tbuckley/cabot-search huggingface dataset:
Abstract LB-042: MCPIP1 suppresses breast tumor progression by targeting anti-apoptosis pathway
Authors: Jianguo Liu, Wenbao Lu, Huan Ning, Hui Peng, Qinghong Wang, Rong Hou
Journal: Cancer Research (2015)

Abstract The ability to evade apoptosis is a hallmark of cancer and also plays a significant role in cancer resistance to conventional therapy. While recent progress has broadened our understanding of the apoptosis-evasion mechanisms by cancer cells, how apoptosis resistance develops in cancer cells through posttranscriptional mechanisms, especially by the newly discovered RNA-binding protein monocyte chemotactic protein induced protein 1 (MCPIP1), remains unknown. Here, we report that MCPIP1 expression is impaired in breast tumors and breast tumor cell lines, with the severest impairment in highly metastatic tumors. Ectopic expression of MCPIP1 causes apoptosis of breast tumor cells through selectively suppression of anti-apoptotic gene transcripts, including Bcl2L1, Bcl2A1, RelB, Birc3 and Bcl3. This suppression is medicated through a physical interaction between the PIN domain of MCPIP1 and the 3′UTRs of anti-apoptotic transcripts, resulting in mRNA degradation and tumor cell apoptosis. In difference from the RNA-binding protein tristetraprolin which binds to the ARE in the 3′UTR of target genes for mRNA decay, MCPIP1 specially recognizes a stem-loop structure in the 3′UTR of anti-apoptotic genes for binding and mRNA decay. Furthermore, induction of MCPIP not only ameliorates breast tumor formation but also completely shrinks the established tumors within six days. Lung metastasis is also significantly reduced by MCPIP1 induction. The tumor suppressive effect of MCPIP1 acts through activation of apoptosis. Importantly, by analysis of the excised breast tumors of 251 patients, we found that low MCPIP1 levels in tumors are strongly associated with poor survival of patients over 13 years of follow up. Taken together, we demonstrate that MCPIP1 is a novel potent tumor suppressor which induces tumor apoptosis through tipping the balance between pro-apoptotic and anti-apoptotic genes via selectively targeting the mRNAs of anti-apoptotic genes for degradation. MCPIP1 can serve as a new therapeutic target for treatment of breast cancer and other cancers as well. Citation Format: Jianguo Liu, Wenbao Lu, Huan Ning, Hui Peng, Qinghong Wang, Rong Hou. MCPIP1 suppresses breast tumor progression by targeting anti-apoptosis pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-042. doi:10.1158/1538-7445.AM2015-LB-042
Association Between a Pro-Inflammatory Axis Comprised By TSP1-TGFβ-CTGF with Three microRNAs, Mir-19a, miR122 and Mir-133a in the Pathophysiology of Diabetic Retinopathy: A Therapeutic Novel Modality
Authors: Raul A Dela Cadena, Melissa Lester, Fabiola Del Carpio-Cano, Alina Shevchenko, John St. Angelo, Jeffery Boakye, Leonardo Deutsch, Philippe Alvarez de la Cadena, William Foster
Journal: Blood (2014)
Reducing Sodium Intake in the Population—Reply
Authors: Thomas R. Frieden
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abstract POSTER-THER-1428: Effects of atypical PKC inhibitors on ovarian cancer proliferation and RNA levels
Authors: Minjel Shah, Christopher Apostolatos, Hercules Apostolatos, Mildred Acevedo-Duncan
Journal: Clinical Cancer Research (2015)

Abstract Ovarian cancers are highly lethal tumors which account for approximately four percent of all women’s cancers and are the fifth leading cause of cancer-related death among women. At diagnosis the majority of patients have metastatic disease and the long-term survival remains low. Certain ovarian cancers are highly lethal tumors due to the emergence of therapy-resistant ovarian cancer cells. Protein kinase C-iota (PKC-ι) has been shown to aid in the ability of cancer cells to resist drug-induced apoptosis. Recently, it has been reported that PKC-ι which is located in chromosome 3 at 3q26.2 is the most common genomic amplicon as identified by comparative genomic hybridization [Proc Natl Acad Sci U S A 102:12519–12524(2005)]. Additionally, an increase in PKC-ι DNA copy number was associated with decreased progression-free survival of ovarian cancer patients. Moreover, only PKC-ι gene amplification is highly correlated with protein overexpression, tumor size, lymph node metastasis and clinical stage out of four genes studied on the 3q26 amplification [Genes Chromosomes Cancer 47:127-136(2008)]. The focus of this research was to determine the in-vitro efficacy of the pan-atypical PKC inhibitor, 2-acetyl-1,3-cyclopentanedione (ACPD; Diabetes. 2014 Apr 4) and the novel PKC-iota inhibitor, ICA-1, (1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy) methyl]cyclopentyl]-,[1R-(1α, 2β, 3 β, 4 α) [The Inter. J. Biochem. &amp; Cell Biol. 43:784-794(2011)] on HEY ovarian cancer cell proliferation and RNA concentration. In contrast to ACPD which inhibits both PKC-ι and PKC-zeta (PKC-ζ), ICA-1 specifically inhibits the activity of PKC-ι but not (PKC-ζ). The effects of ACPD and ICA-1on HEY proliferation was quantified by Trypan blue exclusion assay. RNA was isolated from treated and untreated cells using the Rneasy Mini Kit and protocol. Total RNA concentration was estimated using the NanoDrop1000 Spectrophotometer. Results showed that incubation of HEY ovarian cancer cells with ICA-1(1 μm) decreased proliferation by 41% compared to controls at 72 hours post-treatment. ICA-1(2 μM) reduced RNA levels by 17% at 72 hours post-treatment compared to controls. In contrast, ACPD (2 μM) inhibited proliferation by 82% compared to controls and RNA levels were reduced by 97% at 24 hours post-treatment. These results suggest the potential of ICA-1 and ACPD as chemotherapeutic agents. Citation Format: Minjel Shah, Christopher Apostolatos, Hercules Apostolatos, Mildred Acevedo-Duncan. Effects of atypical PKC inhibitors on ovarian cancer proliferation and RNA levels [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1428.
Large Scale Ex Vivo GMP Expanded, Activated Human T Cells Consistently Induce Lethal GvHD in a Mouse Xenotransplant Model - A New Way To Study Treatments for Acute GvHD.
Authors: Gerhard Bauer, Jon Walker, Bruno Nervi, Julie Ritchey, Jackie Hughes, Bill Eades, Mark Bonyhadi, Jan Nolta, John F. DiPersio
Journal: Blood (2005)
Efficacy and Safety of Esomeprazole in the Prevention of Recurrent Peptic Ulcer in Patients Receiving Low-Dose Acetyl Salicylic Acid for Cardiovascular Protection: A Meta-analysis of Multicenter Double-Blind Randomised Controlled Trial
Authors: Ervan Zuhri, Reza Abidin
Journal: Clinical Gastroenterology and Hepatology (2016)
Sub-Saharan Mortality Hotspots for Children Younger Than 5 Years
Authors: MJ Friedrich
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Abstract 5251: TaqMan® rare mutation assays for QuantStudio® 3D digital PCR system
Authors: Marion Laig, Brian Ho, Nivedita S. Majumdar, Le T. Lac, Frances Chan, Ramesh Sathiyaa, Iain Russel, Paco Cifuentes, Ted Straub, Kamini Varma, David Keys
Journal: Cancer Research (2015)

Abstract Detection and quantification of mutant alleles in tumor tissue allow for research disease monitoring and the research of drug efficacy. Detection of emerging secondary mutations in the same tumor tissue causing resistance to potential treatment will help guide decisions on future treatment plans. A less invasive research method than using tumor tissue is testing for the presence of mutations in circulating free DNA (cfDNA). We created a research tool for mutation detection at a sensitivity level of 1% and below. This allows researchers to find correlation between types of mutations and types of tumors and determination of potential secondary mutations. The tool combines TaqMan® SNP Genotyping Assays with digital PCR. A set of assays was optimized for use in digital PCR with the QuantStudio® 3D Digital PCR System. In digital PCR, partitioning the sample into many individual reaction wells facilitates detection and quantification of rare mutant alleles. TaqMan® SNP Genotyping Assays ensure reliable discrimination of mutant and wild-type allele. Our initial set of 38 assays covers mutations commonly found in tumor tissues: BRAF V600E, mutations in EGFR exons 19, 20 and 21, KRAS codons 12 and 13, PIK3CA exons 9 and 20, and the JAK2 V617F mutations. All assays were wet-lab tested at a 10% mutation rate and a 1% mutation rate using mutant plasmid spiked into wild-type genomic DNA. Additionally, selected assays were tested at the 0.1% mutation rate using mutant cell lines spiked into wild-type genomic DNA. Wet-lab results confirm that all assays showed superior performance discriminating mutant and wild-type alleles. Mutant alleles were successfully detected as low as 0.1%. For Research Use Only. Not for use in diagnostic procedures. Citation Format: Marion Laig, Brian Ho, Nivedita S. Majumdar, Le T. Lac, Frances Chan, Ramesh Sathiyaa, Iain Russel, Paco Cifuentes, Ted Straub, Kamini Varma, David Keys. TaqMan® rare mutation assays for QuantStudio® 3D digital PCR system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5251. doi:10.1158/1538-7445.AM2015-5251
A case of levocetirizine-induced liver injury
Authors: Moon Chan Jung, Ja Kyung Kim, Jae Yeon Cho, Jae Won Song, Bohyun Lee, Ji Won Park, Jinwon Seo, Sung Eun Kim
Journal: Clinical and Molecular Hepatology (2016)

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity. Keywords: Hepatotoxicity; Levocetirizine; Cholestasis
Prospective, Randomized Comparison between Double Transplantation (T) with Melphalan (200 mg/m2) and Triple T with Intermediate Dose Melphalan (100 mg/m2) in Patients with Multiple Myeloma (An Interim Analysis).
Authors: Heinz Ludwig, Werner Linkesch, Hedwig Kasparu, Otto Krieger, Ivan Spicka, Gunther Gastl, Richard Greil, Johannes Drach, Josef Thaler, Ingrid Kuhn, Niklas Zojer, Axel Hinke
Journal: Blood (2006)
The Proteasomal Inhibitor Clioquinol Induces Apoptosis in Leukemia and Myeloma Cells by Inhibiting Histone Deacetylase Activity.
Authors: Biyin Cao, Mingyun Shen, Depei Wu, Jianhong Du, Jingyu Zhu, Suning Chen, Aining Sun, Xiaowen Tang, Zhuan Xu, Yan Kong, Xinliang Mao
Journal: Blood (2012)
Germline Variation in Apoptosis Pathway Genes and Risk of Non-Hodgkin Lymphoma.
Authors: Jennifer L Kelly, Anne J Novak, Zachary S Fredericksen, Mark Liebow, Stephen M Ansell, Ahmet Dogan, Alice H. Wang, Thomas E Witzig, Timothy G Call, Neil E. Kay, Thomas M Habermann, Susan L Slager, James R Cerhan
Journal: Blood (2009)
Review: Revascularization and medical treatment may be similar in atherosclerotic renal artery stenosis
Authors: Vlado Perkovic
Journal: Annals of Internal Medicine (2016)

Source Citation Raman G, Adam GP, Halladay CW, et al. Comparative effectiveness of management strategies for renal artery stenosis: an updated systematic review. Ann Intern Med. 2016;165:635-49. 27536808
Differential Antigenic Profile of High Molecular Weight-Melanoma Associated Antigen (HMW-MAA) Expressed by 11q23-Positive Acute Leukemia: An Immunotherapeutic Target.
Authors: Meir Wetzler, M. T. Brady, S. N.J. Siat, S. Kakati, A. W. Block, X. Wang, S. P. Hunger, A. J. Carroll, S. Ferrone
Journal: Blood (2005)
68Ga-DOTA Ubiquicidin PET/CT in an Infected Implant
Authors: Arun Sasikumar, Ajith Joy, Raviteja Nanabala, M.R.A. Pillai, Hari T.A.
Journal: Clinical Nuclear Medicine (2016)

We describe the case of a 55-year-old man who presented with history of fever for 3 months that began 2 months after he had undergone open reduction and internal fixation of left humerus fracture. Implant infection was suspected, but conventional imaging remained unyielding. Ga-DOTA ubiquicidin PET/CT showed increased tracer uptake along the entire length of the implant in the left humerus. Implant removal and temporary external fixation were done. In 24 hours, the patient became afebrile, and blood culture on the fourth day was sterile.
Inhibition of Immune Thrombocytopenic Purpura (ITP) by an Orally Bioavailable Inhibitor of Syk Kinase Activity.
Authors: Andrew R. Crow, Vinayakumar Siragam, John Freedman, Elliott B. Grossbard, Esteban S. Masuda, Polly Pine, Alan H. Lazarus
Journal: Blood (2005)
200. Advancing a State of the Art Gene Therapy for Parkinson's Disease
Authors: Romina Aron Badin, Katie Binley, Nadja Van Camp, Caroline Jan, Jean Gourlay, Hannah Stewart, Scott Ralph, Yatish Lad, Michelle Kelleher, Julie Loader, Koichi Hosomi, Stephane Palfi, Phillippe Hantraye, Kyriacos Mitrophanous
Journal: Molecular Therapy (2015)

The primary standard of care for Parkinson's disease (PD) is oral dopaminergic treatments and although these are initially highly efficacious, over time they lead to debilitating long term side effects that seriously impact on the quality of life and restrict the long-term effectiveness of such treatments. OXB-102 is a lentiviral-based vector that delivers the genes encoding the three key enzymes in the dopamine (DA) biosynthetic pathway, tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), and GTP-cyclohydrolase (CH1), to nondopaminergic striatal neurons of the sensorimotor putamen, thus providing these cells with the ability to synthesise and release their own DA. The effectiveness of this strategy has already been demonstrated in rodents, non-human primates and Parkinson's (PD) patients (Palfi et. al, Lancet 2014) with a precursor gene therapy vector called ProSavin®. OXB-102 is an improved version of ProSavin® that expresses the same enzymes but with an increased DA production per genetically modified cell. In non-clinical studies the efficacy of a full-strength and a 1/5th dose of OXB-102 has been compared to the efficacy of full-strength ProSavin® in the 'gold standard' MPTP NHP model of PD; a vector that does not express any genes was used as a negative control. The longitudinal follow-up consisted of recording clinical rating scores and video-based quantification of locomotor activity before and after vector administration. The full-strength and the 1/5th dose of OXB-102 were as efficacious as the full-strength dose of ProSavin®, whereas the control-treated macaques maintained a significant PD phenotype, indicating improved dopamine production from OXB-102. Positron emission tomography (PET) was also carried out at baseline and at 3 and 6 months following vector administration using 18F-FMT, a presynaptic biomarker that acts as a substrate of AADC. There was a significant increase in the FMT signal in both of the OXB-102 treatment groups that was greater than in the ProSavin® treated animals whilst there was no significant change in the FMT signal in the control treatment group. Results from a 6-month toxicology and biodistribution study in the NHP indicate that the OXB-102 vector is safe and well tolerated following stereotactic administration into the putamen and the vector does not significantly spread beyond the site of administration GMP manufacture of OXB-102 for a planned clinical trial in PD patients is currently in progress.
125. Purging Latent HIV Infection by CRISPR-Mediated Viral Reactivation
Authors: Prajit Limsirichai, Thomas Gaj, David V. Schaffer
Journal: Molecular Therapy (2016)

Complete eradication of HIV-1 infection is impeded by the existence of cells that harbor chromosomally integrated but transcriptionally inactive provirus. These latently-infected cells can persist for years without producing viral progeny, rendering them refractory to immune surveillance and antiretroviral therapy and providing a permanent reservoir for the stochastic reactivation and reseeding of HIV-1. Strategies for purging this latent reservoir are thus needed to eradicate infection. Here we show that engineered transcriptional activation systems based on CRISPR/Cas9 can be harnessed to activate HIV-1 expression in cell line models of latency. We utilized two distinct CRISPR transcriptional activation systems, dCas9-VP64 and the synergistic activation mediator (SAM) complex, to target numerous sites across the HIV-1 long terminal repeat (LTR) promoter and observed robust expression from the full-length HIV-1 promoter in multiple cell line models of HIV-1 latency. We further demonstrated that complementing Cas9 activators with latency-reversing compounds can enhance latent HIV-1 transcription and that epigenome modulation using CRISPR-based acetyltransferases could also promote viral gene activation. Finally, we showed that latent HIV-1 expression could also be stimulated by CRISPR-mediated activation of endogenous factors not previously implicated in HIV-1 pathogenesis but whose expression could nonetheless reactivate viral gene expression. Collectively, these results demonstrate that CRISPR systems are potentially effective tools for inducing latent HIV-1 expression and that their use, in combination with antiretroviral therapy, could lead to improved therapies for HIV-1 infection.
521. Platelets Transfusion New Role as Brain Therapeutics for Acute Neuronopathic Gaucher Disease
Authors: Mei Dai, Xiaohong Wang, Benjamin Liou, Venette Inskeep, Gregory Grabowski, Ying Sun, Roscoe Brady, Dao Pan
Journal: Molecular Therapy (2016)

There has no effective treatment for neuronopathic Gaucher Disease (nGD) due to the difficulty of therapeutics to cross the blood-brain-barrier. Platelets are blood elements that contain cytoplasmic secretory vesicles containing proteins involved in hemostasis, inflammation and angiogenesis. We have recently shown that platelets/megakaryocytes could serve as efficient and protective depots for lysosomal enzyme generation and distribution. In this study the potential therapeutic benefits of platelet transfusion in treating neuronopathic GD (nGD) was evaluated using a murine model of acute nGD (4L;C), which resembles types 2 and 3 Gaucher disease. Platelets containing significant amounts of wild type acid ß-glucosidase enzyme (GCase) were isolated from GFP mice and transfused weekly into 4L;C mice for four times beginning at 21 days of age, resulting in an average 10-13% of donor-derived GFP+ platelets in circulation with half-life of 52 hr. Importantly, moderate platelet transfusion led to significantly increase of life-span in 4L;C mice from 47 days to 55 days with reduction of splenomegaly. The accumulation of glycosylsphingosin was significantly reduced in spleen, liver and brain. Moreover, the abnormal walk patterns with splaying of hindlimbs exhibited in 4L;C mice were improved significantly in platelet-treated mice, indicating amelioration of motor neuron dysfunction and hindlimb paresis. The improvement of short-term memory deficit in treated 4L;C mice was evidenced in repeated open-field test. Immunohistochemistry analysis showed that the elevated brain CD68+ signals, a marker for activated microglia cells, were normalized in cerebellum folium and middle brain regions, and partially corrected in the cortex, cerebellum DCN, brainstem, thalamus and spinal cord of treated 4L;C mice, indicating the reduction of pro-inflammation by platelet transfusion. Notably, RIPK3-positive signals within Purkinje neurons in cerebellum of nGD mice were significantly reduced, suggesting therapeutic benefit of platelet transfusion on neuronal necroptosis. This study reveals an under-appreciated, unexpected role for platelets in treating CNS diseases. These results provide proof of concept that platelet transfusion can achieve CNS benefits with brain substrate reduction and improvement in neurological function, as well as reducing pro-inflammation and neuronal necroptosis. The findings will open a door for new clinical approaches with platelet transfusion in treating nGD and potentially other brain diseases.