, whereas Tim-3 + CD8 + T cells and CD244 + natural killer cells were enriched in non-viral-related HCC. NGS of isolated T REG and T RM from HBV-related HCC and non-viral-related HCC identified distinct functional signatures associated with T-cell receptor signalling, T-cell costimulation, antigen presentation and programmed cell death protein 1 (PD-1) signalling. T REG and T RM from HBV-related HCC expressed more PD-1 and were functionally more suppressive and exhausted than those from non-virus-related HCC. Furthermore, immunosuppression by PD-1 + T REG could be reversed with anti-PD-1 blockade. Using multiplexed tissue immunofluorescence, we further demonstrated that T REG and T RM contributed to overall patient survival: T REG were associated with a poor prognosis and T RM were associated with a good prognosis in HCC. Conclusion We have shown that the HBV-related HCC microenvironment is more immunosuppressive and exhausted than the non-viral-related HCC microenvironment. Such in-depth understanding has important implications in disease management and appropriate application of immunotherapeutics.
Abstract 607: Inhibition of CDK4/6 and Pi3Kγ modulates mammary tumor immune microenvironment to enhance response to immunotherapy
Authors: Stacey Mont, Kevin Black, Sheau-Chiann Chen, Gregory D. Ayers, Ann Richmond, Anna E. Vilgelm
Journal: Cancer Research (2018)

Abstract An antitumor immune response is critical in achieving immunotherapy-driven tumor regression. Despite remarkable clinical advances in immunotherapies, patients with breast cancer have been only moderately responsive. In this study, we tested whether CDK4/6 inhibition in combination with Pi3Kγ inhibition can augment the immunotherapy response. Tumor growth was inhibited in the MMTV-PyMT breast cancer model when treated with palbociclib (CDK4/6i) in combination with anti-CD137, an antibody agonist of T cell co-stimulatory receptor 4-1BB. We also assessed the effect of palbociclib alone in a postsurgical model, where treatment began 5 days after injecting 37,000 MMTV-PyMT cells into the mammary fat pad, and show a significant inhibition of both average tumor weight and volume. In addition, we demonstrate that palbociclib can be effective in reducing total tumor burden in the PyMT-FVB spontaneous breast cancer model. Furthermore, mice treated with palbociclib in this model had an increase in CD3+ cell infiltrate in tumor lung metastasis. We used the Pi3Kγ-null mice treated with palbociclib or vehicle control to assess the effect of dual inhibition of CDK4/6 and Pi3Kγ on MMTV-PyMT tumors. We found an increase in CD45+ cells within the tumor microenvironment and an increase in MHC class II+, antigen-presenting macrophages upon palbociclib treatment. Additionally, gene expression analysis of chemokines in palbociclib-treated MCF-7 cells showed an increased expression of CCL4, CCL5, CXCL9, CXCL10, and CXCL11, each of which is implicated in T-cell tumor-homing. Overall, our results suggest that dual inhibition of CDK4/6 and Pi3Kγ may enhance tumor immunogenicity. Drugs targeting CDK4/6 and Pi3Kγ are of high clinical relevance and our findings indicate that they may be used in combination with immunotherapies for the treatment for breast cancer. Citation Format: Stacey Mont, Kevin Black, Sheau-Chiann Chen, Gregory D. Ayers, Ann Richmond, Anna E. Vilgelm. Inhibition of CDK4/6 and Pi3Kγ modulates mammary tumor immune microenvironment to enhance response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 607.