tbuckley/cabot-search huggingface dataset:
Anti–Epidermal Growth Factor Receptor Treatment Strategies in Advanced Pancreatic Cancer: Success or Failure?
Authors: Stefan Boeck, Volker Heinemann
Journal: Journal of Clinical Oncology (2010)

TO THEEDITOR: Philip et al 1 recently reported the final results of the Southwest Oncology Group (SWOG) intergroup trial S0205 that evaluated the role of the anti– epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in the treatment of patients with advanced pancreatic cancer (PC). In this large multicenter phase III study, the addition of cetuximab to standard gemcitabine did not result in a significant improvement of efficacy end points like objective response, progression-free, or overall survival. In contrast, a phase III study conducted by Moore et al (PA.3) 2 previously showed that the addition of erlotinib (an oral anti-EGFR tyrosinekinase inhibitor) to gemcitabine achieved a statistically significant— but clinically moderate— gain in overall survival (hazard ratio, 0.82; P .038; 1-year survival rate: 23% v 17%). In the light of the important results from the well-conducted
Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes
Authors: Yue Ma, Lydia Visser, Han Roelofsen, Marcel de Vries, Arjan Diepstra, Gustaaf van Imhoff, Tineke van der Wal, Marjan Luinge, Gloria Alvarez-Llamas, Hans Vos, Sibrand Poppema, Roel Vonk, Anke van den Berg
Journal: Blood (2007)
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Authors: Caroline Robert, Luc Thomas, Igor Bondarenko, Steven O'Day, Jeffrey Weber, Claus Garbe, Celeste Lebbe, Jean-François Baurain, Alessandro Testori, Jean-Jacques Grob, Neville Davidson, Jon Richards, Michele Maio, Axel Hauschild, Wilson H. Miller, Pere Gascon, Michal Lotem, Kaan Harmankaya, Ramy Ibrahim, Stephen Francis, Tai-Tsang Chen, Rachel Humphrey, Axel Hoos, Jedd D. Wolchok
Journal: New England Journal of Medicine (2011)

Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma.
Epithelial Junction Opener JO-1 Improves Monoclonal Antibody Therapy of Cancer
Authors: Ines Beyer, Ruan van Rensburg, Robert Strauss, ZongYi Li, Hongjie Wang, Jonas Persson, Roma Yumul, Qinghua Feng, Hui Song, Jiri Bartek, Pascal Fender, André Lieber
Journal: Cancer Research (2011)

Abstract The efficacy of monoclonal antibodies (mAb) used to treat solid tumors is limited by intercellular junctions which tightly link epithelial tumor cells to each another. In this study, we define a small, recombinant adenovirus serotype 3-derived protein, termed junction opener 1 (JO-1), which binds to the epithelial junction protein desmoglein 2 (DSG2). In mouse xenograft models employing Her2/neu- and EGFR-positive human cancer cell lines, JO-1 mediated cleavage of DSG2 dimers and activated intracellular signaling pathways which reduced E-cadherin expression in tight junctions. Notably, JO-1-triggered changes allowed for increased intratumoral penetration of the anti-Her2/neu mAb trastuzumab (Herceptin) and improved access to its target receptor, Her2/neu, which is partly trapped in tight junctions. This effect translated directly into increased therapeutic efficacy of trastuzumab in mouse xenograft models using breast, gastric, and ovarian cancer cells that were Her2/neu-positive. Furthermore, combining JO-1 with the EGFR-targeting mAb cetuximab (Erbitux) greatly improved therapeutic outcomes in a metastatic model of EGFR-positive lung cancer. A combination of JO-1 with an approach that triggered transient degradation of tumor stroma proteins elicited eradication of tumors. Taken together, our findings offer preclinical proof of concept to employ JO-1 in combination with mAb therapy. Cancer Res; 71(22); 7080–90. ©2011 AACR.
Iatrogenic causes of hilar radiopaque densities
Authors: C. S. H. Ng, T. W. Lee, A. P. C. Yim
Journal: European Respiratory Journal (2005)

Iatrogenic causes of hilar radiopaque densitiesTo the Editors:We read with interest the case by VANDOOREN et al. [1], which highlighted one unusual cause of iatrogenic lung hilar densities.Embolisation of cement following percutaneous application and, indeed, embolisation of other foreign material (for example, cyanoacrylate glue and sclerotherapy agents) following endoscopic injection of gastric or oesophageal varices is well recognised [2].We recently described the novel management of postpneumonectomy empyema with bronchopleural fistula using bronchoscopic glue injection [3,4].Cyanoacrylate glue is mixed with lipiodol for endobronchial injections into the submucosal layer of the proximal end of the bronchopleural fistula, raising the mucosa and thereby reducing the diameter of the fistula.The success rate of bronchoscopic closure of postlung-resectional bronchopleural fistula (,0.5 cm in diameter) using this technique in selected patients was 83% [3].The images shown (figs 1 and 2) are from a 62-yr-old male with left post-pneumonectomy bronchopleural fistula treated with glue and lipiodol injections, and Dumon stent to the right main bronchus, after failed surgical repair of the fistula.The radiopaque lipiodal glue mixture is occluding the left bronchopleural fistula with spillage into the left pleural cavity, which highlights the muscle transposition flap.Clinicians should be aware of this form of bronchoscopic therapy, and recognise it as another cause of iatrogenic hilar radiopaque densities.
Teratology of Retinoids
Authors: Michael D. Collins, Gloria E. Mao
Journal: The Annual Review of Pharmacology and Toxicology (1999)

Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs. Therefore, understanding the mechanisms of retinoid teratogenesis is important. This review first gives an overview of the principles of teratology as they apply to retinoid-induced malformations. It then describes relevant aspects of the biochemical pathway and signal transduction of retinoids. The teratogenic activity of various retinoid compounds, the role of the retinoid receptors, and important toxicokinetic parameters in teratogenesis are reviewed.
Auscultatory Findings in Patients with a Small Ventricular Septal Defect
Authors: LUKE VAN DER HAUWAERT, ALEXANDER S. NADAS
Journal: Circulation (1961)

The auscultatory and phonocardiographic findings were analyzed in 21 cases of small ventricular septal defect. Eleven patients had identical right ventricular and pulmonary artery systolic pressures, whereas in nine a minimal systolic gradient across the infundibulum of the right ventricle was demonstrated. One half of the patients, with or without an infundibular gradient, had a pansystolic plateau-shaped murmur. Several patients, mostly those with an infundibular gradient, had a distinct diamond-shaped murmur. A few children showed an early systolic decrescendo murmur. Appreciable, even wide splitting of the second sound with inspiratory widening, was demonstrated. It is proposed that a sharp differentation between "ejection" and "regurgitant" systolic murmurs may be difficult under certain circumstances. Furthermore, it is suggested that the definition of an "innocent" or "functional" murmur may depend on the sensitivity of the diagnostic methods used.
Donor Cell Cycling, Trafficking, and Accumulation during Adoptive Immunotherapy for Murine Lung Metastases
Authors: Joseph Skitzki, Ronald A. Craig, Ryugi Okuyama, Randall N. Knibbs, Kevin McDonagh, Alfred E. Chang, Lloyd M. Stoolman
Journal: Cancer Research (2004)

Abstract Adoptive cellular immunotherapy treats metastatic cancer by infusing cultured T cells derived from resected tumors or primed lymph nodes. The infused cells must accumulate in metastatic lesions to suppress growth; however, this process and the resulting clinical response are dynamic and evolve during the days and weeks following cell infusion. This study used novel experimental techniques to determine the fate of infused, cultured tumor-draining lymph node (TDLN) cells during the treatment of murine pulmonary micrometastases. After infusion, the cultured TDLN cells accumulated in the pulmonary vasculature, systemic lymph nodes, and spleen. Donor cells were initially confined to alveolar capillaries with no movement into metastases. Within 4 h, TDLN cells began migrating across pulmonary postcapillary venules and first appeared within metastases. After 24 h, most donor cells in the lung were associated with tumor nodules. Donor cell proliferation within the lung and lymphoid organs was detected within 24 h of infusion and continued throughout the 5-day period of observation. Furthermore, those proliferating in lymphoid organs trafficked back to the tumor-bearing lungs, accounting for ∼50% of the donor cells recovered from these sites after 5 days. Finally, donor T cells entering metastases both early (within 1–2 days) and late (after 2 days) suppressed tumor growth, but the early recruits accounted for most of the therapeutic response. Thus, cultured TDLN cells migrate directly into tumor-bearing organs and seed the recirculating pool of lymphocytes after infusion. Small fractions of the later differentiate in lymphoid organs and migrate into the lungs but appear less effective than effector cells in the initial bolus.
Strategies and Opportunities for Drug Development in Heart Failure
Authors: Javed Butler, Gregg C. Fonarow, Mihai Gheorghiade
Journal: JAMA (2013)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
LSC 2013 abstract - Polymicrobial airway bacterial communities in adult bronchiectasis patients
Authors: Stephen Cummings, Paul Purcell, Hannah Jary, Audrey Nicholson, Hazel Ingram, John Perry, Clare Lanyon, Anthony De Soyza, Darren Smith
Journal: European Respiratory Journal (2013)

Introduction:  Bronchiectasis is associated with chronic airway infection that contribute to the disease through lung damage as a result of prolonged inflammatory responses.   Aims:  The aim was to investigate the polymicrobial communities in sputum samples derived from an adult non-cystic fibrosis bronchiectasis cohort (25 males and 45 females), 20 patients were exacerbating, the remainder were clinically stable.   Methods:  DNA was extracted from sputum samples of all patients. Universal primers were used to amplify the 16S gene. The resulting fragments were analysed by denaturing gradient gel electrophoresis. Data was analysed using constrained ordination analyses to identify any significant associations between these data and changes in the sputum microbiota.   Results:  There was a significant difference between the bacterial community structure in the sputum of exacerbating patients compared to those that were clinically stable (P=0.002). In the cohort,  Haemophilus influenza  carriage was associated with a significantly different microbial community structure (P=0.004). Moreover,  H. influenzae  was not identified in samples (n=15) that harboured  Pseudomonas aeruginosa . The persistent presence of  P. aeruginosa  (n=23) determined by culture was significantly correlated with reduced lung function (P   Conclusions:  In adult non-CF bronchiectasis patients bacterial lung communities show significant difference between; exacerbation and clinically stable states and also when  H. influenza  is present. Persistent colonisation by  P. aeruginosa  is significantly associated with reduced lung function, and is negatively correlated with  H. influenza  carriage.
Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism
Authors: Tatsuo Ichinohe, Takashi Uchiyama, Chihiro Shimazaki, Keitaro Matsuo, Shigehisa Tamaki, Masayuki Hino, Arata Watanabe, Motohiro Hamaguchi, Souichi Adachi, Hisashi Gondo, Nobuhiko Uoshima, Takao Yoshihara, Kazuo Hatanaka, Hiroshi Fujii, Keisei Kawa, Kazunobu Kawanishi, Koji Oka, Hideo Kimura, Mitsuru Itoh, Takeshi Inukai, Etsuko Maruya, Hiroh Saji, Yoshihisa Kodera
Journal: Blood (2004)
Different effects of local cryogel and cold air physical therapy in wrist rheumatoid arthritis visualised by power Doppler ultrasound
Authors: K Albrecht, C Albert, U Lange, U Muller-Ladner, J Strunk
Journal: Annals of the Rheumatic Diseases (2009)

Cold is applied in arthritic joints to reduce the inflammatory activity of matrix-degrading enzymes and to ameliorate pain. The effect is based on vasoconstriction, leading to a downregulation of metabolic pathways. An analgesic component can be achieved after short-term cryotherapy by destimulating pain receptors in the cutis. Antiphlogistic effects are achieved after long-term cold treatment by inhibiting the metabolism in the inflammatory cells and repressing the release of lysosomal enzymes.1

Evaluation of the effect inside the joint is impossible without objective measurements. However, published reports are limited to clinical assessment, such as pain and disease activity scores.2 3 A reduction of blood flow has been reported in Achilles …
Infections and Hypocomplementemia
Authors: Ira M. Goldstein, Shelley R. Marder
Journal: Annual Review of Medicine (1983)

The complement system, phagocytic leukocytes, and antibodies constitute the “department of defense” in the battle against infections caused by pyogenie microorganisms. Complement components are capable of directly killing (by lysis) certain susceptible bacteria and are the source of chemotactic peptides and heat-labile opsonin, which facilitate recognition and killing of microbes by phagocytic cells. When these vital functions are compromised, as in individuals with inherited deficiencies of complement components, the result is unusual susceptibility to severe infections.
Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors
Authors: C. Serrano, J. Cortés, L. De Mattos-Arruda, M. Bellet, P. Gómez, C. Saura, J. Pérez, M. Vidal, E. Muñoz-Couselo, M.J. Carreras, G. Sánchez-Ollé, J. Tabernero, J. Baselga, S. Di Cosimo
Journal: Annals of Oncology (2011)
MicroRNA-33–dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis
Authors: Mireille Ouimet, Hasini N. Ediriweera, U. Mahesh Gundra, Frederick J. Sheedy, Bhama Ramkhelawon, Susan B. Hutchison, Kaitlyn Rinehold, Coen van Solingen, Morgan D. Fullerton, Katharine Cecchini, Katey J. Rayner, Gregory R. Steinberg, Phillip D. Zamore, Edward A. Fisher, P’ng Loke, Kathryn J. Moore
Journal: Journal of Clinical Investigation (2015)

Cellular metabolism is increasingly recognized as a controller of immune cell fate and function. MicroRNA-33 (miR-33) regulates cellular lipid metabolism and represses genes involved in cholesterol efflux, HDL biogenesis, and fatty acid oxidation. Here, we determined that miR-33–mediated disruption of the balance of aerobic glycolysis and mitochondrial oxidative phosphorylation instructs macrophage inflammatory polarization and shapes innate and adaptive immune responses. Macrophage-specific Mir33 deletion increased oxidative respiration, enhanced spare respiratory capacity, and induced an M2 macrophage polarization–associated gene profile. Furthermore, miR-33–mediated M2 polarization required miR-33 targeting of the energy sensor AMP-activated protein kinase (AMPK), but not cholesterol efflux. Notably, miR-33 inhibition increased macrophage expression of the retinoic acid–producing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1A2) and retinal dehydrogenase activity both in vitro and in a mouse model. Consistent with the ability of retinoic acid to foster inducible Tregs, miR-33–depleted macrophages had an enhanced capacity to induce forkhead box P3 (FOXP3) expression in naive CD4+ T cells. Finally, treatment of hypercholesterolemic mice with miR-33 inhibitors for 8 weeks resulted in accumulation of inflammation-suppressing M2 macrophages and FOXP3+ Tregs in plaques and reduced atherosclerosis progression. Collectively, these results reveal that miR-33 regulates macrophage inflammation and demonstrate that miR-33 antagonism is atheroprotective, in part, by reducing plaque inflammation by promoting M2 macrophage polarization and Treg induction.
Should general practitioners call patients by their first names?
Authors: B McKinstry
Journal: BMJ (1990)

OBJECTIVE--To assess the acceptability to patients of the use of patients9 first names by doctors and doctors9 first names by patients in general practice. DESIGN--An administered questionnaire survey. SETTING--5 General practices in Lothian. PATIENTS--475 Patients consulting 30 general practitioners. MAIN OUTCOME MEASURE--Response by patients to questionnaire on attitude to use of first names. RESULTS--Most of the patients either liked (223) or did not mind (175) being called by their first names. Only 77 disliked it, most of whom were aged over 65. Most patients (324) did not, however, want to call the doctor by his or her first name. CONCLUSIONS--General practitioners should consider using patients9 first names more often, particularly with younger patients.
Relationship Between Erectile Dysfunction and Silent Myocardial Ischemia in Apparently Uncomplicated Type 2 Diabetic Patients
Authors: Carmine Gazzaruso, Stefano Giordanetti, Emanuela De Amici, Gianandrea Bertone, Colomba Falcone, Diego Geroldi, Pietro Fratino, Sebastiano B. Solerte, Adriana Garzaniti
Journal: Circulation (2004)

Erectile dysfunction (ED) is associated with coronary artery disease (CAD). In diabetic patients, CAD is often silent. Among diabetic patients with silent CAD, the prevalence of ED has never been evaluated. We investigated whether ED is associated with asymptomatic CAD in type 2 diabetic patients.We evaluated the prevalence of ED in 133 uncomplicated diabetic men with angiographically verified silent CAD and in 127 diabetic men without myocardial ischemia at exercise ECG, 48-hour ambulatory ECG, and stress echocardiography. The groups were comparable for age and diabetes duration. Patients were screened for ED using the validated International Index of Erectile Function (IIEF-5) questionnaire. The prevalence of ED was significantly higher in patients with than in those without silent CAD (33.8% versus 4.7%; P=0.000). Multiple logistic regression analysis showed that ED, apolipoprotein(a) polymorphism, smoking, microalbuminuria, HDL, and LDL were significantly associated with silent CAD; among these risk factors, ED appeared to be the most efficient predictor of silent CAD (OR, 14.8; 95% CI, 3.8 to 56.9).Our study first shows a strong and independent association between ED and silent CAD in apparently uncomplicated type 2 diabetic patients. If our findings are confirmed, ED may become a potential marker to identify diabetic patients to screen for silent CAD. Moreover, the high prevalence of ED among diabetics with silent CAD suggests the need to perform an exercise ECG before starting a treatment for ED, especially in patients with additional cardiovascular risk factors.
Cross-talk between Tumor and Endothelial Cells Involving the Notch3-Dll4 Interaction Marks Escape from Tumor Dormancy
Authors: Stefano Indraccolo, Sonia Minuzzo, Massimo Masiero, Irene Pusceddu, Luca Persano, Lidia Moserle, Andrea Reboldi, Elena Favaro, Marco Mecarozzi, Giuseppina Di Mario, Isabella Screpanti, Maurilio Ponzoni, Claudio Doglioni, Alberto Amadori
Journal: Cancer Research (2009)

The Notch ligand Dll4 has a recognized role during both physiologic and tumor angiogenesis, as it contributes to regulate Notch activity in endothelial cells (EC). The effects of Dll4 on Notch signaling in tumor cells expressing Notch receptors remain, however, largely unknown. Here, we report that escape of human T-cell acute lymphoblastic leukemia (T-ALL) cells or colorectal cancer cells from dormancy is associated with Dll4 expression in the tumor microenvironment and increased Notch3 signaling in tumor cells. Dll4 was expressed at early time points during the angiogenic process, and its expression preceded perfusion of the newly established vessels. Treatment of EC with angiogenic factors induced Dll4 expression and increased Notch3 activation in cocultured T-ALL cells. Neutralization of Dll4 greatly reduced EC-mediated activation of Notch 3 signaling in T-ALL cells and blocked tumorigenesis. Moreover, silencing Notch3 by RNA interference had marked antiproliferative and proapoptotic effects on T-ALL cells in vitro and reduced tumorigenicity in vivo. Our results elucidate a novel mechanism by which a direct interplay between endothelial and tumor cells promotes survival and triggers tumor growth.
Prolonged Efficacy of a Single Dose of the Bisphosphonate Zoledronic Acid
Authors: Janet E. Brown, Susan P. Ellis, James E. Lester, Sandra Gutcher, Tina Khanna, Om-Prakesh Purohit, Eugene McCloskey, Robert E. Coleman
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment–induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration. Experimental Design: Sixty-six patients who were osteopenic at &amp;gt;1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay. Results: The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively (P &amp;lt; 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was ∼58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively (P &amp;lt; 0.001). Conclusions: A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption. Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.