tbuckley/cabot-search huggingface dataset:
Abstract IA09: Therapy of lymphoma inspired by functional and structural genomics
Authors: Louis M. Staudt
Journal: Cancer Research (2015)

Abstract Diffuse large B cell lymphoma (DLBCL) is a heterogeneous diagnostic category that is comprised of two prominent molecular subtypes, termed activated B cell-like (ABC) and germinal center B cell-like (GCB). These DLBCL subtypes are now viewed as molecularly distinct diseases since they arise from distinct stages of normal B cell development, require distinct recurrent genetic abnormalities to become malignant, have distinct cure rates with current chemotherapy regimens, and respond differentially to targeting agents. We defined a chronic active form of B cell receptor (BCR) signaling that activates NF-kB in ABC DLBCLs. Such ABC DLBCLs are killed by knockdown of BCR signaling components, such as the kinase BTK or components of the BCR itself. Over one fifth of ABC DLBCLs have mutations affecting the CD79B or CD79A subunits of the BCR that augment BCR signaling. To attack chronic active BCR signaling therapeutically, we initiated clinical trials in relapsed/refractory DLBCL of ibrutinib, an irreversible and highly selective inhibitor of BTK. Ibrutinib monotherapy induced a high rate of complete and partial responses in ABC DLBCL, while GCB DLBCL tumors rarely responded. Genetic analysis of responding tumors demonstrated an enrichment for those with CD79B mutations, but most responses were observed in tumors with wild type BCR subunits. This observation allowed us to define a non-genetic mechanism of BCR activation that depends on reactivity of the lymphoma BCR to self antigens. In addition to chronic active BCR signaling, the signaling adapter MyD88 is activated by oncogenic mutations in 40% of ABC DLBCL cases. Since these mutant MyD88 isoforms act in parallel to BCR signaling to activate the NF-kB pathway in ABC DLBCL, they might have been predicted to mitigate the clinical effects of ibrutinib. On the contrary, ABC DLBCL tumors with both CD79B and MYD88 mutations were highly responsive to ibrutinib, leading us to demonstrate that the BCR and MyD88 pathways positively regulate one another. To extend the efficacy of ibrutinib, we have identified additional therapeutic targets in the oncogenic signaling pathways in ABC DLBCL including: 1) ubiquitin ligases, such as LUBAC, that are required to assemble active signaling complexes downstream of the BCR; 2) the kinase IRAK4, which mediates oncogenic MyD88 signaling; 3) the PI3 kinase pathway, which is activated by chronic active BCR signaling; 4) BCL2, which is expressed highly in most ABC DLBCL tumors and is the target of recurrent amplifications. Several synergistic, mechanism-based drug combinations that exploit these redundant survival pathways will be presented. Citation Format: Louis M. Staudt. Therapy of lymphoma inspired by functional and structural genomics. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA09.
Abstract 12280: Stem Cell Factor Gene Transfer Improves Cardiac Function After Myocardial Infarction in Swine
Authors: kiyotake ishikawa, Elisa Yaniz-Galende, Jaime Aguero, Lisa Tilemann, Lifan Liang, Dennis Ladage, Yoshiaki Kawase, Kenneth Fish, Roger J Hajjar
Journal: Circulation (2012)

Background: Stem cell factor (SCF), a ligand of the c-kit receptor, is a critical cytokine which contributes to cell migration, proliferation, and survival. It has been shown that SCF expression in...
Prevention of Low Back Pain
Authors: Daniel Steffens, Chris G. Maher, Leani S. M. Pereira, Matthew L Stevens, Vinicius C. Oliveira, Meredith Chapple, Luci F. Teixeira-Salmela, Mark J. Hancock
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Existing guidelines and systematic reviews lack clear recommendations for prevention of low back pain (LBP). <h3>Objective</h3> To investigate the effectiveness of interventions for prevention of LBP. <h3>Data Sources</h3> MEDLINE, EMBASE, Physiotherapy Evidence Database Scale, and Cochrane Central Register of Controlled Trials from inception to November 22, 2014. <h3>Study Selection</h3> Randomized clinical trials of prevention strategies for nonspecific LBP. <h3>Data Extraction and Synthesis</h3> Two independent reviewers extracted data and assessed the risk of bias. The Physiotherapy Evidence Database Scale was used to evaluate the risk-of-bias. The Grading of Recommendations Assessment, Development, and Evaluation system was used to describe the quality of evidence. <h3>Main Outcomes and Measures</h3> The primary outcome measure was an episode of LBP, and the secondary outcome measure was an episode of sick leave associated with LBP. We calculated relative risks (RRs) and 95% CIs using random-effects models. <h3>Results</h3> The literature search identified 6133 potentially eligible studies; of these, 23 published reports (on 21 different randomized clinical trials including 30 850 unique participants) met the inclusion criteria. With results presented as RRs (95% CIs), there was moderate-quality evidence that exercise combined with education reduces the risk of an episode of LBP (0.55 [0.41-0.74]) and low-quality evidence of no effect on sick leave (0.74 [0.44-1.26]). Low- to very low–quality evidence suggested that exercise alone may reduce the risk of both an LBP episode (0.65 [0.50-0.86]) and use of sick leave (0.22 [0.06-0.76]). For education alone, there was moderate- to very low–quality evidence of no effect on LBP (1.03 [0.83-1.27]) or sick leave (0.87 [0.47-1.60]). There was low- to very low–quality evidence that back belts do not reduce the risk of LBP episodes (1.01 [0.71-1.44]) or sick leave (0.87 [0.47-1.60]). There was low-quality evidence of no protective effect of shoe insoles on LBP (1.01 [0.74-1.40]). <h3>Conclusion and Relevance</h3> The current evidence suggests that exercise alone or in combination with education is effective for preventing LBP. Other interventions, including education alone, back belts, and shoe insoles, do not appear to prevent LBP. Whether education, training, or ergonomic adjustments prevent sick leave is uncertain because the quality of evidence is low.
Pathological Grief Following Spontaneous Abortion
Authors: ROBERT T. CORNEY, FREDERICK T. HORTON
Journal: American Journal of Psychiatry (1974)

The authors describe a patient who developed acute, disturbing symptoms several months after a spontaneous abortion during early pregnancy. Anamnesis revealed that her symptoms were not the usual symptoms of acute grief but were representative of pathological grief a complication of mourning. The authors feel that the recognition of pathological grief is important because it may prove resistant to the usual treatment measures for depression.
Detection of recurrent or persistent nasopharyngeal carcinomas after radiotherapy with 18-fluoro-2-deoxyglucose positron emission tomography and comparison with computed tomography.
Authors: C H Kao, S P ChangLai, P U Chieng, R F Yen, T C Yen
Journal: Journal of Clinical Oncology (1998)

PURPOSE The effectiveness of positron emission tomography (PET) with 1 8-fluoro-2-deoxyglucose (FDG) for detecting suspected recurrence of nasopharyngeal carcinomas (NPC) was evaluated and compared with computed tomography (CT). PATIENTS AND METHODS FDG-PET studies were performed on 36 NPC patients 4 months after radiotherapy. The images were interpreted visually and quantitatively by calculating standardized uptake values (SUVs). RESULTS The sensitivity, specificity, and accuracy of visually interpreted FDG-PET images, for differentiation of recurrent or persistent NPC from benign lesions, were 100%, 96%, and 97%, respectively. Cases with recurrent or persistent NPC (1.6 to 5.8) had significantly higher SUVs than cases with benign lesions (0.8 to 1.5). The sensitivity, specificity, and accuracy of CT for detecting recurrent or persistent NPC were 72%, 88%, and 83%, respectively. CONCLUSION FDG-PET is a better tool than CT for the detection of recurrent or persistent NPC. Either visual interpretation or SUV can be used to differentiate benign lesions from recurrent or persistent NPC.
The risk of respiratory symptoms on allergen exposure increases with increasing specific IgE levels
Authors: M. Olivieri, J. Heinrich, V. Schlünssen, J. M. Antó, B. Forsberg, C. Janson, B. Leynaert, D. Norback, T. Sigsgaard, C. Svanes, C. Tischer, S. Villani, D. Jarvis, G. Verlato
Journal: Allergy (2016)

The relation between IgE sensitization and allergic respiratory symptoms has usually been evaluated by dichotomizing specific IgE levels. The aim of this study was to evaluate the association between specific IgE levels and risk of symptoms on allergen-related exposure, with special reference to allergen-related asthma-rhinitis comorbidity.We considered 6391 subjects enrolled within the European Community Respiratory Health Survey 2, having information on cat/grass/D. pteronyssinus IgE levels and symptoms on exposure to animals/pollen/dust. The risk of oculonasal/asthmalike/both symptoms was evaluated by a multinomial logistic model.A clear positive association was observed between specific IgE levels to cat/grass/mite and the risk of symptoms on each allergen-related exposure (test for trend with P < 0.001). This trend was particularly pronounced when considering the coexistence of asthmalike and oculonasal symptoms. Compared to non-sensitized subjects, subjects with specific IgE to cat >= 3.5 kU/l presented relative risk ratios of 11.4 (95% CI 6.7-19.2), 18.8 (8.2-42.8), and 55.3 (30.5-100.2) when considering, respectively, only oculonasal symptoms, only asthmalike symptoms, or both. A similar pattern was observed when considering specific IgE to grass/mite and symptoms on exposure to pollen/dust. Also the proportion of people using inhaled medicines or visiting a general practitioner for breathing problems in the previous year increased with increasing sum of specific IgE to cat/grass/mite.Specific IgE level is the most important predictor of allergen-related symptoms. The risk of both oculonasal/asthmalike symptoms increases with specific IgE levels, suggesting that specific IgE contributes to the 'united airways disease'.
Breast Cancer in Women After Repeated Fluoroscopic Examinations of the Chest2
Authors: John D. Boice, Richard R. Monson
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Breast Cancer in Women After Repeated Fluoroscopic Examinations of the Chest Get access John D. Boice, Jr., John D. Boice, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard R. Monson Richard R. Monson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 3, September 1977, Pages 823–832, https://doi.org/10.1093/jnci/59.3.823 Published: 01 September 1977 Article history Received: 28 December 1976 Accepted: 28 March 1977 Published: 01 September 1977
Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy
Authors: Ajay Vora, Anita Andreano, Ching-Hon Pui, Stephen P. Hunger, Martin Schrappe, Anja Moericke, Andrea Biondi, Gabriele Escherich, Lewis B. Silverman, Nicholas Goulden, Mervi Taskinen, Rob Pieters, Keizo Horibe, Meenakshi Devidas, Franco Locatelli, Maria Grazia Valsecchi
Journal: Journal of Clinical Oncology (2016)

We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL).We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission. Using a random effects model, with CRT as a dichotomous covariate, we performed a single-arm meta-analysis to compare event-free survival and cumulative incidence of isolated or any CNS relapse and isolated bone marrow relapse in high-risk subgroups of patients who either did or did not receive CRT.Although there was significant heterogeneity in all outcome end points according to trial, CRT was associated with a reduced risk of relapse only in the small subgroup of patients with overt CNS disease at diagnosis, who had a significantly lower risk of isolated CNS relapse (4% with CRT v 17% without CRT; P = .02) and a trend toward lower risk of any CNS relapse (7% with CRT v 17% without CRT; P = .09). However, this group had a relatively high rate of events regardless of whether or not they received CRT (32% [95% CI, 26% to 39%] v 34% [95% CI, 19% to 54%]; P = .8).CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols.
AB0023 Combination of Igg N-Glycomics and Corresponding Transcriptomics Data to Identify Anti-Tnf-Alpha Treatment Responders in Rheumatoid Arthritis and Inflammatory Bowel Disease
Authors: C. Váradi, A. Guttman, Z. Hollό, S. Poliska, L. Nagy, Z. Szekanecz, A. Váncsa, K. Palatka
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Prediction of responsiveness in biological therapies is an important and challenging issue in different diseases. Analyzing glycosylation pattern changes of key serum glycoproteins is one of the possible avenues to follow disease remission. <h3>Objectives</h3> The aim of this study was to investigate the changes of serum IgG glycoforms in rheumatoid arthritis (RA) and Crohn9s disease (CD) patients in response to anti-tumor necrosis factor alpha (TNFα) treatment. <h3>Methods</h3> IgG was isolated from patient serum samples using Protein A affinity pull-down, followed by the release of N-glycans with peptide-N-glycanase F. The released glycans were fluorescently tagged with aminopyrene-trisulfonate and analyzed by capillary gel electrophoresis with laser induced fluorescent detection. <h3>Results</h3> Significant alterations were detected between responders and non-responders in both disease groups. In RA, three low abundant galactosylated structures were found to be significantly different before the treatment where in all of the cases responders showed higher galactosylation level. Unfortunately, no significant alteration was detected in RA in response to the treatment. In CD significant differences were detected in galactosylation level between responders and non-responders before the treatment (higher in the responder group). FA2G2S1 level was significantly increased in response to anti-TNFα therapy, thus being a possible candidate marker for responder identification. Interestingly, the level of this structure was not significantly altered in any of the RA groups suggesting disease specificity for CD. <h3>Conclusions</h3> IgG N-glycomics and corresponding transcriptomics may be useful to reveal disease-specific alterations when assessing responses to anti-TNFα therapy in chronic inflammatory diseasaes, such as RA or CD. <h3>Disclosure of Interest</h3> None declared
Psychomotor epilepsy and violence in a group of incarcerated adolescent boys
Authors: D O Lewis, J H Pincus, S S Shanok, G H Glaser
Journal: American Journal of Psychiatry (1982)

The authors report the finding of psychomotor epilepsy in 18 of 97 incarcerated delinquent boys. Number of psychomotor symptoms was correlated with degree of violence in the members of this group. In addition, psychomotor symptoms were correlated more strongly with certain psychotic symptoms than with soft neurological signs or intellectual deficits. The relationship of violence to ictal and interictal states is explored.
Effect of Casein, Lactalbumin, and Ovalbumin on 3-Methylcholanthrene-Induced Mammary Carcinoma in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Shay, Harry, Gruenstein, Margot, Shimkin, Michael B.
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Effect of Casein, Lactalbumin, and Ovalbumin on 3-Methylcholanthrene-Induced Mammary Carcinoma in Rats Get access Harry Shay, Harry Shay Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Margot Gruenstein, Margot Gruenstein Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael B. Shimkin Michael B. Shimkin Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 2, August 1964, Pages 243–253, https://doi.org/10.1093/jnci/33.2.243 Published: 01 August 1964 Article history Received: 04 February 1964 Published: 01 August 1964
Cylindromatosis—A Protective Molecule against Liver Diseases
Authors: Claus Hellerbrand, Ramin Massoumi
Journal: Medicinal Research Reviews (2016)

Abstract Cylindromatosis (CYLD) is a deubiquitination enzyme involved in the regulation of different cellular processes including inflammation, fibrosis, and cancer. The function of CYLD is via deubiquitination of specific substrates in different signaling pathways including NF‐κB, Notch, and JNK. CYLD contributes to hepatic homeostasis and restoration upon liver injury. Mutation or disruption of the activity of CYLD in animals aggravates acute as well as chronic liver injury and promotes development and progression of hepatocellular cancer. This is mediated by a shift of the balance toward pro‐inflammatory, pro‐fibrogenic, and pro‐oncogenic pathways. In this review, we will explain the liver‐associated signaling pathways that CYLD regulates in hepatocytes and nonparenchymal liver cells under physiological and pathological conditions. We will also describe the most recent findings concerning CYLD‐mediated downstream signaling in the liver in situations such as injury, infection, inflammation, and cancer. Furthermore, we will discuss the potential of novel diagnostic tools and treatment strategies utilizing CYLD and its target genes.
Abstract 13906: Accentuated Morning Peak in Circadian Patterns of Acute Myocardial Infarction Onset in Patients with Increased Serum Triglyceride Levels
Authors: Ryuya Edahiro, Yasuhiko Sakata, Daisaku Nakatani, Shinichiro Suna, Masaya Usami, Sen Matsumoto, Masahiko Hara, Toshimitsu Hamasaki, Hiroshi Sato, Masatsugu Hori, Shinsuke Nanto, Issei Komuro
Journal: Circulation (2012)

Background: It is well known that onset of acute myocardial infarction (AMI) shows characteristic circadian variations involving a definite morning peak and an indefinite nighttime peak. However, it is also reported that the bimodal peaks of AMI onset vary among subpopulations according to age, gender, and socioeconomic environments. Methods: We investigated the factors that could affect circadian patterns of AMI onset in 7755 consecutive patients registered to the Osaka Acute Coronary Insufficiency Study (OACIS) between 1998 and 2009, whose time of AMI onset was definitely identified. A mixture of two von Mises distributions (VMD) was used to examine whether the pattern of AMI onset is unimodal or bimodal. The goodness of fit of VMD was assessed by likelihood ratio test and Akaike Information Criterion. Results: Overall population had a circadian pattern of AMI onset with two peaks; a sharp morning peak (9:01 AM; 95%CI: 8:53-9:08 AM) and a less sharp nighttime peak (8:11 PM; 95%CI: 7:48-8:34 PM) (Figure,...
Paraprotein management
Authors: W Stuart A Smellie, Gavin P Spickett
Journal: BMJ (2006)

We present two cases illustrating the use of electrophoresis in the diagnosis and monitoring of plasma cell dyscrasias. The presence of monoclonal protein bands (paraproteins) in myeloma is well recognised; other conditions in which paraproteins may be seen are less well understood, as is the relatively common monoclonal gammopathy of unknown significance (MGUS) often previously referred to as benign paraproteinaemia.
Role of Cdc25C phosphatase in benzyl isothiocyanate-mediated G2/M arrest in pancreatic cancer cells.
Authors: Ruifen Zhang, Sivakumar Loganathan, Jeffrey Richards, Sanjay K. Srivastava
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5586 

Epidemiological studies continue to support the existence of an inverse relationship between dietary intake of cruciferous vegetables and incidence of various types of cancer including pancreatic cancer. Recent studies including those from our laboratory suggested that benzyl isothiocyanate (BITC), a constituent of cruciferous vegetables, could inhibit the growth of cultured cancer cells. However, the exact mechanism by which BITC exerts antiproliferative effects is not clear. We therefore, sought to determine the mechanism of BITC-mediated growth arrest in Capan-2 human pancreatic cancer cells. We found that BITC has an antiproliferative effect on Capan-2 cells with an IC50 of about 5 μM, causes cell cycle arrest in G2/M phase and induces apoptosis in a dose-dependent manner. Our results demonstrate that BITC causes irreversible cell cycle arrest in these cells, which is associated with down regulation of the expression of key G2/M cell cycle regulatory proteins such as cdk1, cyclinB1 and Cdc25C as well as phosphorylation of cdk1 and Cdc25C. The BITC-mediated drastic reduction in the level of Cdc25C was almost completely blocked when Capan-2 cells were pretreated with proteasome inhibitor lactacystin. These results suggest that BITC-mediated down-regulation of Cdc25C may involve the proteasomal degradation pathway. Interestingly, lactacystin pretreatment partially protected Capan-2 cells from BITC-induced apoptosis. Taken together our results suggest that BITC-induced cell growth arrest and apoptosis may in part, mediated by Cdc25C. [Supported in part by RO1 grant CA 106953 (to S.K.S.) awarded by the National Cancer Institute].