tbuckley/cabot-search huggingface dataset:
Surveillance Neuroimaging to Detect Relapse in Childhood Brain Tumors: A Pediatric Oncology Group Study
Authors: A. Yuriko Minn, Brad H. Pollock, Linda Garzarella, Gary V. Dahl, Larry E. Kun, Jonathan M. Ducore, Atsuko Shibata, James Kepner, Paul G. Fisher
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the prognostic significance of surveillance neuroimaging for detection of relapse among children with malignant brain tumors. PATIENTS AND METHODS: A historical cohort study examined all children who experienced relapse from 1985 to 1999 on one of 10 Pediatric Oncology Group trials for malignant glioma, medulloblastoma, or ependymoma. RESULTS: For all 291 patients (median age at diagnosis, 8.2 years), median time to first relapse was 8.8 months (range, 0.6 to 115.6 months). Ninety-nine relapses were radiographic, and 192, clinical; median time to relapse was 15.7 versus 6.6 months, respectively (P = .0001). When stratified by pathology, radiographic and clinical groups showed differences in median time to relapse for malignant glioma (7.8 v 4.3 months, respectively; P = .041) and medulloblastoma (23.6 v 8.9 months, respectively; P = .0006) but not ependymoma (19.5 v 13.3 months, respectively; P = .19). When stratified by early (&lt; 8.8 months) or late (≥ 8.8 months) time to relapse, 115 early relapses were clinical, and 32, radiographic; for late relapses, 77 were clinical, and 67, radiographic (P = .001). Overall survival (OS) from relapse was significantly longer for radiographic compared with clinical detection (median, 10.8 months; 1-year OS, 46% v median, 5.5 months; 1-year OS, 33%; P = .002), but this trend did not retain significance when analyzed by pathology subgroups. CONCLUSION: Surveillance neuroimaging detects a proportion of asymptomatic relapses, particularly late relapses, and may provide lead time for other therapies on investigational trials. During the first year after diagnosis, radiographic detection of asymptomatic relapse was infrequent. A prospective study is needed to formulate a rational surveillance schedule based on the biologic behavior of these tumors.
Estimating parameters in the two-compartment model of exhaled nitric oxide
Authors: Sandrah Eckel, William Linn, Kiros Berhane, Muhammad Salam, Edward Rappaport, Yue Zhang, Frank Gilliland
Journal: European Respiratory Journal (2012)

INTRODUCTION: The fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation. FeNO decreases with increasing flow, which has led to the development of mathematical models whose parameters quantify proximal and distal sources. FeNO measured at the conventional 50 ml/s flow rate is primarily from proximal sources, so the parameters may provide additional insight. Parameters are estimated from FeNO data measured at multiple flow rates, but there is no standard estimation method.  AIMS AND OBJECTIVES: To evaluate and compare a comprehensive set of existing and novel regression-based estimators of parameters from the two-compartment model of exhaled nitric oxide.  METHODS: We used simulated multiple flow datasets to assess the statistical properties of the estimators and multiple flow datasets from 1507 schoolchildren from the Southern California Children9s Health Study (CHS) to investigate regression model fit and the sensitivity of estimates across models.  RESULTS: A novel non-linear least squares model with log transformation fit CHS participant datasets very well (median adjusted R2 = 0.99), satisfied model assumptions (homoskedasticity), and produced estimators with good statistical properties (e.g., negligible bias). In the CHS, alveolar NO concentration (CaNO) estimates were only moderately correlated across estimation methods whereas bronchial flux estimates were highly correlated.  CONCLUSIONS: Since CaNO estimation is a key result of multiple flow FeNO analysis, the sensitivity of CaNO estimates highlights the need for standardized methods. No gold standard is available to validate parameter estimators but our work can guide the selection of estimators in future studies.
Insulin-like growth factor-I receptor and binding proteins in rat kidney after nephron loss.
Authors: M K Hise, J S Lahn, Z M Shao, N M Mantzouris, J A Fontana
Journal: Journal of the American Society of Nephrology (1993)

Insulin-like growth factor (IGF)-binding proteins and the IGF-I receptor in rat kidney were studied to gain perspective on their potential roles in the control of renal cell mass. Thirty days after nephrectomy (UNx), membranous whole-kidney binding of IGF-I averaged 9.5 +/- 1.0 pmol/kidney, whereas binding to sham-operated controls (SNx) averaged 6.3 +/- 0.8 pmol/kidney (N = 6; P < 0.01). Scatchard analysis of IGF-I binding per milligram of protein to glomerular membranes or proximal tubule basolateral membranes (BLM) at Day 30 did not reveal significance differences in Bmax or KD between SNx and UNx; however, protein per glomerulus increased from 361 +/- 33 ng/glomerulus in SNx animals to 826 +/- 123 ng/glomerulus in UNx rats (N = 6; P < 0.002). Histomorphometrics documented an increase in proximal tubule circumference per cell and an increase in the basolateral/basement membrane ratio. IGF-I affinity labeling studies demonstrated three proteins in both glomerular membranes and proximal tubule BLM; molecular weight approximately 140,000 d, the alpha subunit of the IGF-I receptor, a protein > 200,000 d, and a protein approximately 31,000 d that was immunostained with IGF-binding protein-5 antibodies. Differences in expression between SNx and UNx were not observed at Day 30 in either glomeruli or BLM. These studies suggest that cytosolic hypertrophy of proximal nephron structures is accompanied by membrane hypertrophy with a fixed density of IGF-I receptor and IGF-binding protein-5.
Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough?
Authors: R Grilli, A D Oxman, J A Julian
Journal: Journal of Clinical Oncology (1993)

PURPOSE To estimate the impact of chemotherapy on survival of patients with advanced non-small-cell lung cancer (NSCLC). METHODS Randomized controlled trials (RCTs) published in the English-language medical literature between 1970 and 1991 were identified through MEDLINE and the reference lists of relevant articles. Six RCTs that accounted for 635 patients and compared first-line chemotherapy with supportive care in advanced NSCLC and reported survival up to at least 1 year were identified. Cumulative proportions of survival at 3, 6, 9, and 12 months for chemotherapy and control groups were derived from survival curves. RESULTS Within each study, the effect of chemotherapy was estimated with a pooled relative risk (RR) across the four 3-month periods. An overall estimate of the RR of death at 1 year (RRM-H) was then calculated and a survival curve for chemotherapy-treated patients was constructed applying the pooled estimate of the RR (RRW) for each 3-month period. Overall, chemotherapy was associated with a 24% (95% confidence interval [CI], 13% to 34%) reduction in the probability of death when compared with supportive care. However, the effect of treatment appeared to decrease significantly after the first 6 months from therapy inception and the mean potential gain in survival, as compared with supportive care, was approximately 6 weeks (95% CI, 1 to 10). CONCLUSION Chemotherapy is effective in the treatment of advanced NSCLC, but its impact on the length of survival is limited. Future RCTs should still include an untreated control group and should measure quality of life in addition to survival.
Enhanced Humoral Immune Response Correlates With Improved Disease-Free and Overall Survival in American Joint Committee on Cancer Stage II Melanoma Patients Receiving Adjuvant Polyvalent Vaccine
Authors: L. Andrew DiFronzo, Rishab K. Gupta, Richard Essner, Leland J. Foshag, Steven J. O’Day, Leslie A. Wanek, Stacey L. Stern, Donald L. Morton
Journal: Journal of Clinical Oncology (2002)

Although the improved overall survival (OS) of patients who receive Canvaxin (CancerVax Corp, Carlsbad, CA) polyvalent vaccine (PV) immunotherapy for metastatic melanoma has been correlated with cellular and humoral immune responses, the mechanisms of vaccine immunotherapy for early-stage melanoma are unclear. Specific immune responses to tumor-associated antigens might correlate with disease-free survival (DFS) and OS in patients receiving adjuvant PV therapy for primary melanoma.Eighty-three patients received PV plus bacille Calmette-Guérin after wide excision of American Joint Committee on Cancer stage II melanoma. Humoral and cellular responses during the first 12 weeks of adjuvant immunotherapy were assessed by serum antibody titers to a tumor-associated 90-kd glycoprotein antigen (TA90) expressed by PV, and by delayed-type hypersensitivity (DTH) skin testing with PV (PV-DTH).At a median follow-up period of 46.6 months (range, 10.7 to 93.6 months), an increased PV-DTH response seemed to be associated with improved 5-year DFS (54% v 20%) and 5-year OS (75% v 60%), but the correlations were not statistically significant. Anti-TA90 immunoglobulin (Ig) M levels > or = 1:800 were significantly correlated with improved 5-year DFS and improved 5-year OS, and multivariate analysis identified anti-TA90 IgM as an independent prognostic factor for OS and DFS.These findings suggest that an increased IgM response in patients receiving PV therapy for stage II melanoma is associated with decreased recurrence and improved survival.
Inhibition by Methylprednisolone of Regression of the Shope Rabbit Papilloma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Harrison McMichael
Journal: JNCI Journal of the National Cancer Institute (1967)

The effects of methylprednisolone on the Shope rabbit papilloma were investigated. Papillomas were followed on 38 domestic rabbits treated with high doses of methylprednisolone for up to 26 weeks after virus inoculation. These papillomas were compared with papillomas on 41 control rabbits. Only 1 steroid-treated rabbit showed papilloma regression (papilloma loss), whereas papillomas regressed on 18 control rabbits. The rabbits treated with methylprednisolone showed both an increased incidence of papillomas at sites not deliberately inoculated with virus and decreased immunity to reinfection by Shope papilloma virus. Steroid treatment caused a decrease in mononuclear-cell inflammatory reaction about the base of the papillomas. Neither the interval between virus inoculation and papilloma appearance nor the growth rate of the papillomas was influenced by steroid treatment. No increase in virus extractable from papillomas of the steroid-treated rabbits was noted, nor was any change noted in frequency of carcinoma development in papillomas of the steroid-treated rabbits. With steroid treatment, it was possible to establish papillomas on rabbits that had previously regressed papillomas, but these papillomas were not indefinitely maintained. The inhibition by steroid of papilloma regression adds further support to the growing evidence indicating that papilloma regression is mediated by an immune mechanism and is consistent with the view that the mechanism is similar to that responsible for homograft rejection.
Decrease in respiratory symptoms in the Danish furniture industry is associated to a decline in wood dust exposure - Results from two cross sectional studies 5 years apart
Authors: Vivi Schlünssen, Gitte Jacobsen, Inger Schaumburg, Torben Sigsgaard
Journal: European Respiratory Journal (2012)

Objective: To investigate associations between wood dust exp. and resp. symptoms in two studies 5 years apart from the same area.  Methods: 2,032 woodworkers from 54 plants in study 1 and 1,889 woodworkers from 52 plants in study 2 returned a questionnaire on resp. symptoms, employment and smoking habits. Assessment of wood dust exp. was based on job exposure matrices including factory size, task and personal dust measurements (2,217 in study 1 and 1,355 in study 2).  Results: The median (range) of inhalable dust conc. was 0.8 (0.4-1.6)mg/m 3  in study 1 and 0.6 (0.3-1.1)mg/m 3  in study 2. The prev. of selfrep. asthma was higher, but the prev. of resp. symptoms were lower in study 2 vs. study 1.  In adj. logistic regression analyses wood dust exposure explained the difference in symptom prevalence between study 1 and study 2, but no effect was found for selfrep. asthma. No influence of sex, smoking and age was seen.  Conclusion: An association between respiratory symptoms and wood dust exposure was confirmed.
Immunosuppression by Moloney Leukemia Virus: Lack of Correlation Between Virus Replication and the Immunosuppressive Effect2
Authors: J. Cerny, M. R. Proffitt, M. Essex
Journal: JNCI Journal of the National Cancer Institute (1976)

Young adult mice were infected with 10(4) plaque-forming units (PFU) or Moloney murine leukemia virus M-MuLV. Two different virus preparations were used: a) M-MuLV obtained from serial passage in mice [animal passage (AP)] and b) tissue culture (TC)-grown virus harvested after three in vitro passages of the AP M-MuLV in fibroblasts. Replication of TC and AP M-MuLV in spleen cells was determined by an infectious center (IC) assay at 1 and 2 weeks after the infection. Immune responsiveness of spleen cells was evaluated in challenge with sheep red blood cells (SRBC) and subsequent enumeration of antibody plaque-forming cells (PFC). TC M-MuLV replicated faster in the spleen than did AP M-MuLV and reached about 10- to 100-fold higher titers. However, the response of anti-SRBC PFC, suppressed to the same degree in the spleens of mice infected with TC or AP virus, was from 10 to 50% of the control response. A comparison of virus replication with the anti-SRBC response in aliquots from the same spleens showed no correlation between virus IC and antibody PFC. Both TC and AP M-MuLV induced the expression of virus-specific, cell membrane antigen on spleen cells. These findings indicated a divergence between virus replication on the one hand and the immunosuppressive effect and the cell membrane alteration on the other.
Role of chest expansion in pulmonary rehabilitation
Authors: Zsuzsanna Balogh, Laszlo Lengyel, Janos Varga
Journal: European Respiratory Journal (2013)

Rationale: Chest wall dynamic hyperinflation and rib cage distortion can be a contributor to breathlessness in patients with COPD. The procedure to increase chest mobility includes specific chest stretching and mobilization. Complex pulmonary rehabilitation, including physiotherapy, breathing- and exercise training has favourable effect.

Materials and methods: 48 patients with COPD (FEV1: 43±17 %pred, age: 62±8 years) was involved in the study. Chest wall-stretching exercises were composed of thoracic rotation and anterior compression with stretching in sitting position, trunk extension and rib torsion in supine lying. Patients were performing personalized exercise training including cycling and treadmill exercise 2-3 times for 20-30 minutes per day at 60-80% of peak work rate for 6 weeks.

Results: Rehabilitation resulted improvement in six minutes walking distance (6MWD: 312±42 vs. 407±35m, p<0,05), chest expansion (3,9±1,2 vs. 5,9±0,7cm, p<0,05) and modified Borg scale (Borg (D): 7,6±2,3 vs. 4,8±1,3, p<0,05). FEV1 did not change significantly (43±17 vs. 45±19 %pred), and there was no correlation between FEV1 and chest expansion. The change of inspiratory- (IRV) and expiratory reserve volume (ERV) values did correlate with chest expansion (IRV: R2=0,38; ERV: R2=0,30, p<0,05).

Conclusion: Chest wall expansion, dyspnea, hyperinflation and 6MWD significantly improved. Chest expansion was correlated with IRV and ERV. Measurement of chest expansion may add valuable information for the effectivity of pulmonary rehabilitation.
Urban Particulate Matter Air Pollution Is Associated With Subclinical Atherosclerosis
Authors: Marcus Bauer, Susanne Moebus, Stefan Möhlenkamp, Nico Dragano, Michael Nonnemacher, Miriam Fuchsluger, Christoph Kessler, Hermann Jakobs, Michael Memmesheimer, Raimund Erbel, Karl-Heinz Jöckel, Barbara Hoffmann
Journal: Journal of the American College of Cardiology (2010)
Effectiveness of a 3-week-in-patient-rehabilitation-program in patients with COPD GOLD-stage IV
Authors: Michael Wittmann, Dragan Stojanovic, Konrad Schultz
Journal: European Respiratory Journal (2013)

Background:  The current GOLD report stated that the minimal length of an effective rehabilitation program is 6 weeks. In Germany the usual duration of rehab-programs are 3 weeks, and they are usually conducted as inpatient programs. Therefore we wanted to evaluate the effectiveness of an intensive 3-week inpatient rehabilitation for COPD-patients and especially patients with COPD GOLD-stage IV, because for whom it is generally assumed that they require a longer period of rehab.   Method:  From 01/2010 until 12/2012 we admitted 544 consecutive patients with COPD GOLD stage IV (criteria GOLD 2010): mean inpatient stay 23.4 days, mean age 59.8 ±8.2 y, 58.5% male, 95.6% either current (28.1%) or former (67,5%) smokers, 60.1% with LTOT. We retrospectively analyzed among other factors the following routine parameters at the beginning (t0) and the end (t1) of the rehab: lung function (FEV1), walking distance (6MWD), dyspnoea (Borg scale) and quality of life (CAT).   Results  are displayed in table 1 (mean ±SD, p value in comparison with t0)   Discussion:  We found significant and clinically meaningful improvements in all analyzed outcomes after the 3-week inpatient rehab program even in this group of patients with very severe COPD. Therefore, we believe that intensive 3-week inpatient rehabilitation programs that are common in Germany represent an effective alternative to prolonged outpatient programs, especially since the drop-out rate of this program was
Phase I trial of paclitaxel in children with refractory solid tumors: a Pediatric Oncology Group Study.
Authors: C A Hurwitz, M V Relling, S D Weitman, Y Ravindranath, T J Vietti, D R Strother, A H Ragab, C B Pratt
Journal: Journal of Clinical Oncology (1993)

PURPOSE A phase I study was performed to describe the principal toxicities and identify the maximum-tolerated dose (MTD) of Taxol (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in children with therapy-resistant solid tumors. Additionally, the pharmacokinetic disposition of Taxol in children was studied, and preliminary evidence of the activity of Taxol against pediatric solid tumors was assessed. PATIENTS AND METHODS Twenty-four-hour continuous infusions of Taxol were administered every 21 days to children (median age, 12 years; range, 2 to 22) with refractory solid tumors. Doses ranged from 200 to 420 mg/m2, there was no intrapatient dose escalation. RESULTS A total of 62 courses of Taxol were administered to 31 patients. Two patients developed acute anaphylaxis during their second infusion of taxol at doses of 200 mg/m2 and 350 mg/m2, respectively. No other allergic reactions were documented. Myelosuppression occurred at all dose levels, but was of short duration (&lt; or = 7 days) and did not appear to increase with consecutive courses or at higher dosage levels. A stocking-and-glove peripheral neuropathy became evident at doses &gt; or = 290 mg/m2. Dose-limiting neurotoxicity occurred at 420 mg/m2 and comprised a significant fine-motor and peripheral neuropathy in one patient, and a tonic-clonic seizure in another. End-of-infusion plasma concentrations ranged from 0.40 to 6.4 mumol/L, and were not found to be dose-dependent over the range of doses studied. A complete response was documented in one patient, partial response in two, and minimal response in one for an overall response rate of 13%. CONCLUSION Neurotoxicity was dose-limiting when Taxol was administered by 24-hour continuous infusion to pediatric patients with relapsed solid tumors. In this population, the recommended dose for phase II trials is 350 mg/m2/d.
P06 Hepatic lumican expression in paediatric non-alcoholic fatty liver disease
Authors: E Fitzpatrick, R Mitry, A Quaglia, A Dhawan
Journal: Gut (2010)

Introduction  Lumican is a glycoprotein involved in collagen cross-linking and modulation of the innate immune system. Overexpression of lumican was recently described in a group of adult patients with histologically progressive non-alcoholic fatty liver disease (NAFLD). It has not yet been evaluated in paediatric NAFLD.  Aim  The aim of this study was to determine the degree of lumican expression in the liver of children with varying stages of NAFLD.  Method  The study group consisted of 24 children (17 boys), median age 13.1 years, with liver biopsy-proven NAFLD and six children with chronic liver disease other than NAFLD (four with autoimmune hepatitis and two with Wilson disease). Paraffin-embedded biopsy sections were scored according to the NAFLD Activity Score (NAS). Sections were immuno-stained for lumican using HRP-DAB. Quantitative analysis was performed using imageJ (NIH, USA), expressing lumican staining as percentage of the total area. In addition, relative quantification real-time PCR for lumican was undertaken on frozen biopsy specimens.  Results  Median BMI z-score of the group with NAFLD was 2.2 and median HOMA-IR; 4.4. 58% had splenomegaly. Thirteen children scored =5 (NASH), 6 scored 3–4 (borderline) and 5 scored=2 (simple steatosis). Fibrosis was minimal in 10 (F  Conclusion  Lumican is expressed with increasing severity of paediatric NAFLD. Upregulation at gene level in those with both minimal and histologically more severe disease is also evident. The role of lumican in progression of disease has not yet been elucidated and should be the focus of further investigation.
Shock the heat shock network
Authors: χiçdem Atay, Serkan Uçurlu, Nesrin ϖzören
Journal: Journal of Clinical Investigation (2009)

The targeting of tumors is made possible through establishing protein signatures specific for each cancer type. The recent recognition of the higher expression levels of HSP90 and its accumulation in tumor cell mitochondria has made the HSP90 network a feasible target for neutralization. HSP90 antagonizes the mitochondrial permeability transition,blocking cytochrome c release and apoptosis. In this issue of the JCI, Kang et al. report the synthesis of Gamitrinibs, which target mitochondrially localized HSP90, specifically killing human cancer cell lines, and provide a fresh approach for cancer treatment.
Susceptibility of Normal and Transformed Cell Lines to Cytostatic and Cytocidal Effects Exerted by Macrophages 2
Authors: R. Keller
Journal: JNCI Journal of the National Cancer Institute (1976)

Activated, nonimmune macrophages exerted profound effects on the proliferation and viability of eukaryotic target cells in vitro. Pronounced macrophage-mediated cytostasis was exerted on every rapidly proliferating cell line examined, irrespective of transformation, species derivation, cell type, or growth characteristics. However, the magnitude of cytostasis effected differed markedly among the 40 cell lines tested. There was no evident correlation between susceptibility to cytostasis and degree of transformation. Transformed cell lines with high and with low malignant attributes were affected equally. A comparable pattern was discerned for cytocidal effects of macrophages, in which the susceptibility of transformed targets was independent of the degree of malignancy.