tbuckley/cabot-search huggingface dataset:
Missense mutations in desmin associated with familial cardiac and skeletal myopathy
Authors: Lev G. Goldfarb, Kye-Yoon Park, Larisa Cervenáková, Svetlana Gorokhova, Hee-Suk Lee, Olavo Vasconcelos, James W. Nagle, Christina Semino-Mora, Kumaraswamy Sivakumar, Marinos C. Dalakas
Journal: Nature Genetics (1998)
Abstract 3967: BET protein inhibitor OTX015 has selective anti-tumoral activity in preclinical models of MYCN- amplified neuroblastoma
Authors: Johannes H. Schulte, Kristina Althoff, Emma Bell, Andrea Odersky, Anneleen Beckers, Frank Speleman, Simon Schäfers, Alexander Schramm, Angelika Eggert, Frank Westermann, Eugenia Riveiro, Esteban Cvitkovic, Anton Henssen
Journal: Cancer Research (2014)

Abstract Neuroblastomas harboring MYCN amplifications are highly lethal tumors. They are often resistant to standard chemotherapy, yet the development of targeted therapies has been hampered by a lack of compounds targeting MYCN. We and others have recently discovered that targeting BET bromodomain proteins, especially BRD4, disrupts epigenetic regulation of MYCN and its targets in neuroblastoma. OTX015, a new BET protein inhibitor, is the first lead into clinical phase I/II trials and has shown promising pharmacological properties in adults. Here, we investigate the preclinical efficacy of OTX015 in MYCN-amplified neuroblastoma. We tested in vitro OTX015 efficacy in 6 established neuroblastoma (NB) cell lines. We performed cell cycle profiling and analyzed markers for apoptosis and proliferation after 72h-treatment at 500 nM OTX015. The effect of OTX015 on MYCN expression and global MYCN-associated transcriptional activity was assessed by quantitative real time PCR and gene expression microarray profiling, respectively. In vivo efficacy of orally OTX015 was assessed in IMR5 xenografts, a N-MYC driven NB model, using diffent treatment schedules (50mg/kg/day, 100mg/kg/day and 50mg/kg/bidaily). Treatment of MYCN-amplified neuroblastoma cells with OTX015 resulted in decreased cell viability, induction of apoptosis and reduced proliferation. Concentrations of 50% inhibition (IC50) ranged between 50nM and 500nM. OTX015 treatment also resulted in an increase in the percentage of cells in G1 phase. This corresponded with the downregulation of MYCN mRNA and protein levels and MYCN-associated transcriptional activity. Interestigly, MYCN amplified cell lines were most sensitive to OTX015 treatment. In contrast, no effect was observed with OTX15 on normal cells. In vivo treatment with OTX015, significantly decreased tumor burden after 4 weeks and prolonged survival as compared to vehicle-treated mice. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYCN-driven neuroblastomas and serve as rationale to move forward with early phase clinical trials for children with these highly lethal tumors. Citation Format: Johannes H. Schulte, Kristina Althoff, Emma Bell, Andrea Odersky, Anneleen Beckers, Frank Speleman, Simon Schäfers, Alexander Schramm, Angelika Eggert, Frank Westermann, Eugenia Riveiro, Esteban Cvitkovic, Anton Henssen. BET protein inhibitor OTX015 has selective anti-tumoral activity in preclinical models of MYCN- amplified neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3967. doi:10.1158/1538-7445.AM2014-3967
Abstract 14804: Transplantation of Human Umbilical Cord Blood Mononuclear Cells Improves LV function and Remodeling After a reperfused Myocardial Infarction
Authors: Kashyap Choksi, Guangming Cheng, Arash Davani, Anweshan Samanta, Magdy Girgis, Amy Cantilena, Robert Vincent, Yanjuan Yang, Harold K Elias, Carl Weiner, Buddhadeb Dawn
Journal: Circulation (2014)

Introduction: Human umbilical cord blood cells (hUCBC) contain numerous stem/progenitor cells, which may help repair damaged hearts after acute myocardial infarction (MI). Previous studies of hUCBC injection were performed in models of permanent occlusion of coronary artery mostly using immunocompromised animals. These experimental conditions have less relevance for cell therapy in humans.

Hypothesis: We hypothesized that hUCBC injection would improve left ventricular (LV) structure and function in rats after a reperfused MI.

Methods: The mononuclear fraction was isolated from human cord blood collected after a term delivery. Age-matched normal (without immunosuppression) male Fischer 344 rats underwent a 30-min occlusion of LAD coronary artery followed by reperfusion, and 48 h later received intramyocardial injection of vehicle (PBS) or 1.2x106 hUCBC mononuclear cells. Echocardiography was performed 4 d prior to coronary occlusion/reperfusion (BSL) and at 48 h and 35 d after cell injection. Detailed assessment of cardiac structure and function was performed. Rats were sacrificed at 35 d.

Results: At 48 h, LVEF in both groups was significantly reduced compared with baseline (Figure). At 35 d after cell injection, rats injected with hUCBCs exhibited significantly higher EF compared with PBS-injected rats (Figure). hUCBC-injected hearts also showed significantly smaller increase in LV end-diastolic and end-systolic diameters after 35 d, indicating improved remodeling compared with PBS-injected hearts.

Conclusions: Transplantation of hUCBCs after a reperfused MI in non-immunosuppressed rats attenuates LV dysfunction and improves LV remodeling. These findings support potential therapeutic use of hUCBC transplantation to improve myocardial function and remodeling in humans after a reperfused MI, a common clinical scenario.

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Abstract 4398: MicroRNA-203 enhances radiosensitivity of human malignant glioma cells
Authors: Yeohyeon Hwang, David J. Lee, Eun Jung Choi, Bong Jun Cho, In-Ah Kim
Journal: Cancer Research (2014)

Abstract Glioblastoma multiform (GBM) is the most common, lethal and aggressive type of primary brain tumor. Despite the improvement of surgical and chemo/radiotherapeutic techniques, the prognosis for GBM is still poor, with median survival of 9-12 months. The occurrence of radio-resistance is one of the major obstacles to treat the GBM. Aberrant expression of miRNAs has been demonstrated to be involved in the initiation, progression, and metastasis of cancers. miRNA expression profiling studies revealed that a number of miRNA were dysregulated in GBM. Here, we investigated the potential role of miR-203, which is one of the downregulated miRNAs, in the modulation of radio-sensitivity in GBM. Transiently overexpressed miR-203 sensitized U251 malignant glioma cells to radiation concurrent with the downregulation of AKT activity. Overexpression of miR-203 prolonged radiation-induced γH2AX foci formation and downregulation of DNA-dependent protein kinases, suppressed invasion, migration potential and vasculogenic mimicry formation. In contrast, antisense-mediated inhibition of miR-203 expression results in decreased radio-sensitivity and features of Epithelial-Mesenchymal Transition (EMT). Taken together, our findings suggest that the miR-203 could be a useful target for overcoming the radio-resistance of GBM. Citation Format: Yeohyeon Hwang, David J. Lee, Eun Jung Choi, Bong Jun Cho, In-Ah Kim. MicroRNA-203 enhances radiosensitivity of human malignant glioma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4398. doi:10.1158/1538-7445.AM2014-4398
New Oral Contraceptive
Authors: Bernard A. Schwetz
Journal: JAMA (2001)

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
Meta-Analysis of the Effectiveness of Atypical Antipsychotics for the Treatment of Behavioural Problems in Persons with Dementia
Authors: Craig A. Yury, Jane E. Fisher
Journal: Psychotherapy and Psychosomatics (2007)

To review published reports of the usage of atypical antipsychotics for behavioural problems of dementia patients.The electronic database Medline was searched from 1999 to 2006 with a combination of search terms including 'behavioural problems' and 'atypical antipsychotics'.Thirteen eligible studies were included in the overall analysis. The total number of participants was 1,683, of whom 1,015 received medication and 668 received placebo. Medications studied were risperidone, olanzapine, and quetiapine. Other studies examined other types of medications, such as typical versus atypical antipsychotics, but only data for atypical antipsychotics were included in the meta-analysis. The mean effect size for 7 placebo-controlled studies was 0.45 (95% CI = 0.16-0.74) for atypical antipsychotics, and 0.32 (95% CI = 0.10-0.53) for placebo. The mean effect size of all 13 studies included in the analysis was 0.31 (95% CI = 0.08-0.54).In general, effect sizes of atypical antipsychotics for behavioural problems are medium, and there are no statistically or clinically significant differences between atypical antipsychotics and placebo.
Abstract 12223: ICD Defibrillation Threshold Testing in Patients With Hypertrophic Cardiomyopathy Should Not be Abandoned
Authors: Kartik R Kumar, Swati N Mandleywala, Jonathan Weinstock, Martin S Maron, Ethan J Rowin, Mark S Link
Journal: Circulation (2014)

Introduction: Defibrillation threshold testing (DFT) in patients undergoing ICD implantation has been routine, until recent data argue against such testing. In addition, a clear trend towards implantation of single coil ICD leads has been advocated because of less risk with extraction compared to dual coil leads. While these trends in patients with ischemic and non-ischemic dilated cardiomyopathy may have merit, whether they can be expanded to patients with hypertrophic cardiomyopathy is not clear. Hypothesis: Hypertrophic cardiomyopathy patients undergoing ICD implantation should undergo DFT’s to ensure adequate defibrillation thresholds. Methods: All patients with a diagnosis of hypertrophic cardiomyopathy who were implanted with an ICD at Tufts Medical Center were examined retrospectively from the year 2000 to 2014. Patient notes as well as medical records were examined for ICD parameters, including DFT’s and ICD system adjustments. A true DFT was defined as DFT testing until failure to defibrillate wa...
78. Enhancement of Retroviral-Mediated Gene Transfer by Purification of Virus Stocks from Inhibitors of Transduction
Authors: Christine R. Rowley, Patrick L. Sinn, Linda Bullinga, Paul B. McCray, Beverly L. Davidson
Journal: Molecular Therapy (2004)

Standard lentiviral production involves transient transfection of viral component expression plasmids into 293T cells followed by centrifugation of the collected supernatants. The end result is a mixture of concentrated viral particles, cellular debris, and serum proteins. In an effort to purify the functional vector particles from the unwanted and immunogenic proteins, multiple protocols have been proposed. Typically, these protocols are expensive, time consuming, and result in significant drops in viral titer. Recently, we have begun to compare standard DEAE cellulose anion exchange columns with the Pall Mustang Q purification strong anion exchange syringe filters to purify lentivirus. Our results using silver stained polyacrylamide gels suggest that both systems decrease total protein in the concentrate. However, the Mustang Q filter has multiple advantages. 1) Filtering time was reduced from 3 hours to 0.5 hours; 2) total protein was reduced to a significantly greater extent; 3) bovine serum albumin (a highly immunogenic protein) was reduced to nearly undetectable levels; and 4) these is no need for specialized equipment. The drop in total protein with the Mustang Q filter was accompanied by drop in titer from ~10e9 to ~10e8 TU/ml of VSV-G pseudotyped FIV, which is still suitable for in vivo applications. Studies to determine the in vivo immunogenicity and inflammatory response to purified versus unpurified vectors are ongoing. This filter approach provides a simple, quick method to purify lentiviral vector preparations.
Evaluation of Antitumor Activity of Bordetella pertussis in Two Murine Tumor Models2
Authors: Dallas M. Purnell, John W. Kreider, Gerald L. Bartlett
Journal: JNCI Journal of the National Cancer Institute (1975)

The antitumor activity of three preparations of killed Bordetella pertussis (Bp) (Eli Lilly crude and fluid pertussis vaccines and Parke-Davis pertussis vaccine) was studied in the B16 melanoma and CaD2 mammary adenocarcinoma models. In these tumor systems; Bp had weak and variable tumor inhibitory activity and did not augment tumor rejection immunity. The intratumor injection of Bp did not affect the growth of the B16 tumor but significantly inhibited the growth of the CaD2 tumor. However, the established tumor did not regress. Admixture of Bp with B16 cells before inoculation inhibited tumor growth and prolonged survival of inoculated mice. Admixture of Bp with CaD2 cells completely suppressed tumor cell growth in 60% of inoculated mice. Intratumor injection of CaD2 with Bp combined with surgery provided no protection against subsequent development of metastases.
36. Permanent Phenotypic Correction of Haemophilia B in Immunocompetent Mice by Prenatal Gene Therapy
Authors: Andrew Gomez Vargas, Gonzalo Hortelano
Journal: Molecular Therapy (2004)

Protein replacement treatments often trigger unwanted immune responses in the host. Induction of immune tolerance would be a desirable goal to mitigate such events, and would eliminate the need for life-long immunosuppressive therapy in affected individuals. Hemophilia B is an X-linked bleeding disorder caused by blood coagulation factor IX (FIX) deficiency. Some hemophiliacs develop neutralizing antibodies to FIX (inhibitors) that render the infused FIX ineffective. In this study we evaluated whether oral delivery of hFIX-DNA nanoparticles can downregulate the immune response against hFIX in immunized mice. A group of C57BL/6 mice was immunized with recombinant hFIX in Freund's adjuvant followed by three boost at day 7, 14, and 21. As expected, all mice developed high titer of anti-hFIX antibodies as measured by day 28. At this time, half the mice were treated with a single oral dose of plasmid DNA nanoparticles containing hFIX cDNA under the control of the b -actin promoter. The other half was left untreated, and served as control. By ELISA, we detected circulating levels of hFIX in the treated mice by day 3 after the oral treatment. In contrast, control mice had undetectable levels of circulating hFIX. Importantly, the titer of inhibitors against hFIX was measured by a Bethesda assay. Control mice had inhibitors, on average, of 40 BU/ml on day 21 after the oral administration of DNA. In contrast, the level of inhibitors became undetectable in the treated group by day 21. The cellular immune response was also assessed. Stimulation of splenocytes from orally treated mice with hFIX resulted in increased secretion of transforming growth factor-b, but no detectable interferon-g production. In contrast, stimulation of splenocytes from immunized control mice with hFIX showed an increase in the production of interferon-g, and no secretion of transforming growth factor-b. Additionally, a hFIX-specific cytotoxic T-lymphocyte (CTL) response was detected in the control, but not in the orally treated mice. Thus, our results suggest that the oral delivery of DNA nanoparticles downregulated the pre-existing immune responses against human FIX. This downregulation may result from the induction of a shift from a proinflammatory T helper cell type 1 to an anti-inflammatory T helper cell type 2 immune response. In conclusion, we have shown that pre-existing immune responses against hFIX can be overcome. This strategy may facilitate the delivery of proteins in a pre-sensitized host. Similar approaches may have potential applications for the induction of immune tolerance in autoimmune diseases. This strategy may also have implications for the prevention of unwanted immune responses elicited by the expression of novel transgenes.
Readiness of Local Public Health Agencies to Respond to Bioterrorism Questioned
Authors: Mike Mitka
Journal: JAMA (2005)

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
Abstract P4-04-05: Contributions of STAT3 to pro-tumorigenic alterations within the microenvironment during mammary tumorigenesis
Authors: Pavlina Chuntova, Laura R Bohrer, Kaylee Schwertfeger
Journal: Cancer Research (2015)

Abstract Interactions between tumor cells and their surrounding microenvironment are critical for the development and progression of breast cancer. Specifically, oncogenic alterations such as aberrant activation of growth factor receptors in epithelial cells lead to a pro-tumorigenic inflammatory response characterized by increased production of inflammatory factors and increased macrophage infiltration. Our studies focus on identifying novel mechanisms through which tumor-derived cytokines act in an autocrine manner to regulate tumor cells and in a paracrine manner to regulate infiltrating inflammatory cells. In recent studies, we have shown that following activation of the fibroblast growth factor receptor 1 (FGFR1) oncogene, mammary epithelial cells produce high levels of interleukin 6 (IL-6) family members. These cytokines activate signal transducer and activator of transcription 3 (STAT3) in both epithelial cells and macrophages. STAT3 is constitutively activated in up to 70% of primary breast tumors, and has been shown to enhance proliferation and angiogenesis as well as aid in immune suppression. Using a novel mouse model of FGFR1-driven tumor growth, we demonstrated that inhibition of STAT3 led to decreased tumor growth. Histological examination revealed high levels of STAT3 activation in both tumor cells and macrophages. Thus, further studies focused on identifying mechanisms through which STAT3 activation in different cellular compartments contributes to mammary tumor growth. Initial studies focused on the consequences of STAT3 activation in epithelial/tumor cells. We found that epithelial cell STAT3 activation resulted in accumulation of the extracellular matrix component hyaluronan, which contributed to epithelial cell proliferation, survival and migration. Meanwhile, STAT3 activation in macrophages led to expression changes within a variety of molecules which are known to enhance tumor cell survival, tumor invasion and regulation of the anti-tumor immune response. Thus, it becomes evident that systemic inhibition of STAT3 function can potentially inhibit tumor growth and progression by acting on both tumor cells and on the surrounding stroma. As STAT3 is being considered as a viable target for breast cancer therapy, understanding the mechanisms through which STAT3 promotes tumor growth and progression will be critical for developing optimal therapeutic strategies. Citation Format: Pavlina Chuntova, Laura R Bohrer, Kaylee Schwertfeger. Contributions of STAT3 to pro-tumorigenic alterations within the microenvironment during mammary tumorigenesis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-05.