tbuckley/cabot-search huggingface dataset:
Abstract PR05: Lineage specifiers SOX2 and NKX2-1 inversely regulate lung tumor immune microenvironment
Authors: Gurkan Mollaoglu, Alex Jones, Anandaroop Mukhopadhyay, Jason Gertz, Kevin Jones, Eric Snyder, Trudy G. Oliver
Journal: Cancer Research (2018)

Abstract The tumor microenvironment is a critical effector of therapeutic response to diverse stimuli including immunotherapies. Lineage-specific drivers of cancer are known to dictate tumor differentiation and response to therapy, but how they influence the tumor immune microenvironment is largely unknown. SOX2 and NKX2-1 are critical regulators of lung development and cancer, with SOX2 amplifications associated with squamous lung cancer and NKX2-1 amplifications associated with lung adenocarcinoma. Here we employ and develop new genetically engineered mouse models (GEMMs) of lung cancer to interrogate the impact of SOX2 and NKX2-1 on innate immune infiltration. Squamous and adenocarcinoma GEMMs accurately recapitulate features of their human counterparts, including an enrichment of tumor-associated neutrophils (TANs) specifically in squamous lung cancer. We show that SOX2 recruits TANs, whereas NKX2-1 suppresses TANs, in the absence of histopathologic changes. SOX2 and NKX2-1 inversely regulate the neutrophil chemoattractant, Cxcl5, which is also upregulated in human squamous lung tumors. Using a novel GEMM of squamous lung cancer with a rapid latency of 3-4 months, preliminary data suggest that neutrophils can regulate adeno- to squamous transdifferentiation in vivo. Together these data reveal how lineage specifiers influence the tumor immune microenvironment, which in turn may regulate cancer cell fate. This abstract is also being presented as Poster B19. Citation Format: Gurkan Mollaoglu, Alex Jones, Anandaroop Mukhopadhyay, Jason Gertz, Kevin Jones, Eric Snyder, Trudy G. Oliver. Lineage specifiers SOX2 and NKX2-1 inversely regulate lung tumor immune microenvironment [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr PR05.
Does Armodafinil Improve Driving Task Performance and Weight Loss in Sleep Apnea? A Randomized Trial
Authors: Julia L. Chapman, Elizabeth A. Cayanan, Camilla M. Hoyos, Yasmina Serinel, Maria Comas, Brendon J. Yee, Keith K. H. Wong, Ronald R. Grunstein, Nathaniel S. Marshall
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Patients with obstructive sleep apnea (OSA) unable to tolerate standard treatments have few alternatives. They may benefit from weight loss, but the major symptom of daytime performance impairment may remain during weight loss programs.We hypothesized that wakefulness-promoter armodafinil would improve driving task performance over placebo in patients undergoing weight loss.This was a placebo-controlled, double-blind, randomized trial of armodafinil versus placebo daily for 6 months in patients who were also randomized to one of two diets for 6 months with follow-up at 1 year in overweight, adult, patients with OSA who had rejected standard treatment and suffered daytime sleepiness.Primary outcome was change in steering deviation in the final 30 minutes of a 90-minute afternoon driving task (AusED) at 6 months. Secondary outcomes were Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and fat mass measured by dual-emission X-ray absorptiometry. Armodafinil improved driving task performance over placebo at 3 months (12.9 cm; 95% confidence interval, 4.1-21.7; P = 0.004), but not the primary time point of 6 months (5.5 cm; 95% confidence interval, -3.3 to 14.3; P = 0.223). Patients on armodafinil lost 2.4 kg more fat than those on placebo at 6 months (95% confidence interval, 0.9-4.0; P = 0.002). Other secondary outcomes were not significantly improved.Armodafinil did not improve driving task performance at the primary endpoint of 6 months. Armodafinil might be a useful adjunctive to weight loss in patients with OSA rejecting conventional treatments but this needs to be directly tested in a specifically designed, properly powered clinical trial. Clinical trial registered with Australian and New Zealand Clinical Trials Registry (ACTRN 12611000847910).
Microbiologic epidemiology depending on time to occurrence of prosthetic joint infection: a prospective cohort study
Authors: C. Triffault-Fillit, T. Ferry, F. Laurent, P. Pradat, C. Dupieux, A. Conrad, A. Becker, S. Lustig, M.H. Fessy, C. Chidiac, F. Valour, T. Ferry, F. Valour, T. Perpoint, A. Boibieux, F. Biron, P. Miailhes, F. Ader, A. Becker, S. Roux, C. Triffault-Fillit, F. Daoud, J. Lippman, E. Braun, C. Chidiac, Y. Gillet, L. Hees, S. Lustig, E. Servien, Y. Herry, R. Gaillard, A. Schneider, M.-H. Fessy, A. Viste, P. Chaudier, R. Desmarchelier, T. Mouton, C. Courtin, L. Louboutin, S. Martres, F. Trouillet, C. Barrey, F. Signorelli, E. Jouanneau, T. Jacquesson, A. Mojallal, F. Boucher, H. Shipkov, J. Château, F. Aubrun, I. Bobineau, C. Macabéo, F. Laurent, F. Vandenesch, J.-P. Rasigade, C. Dupieux, F. Craighero, L. Boussel, J.-B. Pialat, I. Morelec, M. Janier, F. Giammarile, M. Tod, M.-C. Gagnieu, S. Goutelle, S. Gerbier-Colomban, T. Benet, E. Mabrut, P. Pradat
Journal: Clinical Microbiology and Infection (2018)
Health Care Reforms in India
Authors: K. Srinath Reddy
Journal: JAMA (2018)

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
An <i>In Vivo</i> Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer
Authors: Xin Lu, Xiaolu Pan, Chang-Jiun Wu, Di Zhao, Shan Feng, Yong Zang, Rumi Lee, Sunada Khadka, Samirkumar B. Amin, Eun-Jung Jin, Xiaoying Shang, Pingna Deng, Yanting Luo, William R. Morgenlander, Jacqueline Weinrich, Xuemin Lu, Shan Jiang, Qing Chang, Nora M. Navone, Patricia Troncoso, Ronald A. DePinho, Y. Alan Wang
Journal: Cancer Research (2018)

Abstract Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo. In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Finally, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. Together, our results indicate that PYGO2 functions as a driver oncogene in the 1q21.3 amplicon and may serve as a potential prognostic biomarker and therapeutic target for metastatic prostate cancer. Significance: Amplification/overexpression of PYGO2 may serve as a biomarker for prostate cancer progression and metastasis. Cancer Res; 78(14); 3823–33. ©2018 AACR.
Pembrolizumab treatment of a patient with xeroderma pigmentosum with disseminated melanoma and multiple nonmelanoma skin cancers
Authors: K.H. Kraemer, D. Tamura, S.G. Khan
Journal: British Journal of Dermatology (2018)

Linked Article:Salomon et al. Br J Dermatol 2018; 178:1199–1203.
Predictors for detecting circulating tumor DNA (ctDNA) in metastatic colorectal cancer (mCRC).
Authors: Allan Andresson Lima Pereira, Jonathan M. Loree, Jennifer S Davis, Michael Lam, Van Karlyle Morris, Michael J. Overman, Kanwal Pratap Singh Raghav, Bryan K. Kee, David R. Fogelman, Eduardo Vilar Sanchez, Imad Shureiqi, Cathy Eng, Shanequa Manuel, Shadarra Crosby, Robert A. Wolff, Richard B. Lanman, AmirAli Talasaz, Filip Janku, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

634 Background: Utilization of ctDNA has been rapidly adopted as a predictive diagnostic in advanced NSCLC and indications in GI cancers may be emerging. While tissue-based assays have yields above 90%, there is less known about factors that influence the sensitivity of ctDNA for detecting mutations. Methods: We retrospectively evaluated mCRC patients (pts) who had plasma-derived NGS utilizing a highly-sensitive 68-73-gene assay. Tissue from prior resections or biopsies underwent concurrent 46-gene sequencing. In a case-control design, pts with a known mutation on tissue and radiologic evidence of metastatic disease but no detectable ctDNA mutation were matched 1:3 with randomly selected pts with detectable mutations and compared according to clinical, laboratory, and radiologic characteristics. A binary logistic regression was performed and Kaplan-Meier and Cox-proportional hazards models were used to compare overall (OS) and progression-free (PFS) survivals. Results: Of 427 mCRC pts who underwent ctDNA testing, 416 pts met inclusion criteria. Plasma-derived NGS did not find tumor mutations in 66 cases (15.9%); 198 pts with detectable alterations were selected as controls. After multivariate analysis, the lack of detection of ctDNA was associated with decreasing age (OR 0.94; 95%CI 0.91-0.98; p = 0.004), absence of liver (OR 0.19; 95%CI 0.08-0.45; p &lt; 0.001) and lymph node metastases (OR 0.28; 95%CI 0.12-0.70; p = 0.006). A key determinant was timing of collection relative to disease status: plasma collected after evidence of progression was substantially more likely to have detectable alterations (OR 10.95; 95%CI 4.23-28.33; p &lt; .001); in these pts, the modeled rate of detection was 98%, which increased to &gt; 99% if the pts also had either liver or nodal disease. Pts with no detectable ctDNA had better OS (HR 0.38; 95%CI 0.21-0.69, p = 0.002) and PFS (HR 0.52; 95%CI 0.32-0.85; p = 0.009). Conclusions: When limited to ctDNA collected in newly diagnosed or recently progressing pts, the yield of ctDNA is 98%, which equals or exceeds the yield of tissue based testing. Our findings support the notion that ctDNA testing, when appropriately utilized, can replace tissue based testing and may provide prognostic information.
Proposed Stages of Myocardial Phenotype Development in Fabry Disease
Authors: Sabrina Nordin, Rebecca Kozor, Katia Medina-Menacho, Amna Abdel-Gadir, Shanat Baig, Daniel M. Sado, Ilaria Lobascio, Elaine Murphy, Robin H. Lachmann, Atul Mehta, Nicola C. Edwards, Uma Ramaswami, Richard P. Steeds, Derralynn Hughes, James C. Moon
Journal: JACC. Cardiovascular imaging (2018)
siRNA mediated knockdown of Bcl-2 and low-dose taxol treatment in human glioblastoma U251MG cells induces apoptosis, inhibits cell invasion, angiogenesis, and tumor growth in nude mice
Authors: Joseph George, Naren Banik, Swapan Ray
Journal: Cancer Research (2008)

4389  RNA interference using siRNA is a powerful tool to knockdown the mRNA and thus protein level of a target gene. Taxol is an anti-cancer drug that binds to β-tubulin to prevent tumor cell division; however, higher doses of taxol may be toxic to normal cells. The anti-apoptotic molecule Bcl-2 is upregulated in cancer cells for protection from apoptosis. The aim of our present study was to downregulate Bcl-2 expression using cognate siRNA in a highly invasive glioblastoma cell line (U251MG) during a low-dose taxol treatment and to examine apoptosis, inhibition of cell invasion, angiogenesis, and tumor growth. Human glioblastoma U251MG cells were treated with 100 nM taxol or 100 nM Bcl-2 siRNA or both for 72 h. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting demonstrated around 80% knockdown of Bcl-2 mRNA and protein levels. Fluorescent activated cell sorting (FACS) analysis and the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay demonstrated apoptosis in almost 60% of cells after combination treatment with taxol and Bcl-2 siRNA. Matrigel invasion studies demonstrated a significant decrease in cell invasion after treatment with taxol and Bcl-2 siRNA. In vivo angiogenesis assays in immunocompromised mice showed complete inhibition of neo-vasculature after treatment with both agents. The combination treatment with taxol and Bcl-2 siRNA further demonstrated a remarkable decrease in growth of both subcutaneous and intracerebral tumors in nude mice. Taken together, the results of our study indicated that the combination treatment with taxol and Bcl-2 siRNA effectively induced apoptosis and inhibited cell invasion, angiogenesis, and tumor growth. Therefore, this combination therapeutic strategy offers a potential tool for the controlling the growth of human glioblastoma. This work was supported by the R01 CA-91460 grant from the NCI.
Necrotizing Anogenital Ulcer in a Healthy 8-Month-Old Male
Authors: Matthew Mansh, Mona Riskalla, Sheilagh Maguiness
Journal: JAMA Dermatology (2018)

A healthy 8-month-old male infant was admitted for management of a rapidly progressive, painful anogenital ulcer; the lesion had developed acutely over 48 hours and had an associated symptom, but no fevers, chills, or other systemic symptoms. What is your diagnosis?
A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation
Authors: Scott D. Halpern, Michael O. Harhay, Kathryn Saulsgiver, Christine Brophy, Andrea B. Troxel, Kevin G. Volpp
Journal: New England Journal of Medicine (2018)

Whether financial incentives, pharmacologic therapies, and electronic cigarettes (e-cigarettes) promote smoking cessation among unselected smokers is unknown.
The clinicopathologic features and optimal surgical treatment of duodenal gastrointestinal tumor.
Authors: Seungjae Lee, Ki Byung Song
Journal: Journal of Clinical Oncology (2018)

519 Background: Because of unclear clinicopathologic features, the optimal surgical procedure for duodenal gastrointestinal stromal tumor (GIST) remains poorly defined. We analyze clinicopathological features and recommend optimal surgical treatment of duodenal GIST. Methods: From July, 2000 to April 2017, 118 patients who had localized duodenal GIST were treated by curative surgical resection at a single institution. We retrospectively reviewed the clinicopathological characteristics and survival outcomes. Results: In survival analysis of all patients, 5-year overall survival (OS) and disease-free survival (DFS) rate were 94.9 and 79.2%, respectively. 19 patients developed recurrent disease at a median of 26.1 months from surgery and most common recurrence site was liver (63.2%). In multivariate analysis, mitotic count was the statistically significant prognostic factors of DFS. Our 20 cases of duodenal GIST in 1 st or 4 th portion were completely resected by limited resection(LR), regardless of tumor size. 98 patients with GISTs in 2 nd or 3 rd portion of duodenum underwent LR (n = 53) or pancreaticoduodenectomy (PD) (n = 45). Patients in the LR group had a smaller median tumor size (4.0 vs 5.3 cm, p = 0.026), more antimesenteric-sided location (41 vs 7cases, p &lt; 0.001), less late complications (1 vs 7 cases, p = 0.014) and no postoperative newly developed diabetes mellitus (0 vs 4 cases, p = 0.027) than those in the PD group. When 53 patients in LR group further divided into minimal invasive LR (MILR) (n = 12) and open-LR (n = 41), MILR group had shorter operation time (155.0 vs 218.8 minutes, p = 0.013) and postoperative hospital stay (12.0 vs 19.4 days, p = 0.036). Conclusions: Patients with duodenal GIST who underwent complete surgical resection have favorable survival outcomes. Predictor of disease recurrence at multivariate analysis was mitotic count. LR is feasible and effective surgical treatment for the patients with small-sized, and anti-mesenteric sided duodenal GIST in terms of long-term oncologic outcomes and quality of life. MILR has better perioperative outcomes than open LR. Therefore, we should consider MILR as optimal surgical treatment for the selected patients with duodenal GIST.
Whole Lung Lavage Followed By Inhaled Sargramostim As Therapy Of Autoimmune Pulmonary Alveolar ProteINOSis
Authors: I. Campo, F. Mariani, E. Paracchini, Z. Kadija, M. Zorzetto, C. Tinelli, G. Rodi, F. Meloni, M. Griese, B. C. Trapnell, G. Scheuch, B. Muellinger, M. Luisetti
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Immune related adverse events (irAEs): A unique profile based on tumor type.
Authors: Nitika Sharma, Prashanti Atluri, Chipman Robert Geoffrey Stroud, Paul R. Walker, Sulochana Devi Cherukuri, Cynthia R. Cherry, Paul Gibbs, Teresa Parent, Jessica Hardin
Journal: Journal of Clinical Oncology (2017)

e14606 Background: Immune checkpoint blockade(ICB) has revolutionized the treatment of a growing number of malignancies. Real world administration of oncolytics is often associated with increased adverse event rates versus what is demonstrated in clinical trials. Whether the tumor biology, site of disease burden or underlying organ dysfunction dictates the differing immune side effect profile in various malignancies remains to be understood. Methods: The incidence of grade 2-4 irAE was abstracted from medical records of all patients (pts) treated with ICB (ipilimumab and/or nivolumab) from 2011 to 2016 at a single institution. Results: Of the 126 pts reviewed, 82 pts had metastatic lung cancer, 31 pts had unresectable or metastatic melanoma, 13 pts had metastatic renal cancer(RCC). In the melanoma cohort, concurrent or sequential PD-1 and CTLA4 blockade was used in 10/31 pts. All of the lung cancer and RCC patients received anti-PD-1 alone. In the patients with lung cancer: pneumonitis was identified in 24%, SIRS in 16%, thrombosis in 11%, cerebritis in 9%, colitis in 4%, hepatitis in 4%, thyroiditis in 5%. In RCC, 8% pts experienced pneumonitis and 8% had thyroiditis. In the melanoma population, colitis was identified in 19%, SIRS in 10%, pneumonitis in 3%, thrombosis in 6%, adrenalitis in 6%, hepatitis in 3%. Colitis was seen in 2/13(15%) pts who got ipilimumab alone and 4/10(40%) pts who got both ipilimumab and nivolumab. Conclusions: Pneumonitis, SIRS and cerebritisappear to be the most prevalent irAEs in lung cancer as compared to melanoma or RCC. The incidence of pneumonitis was higher in RCC compared to melanoma. Colitis appears to have a higher incidence in melanoma, the incidence of which further increases when CTLA4 inhibitors are used in conjunction with anti-PD-1. The majority of the RCC patients tolerated ICB with no major irAEs. With the expanding use of ICB in advanced malignancies, increased awareness of these clinically significant and potentially serious irAEs is indispensable. Future trials designed to distinguish the incidence of irAEs in relation to specific tumor types would be informative. [Table: see text]
Consequences of mutant TET2 on clonality and subclonal hierarchy
Authors: Cassandra M. Hirsch, Aziz Nazha, Kassy Kneen, Mohamed E. Abazeed, Manja Meggendorfer, Bartlomiej P. Przychodzen, Niroshan Nadarajah, Vera Adema, Yasunobu Nagata, Abhinav Goyal, Hassan Awada, Mohammad Fahad Asad, Valeria Visconte, Yihong Guan, Mikkael A. Sekeres, Ryszard Olinski, Babal Kant Jha, Thomas LaFramboise, Tomas Radivoyevitch, Torsten Haferlach, Jaroslaw P. Maciejewski
Journal: Leukemia (2018)
Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature
Authors: Kunal Malik, Helen He, Thy Nhat Huynh, Gary Tran, Kelly Mueller, Kristina Doytcheva, Yael Renert-Yuval, Tali Czarnowicki, Shai Magidi, Margaret Chou, Yeriel D. Estrada, Huei-Chi Wen, Xiangyu Peng, Hui Xu, Xiuzhong Zheng, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2018)
使用分级5-氨基酮戊酸20%和二级局部氨基乙酰丙酸甲酯通过局部光动力疗法来治疗表浅性基底细胞癌:随机对照试验结果
Authors: J.P.H.M. Kessels, H. Kreukels, P.J. Nelemans, M.H. Roozeboom, H. van Pelt, K. Mosterd, E.R.M. de Haas, N.W.J. Kelleners-Smeets
Journal: British Journal of Dermatology (2018)

光动力疗法(PDT)常用于治疗表浅性基底细胞癌(sBCC)。它通过将卟啉前体膏涂抹于所影响的皮肤部位,并盖上敷料来治疗。几小时后揭开闭合的敷料,使用高强度的可见光照射皮肤部位,使癌细胞死亡。荷兰有两种卟啉前体,分别为5‐氨基酮戊酸20% (ALA)和氨基乙酰丙酸甲酯(MAL)。在传统MAL PDT中,皮肤每隔一周照射一次(光治疗)。对于ALA,皮肤每隔两小时接受两次不同的照射。这被称为分级ALA‐PDT。在这项来自荷兰的研究中,我们调查了这种分级ALA‐PDT是否优于传统MAL‐PDT。162名患者被随机分成两组。82名患者使用分级ALA‐PDT治疗,80名患者使用传统MAL‐PDT。12个月后,ALA‐PDT组有6起治疗失败(sBCC复发),MAL‐PDT组有13起治疗失败。尽管MAL‐PDT组的治疗失败数量高出一倍,但这一差异不具有统计显著性。其次,我们调查了两个治疗组的疼痛分数,因为PDT据悉会引起严重的灼烧感。我们发现与MAL‐PDT相比,ALA‐PDT会导致更剧烈的疼痛和更多副作用,例如红斑(红疹,如晒斑)、伤口/糜烂和囊泡(小水泡)。因此,对于治疗sBCC,相比MAL‐PDT,ALA‐PDT趋向于有更好的疗效,尽管差异并不显著。