tbuckley/cabot-search huggingface dataset:
Abstract 311: Measurements of cAMP Dynamics in the SERCA2 Microdomain in Adult Mouse Cardiomyocytes using a Targeted FRET Biosensor
Authors: Julia U Sprenger, Viacheslav O Nikolaev
Journal: Circulation Research (2013)

PURPOSE: cAMP is a central regulator of cardiac function and disease. This global second messenger acts in a compartmentalized fashion, and changes in cAMP dynamics are linked to cardiac diseases. In this project, we visualized cAMP signals directly in such microdomains to gain insights into the molecular mechanisms involved in cAMP compartmentation and its alterations in hypertrophy. Methods: We generated transgenic mice expressing a new Förster resonance energy transfer (FRET)-based cAMP sensor Epac1-camps-PLN to measure cAMP dynamics in the microdomain around the sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2). This sensor is targeted to SERCA2 via phospholamban (PLN). Results: Colocalization and cell fractionation analysis confirmed proper localization of the sensor in transgenic mouse hearts. qPCR analysis revealed a two-fold overexpression of PLN. However, no adverse cardiac phenotype could be detected by histological analysis and heart weight to body weight ratios. Local cAMP dynamics were measured using freshly isolated adult ventricular myocytes and compared to cAMP signals in the bulk cytosol using cardiomyocytes from Epac1-camps mice. We detected the predominant role of phosphodiesterases (PDEs) 4 and 3 in the SERCA2 compartment under basal conditions. These PDEs were responsible for shaping the microdomain and its segregation from the cytosolic compartment. Interestingly, beta1-adrenergic stimulation led to a stronger increase of local cAMP in the SERCA2 compartment compared to the bulk cytosol. 8 weeks after transverse aortic constriction (TAC), PDE4 activity was downregulated in the SERCA2 microdomain compared to sham cardiomyocytes. Conclusion: We successfully generated transgenic mice expressing the targeted Epac1-camps-PLN biosensor to visualize cAMP dynamics in the SERCA2 compartment. We could show distinct cAMP dynamics around the SERCA2 compartment compared to the bulk cytosol and uncovered its alterations in hypertrophied cardiomyocytes
Precision Medicine Assays Detect Novel Targetable FLT3 Fusions Amenable to Therapeutic Intervention in a Patient with Refractory Acute Myeloid Leukemia
Authors: Bradley A Patay, Andrew Carson, Timothy J Martins, Sylvia Chien, Mary-Elizabeth M. Percival, Taylor Sekizaki, Cody Hammer, Pamela S. Becker
Journal: Blood (2016)
Mifepristone treatment improves length and quality of survival of mice with spontaneous lung cancer
Authors: Jerome Check, Lynn SanSoucie, Joshua Chern, Ebony Dix, Chi Amadi
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1899 

The treatment of spontaneous murine leukemia, with the progesterone receptor antagonist mifepristone has resulted in prolonged survival and improved quality of life (as determined by the body conditioning score). The hypothesized mechanism of action of the drug is not related to a direct effect of mifepristone on the tumor itself but rather to inhibit the secretion of a protein by gamma/delta T cells that is under the influence of the tumor cells that protects the tumor against immune surveillance by natural killer (NK) cells. This protein is also positively influenced by progesterone and in the pregnant state is called the progesterone induced blocking factor (PIBF) and protects the fetus against NK cell attack. The aim of the present study was to evaluate whether mifepristone could prolong and improve quality of life in mice with spontaneous lung cancer. A comparison of gavaging A/J mice that develop a high frequency of spontaneous lung cancer with .3mg 3 times per week of mifepristone (n=39) starting at 8 weeks of life vs. controls (n=31) gavaged with the olive oil vehicle was performed. The survival rates were determined by the Kaplan-Meier estimates of survival rate at the end of the first year of life. The time until death was defined as the number of days from the first treatment until the mice were euthanized or expired naturally. The quality of life was determined by the body conditioning score (BCS) (scored 1-5). A mouse was considered “sick” if the BCS fell to <4. Mice were euthanized at BCS 2 or 3- or 2+ if they are having trouble breathing, eating, or moving. BCS was determined by members of the vivarium staff and not the research staff. They did not know what treatment was being rendered to the mice. The Kaplan-Meier estimate of survival rate following one year of treatment was 57.6% (SE 9.6%) for mifepristone treated mice vs. 26.6% (SE 8.4%) for olive oil controls. The rates were statistically significant (long rank test, p=.056). These included mice that died spontaneously or were euthanized . Evaluating just spontaneous death the survival rate was 67.4% (SE 8.9%) for mice gavaged with mifeprstone vs. 27.0% (SE 8.5%) for mice gavaged with olive oil (p<.05). The mean number of days sick for those mice who survived was significantly longer for the controls (11.6+5 days with n=15 for mifepristone vs. 57.6+19.3 with n=8 for olive oil control) (p=.05). Breaking down the survival group further showed that 66.7% (n=10) of the mifepristone group had no sick days vs. 0.0% for the controls. These data thus demonstrate that treatment with mifepristone can improve both the length and quality of life in mice with spontaneous lung cancer. Thus progesterone receptor antagonists have now been demonstrated to be effective in solid cancers not known to be hormonally dependent as well as leukocyte cancers as previously demonstrated.
Transarterial chemoembolizaton combined with sorafenib for intermediate-stage hepatocellular carcinoma: a window of tumor burden for survival benefit
Authors: E. Wang, W. Bai, D. Xia, L. Liu, W. Wang, H. Chen, Q. Wang, L. Zuo, Y. Lv, H. Liu, Z. Yin, J. Xia, D. Fan, G. Han
Journal: Journal of Hepatology (2017)
Abstract B27: Morphological changes, cadherin switching, and growth suppression in pancreatic cancer by GALNT6 knockdown
Authors: Yunus Emre Tarhan, Kato Taigo, Miran Jang, Yusuke Nakamura, Jae-Hyun Park
Journal: Cancer Research (2017)

Abstract Pancreatic Cancer has one of the lowest rates of survival among other cancers. Although molecular targeted therapy has been widely applied for many types of cancer, no effective treatment has been developed for the patients of pancreatic cancer. We previously suggested that GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) is a promising molecular target in breast cancer by O-type glycosylation of Mucin1. Interestingly, GALNT6 is also up-regulated in pancreatic cancer where Mucin proteins are intensively O-glycosylated, indicating a critical role of GALNT6 in pancreatic cancer. In this study we found that knockdown of GALNT6 using siRNAs decreased Muc4 protein as well as transcription level in pancreatic cancer cells. The knockdown of GALNT6 also decreased HER2 and ERK, interacting proteins of Mucin 4, accompanied by drastic reduction of pancreatic cancer cell viability. Further analysis revealed that knockdown of GALNT6 led to cell morphologic changes like the mesenchymal to epithelial transition, which was in concordant with the cadherin switching mechanism—increase of E-cadherin meanwhile decrease of P-cadherin level. Taking into considerations of important roles of Mucin 4 in growth, invasion and resistance to gemcitabine, our findings imply that targeting GALNT6 is a very promising therapeutic strategy for the treatment of pancreatic cancer patients who still have very limited treatment modalities Citation Format: Yunus Emre Tarhan, Kato Taigo, Miran Jang, Yusuke Nakamura, Jae-Hyun Park. Morphological changes, cadherin switching, and growth suppression in pancreatic cancer by GALNT6 knockdown. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B27.
The primary care sports medicine fellowship: American Medical Society for Sports Medicine proposed standards of excellence
Authors: Irfan M Asif, Mark Stovak, Tracy Ray, Amanda Weiss-Kelly
Journal: British Journal of Sports Medicine (2017)

The American Medical Society for Sports Medicine recognises a need to provide direction and continually enhance the quality of sports medicine fellowship training programmes. This document was developed to be an educational resource for sports medicine physicians who teach in a 1-year primary care sports medicine fellowship training programme. It is meant to provide high standards and targets for fellowship training programmes that choose to re-assess their curriculum and seek to make improvements.
Hans Tol #PromiseAndDeliver #ToughBrainyStraightforward
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2017)

My first trip as a young sports medicine trainee to the Intercontinental Baseball Cup in Havana, Cuba. It was my very first baseball game, the first time I had to deal with an on-field artery injury and I even rescheduled my PhD defence because I felt that the trip was more valuable than the defence.

Dear Hans, I know your parents emphasised the value of attending classes, but I fully agree that surviving in elite youth football has probably given you more skills.

Without any doubt, the Euro 1988 soccer final between Russia and The Netherlands. Watched the game in a dark room with sunglasses (because of a severe concussion) and just remember the incredible goal of Van Basten (in case you don’t recall, Netherlands won 2–0).

On a macrolevel there is no valuable contribution, but on a microlevel I hope that I motivated some young PhDs, given them freedom and responsibility, assisted them on their way to personal success.

Five golden tips that were useful during my traineeship:

1.  It is all about the numbers. See as many as …
Abstract IA14: Rare codons capacitate Kras-driven de novo tumorigenesis
Authors: Nicole L.K. Pershing, Benjamin L. Lampson, Christopher M. Counter
Journal: Cancer Research (2017)

Abstract The KRAS gene is commonly mutated in human cancers, rendering the encoded small GTPase constitutively active and oncogenic. We discovered that this gene has the unusual feature of having a bias towards rare codons, which are associated with poor translation. Indeed, by changing rare codons to common the amount of KRAS mRNA detected in the heavy fraction by polysome profiling was reduced in lockstep with an increase in protein expression. This poor translation of KRAS has a direct impact on oncogenesis, but curiously, not in the direction one might expect. Specifically, we treated mice in which rare codons in the Kras gene were changed to common with a carcinogen known to induce lung tumors characterized by oncogenic Q61L/R mutations in Kras. Interestingly, these mice exhibited a reduction in tumor burden. Moreover, not only was the altered Kras allele mutated less often, but when it was mutated, completely different mutations were detected, namely G12V/D. We attribute this to a selection against the stronger Q61L/R mutations in favor of weaker G12V mutations in the higher expressed modified Kras allele, as strong oncogenic signaling leads to growth arrest instead of proliferation. As such, the poor translation of KRAS may reduce the chance that an oncogenic mutation induces growth arrest, which perhaps is related to the high frequency this gene is mutated in human cancers or even why specific KRAS mutations map to certain cancers. Citation Format: Nicole L.K. Pershing, Benjamin L. Lampson, Christopher M. Counter. Rare codons capacitate Kras-driven de novo tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA14.
Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution
Authors: Lei Li, Liren Zhu, Cheng Ma, Li Lin, Junjie Yao, Lidai Wang, Konstantin Maslov, Ruiying Zhang, Wanyi Chen, Junhui Shi, Lihong V. Wang
Journal: Nature Biomedical Engineering (2017)
Trends in Hepatitis C-related mortality in Switzerland
Authors: O. Keiser, F. Giudici, P. Bruggmann, J.-F. Dufour, D. Moradpour, D. Semela, M. Heim, B. Müllhaupt, B.T. Beretta-Piccoli, R. Malinverni, F. Negro, A. Spörri
Journal: Journal of Hepatology (2017)
Final Safety and Efficacy Data of Long-Term Open-Label Dosing of Subcutaneous (SC) Romiplostim in Children with Immune Thrombocytopenia (ITP)
Authors: Michael Tarantino, James B. Bussel, Victor S. Blanchette, Donald Beam, John Roy, Jenny M. Despotovic, Ashok Raj, Nancy Carpenter, Bhakti Mehta, Melissa Eisen
Journal: Blood (2016)
A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1)
Authors: J. Inhestern, H. Schmalenberg, A. Dietz, N. Rotter, G. Maschmeyer, M. Jungehülsing, C. Grosse-Thie, T. Kuhnt, M. Görner, H. Sudhoff, C. Wittekindt, O. Guntinas-Lichius
Journal: Annals of Oncology (2017)
Second-line treatments in metastatic gastric cancer: Pooled analysis of randomized clinical trials.
Authors: Manuela Fantini, Lucia Stocchi, Stefania Nicoletti, Emiliano Tamburini, Paolo Fabbri, Antonio Polselli, Fabrizio Drudi, Alessandra Affatato, Lorenzo Gianni, Davide Tassinari
Journal: Journal of Clinical Oncology (2015)

e15062 Background: To assess the role of Second Line Treatments (SLTs) in the treatment of metastatic, pre-treated gastric cancer. Methods: A systematic review of literature in the MEDLINE and EMBASE data bases from 1966 to 2014 was independently performed by two authors (DT and ET) All the randomized phase III trials comparing SLTs with Best Supportive Care (BSC) in the treatment of metastatic, pre-treated gastric cancer were considered eligible and included into the pooled analysis. Overall Survival was the primary end point of the trial; overall survival in the groups of patients treated with chemotherapy (CHT) or biological agents (BA) as SLTs were the secondary ones. Primary and secondary end points were assessed as Hazard Ratio (HR) and 95% Confidence Interval (95CI). Heterogeneity between the trials was assessed using the I2 test; the outcome analysis was performed using a random effects model with an alpha error of 5%. The quality of the selected trials was assessed using the Jadad score. Results: 5 trials met the selection criteria and were included into the pooled analysis. 3 trials compared CHT (docetaxel or irinotecan) vs BSC and 2 trials compared BA (ramucirumab or everolimus) vs BSC. The outcome of 1417 patients included into the 5 trials was analyzed. 911 patients were treated with SLTs and 506 with BSC. 236 patients were treated with CHT and 675 with BA. The pooled HR for the entire population was 0.78 (95CI: 0.565-0.99, p = 0.043) in favour of SLTs and it was 0.642 (95CI: 0.522-0.79, p < 0.001) and 0.855 (95CI: 0.738-0.991, p = 0.039) respectively for the subgroups of CHT and BA. I2 for the entire population was 39.5%, and the quality of all the selected trials was high-to-moderate using the Jadad score. Conclusions: Our analysis confirms that SLTs have to be considered the standard treatment in metastatic, pre-treated gastric cancer. Further trials are probably needed to identify the better schedule in this class of patients with metastatic gastric cancer.
Albumin-Bilirubin grade based novel risk prediction model for patients with hepatocellular carcinoma undergoing chemoembolization
Authors: D.H. Sinn, B.G. Song, W. Kang, G.-Y. Gwak, Y.-H. Paik, J.H. Lee, K.C. Koh, S.W. Paik, M.S. Choi
Journal: Journal of Hepatology (2017)
Suppression of hepatic fibrosis by efficient Col1a1 silencing using shRNA inducible mouse models
Authors: O. Molokanova, K. Schönig, S.-Y. Weng, X. Wang, M. Bros, M. Diken, S. Ohngemach, M. Karsdal, A. Nikolaev, L. Eshkind, D. Schuppan
Journal: Journal of Hepatology (2017)
Mental Health Outcomes After Having or Being Denied an Abortion
Authors: Maureen Curley, Joseph E. Thornton
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
Four weeks of sofosbuvir, ledipasvir and ribavirin with or without interferon give high cure rates in drug users with hepatitis C - a randomized controlled trial (4WIDUC)
Authors: A. L. Øvrehus, I. Birkemose, D. K. Holm, B. K. Moessner, H. Krarup, P. B. Christensen
Journal: Hepatology (2016)
Efficacy of ceritinib in a "real-world" population of crizotinib-refractory ALK-positive NSCLCs: Results of the Italian compassionate use program
Authors: G. Metro, A. Passaro, G. Lo Russo, V. Gregorc, R. Giusti, E. Capelletto, O. Martelli, F.L. Cecere, L. Bonanno, R. Chiari
Journal: Annals of Oncology (2017)
Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing
Authors: Christina Guzzo, David Ichikawa, Chung Park, Damilola Phillips, Qingbo Liu, Peng Zhang, Alice Kwon, Huiyi Miao, Jacky Lu, Catherine Rehm, James Arthos, Claudia Cicala, Myron S. Cohen, Anthony S. Fauci, John H. Kehrl, Paolo Lusso
Journal: Science Immunology (2017)

The intestinal mucosa is a key anatomical site for HIV-1 replication and CD4+ T cell depletion. Accordingly, in vivo treatment with an antibody to the gut-homing integrin α4β7 was shown to reduce viral transmission, delay disease progression, and induce persistent virus control in macaques challenged with simian immunodeficiency virus (SIV). We show that integrin α4β7 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated α4β7 is functionally active as it binds mucosal addressin cell adhesion molecule-1 (MAdCAM-1), promoting HIV-1 capture by and infection of MAdCAM-expressing cells, which in turn mediate trans-infection of bystander cells. Functional α4β7 is present in circulating virions from HIV-infected patients and SIV-infected macaques, with peak levels during the early stages of infection. In vivo homing experiments documented selective and specific uptake of α4β7+ HIV-1 virions by high endothelial venules in the intestinal mucosa. These results extend the paradigm of tissue homing to a retrovirus and are relevant for the pathogenesis, treatment, and prevention of HIV-1 infection.
Impact of itraconazole after first-line chemotherapy on the survival of patients with distant metastatic biliary tract cancer.
Authors: Hiroshi Tsubamoto, Takashi Sonoda, Kayo Inoue, Shinichi Ikuta, Satoshi Tani, Naoki Yamanaka
Journal: Journal of Clinical Oncology (2015)

e15145 Background: The treatment of progressive biliary tract cancer (BTC) after first-line chemotherapy is under investigation. Itraconazole, a common antifungal agent, is a potent inhibitor of P-glycoprotein and the Hedgehog signaling pathway. We aimed to evaluate the efficacy and safety of itraconazole after first-line chemotherapy in patients with BTC. Methods: We retrospectively reviewed data from patients with histologically diagnosed metastatic BTC who had received ≥ 1 lines of chemotherapy and subsequent itraconazole chemotherapy. Results: Twenty-eight patients were enrolled. All these were referred to our institution from tertiary care hospitals. Twenty-three (82%) patients had progressive disease during prior chemotherapy, and 25 (89%) had an Eastern Cooperative Oncology Group performance status of 0. Twenty-six (93%) patients received docetaxel (35 mg/m2), gemcitabine (1,000 mg/m2), and carboplatin (area under the curve, 4 mg·min−1·mL−1) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2. Two patients received docetaxel plus itraconazole with irinotecan. The regimen was repeated every 2 weeks. Two complete responses and 14 partial responses were observed, with a response rate of 57%. Twenty-five (89%) patients switched cytotoxic regimens within 6 cycles. During 160 cycles, 19 (68%), 21 (75%), and 17 (61%) patients had grade 3/4 anemia, neutropenia, and thrombocytopenia, respectively. Nineteen (68%) patients received packed red blood cells, and two (7%) experienced febrile neutropenia. The median overall survival was 12.0 months. Conclusions: Combination chemotherapy with itraconazole after first-line chemotherapy demonstrated favorable efficacy with acceptable toxicities in patients with metastatic BTC.
Clinical characterization and economic impact evaluation of anti-HCV DAA treatment failure: real life data from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER)
Authors: L.A. Kondili, A. Di Leo, A. Iannone, T. Santantonio, A. Giammario, G. Raimondo, R. Filomia, C. Coppola, D. Amoruso, P. Blanc, B. Del Pin, L. Chemello, L. Cavalletto, F. Morisco, L. Donnarumma, M.G. Rumi, A. Gasbarrini, M. Siciliano, M. Massari, R. Corsini, M.R. Brunetto, B. Coco, S. Madonia, A.L. Zignego, M. Monti, F.P. Russo, A. Zanetto, M. Persico, M. Masarone, E. Villa, V. Bernabucci, G. Taliani, E. Biliotti, L. Chessa, M.C. Pasetto, P. Andreone, M. Margotti, G.B. Gaeta, V. Rizzo, D. Ieluzzi, G. Borgia, E. Zappulo, V. Calvaruso, S. Petta, F.R. Rolli, L. Falzano, S. Rosato, M. Ruggeri
Journal: Journal of Hepatology (2017)