tbuckley/cabot-search huggingface dataset:
Clinical features and treatment outcome for children with CD30+ large-cell non-Hodgkin's lymphoma.
Authors: J T Sandlund, C H Pui, V M Santana, H Mahmoud, W M Roberts, S Morris, S Raimondi, R Ribeiro, W M Crist, J S Lin
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the frequency of CD30 expression and its relationship to clinical features, immunophenotype, histotype, and outcome in childhood large-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS We reviewed 45 cases of large-cell NHL in children treated at St Jude Children's Research Hospital from 1975 to 1990 for whom there was sufficient tissue to perform immunophenotypic studies. All 45 were screened with a panel of antibodies to detect the presence of CD30 and T-cell and B-cell antigens. Cases were classified according to the National Cancer Institute (NCI) Working Formulation and the Kiel classification system. Clinical features, immunophenotype, pathologic classification, and treatment outcome were compared for CD30+ and CD30- cases. RESULTS CD30 expression was documented in 18 cases (40%). These 13 boys and five girls had a median age of 13 years at diagnosis. Most (n = 14) had advanced-stage (III and IV) disease. Nodal disease was equally common in CD30+ and CD30- cases, whereas skin involvement was significantly more frequent in CD30+ cases (P = .007). There was no significant association of CD30 expression with histologic subtype according to the NCI Working Formulation, but CD30+ cases were more likely to be anaplastic by the Kiel classification (P &lt; .001). All CD30+ cases had either T-cell or null-cell phenotype, while the majority of CD30- cases were B-cell phenotype (P &lt; .001). Among patients with limited-stage disease, the mean +/- SE estimated 5-year event-free survival (EFS) was 75% +/- 22% for CD30+ cases and 92% +/- 9% for CD30- cases (P = .10); estimates for advanced-stage disease were 57% +/- 17% and 29% +/- 17%, respectively (P = .096). For patients with advanced-stage disease, CD30 expression was associated with a significantly better overall 5-year survival probability (84% +/- 12% v 27% +/- 16%, P = .0016). CONCLUSION CD30 is frequently expressed in pediatric large-cell NHL and is significantly associated with T-cell or null-cell phenotype, anaplastic morphology, skin involvement, and better overall survival among advanced-stage patients.
746 EFFECTIVENESS AND SAFETY OF TELBIVUDINE IN FIELD PRACTICE: A MULTICENTER GERMAN REAL-LIFE OBSERVATIONAL STUDY
Authors: J. Petersen, A. Zipf, E. Schott, M. Wiese, H. Loehr, K. Boeker, B. Moeller, K.E. Pfaff, R. Heyne, C. John, J.C. Arnold, D. Hueppe, S. Mauss, P. Buggisch
Journal: Journal of Hepatology (2011)
187 A PHASE I/II, OPEN-LABEL, DOSE-ESCALATION TRIAL USING THE ONCE-DAILY ORAL CHELATOR DEFERASIROX TO TREAT IRON OVERLOAD IN HFE-RELATED HEREDITARY HEMOCHROMATOSIS: FINAL RESULTS
Authors: P. Phatak, P. Brissot, M. Wurster, P.C. Adams, H.L. Bonkovsky, J. Gross, P. Malfertheiner, G.D. McLaren, C. Niederau, A. Piperno, L.W. Powell, M. Russo, U. Stoelzel, W. Stremmel, L. Griffel, N. Lynch, Y. Zhang, A. Pietrangelo
Journal: Journal of Hepatology (2010)
Mass spectrometry quantification of clusterin in the human brain
Authors: Junjun Chen, Meiyao Wang, Illarion V Turko
Journal: Molecular Neurodegeneration (2012)

Abstract Background The multifunctional glycoprotein clusterin has been associated with late-onset Alzheimer’s disease (AD). Further investigation to define the role of clusterin in AD phenotypes would be aided by the development of techniques to quantify level, potential post-translational modifications, and isoforms of clusterin. We have developed a quantitative technique based on multiple reaction monitoring (MRM) mass spectrometry to measure clusterin in human postmortem brain tissues. Results A stable isotope-labeled concatenated peptide (QconCAT) bearing selected peptides from clusterin was expressed with an in vitro translation system and purified. This clusterin QconCAT was validated for use as an internal standard for clusterin quantification using MRM mass spectrometry. Measurements were performed on the human postmortem frontal and temporal cortex from control and severe AD cases. During brain tissues processing, 1% SDS was used in the homogenization buffer to preserve potential post-translational modifications of clusterin. However, MRM quantifications in the brain did not suggest phosphorylation of Thr 393 , Ser 394 , and Ser 396 residues reported for clusterin in serum. MRM quantifications in the frontal cortex demonstrated significantly higher ( P &lt; 0.01) level of clusterin in severe AD group (39.1 ± 9.1 pmol/mg tissue protein) in comparison to control group (25.4 ± 4.4 pmol/mg tissue protein). In the temporal cortex, the clusterin levels were not significantly different, 29.0 ± 7.9 pmol/mg tissue protein and 28.0 ± 8.4 pmol/mg tissue protein in control and severe AD groups, respectively. Conclusions The proposed protocol is a universal quantitative technique to assess expression level of clusterin. It is expected that application of this protocol to quantification of various clusterin isoforms and potential post-translational modifications will be helpful in addressing the role of clusterin in AD.
Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis
Authors: E. Bria, M. Milella, F. Cuppone, S. Novello, A. Ceribelli, V. Vaccaro, I. Sperduti, A. Gelibter, G.V. Scagliotti, F. Cognetti, D. Giannarelli
Journal: Annals of Oncology (2011)
Concomitant mutations and splice variants in KRAS and BRAF demonstrate complex perturbation of the Ras/Raf signalling pathway in advanced colorectal cancer
Authors: R Seth, S Crook, S Ibrahem, W Fadhil, D Jackson, M Ilyas
Journal: Gut (2009)

<h3>Background and aims:</h3> <i>KRAS</i> and <i>BRAF</i> mutations occur in colorectal cancers (CRCs) and are considered mutually exclusive methods of activating the RAS/RAF/MEK/ERK pathway. This pathway is a therapeutic target and <i>KRAS</i> mutation may predict tumour responsiveness. The purpose of this study was to investigate the relationship between <i>KRAS</i> and <i>BRAF</i> mutations in 24 CRC cell lines and 29 advanced CRCs. <h3>Methods:</h3> <i>KRAS</i> and <i>BRAF</i> mutations were detected using high resolution melting and sequencing. Expression of mutations was confirmed by reverse transcription- PCR (RT-PCR) and sequencing. CpG island methylator phenotype (CIMP) was tested by methylation-specific PCR. <h3>Results:</h3> <i>KRAS</i> or <i>BRAF</i> mutation occurred in 79% of cell lines and 59% of CRCs. In the cell lines, <i>KRAS</i> mutations occurred in 54% of cases (with 62% in codons 12/13 and 38% in other codons). Four cell lines had a homozygous mutation. Only heterozygous <i>BRAF</i> mutations were detected in 29% cell lines. The V600E mutation occurred most commonly and was associated with CIMP+ status (p = 0.005). Mutations at codons 529 and 581 were also found and, in one case, <i>BRAF</i> and <i>KRAS</i> mutation co-occurred. Unexpectedly, <i>BRAF</i> splice variants (with a predicted kinase-dead protein) were found in 5/24 (21%) cell lines. In advanced CRCs, <i>KRAS</i> mutations occurred in 48% of cases (64% codons 12/13, 36% other codons) and <i>BRAF</i> mutations in 10% (66% V600E, 33% exon 11). A compound <i>KRAS/BRAF</i> mutation was not seen. <h3>Conclusions:</h3> Disrupted Ras/Raf signalling is common in CRC. Homozygous <i>KRAS</i> mutations and concomitant <i>KRAS/BRAF</i> mutations may be indicative of a gene dosage effect. The significance of BRAF splice variants is uncertain but may represent another layer of complexity. Finally, if <i>KRAS</i> mutation is to be used for predictive testing, then the whole gene may need to be screened as mutations occur outside codons 12/13.
Aprepitant Versus Dexamethasone for Preventing Chemotherapy-Induced Delayed Emesis in Patients With Breast Cancer: A Randomized Double-Blind Study
Authors: Fausto Roila, Benedetta Ruggeri, Enzo Ballatori, Albano Del Favero, Maurizio Tonato
Journal: Journal of Clinical Oncology (2013)

Purpose A combination of aprepitant, a 5-HT3 receptor antagonist, and dexamethasone is recommended for the prophylaxis of acute or delayed emesis induced by chemotherapy containing anthracyclines plus cyclophosphamide in patients with breast cancer. The aim of this study was to verify whether dexamethasone is superior to aprepitant in preventing delayed emesis in patients receiving the same prophylaxis for acute emesis. Patients and Methods A randomized double-blind study comparing aprepitant versus dexamethasone was completed in chemotherapy-naive patients with breast cancer treated with anthracyclines plus cyclophosphamide. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg, dexamethasone 8 mg, and oral aprepitant 125 mg. On days 2 and 3, patients randomly received oral dexamethasone 4 mg twice per day or aprepitant 80 mg once per day. Primary end point was rate of complete response (ie, no vomiting or rescue treatment) from days 2 to 5 after chemotherapy. Results Of 580 enrolled patients, 551 were evaluable: 273 received dexamethasone, and 278 received aprepitant. Day 1 complete response rates were similar: 87.6% for dexamethasone and 84.9% for aprepitant (P &lt; .39). From days 2 to 5, complete response rates were the same with both antiemetic prophylaxes (79.5%; P &lt; 1.00), as were results of secondary end points (ie, complete protection, total control, no vomiting, no nausea, score of Functional Living Index–Emesis; P &lt; .24). Incidences of insomnia (2.9% v 0.4%; P &lt; .02) and heartburn (8.1% v 3.6%; P &lt; .03) were significantly greater with dexamethasone on days 2 to 5. Conclusion In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis, dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis.
A comparative study of proliferative activity and tumor stage of pregnancy-associated melanoma (PAM) and non-PAM in gestational age women
Authors: Emily A. Merkel, Mary C. Martini, Sapna M. Amin, Oriol Yélamos, Christina Y. Lee, Lauren M. Sholl, Alfred W. Rademaker, Joan Guitart, Pedram Gerami
Journal: Journal of the American Academy of Dermatology (2015)
The Effect of Pitressin on Sodium Tolerance in Experimental Hypertension
Authors: SYDNEY M. FRIEDMAN, DAVID F. HARDWICK, J. A. M. HINKE
Journal: Circulation Research (1955)

Rats subjected to diverse hypertension-inducing procedures develop an abnormal sodium tolerance characterized by an accelerated rate of excretion of an administered load. Pitressin reverses this abnormality in sodium tolerance during the period corresponding to the delayed depressor phase of the response to the extract.
Studies on congenital osteopetrosis in microphthalmic mice using organ cultures: impairment of bone resorption in response to physiologic stimulators.
Authors: L G Raisz, H A Simmons, S C Gworek, G Eilon
Journal: The Journal of Experimental Medicine (1977)

The mechanism of congenital osteopetrosis in microphthalmic (mi) mice has been examined in bone organ cultures. Resorption was measured by the release of previously incorporated 45Ca in fetal long bones and newborn calvaria from mi mice and heterozygous or homozygous normal litter mates. Bones from mi mice showed a generalized resorption defect with decreased spontaneous or control resorption and failure to respond to parathyroid hormone (PTH), prostaglandin E2, 1,25 dihydroxy vitamin D3, vitamin A, or osteoclast activating factor (OAF) from human peripheral leukocytes or mouse spleen cells. Bones from heterozygotes showed a smaller response to PTH than bones from homozygous normals. Mutant bones failed to show an increase in lysosomal enzyme release in response to PTH or vitamin A, agents which increased release from bones of homozygous normals. Proline incorporation into collagenase-digestible protein was similar in cultures of normal and mutant bone and was inhibited by PTH and OAF. These results indicate that congenital osteopetrosis in mi mice is due to a generalized defect in the function and hormonal response of osteoclasts and suggests that this cell line is separate from the osteoblast cell line which shows no impairment of hormonal response.
Cyclosporin A stimulates transcription and procollagen secretion in tubulointerstitial fibroblasts and proximal tubular cells.
Authors: G Wolf, P D Killen, E G Neilson
Journal: Journal of the American Society of Nephrology (1990)

The brief study described in this report was undertaken to determine whether cyclosporin A had any direct effect on the expression of tubulointerstitial procollagens in cultured renal cells. Our findings indicate that murine tubulointerstitial fibroblasts secreted significantly more procollagen type I after the addition of cyclosporin A, whereas syngeneic proximal tubular cells expressed significantly more types I and IV procollagen after cyclosporin stimulation. These increases in procollagen gene product correlated concordantly with changes in the levels of cytoplasmic mRNA with procollagen-specific cDNA probes. Transfection of these fibroblasts and proximal tubular cells with chimeric gene constructs containing enhancer/promoter elements for alpha2(I) and alpha 1(IV) procollagen linked to a chloramphenicol acetyltransferase reporter gene indicates that the stimulatory effect of cyclosporin on procollagen expression depends, at least to some extent, on an increase in transcriptional activity.
M<scp>olecular</scp>D<scp>efects in</scp>H<scp>uman</scp>S<scp>evere</scp>C<scp>ombined</scp>I<scp>mmunodeficiency and</scp>A<scp>pproaches to</scp>I<scp>mmune</scp>R<scp>econstitution</scp>
Authors: Rebecca H. Buckley
Journal: Annual Review of Immunology (2004)

▪ Abstract Mutations in nine different genes have been found to cause the human severe combined immunodeficiency syndrome. The products of three of the genes—IL-2RG, Jak3, and IL-7Rα—are components of cytokine receptors, and the products of three more—RAG1, RAG2, and Artemis—are essential for effecting antigen receptor gene rearrangement. Additionally, a deficiency of CD3δ, a component of the T-cell antigen receptor, results in a near absence of circulating mature CD3+ T cells and a complete lack of γ/δ T cells. Adenosine deaminase deficiency results in toxic accumulations of metabolites that cause T cell apoptosis. Finally, a deficiency of CD45, a critical regulator of signaling thresholds in immune cells, also causes SCID. Approaches to immune reconstitution have included bone marrow transplantation and gene therapy. Bone marrow transplantation, both HLA identical unfractionated and T cell–depleted HLA haploidentical, has been very successful in effecting immune reconstitution if done in the first 3.5 months of life and without pretransplant chemotherapy. Gene therapy was highly successful in nine infants with X-linked SCID, but the trials have been placed on hold due to the development of a leukemic process in two of the children because of insertional oncogenesis.
THE IMMUNOTHERAPY OF SOLID CANCERS BASED ON CLONING THE GENES ENCODING TUMOR-REJECTION ANTIGENS
Authors: Steven A. Rosenberg, M.D., Ph.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Cellular immune reactions play a major role in the host reaction to growing cancers. Tumor infiltrating lymphocytes (TIL) can be isolated from melanomas and can specifically recognize unique tumor antigens. The adoptive transfer of TIL plus interleukin-2 can mediate tumor regression in patients with metastatic melanoma. TIL capable of mediating tumor regression have been used to clone and sequence a variety of the genes that encode the tumor-regression antigens recognized by these TIL. This information has opened new opportunities for the development of cancer immunotherapies. These gene products can be used to generate lymphocytes, in vitro, with improved antitumor activity for use in adoptive transfer. Active immunization can be performed using either the immunodominant peptides present in these proteins or by incorporating the tumor antigen genes into recombinant viruses. Cancer vaccine trials using many of these approaches have recently begun. Attempts to apply a similar strategy to epithelial tumors such as breast and ovarian cancer are underway.
The use of rabbit intestinal permeability as an in vitro assay in the search for orally active GPIIb/IIIa antagonists
Authors: James M. Samanen, Chao-Pin Lee, Philip L. Smith, William E. Bondinell, Raul R. Calvo, Dalia R. Jakas, Kenneth A. Newlander, Michael Parker, Irene Uzinskas, Tobias O. Yellin, Andrew J. Nichols
Journal: Advanced Drug Delivery Reviews (1997)
Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women
Authors: Alexandra J. Lansky, Judith S. Hochman, Patricia A. Ward, Gary S. Mintz, Rosalind Fabunmi, Peter B. Berger, Gishel New, Cindy L. Grines, Cody G. Pietras, Morton J. Kern, Margaret Ferrell, Martin B. Leon, Roxana Mehran, Christopher White, Jennifer H. Mieres, Jeffrey W. Moses, Gregg W. Stone, Alice K. Jacobs
Journal: Circulation (2005)

More than 1.2 million percutaneous coronary interventions are performed annually in the United States, with only an estimated 33% performed in women, despite the established benefits of percutaneous coronary intervention and adjunctive pharmacotherapy in reducing fatal and nonfatal ischemic complications in acute myocardial infarction and high-risk acute coronary syndromes. This statement reviews sex-specific data on the safety and efficacy of contemporary interventional therapies in women.
Metabolic Imaging of Pancreatic Ductal Adenocarcinoma Detects Altered Choline Metabolism
Authors: Marie-France Penet, Tariq Shah, Santosh Bharti, Balaji Krishnamachary, Dmitri Artemov, Yelena Mironchik, Flonné Wildes, Anirban Maitra, Zaver M. Bhujwalla
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease that develops relatively symptom-free and is therefore advanced at the time of diagnosis. The absence of early symptoms and effective treatments has created a critical need for identifying and developing new noninvasive biomarkers and therapeutic targets. Experimental Design: We investigated the metabolism of a panel of PDAC cell lines in culture and noninvasively in vivo with 1H magnetic resonance spectroscopic imaging (MRSI) to identify noninvasive biomarkers and uncover potential metabolic targets. Results: We observed elevated choline-containing compounds in the PDAC cell lines and tumors. These elevated choline-containing compounds were easily detected by increased total choline (tCho) in vivo, in spectroscopic images obtained from tumors. Principal component analysis of the spectral data identified additional differences in metabolites between immortalized human pancreatic cells and neoplastic PDAC cells. Molecular characterization revealed overexpression of choline kinase (Chk)-α, choline transporter 1 (CHT1), and choline transporter–like protein 1 (CTL1) in the PDAC cell lines and tumors. Conclusions: Collectively, these data identify new metabolic characteristics of PDAC and reveal potential metabolic targets. Total choline detected with 1H MRSI may provide an intrinsic, imaging probe–independent biomarker to complement existing techniques in detecting PDAC. The expression of Chk-α, CHT1, and CTL1 may provide additional molecular markers in aspirated cytological samples. Clin Cancer Res; 21(2); 386–95. ©2014 AACR.
Rescue of the lethal scl−/− phenotype by the human SCL locus
Authors: Angus M. Sinclair, Anthony J. Bench, Adrian J. C. Bloor, Juan Li, Berthold Göttgens, Maureen L. Stanley, Jane Miller, Sandie Piltz, Susie Hunter, Elisabeth P. Nacheva, Marı́a-José Sanchez, Anthony R. Green
Journal: Blood (2002)
Triggering of Acute Myocardial Infarction Onset by Episodes of Anger
Authors: Murray A. Mittleman, Malcolm Maclure, Jane B. Sherwood, Richard P. Mulry, Geoffrey H. Tofler, Sue C. Jacobs, Richard Friedman, Herbert Benson, James E. Muller
Journal: Circulation (1995)

Background Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. Methods and Results We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) ( P &lt;.05). Conclusions Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.
Early Changes in Auditory Function As a Result of Platinum Chemotherapy: Use of Extended High-Frequency Audiometry and Evoked Distortion Product Otoacoustic Emissions
Authors: Kristin R. Knight, Dale F. Kraemer, Christiane Winter, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2007)

The objective is to describe progressive changes in hearing and cochlear function in children and adolescents treated with platinum-based chemotherapy and to begin preliminary evaluation of the feasibility of extended high-frequency audiometry and distortion product otoacoustic emissions for ototoxicity monitoring in children.Baseline and serial measurement of conventional pure-tone audiometry (0.5 to 8 kHz) and evoked distortion product otoacoustic emissions (DPOAEs) were conducted for 32 patients age 8 months to 20 years who were treated with cisplatin and/or carboplatin chemotherapy. Seventeen children also had baseline and serial measurement of extended high-frequency (EHF) audiometry (9 to 16 kHz). Audiologic data were analyzed to determine the incidence of ototoxicity using the American Speech-Language-Hearing Association criteria, and the relationships between the different measures of ototoxicity.Of the 32 children, 20 (62.5%) acquired bilateral ototoxicity in the conventional frequency range during chemotherapy treatment, and 26 (81.3%) had bilateral decreases in DPOAE amplitudes and dynamic range. Of the 17 children with EHF audiometry results, 16 (94.1%) had bilateral ototoxicity in the EHF range. Pilot data suggest that EHF thresholds and DPOAEs show ototoxic changes before hearing loss is detected by conventional audiometry.EHF audiometry and DPOAEs have the potential to reveal earlier changes in auditory function than conventional frequency audiometry during platinum chemotherapy in children.