tbuckley/cabot-search huggingface dataset:
Functional coupling of endoplasmic reticulum signaling to drug resistance of dormant carcinoma cells
Authors: Aparna C. Ranganathan, Alejandro Adam, Lin Zhang, Sharon J. Sequeira, Julio A. Aguirre-Ghiso
Journal: Cancer Research (2005)

5951   Minimal residual disease, a stage in cancer progression where tumor cells after disseminating from the primary tumor enter into a protracted state of dormancy, is a common clinical phenomenon. Dormancy requires the simultaneous induction of growth arrest and survival programs and dormant disseminated cells are believed to resist chemotherapy due to their low or lack of proliferation. However, due to the lack of proper models to study dormancy, the exact mechanism(s) that allow dormant cells to resist chemotherapy remains unclear. We have established a model of tumor dormancy in human squamous carcinoma (Hep3), where prolonged passaging of these cells in vitro results in a non-clonal acquisition of a dormant phenotype characterized by a spontaneous induction of p38 signaling. Here we show that constitutively activated p38 signaling pathway in dormant cells is linked to the upregulation of BiP/Grp78 and activation of PERK and XBP-1 pathways, all characteristic of an endoplasmic reticulum (ER) stress response. Further, we found that the active ER stress rather than inducing apoptosis selectively protects dormant cells from chemotherapy-induced apoptosis in a proliferation independent manner. Moreover, the signals emanating from ER stress prevent Bax activation, cytochrome-C release and caspase-12 processing. Furthermore, we demonstrate that the mechanism of drug resistance in dormant cells is independent of P-glycoprotein mediated multidrug resistance. We therefore propose that in disseminated dormant cells the high p38 activation and ER stress signaling may serve as a survival mechanism protecting them from stress insults such as chemotherapy. Hence a combinatorial treatment using both conventional chemotherapy and specific ER stress signaling inhibitors may sensitize dormant cells to chemotherapy and favor the eradication of minimal residual disease.
Hemoglobin A<sub>1c</sub> as a Surrogate for Clinical Outcomes in Diabetes Studies
Authors: Brett T. Venker
Journal: JAMA (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 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
Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease
Authors: Derek Klarin, Qiuyu Martin Zhu, Connor A Emdin, Mark Chaffin, Steven Horner, Brian J McMillan, Alison Leed, Michael E Weale, Chris C A Spencer, François Aguet, Ayellet V Segrè, Kristin G Ardlie, Amit V Khera, Virendar K Kaushik, Pradeep Natarajan, Sekar Kathiresan
Journal: Nature Genetics (2017)
Prognostic Significance of IDH1 and IDH2 mutations in Older Patients with Primary Cytogenetically Normal Acute Myeloid Leukemia
Authors: Jinghan Wang, Zhixin Ma, Qinrong Wang, Mengxia Yu, Xiufeng Yin, Xia Li, Shanshan Suo, Dan Shen, Yungui Wang, Xin Huang, Hanzhang Pan, Huanping Wang, Zhimei Chen, Jiansong Huang, Liping Mao, Wenjuan Yu, Juying Wei, Wenbin Qian, Wenyuan Mai, Haitao Meng, Hongyan Tong, Suning Chen, Guido Marcucci, Saijuan Chen, Jie Jin
Journal: Blood (2016)
Resistance Mechanisms to AZD9291 and Rociletinib—Letter
Authors: Nele Van Der Steen, Christian Rolfo, Patrick Pauwels, Adrianus J. de Langen, Godefridus J. Peters, Elisa Giovannetti
Journal: Clinical Cancer Research (2017)

We have read with interest the article by Ortiz-Cuaran and colleagues ([1][1]) on resistance mechanisms to third-generation EGFR tyrosine kinase inhibitors (EGFR-TKI) in lung cancer patients. FISH analysis and targeted sequencing on rebiopsies of these patients were performed, showing that
Interim joint analysis of the ABC (anthracyclines in early breast cancer) phase III trials (USOR 06-090, NSABP B-46I/USOR 07132, NSABP B-49 [NRG Oncology]) comparing docetaxel + cyclophosphamide (TC) v anthracycline/taxane-based chemotherapy regimens (TaxAC) in women with high-risk, HER2-negative breast cancer.
Authors: Joanne Lorraine Blum, Patrick J. Flynn, Greg Yothers, Lina Asmar, Charles E. Geyer, Samuel A. Jacobs, Nicholas J. Robert, James Norman Atkins, Joyce O'Shaughnessy, Chau T. Dang, Henry Leonidas Gomez, Louis Fehrenbacher, Svetislava J. Vukelja, Alan P. Lyss, Devchand Paul, Adam M. Brufsky, Sandra M. Swain, Eleftherios P. Mamounas, Stephen E. Jones, Norman Wolmark
Journal: Journal of Clinical Oncology (2016)

1000 Background: The ABC adjuvant trials (5/2007-11/2013) were developed by USOR and NSABP to determine if a regimen of TC for 6 cycles is non-inferior to combination regimens of doxorubicin/cyclophosphamide with docetaxel or paclitaxel (TaxAC) in women with resected high-risk, HER2-negative breast cancer. 1870 patients (pts) from B-49 were combined with 1077 from the TaxAC and TC groups of B-46-I/USOR 07132, and 1295 from USOR 06-090, for a total of 4242. A detailed history of this collaborative effort will be discussed. Methods: The primary endpoint was invasive disease-free survival (iDFS), defined as time to local, regional or distant recurrence, invasive contralateral breast cancer, second primary cancer, or death. Pts were stratified for: parent trial, pos nodes (0, 1-3, 4-9, 10+), and hormonal status (neg, pos). A hazard ratio (HR) from a stratified Cox model of 1.18 or more was pre-defined as inferior. HRs above 1 favor TaxAC. Our pre-specified interim monitoring plan was to report early for futility if HR was >1.18 when 334 iDFS events were observed (50% of planned 668 events for definitive analysis). Results: 2078 pts randomized to TC and 2052 to TaxAC (total 4130) began assigned therapy and comprise the analysis set. Median follow-up: 3.2 yrs. Pt and tumor characteristics are balanced by treatment: 69% hormone pos, 41% node neg, 51% high grade. With 334 iDFS events, observed HR for TC v TaxAC is 1.202 (95% CI 0.97-1.49), which exceeds 1.18, thus we are reporting early for futility. With 397 iDFS events, 3 yr iDFS is 91.7% for TC v 92.4% for TaxAC. For TNBC: 86.6% v 89.6%, HR, 1.42, (1.04-1.94). For hormone pos: 94.1% v 93.7%, HR, 1.08 (0.84-1.40). Tests for treatment interaction by hormone receptor, nodal status, and protocol were negative. Conclusions: Statistical non-inferiority of the non-anthracycline regime could not be demonstrated. Longer follow-up should clarify the clinical utility of these initial findings. SUPPORT: U10CA-180868, -21115, -189867, -180822, -180820; 180821; 180791; Genentech Clinical trial information: NCT01547741.
Knowledge mapping visualization analysis of the military health and medicine papers published in the web of science over the past 10 years
Authors: Xuan-ming Zhang, Xuan Zhang, Xu Luo, Hai-tao Guo, Li-qun Zhang, Ji-wei Guo
Journal: Military Medical Research (2017)

Military medicine is a research field that seeks to solve the medical problems that occur in modern war conditions based on public medicine theory. We explore the main research topics of military health and medical research in the web of science™ core collection (WoSCC) from 2007 to 2016, and the goal of this work is to serve as a reference for orientation and development in military health and medicine. Based on CiteSpace III, a reference co-citation analysis is performed for 7921 papers published in the WoSCC from 2007 to 2016. In addition, a cluster analysis of research topics is performed with a comprehensive analysis of high-yield authors, outstanding research institutions and their cooperative networks. Currently, the research topics in military health and medicine mainly focus on the following seven aspects: mental health diagnoses and interventions, an army study to assess risk and resilience in service members (STARRS), large-scale military action, brain science, veterans, soldier parents and children of wartime, and wound infection. We also observed that the annual publication rate increased with time. Wessely S, Greenberg N, Fear NT, Smith TC, Smith B, Jones N, Ryan MAK, Boyko EJ, Hull L, and Rona RJ were the top 10 authors in military health and medicine research. The top 10 institutes were the Uniformed Services University of the Health Sciences, the United States Army, the United States Navy, Kings College London, Walter Reed National Military Medical Center, Boston University, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Naval Health Research Center, and the VA Boston Healthcare System. We are able to perform a comprehensive analysis of studies in military health and medicine research and summarize the current research climate and the developmental trends in the WoSCC. However, further studies and collaborations are needed worldwide. Overall, our findings provide valuable information and new perspectives and shape future research directions for further research in the area of military health and medicine.
Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells
Authors: Simon Rauber, Markus Luber, Stefanie Weber, Lisa Maul, Alina Soare, Thomas Wohlfahrt, Neng-Yu Lin, Katharina Dietel, Aline Bozec, Martin Herrmann, Mark H Kaplan, Benno Weigmann, Mario M Zaiss, Ursula Fearon, Douglas J Veale, Juan D Cañete, Oliver Distler, Felice Rivellese, Costantino Pitzalis, Markus F Neurath, Andrew N J McKenzie, Stefan Wirtz, Georg Schett, Jörg H W Distler, Andreas Ramming
Journal: Nature Medicine (2017)
Association of Changes in Diet Quality with Total and Cause-Specific Mortality
Authors: Mercedes Sotos-Prieto, Shilpa N. Bhupathiraju, Josiemer Mattei, Teresa T. Fung, Yanping Li, An Pan, Walter C. Willett, Eric B. Rimm, Frank B. Hu
Journal: New England Journal of Medicine (2017)

Few studies have evaluated the relationship between changes in diet quality over time and the risk of death.
FAS expression inversely correlates with the expression of PTEN and an Akt inhibitor synergizes with FAS siRNA to induce apoptosis in prostate cancer cells
Authors: Sucharita Bandyopadhyay, Sudha K. Pai, Misako Watabe, Steven C. Gross, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Ken Saito, Stephen J. Markwell, Ying Wang, Rui Zhan, Kounosuke Watabe
Journal: Cancer Research (2005)

2260   Fatty Acid Synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer, and is therefore, considered to be an attractive target for anti-cancer therapy. However, relatively little is known about the regulatory mechanisms of the FAS gene in human tumor, and understanding these mechanisms is of paramount interest to design intervention of the FAS enzymatic pathway. Thus far, several factors including androgen, epidermal growth factor (EGF), PTEN and p53 have been demonstrated to modulate the expression of the FAS gene  in vitro , however, none of these results have been validated in the clinical setting. In the present study, by immunohistochemical analysis of 81 prostate cancer specimens, we demonstrate that expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression  in vivo . Furthermore, we used siRNA to inhibit the PTEN gene expression  in vitro  and found that knocking down the PTEN gene leads to overexpression of FAS  in vitro . Together, these results suggest that the tumor suppressor gene, PTEN, negatively regulates the expression of the FAS gene. Our immunohistochemical analysis followed by Cox regression analysis also revealed that the combination of PTEN and FAS gene expression was an independent prognostic marker for prostate cancer. These data underscore the prognostic importance of combination of the FAS and PTEN genes, and also point toward the clinical relevance of the PTEN-FAS pathway in prostate tumorigenesis. As an initial trial for therapeutic targeting, we also used siRNA specific to the FAS gene  in vitro . Our results indicated that the treatment of prostatic tumor cells with FAS siRNA leads to growth inhibition followed by apoptosis. Furthermore, in order to explore the possibility that the PTEN signaling pathway can be utilized to synergize the FAS siRNA mediated apoptosis, we introduced FAS siRNA and PI3K inhibitor into prostate cancer cells, and found that the PI3K inhibitor indeed synergized the effect of siRNA leading to tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.
Central nervous system relapse of diffuse large B-cell lymphoma in the rituximab era: results of the UK NCRI R-CHOP-14 versus 21 trial
Authors: M. Gleeson, N. Counsell, D. Cunningham, N. Chadwick, A. Lawrie, E.A. Hawkes, A. McMillan, K.M. Ardeshna, A. Jack, P. Smith, P. Mouncey, C. Pocock, J.A. Radford, J. Davies, D. Turner, A. Kruger, P. Johnson, J. Gambell, D. Linch
Journal: Annals of Oncology (2017)

BackgroundCentral nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial.Patients and methodsThe R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥18 years with bulky stage I–IV DLBCL (n = 1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated.Results177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX)n = 163, intravenous (IV) MTXn = 2, prophylaxis type unknownn = 11 and IT MTX and cytarabinen = 1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolatedn = 11, with systemic relapsen = 10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI, >1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively.ConclusionDespite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence.ClinicalTrials.govISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.
British Society for Paediatric Dermatology
Journal: British Journal of Dermatology (2009)

British Journal of DermatologyVolume 161, Issue s1 p. 115-127 British Society for Paediatric Dermatology First published: 01 June 2009 https://doi.org/10.1111/j.1365-2133.2009.09172.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume161, Issues1Special Issue: Abstracts of the 89th Annual Meeting of the British Association of Dermatologists, 7-10 July 2009, Glasgow, UKJuly 2009Pages 115-127 RelatedInformation
An open-label, multicohort, phase I/II study to evaluate nivolumab in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC).
Authors: Jean-Pierre Delord, Antoine Hollebecque, J. P. De Boer, Jacques De Greve, Jean-Pascal H. Machiels, Rom S. Leidner, Robert L. Ferris, Shangbang Rao, Ibrahima Soumaoro, Z. Alexander Cao, Hyunseok Kang, Suzanne Louise Topalian
Journal: Journal of Clinical Oncology (2017)

6025 Background: Treatment options for patients (pts) with R/M NPC are limited to palliative chemotherapy. NPC is often associated with the Epstein–Barr virus (EBV), a potential antigen for immune recognition, and high expression levels of the immune checkpoint receptor programmed death-1 (PD-1) and its major ligand PD-L1. Nivolumab disrupts PD-1–mediated signaling, restoring T-cell antitumor function. Methods: In CheckMate 358 (NCT02488759), PD-L1–unselected adults with R/M NPC, ECOG PS of 0–1, and ≤2 prior systemic therapies in the R/M setting were eligible to receive nivolumab 240 mg every 2 weeks until progression or unacceptable toxicity, as part of an ongoing multicohort study of 5 virus-associated cancers. Human papillomavirus-associated NPC and keratinizing squamous cell carcinoma (WHO Type 1) were excluded. Primary endpoints were objective response rate (ORR) and safety; secondary endpoints were duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: Of 24 treated pts with R/M NPC, median age was 51 years, 88% were male, 62% were white, 88% were European, and 88% had EBV+ tumors. At a median follow-up of 26 weeks (range: 4–40), ORR was 20.8% and appeared to be higher in pts with no prior R/M therapy (Table). The disease control rate (ORR + SD) was 45.8%. Responses were observed regardless of PD-L1 or EBV status. Median PFS was 2.4 mo (95% CI: 1.5, NR); median OS was NR. Conclusions: Nivolumab demonstrated clinical activity and a manageable safety profile in R/M NPC, supporting ongoing research with nivolumab in this disease. Updated efficacy and biomarker data will be presented. Clinical trial information: NCT02488759. [Table: see text]
Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation
Authors: Adem Yildirim, Rajarshi Chattaraj, Nicholas T. Blum, Dennis Shi, Kaushlendra Kumar, Andrew P. Goodwin
Journal: Advanced Healthcare Materials (2017)

The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL-1 (7 × 109 particles mL-1 ). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C.
Fabrication of Tissue-Engineered Bionic Urethra Using Cell Sheet Technology and Labeling By Ultrasmall Superparamagnetic Iron Oxide for Full-Thickness Urethral Reconstruction
Authors: Shukui Zhou, Ranxin Yang, Qingsong Zou, Kaile Zhang, Ting Yin, Weixin Zhao, Joseph G. Shapter, Guo Gao, Qiang Fu
Journal: Theranostics (2017)

Urethral strictures remain a reconstructive challenge, due to less than satisfactory outcomes and high incidence of stricture recurrence.An "ideal" urethral reconstruction should establish similar architecture and function as the original urethral wall.We fabricated a novel tissue-engineered bionic urethras using cell sheet technology and report their viability in a canine model.Small amounts of oral and adipose tissues were harvested, and adipose-derived stem cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated and used to prepare cell sheets.The cell sheets were hierarchically tubularized to form 3-layer tissue-engineered urethras and labeled by ultrasmall super-paramagnetic iron oxide (USPIO).The constructed tissue-engineered urethras were transplanted subcutaneously for 3 weeks to promote the revascularization and biomechanical strength of the implant.Then, 2 cm length of the tubularized penile urethra was replaced by tissue-engineered bionic urethra.At 3 months of urethral replacement, USPIO-labeled tissue-engineered bionic urethra can be effectively detected by MRI at the transplant site.Histologically, the retrieved bionic urethras still displayed 3 layers, including an epithelial layer, a fibrous layer, and a myoblast layer.Three weeks after subcutaneous transplantation, immunofluorescence analysis showed the density of blood vessels in bionic urethra was significantly increased following the initial establishment of the constructs and was further up-regulated at 3 months after urethral replacement and was close to normal level in urethral tissue.Our study is the first to experimentally demonstrate 3-layer tissue-engineered urethras can be established using cell sheet technology and can promote the regeneration of structural and functional urethras similar to normal urethra.