tbuckley/cabot-search huggingface dataset:
PD-L1 Negative Status is Associated with Lower Mutation Burden, Differential Expression of Immune-Related Genes, and Worse Survival in Stage III Melanoma
Authors: Jason Madore, Dario Strbenac, Ricardo Vilain, Alexander M. Menzies, Jeen Y. H. Yang, John F. Thompson, Georgina V. Long, Graham J. Mann, Richard A. Scolyer, James S. Wilmott
Journal: Clinical Cancer Research (2016)

Understanding why some melanomas test negative for PD-L1 by IHC may have implications for the application of anti-PD-1 therapies in melanoma management. This study sought to determine somatic mutation and gene expression patterns associated with tumor cell PD-L1 expression, or lack thereof, in stage III metastatic melanoma to better define therapeutically relevant patient subgroups.IHC for PD-L1 was assessed in 52 American Joint Committee on Cancer stage III melanoma lymph node specimens and compared with specimen-matched comprehensive clinicopathologic, genomic, and transcriptomic data.PD-L1-negative status was associated with lower nonsynonymous mutation (NSM) burden (P = 0.017) and worse melanoma-specific survival [HR = 0.28 (0.12-0.66), P = 0.002] in stage III melanoma. Gene set enrichment analysis identified an immune-related gene expression signature in PD-L1-positive tumors. There was a marked increase in cytotoxic T-cell and macrophage-specific genes in PD-L1-positive melanomas. CD8A(high) gene expression was associated with better melanoma-specific survival [HR = 0.2 (0.05-0.87), P = 0.017] and restricted to PD-L1-positive stage III specimens. NF1 mutations were restricted to PD-L1-positive tumors (P = 0.041).Tumor negative PD-L1 status in stage III melanoma lymph node metastasis is a marker of worse patient survival and is associated with a poor immune response gene signature. Lower NSM levels were associated with PD-L1-negative status suggesting differences in somatic mutation profiles are a determinant of PD-L1-associated antitumor immunity in stage III melanoma. Clin Cancer Res; 22(15); 3915-23. ©2016 AACR.
Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1 in mice
Authors: Qi Gong, Zhimin Hu, Feifei Zhang, Aoyuan Cui, Xin Chen, Haoyang Jiang, Jing Gao, Xuqing Chen, Yamei Han, Qingning Liang, Dewei Ye, Lei Shi, Y. Eugene Chin, Yu Wang, Hui Xiao, Feifan Guo, Yong Liu, Mengwei Zang, Aimin Xu, Yu Li
Journal: Hepatology (2016)

Among the 22 fibroblast growth factors (FGFs), FGF21 has now emerged as a key metabolic regulator. However, the mechanism whereby FGF21 mediates its metabolic actions per se remains largely unknown. Here, we show that FGF21 represses mammalian target of rapamycin complex 1 (mTORC1) and improves insulin sensitivity and glycogen storage in a hepatocyte-autonomous manner. Administration of FGF21 in mice inhibits mTORC1 in the liver, whereas FGF21-deficient mice display pronounced insulin-stimulated mTORC1 activation and exacerbated hepatic insulin resistance (IR). FGF21 inhibits insulin- or nutrient-stimulated activation of mTORC1 to enhance phosphorylation of Akt in HepG2 cells at both normal and IR condition. TSC1 deficiency abrogates FGF21-mediated inhibition of mTORC1 and augmentation of insulin signaling and glycogen synthesis. Strikingly, hepatic βKlotho knockdown or hepatic hyperactivation of mTORC1/ribosomal protein S6 kinase 1 abrogates hepatic insulin-sensitizing and glycemic-control effects of FGF21 in diet-induced insulin-resistant mice. Moreover, FGF21 improves methionine- and choline-deficient diet-induced steatohepatitis. FGF21 acts as an inhibitor of mTORC1 to control hepatic insulin action and maintain glucose homeostasis, and mTORC1 inhibition by FGF21 has the therapeutic potential for treating IR and type 2 diabetes. (Hepatology 2016;64:425-438).
Patients’ Knowledge, Beliefs, and Distress Associated with Detection and Evaluation of Incidental Pulmonary Nodules for Cancer: Results from a Multicenter Survey
Authors: Marc R. Freiman, Jack A. Clark, Christopher G. Slatore, Michael K. Gould, Steven Woloshin, Lisa M. Schwartz, Renda Soylemez Wiener
Journal: Journal of Thoracic Oncology (2016)
Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure
Authors: Paul G. Richardson, Marcie L. Riches, Nancy A. Kernan, Joel A. Brochstein, Shin Mineishi, Amanda M. Termuhlen, Sally Arai, Stephan A. Grupp, Eva C. Guinan, Paul L. Martin, Gideon Steinbach, Amrita Krishnan, Eneida R. Nemecek, Sergio Giralt, Tulio Rodriguez, Reggie Duerst, John Doyle, Joseph H. Antin, Angela Smith, Leslie Lehmann, Richard Champlin, Alfred Gillio, Rajinder Bajwa, Ralph B. D’Agostino, Joseph Massaro, Diane Warren, Maja Miloslavsky, Robin L. Hume, Massimo Iacobelli, Bijan Nejadnik, Alison L. Hannah, Robert J. Soiffer
Journal: Blood (2016)
Correlates and determinants of nuclear epidermal growth factor receptor (EGFR) content in an oropharyngeal cancer tissue microarray
Authors: A. Psyrri, P. Weinberger, Z. Yu, C. Sasaki, B. Haffty, D. Kowalski, B. Burtness
Journal: Journal of Clinical Oncology (2007)

6022 Background: We have previously reported nuclear localization of EGFR protein in oropharyngeal cancer tissue. Nuclear EGFR levels were inversely correlated with survival and response to radiotherapy. Here, we sought to identify determinants and correlates of nuclear EGFR content. Methods: We analyzed an oropharyngeal cancer tissue microarray for expression of key molecules of EGFR signaling cascade utilizing an automated image analysis technique (AQUA) scored on a scale of 0–255 which permits protein quantitation and subcellular localization. Patients with OSCC treated with radiotherapy (RT) or surgery and RT were eligible. Data were analyzed using Pearson correlations and multiple linear regression with robust standard errors. Results: Of the 95 tumors included in this study, 72 (75%) had sufficient tissue for analysis of nuclear EGFR. Nuclear EGFR levels were associated with membranous/cytoplasmic EGFR levels (rho=0.85, p&lt;0.01), nuclear ERK2 (rho=0.34, p=0.01), tumor cyclin D1 (rho=−0.25, p=0.06) and the proliferation markers Ki-67 (rho=0.24,p=0.06) and PCNA (rho=0.38, p&lt;0.01). Nuclear phosphorylated-Akt, PTEN, p53 levels did not correlate with nuclear EGFR level. In multivariable analysis, only PCNA retained its significant association (p=0.01). Conclusions: Our results are consistent with the preclinical model of translocation of membranous EGFR to the nucleus acting as a transcriptional factor and fostering cell proliferation. Nuclear EGFR may constitute a mechanism of resistance to current EGFR-targeted therapies. No significant financial relationships to disclose.
Prognostic Significance of Procalcitonin in Small Cell Lung Cancer
Authors: Satoshi Watanabe, Ko Sato, Satoru Miura, Hiroshi Kagamu, Tomohiro Tanaka, Yu Saida, Rie Kondo, Masaaki Okajima, Ichiei Narita, Hirohisa Yoshizawa
Journal: Annals of Oncology (2014)
Potential Benefits of Computer-Aided Detection for Cancer Identification and Treatment—Reply
Authors: Constance Lehman
Journal: JAMA Internal Medicine (2016)

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
Deletion of Pten in CD45-expressing cells leads to development of T-cell lymphoblastic lymphoma but not myeloid malignancies
Authors: Cristina Mirantes, Maria Alba Dosil, David Hills, Jian Yang, Núria Eritja, Maria Santacana, Sònia Gatius, Felip Vilardell, Alexander Medvinsky, Xavier Matias-Guiu, Xavier Dolcet
Journal: Blood (2016)
Massachusetts Department of Public Health
Authors: Susan S. Gallagher, Bernard Guyer, Milton Kotelchuck, Joel Bass, Frederick H. Lovejoy, Elizabeth McLoughlin, Kishor Mehta
Journal: New England Journal of Medicine (1982)

Accidental injuries are the leading cause of childhood mortality and disability.1 Both the Surgeon General's Report on Health Promotion and Disease Prevention1 and the Massachusetts Department of Public Health's report, "A Program for Prevention in Massachusetts,"2 propose that the reduction of childhood injuries be a major goal in preventive health care.Little progress has been made in controlling accidental injuries, despite the recognized importance of injuries as a cause of childhood morbidity and mortality. There are several reasons for this. First of all, because the word "accident" is used to describe these events, both the public and the health-care profession . . .
Folate receptor mediated targeted drug delivery into cancer cells
Authors: Bijesh Biswal, Rama Verma, Edamana Prasad
Journal: Clinical Cancer Research (2008)

A4   Folic acid is an essential vitamin and enters the cells in its reduced form through two ways via folate receptor (FR) and by reduced folate carrier (RFC). Folate receptor (FR) is a glycosylphosphatidyl inositol (GPI) membrane anchored protein, which mediate the unidirectional uptake of folate and methotrexate. Folate receptors are over expressed in certain tumors and used as markers for targeted drug delivery to cancerous tissue. Methotrexate (MTX) acts as a potent competitive inhibitor of dihydrofolate reductase (DHFR), used as chemotherapeutic agent in cancer therapy however the transport mechanism for MTX is unknown. Altered folate metabolism results in numerous diseases like megaloblastic anemia, carcinogenesis, and cardiovascular disease and in the occurrence of neural tube defect pregnancies. Involvement of folate in carcinogenesis and use of antifolate methotrexate (MTX) as an anti-cancer agent, have kindled interest in the transport and metabolism of folate and methotrexate in T cells.  We tried folate receptor mediated targeted drug delivery approach. We have synthesized FOL-PEG-PEI (Folic acid - polyethylene glycol - Polyethyleneimine) conjugate for targeted delivery into cancer cells through folate receptor. In this conjugate PEI was used as transfection reagent and attachment factor, folate is used as targeting moiety to specifically target cancer cells that over express folate receptor. Cytotoxic agent like methotrexate was used along with this conjugate to make it a complete therapeutic agent. Radioactive methotrexate and folate were used for checking the efficacy. The synthesized construct was transfected into cell lines and it has shown promising results in leukemic cell line MOLT4.
Too Much of a Good Thing
Authors: Lauren A. Beste, Richard H. Moseley, Sanjay Saint, Paul B. Cornia
Journal: New England Journal of Medicine (2016)

A 54-year-old man presented to the emergency department with a 1-month history of edema in the lower legs and a 1-week history of upper abdominal pain. He also reported intermittent nausea, early satiety, and diarrhea but did not have fevers, chills, or vomiting.
Continuous intravenous lidocaine controls abdominal pain secondary to peritoneal carcinomatosis as a consequence of diffusion into ascites
Authors: T. Tanaka, R. Tsukui, S. Okano, M. Tsuchiya, K. Obokata, T. Ogawa, T. Abe, T. Ikeya, M. Miyasaki
Journal: Journal of Clinical Oncology (2007)

9031 Background: Our team reported at the 42 nd ASCO meeting that continuous, low-dose intravenous (IV) lidocaine is an effective method for pain relief in terminal patients with peritoneal carcinomatosis. Our aim was to explore the mechanism by which abdominal pain of terminally-ill patients with peritoneal carcinomatosis was improved by continuous IV lidocaine. Methods: 48 patients with peritoneal carcinomatosis due to GI (46) and GYN (2) malignancies were administered lidocaine at low-doses (0.4 and/or 0.8mg/kg- h) for &gt;24 hours, because opiates, NSAIDs, and other adjuvants were ineffective in relieving their abdominal pain. Pain (faces rating scale; 0-no pain, 5-worst pain), oral intake, side effects, and activities of daily life were quantified. Two days after beginning lidocaine, ascites was sampled to measure ascitic concentration of lidocaine, tumor markers and cytology. Results: Mean age (±SE) was 60±2. The volume of ascites was estimated to be 2,700±400ml by the ultrasound 5 points methodology. Abdominal symptoms improved in 1.5±0.2days after beginning lidocaine, and the pain scale decreased from 1.9±0.2 to 0.5±0.1; p&lt;0.001; 75% of patients had improvement in pain of whom 78% had complete relief of pain. Oral intake increased from 18% to 49% of baseline (p&lt;0.001), and 67% in those with improvement in pain had an increased volume of oral intake. There were no obvious differences in response to 0.4 and 0.8 mg/kg-h in patients receiving both doses. Serum concentrations of lidocaine at 0.4 and 0.8 mg/kg-h were 1.7±0.2 and 3.2±0.2 μg/ml, respectively; lidocaine concentrations in the ascites were 1.2±0.2 and 2.1±0.2 μg/ml. No patient complained of pain at the time of peritoneal puncture. Side effects included bradycardia of &lt;60 beats per minutes (3 patients). The duration of lidocaine administration was 23±3 days; 43% of patients were able to be discharged home for end-of-life care, with parenteral nutrition and continuation of lidocaine administration or oral mexiletine (300–450 mg/day) for adjuvant analgesia. Conclusions: Lidocaine diffuses into ascites and almost equilibrates with serum concentrations acting as a peritoneal anesthesia which, as a result, controls abdominal pain in patients with peritoneal carcinomatosis. No significant financial relationships to disclose.
Impaired Efferocytosis and Production of Mitochondrial Reactive Oxygen Species (mitoROS) By Monocytes in Human Chronic Granulomatous Disease (CGD) Is Reversed By Treatment with the Ppargamma Agonist Pioglitazone (Pio)
Authors: Donna Bratton, Ruby Fernandez-Boyanapalli, Emilia Liana Falcone, Christa Zerbe, Beatrix Marciano, Steven M. Holland
Journal: Journal of Allergy and Clinical Immunology (2016)
Regulation of platelet clearance receptors for atrial natriuretic peptide in diabetic nephropathy.
Authors: S Canaan-Kuhl, L Parra-Roide, J W Bialek, R L Jamison, B D Myers
Journal: Journal of the American Society of Nephrology (1992)

The findings that circulating levels of atrial natriuretic peptide (ANP) are elevated in diabetic nephropathy and that the magnitude of the urinary excretion rate of cGMP in response to hypervolemia-induced ANP release is blunted have recently been reported. The purpose of this study was to determine whether these abnormalities are associated with the down-regulation of ANP receptors. Because biologically active (A) ANP receptors in the kidney are inaccessible, we have examined the binding of (125I alpha)ANP to clearance (C) receptors on platelets obtained from patients with diabetic nephropathy. Scatchard analysis revealed a reduction in such binding sites compared with those in healthy controls: 12 +/- 2 versus 19 +/- 2 per platelet, respectively (P less than 0.001). The dissociation constant, Kd, was higher: 66.7 +/- 33.1 versus 38.5 +/- 11 pM, respectively (P less than 0.02). The reduced number of receptors could reflect the down-regulation of ANP C receptors in response to an elevation of plasma levels of ANP, the median value of which was 10.6 versus 7.1 pmol/L in controls (P less than 0.05). Alternatively, the findings could represent a primary adaptation by C receptors to elevate plasma ANP levels and increase the availability of the peptide to biologically active renal receptors. The latter adaptation would serve to mitigate the sodium retention that attends diabetic nephropathy.
Abstract 18324: Complication Rates of Atrial Fibrillation Ablations: A Comparison of Outcomes From a National Administrative Database to Contemporary Randomized Control Trials
Authors: Naga Venkata K Pothineni, Amit Noheria, Sadip Pant, Nileshkumar J Patel, Ankit Chothani, Neeraj Shah, Kathan Mehta, Ghanshyambhai T Savani, Peeyush Grover, Vipulkumar Bhalara, Ankit Rathod, Abhishek Deshmukh, Juan Viles-Gonzalez, Hakan Paydak
Journal: Circulation (2013)

Introduction: The availability, national scope and perceived unbiased nature of administrative data make it the preferred choice for evaluating quality and outcomes. We calculated Atrial Fibrillation ablation complication rates from national administrative data and compared them with data from randomized control trials (RCT). Methods: Using the Nationwide Inpatient Sample (NIS) we identified patients treated with AF ablations. We investigated complications described with AF ablation and defined them by validated Clinical Modification (ICD-9-CM) diagnosis codes. We compared them with the complication rates reported from AF ablation from widely quoted RCTs. (AF ablation vs. Antiarrhythmics) Results: We analyzed complication rates from 47042 AF ablations performed from the years 2000 to 2008 from the NIS. We also analyzed pooled complication rates from large RCTs. Cardiac tamponade and/or effusion and vascular access complication appear to be the most frequent complications. The NIS data had a higher rate of cardiac tamponade/effusion (21.5 vs. 12.5), vascular access complications (21.2 vs. 19.7) and deaths (4.0 vs. 3.0) when compared to RCTs. Interestingly, RCTs reported a higher rate of stroke/TIA (13.2 vs. 7) when compared to the national administrative data. Conclusion: Despite substantial improvement, “real-world” complication rates from administrative data remain higher than those reported in RCTs. The discrepancy may be attributable to differences in operator skills, selection bias and variation in data quality.
Depression and suicide ideation in the young adult
Authors: E L Goldberg
Journal: American Journal of Psychiatry (1981)

As part of the Community Mental Health Epidemiology Program 489 18--24-year-olds in Washington County, Md., and Kansas City, Mo., were studied to learn which factors are related to thoughts of suicide in young adults. Depressive symptomatology, poor physical health, and minor psychiatric symptoms were present in this population, as they are in adults of all ages who have suicide ideation. Overt aggression and separation from the mother before 16 years of age were also present. These factors have been previously shown to be characteristic of suicide attempters and completers, so early identification of people at high risk for suicide by use of these factors may be feasible.
Probable Hospital Cluster of H7N9 Influenza Infection
Authors: Amber Farooqui, Weidong Liu, Tiansheng Zeng, Yisu Liu, Li Zhang, Adnan Khan, Xiuming Wu, Renhua Wu, Suwu Wu, Linxi Huang, Yingmu Cai, Alyson A Kelvin, Stephane G Paquette, Kezhao Hu, Nanlan Zheng, Hongxia Chen, Sheng Xu, Chunnuan Lin, Peng Sun, Zhancheng Yao, Jun Wang, Huanjie Ma, Zhijian Zhu, Pengzhou Lin, Weihong Chen, Xibing Fang, Jesus F Bermejo-Martin, Alberto J Leon, David J Kelvin
Journal: New England Journal of Medicine (2016)

This report shows evidence for nosocomial transmission of H7N9 influenza from a patient to two physicians who provided care.
A Textile‐Based Stretchable Multi‐Ion Potentiometric Sensor
Authors: Marc Parrilla, Rocío Cánovas, Itthipon Jeerapan, Francisco J. Andrade, Joseph Wang
Journal: Advanced Healthcare Materials (2016)

A textile-based wearable multi-ion potentiometric sensor array is described. The printed flexible sensors operate favorably under extreme mechanical strains (that reflect daily activity) while offering attractive real-time noninvasive monitoring of electrolytes such as sodium and potassium.
MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children’s Oncology Group Study
Authors: K Matlawska-Wasowska, H Kang, M Devidas, J Wen, R C Harvey, C K Nickl, S A Ness, M Rusch, Y Li, M Onozawa, C Martinez, B L Wood, B L Asselin, I-M Chen, K G Roberts, A Baruchel, J Soulier, H Dombret, J Zhang, R S Larson, E A Raetz, W L Carroll, N J Winick, P D Aplan, M L Loh, C G Mullighan, S P Hunger, N A Heerema, A J Carroll, K P Dunsmore, S S Winter
Journal: Leukemia (2016)
M011L-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma
Authors: Alexandra Pisklakova, Brienne McKenzie, Franz Zemp, Xueqing Lun, Rajappa S. Kenchappa, Arnold B. Etame, Masmudur M. Rahman, Karlyne Reilly, Shari Pilon-Thomas, Grant McFadden, Ebba Kurz, Peter A. Forsyth
Journal: Neuro-Oncology (2016)

Myxoma virus (MYXV) is a promising oncolytic agent and is highly effective against immortalized glioma cells but less effective against brain tumor initiating cells (BTICs), which are believed to mediate glioma development/recurrence. MYXV encodes various proteins to attenuate host cell apoptosis, including an antiapoptotic Bcl-2 homologue known as M011L. Such proteins may limit the ability of MYXV to kill BTICs, which have heightened resistance to apoptosis. We hypothesized that infecting BTICs with an M011L-deficient MYXV construct would overcome BTIC resistance to MYXV.We used patient-derived BTICs to evaluate the efficacy of M011L knockout virus (vMyx-M011L-KO) versus wild-type MYXV (vMyx-WT) and characterized the mechanism of virus-induced cell death in vitro. To extend our findings in a novel immunocompetent animal model, we derived, cultured, and characterized a C57Bl/6J murine BTIC (mBTIC0309) from a spontaneous murine glioma and evaluated vMyx-M011L-KO efficacy with and without temozolomide (TMZ) in mBTIC0309-bearing mice.We demonstrated that vMyx-M011L-KO induces apoptosis in BTICs, dramatically increasing sensitivity to the virus. vMyx-WT failed to induce apoptosis as M011L protein prevented Bax activation and cytochrome c release. In vivo, intracranial implantation of mBTIC0309 generated tumors that closely recapitulated the pathological and molecular profile of human gliomas. Treatment of tumor-bearing mice with vMyx-M011L-KO significantly prolonged survival in immunocompetent-but not immunodeficient-mouse models, an effect that is significantly enhanced in combination with TMZ.Our data suggest that vMyx-M011L-KO is an effective, well-tolerated, proapoptotic oncolytic virus and a strong candidate for clinical translation.
Involvement of Chromosome #2 in Chromosome Changes in Primary Leukemia Induced in Rats by N -Nitroso- N -butylurea 2
Authors: Hiroshi Uenaka, Norifumi Ueda, Sakan Maeda, Taketoshi Sugiyama
Journal: JNCI Journal of the National Cancer Institute (1978)

Cytogenetic studies were done on 34 primary leukemias induced by N-nitroso-N-butylurea (NBU) in outbred Long-Evans rats. The results revealed leukemia cells with #2 trisomy and long #2 chromosome, which characterized the leukemias induced by polycyclic hydrocarbon carcinogens such as 7,12- dimethylbenz[a]anthracene and 7,8,12-trimethylbenz[a]anthracene. These findings suggest a common mode of action of different carcinogenic chemicals at the chromosome level, although the lower incidence of these chromosome changes and of erythroblastic leukemias with NBU suggests subtle differences in their actions.