tbuckley/cabot-search huggingface dataset:
Enhanced Efficacy of Radioimmunotherapy with 90Y-CHX-A″-DTPA-hu3S193 by Inhibition of Epidermal Growth Factor Receptor (EGFR) Signaling with EGFR Tyrosine Kinase Inhibitor AG1478
Authors: Fook T. Lee, Angela J. Mountain, Marcus P. Kelly, Cathrine Hall, Angela Rigopoulos, Terrance G. Johns, Fiona E. Smyth, Martin W. Brechbiel, Edouard C. Nice, Antony W. Burgess, Andrew M. Scott
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Monoclonal antibodies and tyrosine kinase inhibitors specific for the epidermal growth factor receptor (EGFR) have been shown to enhance the effect of external beam radiation on EGFR-positive tumors. The effect of EGFR signaling abrogation by EGFR tyrosine kinase inhibitor on the efficacy of radioimmunotherapy has not been reported previously. This study investigated the effect of EGFR tyrosine kinase inhibition on the efficacy of radioimmunotherapy in a human cancer xenograft model. Experimental Design: The humanized anti–Lewis Y antibody hu3S193 and the EGFR tyrosine kinase inhibitor AG1478 were studied. BALB/c nude mice were engrafted with A431 squamous carcinoma cells. Initial biodistribution properties of the 90Y-CHX-A″-DTPA-hu3S193 were evaluated in this model. In therapy experiments, cohorts of four to five xenografted mice were treated with saline as placebo, 0.4 mg AG1478 i.p. (six doses over 2 weeks), single i.v. injections of unlabeled hu3S193, or 90Y-CHX-A″-DTPA-hu3S193 (12.5, 25, 50, or 100 μCi). The combination of 0.4 mg AG1478 i.p. and 25 μCi 90Y-CHX-A″-DTPA-hu3S193 i.v. was subsequently evaluated in the A431 model. Results: 90Y-CHX-A″-DTPA-hu3S193 retained excellent immunoreactivity after radiolabeling. The biodistribution study showed excellent uptake in tumor (90.33 ± 38.84%ID/g) peaking at 24 to 72 hours after injection and with prolonged retention. 90Y-CHX-A″-DTPA-hu3S193 significantly inhibited A431 xenograft growth at 25, 50, and 100 μCi doses. The combination of 0.4 mg AG1478 with a single dose of 25 μCi 90Y-CHX-A″-DTPA-hu3S193 resulted in a significant enhancement of efficacy compared with either agent alone (P = 0.013). Conclusions: The efficacy of radioimmunotherapy with 90Y-CHX-A″-DTPA-hu3S193 is significantly enhanced by EGFR tyrosine kinase inhibitor AG1478. Further investigations of dosing regimens using EGFR tyrosine kinase inhibitors and radioimmunotherapy in the treatment of EGFR expressing tumors are warranted.
Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones.
Authors: A Bensussan, S C Meuer, S F Schlossman, E L Reinherz
Journal: The Journal of Experimental Medicine (1984)

Autoreactive T lymphocytes were generated by culturing human peripheral blood mononuclear cells with an antigen-specific major histocompatibility complex (MHC)-restricted autologous inducer T cell, termed RW17C and subsequently cloned in soft agar. The majority of such clones (AC1-13) expressed the T3+T4+T8-T11+Ia+ phenotype and were directed at autologous class II MHC gene products found on B cells, macrophages, and B lymphoblastoid cells as judged by their proliferative response to the latter. For this recognition, the clones employed a T3-Ti molecular complex and a T4 structure analogous to those found on allospecific T cells. Perhaps more importantly, it was observed that the same AC1-13 autoreactive clones (AC) induced autologous B cells to produce high levels of immunoglobulin in the absence of exogenous antigen and could synergize with the RW17C clone to effect maximal B cell Ig production. These results support the notion that such autoreactive cells can function in a physiologic amplifier role by facilitating induction via an internal set of signals (i.e. autologous MHC).
Assessment of Tumor Size Reduction Improves Outcome Prediction of Positron Emission Tomography/Computed Tomography After Chemotherapy in Advanced-Stage Hodgkin Lymphoma
Authors: Carsten Kobe, Georg Kuhnert, Deniz Kahraman, Heinz Haverkamp, Hans-Theodor Eich, Mareike Franke, Thorsten Persigehl, Susanne Klutmann, Holger Amthauer, Andreas Bockisch, Regine Kluge, Hans-Heinrich Wolf, David Maintz, Michael Fuchs, Peter Borchmann, Volker Diehl, Alexander Drzezga, Andreas Engert, Markus Dietlein
Journal: Journal of Clinical Oncology (2014)

Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT).The analysis set consisted of 739 patients with residues≥2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkin's disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkin's disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression.In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P=.022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P=.9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%).Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse.
Transformation of HIV from pandemic to low-endemic levels: a public health approach to combination prevention
Authors: Alexandra Jones, Ide Cremin, Fareed Abdullah, John Idoko, Peter Cherutich, Nduku Kilonzo, Helen Rees, Timothy Hallett, Kevin O'Reilly, Florence Koechlin, Bernhard Schwartlander, Barbara de Zalduondo, Susan Kim, Jonathan Jay, Jacqueline Huh, Peter Piot, Mark Dybul
Journal: The Lancet (2014)
Systemic and intrathecal chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) for CNS relapse of aggressive lymphomas: A potentially curative approach?
Authors: L. Fischer, M. Haenel, R. Moehle, R. Schroers, T. Elter, M. Reiser, M. H. Dreyling, G. Illerhaus, J. Eucker, C. W. Scholz, B. Metzner, A. Roeth, J. Birkmann, U. Schlegel, P. Martus, E. Thiel, A. Korfel
Journal: Journal of Clinical Oncology (2011)

8005 Background: CNS relapse of aggressive lymphoma has a poor prognosis with a median survival below six months. No standard of therapy has been defined. In this prospective multicenter phase II study a chemotherapy-only regimen including HD-ASCT is evaluated. Methods: Adult (18-65 yrs.) immunocompetent patients with CNS relapse of aggressive lymphoma were eligible. Induction chemotherapy consisted of two cycles of high-dose methotrexate 4g/m2 iv. (d1), ifosfamide 2g/m2 iv. (d3-5) and ith. liposomal cytarabine 50mg (d6) and one cycle of high-dose cytarabine 3g/m2 (d1-2), thiotepa 40mg/m2 iv. (d2) and ith. liposomal cytarabine 50mg (d3). Then, patients without progression (PD) received carmustine 400mg/m2 iv. (d -5), thiotepa 2x5mg/kg iv. (d -4 to -3) and etoposide 150mg/m2 iv. (d -5 to -3) followed by ASCT. Results: Thirty patients (median age 58 yrs.) were enrolled. Three patients had T-cell and 27 aggressive B-cell lymphoma. Median time to CNS relapse was 8.5 (3-80) mo. and was intracerebral in 24 and meningeal in 13 (combined in seven) patients; six had concomitant systemic lymphoma. Pretreatment was CHOP-like in 29 patients, including rituximab in 26. CNS disease responded to induction therapy in 22 (73%) patients (CR=10, PR=12); two had stable disease, four PD, and two were not evaluable for response. HD-ASCT was thus far performed in 23 patients; CNS response was 70%: CR=11, PD=5, and not yet evaluated =7. Systemic lymphoma responded in three evaluable patients: CR=2 and PR=1. Grade ≥3° toxicities included leucopenia (47%) and infection (20%); and - following HD-ASCT - mucositis (33%) and infection (61%). One patient died due to septic diverticulitis and one developed persisting fecal incontinence 4°. After a median follow up of 12.6 mo. the median progression free survival was not reached. Conclusions: This is the first prospective evaluation of HD-ASCT in this setting. The protocol used is highly active with tolerable toxicity. A prolonged follow up will determine its curative potential.
Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis: Table 1
Authors: D Daoussis, V F Panoulas, I Antonopoulos, H John, T E Toms, P Wong, P Nightingale, K M J Douglas, G D Kitas
Journal: Annals of the Rheumatic Diseases (2009)

The present study aimed to evaluate the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). It specifically addressed the hypotheses that renal dysfunction in these patients may associate with the presence of insulin resistance, dyslipidaemia, uric acid levels and/or current levels of systemic inflammation.Renal function was assessed by estimated glomerular filtration rate (GFR) using the modification of diet in renal disease equation in 400 consecutive RA patients for this cross-sectional, single-centre study. Risk factors for renal dysfunction were recorded/measured in all participants. Correlations between GFR and other variables were analysed by Pearson or Spearman test as appropriate. Linear regression was used to test the independence of the associations between GFR and other variables.In this RA patient cohort, 67.75% of patients had a reduced GFR of less than 90 ml/minute per 1.73 m(2) and 12.75% had a GFR of less than 60 ml/minute per 1.73 m(2). Multivariable analysis revealed significant associations between GFR and age (beta = -0.370, p<0.001), female sex (beta = -0.181, p=0.002), total cholesterol (beta = -0.112, p=0.022), serum uric acid (SUA) (beta = -0.425, p<0.001) and the presence of extra-articular disease, apart from sicca and/or nodules (beta = -0.084, p=0.040).Renal dysfunction in RA is quite common and associates with classic cardiovascular risk factors such as advanced age and dyslipidaemia, levels of SUA and the presence of extra-articular disease. Renal dysfunction was not related to other RA-related factors including disease activity and duration, disability and past or present use of nephrotoxic medications.
Risk of Estrogen Receptor–Positive and –Negative Breast Cancer and Single–Nucleotide Polymorphism 2q35-rs13387042
Authors: Roger L. Milne, Javier Benítez, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, José Ignacio Arias, M. Pilar Zamora, Barbara Burwinkel, Claus R. Bartram, Alfons Meindl, Rita K. Schmutzler, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W. R. Reed, Melissa C. Southey, Letitia Smith, Amanda B. Spurdle, John L. Hopper, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Peter Schürmann, Michael Bremer, Peter Hillemanns, Thilo Dörk, Peter Devilee, Christie J. van Asperen, Rob A. E. M. Tollenaar, Caroline Seynaeve, Per Hall, Kamila Czene, Jianjun Liu, Yuqing Li, Shahana Ahmed, Alison M. Dunning, Melanie Maranian, Paul D. P. Pharoah, Georgia Chenevix-Trench, Jonathan Beesley, Natalia V. Bogdanova, Natalia N. Antonenkova, Iosif V. Zalutsky, Hoda Anton-Culver, Argyrios Ziogas, Hiltrud Brauch, Christina Justenhoven, Yon-Dschun Ko, Susanne Haas, Peter A. Fasching, Reiner Strick, Arif B. Ekici, Matthias W. Beckmann, Graham G. Giles, Gianluca Severi, Laura Baglietto, Dallas R. English, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Clare Turnbull, Sarah Hines, Anthony Renwick, Nazneen Rahman, Børge G. Nordestgaard, Stig E. Bojesen, Henrik Flyger, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Montserrat García-Closas, Stephen Chanock, Jolanta Lissowska, Louise A. Brinton, Jenny Chang-Claude, Shan Wang-Gohrke, Chen-Yang Shen, Hui-Chun Wang, Jyh-Cherng Yu, Sou-Tong Chen, Marina Bermisheva, Tatjana Nikolaeva, Elza Khusnutdinova, Manjeet K. Humphreys, Jonathan Morrison, Radka Platte, Douglas F. Easton
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)–positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.
A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility and effects
Authors: Philippa C Lavallée, Elena Meseguer, Halim Abboud, Lucie Cabrejo, Jean-Marc Olivot, Olivier Simon, Mikael Mazighi, Chantal Nifle, Philippe Niclot, Bertrand Lapergue, Isabelle F Klein, Eric Brochet, Philippe Gabriel Steg, Guy Lesèche, Julien Labreuche, Pierre-Jean Touboul, Pierre Amarenco
Journal: The Lancet Neurology (2007)
Evolution of Liver Transplantation
Authors: Thomas E. Starzl, Shunzaburo Iwatsuki, David H. Van Thiel, Carlton J. Gartner, Basil J. Zitelli, Jeffrey J. Malatack, Robert R. Schade, Byers W. Shaw, Thomas R. Hakala, Thomas J. Rosenthal, Kendrick A. Porter
Journal: Hepatology (1982)

Two general kinds of liver transplantation have been attempted clinically.With one approach, the host liver is removed and replaced with a homograft (orthotopic liver transplantation); alternatively, an extra liver is inserted at an ectopic site (auxiliary homotransplantation).This review concerns only orthotopic liver transplantation.r The first effort to replace a human liver was made at !
Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response.
Authors: F Cozzolino, M Torcia, A M Carossino, R Giordani, C Selli, G Talini, E Reali, A Novelli, V Pistoia, M Ferrarini
Journal: The Journal of Experimental Medicine (1987)

The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.
Impact of Single Nucleotide Polymorphisms on Severe Hepatotoxicity Induced By Gefitinib or Erlotinib in Non-Small Cell Lung Cancer Patients Harboring Egfr Mutations
Authors: E. Sugiyama, S. Umemura, S. Nomura, S. Matsumoto, K. Yoh, S. Niho, H. Ohmatsu, Y. Ohe, M. Tsuboi, K. Goto
Journal: Annals of Oncology (2014)
Antibiotic Use in Relation to the Risk of Breast Cancer
Authors: Christine M. Velicer
Journal: JAMA (2004)

Use of antibiotics may be associated with risk of breast cancer through effects on immune function, inflammation, and metabolism of estrogen and phytochemicals; however, clinical data on the association between antibiotic use and risk of breast cancer are sparse.To examine the association between use of antibiotics and risk of breast cancer.Case-control study among 2266 women older than 19 years with primary, invasive breast cancer (cases) enrolled in a large, nonprofit health plan for at least 1 year between January 1, 1993, and June 30, 2001, and 7953 randomly selected female health plan members (controls), frequency-matched to cases on age and length of enrollment. Cases were ascertained from the Surveillance, Epidemiology, and End Results cancer registry. Antibiotic use was ascertained from computerized pharmacy records.Association between extent of antibiotic use and risk of breast cancer.Increasing cumulative days of antibiotic use were associated with increased risk of incident breast cancer, adjusted for age and length of enrollment. For categories of increasing use (0, 1-50, 51-100, 101-500, 501-1000, and > or =1001 days), odds ratios (95% confidence intervals) for breast cancer were 1.00 (reference), 1.45 (1.24-1.69), 1.53 (1.28-1.83), 1.68 (1.42-2.00), 2.14 (1.60-2.88), and 2.07 (1.48-2.89) (P<.001 for trend). Increased risk was observed in all antibiotic classes studied and in a subanalysis having breast cancer fatality as the outcome. Among women with the highest levels of tetracycline or macrolide use, risk of breast cancer was not elevated in those using these antibiotics exclusively for acne or rosacea (indications that could be risk factors for breast cancer due to altered hormone levels), compared with those using them exclusively for respiratory tract infections, adjusted for age and length of enrollment (odds ratio, 0.91; 95% confidence interval, 0.44-1.87).Use of antibiotics is associated with increased risk of incident and fatal breast cancer. It cannot be determined from this study whether antibiotic use is causally related to breast cancer, or whether indication for use, overall weakened immune function, or other factors are pertinent underlying exposures. Although further studies are needed, these findings reinforce the need for prudent long-term use of antibiotics.
Long-term pulmonary sequelae in children with congenital diaphragmatic hernia.
Authors: H Ijsselstijn, D Tibboel, W J Hop, J C Molenaar, J C de Jongste
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Neonates with congenital diaphragmatic hernia (CDH) often suffer from respiratory insufficiency due to lung hypoplasia and pulmonary hypertension. Artificial ventilation is frequently required, and this leads to a high incidence of bronchopulmonary dysplasia. Long-term follow-up studies have shown persisting airway obstruction. To evaluate the long-term pulmonary sequelae in CDH, we studied 40 CDH patients of age 7 to 18 yr (median 11.7 yr) and 65 age-matched controls without CDH and lung hypoplasia who underwent similar neonatal treatment. Mild airway obstruction was found in both groups with more peripheral airway obstruction in CDH patients than in control subjects. Both groups had normal TLC and single-breath carbon monoxide diffusion capacity (DLCO). CDH patients had increased residual volume (RV) and RV/TLC compared with controls. Increased airway responsiveness to methacholine (MCH) was common but bronchoconstriction to inhaled metabisulfite (MBS) was rare both in CDH and control subjects. We conclude that this group of CDH patients has minor residual lung function impairment. Mild airway obstruction and increased airway responsiveness to inhaled MCH but not to MBS suggest that structural changes in distal airways are involved and not autonomic nerve dysfunction. Both artificial ventilation in the neonatal period and residual lung hypoplasia seem important determinants of persistent lung function abnormalities in CDH patients.
“Choice” and “emotion” in altruism: Reflections on the morality of justice versus the morality of caring
Authors: Ross Buck
Journal: Behavioral and Brain Sciences (2002)

Rachlin uses the word “choice” 80 times, whereas “emotion” does not appear. In contrast, “Empathy: Its ultimate and proximate bases” by Preston and de Waal, uses the word “emotion” 139 times and “choice” once. This commentary compares these ways of approaching empathy and altruism, relating Rachlin's approach to Gilligan's Morality of Justice and Preston and de Waal's to the Morality of Caring.
Fluvastatin for Prevention of Cardiac Events Following Successful First Percutaneous Coronary Intervention&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Patrick W. J. C. Serruys
Journal: JAMA (2002)

ERCUTANEOUS CORONARY INTERvention (PCI) comprises a group of procedures that are used to relieve ischemic symptoms due to coronary atherosclerotic narrowing in patients with increasingly earlier stages of coronary heart disease (CHD).The most frequently performed PCI procedure is balloon angioplasty with or without stenting.In the United States, balloon angioplasty procedures increased nearly 4-fold between 1987 and 1999, and in 1999, 1.1 million angioplasty procedures, both with and without stent placement, were performed in the United States alone. 1 Percutaneous coronary intervention has been demonstrated to be at least as effective as coronary artery bypass grafting (CABG) in terms of survival and pre-vention of myocardial infarction (MI) in appropriately selected patients with either single-vessel or multivessel disease. 2,3Although PCI achieves shortterm improvements in ischemic
Precordial counting: Evaluation and comparison of iodine-131 labelled albumin and technetium-99m in detection of left-to-right shunts
Authors: A. R. Lorimer, D. McCall, G. Boyd
Journal: Thorax (1969)

Methods of precordial counting of radio-active isotopes in the detection of left-to-right intracardiac shunts are presented. Both iodine-131 labelled albumin and technetium-99m were used but the latter is preferred, especially for children, since it has a short physical half-life and emits a single gamma ray. Investigations were done to establish normal values and those in patients who had either rheumatic or congenital heart disease. All left-to-right shunts were confirmed at cardiac catheterization. False negative results were rare but false positive results can occur in the presence of congestive cardiac failure. It is possible to detect left-to-right shunts with a pulmonary to systemic flow ratio as low as 1·2:1 and an estimate of this ratio can be made from the precordial curve. The main value of the method is as a preliminary investigation in the detection of intracardiac shunts.