tbuckley/cabot-search huggingface dataset:
EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis
Authors: Zu-Yao Yang, Wei-Xi Shen, Xue-Feng Hu, Da-Yong Zheng, Xin-Yin Wu, Ya-Fang Huang, Jin-Zhang Chen, Chen Mao, Jin-Ling Tang
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Epidermal growth factor receptor gene copy number ( EGFR GCN) has been heavily investigated as a potential predictive biomarker for the treatment of metastatic colorectal cancer (mCRC) with anti-EGFR monoclonal antibodies (MAbs). The objective of this study was to systematically review current evidences on this issue. Methods PubMed, EMBASE, The Cochrane Library, Chinese Biomedical Literature Database, Wanfang Data, and the conference abstracts of American Society of Clinical Oncology and European Society of Medical Oncology were comprehensively searched. Studies that reported the objective response rate (ORR), progression-free survival, and/or overall survival of mCRC patients treated with anti-EGFR MAbs, stratified by EGFR GCN status, were included. The effect measures for binary outcome (response) and time-to-event outcomes (progression-free survival and overall survival) were risk difference and hazard ratio, respectively. Statistical heterogeneity among the studies was assessed by the Cochran’s Q -test and the I 2 statistic. If appropriate, a quantitative synthesis of data from different studies would be conducted with a random-effects model. Results Nineteen eligible studies were identified. The criteria for increased EGFR GCN (GCN+) were highly inconsistent across different studies. The prevalence of GCN + ranged from 6.9% to 88.9%, and the difference in ORR between patients with GCN + and those with non-increased EGFR GCN (GCN-) varied from −28% to 84%. Because of the significant heterogeneity, no quantitative synthesis of data was performed. There was a general trend towards higher ORR in patients with GCN+. The difference in ORRs between patients with GCN + and those with GCN- was even greater in KRAS wild-type patients, while in KRAS mutated patients the difference often did not exist. Almost all patients with EGFR amplification responded to the treatment. However, the prevalence of EGFR amplification was generally low. Incomplete data on progression-free survival and overall survival seemingly supported the findings on ORR. Conclusions Although increased EGFR GCN is generally associated with a better outcome of anti-EGFR MAbs treatment, especially among patients with wild-type KRAS , the clinical utility of this biomarker for selecting recipients of anti-EGFR MAbs would be severely limited by the heterogeneous scoring system and the poor reproducibility of EGFR GCN enumeration due to technical reasons.
Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.
Authors: E E Ustinova, H D Schultz
Journal: Circulation Research (1994)

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are well known to be produced during prolonged ischemia and reperfusion, contribute to this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate abdominal sympathetic afferents and produce reflex excitation of the cardiovascular system. However, it is not known whether inhibitory vagal cardiac afferents are activated by oxygen-derived free radicals. We recorded activity from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were located in the walls of all four chambers of the heart. Thirty-three (63%) of these fibers were classified as chemosensitive C-fiber endings because of their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1 to 10 micrograms) to the surface of the heart encompassing the receptive field, and their conduction velocities. Fourteen (27%) of the remaining fibers were found to be mechanoreceptors. Topical application of H2O2 to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of 3 mumol (P &lt; .001). This effect was reproducible and dose dependent and was not due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU) activated 8 of the 12 chemosensitive fibers tested and had no direct effect on mechanosensitive fibers. Activity increased by 287% (P &lt; .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Aromatase Inhibitors and Safety: Clinical or Statistical Significance?
Authors: Ece Esin, Deniz Yuce, Saadettin Kilickap, Mustafa Erman
Journal: Journal of Clinical Oncology (2013)

tionandreportedthattherewerestatisticallysignificantdifferencesin the frequencies of many adverse effects between the two treatment arms. The authors also concluded that these drugs were not superior to each other, but that they had different adverse effect profiles, especially with respect to bone health. We want to emphasize the statistical difference between adverse effects profiles of each treatment. When the adverse event table is examined, it does not seem that there are any clinically significant differences between the rates of adverse events in the treatment arms, althoughmanyoftheseparametershavestatisticallysignificantdifferences (eg, AST and ALT levels of 1% in both groups, but P .001). According to the general perception of clinical and statistical inference, it is favorable for them to support each other. However, on the basis of the results of the study by Goss et al, 1 we are unable to draw conclusions concerning the clinical significance of differences in adverseeventsthatareattributedtoeachmedication.Becausethedifference in adverse events rates is not clinically very distinct, we cannot make conclusions with respect to comparisons of these drugs’ safety. Moreover,whentheboneeffectsofthetwotreatmentoptionsare considered, we would expect the baseline characteristics of the two arms to be similar. But the baseline characteristics table indicates that concurrentbisphosphonateusewasnotedinonly11%ofparticipants in each treatment arm, whereas there is an “unknown” percentage of participants in the remaining 89% who did not receive bisphosphonates. In addition, bisphosphonate use after random assignment was reported as 1% and 0% in exemestane and anastrozole arms, respectively, but osteoporosis was observed in 31% and 35% of participants of these two groups. By examining these ratios, we would suggest that
Comparison of Bayesian and Maximum Likelihood Bootstrap Measures of Phylogenetic Reliability
Authors: C. J. Douady
Journal: Molecular Biology and Evolution (2003)

Owing to the exponential growth of genome databases, phylogenetic trees are now widely used to test a variety of evolutionary hypotheses. Nevertheless, computation time burden limits the application of methods such as maximum likelihood nonparametric bootstrap to assess reliability of evolutionary trees. As an alternative, the much faster Bayesian inference of phylogeny, which expresses branch support as posterior probabilities, has been introduced. However, marked discrepancies exist between nonparametric bootstrap proportions and Bayesian posterior probabilities, leading to difficulties in the interpretation of sometimes strongly conflicting results. As an attempt to reconcile these two indices of node reliability, we apply the nonparametric bootstrap resampling procedure to the Bayesian approach. The correlation between posterior probabilities, bootstrap maximum likelihood percentages, and bootstrapped posterior probabilities was studied for eight highly diverse empirical data sets and were also investigated using experimental simulation. Our results show that the relation between posterior probabilities and bootstrapped maximum likelihood percentages is highly variable but that very strong correlations always exist when Bayesian node support is estimated on bootstrapped character matrices. Moreover, simulations corroborate empirical observations in suggesting that, being more conservative, the bootstrap approach might be less prone to strongly supporting a false phylogenetic hypothesis. Thus, apparent conflicts in topology recovered by the Bayesian approach were reduced after bootstrapping. Both posterior probabilities and bootstrap supports are of great interest to phylogeny as potential upper and lower bounds of node reliability, but they are surely not interchangeable and cannot be directly compared.
Methionine Dependency of Malignant Tumors: A Possible Approach for Therapy
Authors: F. Breillout, E. Antoine, M. F. Poupon
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Methionine Dependency of Malignant Tumors: A Possible Approach for Therapy Get access F. Breillout, F. Breillout Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Antoine, E. Antoine Search for other works by this author on: Oxford Academic PubMed Google Scholar M. F. Poupon M. F. Poupon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 20, 17 October 1990, Pages 1628–1632, https://doi.org/10.1093/jnci/82.20.1628 Published: 17 October 1990 Article history Received: 16 April 1990 Revision received: 18 July 1990 Accepted: 25 July 1990 Published: 17 October 1990
MISFITS: Evaluating the Goodness of Fit between a Phylogenetic Model and an Alignment
Authors: Minh Anh Thi Nguyen, Steffen Klaere, Arndt von Haeseler
Journal: Molecular Biology and Evolution (2010)

As models of sequence evolution become more and more complicated, many criteria for model selection have been proposed, and tools are available to select the best model for an alignment under a particular criterion. However, in many instances the selected model fails to explain the data adequately as reflected by large deviations between observed pattern frequencies and the corresponding expectation. We present MISFITS, an approach to evaluate the goodness of fit (http://www.cibiv.at/software/misfits). MISFITS introduces a minimum number of "extra substitutions" on the inferred tree to provide a biologically motivated explanation why the alignment may deviate from expectation. These extra substitutions plus the evolutionary model then fully explain the alignment. We illustrate the method on several examples and then give a survey about the goodness of fit of the selected models to the alignments in the PANDIT database.
Pathogenesis of Vascular Inflammation by Anti-Neutrophil Cytoplasmic Antibodies
Authors: J. Charles Jennette, Hong Xiao, Ronald J. Falk
Journal: Journal of the American Society of Nephrology (2006)

The reports of a newborn who developed glomerulonephritis and pulmonary hemorrhage after transplacental transfer of anti-neutrophil cytoplasmic antibody (ANCA) IgG with specificity for myeloperoxidase (MPO) is compelling clinical evidence that ANCA are pathogenic. In vitro studies indicate that ANCA activate cytokine-primed neutrophils and monocytes through both direct Fab'2 binding and Fc receptor engagement. Neutrophils that have been activated by ANCA release oxygen radicals, lytic enzymes, and inflammatory cytokines and adhere to and kill endothelial cells. A murine model caused by passive administration of mouse anti-mouse MPO IgG provides convincing evidence that ANCA IgG alone in the absence of antigen-specific T cells can cause necrotizing glomerulonephritis and vasculitis. This pathogenic process is enhanced by synergistic inflammatory factors, probably through priming of neutrophils. Immunization of rats with human MPO induces antibodies that cross-react with rat MPO and cause glomerulonephritis and vasculitis. These ANCA act in concert with chemokines to cause adherence of leukocytes to the walls of small vessels with subsequent injury. To date, animal models of disease that is induced by anti-proteinase 3 are less robust. Clinical and experimental data suggest but do not prove that the ANCA autoimmune response is initiated by an immune response to an antisense peptide of the ANCA antigen or its mimic that may be introduced into the body by an infectious pathogen. This antibody response elicits anti-idiotypic antibodies that cross-react with ANCA antigens. The pathogenesis of ANCA disease is multifactorial, with genetic and environmental factors influencing onset of the autoimmune response, the mediation of acute injury, and the induction of the chronic response to injury.
T-cell receptor γ gene rearrangement by multiplex polymerase chain reaction/heteroduplex analysis in patients with cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome) and benign inflammatory disease: correlation with clinical, histological and i
Authors: R. Ponti, P. Quaglino, M. Novelli, M.T. Fierro, A. Comessatti, A. Peroni, L. Bonello, M.G. Bernengo
Journal: British Journal of Dermatology (2005)

A dominant T-cell clone can be detected by polymerase chain reaction (PCR) in 40-90% of cutaneous samples from patients with cutaneous T-cell lymphoma (CTCL).From 1996 to 2003 we analysed 547 cutaneous biopsies performed to exclude CTCL (mycosis fungoides, MF/Sézary syndrome, SS). The final diagnosis was benign inflammatory disease (BID) in 353 samples (64.5%) and CTCL in 194 (35.5%). T-cell receptor (TCR)-gamma gene rearrangement was studied by using a multiplex PCR/heteroduplex (HD) analysis. The PCR results were correlated with the clinical picture, the histological pattern and the presence of T-cell lineage antigen loss, using univariate and multivariate logistic regression analyses.To determine the sensitivity and specificity of the multiplex PCR/HD analysis and to identify which are the clinical, histopathological or immunophenotypical features significantly associated with a positive T-cell clonality.A clonality was demonstrated in 83.5% of CTCL and in 2.3% of BID (P < 0.001). A significantly higher percentage of clonal cases was associated with the cutaneous T-score (71.4% in T1, 76.1% in T2 and 100% in nodular and erythrodermic MF samples) and with the presence of a T-cell lineage antigen loss (93.9% vs. 77.4%). Moreover, clonality was closely related to an increase in the histopathological score (51.3% in the samples with a score < 5, compared with 92% in the lesions with > or = 5). No significant difference in the percentage of clonal cases was found between T1/T2 and T3/T4 lesions with a histopathological score > or = 5. The multivariate logistic regression showed that the density and extent of the cell infiltrate, the degree of epidermotropism and the presence of cytological atypia share an independent predictive value for clonality in T1/T2 samples, even if the highest odds ratios (3.6) were associated with the density of the cell infiltrate. The disease course of T1/T2 patients was analysed according to the PCR findings. All the PCR-negative patients showed a long-standing stable disease course; on the other hand, a disease progression occurred in 12/87 (13.8%) positive patients.The multiplex PCR/HD analysis is associated with a high diagnostic accuracy (92.7%) in CTCL patients. The finding of a clonal T-cell rearrangement is more closely associated with the histological pattern (in particular with the density and extent of the cell infiltrate) rather than with the MF cutaneous T-score or immunophenotype.
Effectiveness of headgear in a pilot study of under 15 rugby union football
Authors: A S McIntosh, P McCrory
Journal: British Journal of Sports Medicine (2001)

Objective —To determine whether protective headgear reduced the incidence of concussion in a pilot study of under 15 rugby union. Methods —Sixteen under 15 rugby union teams were recruited from three interschool competitions in metropolitan Sydney and the adjacent country region. A prospective study was undertaken over a single competitive season. The study had two arms: a headgear arm and a control arm. Headgear wearing rates and injury data were reported to the investigators and verified using spot checks. Results —A total of 294 players participated in the study. There were 1179 player exposures with headgear and 357 without headgear. In the study time frame, there were nine incidences of concussion; seven of the players involved wore headgear and two did not. There was no significant difference between concussion rates between the two study arms. Conclusions —Although there is some controversy about the desirability of wearing protective headgear in football, this pilot study strongly suggests that current headgear does not provide significant protection against concussion in rugby union at a junior level.
Phase I Study of ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2 in Children With Neuroblastoma After Autologous Bone Marrow Transplantation or Stem-Cell Rescue: A Report From the Children's Oncology Group
Authors: Andrew L. Gilman, M. Fevzi Ozkaynak, Katherine K. Matthay, Mark Krailo, Alice L. Yu, Jacek Gan, Adam Sternberg, Jacquelyn A. Hank, Robert Seeger, Gregory H. Reaman, Paul M. Sondel
Journal: Journal of Clinical Oncology (2008)

Recurrence of high-risk neuroblastoma is common despite multimodality therapy. ch14.18, a chimeric human/murine anti-G(D2) antibody, lyses neuroblastoma cells. This study determined the maximum tolerable dose (MTD) and toxicity of ch14.18 given in combination with interleukin-2 (IL-2) after high-dose chemotherapy (HDC)/stem-cell rescue (SCR). Biologic correlates including ch14.18 levels, soluble IL-2 receptor levels, and human antichimeric antibody (HACA) activity were evaluated.Patients were given ch14.18 for 4 days at 28-day intervals. Patients received IL-2 during the second and fourth courses of ch14.18 and granulocyte-macrophage colony-stimulating factor (GM-CSF) during the first, third, and fifth courses. The MTD was determined based on toxicities occurring with the second course. After the determination of the MTD, additional patients were treated to confirm the MTD and to clarify appropriate supportive care.Twenty-five patients were enrolled. The MTD of ch14.18 was determined to be 25 mg/m(2)/d for 4 days given concurrently with 4.5 x 10(6) U/m(2)/d of IL-2 for 4 days. IL-2 was also given at a dose of 3 x 10(6) U/m(2)/d for 4 days starting 1 week before ch14.18. Two patients experienced dose-limiting toxicity due to ch14.18 and IL-2. Common toxicities included pain, fever, nausea, emesis, diarrhea, urticaria, mild elevation of hepatic transaminases, capillary leak syndrome, and hypotension. No death attributable to toxicity of therapy occurred. No additional toxicity was seen when cis-retinoic acid (cis-RA) was given between courses of ch14.18. No patient treated at the MTD developed HACA.ch14.18 in combination with IL-2 was tolerable in the early post-HDC/SCR period. cis-RA can be administered safely between courses of ch14.18 and cytokines.
Experience of parental cancer in childhood is a risk factor for psychological distress during genetic cancer susceptibility testing
Authors: I. van Oostrom, H. Meijers-Heijboer, H.J. Duivenvoorden, A.H.J.T. Bröcker-Vriends, C.J. van Asperen, R.H. Sijmons, C. Seynaeve, A.R. Van Gool, J.G.M. Klijn, A. Tibben
Journal: Annals of Oncology (2006)
Lost in Transcription: p21 Repression, Mechanisms, and Consequences
Authors: Andrei L. Gartel, Senthil K. Radhakrishnan
Journal: Cancer Research (2005)

Abstract The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is a major player in cell cycle control and it is mainly regulated at the transcriptional level. Whereas induction of p21 predominantly leads to cell cycle arrest, repression of p21 may have a variety of outcomes depending on the context. In this review, we concentrate on transcriptional repression of p21 by cellular and viral factors, and delve in detail into its possible biological implications and its role in cancer. It seems that the major mode of p21 transcriptional repression by negative regulators is the interference with positive transcription factors without direct binding to the p21 promoter. Specifically, the negative factors may either inhibit binding of positive regulators to the promoter or hinder their transcriptional activity. The ability of p21 to inhibit proliferation may contribute to its tumor suppressor function. Because of this, it is not surprising that a number of oncogenes repress p21 to promote cell growth and tumorigenesis. However, p21 is also an inhibitor of apoptosis and p21 repression may also have an anticancer effect. For example, c-Myc and chemical p21 inhibitors, which repress p21, sensitize tumor cells to apoptosis by anticancer drugs. Further identification of factors that repress p21 is likely to contribute to the better understanding of its role in cancer.
Crohn's disease and discitis
Authors: S Kavia, J M Gilbert
Journal: Journal of the Royal Society of Medicine (2004)

Abscess formation, from deep fissuring of the bowel wall or suppuration within lymph nodes and local fistulation, develops in as many as 20% of patients with Crohn’s disease.1 Several cases of vertebral and paravertebral infection have been described in association with enteric fistulas. Isolated discitis, however, has been little reported.
Multiphoton Imaging Can Be Used for Microscopic Examination of Intact Human Gastrointestinal Mucosa Ex Vivo
Authors: Jason N. Rogart, Jun Nagata, Caroline S. Loeser, Robert D. Roorda, Harry Aslanian, Marie E. Robert, Warren R. Zipfel, Michael H. Nathanson
Journal: Clinical Gastroenterology and Hepatology (2007)
Efficacy and Cost-Effectiveness of Psychotherapy,
Authors: JOHN A. TALBOTT
Journal: American Journal of Psychiatry (2000)

This volume is a background paper for OTA's assessment, The lmplications of Cost-Effectiveness Analysis of Medical Technology.That assessment analyzes the feasibility, implications, and usefulness of applying cost-effectiveness and cost-benefit analysis (CEA/CBA) in health care decisionmaking.The major, policy-oriented report of the assessment was published in August 1980.In addition to the main report and this background report, there will be four other background papers: 1) a document which addresses methodological issues and reviews the CEA/CBA literature, 2) a diagnostic X-ray case study, 3) 17 other case studies of individual medical technologies, and 4) a review of international experience in managing medical technology.Another related report was
Randomized Phase II Study of Dacomitinib (PF-00299804), an Irreversible Pan–Human Epidermal Growth Factor Receptor Inhibitor, Versus Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Suresh S. Ramalingam, Fiona Blackhall, Maciej Krzakowski, Carlos H. Barrios, Keunchil Park, Isabel Bover, Dae Seog Heo, Rafael Rosell, Denis C. Talbot, Richard Frank, Stephen P. Letrent, Ana Ruiz-Garcia, Ian Taylor, Jane Q. Liang, Alicyn K. Campbell, Joseph O'Connell, Michael Boyer
Journal: Journal of Clinical Oncology (2012)

This randomized, open-label trial compared dacomitinib (PF-00299804), an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, with erlotinib, a reversible EGFR inhibitor, in patients with advanced non-small-cell lung cancer (NSCLC).