tbuckley/cabot-search huggingface dataset:
Abstract #536: Analysis of the Notch pathway-specific genes in human cancer cells
Authors: Shuibin Lin, Jian-Liang Li, Baofeng Jin, Lizi Wu
Journal: Cancer Research (2009)

The Notch signaling pathway is an evolutionarily conserved cell signaling mechanism that regulates various developmental processes. Aberrant Notch signaling has been implicated in the pathogenesis of a growing number of hematological and epithelial cancers via its potential roles in deregulated cell growth, differentiation and cell death. Moreover, Notch signaling may promote or suppress tumorigenesis depending on specific cancer types. Comprehensive understandings of the molecular mechanisms underlying diverse Notch-mediated functions in the development and cancer will be crucial for developing new therapeutics that manipulate this pathway. However, downstream genes and pathways known to be regulated by Notch signaling remain very limited and cannot account for Notch-mediated diverse biological activities. To gain insights into how such a highly conserved signaling pathway mediates biological diversity in development and cancer, we took advantage of the ChIP-Seq approach that combine chromatin immunoprecipitation with high-throughput sequencing technology to identify potential Notch target genes that bind to the key Notch transcription factor CSL in cervical cancer cells. Combined with the genome-wide in silico identification and microarray mRNA profiling analysis, our preliminary studies reveal a number of target genes that may contribute to the varied biological activities of Notch signaling in cancer cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 536.
Enzymatically-targeted <sup>131</sup>I therapy for herpesvirus-associated malignancies
Authors: D. Fu, V. Lemas, C. Foss, J. Fox, M. Pomper, R. F. Ambinder
Journal: Journal of Clinical Oncology (2006)

3010 Background: Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) are associated with tumors including AIDS-related lymphoma, Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma and Kaposi’s sarcoma. Both viruses encode kinases that selectively phosphorylate nucleoside analogs such as ganciclovir and FIAU. We hypothesized that it might be possible to use the viral enzymes to specifically concentrate 131 I-FIAU in tumor cells harboring virus and thus deliver therapeutic radiation. Bortezomib is a potent stimulator of viral kinase expression in gammaherpesvirus tumor cell lines. Methods: We evaluated the effect of 131 I-FIAU on human cancer xenografts in SCID mice. These included a tumor line engineered to constitutively express the EBV thymidine kinase (EBVTK), and a control engineered with a sham vector (SHAM), as well 2 EBV(+) Burkitt’s lymphoma (BL) lines, and 1 KSHV(+) primary effusion lymphoma (PEL) cell line. Mice were treated with buffer, bortezomib 2 ug/gm, or I-FIAU, or I-FIAU and bortezomib in combination. For imaging, mice, 125 I -FIAU and SPECT were used. For therapy, 131 I-FIAU was used and tumor dimensions were monitored with calipers. Results: Treatment with buffer had no effect on on 3 EBVTK tumors and 3 SHAM tumors all of which increased in volume. Treatment with 1.4 mCi 131 I-FIAU alone led to tumor responses (&gt;90% volume reduction at 10 days) in 3/3 mice with EBVTK tumors and 0/3 mice with SHAM tumors. Treatment with 131 I-FIAU alone had no effect on BL (0/3) or PEL (0/9) xenografts and all tumors increased in volume. Treatment with bortezomib induced modest responses in all tumors but had no greater effect on EBVTK tumors than SHAM tumors. However, treatment with bortezomib and 131 I-FIAU led to marked tumor regression (&gt;95%) in each of the virus-associated tumors (3/3 BL, 9/9 PEL). SPECT imaging with 125 I-FIAU showed selective concentration of radiolabel in tumor tissue in the EBVTK tumor (2/2) and in viral tumors (6/6) when bortezomib was administered. There was no selective concentration in the absence of bortezomib treatment in the viral tumors (0/8). Conclusions: Treatment with bortezomib leads to selective concentration of labeled FIAU in the herpesvirus-associated tumor xenografts evaluated and to regression of tumor when the isotope is 131 I. No significant financial relationships to disclose.
49 Supra gastric belching symptoms, prevalence and associated disease
Authors: G Elsafi, A Alhanaee, L Barry, L Quinlivan, M Farman, J McCarthy, M Buckley
Journal: Gut (2017)

Background  Supragastric belching (SGB) is considered a behavioural disorder where air is ingested in to eosophagus and immediately expelled again; it can result in symptoms of excessive belching and has a significant impact on quality of life.  With the advent of the intraluminal impedance recording technique, it has become possible to monitor the passage of air through the oesophagus, either in ab-oral or ad-oral directions.  Aim  Determine the prevalence of excessive SGB within our tertiary referral gastrointestinal physiology unit and evaluate the predominant presenting symptoms and examine its association with gastro-esophageal reflux disease and motility disorders.  Method  Data was collected retrospectively from our data base system, we reviewed 442 reports of 24 hours PH-Impedance and high resolution oesophageal manometry from January 2015 to December 2016.  Symptoms were reviewed from patients’ charts. These included the predominant presenting symptom, symptoms of acid reflux and heartburn, regurgitation and dysphagia.  Results  A total of 98 (22%) patients were found to have excessive SGB. predominant presenting symptom was heartburn (55%), only 18% had pathological acid exposure. Dysphagia was reported in 23% and regurgitation in 7%. only 7% presented with isolated symptom of belching,Esophageal hypomotility was seen in 48%.  Conclusions  Excessive SGB was common finding in 24 hours PH-impedance manometry studies, the main predominant symptom was heartburn, and there appears to be an association with oesophageal hypomotility and to a lesser extent with gastroeosphageal reflux disease.
Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia
Authors: Yinghui Zhu, Xin He, Yi-Chun Lin, Haojie Dong, Lei Zhang, Xianwei Chen, Zhihao Wang, Yudao Shen, Min Li, Hanying Wang, Jie Sun, Le Xuan Nguyen, Han Zhang, Wenjuan Jiang, Yanzhong Yang, Jianjun Chen, Markus Müschen, Chun-Wei Chen, Marina Y. Konopleva, Weili Sun, Jian Jin, Nadia Carlesso, Guido Marcucci, Yun Luo, Ling Li
Journal: Blood (2019)
Playground Shade Availability and Socioeconomic Position of Students at St Louis Public Elementary Schools
Authors: Jolee G. Potts, Carrie C. Coughlin
Journal: JAMA Dermatology (2019)

Elementary schools should provide a minimum of 20 minutes of daily recess. 1 Although outdoor play is important for child wellness, a lack of proper sun protection can increase the risk of developing skin cancer.Approximately 40% to 50% of UV exposure occurs before 20 years of age 2 ; therefore, school playgrounds must provide adequate shade to help protect children from the dangers of sun exposure.Few studies have focused on quantifying playground shade, especially in the United States.Recent New Zealand and German estimates range from 11.6% 3 and 14.5% 4 to 41%. 5 Two-thirds of US school principals reported that their playgrounds had less than 20% shade cover. 6 Herein we quantify shade availability on public elementary school playgrounds in a US city-St Louis, Missouri-and determine whether shade is associated with the socioeconomic position of students' families.
Mass spectrometric study of drug binding to proteins
Authors: Sool Cho, John Roboz, Takao Ohnuma, James Holland
Journal: Cancer Research (2007)

3182  The objective was to characterize intact complexes of drugs with proteins, particularly human serum albumin and a variety of enzymes using mass spectrometry to calculate the number of bound drug molecules. Drugs studied: (a) Antineoplastic: tamoxifen (372 Da); doxorubicin (544 Da), methotrexate (454 Da), bleomycin (1416 Da), suramin (1429 Da) and the novel benzyl styryl sulfone analog ON 1910Na (474 Da); (b) Other Drugs: Digoxin (791 Da); fluphenazine (438 Da), and trifluoroperazin (408 Da). Proteins studied: albumin (66 kDa) and the enzymes: papain (21 kDa), elastase (25 kDa), trypsin (24 kDa) and carbonic anhydrase (29 kDa). Methodology: One µL aliquots of incubates (30 min, 37°C) or plasma sample from patients on Phase I clinical trials with ON 01910.Na were injected directly into the ion source of a triple quadrupole mass spectrometer. Positive electrospray or nanospray mass spectra were obtained and molecular masses of the intact drug-protein complexes were obtained from multiple charged ion patterns.  Results: (a) Complex formation between the drug and protein commenced immediately upon exposure. (b) Albumin-drug interactions yielded mixtures simultaneously containing complexes with a varying number of bound drug molecules, e.g., up to 21 molecules of tamoxifen per albumin molecule vs. only up to 8 molecules of digoxin per albumin; (c) The number of bound molecules for each drug was different for different enzymes, e.g., carbonic anhydrase attached 13 molecules of tamoxifen vs. 11 molecules of digoxin; (d) Drug binding followed an apparently discontinuous digital progression, e.g., 10, 11, 13, 17, 19, and 21 molecules of tamoxifen bound to albumin but not 12, 14, 15, 16, 18, or 20; (e) Similar unique phenomena occurred using several antineoplastic drugs as well as other drugs; and also using several different enzymes. We hypothesize that conformational changes caused by binding may account for the exclusion of certain binding complexes, and that conformational changes may influence protein behavior and enzymatic activity. (Supported by the T. J. Martell Foundation for Leukemia, Cancer and AIDS Research and by Onconova Therapeutics, Inc.)
With Neuroimaging, Large NIH Study Could Shine a Light on the Adolescent Brain
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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
Pilot Study of Pembrolizumab for Immunoprevention in Smoldering Multiple Myeloma
Authors: Elisabet E. Manasanch, Rohit Mathur, Hans C. Lee, Donna M. Weber, Krina K. Patel, Sheeba K. Thomas, Silvia C. Munoz, Claudia Morales de Partovi, Catherine M. Claussen, Pei Lin, Behrang Amini, Linghua Wang, Man Chun John Ma, Yun Qing, Feng Lei, Veera Baladandayuthapani, R. Eric Davis, Sattva S. Neelapu, Robert Z. Orlowski
Journal: Blood (2017)
The outcome of peptide receptor radionuclide therapy (PRRT) in North American patients with advanced well-differentiated neuroendocrine tumors (WD-NETs).
Authors: Boris Naraev, Nancy Sharma, Eric Steven Engelman, David L Bushnell, Thomas M. O'Dorisio, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2012)

e14600 Background: PRRT is frequently used in Europe for patients with advanced WD-NETs, but it is not yet readily available in the USA. We analyzed data on 135 North American patients seen at our institution who underwent PRRT. Methods: Cases were identified by searching the University of Iowa Neuroendocrine Tumors Database. Groups were compared using a Wilcoxon rank-sum test, and survival was calculated with the Kaplan-Meier method. Results: Men were 64%, women 36%; median age at diagnosis was 51 years (18 – 78). The primary tumor originated in the small bowel (SBNET) in 37.8%, pancreas (PNET) 26.0%, lung 13.3%, unknown primary 9.6%, other sites 13.3%. PRRT was performed at the University of Basel, Switzerland in 68.8%, University of Iowa in 25.2%, and elsewhere in 6%. 90 Y was used in 83.2% and 177 Lu in 15.3% for the first PRRT. Median dose of radiation was 180 mCi (range 7.6 – 360). 116 patients received two treatments with median time between the treatments 2.1 months (range 0.4 – 110). Survival is shown in the table. Radiographic responses (any) at 1-6 months after PRRT were observed in 65.8%, 11.1% had a mixed response, and 15.4% progressed. A biochemical response (&gt;50% reduction in chromogranin A and pancreastatin levels) was seen in 18% and 17.3% respectively but data was frequently missing. Conclusions: North American patients with WD-NETs have a relatively long survival. The OS from 1 st PRRT was much less than OS after diagnosis, suggesting that PRRT is used late in the disease course. PRRT appears to be a valuable treatment option for WD-NETs, especially SBNETS, and its role earlier in the disease course warrants investigation. [Table: see text]
Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems
Authors: Amanda B. Zheutlin, Jessica Dennis, Richard Karlsson Linnér, Arden Moscati, Nicole Restrepo, Peter Straub, Douglas Ruderfer, Victor M. Castro, Chia-Yen Chen, Tian Ge, Laura M. Huckins, Alexander Charney, H. Lester Kirchner, Eli A. Stahl, Christopher F. Chabris, Lea K. Davis, Jordan W. Smoller
Journal: American Journal of Psychiatry (2019)

Individuals at high risk for schizophrenia may benefit from early intervention, but few validated risk predictors are available. Genetic profiling is one approach to risk stratification that has been extensively validated in research cohorts. The authors sought to test the utility of this approach in clinical settings and to evaluate the broader health consequences of high genetic risk for schizophrenia.
Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induce apotosis
Authors: Yadi Wu, Geoffre Bartholomeusz
Journal: Cancer Research (2005)

3499  Induction of apoptosis by the pro-apoptotic Bcl-2 family member Bok is not antagonized by either Bcl-2 or Bcl-XL suggesting that Bok might have a unique role in the apoptotic cascade. We show that human Bok is the only member of the Bcl-2 family having a leucine rich sequence indicative of a nuclear export sequence [NES] within the BH3 domain. Bok is detectable both in the nucleus and cytoplasm of cells and its nuclear concentration increases following treatment with leptomycin B. Mutating the NES of Bok results in an increase in its nuclear localization and apoptotic activity. Further, we show that Crm1 interacted with wildtype Bok. These results suggest that nuclear export of Bok is a regulated process mediated by Crm1 and for the first time link the association between the apoptotic activity and nuclear localization of a pro-apoptotic Bcl-2 family member.
Anticancer activities of proteasome inhibitor MG132 on human malignant pleural mesothelioma cells
Authors: Bao-Zhu Yuan, Joshua Chapman, David Lowry, Steven Reynolds
Journal: Cancer Research (2007)

1459  Malignant pleural mesothelioma (MPM), caused mainly by occupational or environmental exposure to asbestos, is an aggressive malignancy with a very poor prognosis. The general resistance of MPM to current therapeutic modalities and an ongoing increase in the incidence of MPM demonstrate the need for new treatments for this deadly disease. Proteasome inhibitors have emerged as a category of promising reagents for treating human cancers. MG132, the most commonly used proteasome inhibitor, has demonstrated its ability to induce apoptosis in some types of human cancer. In our initial attempt to determine the therapeutic effect of the proteasome inhibitors on human MPM, we chose MG132 as a prototype of the proteasome inhibitors and characterized its anti-cancer effects on NCI-H2502 and NCI-H2452, two human thoracic MPM cell lines. It was observed that as low as 0.5μM MG132 caused significant cell death in both MPM cell lines. Cell death derived mainly from apoptosis as evidenced by the appearance of a pre-G1 peak in flow cytometry analysis and propidium iodide staining. It was also observed that MG132-induced apoptosis in both MPM cell lines was accompanied by cleavage of the PARP and caspase 3 and 7 proteins. Treatment with either casapse 3 inhibitor or Z-VAD, a broad spectrum caspase inhibitor, resulted in inhibition of MG132-induced apoptosis, suggesting that MG132-induced apoptosis operates through a caspase-dependent mechanism. Further demonstration of caspase 9 activation, which is likely the consequence of MG132-induced Bid protein activation and the subsequent release of the Smac/Diablo protein from the mitochondria, suggests that a mitochondria-caspase 3 apoptosis pathway is responsible for mediating MG132-induced apoptosis in MPM cells. Analysis of MG132’s effect on invasion by MPM cells, as tested by an in vitro Matrigel invasion assay, demonstrated that 0.1μM MG132, which showed no effect on apoptosis induction, significantly inhibited invasion by both NCI-H2452 and NCI-H2502 cells. MG132-inhibited tumor cell invasion was found to be associated with reduced Rac1 activity. These observations demonstrate proapoptotic and anti-invasion activities of MG132 on human MPM cells and lead to the suggestion that MG132 may be a useful reagent for clinical treatment of human MPM.
Modulation of redox metabolism negates cancer-associated fibroblasts-induced treatment resistance in a heterotypic 3D culture platform of pancreatic cancer
Authors: Mans Broekgaarden, Sriram Anbil, Anne-Laure Bulin, Girgis Obaid, Zhiming Mai, Yan Baglo, Imran Rizvi, Tayyaba Hasan
Journal: Biomaterials (2019)
Abstract 12746: Impaired Autophagic Flux in Ischemic/Reperfused Diabetic Heart and Its Reversal by a Novel Orally Active Adiponectin Receptor Agonist via AMPK-Mediated Autophagosome Formation and AMPK-Independent Autophagosome Clearance
Authors: Yajing Wang, Wayne B Lau, Erhe Gao, Walter Koch, Xin Ma
Journal: Circulation (2015)

Autophagy is increasingly recognized as an important regulator of myocardial ischemia/reperfusion (MI/R) injury. However, whether and how autophagy is altered in the ischemic/reperfused diabetic heart remains unknown. Normal control (NC), high-fat-diet-induced diabetic (HFD), and adiponectin (APN) knockout (APNKO) mice were subjected to MI/R (30 minutes/3-24 hours) and treated with vehicle or AdipoRon (50 mg/kg gavage, 10 minutes before MI; or 10 mg/kg IP, 10 min before R). Compared to NC mice, autophagosome formation was significantly inhibited and autophagosome clearance was nearly completely blocked in the HFD heart after MI/R (P&lt;0.01). APNKO largely reproduced the phenotypic alterations observed in the HFD heart, with both autophagosome formation and clearance inhibited after MI/R (P&lt;0.01 vs. WT). Treatment of HFD and APKNO mice with AdipoRon stimulated autophagosome formation, increased autophagosome clearance, reduced infarct size, and improved cardiac function (P&lt;0.01). Mechanistically, AdipoRon caused significant phosphorylation of AMPK, BeclineT119, and VPS34S16, and enhanced expression of lysosome protein LAMP2. Compound C pretreatment abolished AdipoRon-induced BeclineT119 and VPS34S164 phosphorylation without altering AdipoRon-induced LAMP2 expression. In vitro AdipoRon treatment of adult wild type cardiomyocytes enhanced phosphorylation of AMPK, BeclineT119, and VPS34S164. These effects are lost in cardiomyocytes isolated from cardiomyocyte-specific AMPK dominant negative mice (AMPK-DN). In contrast, AdipoRon-stimulated LAMP2 expression was preserved in AMPK-DN cardiomyocytes. Collectively, these results demonstrated for the first time that hypoadiponectinemia during diabetic conditions impairs autophagic flux in cardiomyocytes after MI/R via marked inhibition of both autophagosome clearance and formation. Administration of an orally active APN receptor agonist increased autophagosome formation via AMPK activation, and stimulated autophagosome clearance in an AMPK-independent fashion. Improving autophagic flux by restoring APN signaling systems might be a novel intervention against MI/R injury in diabetic conditions.
Preserving fertility in female patients with hematological malignancies: a multidisciplinary oncofertility approach
Authors: M. Salama, A. Anazodo, T.K. Woodruff
Journal: Annals of Oncology (2019)

Oncofertility is a new interdisciplinary field at the intersection of oncology and reproductive medicine that expands fertility options for young cancer patients. The most common forms of hematological malignancies that occur in girls and young women and therefore necessitate oncofertility care are acute lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, and Hodgkin's lymphoma. Aggressive gonadotoxic anticancer regimens including alkylating chemotherapy and total body irradiation are used often in treating girls and young women with hematological malignancies. The risks of gonadotoxicity and subsequent iatrogenic premature ovarian insufficiency and fertility loss depend mainly on the type and stage of the disease, dose of anticancer therapy as well as the age of the patient at the beginning of treatment. To avoid or at least mitigate the devastating complications of anticancer therapy-induced gonadotoxicity, effective and comprehensive strategies that integrate different options for preserving and restoring fertility ranging from established to experimental strategies should be offered before, during, and after chemotherapy or radiotherapy. A multidisciplinary approach that involves strong coordination and collaboration between hemato-oncologists, gynecologists, reproductive biologists, research scientists, and patient navigators is essential to guarantee high standard of care.
Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial
Authors: Robert J Motzer, Brian I Rini, David F McDermott, Osvaldo Arén Frontera, Hans J Hammers, Michael A Carducci, Pamela Salman, Bernard Escudier, Benoit Beuselinck, Asim Amin, Camillo Porta, Saby George, Victoria Neiman, Sergio Bracarda, Scott S Tykodi, Philippe Barthélémy, Raya Leibowitz-Amit, Elizabeth R Plimack, Sjoukje F Oosting, Bruce Redman, Bohuslav Melichar, Thomas Powles, Paul Nathan, Stéphane Oudard, David Pook, Toni K Choueiri, Frede Donskov, Marc-Oliver Grimm, Howard Gurney, Daniel Y C Heng, Christian K Kollmannsberger, Michael R Harrison, Yoshihiko Tomita, Ignacio Duran, Viktor Grünwald, M Brent McHenry, Sabeen Mekan, Nizar M Tannir
Journal: The Lancet Oncology (2019)
Clinical Impact of Somatic Copy Number Alterations in Circulating Tumor DNA from Diverse Lymphoma Subtypes
Authors: Michael Jin, David M. Kurtz, Mohammad S Esfahani, Joanne Soo, Alexander Craig, Florian Scherer, Henning Stehr, Joseph G Schroers-Martin, Charles Dana Bangs, Athena Cherry, Yasodha Natkunam, Mark Roschewski, Wyndham H. Wilson, Ulrich Duehrsen, Andreas Hüttmann, Davide Rossi, Gianluca Gaidano, Jason R. Westin, Ranjana H. Advani, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2017)