tbuckley/cabot-search huggingface dataset:
Tumor-infiltrating immature myeloid cells do not mature into conventional or plasmacytoid dendritic cells but rather mature toward monocyte/macrophage at the tumor site
Authors: Saio Masanao, Suwa Tatsuhiko, Kenichi Nonaka, Naoki Umemura, Makoto Okada, Yusuke Kitoh, Juncheng Bai, Guan-Feng Ouyang, Lihong Bao, Akira Hara, Tsuyoshi Takami
Journal: Cancer Research (2008)

251  Background: Myeloid-derived suppressor cells (MDSCs) are originally defined in bone marrow and spleen of tumor-bearing host. Recent review articles suggest potential differentiation of MDSCs towards conventional DC (cDC), plasmacytoid DC (pDC) in addition to macrophages. If so, we could frequently observe cDC or pDC at the tumor site in addition to myeloid cells holding MDSC cell surface phenotype. Therefore, in this presentation, we tried to check how often cDC and pDC are observed in the tumor-infiltrating myelomonocyte population.  Methods: MCA38 murine adenocarcinoma or GL261 murine glioma was subcutaneously or intracranially inoculated. On day 14 after tumor inoculation, tumor-infiltrating myelomonocytoid cell marker CD11b+ cells, cDC marker CD11c+ cells or pDC marker PDCA-1+ cells were recovered by magnetic immuno-beading method. For each population, multiple PCR analysis for cytokines, chemokines or their receptors, and flow cytometric analysis were performed.  Results: When 1.22g of tumor mass was digested and total tumor digest was equally divided into 3 samples for the separation with CD11b, CD11c, or PDCA-1 immuno-beading, recovered each cell population (x one million cells) was CD11b+: 2.2, CD11c+: 2.0, and PDCA-1+: 5.1. Furthermore, Cytokine, chemokine, or their receptor expression patterns of each population was almost the same. In addition, when CD11b+ cells were depleted first and remained PDCA-1+ population was recovered from GFP mice, CD11b+ cells were GFP positive. However, CD11b(-)PDCA-1+ population was GFP negative and was grown when it was inoculated into murine subcutaneous space. These data indicated that almost all myelomonocytoid cells hold CD11c and PDCA-1 antigen at the tumor site and CD11b(-)PDCA-1 positive population was contamination of tumor cells. Therefore, we checked CD24 and B220 expression to further characterize CD11b+ populations. Less than 1% of CD11b+ population was clearly B220+ (pDC) and 0.5 to 1% of CD11b+ population was clearly CD24+ (cDC). Remaining over 90% of CD11b+ population was Gr-1+, F4/80+, IL-4Ra+ MDSC phenotype with intermediate CD11c expression and weak PDCA-1 expression. Sorted CD11b+ population seldom contain polymorphonuclear cells and mainly showed monocyte/macrophage appearance in addition to immature myelomonocytoid appearance. According to multiple PCR analysis mRNA expression pattern, tumor inoculated site did not strongly influence the characteristics of MDSCs rather tumor type itself did affect the characteristics of MDSCs  Conclusions: Our data clearly indicates that tumor-infiltrating MDSCs partially hold DC markers; CD11c and PDCA-1 but did not categorized into DC and remains as MDSC or rather differentiated into monocyte/macrophage lineage cells at the tumor microenvironment.
Annual Review of Microbiology. Volume 5.
Journal: JAMA (1952)

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 Journals 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 2024 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
Primary CNS Lymphoma
Authors: Christian Grommes, Lisa M. DeAngelis
Journal: Journal of Clinical Oncology (2017)

Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. To our knowledge, no randomized trial has been conducted for recurrent/refractory disease, leaving many questions unanswered about optimal first-line and salvage treatments. This review will give an overview of the presentation, evaluation, and treatment of immunocompetent patients with PCNSL.
Obesity and breast cancer: Analysis of Breast Cancer Collaborative Registry (BCCR) data in a rural community cancer center.
Authors: Mehmet Sitki Copur, Shayla Bigley, Nathan Frey, Mithat Gonen, Rebecca Hadenfeldt, Mary Gulzow, Sarah Einspahr, Katherine Usasz, Maureen Thomson, Curtis Gnewuch, Lois Greenwalt, Jennifer Scott, Ryan C. Ramaekers, Dron Gauchan, Douglas Clark, Max Norvell, Kenneth H. Cowan
Journal: Journal of Clinical Oncology (2016)

e13103 Background: Developed by NCI-designated Eppley Cancer Institute in Omaha Nebraska, BCCR is a web-based multisite regional/national breast cancer data registry system enabling rapid/uniform clinical/biological data collection/utilization strategies in breast cancer (BC). As one of the 38 cancer centers from 3 states participating in BCCR, we analyzed our local registry data to evaluate the impact of obesity in BC. Methods: A detailed registry questionnaire used to prospectively register BC pts into registry. Oct 2012 to Oct 2014, data entered at our rural community cancer program, CHI-Health St-Francis, was analyzed. Pts were stratified into obese, Body Mass Index (BMI) ≥ 30 vs non-obese BMI<30 groups. Association of obesity with clinicopathologic characteristics was investigated. Results: Overall, there were more non-obese than obese pts, (P=0.04). There was no difference in age between obese vs non-obese groups. Prevalence of obesity between postmenopausal vs premenopausal pts was similar. Non-invasive breast cancers were more prevalent in obese group (P=0.02). Disease stage, hormone/her-2-neu receptor status were not different.Family history and identified genetic syndromes were also similar (Table). Conclusions: Our localBCCR data suggest an association of obesity with non-invasive breast cancer but no association with age, hormone/her-2-neu receptor status, family history or identified genetic syndromes. Effect of BMI on patient outcomes and biospecimen data will be analyzed separately. Collaborative tumor registries like ours can provide valuable tools, and resources in addressing clinical pathological questions at the local community level where majority of cancer patients live. Non-Obese (BMI<30) Obese (BMI>30) P # % # % Pts # (%) 136 57 104 43 0.04 Mean Age 56.2 58.5 0.14 Non-Invasive 6 4.4 13 12.5 0.02 Invasive 130 95.5 91 87.5 Premenopausal 24 17.6 10 9.6 0.09 Postmenopausal 112 82.3 94 90.3 Early Stage (I-II) 115 84.5 86 82.6 0.08 Locally Advanced ( III) 8 5.8 11 10.5 Metastatic (IV) 7 5.1 13 12.5 HR + 103 75.7 82 78.8 0.64 HR - 33 24.2 22 21.1 Her-2-neu + 33 24.2 21 20.1 0.53 Her-2-neu - 103 75.7 83 79.8 Family History 9 6.6 5 4.8 0.59 Genetic Syndromes 1 0.7 1 0.9 1.00
Allometric scaling of STEALTH® liposomal anticancer agents
Authors: William C. Zamboni, Holly Whitner, Douglas M. Potter, Ramesh K. Ramanathan, Sandra Strychor, Margaret E. Tonda, Barbara Stewart, Nishit Modi, Charles Engbers, Robert L. Dedrick
Journal: Cancer Research (2005)

1394  Introduction: STEALTH® liposomal (SL) formulations contain lipid conjugated to polyethylene glycol. SL formulations of anticancer agents have been designed to prolong the drug circulation time, increase tumor delivery, and improve the therapeutic index. The disposition of SL-encapsulated drug is dictated by the composition of the liposome, thus altering the pharmacokinetic (PK) profile of the drug. Allometric scaling (AS) is based on a power-law relationship between body weight (BW) and drug clearance (CL) among mammals and has been used to compare the disposition of nonliposomal drugs across species. The objectives of this study were to use AS to do the following: 1) compare the disposition of SL drugs across species, and 2) predict the CL of SL drugs in humans. Methods: The PK of SL doxorubicin (Doxil®), SL cisplatin (SPI-077) and SL CKD-602 (S-CKD602; a camptothecin analogue) were compared. Data for Doxil and SPI-077 in humans were available at clinically relevant doses. For S-CKD602, PK data were available in rats and dogs, with preliminary data from an ongoing dose escalation trial in humans. Plasma samples were analyzed for forms of encapsulated plus released (sum total) of S-CKD602 total (lactone + hydroxy acid), Doxil, and SPI-077. The allometric equation used to evaluate the relationship between BW and CL in each species was CL = a(BW)m (a = empirical coefficient; m = allometric exponent). For each agent, a log regression of the log BW (kg) vs log CL (L/h) in available species was used to estimate parameters in the allometric equation. The Complex Dedrick Plot (CDP) was used to normalize interspecies exposure and time by dividing the plasma concentration (ng/mL) by the dose (mg/kg) and by dividing the time (h) interval by BW0.25. Results: Doxil CL values measured in humans and predicted in humans from the log regression of log CL vs log BW from rats, rabbits, and dogs were 0.053 and 0.076 L/h, respectively. SPI-077 CL values measured in humans and predicted in humans from mice, rats, and dogs were 0.021 and 0.086 L/h, respectively. The allometric equations from plots of log BW versus log CL in rats, dogs, and humans for S-CKD602, Doxil, and SPI-077 were CL = 0.0051(BW)1.07, CL = 0.0017(BW)0.86, and CL = 0.0014(BW)0.73, respectively. Based on the CDP, the disposition of S-CKD602 in rats is not allometrically comparable to dogs and humans. The disposition of S-CKD602 and Doxil is similar in rats but different in dogs and humans. Conclusions: S-CKD602 CL was greater in rats and dogs compared to Doxil or SPI-077, but PK data were not yet available at clinically meaningful doses for S-CKD602 to compare the disposition of the 3 formulations in humans. Using the AS approach described here, the disposition of STEALTH liposome formulations was not predictive across species. Supported by ALZA Corporation, Inc.
The Use of Monoclonal Antibody Directed Chimeric Antigen Receptors to Facilitate Conventional T Cell and Treg Control of GvHD and Tissue Tolerance in Murine Models
Authors: Antonio Pierini, Bettina Iliopoulou, Heshan Peiris, Magdiel Perez Cruz, Jeanette Baker, Katie Hsu, William Strober, Ping-Ping Zheng, Tom Erkers, Aaron Ring, Andrea Velardi, Robert S. Negrin, Seung Kim, Everett Meyer
Journal: Blood (2016)
Abstract 2453: Effect of Ranolazine on Hemoglobin A1c in the MERLIN-TIMI 36 Randomized Controlled Trial
Authors: David A Morrow, Benjamin M Scirica, Bernard R Chaitman, Sabina A Murphy, Ewa Karwatowska-Prokopczuk, Carolyn H McCabe, Eugene Braunwald
Journal: Circulation (2007)
Dilatation endoscopique des sténoses ulcéreuses pyloro-bulbaires: A propos de 42 cas
Authors: MN Abdelli, F Houissa, MR Bouali, H Ben Abdallah, MF Khediri
Journal: Endoscopy (2006)

La sténose pyloro-bulbaire constitue classiquement une complication tardive de la maladie ulcéreuse gastroduodénale nécessitant souvent le recours à un traitement chirurgical. Dans notre service depuis 1996, nous avons introduit la dilatation endoscopique comme une alternative au traitement chirurgical des sténoses ulcéreuses pyloro-bulbaires.
Etude du réseau vasculaire de la jonction oesogastrique en endoscopie avec le système NBI
Authors: K Kuznietsov, E Vázquez-Ballesteros, R Lambert, JF Rey
Journal: Endoscopy (2006)

La détection endoscopique des segments ultra courts de l'oesophage de Barrett au niveau de la jonction oesogastrique repose sur l'analyse du réseau vasculaire superficiel de l'eosophage distal (vaisseaux palissadiques). L'utilité du traitement de l'image développé par Olympus Medical System avec la technique du Narrow Band Imaging (NBI) est évaluée dans cette indication.
Enrichment of germline DNA-repair gene mutations in patients with colorectal cancer.
Authors: Saud H Aldubayan, Marios Giannakis, Nathanael Moore, Xinmeng Jasmine Mu, G. Celine Han, Reiko Nishihara, Zhi Rong Qian, Li Liu, Shuji Ogino, Levi A. Garraway, Charles S. Fuchs, Eliezer Mendel Van Allen
Journal: Journal of Clinical Oncology (2017)

1500 Background: Twin studies showed that 30% of all colorectal cancer (CRC) patients have an inherited genetic susceptibility. Several CRC predisposition genes have been described to date. However, mutations in these genes explain the risk in only 5-10% of CRC cases. In this study, we hypothesized that some of the CRC heritability may be explained by excess disruptive germline mutations in DNA repair genes (DRGs). Methods: Exome sequencing data of 716 in the discovery cohort (CanSeq and NHS/HPFS studies) and 1609 CRC patients in the validation cohort (TCGA and NSCCG studies) were used to evaluate germline variants in a pre-selected group of 42 DRGs and 12 known CRC risk genes. Frequencies of disruptive mutations in our cohorts were examined relative to 27173 non-Finnish European cancer-free adults from the ExAC cohort to evaluate for enrichment. Results: Of 716 patients in the discovery cohort, 27 (3.8%) patients harbored germline mutations in APC (n = 11), MSH6 (n = 2), MUTYH (n = 11), CHEK2 (n = 1) and TP53 (n = 2). Interestingly, germline mutations in ATM and PALB2 were significantly enriched in our CRC discovery cohort (OR = 2.7; P = 0.044; and OR = 4.8; P = 0.026, respectively). Evaluation of germline data from another 1609 CRC patients (validation cohort) also showed significantly higher rates of ATM mutations (5; 0.7%; OR = 2.1; P = 0.044), and a trend for enrichment of PALB2 mutations (3; 0.4%; OR = 2.8; P = 0.056). Secondary analysis of actionable germline mutations in a highly penetrant cancer risk gene set ( ATM, BRCA1, BRCA2, BRIP1 and PALB2) suggest a broader enrichment trend in CRC patients for these genes (Discovery: OR = 1.7; P = 0.06; Validation: OR = 2; P = 1.96e-04). Conclusions: Our analysis of germline variants in 2325 CRC patients showed the first robust evidence for germline ATM mutations to confer a higher risk of developing CRC. We also presented evidence to support PALB2 as a potential novel CRC risk gene. Overall, our study shows that mutations in some DRGs may explain some of the missing CRC heritability. It also indicates that a significant percentage of CRC patients, who carry mutations in highly actionable genes where cancer screening recommendations for patients and families do exist, are not captured with current testing recommendations.
Guideline: In low back pain, nonpharmacologic treatments are recommended
Authors: Simon Somerville
Journal: Annals of Internal Medicine (2017)

Source Citation Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166:514-30. 28192789
<scp>PASH</scp> syndrome (pyoderma gangrenosum, acne and hidradenitis suppurativa): a disease with genetic heterogeneity
Authors: H. Sonbol, S. Duchatelet, S. Miskinyte, B. Bonsang, A. Hovnanian, L. Misery
Journal: British Journal of Dermatology (2017)

PASH syndrome is a clinical entity associating pyoderma gangrenosum (PG), severe acne and hidradenitis suppurativa (HS)1. Absence of pyogenic sterile arthritis (PA) distinguishes PASH syndrome from PAPASH and PAPA syndromes which associate PA in combination with PG, severe acne with or without HS, respectively2,3. Mutations in PSTPIP1 (proline-serine-threonine-phosphatase interacting protein 1) gene were identified in patients with PAPA and PAPASH syndromes, although genetic heterogeneity was observed in PAPA syndrome2,3. Loss-of-function mutations in the y-secretase genes, Nicastrin (NCSTN), Presenilin Enhancer-2 (PSENEN), and Presenilin-1 (PSEN1), have been reported in a small proportion of HS patients4,5.

This article is protected by copyright. All rights reserved.
Compliance and impact of screening on individuals at high risk of breast and ovarian cancer syndrome (BOCS).
Authors: Carmen Guillen, Maria-Teresa Salazar-Lopez, Maria-Dolores Rubio, Miguel Chiva, Silvia Perez-Rodrigo, Jesus Solera, Pilar Martinez, Vanessa Pachón Olmos, Reyes Ferreiro Monteagudo, Julie Earl, Silvia Patricia Cortez Castedo, Maria Villamayor-Delgado, Samuel Hernandez Sarmiento, Maria-Isabel Humanes
Journal: Journal of Clinical Oncology (2016)

e13054 Background: Recommendations of screening are well defined in carriers of mutation of BRCA1 and BRCA2 genes. The aim of this study was to determine the compliance and impact of screening follow-up in individuals at high risk of breast and ovarian cancer syndrome (BOCS), in terms of the detection of cancer. Methods: Between 02/12/2011 and 12/31/2015, 755 individuals with BOCS underwent regular follow-up. All patients met criteria BOCS. The genetic study of BRCA1/BRCA2 genes was based on PCR and Sanger sequencing in 720 individuals (198 had a mutation in BRCA1/BRCA2 genes; 368 had variants of unknown significance [VUS]; 154 had a non-informative result). In 35 individuals the genetic test was not possible, but they were also recommended screening. At baseline, 560 patients had cancer and 195 were healthy individuals. Compliance and results of the screening tests were evaluated annually. Results: Of the 755 individuals, 246 (32.6%) did not perform the recommended annual screening. The reasons were: 165 (67% of 246) physician didn’t prescribe the tests; 9 (3.6%) citation problems; 20 (8.1%) due to the patient; 52 (21.1%) for others. The determination of CA 125 and breast MRI were performed to a lesser extent. During the follow-up period, 12/755 (1.6%) new cancers were detected. In total 8 new breast cancers (BC) and one ovarian (OC) were diagnosed. In healthy patients at baseline (195), 4 new cancers (2.1%): 2 BC (1 in a healthy carrier of VUS and 1 in a carrier of a BRCA mutation); 1 lymphoma (in BRCA VUS carrier) and; 1 endometrial cancer (in a BRCA mutation carrier). In patients suffering from cancer at baseline, 8/560 (1.4%) new cancers were detected: 6 BC (3 in women with a contralateral BC; 2 of these had a BRCA mutation and the rest had BRCA VUS); 1 OC; and 1 rectal cancer (in a BRCA VUS carrier). Conclusions: Almost one third (32.6%) of the patients do not meet the recommended annual screening for BOCS. The most important limitation for compliance is the lack of prescribing the test by the physician performing the screening. BC is a type of cancer most frequently detected by the screening tests. The detection rates of screening are higher in healthy patients at baseline than in those previously affected by cancer.
A Pilot Study of Eltrombopag Plus G-CSF for Human CD34+ Cell Mobilization in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant
Authors: Jacob P. Laubach, Revital Freedman, Robert A Redd, Mason Tippy, Kristen Cummings, Heidi Dipietro, Nivisha Upendra Naik, Kelly Nicol, Paul G. Richardson, Julie Najita, Nancy Berliner
Journal: Blood (2016)
Anlotinib in metastatic renal cell carcinoma (mRCC) with a previous anti-VEGFR TKI: Preliminary results from a multicenter, phase II trial.
Authors: Ai-Ping Zhou, Yuxian Bai, Yan Song, Hangzhong Li, Xiaodong Xie, Xiu-Bao Ren, Dingwei Ye, Jiyan Liu, Hong Luo, Xianzhong Bai, Shukui Qin, Cheng Fu, Jinwan Wang, Jianhui Ma
Journal: Journal of Clinical Oncology (2016)

e16082 Background: Fibroblast growth factor (FGF) signaling regulates tumor growth and vascularization and partly mediates antiangiogenic escape from VEGFR inhibitors. Sequential TKI treatment has been proved to be effective in some patients with mRCC failed with a previous TKI. Anlotinib is a potent oral, small molecular TKI with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR2. This multicenter phase II trial (NCT02072044) evaluated the efficacy of anlotinib in mRCC patients with clear cell being the predominant component who failed with a previous anti-VEGFR TKI. Methods: Patients who progressed on or were intolerant to sorafenib or sunitinib were enrolled. Anlotinib was administered orally at dose of 12 mg daily for 2 weeks followed by 1 week rest. The primary endpoint was PFS. Secondary end points included OS, ORR, safety. Results: Of 43 patients enrolled, 1 patient withdrawn his informed consent before treatment started. Of 42 patients received anlotinib, 30 patients had disease progression on and 10 were intolerant to previous sofafenib or sunitinib treatment. Data cutoff was May 15, 2015. Median PFS was 11.8 (95% CI, 8.5- ) months for the whole group, while 8.5 (95% CI, 4.4- ) months for those progressed on previous TKI treatment, not reached for those intolerant to previous TKI treatment. Overall response rate (ORR) for intent-to-treatment patients (ITT) was 19.1% (95%CI, 8.60-34.12). 6-week disease control rate was 90.5% (95%CI, 77.4%-97.3%). The most frequently reported treatment-related adverse events of all grades included hypertension 45.2%, hand-foot skin reaction 42.9%, fatigue 35.7%, proteinuria 35.7%, anorexia 33.3%, hypothyroidism 28.6%, hoarseness 23.8%, hypertriglyceridemia 21.3%, hypercholesterolemia 21.4%, oral mucositis 21.4%, skin rash 21.4%, thrombocytopenia 14.3%. The most common grade 3 or 4 side effects included lymphopenia 7.1%, hypertension 4.8% and hypothyroidism 4.8%. Conclusions: Anlotinib was preliminary shown to have promising efficacy with a favourable toxicity profile for patients with metastatic RCC who failed with previous sorafenib or sunitinib. Clinical trial information: NCT02072044.
Cytomegalovirus <scp>DNA</scp> is highly prevalent in the blood of patients with asthma and is associated with age and asthma traits
Authors: M. L. Kowalski, A. Wardzynska, M. Studzinska, M. Pawelczyk, Z. J. Lesnikowski, E. Paradowska
Journal: Allergy (2017)

Cytomegalovirus (CMV) IgG antibodies have been associated with inflammaging and immunosenescence. We aimed to assess the presence of CMV DNA in the blood of adult and elderly patients with bronchial asthma to establish potential association of CMV DNAemia with asthma and asthma characteristics. Eighty-five elderly asthmatics, 74 younger asthma patients, and 114 age-matched controls were recruited. The CMV DNA was detected using commercial artus assay in 10.7% of asthma patients, but was negative in all control individuals. The secondary assay identified CMV DNA in 41.5% of asthmatics and 13.3% of control subjects (P < .001). Presence of CMV DNA was associated with an increased risk of asthma and CMV DNA copy numbers correlated with some asthma traits, including respiratory parameters and exhaled breath nitric oxide. We conclude that CMV infection is associated with asthma and may contribute to the pathogenesis of asthmatic inflammation.