tbuckley/cabot-search huggingface dataset:
Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance
Authors: B. Solomon, R.J. Young, M. Bressel, J. Cernelc, P. Savas, H. Liu, D. Urban, A. Thai, C. Cooper, T. Fua, P. Neeson, S. Loi, S.V. Porceddu, D. Rischin
Journal: Annals of Oncology (2019)

BackgroundAccurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC.Patients and methodsThe abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis.ResultsHigh intratumoral abundance of CD103+ immune cells using a ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02–0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02–1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs.ConclusionQuantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies.
Targeted Inhibition of STAT/TET1 Axis As a Potent Therapeutic Strategy for Acute Myeloid Leukemia
Authors: Xi Jiang, Chao Hu, Kyle Ferchen, Ji Nie, Xiaolong Cui, Chih-Hong Chen, Liting Cheng, Zhixiang Zuo, William Seibel, Chunjiang He, Yixuan Tang, Jennifer R Skibbe, Mark Wunderlich, William C Reinhold, Lei Dong, Chao Shen, Stephen Arnovitz, Bryan Ulrich, Jiuwei Lu, Hengyou Weng, Rui Su, Huilin Huang, Yungui Wang, Chenying Li, Xi Qin, James C. Mulloy, Yi Zheng, Jiajie Diao, Jie Jin, Chong Li, Paul P Liu, Chuan He, Yuan Chen, Jianjun Chen
Journal: Blood (2017)
Hernia: Its Etiology, Symptoms and Treatment.
Journal: JAMA (1901)

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
Pregnancy duration and endometrial cancer risk: nationwide cohort study
Authors: Anders Husby, Jan Wohlfahrt, Mads Melbye
Journal: BMJ (2019)

Abstract Objective To explore the association between pregnancy duration and risk of endometrial cancer. Design Nationwide register based cohort study. Setting Denmark. Participants All Danish women born from 1935 to 2002. Main outcome measures Relative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression. Results Among 2 311 332 Danish women with 3 947 650 pregnancies, 6743 women developed endometrial cancer during 57 347 622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results. Conclusions The risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.
Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study
Authors: Navein Arumugasaamy, Alana Gudelsky, Amelia Hurley‐Novatny, Peter C. W. Kim, John P. Fisher
Journal: Advanced Healthcare Materials (2019)

Abstract Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple studies have shown that taking SSRIs during pregnancy can lead to preterm birth and potential health concerns for the baby. Therefore, a biomimetic placental barrier model is utilized herein to assess transport profiles and phenotypic effects resulting from SSRI exposure, comparing fluoxetine and sertraline. Results show that the placental barrier quickly uptakes drug from the maternal side, but slowly releases on the fetal side. Phenotypically, there is a dose‐dependent change in cell adhesion molecule (CAM) and transforming growth factor beta (TGFβ) secretions, markers of cell adhesion and angiogenesis. Both drugs impact CAM secretions, whereas sertraline alone impacts TGFβ secretions. When evaluating cell type, it becomes clear that endothelial cells, not trophoblast, are the main cell type involved in these phenotypic changes. Overall, these findings further the understanding of SSRI transplacental transport and drug‐induced effects on the placental barrier.
Sex Differences in Grant Funding
Authors: Howard M. Kravitz
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Quantitative analysis of EGFR-mediated glioblastoma migration reveals increased directional persistence in 3D extracellular matrices in contrast to decreased persistence on 2D substrata.
Authors: Hyung-Do Kim, Angela Wu, Frank Gertler, Douglas Lauffenburger
Journal: Cancer Research (2007)

2548  Enhanced chemokinetic and chemotactic motility stimulated by signals transduced through the ErbB family of receptors has been shown to play a critical role in tissue invasion by a variety of solid tumor types. Most efforts in studying the role of the epidermal growth factor receptor (EGFR) and its downstream signals in regulating the biophysical processes of cell motility have been carried out in two-dimensional (2D) systems, whereas in vivo migration occurs through three-dimensional (3D) spaces consisting of the extracellular matrix (ECM). With the additional mechanical and sterical influences posed by the ECM, disruption of EGFR-signaling components of cells migrating in 3D may exhibit effects that are distinct from 2D cell migration.  In this work, we developed and optimized a 3D time-lapse confocal microscopy technique to image and quantify real-time 3D migration behavior of individual U87MG human glioblastoma cells sparsely seeded in collagen I gels. EGF stimulation exhibited matrix-concentration dependent increase in 3D cell scattering through both greater cell speed and greater directional persistence. This was in contrast to previous reports that EGF stimulation leads to an increased cell speed, but a decrease in persistence in 2D. Over-expression of Mena, a target downstream of EGFR, in U87MG cells led to decrease in persistence on 2D surfaces, but was correlated with increased persistence in 3D and in vivo. Supported by computer simulations, we propose that low directional persistence in 2D may, at least under some conditions, translate into high directional persistence in a porous 3D ECM network.
Is it time to change the reference genome?
Authors: Sara Ballouz, Alexander Dobin, Jesse A. Gillis
Journal: Genome biology (2019)

The use of the human reference genome has shaped methods and data across modern genomics. This has offered many benefits while creating a few constraints. In the following opinion, we outline the history, properties, and pitfalls of the current human reference genome. In a few illustrative analyses, we focus on its use for variant-calling, highlighting its nearness to a ‘type specimen’. We suggest that switching to a consensus reference would offer important advantages over the continued use of the current reference with few disadvantages.
The Indenoisoquinoline TOP1 Inhibitors Selectively Target Homologous Recombination-Deficient and Schlafen 11-Positive Cancer Cells and Synergize with Olaparib
Authors: Laetitia Marzi, Ludmila Szabova, Melanie Gordon, Zoe Weaver Ohler, Shyam K. Sharan, Michael L. Beshiri, Moudjib Etemadi, Junko Murai, Kathleen Kelly, Yves Pommier
Journal: Clinical Cancer Research (2019)

Irinotecan and topotecan are used to treat a variety of different cancers. However, they have limitations, including chemical instability and severe side effects. To overcome these limitations, we developed the clinical indenoisoquinolines: LMP400 (indotecan), LMP776 (indimitecan), and LMP744. The purpose of the study is to build the molecular rationale for phase II clinical trials.
A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia
Authors: Philip T. James, Ousubie Jawla, Nuredin I. Mohammed, Kabiru Ceesay, Fatai M. Akemokwe, Bakary Sonko, Ebrima A. Sise, Andrew M. Prentice, Matt J. Silver
Journal: PLoS Medicine (2019)

Infant DNA methylation profiles are associated with their mother's periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials.We designed a novel drink powder based on determinants of plasma homocysteine in the target population and tested it in a three-arm, randomised, controlled trial. Nonpregnant women aged between 18 and 45 from the West Kiang region of The Gambia were randomised in a 1:1:1 allocation to 12 weeks daily supplementation of either (a) a novel drink powder (4 g betaine, 800 μg folic acid, 5.2 μg vitamin B12, and 2.8 mg vitamin B2), (b) a widely used multiple micronutrient tablet (United Nations Multiple Micronutrient Preparation [UNIMMAP]) containing 15 micronutrients, or (c) no intervention. The trial was conducted between March and July 2018. Supplementation was observed daily. Fasted venepuncture samples were collected at baseline, midline (week 5), and endline (week 12) to measure plasma homocysteine. We used linear regression models to determine the difference in homocysteine between pairs of trial arms at midline and endline, adjusted for baseline homocysteine, age, and body mass index (BMI). Blood pressure and pulse were measured as secondary outcomes. Two hundred and ninety-eight eligible women were enrolled and randomised. Compliance was >97.8% for both interventions. At endline (our primary endpoint), the drink powder and UNIMMAP reduced mean plasma homocysteine by 23.6% (-29.5 to -17.1) and 15.5% (-21.2 to -9.4), respectively (both p < 0.001), compared with the controls. Compared with UNIMMAP, the drink powder reduced mean homocysteine by 8.8% (-15.8 to -1.2; p = 0.025). The effects were stronger at midline. There was no effect of either intervention on blood pressure or pulse compared with the control at endline. Self-reported adverse events (AEs) were similar in both intervention arms. There were two serious AEs reported over the trial duration, both in the drink powder arm, but judged to be unrelated to the intervention. Limitations of the study include the use of a single targeted metabolic outcome, homocysteine.The trial confirms that dietary supplements can influence metabolic pathways that we have shown in previous studies to predict offspring DNA methylation. Both supplements reduced homocysteine effectively and remain potential candidates for future epigenetic trials in pregnancy in rural Gambia.Clinicaltrials.gov Reference NCT03431597.
Intracellular glutathione levels determine sensitivity to fenretinide.
Authors: Tapiwanashe Magwere, Susan Burchill
Journal: Cancer Research (2008)

3758  Glutathione (GSH) is a multi-functional tripeptide that plays a crucial role in antioxidant defence, detoxification of xenobiotics, and maintenance of cellular redox balance. The antioxidant capacity of GSH could thus be involved in modulating the cytotoxicity of reactive oxygen species (ROS)-producing anticancer agents such as fenretinide. In this study we have tested the hypothesis that the sensitivity of Ewing’s sarcoma family of tumours (ESFT) to fenretinide is determined by the antioxidant capacity of GSH, and investigated whether the decreased sensitivity of cells to fenretinide in hypoxia is dependent on modulation of GSH. Whether depletion of intracellular GSH enhances the cytotoxicity of fenretinide was also investigated.  Cellular GSH levels were measured using the Glutathione Assay Kit™ (Cayman Europe). Viable cell number was determined using the trypan blue exclusion assay (Beckman Coulter). GSH was depleted by treating cells with L-buthionine-S,R-sulfoximine (BSO, 0-50µM).  Total GSH and mitochondrial GSH levels were variable by up to 8- and 13-fold respectively in the ESFT cell lines studied. The GSH/GSSG ratio (a marker for cellular redox status) was below 20 for all ESFT cell lines, indicating that they were oxidatively stressed in culture and might be extremely sensitive to oxidative challenges. There was a positive correlation between total (p
Symmetric conflicts also allow for the investigation of attack and defense
Authors: Joachim Hüffmeier, Jens Mazei
Journal: Behavioral and Brain Sciences (2019)

Abstract De Dreu and Gross argue that only asymmetric games allow the motives underlying defense and attack to be disentangled. However, the Prisoner's Dilemma Game Alt matrix (PDG-Alt matrix), a modified symmetric PDG, also allows these motives to be disentangled. Studies using the PDG-Alt matrix produced findings contradicting a central claim of De Dreu and Gross.
Normalization of Survival and No Relapses after One Year in Adult Burkitt Lymphoma Patients Treated with Intensive Immunochemotherapy: An International Study of 159 Real-World Patients
Authors: Lasse H. Jakobsen, Fredrik Ellin, Knut B. Smeland, Tove Wästerlid, Jacob H. Christensen, Judit Jørgensen, Pär L. Josefsson, Harald Holte, Yngvild N. Blaker, Jacob H. Grauslund, Jon Bjørn, Daniel Molin, Ingemar Lagerlöf, Karin Ekstroem Smedby, Katherine Colvin, Gita Thanarajasingam, Alina S. Gerrie, Chan Y. Cheah, Tarec C. El-Galaly
Journal: Blood (2018)
Endothelial IQGAP1 regulates leukocyte transmigration by directing the LBRC to the site of diapedesis
Authors: David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller
Journal: The Journal of Experimental Medicine (2019)

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. This is the first reported function of IQGAP1 requiring two domains to be present on the same polypeptide. Additionally, we show for the first time that IQGAP1 in the endothelium is required for efficient TEM in vivo. These findings reveal a novel function for IQGAP1 and demonstrate that IQGAP1 in endothelial cells facilitates TEM by directing the LBRC to the site of TEM.
Abstract #1962: The Androgen Receptor regulates miR-21 to promote hormone dependent and independent prostate cancer growth
Authors: Judit Ribas, Xiaohua Ni, Michael Haffner, Erik Wentzel, Amirali Salmasi, Wasim Chowdhury, Tarana KudrollI, Srinivasa Yegnasubramanian, Jun Luo, Ron Rodriguez, Joshua Mendell, Shawn Lupold
Journal: Cancer Research (2009)

Abnormal Androgen Receptor (AR) activity contributes to prostate cancer pathogenesis, including hormone refractory disease. However, the downstream AR proliferative pathways are not fully described. We hypothesized that the activated androgen receptor may directly regulate the expression of certain microRNAs (miRNAs), and that these miRNAs may then contribute to the prostate cancer phenotype. In pursuit of these studies, we have established conditions whereby the expected androgen-regulated cell growth and gene expression responses were reproduced in LNCaP and LAPC-4 prostate cancer models. Using these conditions and microarray technology, we evaluated dose-responsive androgen-regulated microRNA expression of over 400 known microRNAs. Here we report the identification of 19 AR responsive miRNAs including the oncogenic miRNA miR-21. We present data demonstrating that miR-21 is directly regulated by the activated AR through chromatin immunoprecipitation assays. This induced miR-21 contributes to androgen induced cell proliferation. Further, we report that ectopic expression of miR-21 alone is sufficient to drive androgen-independent growth. LNCaP cells expressing miR-21 develop more tumors and at an earlier time point than those expressing a vector control. Moreover, miR-21 expressing LNCaP tumors are resistant to castration. Elevated miR-21 expression was also found in human CaP tumors. Collectively, these data place miR-21 in the AR signaling pathway and suggest that miR-21 can contribute to the castration resistant prostate cancer phenotype.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1962.
Overexpression of Histone H3 Lysine 27 Trimethylation Is Associated with Aggressiveness and Dedifferentiation of Thyroid Cancer
Authors: Chia-Chi Tsai, Ming-Nan Chien, Yuan-Ching Chang, Jie-Jen Lee, Shuen-Han Dai, Shih-Ping Cheng
Journal: Endocrine Pathology (2019)
Dual epidermal growth factor receptor (EGFR) inhibition: Phase I study combining cetuximab (C225) and erlotinib (E) in advanced solid tumors
Authors: R. Sangha, C. Ho, L. Beckett, D. H. Lau, P. N. Lara, A. M. Davies, P. C. Mack, G. M. Koslan, W. S. Holland, D. R. Gandara
Journal: Journal of Clinical Oncology (2009)

3552 Background: The EGFR pathway is implicated in lung tumorigenesis by aberrantly regulating cell proliferation, apoptosis, and invasion. Maximal blockade of the EGFR can be achieved by dually inhibiting the extracellular and intracellular domain with the monoclonal antibody C225 and the tyrosine kinase inhibitor, E. Given preclinical synergy of C225 and E, we hypothesized this combination would be feasible and result in improved therapeutic benefit. Methods: Patients (pts) with advanced solid tumors were enrolled using a standard phase I dose escalation design. C225 was administered IV weekly, with no loading dose, and E given orally daily on a 28-day cycle. Four dose levels were studied: C225 150 mg/m 2 , E 100 mg; C225 200 mg/m 2 , E 100 mg; C225 250 mg/m 2 , E 100 mg; and C225 250 mg/m 2 , E 150 mg. Dose limiting toxicity (DLT) was defined as: grade (Gr) 4 platelets, Gr 3 platelets with bleeding, febrile neutropenia, ≥ Gr 3 ANC with documented infection, or clinically significant &gt; Gr 3 non-hematologic toxicity. Gr 3 rash based solely on pain or Gr 3 hypersensitivity infusion reactions were not considered DLTs. Results: 18 pts were treated: 13 NSCLC, 3 H&amp;N, 1 pancreas, and 1 invasive thymoma. Characteristics: Age range 41–80, median 62.5; Gender: 7 M; ECOG PS ≤1 = 17; Prior chemo ≤1 = 10. Planned dose escalation was completed without reaching the MTD. The highest dose level was expanded to 6 pts. A single DLT for Gr 3 diarrhea was observed at the second dose level (C225 200 mg/m 2 , E 100 mg). Gr 3/4 toxicities were: lymphopenia (3), acneiform rash (3), nausea/vomiting (3), pruritis (1), fatigue (1), diarrhea (1), confusion (1), hypomagnesemia (1), hypocalcemia (1), hyponatremia (1), hyperkalemia (1), and anemia (1). Of 13 evaluable pts, 1 PR (NSCLC) and 4 with SD (2 NSCLC, 2 H&amp;N). Median cycles: 2 (1–14) with one NSCLC pt on therapy for 8 cycles and one H&amp;N pt receiving 14 cycles. Biomarker analysis of EGFR polymorphisms, gene copy number via FISH, and protein expression will be presented, along with the mutation status of EGFR and KRAS. Conclusions: 1) Dual EGFR inhibition with C225 250 mg/m 2 weekly and E 150 mg daily is feasible, well tolerated, and the recommended phase II dose. 2) Efficacy of this combination in NSCLC is being evaluated in a phase II trial. [Table: see text]