tbuckley/cabot-search huggingface dataset:
From the CLEOPATRA study to real life: An observational study from 11 Italian Centres; Preliminary report from the G.O.N.O. SUPER trial.
Authors: Ornella Garrone, Chiara Saggia, Alessandra Beano, Federica Cicchiello, Andrea Milani, Ilaria Bertolini, Luigi Coltelli, Nicla Maria La Verde, Elena Collovà, Enrico De Conciliis, Fulvia Pedani, Anna Maria Vandone, Michela Donadio, Marina Elena Cazzaniga, Andrea Michelotti, Marco Carlo Merlano
Journal: Journal of Clinical Oncology (2017)

e12510 Background: Approximately 20% of breast cancers (BC) are HER-2+. Trastuzumab (T) has substantially improved the outcome, both in early and in advanced settings, in HER-2+BC. Pertuzumab (P), combined with T and taxanes, ameliorated progression free survival (PFS) and overall survival (OS) in the phase III CLEOPATRA study. In order to verify the results of the trial in unselected patients (pts), we performed a multicenter, retrospective-prospective, observational study, in HER-2+ metastatic BC (MBC) pts. Methods: We analyze the outcome of all HER-2+ MBC pts treated with P+T and taxanes, as first line therapy since the availability of P in Italy, at 11 general and university hospitals. Results: Up to February 1 st data from 103 HER-2+ MBC pts were recorded. Main pts’ characteristics were: median (M) age 52 y (28-78), m ECOG PS 0 (0-2), ER/PgR positive 68 pts (66%). Most common metastatic sites: liver 51 pts (49.5%), bone 64 pts (62.1%), lung 26 pts (25.2%). Thirty pts (29.1%) had bone and soft tissue disease only; 78 pts (75.7%) had metastatic disease on presentation. m number of metastatic sites was 3 (1-7); 25 pts (24.3%) received neo/adjuvant chemotherapy (CT) + T and 36 pts (34.9%) adjuvant endocrine therapy; 71 pts (69%) and 32 pts (31%) received docetaxel (D) and paclitaxel (P) respectively. m number of CT cycles was 6 for both drugs (D range 3-12; P range 1-18).At the time of the present analysis 12 pts are still on CT and 78 on maintenance; response is available for 91 pts and ORR is 80.2% (22 pts and 51 pts obtained CR and PR respectively), 6 pts experienced PD during CT. Median PFS is 13.9 months (1.5+ - 33.8+).Among hematological toxicities leucopenia (any grade) was recorded in 29 pts (28.1%), g 3 febrile neutropenia in 6 pts (5.8%). No change of left ventricular ejection fraction (LVEF) was recorded during CT; 4 pts interrupted maintenance P due to drop in LVEF and 1 due to rash. Onicopathy, nausea, alopecia, rash and arthro-myalgia were the most common non-hematological toxicities. Conclusions: Our preliminary results highlight the activity and the safety of the combination of CT plus P and T in unselected HER2+ MBC patients. The study is ongoing and updated results will be presented.
Covalent nano delivery systems for selective imaging and treatment of brain tumors
Authors: Julia Y. Ljubimova, Tao Sun, Leila Mashouf, Alexander V. Ljubimov, Liron L. Israel, Vladimir A. Ljubimov, Vida Falahatian, Eggehard Holler
Journal: Advanced Drug Delivery Reviews (2017)

Nanomedicine is a rapidly evolving form of therapy that holds a great promise for superior drug delivery efficiency and therapeutic efficacy than conventional cancer treatment. In this review, we attempt to cover the benefits and the limitations of current nanomedicines with special attention to covalent nano conjugates for imaging and drug delivery in the brain. The improvement in brain tumor treatment remains dismal despite decades of efforts in drug development and patient care. One of the major obstacles in brain cancer treatment is the poor drug delivery efficiency owing to the unique blood-brain barrier (BBB) in the CNS. Although various anti-cancer agents are available to treat tumors outside of the CNS, the majority fails to cross the BBB. In this regard, nanomedicines have increasingly drawn attention due to their multi-functionality and versatility. Nano drugs can penetrate BBB and other biological barriers, and selectively accumulate in tumor cells, while concurrently decreasing systemic toxicity.
Blockade of adenosine A2A receptor enhances CD8+ T cells response and decreases regulatory T cells in head and neck squamous cell carcinoma
Authors: Si-Rui Ma, Wei-Wei Deng, Jian-Feng Liu, Liang Mao, Guang-Tao Yu, Lin-Lin Bu, Ashok B. Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
Journal: Molecular Cancer (2017)

Cancer immunotherapy offers a promising approach in cancer treatment. The adenosine A2A receptor (A2AR) could protect cancerous tissues from immune clearance via inhibiting T cells response. To date, the role of A2AR in head and neck squamous cell carcinoma (HNSCC) has not been investigated. Here, we sought to explore the expression and immunotherapeutic value of A2AR blockade in HNSCC.The expression of A2AR was evaluated by immunostaining in 43 normal mucosae, 48 dysplasia and 165 primary HNSCC tissues. The immunotherapeutic value of A2AR blockade was assessed in vivo in genetically defined immunocompetent HNSCC mouse model.Immunostaining of HNSCC tissue samples revealed that increased expression of A2AR on tumor infiltrating immune cells correlated with advanced pathological grade, larger tumor size and positive lymph node status. Elevated A2AR expression was also detected in recurrent HNSCC and HNSCC tissues with induction chemotherapy. The expression of A2AR was found to be significantly correlated with HIF-1α, CD73, CD8 and Foxp3. Furthermore, the increased population of CD4+Foxp3+ regulatory T cells (Tregs), which partially expressed A2AR, was observed in an immunocompetent mouse model that spontaneously develops HNSCC. Pharmacological blockade of A2AR by SCH58261 delayed the tumor growth in the HNSCC mouse model. Meanwhile, A2AR blockade significantly reduced the population of CD4+ Foxp3+ Tregs and enhanced the anti-tumor response of CD8+ T cells.These results offer a preclinical proof for the administration of A2AR inhibitor on prophylactic experimental therapy of HNSCC and suggest that A2AR blockade can be a potential novel strategy for HNSCC immunotherapy.
Could the Adoption of Unleaded Gasoline in the 1970s Play a Role in the Precipitous Decline in Dementia Prevalence?—Reply
Authors: Kenneth M. Langa, Eric B. Larson, David R. Weir
Journal: JAMA Internal Medicine (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 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
CMV-specific T-cell immunity in solid organ transplant recipients at low risk of CMV infection. Chronology and applicability in preemptive therapy
Authors: Juan Damián Mena-Romo, Pilar Pérez Romero, Cecilia Martín-Gandul, Miguel Ángel Gentil, Gonzalo Suárez-Artacho, Ernesto Lage, Magdalena Sánchez, Elisa Cordero
Journal: Journal of Infection (2017)
Prospective study of magnetic resonance imaging (MRI) and multiparameter gene expression assay in ductal carcinoma in situ (DCIS): A trial of the ECOG-ACRIN Cancer Research Group (E4112).
Authors: Seema Ahsan Khan, Constantine Gatsonis, Brad Snyder, Constance D Lehman, Joseph A. Sparano, Lawrence J. Solin, Sunil S. Badve, Ralph L Corsetti, Habib Rahbar, Derrick W Spell, Kenneth Bruce Blankstein, LInda K Han, Jennifer L. Sabol, John R Bumberry, Kathy D. Miller, Christopher Comstock
Journal: Journal of Clinical Oncology (2017)

534 Background: Prior retrospective studies have evaluated breast MRI in DCIS, and prospective-retrospective biomarker studies have shown that the DCIS Score is prognostic for recurrence after BCS alone. E4112 is a prospective cohort study designed to assess the combined impact of breast MRI and DCIS Score on surgical and RT management. Methods: Women diagnosed with screen-detected DCIS on core biopsy, if BCS eligible, underwent breast MRI. Those remaining so following MRI and related biopsies, with no invasive disease, underwent BCS. If final surgical margins were ≥2 mm, the DCIS lesion was submitted for DCIS Score assay. Women with low DCIS Score (≤39, LS) were advised that RT could be avoided; RT was recommended to those with high/intermediate (H/I) scores. The primary objective was to estimate the fraction converting to mastectomy (Mx) following MRI. Secondary objectives included estimation of re-operation rates after first BCS, and DCIS Score distribution.A sample size of 333 evaluable women would allow estimation of Mx rate of 12% with 95% confidence interval 9-16%. Results: 334 enrolled women had completed surgery; the first surgical procedure was Mx in 54 (16.2%) and BCS in 280 (83.8%), of whom 62 (22.1%) required at least one re-excision, and 11 (3.9%) converted to Mx. DCIS Scores were obtained on 171 patients who completed BCS, of whom 82 were LS and 89 were H/I. Demographics were similar between the two groups, other features will be reported. Only 7/82 (8.5%) of the LS group received RT, whereas 82/89 (92.1%) of the H/I group received RT. Of the 98 BCS patients who did not qualify for DCIS Score-based therapy, 23 had invasive disease, 34 had final surgical margins &lt; 2 mm, and 13 had both. There was insufficient tissue for DCIS Score in 11, and 17 did not complete follow-up. Conclusions: In this study, among DCIS patients who were BCS-eligible following MRI, total mastectomy rate was 19.5%; re-excision rate was 22.1% for women who had BCS. Approximately half had low DCIS Scores, and RT recommendations based on the DCIS Score were acceptable to most women. Clinical trial information: E4112.
Alternative splicing of hepatitis B virus: A novel virus/host interaction altering liver immunity
Authors: Marion Duriez, Yassmina Mandouri, Bouchra Lekbaby, Hualin Wang, Aurélie Schnuriger, Francois Redelsperger, Chiara Ida Guerrera, Marine Lefevre, Veronique Fauveau, James Ahodantin, Ivan Quetier, Cerina Chhuon, Samir Gourari, Alexandre Boissonnas, Upkar Gill, Patrick Kennedy, Nabil Debzi, Delphine Sitterlin, Mala K. Maini, Dina Kremsdorf, Patrick Soussan
Journal: Journal of Hepatology (2017)
c-Myc is Required for BRAF<sup>V600E</sup>-Induced Epigenetic Silencing by H3K27me3 in Tumorigenesis
Authors: Yiping Qu, Qi Yang, Juan Liu, Bingyin Shi, Meiju Ji, Gang Li, Peng Hou
Journal: Theranostics (2017)

BRAFV600E mutation is frequently found in human cancers particularly thyroid cancer and melanoma, and is involved in the regulation of gene expression through activating MAPK/Erk signaling. Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing in tumorigenesis. However, molecular mechanism underlying the complex interplay between these two molecular events remains to be explored. In the present study, we conducted chromatin immunoprecipitation combined with next-generation sequencing (ChIP-Seq) and expression microarray analysis in NIH3T3 cells to explore the relationship between H3K27me3 and transcriptional regulation by BRAFV600E mutation. Our results showed that activated MAPK/Erk signaling by BRAFV600E mutation was a trigger of this epigenetic processing at many downstream target genes in cancer cell lines and BrafV600E-induced thyroid cancer of transgenetic mice. By integrating ChIP-Seq and gene expression microarray data, we identified 150 down-regulated loci with increased levels of H3K27me3 in BRAF-mutant cells relative to BRAF wild-type cells. Our data also demonstrated that c-Myc, a downstream key effector of BRAFV600E signaling, was required for BRAFV600E-induced changes in H3K27me3 through regulating the components of the polycomb repressive complex 2 (PRC2) genes Ezh2, Suz12 and Jarid2 at both transcriptional levels via direct binding to their regulatory elements and post-transcriptional levels via repressing the miR-26a, miR-200b and miR-155. In addition, BRAFV600E also caused gene silencing through Erk1/2-induced RNA polymerase II (RNAPII) poising and chromatin architecture. Collectively, our data uncover a previously unknown epigenetic mechanism in the tumorigenesis of BRAFV600E-driven cancers.
Combined immune checkpoint blockade as a therapeutic strategy for <i>BRCA1</i> -mutated breast cancer
Authors: Emma Nolan, Peter Savas, Antonia N. Policheni, Phillip K. Darcy, François Vaillant, Christopher P. Mintoff, Sathana Dushyanthen, Mariam Mansour, Jia-Min B. Pang, Stephen B. Fox, Charles M. Perou, Jane E. Visvader, Daniel H. D. Gray, Sherene Loi, Geoffrey J. Lindeman
Journal: Science Translational Medicine (2017)

BRCA1 -mutated tumors may be particularly vulnerable to dual checkpoint inhibition.
Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment.
Authors: Ethan M. Basch, Allison Mary Deal, Amylou C. Dueck, Antonia Vickery Bennett, Thomas Michael Atkinson, Howard I. Scher, Mark G. Kris, Clifford A. Hudis, Paul Sabbatini, Dorothy Dulko, Lauren J. Rogak, Allison Emily Barz, Deborah Schrag
Journal: Journal of Clinical Oncology (2017)

LBA2 Background: We previously reported significant benefits in quality of life, patient satisfaction, and emergency room utilization outcomes from a large single-center randomized controlled trial comparing web-based symptom monitoring with patient-reported outcomes (PROs) vs. usual care in patients receiving chemotherapy for metastatic solid tumors (Clinicaltrials.gov: NCT00578006). We now present overall survival results from this trial. Methods: Patients receiving routine outpatient chemotherapy for metastatic solid tumors at Memorial Sloan Kettering Cancer Center were randomly assigned to self-report 12 common symptoms via tablet computers (“PRO intervention”), or to usual care. Treating physicians received symptom printouts at visits and nurses received email alerts when participants reported severe or worsening symptoms. Overall survival was tabulated based on medical records and Social Security Death Index data, estimated using the Kaplan-Meier method, and compared between arms using a log-rank test and Cox proportional hazards regression adjusting for age, sex, race, education level, and cancer type. Results: Between September 2007 and January 2011, 766 patients were randomized, with median age 61 (range 26-91), 86% white, 58% female, and 22% with less than high school education. Cancer types included genitourinary (32% of patients), gynecologic (23%), breast (19%), and lung cancer (26%). Survival results were assessed in June 2016 after a median follow up of 7 years and 517/766 (67%) of participants had died. Median overall survival in the PRO intervention arm was 5 months longer than the control arm (31.2 vs. 26.0 months, p = 0.03). In the multivariable model, results remained statistically significant with a hazard ratio of 0.832 (p = 0.04; 95% CI; 0.696, 0.995). Conclusions: Systematic symptom monitoring during outpatient chemotherapy using web-based patient-reported outcomes confers overall survival benefits. These single-center results are being further evaluated in a national multicenter implementation trial. Clinical trial information: NCT00578006.
Anti-60S ribosomal protein L29 antibody: New anticancer agent discovered from human sera.
Authors: Yasuhiro Miyake, Hiroshi Matsushita, Kazuhide Yamamoto
Journal: Journal of Clinical Oncology (2013)

3071 Background: Incidence of hepatocellular carcinoma (HCC) is lower in autoimmune hepatitis (AIH) than chronic viral hepatitis. In AIH, serum immunoglobulin G (IgG) levels are associated with the clinical features. In this study, we searched IgG showing anti-tumor effect in sera of AIH patients. Methods: Total IgG was extracted from sera of AIH patients by using protein G. Anti-tumor effects of the total IgG were evaluated by MTT assay using human HCC Huh7 cells and PLC/PRF/5 cells. Autoantigens in membrane proteins of Huh7 cells were screened by immunoprecipitation followed by liquid chromatography-mass spectrometry (LC-MS) shotgun analysis. Results: In one AIH patient without any cancers, addition of total IgG extracted from her serum to the culture inhibited the proliferation of Huh7 cells and PLC/PRF/5 cells, and decreased intracellular levels of β-Catenin and Cyclin-D1. In this patient, autoantigens in membrane proteins were screened, and 60S ribosomal protein L29 (RPL29) was identified from the MS/MS spectra and the SwissProt database using the Mascot Search engine. RPL29 expression in human HCC cell lines including Huh7, PLC/PRF/5, Hep3B, HepG2, HLE, HLF and SK-Hep-1 were identified by Western blot. Next, in the other 25 AIH patients, we investigated the correlation between serum anti-RPL29 levels by indirect ELISA using recombinant RPL29 and anti-tumor effects of total IgG extracted from their sera. Serum anti-RPL29 levels were significantly correlated with anti-tumor effects of total IgG extracted from their sera (P &lt;0.0001). On the other hand, addition of recombinant RPL29 to the culture canceled anti-tumor effects of total IgG extracted from sera of AIH patients showing higher serum anti-RPL29 levels. Additionally, these anti-tumor effects of total IgG extracted from sera of AIH patients were shown by MTT assay using human pancreatic cancer AsPC-1 cells and Panc-1 cells. Conclusions: Anti-RPL29 antibodies showing anti-tumor effect were discovered from human sera. Anti-RPL29 inhibits cancer cell proliferation via down-regulation of Wnt/β-Catenin signaling pathway. Serum anti-RPL29 may be one of immune systems by which the human does not develop cancers.
Abstract 295: Enhanced Cardiac Function And Lower Circulating Aldosterone Levels In βArrestin1 Knockout Mice During Post-myocardial Infarction Heart Failure Progression
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Ashley Siryk, Samalia Dabul, Walter J Koch
Journal: Circulation Research (2013)

Introduction: Chronic heart failure (HF) is characterized by enhanced circulating cardiotoxic hormones, among the most prominent of which is aldosterone, which contributes to the increased morbidity and mortality of the disease by promoting cardiac adverse remodeling post-myocardial infarction (MI). Cardiac β-adrenergic receptor (ΑR) desensitization and downregulation are a hallmark abnormality in HF at the molecular level and are due to the concerted action of cardiac G protein-coupled receptor kinase-2 (GRK2), together with its co-factors in receptor desensitization, the βarrestins (βarrs). We have also recently established that βarr1 promotes angiotensin II-dependent aldosterone production in the adrenal cortex, and this leads to elevated circulating aldosterone levels in vivo, both under normal conditions and during post-MI HF progression. Hypothesis: Herein, we sought to investigate the effects of genetically deleting βarr1 on post-MI cardiac function and hyperaldosteronic status in mice progressing to HF. Methods: We uitilized the βarr1KO mouse model and studied these mice at 4 weeks after surgically induced MI, in parallel with C57/B6 wild type (WT) controls. Cardiac function was assessed by echocardiography and in vivo catheterization. Plasma aldosterone was measured by ELISA. Results: Cardiac function is markedly improved in βarr1KO`s at 4 weeks post-MI, as evidenced by increased ejection fraction compared to WT mice (41.5 + 2.8 % vs. 21.8 + 2.4 %, respectively, n=9, p&lt;0.0001) and increased isoproterenol-induced contractility. Additionally, cardiac dimensions are significantly reduced compared to WT`s, indicating attenuation of adverse cardiac remodeling. Importantly, plasma circulating aldosterone levels are significantly lowered and cardiac βAR signaling and function appear elevated in post-MI βarr1KO`s compared to control WT`s. Conclusions: Genetic deletion of βarr1 substantially improves cardiac function, adverse remodeling, hyperaldosteronism, and cardiac βAR function during post-MI HF progression. The underlying mechanism is attenuation of both cardiac βAR desensitization/downregulation and adrenal aldosterone production, which is βarr1-dependent.
Abstract 339: Vasonatrin Peptide Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats through PKG-Mediated Inhibition of Endoplasmic Reticulum Stress
Authors: Haifeng Zhang, Liming Yu, Zhenwei Shi, Weifeng Lv, Ru Tie, Xiangyan Liang, Jun Yu, Ling Tao
Journal: Circulation Research (2013)

Diabetes mellitus (DM) increases morbidity/mortality of ischemic heart disease (IHD). Although atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) reduce the myocardial ischemia/reperfusion (MI/R) damage in non-diabetic rats, whether vasonatrin peptide (VNP), the artificial synthetic chimera of ANP and CNP, confers cardioprotective effect against acute MI/R injury, especially in diabetic patients, is still unclear. This study aimed to investigate the effects of VNP on MI/R injury in diabetic rats and the involved mechanisms. The high-fat diet-fed streptozotocin (HFD-STZ) induced diabetic rats were subjected to MI/R (30 min/4 h). VNP treatment (100 µg/kg, i.v., 10 min before R) significantly improved ± LV d P /dt max [(3242 ± 103) and -(2731 ± 79) mm Hg/s vs. (2936 ± 90) and -(2422 ± 83) mm Hg/s in DM group] and LVSP and reduced LVEDP, and reduced infarct size [(43.3 ± 3.6) % vs (53.5 ± 2.8) %], apoptosis index [(36.0 ± 2.1) % vs. (45.7 ± 3.5) %], caspase-3 activity, serum CK and LDH levels (n=8, P &lt;0.05). Moreover, VNP inhibited endoplasmic reticulum (ER) stress by suppressing GRP78 and CHOP (n=3, P &lt;0.05), and consequently increased the antiapoptotic protein Akt and ERK1/2 expression and phosphorylation levels ( P &lt;0.05). These effects were mimicked by 8-Br-cGMP (1 mg/kg, i.p., 20 min before R), a cGMP analogue, whereas inhibited by KT-5823 (0.5 mg/kg, i.p.), the selective inhibitor of PKG (both P &lt;0.05). In addition, pretreated DM rats with TUDCA (50 mg/kg, i.p.), a specific inhibitor of ER stress, couldn’t further promote the VNP’s cardioprotective effect ( P &gt;0.05). In vitro study was performed using H9c2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R, 3 h/6 h) and incubated with or without VNP (10 -8 mol/L). Gene knockdown of PKG1α with siRNA blunted VNP’s inhibition of ER stress and apoptosis (n=6, P &lt;0.05), while overexpression of PKG1α resulted in significant decreased ER stress and apoptosis (n=6, P &lt;0.01). In conclusion, VNP protects diabetic heart against MI/R injury by inhibiting ER stress via cGMP-PKG signaling pathway. These results suggest that VNP may have potential therapeutic value for the diabetic patients with ischemic heart disease.