tbuckley/cabot-search huggingface dataset:
Impact of<i>IGF-I</i>and<i>CYP19</i>Gene Polymorphisms on the Survival of Patients With Metastatic Prostate Cancer
Authors: Norihiko Tsuchiya, Lizhong Wang, Hiroyoshi Suzuki, Takehiko Segawa, Hisami Fukuda, Shintaro Narita, Masaki Shimbo, Toshiyuki Kamoto, Kenji Mitsumori, Tomohiko Ichikawa, Osamu Ogawa, Akira Nakamura, Tomonori Habuchi
Journal: Journal of Clinical Oncology (2006)

Purpose The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer. Patients and Methods One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software. Results Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001). Conclusion The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.
Cost-Effectiveness of Screening for Microalbuminuria among African Americans
Authors: Thomas J. Hoerger, John S. Wittenborn, Xiaohui Zhuo, Meda E. Pavkov, Nilka R. Burrows, Paul Eggers, Regina Jordan, Sharon Saydah, Desmond E. Williams
Journal: Journal of the American Society of Nephrology (2012)

Compared with other racial groups, African Americans have a similar prevalence of CKD but are much more likely to progress to ESRD, suggesting that the cost-effectiveness of screening strategies requires dedicated study in this population. Here, we calibrated the CKD Health Policy Model so that it accurately forecasts the higher rates for ESRD observed for African Americans. We then used the calibrated model to estimate the cost-effectiveness of screening for microalbuminuria followed by treatment with angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers. Incorporating racial differences in risk factors did not fully explain the much higher lifetime incidence of ESRD among African Americans. Thus, to calibrate the model, we applied a 20% increase in the rate of GFR decline at stage 3 and a 60% increase in the rate of GFR decline at stage 4, which resulted in a model that closely reflects lifetime ESRD incidence among African Americans. Compared with usual care, screening African Americans for microalbuminuria at 10-, 5-, 2-, and 1-year intervals had incremental cost-effectiveness ratios of $9000, $11,000, $19,000, and $35,000 per quality-adjusted life year, respectively. Incremental cost-effectiveness ratios for the same screening intervals were higher for non-African Americans: $17,000, $23,000, $44,000, and $81,000 per quality-adjusted life year, respectively. In summary, these models suggest that screening African Americans for microalbuminuria at either 5- or 10-year intervals is highly cost-effective.
Bronchioloalveolar Adenocarcinoma and Pulmonary Langerhans Cell Histiocytosis in a Patient With <i>MUTYH</i>-Associated Polyposis
Authors: Jan H. von der Thüsen, Marianne D. van de Wetering, Anneke M. Westermann, Daniëlle A.M. Heideman, Erik Thunnissen
Journal: Journal of Clinical Oncology (2010)
Child psychiatric disorder and relative age within school year: cross sectional survey of large population sample
Authors: R. Goodman
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To test the hypothesis that younger children in a school year are at greater risk of emotional and behavioural problems. <b>Design</b>Cross sectional survey. <b>Setting</b> Community sample from England, Scotland, and Wales. <b>Participants</b> 10 438 British 5-15 year olds. <b>Main outcome measures</b> Total symptom scores on psychopathology questionnaires completed by parents, teachers, and 11-15 year olds; psychiatric diagnoses based on a clinical review of detailed interview data. <b>Results</b> Younger children in a school year were significantly more likely to have higher symptom scores and psychiatric disorder. The adjusted regression coefficients for relative age were 0.51 (95% confidence interval 0.36 to 0.65, P &lt; 0.0001) according to teacher report and0.35 (0.23 to 0.47, P = 0.0001) for parental report. The adjusted odds ratio for psychiatric diagnoses for decreasing relative age was 1.14 (1.03 to 1.25, P = 0.009). The effect was evident acrossdifferent measures, raters, and age bands. Cross national comparisons supported a "relative age" explanation based on the disadvantages of immaturity rather than a "season of birth" explanation based on seasonal variation in biological risk. <b>Conclusions</b> The younger children in a school year are at slightly greater psychiatric risk than older children. Increased awareness by teachers of the relative age of their pupils and a more flexible approach to children9s progression through school might reduce the number of children with impairing psychiatric disorders in the general population.
Regulatory module network of basic/helix-loop-helix transcription factors in mouse brain
Authors: Jing Li, Zijing J Liu, Yuchun C Pan, Qi Liu, Xing Fu, Nigel GF Cooper, Yixue Li, Mengsheng Qiu, Tieliu Shi
Journal: Genome biology (2007)

Abstract Background The basic/helix-loop-helix (bHLH) proteins are important components of the transcriptional regulatory network, controlling a variety of biological processes, especially the development of the central nervous system. Until now, reports describing the regulatory network of the bHLH transcription factor (TF) family have been scarce. In order to understand the regulatory mechanisms of bHLH TFs in mouse brain, we inferred their regulatory network from genome-wide gene expression profiles with the module networks method. Results A regulatory network comprising 15 important bHLH TFs and 153 target genes was constructed. The network was divided into 28 modules based on expression profiles. A regulatory-motif search shows the complexity and diversity of the network. In addition, 26 cooperative bHLH TF pairs were also detected in the network. This cooperation suggests possible physical interactions or genetic regulation between TFs. Interestingly, some TFs in the network regulate more than one module. A novel cross-repression between Neurod6 and Hey2 was identified, which may control various functions in different brain regions. The presence of TF binding sites (TFBSs) in the promoter regions of their target genes validates more than 70% of TF-target gene pairs of the network. Literature mining provides additional support for five modules. More importantly, the regulatory relationships among selected key components are all validated in mutant mice. Conclusion Our network is reliable and very informative for understanding the role of bHLH TFs in mouse brain development and function. It provides a framework for future experimental analyses.
Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial
Authors: A. Bahl, S. Oudard, B. Tombal, M. Özgüroĝlu, S. Hansen, I. Kocak, G. Gravis, J. Devin, L. Shen, J.S. de Bono, A.O. Sartor;
Journal: Annals of Oncology (2013)

BackgroundCabazitaxel significantly improves overall survival (OS) versus mitoxantrone in patients with metastatic castration-resistant prostate cancer after docetaxel failure. We examined patient survival at 2 years and tumour-related pain with cabazitaxel versus mitoxantrone.MethodsUpdated TROPIC data (cut-off 10 March 2010) were used to compare 2-year survival between treatment groups and assess patient demographics and disease characteristics. Factors prognostic for survival ≥2 years were assessed. Pain and Eastern Cooperative Oncology Group performance status were evaluated in the overall patient population.ResultsMedian follow-up was 25.5 months. After 2 years, more patients remained alive following cabazitaxel than mitoxantrone [odds ratio 2.11; 95% confidence interval (CI) 1.33–3.33]. Treatment with cabazitaxel was prognostic for survival ≥2 years. Demographics/baseline characteristics were balanced between treatment arms irrespective of survival. Pain at baseline and pain response were comparable between treatment groups. Average daily pain performance index was lower for cabazitaxel versus mitoxantrone (all cycles; 95% CI –0.27 to –0.01; P = 0.035) and analgesic scores were similar. Grade ≥3 peripheral neuropathies were uncommon and comparable between treatment groups.ConclusionsCabazitaxel prolongs OS at 2 years versus mitoxantrone and has low rates of peripheral neuropathy. Palliation benefits of cabazitaxel were comparable to those of mitoxantrone.The study was registered with www.ClinicalTrials.gov (NCT00417079).
890 HETEROGENEITY IN PRIMARY HUMAN HEPATOCELLULAR CARCINOMA IS DUE TO DIFFERENT SUBSETS OF CANCER STEM-LIKE CELLS WITHIN THE TUMOUR
Authors: F. Baldan, S. Mazzucchelli, F. Colombo, I. Martin-Padura, A. Cattaneo, G. Rossi, V. Mazzaferro, B. Foglieni, F. Bertolini, D. Prati, L. Porretti
Journal: Journal of Hepatology (2010)
Changes in myosin isoenzymes, ATPase activity, and contraction duration in rat cardiac muscle with aging can be modulated by thyroxine.
Authors: M B Effron, G M Bhatnagar, H A Spurgeon, G Ruaño-Arroyo, E G Lakatta
Journal: Circulation Research (1987)

To determine whether the relative decline in cardiac myosin isoenzyme V1 with maturation continues progressively into senescence and whether thyroxine could reverse age-associated changes in the myosin isoenzyme profile and contraction, rats 2, 8, and 24 months old were treated with thyroxine, 6.4 mg/kg, for 7 days. Myosin isoenzymes, Ca2+-myosin ATPase activities, and isometric contractile function were measured in cardiac preparations from thyroxine-treated animals and age-matched controls. Right ventricular hypertrophy did not occur with aging in controls. Thyroxine increased right ventricular weight in each age group compared to the control group. Body weight decreased by 10% in all thyroxine-treated rats. The relative right ventricular V1 isoenzyme content progressively decreased from 75 +/- 1% to 54 +/- 1% and 14 +/- 1% in controls at 2, 8, and 24 months, respectively, and was associated with a reciprocal increase in V3 myosin isoenzyme. Ca2+-myosin ATPase activity also progressively declined monotonically with age in the control rats from 854 +/- 28 nmol Pi/mg prot/min at 2 months to 529 +/- 28 nmol Pi/mg prot/min at 24 months. Thyroxine administration increased right ventricular V1 at each age to 97 +/- 2%, 73 +/- 2%, and 59 +/- 2% at 2, 8, and 24 months, respectively. A thyroxine induced increase in the Ca2+-myosin ATPase activity could be detected only in the 24-month-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Low-Intensity Warfarin Is Ineffective for the Prevention of PTFE Graft Failure in Patients on Hemodialysis
Authors: Mark A. Crowther, Catherine M. Clase, Peter J. Margetts, Jim Julian, Kim Lambert, Denise Sneath, Ryuta Nagai, Sarah Wilson, Alistair J. Ingram
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal disease (ESRD) are prone to thrombotic failure. The objective of this multicenter, randomized, double-blind, placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts. Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario. Patients were allocated to receive warfarin or matching placebo, with the warfarin administered to achieve a target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A total of 107 patients (56 allocated to warfarin) were randomized. The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups (odds ratio, 1.76 in favor of placebo; 95% confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo (P = 0.03). In conclusion, low-dose warfarin was associated with an excess of clinically important major bleeding in patients with ESRD enrolled in this study. Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong PTFE graft survival.
Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells
Authors: Pinar Uysal-Onganer, Yoshiaki Kawano, Mercedes Caro, Marjorie M Walker, Soraya Diez, R Siobhan Darrington, Jonathan Waxman, Robert M Kypta
Journal: Molecular Cancer (2010)

Wnt-11 is a secreted protein that modulates cell growth, differentiation and morphogenesis during development. We previously reported that Wnt-11 expression is elevated in hormone-independent prostate cancer and that the progression of prostate cancer from androgen-dependent to androgen-independent proliferation correlates with a loss of mutual inhibition between Wnt-11- and androgen receptor-dependent signals. However, the prevalence of increased expression of Wnt-11 in patient tumours and the functions of Wnt-11 in prostate cancer cells were not known. Wnt-11 protein levels in prostate tumours were determined by immunohistochemical analysis of prostate tumour tissue arrays. Wnt-11 protein was elevated in 77/117 of tumours when compared with 27 benign prostatic hypertrophy specimens and was present in 4/4 bone metastases. In addition, there was a positive correlation between Wnt-11 expression and PSA levels above 10 ng/ml. Androgen-depleted LNCaP prostate cancer cells form neurites and express genes associated with neuroendocrine-like differentiation (NED), a feature of prostate tumours that have a poor prognosis. Since androgen-depletion increases expression of Wnt-11, we examined the role of Wnt-11 in NED. Ectopic expression of Wnt-11 induced expression of NSE and ASCL1, which are markers of NED, and this was prevented by inhibitors of cyclic AMP-dependent protein kinase, consistent with the known role of this kinase in NED. In contrast, Wnt-11 did not induce NSE expression in RWPE-1 cells, which are derived from benign prostate, suggesting that the role of Wnt-11 in NED is specific to prostate cancer. In addition, silencing of Wnt-11 expression in androgen-depleted LNCaP cells prevented NED and resulted in apoptosis. Silencing of Wnt-11 gene expression in androgen-independent PC3 cells also reduced expression of NSE and increased apoptosis. Finally, silencing of Wnt-11 reduced PC3 cell migration and ectopic expression of Wnt-11 promoted LNCaP cell invasion. These observations suggest that the increased level of Wnt-11 found in prostate cancer contributes to tumour progression by promoting NED, tumour cell survival and cell migration/invasion, and may provide an opportunity for novel therapy in prostate cancer.
Patient-reported health outcomes in a trial of etanercept monotherapy versus combination therapy with etanercept and methotrexate for rheumatoid arthritis: the ADORE trial
Authors: P L C M van Riel, B Freundlich, D MacPeek, R Pedersen, J R Foehl, A Singh
Journal: Annals of the Rheumatic Diseases (2007)

This study assessed the relative efficacy of etanercept (ETN) or etanercept and methotrexate (ETN+MTX) for patients with rheumatoid arthritis (RA) who had an unsatisfactory response to MTX, using patient-reported outcomes (PROs) of function, pain, general health, disease activity and morning stiffness.The PROs were secondary assessments in a 16-week, prospective, randomised, parallel-group study conducted at 60 European centres. Patients with RA were randomly assigned either to monotherapy with ETN or combination therapy with ETN+MTX. PRO instruments administered included the Stanford Health Assessment Questionnaire, the pain visual analogue scale, the EuroQoL assessment of current health state (EQ-5D), the EQ-5D visual analogue scale, a patient global assessment of disease activity and an assessment of morning stiffness. Treatment groups were compared by percentage of patients within clinically meaningful categories. The primary endpoint for all PROs was comparison of mean improvement from baseline to week 16 between ETN and ETN+MTX groups.Three hundred and fifteen patients were randomised to ETN or ETN+MTX. Both treatment arms had similar Health Assessment Questionnaire Disability Index DI, EQ-5D, patient global assessment of disease activity, pain or morning stiffness scores and improvement from baseline to week 16.For patients with active RA and intolerance or unsatisfactory response to MTX, substituting ETN for MTX and adding ETN to MTX are both effective ways of reducing disability, pain, disease activity, morning stiffness, and improving general health.
Particulate matter and lung function growth in children: a 3-yr follow-up study in Austrian schoolchildren
Authors: F. Horak, M. Studnicka, C. Gartner, J.D. Spengler, E. Tauber, R. Urbanek, A. Veiter, T. Frischer
Journal: European Respiratory Journal (2002)

The effects of particulate matter &lt;10 µm in diameter (PM<sub>10</sub>) and other air pollutants on lung function were assessed in 975 schoolchildren, from eight communities in Lower Austria between 1994–1997. In each community, air pollution data were collected. Spirometry was performed twice a year. PM<sub>10</sub> concentration (mean concentration between two subsequent lung-function measures in spring and autumn (summer interval) or between autumn and spring (winter interval)) showed a mean value of 17.36 µg·m<sup>−3</sup> in the summer interval and 21.03 µg·m<sup>−3</sup> in the winter interval. A slower increase in the forced expiratory volume in one second (FEV<sub>1</sub>) and midexpiratory flow between 25 and 75% of the forced vital capacity (MEF<sub>25–75</sub>) with age in children exposed to higher summer PM<sub>10</sub> was observed in the 3-yr study period. After adjusting for potential confounders (sex, atopy, passive smoking, initial height, height difference, site, initial lung function) an increase of summer PM<sub>10</sub> by 10 µg·m<sup>−3</sup> was associated with a decrease in FEV<sub>1</sub> growth of 84 mL·yr<sup>−1</sup> and 329 mL·s<sup>−1</sup>·yr<sup>−1</sup> for MEF<sub>25–75</sub>. Nitrogen dioxide and ozone also showed a negative effect on lung-function growth, confirming previous work. The authors concluded that long-term exposure to particulate matter &lt;10 µm in diameter had a significant negative effect on lung-function proxy for the development of large (forced expiratory volume in one second) and small (midexpiratory flow between 25 and 75% of the forced vital capacity) airways, respectively, with strong evidence for a further effect of ozone and nitrogen dioxide on the development of forced vital capacity and forced expiratory volume in one second.
CHANGES IN THE NUMBER OF SMALL LYMPHOCYTES OF THE BLOOD FOLLOWING LIGATION OF THE THORACIC DUCT
Authors: Ferdinand C. Lee
Journal: The Journal of Experimental Medicine (1922)

This report has attempted to analyze the changes in the absolute number of small lymphocytes in the blood stream of the cat following the intrathoracic ligation of the thoracic duct. Such a ligation produced an immediate decrease in the number of small lymphocytes to the extent of 56 per cent, but it was found that the preoperative level was again reached at about the end of 3 weeks. One is led to believe that the gradual return of the number of small lymphocytes to the preligation level took place pari passu with the establishment of the collateral circulation of the thoracic duct, although there is no absolute proof of this. Yet it is definite that the thoracic duct is an important avenue for the entrance of small lymphocytes into the blood stream, and that it is the pathway through which at least half of the small lymphocytes reach the circulating blood in the cat.
A Comparison Of The Effects Of TNF, IL-12/IL-23p40, And TGFβ1 Peptide-based Vaccines In The Amelioration Of TNBS-induced Chronic Colitis
Authors: q. guan, Y. Ma, C. Hillman, A.G. Ma, G. Zhou, G. Qin, C.R. Weiss, Z. Peng
Journal: Journal of Allergy and Clinical Immunology (2010)
Abstract IA20: Targeted lung cancer chemoprevention through reverse migration
Authors: Waun Ki Hong
Journal: Clinical Cancer Research (2012)

Abstract The hypothesis that lung cancer can be prevented with agents selected on the basis of epidemiologic data has, unfortunately, been disproven in many large randomized trials conducted in the last 25 years. The results of these trials have overwhelmingly demonstrated not only the lack of benefit of most chemopreventive agents selected in this manner but also, importantly, the harmful effects of some of these agents in subsets of patients including current smokers. Despite limited progress in the multimodality treatment of lung cancer, the cure rate for this disease is very disappointing; however, more recent discoveries of molecular “driver mutation” targets in lung cancer and treatment approaches with “matched” targeted agents in selected patient cohorts has been highly promising. This latter approach demonstrates that progression of even heterogeneous cancers can be intercepted by “molecularly relevant” targeted agents for the treatment of advanced disease. A proposed new strategy for lung cancer prevention, therefore, is to apply a “reverse migration” of agents from the advanced disease to the chemopreventive setting; that is, to first identify the molecular drivers in the premalignant target tissue, and then to match these “hallmark” changes with molecularly targeted agents seen to be effective in advanced disease. This approach can be applied in the adjuvant as well as prevention settings, as has been demonstrated by the use of tamoxifen in breast cancer. Thus, the major points I am going to present include the current landscape of chemoprevention in lung cancer and a new strategy of “reverse migration” for future chemoprevention trials in the 21st century.