tbuckley/cabot-search huggingface dataset:
Intergroup Rhabdomyosarcoma Study-IV: Results for Patients With Nonmetastatic Disease
Authors: William M. Crist, James R. Anderson, Jane L. Meza, Christopher Fryer, R. Beverly Raney, Frederick B. Ruymann, John Breneman, Stephen J. Qualman, Eugene Wiener, Moody Wharam, Thom Lobe, Bruce Webber, Harold M. Maurer, Sarah S. Donaldson
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P = .42). No significant difference in outcome was noted with HF-RT versus C-RT (P = .85 and P = .90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.
Abstract 8: Differential roles of OCT3/4, SOX2 and NANOG for constitutive high NOXA expression levels in embryonal carcinoma (EC) cells
Authors: Christine Bayha, Matthias Gutekunst, Walter E. Aulitzky, Heiko van der Kuip
Journal: Cancer Research (2015)

Abstract Recently we found that hypersensitivity of embryonal carcinoma (EC) to chemotherapy is mediated by high constitutive levels of NOXA protein. This pro-apoptotic BH3-only protein primes EC cells to undergo rapid and massive apoptosis in response to p53 activation. Both hypersensitivity as well as high NOXA protein levels were lost upon differentiation in these cells. We here investigated the role of three key regulators of pluripotency, namely OCT3/4, SOX2 and NANOG for NOXA protein and transcript (PMAIP1) expression in two EC cell lines, the pluripotent NTERA-2D1 and the nullipotent 2102EP. We found that siRNA-mediated silencing of POU5F1 (OCT3/4) led to a down-regulation of PMAIP1 mRNA by ∼80% and to an almost complete loss of NOXA protein (by &amp;gt;90%). On the other hand, silencing of SOX2 or NANOG only slightly reduced transcript levels (by ∼20% and ∼30%, respectively). At the same time, a distinct down-regulation of NOXA protein levels (by ∼75%) was observed in SOX2- and NANOG-deprived cells, respectively. These data indicate that the high constitutive levels of NOXA in EC cells depend on two independent mechanisms, (1) transcriptional regulation predominantly mediated by OCT3/4, and (2) post-transcriptional regulation mediated by either one of the stem cell factors. Indeed, we found that siRNA-mediated loss of one stem cell factor led to a ∼2fold reduction of NOXA protein stability in both cell lines reaching a NOXA half-life of approximately 2 hours, which was comparable to that observed in PHA stimulated lymphocytes from normal donors. These data demonstrate that the high constitutive levels of NOXA protein in EC cells are due to OCT3/4 dependent induction of the PMAIP1 transcript and a prolonged NOXA protein stability mediated by either one of the stem cell factors. Citation Format: Christine Bayha, Matthias Gutekunst, Walter E. Aulitzky, Heiko van der Kuip. Differential roles of OCT3/4, SOX2 and NANOG for constitutive high NOXA expression levels in embryonal carcinoma (EC) cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 8. doi:10.1158/1538-7445.AM2015-8
p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.
Authors: P Hirvikoski, E Kumpulainen, J Virtaniemi, R Johansson, H Haapasalo, S Marin, P Halonen, H Helin, H Raitiola, J Pukander, P Kellokumpu-Lehtinen, V M Kosma
Journal: Journal of Clinical Oncology (1997)

PURPOSE To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.
Ethnic Patterns of Hodgkin's Disease Incidence Among Children and Adolescents in the United States, 1973–82
Authors: Margaret R. Spitz, Joanne G. Sider, Christine Cole Johnson, James J. Butler, Earl S. Pollack, Guy R. Newell
Journal: JNCI Journal of the National Cancer Institute (1986)

The descriptive epidemiologic findings were summarized on 1,109 patients (white, black, and Hispanic) under 20 years of age who were diagnosed with Hodgkin's disease as reported to the Surveillance, Epidemiology, and End Results (“SEER”) Program of the National Cancer Institute from 1973 to 1982. Across all ethnic strata, incidence rates increased with advancing age at diagnosis, with white adolescents 15–19 years old exhibiting the highest rates (male, 3.67; female, 4.18). Gender difference among children 0–14 years of age was most evident in blacks (male:female ratio: 4.0 for blacks, 1.0 for whites). Highest adolescent:childhood ratios of incidence rates were noted for females (5.81 for whites and 8.29 for New Mexico Hispanics) and lowest, for Hispanic males (1.25, New Mexico; 2.15, Puerto Rico). Whites exhibited the highest percentage of the nodular sclerosis histologic subtype (65%) and Hispanics, the lowest (45%). Conversely, Hispanics had higher rates of histologic types associated with a poorer prognosis (mixed cellularity and lymphocyte depletion). These differing age and histologic patterns were consistent with previously described international patterns of disease occurrence. Analysis of secular trends for whites from 1969 to 1982 revealed relatively stable rates for youngest ages and male adolescents. Rates increased over time for white female adolescents, but the trend was not statistically significant.
Right ventricular contractility at rest and during exercise in COPD
Authors: Pia Trip, Bart Boerrigter, Taco Kind, Harm-Jan Bogaard, Nico Westerhof, Anton Vonk Noordegraaf
Journal: European Respiratory Journal (2011)

Rationale:  COPD patients show a limited stroke volume response to exercise. This is thought to be due to an increased right ventricular (RV) afterload. Whether an impairment to increase RV contractility contributes to the impaired stroke volume response is unknown.  Therefore, the aim of this study is to determine whether RV contractility changes during exercise in COPD patients.   Methods:  Nine patients with COPD (GOLD II-IV) underwent right heart catheterisation and subsequently cardiac MRI at rest and during submaximal exercise. With cardiac MRI RV volumes were measured. During right heart catheterisation RV pressure curves were continuously measured. As a measure of contractility, the maximum rate of rise of RV pressure (dP/dt max ) was obtained from an averaged RV pressure waveform over several respiratory cycles, see figure 1. Then, dP/dt max  was normalized for RV end-diastolic volume, i.e. dP/dt max /EDV (1).   Results:  In all patients dP/dt max /EDV increased with exercise. At rest mean dP/dt max /EDV was 3.6±1.3 mmHg/s/ml, while during exercise it was 6.9±3.7 mmHg/s/ml (p=0.001). RV end-systolic volume did not change with exercise.   Conclusions:  COPD patients show an increase in RV contractility. The increase in contractility does not result in a decrease in RV end-systolic volume.   Reference:   1Kass DA, Maughan WL, Guo ZM, et al.  Circulation  1987 Dec; 76(6):1422-36.
Estimated Cervical Cancer Disease State Incidence and Transition Rates<xref ref-type="fn" rid="fn2">2</xref>
Authors: A Albert
Journal: JNCI Journal of the National Cancer Institute (1981)

Cervical cancer was modeled as a disease of four states: disease-free (DF), carcinoma in situ (CIS), occult invasive (OI), and clinically invasive (CI). This model allowed transitions from DF to CIS, CIS to DF, CIS to OI, OI to CI, and DF to OI. Cases transiting from DF to OI after less than a year in the CIS state were included in the last category, which was called rapid-onset invasive disease. With the data from the British Columbia Cervical Cancer Screening Program (1955 through 1971) the disease-state transition-rate parameters for this model were estimated by least squares, and the fitted model was found to be in good agreement with the data. The estimates for parameters of particular interest were: average annual transition rate from CIS to OI, 3.7% +/- 0.6%/year; average annual transition rate from OI to CI, 48% +/- 1%/year; average annual transition rate from DF to CIS (after 1963), 1.1 +/- 0.1/1,000 person-years/year (= incidence rate of CIS); and average annual transition rate from DF to OI, 7.4 +/- 2/100,000 person-years/year (= incidence rate of rapid-onset invasive disease). Each year between 1.7 and 9.7% of all new cervical cancers and about one-third of all new OI cases were estimated to be of the rapid-onset variety.
Adjuvant Chemotherapy Decisions in Clinical Practice for Early-Stage Node-Negative, Estrogen Receptor-Positive, HER2-Negative Breast Cancer: Challenges and Considerations
Authors: Gayathri Nagaraj, Cynthia X. Ma
Journal: Journal of the National Comprehensive Cancer Network (2013)

Decisions regarding adjuvant chemotherapy for patients with estrogen receptor (ER)-positive, HER2-negative, lymph node-negative breast cancer have traditionally relied on clinical and pathologic parameters. However, the molecular heterogeneity and the complex tumor genome demand more sophisticated approaches to the problem. Several multigene-based assays have been developed to better prognosticate the risk of recurrence and death and predict benefit of therapy in this patient population. Oncologists are often faced with the challenge of incorporating these various complex genome-based biomarkers along with the traditional biomarkers in clinical decision-making. The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer are helpful in providing a general recommendation. However, uncertainty remains in the absence of definitive data for various clinical scenarios. This case report describes a postmenopausal woman with stage I breast cancer that is low-grade and ER-rich, and has an intermediate Oncotype DX recurrence score of 28.
Short-term ingestion of salbutamol increases isometric muscle power in endurance athletes
Authors: Anders Kalsen, Morten Hostrup, Jens Bangsbo, Vibeke Backer
Journal: European Respiratory Journal (2012)

Rationale: Salbutamol is on WADA's prohibited but is allowed by athletes in therapeutic doses. Positive effects of oral salbutamol have been shown in active males and females. Yet, studies are needed examining the effects in athletes. Furthermore, no studies have examined whether oral salbutamol improves isometric muscle power and endurance. We examined whether acute and short-term intake of oral salbutamol improved isometric muscle power and endurance, and submaximal exercise performance in endurance athletes.

Method: Twenty non-asthmatic endurance athletes (M), aged 25.8±4.4yrs, wattmax 440.9±29.3W, were enrolled in a randomized double-blinded parallel study, into either oral salbutamol 8 mg (SAL) or placebo (PLA). The protocol consisted of three tests. Isometric muscle power of m. quadriceps was measured by maximal voluntary contraction, followed by an isometric endurance test of m. deltoideus to exhaustion and a submaximal cycling test to exhaustion at 90% of VO2max (TTE@90%). The protocol was performed at baseline, after acute ingestion, and after 14 days of daily ingestion.

Results: Short-term intake of salbutamol significantly increased isometric muscle power, 709±115N versus 662±100N at baseline (p<0.05). Furthermore, there was a significant linear trend of increased isometric muscle power with SAL throughout the intervention (p<0.05). No differences were found in the PLA-group. Neither SAL nor PLA had any impact on isometric endurance or TTE@90%.

Conclusions: Short-term intake of salbutamol might augment training response and increase isometric muscle power in endurance athletes. Salbutamol had no effect on submaximal exercise at 90% of VO2max or on isometric endurance.
A role for WNT-5B in airway remodeling in COPD by activation of TGF-β/Smad3 signaling?
Authors: Irene Heijink, Harold de Bruin, Robin Dennebos, Maarten van den Berge, Reinoud Gosens, Antoon van Oosterhout, Dirkje Postma
Journal: European Respiratory Journal (2013)

Aberrant epithelial repair responses to cigarette smoke contribute to airway remodeling in COPD, a chronic inflammatory respiratory disease. The WNT pathway is re-activated upon inflammation, tissue injury and repair in multiple organs, including the lung, but its role in COPD is unknown. We aimed to investigate whether dysregulated expression of WNT genes may contribute to airway remodeling in COPD.  We studied expression of various WNT ligands, WNT receptors and WNT target/remodeling genes (e.g. fibronectin, periostin, MMP-2 and MMP-9) in the presence and absence of cigarette smoke extract (CSE) in primary bronchial epithelial cells (PBECs) from COPD patients and (non-)smoking controls and/or human bronchial epithelial BEAS-2B cells (qPCR, immunodetection). Additionally, we studied mRNA expression of WNT genes in lung homogenates from Balb/c mice upon 5 days of smoking.  CSE induced a significant increase in the mRNA expression of WNT-5A and WNT-5B, but not of the other detected WNT ligands (WNT-4,-7B,-10B) or FZD receptors (FZD-2,-8) in PBECs from COPD patients, but not in control PBECs. CSE also increased WNT-5B mRNA and protein expression in BEAS-2B cells, which did not express WNT-5A. Further, lungs of smoke-exposed mice displayed 2-fold higher WNT-5B mRNA expression than air-exposed mice. Recombinant human WNT-5B induced Smad3 activation and TGF-β/Smad3 signaling-dependent upregulation of fibronectin, periostin, MMP-2 and MMP-9 expression in BEAS-2B cells.  Together, our results indicate that exaggerated WNT-5B expression in cigarette smoke-exposed bronchial epithelium may lead to TGF-β/Smad3-dependent expression of multiple remodeling genes and thus contribute to airway remodeling in COPD.
Outcomes of β-blocker use in pulmonary arterial hypertension: a propensity-matched analysis
Authors: Debabrata Bandyopadhyay, Navkaranbir S. Bajaj, Joe Zein, Omar A. Minai, Raed A. Dweik
Journal: European Respiratory Journal (2015)

The utility and safety of β-blockers in pulmonary hypertension is controversial. Anecdotal reports suggest that β-blockers may be harmful in these patients. The aim of our study was to evaluate outcomes of β-blocker use in pulmonary hypertension. We reviewed patients from our pulmonary hypertension registry between 2000 and 2011. Patients who continued to use β-blockers were compared to those who never used β-blockers for all-cause mortality, time to clinical worsening events, defined as death, lung transplantation and hospitalisation due to pulmonary hypertension. We also evaluated the effect of β-blockers on 6-min walking distance and New York Heart Association (NYHA) functional class. 133 patients used β-blockers and 375 patients never used β-blockers. Mean± sd age was 57±16 years and the median follow-up period was 78 months. Propensity-matched analysis showed that the adjusted odds ratio (95% CI) for mortality with β-blocker use was 1.13 (0.69–1.82) and for clinical worsening events was 0.96 (0.55–1.68). No significant difference was noted in probability of survival and time to clinical worsening events. Patients on β-blockers walked a shorter distance on follow-up 6 min walk test; follow-up NYHA class was similar between groups. Pulmonary hypertension patients receiving β-blockers had a similar survival and time to clinical worsening events compared to patients not receiving them. Functional outcomes were similar, although β-blocker use was associated with a tendency towards shorter walking distance.
Histochemistry of Liver Tumors Induced by Diethylnitrosamine and Differential Sex Susceptibility to Carcinogenesis in &lt;italic&gt;Oryzias latipes&lt;/italic&gt;
Authors: T Nakazawa, S Hamaguchi, Y Kyono-Hamaguchi
Journal: JNCI Journal of the National Cancer Institute (1985)

Liver tumor nodules were induced by the administration of diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine] to the fish, Oryzias latipes. A histochemical study showed decreased ATPase and glucose 6-phosphatase (Glc-6-Pase) activities in most of the tumor nodules. Increased ATPase staining and, occasionally, Glc-6-Pase staining were also observed. In some nodules, the distribution of bile canaliculi was disordered, indicating positive ATPase activity. Basophilic and eosinophilic nodules could be discriminated by histologic examination. The observations on serial histochemical and histologic sections revealed extreme heterogeneity in the phenotypes of the nodules. Measurement of the enzyme-altered areas indicated that the development of nodules was more prominent in male than in female fish. Experiments with sex-reversed fish, XX males and XY females, suggested that the sex difference in the susceptibility to DENA does not result from the difference in sex chromosomes but from the difference in sexual phenotypes.
Clinical asthma prediction score (CAPS): Predicting asthma in preschool children at high risk, presenting in primary healthcare
Authors: Lonneke van der Mark, Karina van Wonderen, Jacob Mohrs, Wim van Aalderen, Gerben ter Riet, Patrick Bindels
Journal: European Respiratory Journal (2013)

Rationale: A setting-specific asthma prediction score for preschool children with wheezing and/or dyspnoea presenting in primary healthcare is needed, since existing indices are mainly based on general populations.  Objective: To find an optimally informative, yet practical set of predictors for the prediction of asthma in preschool children at high risk who present in primary healthcare.  Method: 771 Dutch preschoolers at high risk of asthma were followed prospectively until the age of 6 years. Data on asthma symptoms and environmental conditions were obtained using validated questionnaires, and specific IgE was measured. At the age of 6 years, the presence of asthma was assessed (masked for predictor values), based on asthma symptoms, medication, and bronchial hyperresponsiveness. We developed a clinical asthma prediction score (CAPS) using expert knowledge and bootstrapped multivariable regression methods.  Results: 438 children (56.8%) completed the study; asthma prevalence at 6 years was 42.7%. Five parameters optimally predicted asthma: age, family history of asthma or allergy, wheezing-induced sleep disturbances, wheezing in absence of common colds, and specific IgE. CAPS ranges from 0 to 11 points.  CAPS scores 3 signify a negative predictive value of 78.4%; scores of >6 signify a positive predictive value of 74.3%.  Conclusions: We developed an easy-to-use clinical asthma prediction score (CAPS) for preschoolers with symptoms suggesting asthma who present in primary healthcare. CAPS may guide shared decision-making to tailor the need for medical or nonmedical interventions, and may prove useful in the design and analysis of randomized trials.
Chromosome Fragility in New Zealand Black Mice: Effect of Ultraviolet and Gamma Radiations on Fetal Fibroblasts In Vitro&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A. Lakshma Reddy
 5, Philip J. Flalkow
Journal: JNCI Journal of the National Cancer Institute (1980)

The sensitivity of fibroblasts cultured from New Zealand Black (NZB) and BALB/c mouse fetuses to UV and gamma radiations was tested with two methods: 1) colony-forming ability and 2) chromosome abnormalities. When compared with BALB/c cells, NZB cells had reduced colony-forming ability and Increased chromosome abnormalities after UV irradiation. However, no differences were seen in colony formation or frequency of chromosome abnormalities between NZB and BALB/c cells after exposure to gamma radiation. This apparent UV specificity strengthens the suggestion that NZB mice might be used as a model to study the relationship between chromosome abnormalities and cancer in human syndromes such as xeroderma pigmentosum, which is characterized by chromosome instability.