tbuckley/cabot-search huggingface dataset:
High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication
Authors: F. Cabanillas, I. Liboy, O. Pavia, E. Rivera
Journal: Annals of Oncology (2006)

Background: Rituximab is associated with low incidence of hypogammaglobulinemia and little morbidity. Our experience with the combination of rituximab + chemotherapy suggested the opposite.Patients and methods: We analyzed our experience with rituximab plus chemotherapy in 97 patients to determine: frequency and type of non-neutropenic infection (NNI); frequency and type of hypogammaglobulinemia; response to gammaglobulin therapy; and factors associated with NNI.Results: We observed 40 episodes of NNI in 19 of 97 (20%) patients. By 3 years, 43% of patients treated with rituximab + chemotherapy were projected to have developed at least one NNI. Of 19 with NNI, 15 had Ig levels studied and all 15 had hypogammaglobulinemia. Most frequently affected Ig were IgG (14 of 15) and IgM (13 of 14). IgA was usually spared (six of 14 cases affected). NNIs observed were 18 bronchitis, 16 sinusitis, four pneumonias, three otitis media, two fevers of unknown origin (FUOs) and three herpes zoster. Hospitalization was required in seven of 19. Ten received gammaglobulin infusions and all responded promptly. Gammaglobulin was given only when NNIs recurred. We examined sex, age, histology, type of rituximab–chemotherapy (fludarabine + rituximab versus other chemotherapy + rituximab) for correlation with NNI.Conclusions: Indolent histology, female sex and fludarabine + rituximab significantly correlated with frequency of NNI but multivariate analysis picked fludarabine + rituximab followed by female gender as the only two independent variables predictive of NNI.
<i>HER2</i> in Brain Metastases: Issues of Concordance, Survival, and Treatment
Authors: Ilka B. Fuchs, Maren Loebbecke, Helmut Buhler, Gisela Stoltenburg-Didinger, Bernhard Heine, Werner Lichtenegger, Gerard Schaller
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.04.016 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12351617 HER2 in Brain Metastases: Issues of Concordance, Survival, and Treatment Ilka B. FuchsxIlka B. FuchsSearch for articles by this author , Maren LoebbeckexMaren LoebbeckeSearch for articles by this author , Helmut BuhlerxHelmut BuhlerSearch for articles by this author , Gisela Stoltenburg-DidingerxGisela Stoltenburg-DidingerSearch for articles by this author , Bernhard HeinexBernhard HeineSearch for articles by this author , Werner LichteneggerxWerner LichteneggerSearch for articles by this author , Gerard SchallerxGerard SchallerSearch for articles by this author Show More Frauenklinik, Charite C. Virchow, Berlin, Germany https://doi.org/10.1200/JCO.2002.04.016 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
The use of chest X-rays as a routine staging investigation for patients with invasive breast cancer – An audit of current practice
Authors: Hollie Sapsford, Nick Abbott
Journal: International Journal of Surgery (2013)

Introduction   Chest x-ray (CXR) has traditionally been performed as a staging tool searching for pulmonary metastases in patients with invasive breast cancer.            Aims   To investigate whether patients diagnosed with invasive breast cancer in NHS Highland received a pre-operative CXR in line with local preoperative assessment guidelines.          M  et  hod  s    Data from all patients with invasive breast cancer diagnosed over a 6 month period were retrieved from a prospectively maintained database.   Hospital notes and computer records identified if patients received a pre-operative CXR.      Performing CXRs in 95% was deemed an acceptable audit standard.   Abnormal CXRs were identified and investigated in more detail.      (Ethical approval not required for local audit)         Results   Only 89% of patients undergoing surgery for invasive breast cancer received a pre-operative CXR.  Metastatic disease was subsequently identified in a small proportion of patients.         Conclusions   Routine preoperative CXRs were not being performed in accordance with local guidelines.      SIGN (1)  Guidelines (84) suggest CXRs are not indicated in asymptomatic patients with invasive breast cancer and clearly are not an effective tool in our population .      Completing the audit loop was thought unhelpful as this local data has changed practice and helped suggest a more effective, CT-based, staging strategy.         References   (1)  SIGN 84 Management of Breast Cancer in Women: A National Clinical Guideline December 2005
Evaluation of the functional equivalence of major histocompatibility complex class II A and E complexes.
Authors: D Cosgrove, H Bodmer, M Bogue, C Benoist, D Mathis
Journal: The Journal of Experimental Medicine (1992)

Most mice display two conventional major histocompatibility complex class II isotypes, A and E. Several A+E- strains have been observed, but never any that are A-E+. Because of this and because of hints from several lines of functional analysis, it has been proposed that the two isotypes might not operate equivalently. This proposition has not been directly testable until now because of the lack of an E-only strain. We report the production of such mice, exploiting previously created class II-transgenic and class II-"knock-out" lines. A+E-, A-E-, and A-E+ littermates have been compared by a number of parameters. We find that E and A molecules are, for the most part, functionally equivalent. However, subtle differences are seen in their ability to engage CD4 molecules on immature thymocytes, and in the profile of receptors on T cells selected into the periphery.
Mechanisms of Cell Sensitization to α Radioimmunotherapy by Doxorubicin or Paclitaxel in Multiple Myeloma Cell Lines
Authors: Stephane Supiot, Sebastien Gouard, Josiane Charrier, Christos Apostolidis, Jean-Francois Chatal, Jacques Barbet, François Davodeau, Michel Cherel
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The purpose of this study was to analyze different mechanisms (cell cycle synchronization, DNA damage, and apoptosis) that might underlie potential synergy between chemotherapy (paclitaxel or doxorubicin) and radioimmunotherapy with α radionuclides. Experimental Design: Three multiple myeloma cell lines (LP1, RMI 8226, and U266) were treated with 213Bi-radiolabeled B-B4, a monoclonal antibody that recognizes syndecan-1 (CD138) 24 hours after paclitaxel (1 nmol/L) or doxorubicin (10 nmol/L) treatment. Cell survival was assessed using a clonogenic survival assay. Cell cycle modifications were assessed by propidium iodide staining and DNA strand breaks by the comet assay. Level of apoptosis was determined by Apo 2.7 staining. Results: Radiation enhancement ratio showed that paclitaxel and doxorubicin were synergistic with α radioimmunotherapy. After a 24-hour incubation, paclitaxel and doxorubicin arrested all cell lines in the G2-M phase of the cell cycle. Doxorubicin combined with α radioimmunotherapy increased tail DNA in the RPMI 8226 cell line but not the LP1 or U266 cell lines compared with doxorubicin alone or α radioimmunotherapy alone. Neither doxorubicin nor paclitaxel combined with α radioimmunotherapy increased the level of apoptosis induced by either drug alone or α radioimmunotherapy alone. Conclusion: Both cell cycle arrest in the G2-M phase and an increase in DNA double-strand breaks could lead to radiosensitization of cells by doxorubicin or paclitaxel, but apoptosis would not be involved in radiosensitization mechanisms.
Peroxisome proliferator-activated receptor δ (PPARδ) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis
Authors: M PESANT, S SUEUR, P DUTARTRE, M TALLANDIER, P GRIMALDI, L ROCHETTE, J CONNAT
Journal: Cardiovascular Research (2005)

Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of PPARdelta remains poorly studied.We focused on PPARdelta function in the regulation of oxidative stress-induced apoptosis in the rat cardiomyoblast cell line H9c2. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we showed that PPARdelta is the predominantly expressed isotype whereas PPARalpha was weakly detected. By performing cell viability assays, we also showed that the selective PPARdelta agonist GW501516 protected cells from H(2)O(2)-induced cell death. The protective effect of GW501516 was due to an inhibition of H(2)O(2)-triggered apoptosis as shown by annexin-V labeling, DNA fragmentation analysis, and caspase-3 activity measurement. We demonstrated by transient transfection of a dominant negative mutant of PPARdelta that the protection induced by GW501516 was totally dependent on PPARdelta. Semi-quantitative RT-PCR and Western blotting analysis demonstrated that GW501516 treatment upregulated catalase. Moreover, forced overexpression of catalase inhibited H(2)O(2)-triggered apoptosis, as evidenced by annexin-V labeling.Taken together, our results account for an important role of PPARdelta in inhibiting the onset of oxidative stress-induced apoptosis in H9c2 cells. PPARdelta appears to be a new therapeutic target for the regulation of heart reperfusion-associated oxidative stress and stimulation of enzymatic antioxidative defences.
DNA Methylation, Isocitrate Dehydrogenase Mutation, and Survival in Glioma
Authors: Brock C. Christensen, Ashley A. Smith, Shichun Zheng, Devin C. Koestler, E. Andres Houseman, Carmen J. Marsit, Joseph L. Wiemels, Heather H. Nelson, Margaret R. Karagas, Margaret R. Wrensch, Karl T. Kelsey, John K. Wiencke
Journal: JNCI Journal of the National Cancer Institute (2010)

Although much is known about molecular and chromosomal characteristics that distinguish glioma histological subtypes, DNA methylation patterns of gliomas and their association with other tumor features such as mutation of isocitrate dehydrogenase (IDH) genes have only recently begun to be investigated.DNA methylation of glioblastomas, astrocytomas, oligodendrogliomas, oligoastrocytomas, ependymomas, and pilocytic astrocytomas (n = 131) from the Brain Tumor Research Center at the University of California San Francisco, as well as nontumor brain tissues (n = 7), was assessed with the Illumina GoldenGate methylation array. Methylation data were subjected to recursively partitioned mixture modeling (RPMM) to derive methylation classes. Differential DNA methylation between tumor and nontumor was also assessed. The association between methylation class and IDH mutation (IDH1 and IDH2) was tested using univariate and multivariable analysis for tumors (n = 95) with available substrate for sequencing. Survival of glioma patients carrying mutant IDH (n = 57) was compared with patients carrying wild-type IDH (n = 38) using a multivariable Cox proportional hazards model and Kaplan-Meier analysis. All statistical tests were two-sided.We observed a statistically significant association between RPMM methylation class and glioma histological subtype (P < 2.2 × 10(-16)). Compared with nontumor brain tissues, across glioma tumor histological subtypes, the differential methylation ratios of CpG loci were statistically significantly different (permutation P < .0001). Methylation class was strongly associated with IDH mutation in gliomas (P = 3.0 × 10(-16)). Compared with glioma patients whose tumors harbored wild-type IDH, patients whose tumors harbored mutant IDH showed statistically significantly improved survival (hazard ratio of death = 0.27, 95% confidence interval = 0.10 to 0.72).The homogeneity of methylation classes for gliomas with IDH mutation, despite their histological diversity, suggests that IDH mutation is associated with a distinct DNA methylation phenotype and an altered metabolic profile in glioma.
18F-fluorodeoxyglucose–positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group
Authors: X. Cahu, C. Bodet-Milin, E. Brissot, H. Maisonneuve, R. Houot, N. Morineau, P. Solal-Celigny, P. Godmer, T. Gastinne, P. Moreau, A. Moreau, T. Lamy, F. Kraber-Bodere, S. Le Gouill
Journal: Annals of Oncology (2010)
Prospective study of post-traumatic stress disorder in children involved in road traffic accidents
Authors: P. Stallard, R. Velleman, S. Baldwin
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To determine the prevalence of severe psychological trauma—that is, post-traumatic stress disorder—in children involved in everyday road traffic accidents. <b>Design:</b> 12 month prospective study. <b>Setting:</b> Accident and emergency department, Royal United Hospital, Bath. <b>Subjects:</b> 119 children aged 5-18 years involved in road traffic accidents and 66 children who sustained sports injuries. <b>Main outcome measure:</b> Presence of appreciable psychological distress; fulfilment of diagnostic criteria for post-traumatic stress disorder. <b>Results:</b> Post-traumatic stress disorder was found in 41 (34.5%) children involved in road traffic accidents but only two (3.0%) who sustained sports injuries. The presence of post-traumatic stress disorder was not related to the type of accident, age of the child, or the nature of injuries but was significantly associated with sex, previous experience of trauma, and subjective appraisal of threat to life. None of the children had received any psychological help at the time of assessment. <b>Conclusions:</b> One in three children involved in road traffic accidents was found to suffer from post-traumatic stress disorder when they were assessed 6 weeks after their accident. The psychological needs of such children after such accidents remain largely unrecognised.
Long-term follow-up of a randomised trial designed to determine the need for irradiation following conservative surgery for the treatment of invasive breast cancer
Authors: H.T. Ford, R.C. Coombes, J.-C. Gazet, R. Gray, C.C. McConkey, R. Sutcliffe, J. Quilliam, S. Lowndes
Journal: Annals of Oncology (2005)
A Phase I and Pharmacological Study with Imidazolium-<b> <i>trans-</i> </b>DMSO-imidazole-tetrachlororuthenate, a Novel Ruthenium Anticancer Agent
Authors: Jeany M. Rademaker-Lakhai, Desiree van den Bongard, Dick Pluim, Jos H. Beijnen, Jan H. M. Schellens
Journal: Clinical Cancer Research (2004)

Abstract Purpose: NAMI-A {H2Im[trans-RuCl4(DMSO)HIm] or imidazolium-trans-DMSO-imidazole-tetrachlororuthenate} is a novel ruthenium-containing compound that has demonstrated antimetastatic activity in preclinical studies. This Phase I study was designed to determine the maximum-tolerated dose (MTD), profile of adverse events, and dose-limiting toxicity of NAMI-A in patients with solid tumors. Furthermore, the ruthenium pharmacokinetics (PK) after NAMI-A administration and preliminary antitumor activity were evaluated. Patients and Methods: Adult patients with solid tumors received NAMI-A as an i.v. infusion over 3 h daily for 5 days every 3 weeks. PK of total and unbound ruthenium was determined during the first and second treatment using noncompartmental pharmacokinetic analysis. The total accumulation of ruthenium in WBCs was also quantified. Results: Twenty-four patients were treated at 12 dose levels (2.4–500 mg/m2/day). At 400 mg/m2/day, blisters developed on the hands, fingers, and toes. At 500 mg/m2/day, blisters persisted from weeks to months and slowly regressed. Although no formal common toxicity criteria (CTC) grade 3 developed, painful blister formation was considered dose limiting. Because the first signs developed at 400 mg/m2/day, the advised dose for further testing of NAMI-A was determined to be 300 mg/m2/day on this schedule. PK analysis revealed a linear relationship between dose and area under the concentration-time curve (AUC) of total and unbound ruthenium (R2 = 0.75 and 0.96, respectively) over the whole dose range. Plasma clearance of total ruthenium was 0.17 ± 0.09 liter/h, and terminal half-life was 50 ± 19 h. The volume of distribution at steady state of total ruthenium was 10.1 ± 2.8 liters. The accumulation of ruthenium in WBC was not directly proportional to the increasing total exposure to ruthenium. One patient with pretreated and progressive nonsmall cell lung cancer had stable disease for 21 weeks. Conclusion: NAMI-A can be administered safely as a 3-h i.v. infusion at a dose of 300 mg/m2/day for 5 days, every 3 weeks.
Thymus and autoimmunity. Transplantation of the thymus from cyclosporin A-treated mice causes organ-specific autoimmune disease in athymic nude mice.
Authors: S Sakaguchi, N Sakaguchi
Journal: The Journal of Experimental Medicine (1988)

Organ-specific autoimmune diseases such as gastritis, oophoritis, thyroiditis, or insulitis developed in athymic nu/nu mice after engraftment of the thymus from euthymic nu/+ mice treated with cyclosporin A (CsA), a potent immuno-suppressant. The development of autoimmune disease in the nu/nu mice was prevented by inoculation of thymocyte suspensions prepared from normal nu/+ mice, but not by thymocyte suspensions from CsA-treated nu/+ mice. Cotransplantation of normal nu/+ mouse thymus with CsA-treated thymus also suppressed the development of autoimmune disease. Inoculation of spleen cell suspensions prepared from normal adult nu/+ mice prevented autoimmune disease, but inoculation of those from newborn nu/+ mice did not. Thus, CsA appears to interfere selectively with the thymic production of certain suppressor T cells controlling self-reactive (autoimmune) T cells, allowing the latter to expand and cause autoimmune disease.
The European Respiratory Society spirometry tent: a unique form of screening for airway obstruction
Authors: Sara Maio, Duane L. Sherrill, William MacNee, Peter Lange, Ulrich Costabel, Sven-Erik Dahlén, Gerhard W. Sybrecht, Otto C. Burghuber, Robin Stevenson, Philip Tønnesen, Karl Haeussinger, Gunilla Hedlin, Torsten T. Bauer, Josef Riedler, Laurent Nicod, Kai-Håkon Carlsen, Giovanni Viegi
Journal: European Respiratory Journal (2012)

In order to raise public awareness of the importance of early detection of airway obstruction and to enable many people who had not been tested previously to have their lung function measured, the European Lung Foundation and the European Respiratory Society (ERS) organised a spirometry testing tent during the annual ERS Congresses in 2004–2009. Spirometry was performed during the ERS Congresses in volunteers; all participants answered a simple, brief questionnaire on their descriptive characteristics, smoking and asthma. Portable spirometers were freely provided by the manufacturer. Nurses and doctors from pulmonary departments of local hospitals/universities gave their service for free. Lower limit of normal (LLN) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for diagnosing and grading airway obstruction were used. Of 12,448 participants in six congress cities, 10,395 (83.5%) performed acceptable spirometry (mean age 51.0±18.4 yrs; 25.5% smokers; 5.5% asthmatic). Airway obstruction was present in 12.4% of investigated subjects according to LLN criteria and 20.3% according to GOLD criteria. Through multinomial logistic regression analysis, age, smoking habits and asthma were significant risk factors for airway obstruction. Relative risk ratio and 95% confidence interval for LLN stage I, for example, was 2.9 (2.0–4.1) for the youngest age (≤19 yrs), 1.9 (1.2–3.0) for the oldest age (≥80 yrs), 2.4 (2.0–2.9) for current smokers and 2.8 (2.2–3.6) for reported asthma diagnosis. In addition to being a useful advocacy tool, the spirometry tent represents an unusual occasion for early detection of airway obstruction in large numbers of city residents with an important public health perspective.
PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET Bromodomains
Authors: Sarah Picaud, David Da Costa, Angeliki Thanasopoulou, Panagis Filippakopoulos, Paul V. Fish, Martin Philpott, Oleg Fedorov, Paul Brennan, Mark E. Bunnage, Dafydd R. Owen, James E. Bradner, Philippe Taniere, Brendan O'Sullivan, Susanne Müller, Juerg Schwaller, Tatjana Stankovic, Stefan Knapp
Journal: Cancer Research (2013)

Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT) are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression. BET proteins are recruited on transcriptionally active chromatin via their two N-terminal bromodomains (BRD), a protein interaction module that specifically recognizes acetylated lysine residues in histones H3 and H4. Inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer. Here, we present a potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails. Cocrystal structures showed that PFI-1 acts as an acetyl-lysine (Kac) mimetic inhibitor efficiently occupying the Kac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G1 cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Intriguingly, cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target.