tbuckley/cabot-search huggingface dataset:
Towards Personalized Treatment of Prostate Cancer: PSMA I&amp;T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent
Authors: Kristell L.S. Chatalic, Sandra Heskamp, Mark Konijnenberg, Janneke D.M. Molkenboer-Kuenen, Gerben M. Franssen, Marian C. Clahsen-van Groningen, Margret Schottelius, Hans-Jürgen Wester, Wytske M. van Weerden, Otto C. Boerman, Marion de Jong
Journal: Theranostics (2016)

Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa).Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics-they rapidly and efficiently localize in tumor lesions.However, high tracer uptake in kidneys and salivary glands are major concerns for therapeutic applications.Here, we present the preclinical application of PSMA I&T, a DOTAGA-chelated urea-based PSMA inhibitor, for SPECT/CT imaging and radionuclide therapy of PCa. 111 In-PSMA I&T showed dose-dependent uptake in PSMA-expressing tumors, kidneys, spleen, adrenals, lungs and salivary glands.Coadministration of 2-(phosphonomethyl)pentane-1,5-dioic acid (2-PMPA) efficiently reduced PSMA-mediated renal uptake of 111 In-PSMA I&T, with the highest tumor/kidney radioactivity ratios being obtained using a dose of 50 nmol 2-PMPA.SPECT/CT clearly visualized subcutaneous tumors and sub-millimeter intraperitoneal metastases; however, high renal and spleen uptake in control mice (no 2-PMPA) interfered with visualization of metastases in the vicinity of those organs.Coadministration of 2-PMPA increased the tumor-to-kidney absorbed dose ratio during 177 Lu-PSMA I&T radionuclide therapy.Hence, at equivalent absorbed dose to the tumor (36 Gy), coinjection of 2-PMPA decreased absorbed dose to the kidneys from 30 Gy to 12 Gy.Mice injected with 177 Lu-PSMA I&T only, showed signs of nephrotoxicity at 3 months after therapy, whereas mice injected with 177 Lu-PSMA I&T + 2-PMPA did not.These data indicate that PSMA I&T is a promising theranostic tool for PCa.PSMA-specific uptake in kidneys can be successfully tackled using blocking agents such as 2-PMPA.
Pellicano F, Cilloni D, Helgason GV, Messa F, Panuzzo C, Arruga F, Bracco E, Allan E, Huntly BJ, Holyoake TL, Saglio G. FOXO transcription factor activity is partially retained in quiescent CML stem cells and induced by tyrosine kinase inhibitors in CML progenitor cells [published online ahead of print December 1, 2009]. Blood. doi 10.1182/blood-2009-06-226621.
Journal: Blood (2010)
Disparities in Health Care in Puerto Rico Compared With the United States
Authors: Héctor M. Colón, Marizaida Sánchez-Cesareo
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Clinical relevance of molecular diagnosis in pet allergy
Authors: S. A. Uriarte, J. Sastre
Journal: Allergy (2016)

We describe the pattern of sensitisation to pet IgE components and its association with clinical symptoms. Hundred and fifty nine consecutive patients with rhinitis/asthma sensitised to dog, cat, and horse were recruited. Specific IgE to whole extracts and to pet recombinant allergens were performed. Only 5% of patients were monosensitised to animal allergens. Specific IgE to Can f 1 was significantly associated with persistent rhinitis, Can f 2 with asthma diagnosis, Can f 3 with moderate/severe rhinitis (M/S-R) and asthma diagnosis (AD), and Can f 5 with persistent and M/S-R. Positive IgE to Fel d 2 was significantly associated with M/S-R and AD, Equ c 1 with M/S-R and Equ c 3 with persistent rhinitis, AD and severe asthma. Sensitisation to ≥2 molecules or to pet albumins was associated with more severe respiratory symptoms. Molecular diagnosis in patients with pet allergy may also help clinicians to predict clinical symptoms and their severity.
CBIO-19IBUPROFEN AND DICLOFENAC INHIBIT MIGRATION AND PROLIFERATION OF HUMAN GLIOMA CELL LINES IN VITRO
Authors: Verena Leidgens, Corinna Seliger, Petra Leukel, Birgit Jachnik, Arabel Vollmann-Zwerenz, Lisa Rauer, Ulrich Bogdahn, Marina Kreutz, Oliver Grauer, Peter Hau
Journal: Neuro-Oncology (2015)

Hallmarked by infiltrating tumor cells, GBM are characterized as highly malignant brain tumors.Nonsteroidal anti-inflammatory drugs (NSAIDs) have Overall survival
Development and validation of a comprehensive genomic diagnostic tool for myeloid malignancies
Authors: Thomas McKerrell, Thaidy Moreno, Hannes Ponstingl, Niccolo Bolli, João M. L. Dias, German Tischler, Vincenza Colonna, Bridget Manasse, Anthony Bench, David Bloxham, Bram Herman, Danielle Fletcher, Naomi Park, Michael A. Quail, Nicla Manes, Clare Hodkinson, Joanna Baxter, Jorge Sierra, Theodora Foukaneli, Alan J. Warren, Jianxiang Chi, Paul Costeas, Roland Rad, Brian Huntly, Carolyn Grove, Zemin Ning, Chris Tyler-Smith, Ignacio Varela, Mike Scott, Josep Nomdedeu, Ville Mustonen, George S. Vassiliou
Journal: Blood (2016)
Abstract 15656: Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells (CDCs) Immediately After Reperfusion Stimulates Myocyte Regeneration in Remote Viable Myocardium in Swine With Acute Myocardial Infarction
Authors: Gen Suzuki, Brian R Weil, Merced M Leiker, Andrew Goelz, James A Fallavollita, John M Canty
Journal: Circulation (2014)

Introduction: Previous studies evaluating regenerative strategies have focused on administering stem cells to the infarct related artery. Unfortunately, this does not stimulate cardiac regeneration nor prevent myocyte loss in viable remote myocardium that becomes dysfunctional due to LV remodeling. Hypothesis: We hypothesized that administrating allogeneic CDCs to the entire heart (global CDC infusion) at the time of reperfusion could improve function, stimulate myocyte regeneration and prevent myocyte loss throughout the LV. Methods: Yorkshire swine (n=12) underwent a one hour LAD occlusion. Ejection fraction (EF) decreased from 63 ± 2% at baseline to 44 ± 2% after infarction (p&lt;0.05 vs. baseline). Immediately after reperfusion animals were randomized to allogeneic intracoronary CDCs or vehicle in a blinded fashion (n=6 each). Allogeneic CDCs (20 x 10^6 CDCs, cyclosporine 100 mg/day) were infused into the 3 major coronary distributions without interrupting flow. Four weeks later we assessed myocardial function (echo), myocyte proliferation (Ki67), infarct size (TTC), myocyte nuclear density and cell size in comparison to vehicle. Results: After 4 weeks, global CDC infusion increased wall thickening and ejection fraction despite the fact that infarct volume was not different (Table). CDCs stimulated myocyte proliferation (Ki67) in border and remote regions by 3-fold. As a result, myocyte number (nuclear density) increased by 34 % and cell size decreased by 7% in viable infarct border and remote regions. Conclusion: Global infusion of allogeneic CDCs immediately after reperfusion 1.) stimulates myocyte regeneration in viable myocardium remote from the infarct and 2.) improves regional and global LV function without altering infarct size. Thus, treating viable remote myocardium as well as the infarct related artery with allogeneic CDCs may afford a widely available approach to reverse LV dysfunction in patients with acute myocardial infarction.
MAGE-D2 and the Regulation of Renal Salt Transporters
Authors: Nine V.A.M. Knoers, René J. Bindels
Journal: New England Journal of Medicine (2016)

Bartter’s syndrome is a rare, genetically heterogeneous disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis, and secondary hyperaldosteronism with normal to low blood pressure. Two distinct presentations of the syndrome exist: antenatal Bartter’s syndrome and classical Bartter’s syndrome. Both forms are inherited as autosomal recessive traits.Patients with antenatal Bartter’s syndrome may carry loss-of-function mutations in the genes encoding the furosemide-sensitive sodium–potassium–chloride cotransporter NKCC2, the inwardly rectifying potassium channel ROMK, or the chloride channel β-subunit barttin.1 The concerted action of these transporters in the renal thick ascending limb of the loop of Henle ensures transcellular sodium chloride reabsorption in . . .
IgG subclasses determine pathways of anaphylaxis in mice
Authors: Héloïse Beutier, Caitlin M. Gillis, Bruno Iannascoli, Ophélie Godon, Patrick England, Riccardo Sibilano, Laurent L. Reber, Stephen J. Galli, Mark S. Cragg, Nico Van Rooijen, David A. Mancardi, Pierre Bruhns, Friederike Jönsson
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 46-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Ashby C. Moncure, Robert H. Young
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 71-year-old woman was admitted to the hospital because of abdominal pain, fever, and bloody stools.She was well until six weeks earlier, when abdominal cramps and distention developed, accompanied by obstipation and fever. Ten days later she entered another hospital, where examination revealed tenderness in both lower abdominal quadrants, especially the left; no mass was palpated on abdominal or rectal examination. An x-ray film of the abdomen showed a normal gas pattern; no masses were visible. Results of liver-function tests were abnormal, with persistent elevation of the alkaline phosphatase level and hyperglobulinemia. A barium-enema examination and . . .
Abstract 1005: Dual targeting of MEK/MAPK1/2 and pro-survival autophagy to optimize antiestrogen treatment toward the eradication of antiestrogen resistant breast cancer
Authors: Mathew Manning, Suchreet Takhar, Sudharsan Periyasamy-Thandavan, Michael Cheng, Thomas Barrett, William Hill, Darren Browning, Muthusamy Thangaraju, Meghan McGee-Lawrence, Patricia V. Schoenlein
Journal: Cancer Research (2015)

Abstract In past studies, we showed that pro-survival autophagy mediates resistance to antiestrogen-induced apoptosis and facilitates the emergence of antiestrogen resistant breast cancer cells (Sammadar et al., Molecular Cancer Ther. 9, 2008). We also identified the pro-apoptotic BimEL protein as a key death effector of antiestrogen treatment and determined that BimEL pro-apoptotic activity is abrogated by a MEK1/MAPK1/2-dependent phosphorylation (Periyasamy-Thandavan et al., Breast Cancer Res. 14, 2012). In this study, we tested the hypothesis that the MEK1/MAPK1/2/BimEL signaling node simultaneously regulates antiestrogen- induced pro-survival autophagy and apoptosis in ER+ breast cancer cells. In our approach, we utilized T47-D and MCF-7 breast cancer cells and modulated the activity of MEK1/MAPK1/2/ BimEL expression with U0126, a small molecule inhibitor of MEK1, BimEL cDNA over-expression, or siRNA targeting under a variety of endocrine treatments. We also conducted studies in the presence or absence of the pan-caspase inhibitor ZVAD-fmk so that autophagy levels/function could be analyzed independent of effects mediated by BimEL-dependent caspase activation. Autophagic flux was measured by comparing the levels of lipidated LC3II in cell populations undergoing the different treatments in the presence or absence of chloroquine (CQ), a lysosomotropic agent that prevents autolysosomal turnover. These studies determined that: 1) dephosphorylated BimEL significantly attenuates autophagic flux, but primarily as a consequence of BimEL-induced caspase-activation; (2) BimEL-dependent apoptotic death induced in antiestrogen-treated ER+ breast cancer cells by MEK1 inhibition is not dependent on autophagy; and (3) agents that selectively target autophagy (i.e. CQ and spautin) enhance apoptosis induced by MEK1 blockade in breast cancer cells undergoing endocrine treatment. Based on these pre-clinical in vitro studies, we postulate that the eradication of antiestrogen resistant breast cancer will require the targeting of MEK1/MAPK1/2 to activate BimEL and pro-survival autophagy to eradicate cells surviving BimEL-dependent apoptosis. Citation Format: Mathew Manning, Suchreet Takhar, Sudharsan Periyasamy-Thandavan, Michael Cheng, Thomas Barrett, William Hill, Darren Browning, Muthusamy Thangaraju, Meghan McGee-Lawrence, Patricia V. Schoenlein. Dual targeting of MEK/MAPK1/2 and pro-survival autophagy to optimize antiestrogen treatment toward the eradication of antiestrogen resistant breast cancer. [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 1005. doi:10.1158/1538-7445.AM2015-1005
Clinicians’ prescription preferences for treating patients with Alzheimer’s disease in Shanghai
Authors: Chun-Xia Ban, Shi-Fu Xiao, Xiang Lin, Tao Wang, Qi Qiu, Min-Jie Zhu, Xia Li
Journal: Translational Neurodegeneration (2016)

China has more cases of Alzheimer's disease (AD) than any other country in the world. As training to recognize and manage dementia is in its early stage, it is important to study clinicians' current prescription preferences for treating patients with AD.This study surveyed neurologists, psychiatrists, and general physicians (GPs) in Shanghai who had outpatients with AD, using a questionnaire asking about their prescription preferences for these patients.Among the 148 clinicians in the study, 26.4 % were psychiatrists, 44.6 % were neurologists, and 29.1 % were GPs. The groups did not differ significantly in age, gender, or their monthly cases of new patients with mild or moderate AD (P > 0.05). Most clinicians prescribed Cholinesterase inhibitors (ChEIs), including Huperzine A, but there were significant group-differences in prescribing specific ChEIs (P < 0.05). The daily dosages of ChEI and Memantine prescribed by all three groups were small (P > 0.05), and all three groups prescribed piracetam, ergot, and ginkgo biloba drugs. All three groups also tended to treat AD patients with a combination of antidepressants and anxiolytics, although psychiatrists were significantly more likely than neurologists to combine antipsychotics with other drugs (P < 0.05).Clinicians in Shanghai prescribed low doses of ChEIs and Memantine for patients with AD. A relatively high proportion also prescribed cognitive enhancers, which lack evidence-based support of their use, and antipsychotics. There is a need for more training about treating patients with AD and for clinicians to standardize their clinical practice.
No increased heart failure risk is reported with DPP-4 inhibitors
Authors: Jacqui Wise
Journal: BMJ (2016)

The risk of heart failure is no higher in patients taking the dipeptidyl peptidase-4 inhibitors (DPP-4) saxagliptin or sitagliptin than in those taking other drugs commonly prescribed for type 2 diabetes, researchers have found.1

A large retrospective cohort study published in the Annals of Internal Medicine compared new users of DPP-4 inhibitors with new users of second generation sulphonylureas, pioglitazone, or …
Abstract 214: Reduction of Scar Tissue after GHRH-A Treatment in a Swine Model of Sub-acute Ischemic Cardiomyopathy
Authors: Luiza L Bagno, Rosemeire Kanashiro Takeuchi, Bo Wang, Viky Suncion, Vasileios Karantalis, Courtney Premer, Samuel Golpanian, Wayne Balkan, José E Rodriguez, David Valdes, Marcos Rosado, Ariel Wolf, Norman L Block, Peter Goldstein, Azorides Morales, Andrew V Schally, Joshua M Hare
Journal: Circulation Research (2014)

Background: Growth hormone-releasing hormone receptor agonists (GHRH-A) stimulate cardiac repair following myocardial infarction (MI) through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH-A prevents ventricular remodeling in a swine sub-acute MI model. Methods: Twelve female Yorkshire swine (25-30 Kg) underwent transient occlusion of the LAD coronary artery (MI). Two-weeks post-MI, swine were randomized to receive injections of either 30 μg/Kg GHRH-A (MR-409) (GHRH-A group; n=6) or vehicle (placebo group; n=6). Cardiac MRI, pressure volume loops and measures of endothelial function were obtained at multiple time points. Infarct-, border- and remote- (non-infarcted) zones were assessed by immunohistochemistry for the growth hormone-releasing hormone receptor (GHRHR). Results: Four-weeks of GHRH-A treatment resulted in reduced scar mass (GHRH-A group: –21.9±6.42%; p=0.02; placebo group: 10.9±5.88%; p=0.25; Two-way ANOVA; p=0.003), and reduced scar size (percent of left ventricle mass) (GHRH-A group: –38.38±4.63; p=0.0002; placebo group: –14.56± 6.92; p=0.16; Two-way ANOVA; p=0.02). Moreover, peripheral endothelial function was significantly increased compared to baseline values in the GHRH-A group (paired t-test; p=0.006) but not in the placebo group (p=0.99). Unlike in rats, this reduced infarct size in swine was not accompanied by improved cardiac function as measured by serial hemodynamic pressure-volume analysis. GHRH receptors were abundant in cardiac tissue, with a greater density in the border zone of the GHRH-A group compared to the placebo group. These data support the concept of direct post-infarction activation of cardiac signal transduction, and of enhancing this activation with systemic treatment by GHRH. Conclusions: Daily subcutaneous administration of GHRH-A is feasible and safe in female swine. Furthermore, GHRH-A therapy significantly reduced infarct size and increased endothelial function, suggesting that a local activation of the GHRH pathway leads to the regenerative process and preservation of peripheral endothelial function.
Superior Therapeutic Index in Lymphoma Therapy: CD30+ CD34+ Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack
Authors: Andreas A Hombach, André Görgens, Markus Chmielewski, Florian Murke, Janine Kimpel, Bernd Giebel, Hinrich Abken
Journal: Molecular Therapy (2016)

Recent clinical trials with chimeric antigen receptor (CAR) redirected T cells targeting CD19 revealed particular efficacy in the treatment of leukemia/lymphoma, however, were accompanied by a lasting depletion of healthy B cells. We here explored CD30 as an alternative target, which is validated in lymphoma therapy and expressed by a broad variety of Hodgkin's and non-Hodgkin's lymphomas. As a safty concern, however, CD30 is also expressed by lymphocytes and hematopoietic stem and progenitor cells (HSPCs) during activation. We revealed that HRS3scFv-derived CAR T cells are superior since they were not blocked by soluble CD30 and did not attack CD30(+) HSPCs while eliminating CD30(+) lymphoma cells. Consequently, normal hemato- and lymphopoiesis was not affected in the long-term in the humanized mouse; the number of blood B and T cells remained unchanged. We provide evidence that the CD30(+) HSPCs are protected against a CAR T-cell attack by substantially lower CD30 levels than lymphoma cells and higher levels of the granzyme B inactivating SP6/PI9 serine protease, which furthermore increased upon activation. Taken together, adoptive cell therapy with anti-CD30 CAR T cells displays a superior therapeutic index in the treatment of CD30(+) malignancies leaving healthy activated lymphocytes and HSPCs unaffected.
Use of the patency capsule in daily practice
Authors: Alba Cebrián, Ignacio Fernández-Urién, Juan Vila
Journal: Endoscopy (2016)

We read with great interest the article entitled “Use of patency capsule in patients with established Crohn’s disease” by Nemeth et al. [1]. Although some studies have evaluated the role of the patency capsule in patients with suspected small-bowel strictures [2] [3] [4], little is known regarding its use in daily practice. The study by Nemeth et al. included 406 video capsule ingestions in patients with established Crohn’s disease: 132 patients (32.5 %) underwent video capsule endoscopy without previous patency capsule test and 274 (67.5 %) received the patency capsule prior to capsule endoscopy. The patency capsule test was negative in 193 patients (70.4 %) and positive in 81 patients (29.6 %). A negative patency test did not eliminate the risk of capsule retention, as four patients (2.1 %) retained theirs, but the result was a very high negative predictive value (97.9 %). Conversely, a positive patency test resulted in video capsule retention in 11.1 % of performed cases (n = 18), and even the second-generation patency capsule resulted in a small-bowel obstruction in some cases (2.2 %). Nevertheless, as the present paper concludes, retained capsules could be resolved by nonsurgical methods.
A multicenter, open-label trial of talimogene laherparepvec (T-VEC) plus pembrolizumab vs pembrolizumab monotherapy in previously untreated, unresected, stage IIIB-IV melanoma.
Authors: Antoni Ribas, Igor Puzanov, Thomas Gajewski, Georgina V. Long, Reinhard Dummer, John M. Kirkwood, Ari VanderWalde, Jonathan S. Cebon, Grant A. McArthur, Christine K. Gause, Lisa Chen, David Ross Kaufman, Jeffrey Chou, Robert Hans Ingemar Andtbacka, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2015)

TPS9081 Background: T-VEC is a herpes simplex virus-1-based oncolytic immunotherapy designed to preferentially replicate in tumors, produce GM-CSF and stimulate an anti-tumor immune response. OPTiM, a phase III trial of T-VEC vs GM-CSF in unresected stage IIIB-IV melanoma (n = 436), met the primary endpoint of improved durable response rate (DRR) in the T-VEC arm (16 vs 2%; Andtbacka et al ASCO 2013). Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated in the U.S. for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Combining T-VEC with pembrolizumab may enhance the anti-tumor immune response vs either therapy alone. Here, we describe a study (NCT02263508) assessing safety and efficacy of T-VEC + pembrolizumab in previously untreated, unresected stage IIIB-IV melanoma. Phase 1b enrolment began 12/2014. Methods: 1o objectives: Phase 1b: assess dose-limiting toxicities of T-VEC + pembrolizumab. Phase 2: compare confirmed ORR by immune-related response criteria (irRC) at Wk 24 for T-VEC + pembrolizumab vs pembrolizumab alone 2o objectives: Best OR, DRR, duration of response (DOR), PFS, OS, treatment-emergent/related AEs Treatment: T-VEC is injected into cutaneous, subcutaneous or nodal lesions at up to 4 mL of 106 plaque forming units (PFU)/mL Day 1, then at up to 4 mL of 108 PFU/mL Day 22 and Q2W (phases 1b and 2). Pembrolizumab is given at 200 mg IV Q2W from Day 36 in phase 1b (n = 20) and Day 1 in phase 2 (n = 90). Treatment with both therapies will continue until (whichever comes first): CR or PD per irRC, intolerance, for up to 2 yrs or, for T-VEC only, when there are no longer injectable lesions. Pts in phase 2 will be randomized 1:1 to T-VEC + pembrolizumab vs pembrolizumab alone. Key eligibility: Stage IIIB-IV melanoma naïve to systemic treatment (except adjuvant), injectable lesions, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression, no active herpetic infection. Clinical trial information: NCT02263508.