tbuckley/cabot-search huggingface dataset:
T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen.
Authors: S R Burrows, S L Silins, D J Moss, R Khanna, I S Misko, V P Argaet
Journal: The Journal of Experimental Medicine (1995)

Two unusual characteristics of the memory response to the immunodominant Epstein-Barr virus (EBV) epitope FLRGRAYGL, which associates with HLA B8, have provided an unique opportunity to investigate self tolerance and T cell receptor (TCR) plasticity in humans. First, the response is exceptionally restricted, dominated by cytotoxic T lymphocytes (CTL) with identical TCR protein sequences (Argaet, V. P., C. W. Schmidt, S. R. Burrows, S. L. Silins, M. G. Kurilla, D. L. Doolan, A. Suhrbier, D. J. Moss, E. Kieff, T. B. Sculley, and I. S. Misko. 1994. J. Exp. Med. 180:2335-2340). Second, CTL expressing this receptor are cross-reactive with the alloantigen HLA B* 4402 on uninfected cells (Burrows, S. R., R. Khanna, J. M. Burrows, and D. J. Moss. 1994. J. Exp. Med. 179:1155-1161). No CTL using this conserved public TCR could be reactivated from the peripheral blood of EBV exposed individuals expressing both HLA B8 and B*4402, demonstrating the clonal inactivation of potentially self-reactive T cells in humans. A significant FLRGRAYGL-specific response was still apparent, however, and TCR sequence analysis of multiple CTL clones revealed an oligoclonal TCR repertoire for this determinant within these individuals, using diverse V and J gene segments and CDR3 regions. In addition, a significant public TCR component was identified in which several distinct alpha/beta rearrangements are shared by CTL clones from a number of unrelated HLA B8+, B*4402+ donors. The striking dominance of public TCR in the response to this EBV epitope suggests a strong genetic bias in TCR gene recombination. Fine specificity analysis using peptide analogues showed that, of six different antigen receptors for FLRGRAYGL/HLA B8, none associate closely with the peptide's full array of potential TCR contact residues. Whereas the HLA B*4402-cross-reactive receptor binds amino acids toward the COOH terminus of the peptide, others preferentially favor an NH2-terminal determinant, presumably evading an area that mimics a structure presented on HLA B*4402. Thus, tolerance to a background major histocompatibility antigen can effectively diversify the TCR repertoire for a foreign epitope by deflecting the response away from an immunodominant combination of TCR-binding residues.
Imaging Brain Networks After Cancer and Chemotherapy
Authors: Kelly N. H. Nudelman, Brenna C. McDonald, Andrew J. Saykin
Journal: JAMA Oncology (2015)

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 Oncology 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 Oncology journal
Photodynamic Therapy in Cholangiocarcinoma
Authors: Michel Kahaleh
Journal: Journal of the National Comprehensive Cancer Network (2012)

Most patients with hilar cholangiocarcinoma have unresectable disease and require palliation with biliary stenting to alleviate symptoms. Although chemotherapy and radiotherapy have been ineffective, many studies have suggested that the use of photodynamic therapy (PDT) may improve quality of life and perhaps survival in these patients. The ability of PDT to transmit through bile makes it a unique platform for intervention in the biliary tree. This article addresses the clinical implications of endoscopic biliary drainage, explores past and present study findings with PDT for cholangiocarcinoma, and offers an introduction to the novel techniques for direct visualization.
Association of hip pain with radiographic evidence of hip osteoarthritis: diagnostic test study
Authors: Chan Kim, Michael C Nevitt, Jingbo Niu, Mary M Clancy, Nancy E Lane, Thomas M Link, Steven Vlad, Irina Tolstykh, Pia M. Jungmann, David T Felson, Ali Guermazi
Journal: BMJ (2015)

<b>Study question</b> Is there concordance between hip pain and radiographic hip osteoarthritis? <b>Methods</b> In this diagnostic test study, pelvic radiographs were assessed for hip osteoarthritis in two cohorts: the Framingham Osteoarthritis Study (community of Framingham, Massachusetts) and the Osteoarthritis Initiative (a multicenter longitudinal cohort study of osteoarthritis in the United States). Using visual representation of the hip joint, participants reported whether they had hip pain on most days and the location of the pain: anterior, groin, lateral, buttocks, or low back. In the Framingham study, participants with hip pain were also examined for hip pain with internal rotation. The authors analysed the agreement between radiographic hip osteoarthritis and hip pain, and for those with hip pain suggestive of hip osteoarthritis they calculated the sensitivity, specificity, positive predictive value, and negative predictive value of radiographs as the diagnostic test. <b>Study answer and limitations</b> In the Framingham study (n=946), only 15.6% of hips in patients with frequent hip pain showed radiographic evidence of hip osteoarthritis, and 20.7% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of radiographic hip osteoarthritis for hip pain localised to the groin was 36.7%, specificity 90.5%, positive predictive value 6.0%, and negative predictive value 98.9%. Results did not differ much for hip pain at other locations or for painful internal rotation. In the Osteoarthritis Initiative study (n=4366), only 9.1% of hips in patients with frequent pain showed radiographic hip osteoarthritis, and 23.8% of hips with radiographic hip osteoarthritis were frequently painful. The sensitivity of definite radiographic hip osteoarthritis for hip pain localised to the groin was 16.5%, specificity 94.0%, positive predictive value 7.1%, and negative predictive value 97.6%. Results also did not differ much for hip pain at other locations. <b>What this study adds</b> Hip pain was not present in many hips with radiographic osteoarthritis, and many hips with pain did not show radiographic hip osteoarthritis. Most older participants with a high suspicion for clinical hip osteoarthritis (groin or anterior pain and/or painful internal rotation) did not have radiographic hip osteoarthritis, suggesting that in many cases, hip osteoarthritis might be missed if diagnosticians relied solely on hip radiographs. <b>Funding, competing interests, data sharing</b> See the full paper on thebmj.com for funding. The authors have no competing interests. Additional data are available from bevochan@bu.edu.
Clinical significance of PD-L1 protein expression on tumor-associated macrophages in lung cancer
Authors: Kurt Alex Schalper, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Vamsidhar Velcheti, Lieping Chen, Miguel Sanmamed, Roy S Herbst, David L Rimm
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumor PD-L1 expression is associated with increased tumor-infiltrating lymphocytes (TILs) in diverse solid tumors, including lung cancer. In addition, PD-L1 upregulation in tumor and/or stromal immune cells has been associated with increased clinical benefit to PD-1/PD-L1 axis
Subacute Invasive Pulmonary Aspergillosis Associated with Ankylosing Spondylitis
Authors: Amy Houghton Attaway, Frank Jacono, Robert Gilkeson, Jihane Abdelmassih Faress
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

A 72-year-old smoker with a history of ankylosing spondylitis, who was not receiving immunosuppressants, was hospitalized for severe influenza pneumonia in January. He was treated with oseltamivir and antibiotics and enrolled in a clinical trial that evaluated steroids for the treatment of community-acquired pneumonia. It is unknown whether he was in the placebo or treatment group; however, treatment involved an initial methylprednisolone 40mgbolus, followed by 40mg/d for 5 days, and then a rapid taper over 1week. He then presented in March with worsening dyspnea, productive cough, weight loss, lethargy, and an overall decline in clinical status. Imaging during this admission revealed bilateral upper lobe cavitary lesions with fungus balls and associated infiltrates. Multiple sputum cultures were positive for Aspergillus fumigatus, and Aspergillus antibodies were detected by immunodiffusion and complement fixation (1:64). He was diagnosed presumptively with subacute invasive pulmonary aspergillosis and began treatment with voriconazole. Patients with ankylosing spondylitis can develop pulmonary manifestations of their disease, including apical fibrobullous disease (1). They are more likely to develop apical superinfections with mycobacterial or fungal infections as well, the most common of which is Aspergillus (2, 3). Influenza is associated with increased risk for invasive aspergillosis; this is believed to be because of the disruption of the bronchial mucosa, which leads to an impaired immune response (4). This, possibly coupled with the use of steroids, could have promoted further immune dysregulation and facilitated an environment for Aspergillus to grow. n
Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease
Authors: Jeanne Palmer, Xiaoyu Chai, Joseph Pidala, Yoshihiro Inamoto, Paul J. Martin, Barry Storer, Iskra Pusic, Mary E. D. Flowers, Mukta Arora, Steven Z. Pavletic, Stephanie J. Lee
Journal: Blood (2015)
Studies on Fatty Acid Oxidation by Normal and Neoplastic Liver
Authors: Carl G. Baker, Alton Meister
Journal: JNCI Journal of the National Cancer Institute (1950)

Journal Article Studies on Fatty Acid Oxidation by Normal and Neoplastic Liver Get access Carl G. Baker, Carl G. Baker Search for other works by this author on: Oxford Academic PubMed Google Scholar Alton Meister Alton Meister National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 5, April 1950, Pages 1191–1198, https://doi.org/10.1093/jnci/10.5.1191 Published: 01 April 1950 Article history Received: 31 January 1950 Published: 01 April 1950
Updated Clinical Classification of Pulmonary Hypertension
Authors: Gerald Simonneau, Michael A. Gatzoulis, Ian Adatia, David Celermajer, Chris Denton, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, R. Krishna Kumar, Michael Landzberg, Roberto F. Machado, Horst Olschewski, Ivan M. Robbins, Rogiero Souza
Journal: Journal of the American College of Cardiology (2013)
Altered Drug Binding to Serum Proteins in Pregnant Women: Therapeutic Relevance
Authors: E Peruccam, M Ruprah, A Richens
Journal: Journal of the Royal Society of Medicine (1981)

The binding of diazepam, phenytoin and valproic acid to serum proteins in vitro has been compared in pregnant women of different gestational ages and in controls. The unbound fraction of each of the three drugs was elevated during pregnancy (particularly during the last 8 weeks) probably due, at least in part, to a fall in serum albumin concentration. These findings may provide a partial explanation for the increase in the clearance of certain drugs during pregnancy and need to be taken into account when interpreting serum drug levels in clinical practice.
Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin‐8 (CXCL8), Myeloid‐Related Protein 8/Myeloid‐Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease
Authors: Laura B. E. Kienhorst, Ellen van Lochem, Wietske Kievit, Nicola Dalbeth, Marilyn E. Merriman, Amanda Phipps‐Green, Arnoud Loof, Waander van Heerde, Sita Vermeulen, Lisa K. Stamp, Elly van Koolwijk, Jacqueline de Graaf, Dirk Holzinger, Johannes Roth, Hein J. E. M. Janssens, Tony R. Merriman, Jasper C. A. Broen, Matthijs Janssen, Timothy R. D. J. Radstake
Journal: Arthritis & Rheumatology (2015)

The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients.We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls. We measured circulating levels of interleukin-8 (IL-8)/CXCL8, IL-1β, IL-6, IL-10, IL-12, and tumor necrosis factor, after which we performed proteome-wide analysis in a selection of samples to identify proteins that were possibly prognostic for the development of comorbidities. Replication analysis was performed specifically for myeloid-related protein 8 (MRP-8)/MRP-14 complex.Compared to healthy controls and disease control patients, patients with gouty arthritis (n = 48) had significantly higher mean levels of CXCL8 (P < 0.001), while other cytokines were almost undetectable. Similarly, patients with intercritical gout showed high levels of CXCL8. CXCL8 was independently associated with diabetes mellitus in patients with intercritical gout (P < 0.0001). Proteome-wide analysis in gouty arthritis (n = 18) and intercritical gout (n = 39) revealed MRP-8 and MRP-14 as the proteins with the greatest differential expression between low and high levels of CXCL8 and also showed a positive correlation of MRP8/MRP14 complex with CXCL8 levels (R(2) = 0.49, P < 0.001). These findings were replicated in an independent cohort. The proteome of gout patients with high levels of CXCL8 was associated with diabetes mellitus (odds ratio 16.5 [95% confidence interval 2.8-96.6]) and CVD (odds ratio 3.9 [95% confidence interval 1.0-15.3]).Circulating levels of CXCL8 are increased during both the acute and intercritical phases of gout, and they coincide with a specific circulating proteome that is associated with risk of diabetes mellitus and CVD. Further research focused on the roles of CXCL8 and MRP8/MRP14 complex in patients with gout is warranted.
The nephropathy of non-insulin-dependent diabetes
Authors: P Ruggenenti, V Gambara, A Perna, T Bertani, G Remuzzi
Journal: Journal of the American Society of Nephrology (1998)

Nephropathy of non-insulin-dependent diabetes mellitus (NIDDM) is the most common cause of end-stage renal failure (ESRF) in Western countries. This study investigates the clinical and histologic putative predictors of disease progression, with the final goal to identify patients at risk who may benefit from early diagnosis and intervention. It examines by repeated measurements of BP, blood glucose, serum creatinine, and urinary protein excretion rate 65 consecutive NIDDM patients with clinical, persistent proteinuria and biopsy-documented typical diabetic glomerulopathy (class I; n = 30), predominant nephroangiosclerosis (class II; n = 23), or nondiabetic type glomerulopathy (class III; n = 12), whose severity of renal tissue involvement was precisely quantified by a global histologic score. Baseline parameters and progression to renal end points, i.e., doubling of baseline serum creatinine, dialysis, or transplantation, were univariately and multivariately correlated by proportional hazards regression models. The median kidney survival time in the overall study population was 3.07 yr. Thirty-seven percent of patients reached an end point during a median (range) follow-up of 1.8 yr (0.4 to 5.7 yr). By univariate and multivariate analysis, kidney survival significantly correlated with baseline urinary protein excretion rate (P = 0.04 and P = 0.04, respectively) and renal tissue injury score (P = 0.0001 and P = 0.02, respectively), but not with the histologic classes. Patients with a urinary protein excretion rate < or = 2 g/24 h, or > 2 g/24 h with a histologic score < 7, never reached an end point. All patients with urinary protein excretion > 2 g/24 h and a histologic score > 13 progressed to ESRF over a median of 1.6 yr. No differences in other baseline parameters or in BP and diabetes control during follow-up accounted for these different outcomes. In NIDDM as well as in nondiabetic chronic renal disease, quantification of urinary protein excretion rate--independent of the pattern of underlying glomerular involvement--reliably discriminates progressors from nonprogressors and, combined with precise quantification of renal tissue injury, reliably predicts risk of ESRF. This information may be used to set guidelines for early diagnosis and appropriate intervention to reduce the number of diabetic patients who will need renal replacement therapy in years to come.
Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition
Authors: Anton Henssen, Kristina Althoff, Andrea Odersky, Anneleen Beckers, Richard Koche, Frank Speleman, Simon Schäfers, Emma Bell, Maike Nortmeyer, Frank Westermann, Katleen De Preter, Alexandra Florin, Lukas Heukamp, Annika Spruessel, Kathy Astrahanseff, Sven Lindner, Natalie Sadowski, Alexander Schramm, Lucile Astorgues-Xerri, Maria E. Riveiro, Angelika Eggert, Esteban Cvitkovic, Johannes H. Schulte
Journal: Clinical Cancer Research (2015)

Targeting BET proteins was previously shown to have specific antitumoral efficacy against MYCN-amplified neuroblastoma. We here assess the therapeutic efficacy of the BET inhibitor, OTX015, in preclinical neuroblastoma models and extend the knowledge on the role of BRD4 in MYCN-driven neuroblastoma.The efficacy of OTX015 was assessed in in vitro and in vivo models of human and murine MYCN-driven neuroblastoma. To study the effects of BET inhibition in the context of high MYCN levels, MYCN was ectopically expressed in human and murine cells. The effect of OTX015 on BRD4-regulated transcriptional pause release was analyzed using BRD4 and H3K27Ac chromatin immunoprecipitation coupled with DNA sequencing (ChIP-Seq) and gene expression analysis in neuroblastoma cells treated with OTX015 compared with vehicle control.OTX015 showed therapeutic efficacy against preclinical MYCN-driven neuroblastoma models. Similar to previously described BET inhibitors, concurrent MYCN repression was observed in OTX015-treated samples. Ectopic MYCN expression, however, did not abrogate effects of OTX015, indicating that MYCN repression is not the only target of BET proteins in neuroblastoma. When MYCN was ectopically expressed, BET inhibition still disrupted MYCN target gene transcription without affecting MYCN expression. We found that BRD4 binds to super-enhancers and MYCN target genes, and that OTX015 specifically disrupts BRD4 binding and transcription of these genes.We show that OTX015 is effective against mouse and human MYCN-driven tumor models and that BRD4 not only targets MYCN, but specifically occupies MYCN target gene enhancers as well as other genes associated with super-enhancers. Clin Cancer Res; 22(10); 2470-81. ©2015 AACR.
Biweekly irinotecan or raltitrexed plus 6S-leucovorin and bolus 5-fluorouracil in advanced colorectal carcinoma: A Southern Italy Cooperative Oncology Group phase II–III randomized trial
Authors: P. Comella, F. De Vita, S. Mancarella, L. De Lucia, M. Biglietto, R. Casaretti, A. Farris, G.P. Ianniello, V. Lorusso, A. Avallone, G. Carteni, S. Leo, G. Catalano, M. De Lena, G. Comella
Journal: Annals of Oncology (2000)
Response to primary chemotherapy in breast cancer patients with tumors not expressing estrogen and progesterone receptors
Authors: M. Colleoni, I. Minchella, G. Mazzarol, F. Nolè, G. Peruzzotti, A. Rocca, G. Viale, L. Orlando, G. Ferretti, G. Curigliano, P. Veronesi, M. Intra, A. Goldhirsch
Journal: Annals of Oncology (2000)
Expression of Cxcr4 in Tumor and Bone Marrow of Gastric Cancer Patients: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells and Survival
Authors: D. Osinsky, A. Kovelskaya, L. Bubnovskaya, I. Ganusevich, L. Gumenyuk, S. Merentsev, S. Osinsky, L. Mamontova
Journal: Annals of Oncology (2014)
Chemotherapy-Related Chronic Myelogenous Leukemia
Authors: Nabil Adra, Hamid Sayar, Lawrence H. Einhorn
Journal: JAMA Oncology (2015)

This Research Letter reports 3 cases of chromosome-positive chronic myelogenous leukemia (CML) following therapy for germ-cell tumors and poses questions regarding the connection of etoposide and cisplatin-containing combination chemotherapy and secondary CML.
Biomarkers (BM) France: Results of routine EGFR, HER2, KRAS, BRAF, PI3KCA mutations detection and EML4-ALK gene fusion assessment on the first 10,000 non-small cell lung cancer (NSCLC) patients (pts).
Authors: Fabrice Barlesi, Helene Blons, Michele Beau-Faller, Isabelle Rouquette, L'houcine Ouafik, Jean Mosser, Jean-Philippe Merlio, Pierre Paul Bringuier, Philippe Jonveaux, Cedric Le Marechal, Marc G. Denis, Frederique Madeleine Penault-Llorca, Didier Debieuvre, Jean-Charles Soria, Jacques Cadranel, Julien Mazieres, Pascale Missy, Franck Morin, Frederique Nowak, Gerard Zalcman
Journal: Journal of Clinical Oncology (2013)

8000 Background: Personalized medicine is now a reality for advanced NSCLC pts on the basis of routine screening for EGFR mutation and ALK gene fusion assessment. The French NCI (INCa) also decided to additionally fund the routine assessment of 4 additional BM (HER2, KRAS, BRAF, PI3KCA). Methods: Starting on April 2012, these BM analyses were prospectively collected into a database head by the IFCT (www.ifct.fr) with 15-20,000 analyses awaited after one year. The physicians prescribing each of these BM analyses were then connected to this database and were asked to regularly complete epidemiological, clinical and therapeutic data for each corresponding patient. Results: 10,000 BM analyses were collected and entered into the BM France database at the time of this first analysis (January 2013). On the basis of available data, the patients were mainly male (63.8%), (ex)smokers (83.3%) and stage IV pts (64%). The tumors were mainly adenocarcinomas (76.1%). The samples for BM analysis were collected under bronchoscopy, surgery or transthoracic biopsy in 27.4, 28.1 and 24.2%, respectively. The 10,000 molecular profiles were characterized by 9.4% EGFR (including 0.8% EGFR resistant), 0.9% HER2, 26.9% KRAS, 1.6% BRAF, and 2.6% PI3KCA mutated and 4.0% EML4-ALK fusion genes. Double mutations were seen in 0.9% of the tumors. On January 2013, data on treatment were available for 18.6% of patients among whom 56.9% of patients received a treatment according to their molecular profile (labeled drugs or bio-guided trials). Updated data will be presented during the meeting. Conclusions: Biomarkers France is the largest ever conducted biomolecular study on advanced NSCLC patients and provides solid data on the value of a nationwide BM screening policy for NSCLC patients.
Human Megakaryocytopoiesis
Authors: R. Sims
Journal: Annual Review of Medicine (1989)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More