tbuckley/cabot-search huggingface dataset:
Growth and Survival Mechanisms Associated with Perineural Invasion in Prostate Cancer
Authors: Gustavo E. Ayala, Hong Dai, Michael Ittmann, Rile Li, Michael Powell, Anna Frolov, Thomas M. Wheeler, Timothy C. Thompson, David Rowley
Journal: Cancer Research (2004)

Abstract Perineural invasion (PNI) is the major mechanism of prostate cancer spread outside the prostate. Apoptotic and proliferation indices were determined in PNI cells using the PNI in vitro model and human PNI in tissue microarrays. RNA was extracted from the PNI model and controls and evaluated by cDNA microarray analysis. Differential expression of candidate genes was confirmed by real-time quantitative PCR, fluorescence, and immunohistochemistry using tissue microarrays. Genistein and BAY 11-7085 were added to the supernatant of cocultures and controls in microchamber cultures. The significance of nuclear factor κB (NFκB) nuclear translocation in human PNI was analyzed using Kaplan-Meier analysis. An increase in proliferation and a decrease in apoptosis were observed in human PNI cells and the PNI model as compared with controls. Three of 15 genes up-regulated in the cDNA microarray were involved in the apoptosis signaling pathway (NFκB), and its downstream targets defender against cell death 1 and PIM-2. The increase was corroborated by real-time quantitative PCR and immunofluorescence. NFκB nuclear translocation was seen in the in vitro model and human tissues, where strong nuclear expression was associated with a decrease in recurrence-free survival. Addition of genistein and BAY 11-7085 resulted in a decrease in NFκB, PIM-2 and defender against cell death 1 as well as a reversal of the inhibition of apoptosis. This is the first description of a biological mechanism and functional significance of PNI. Cancer cells in a perineural location acquire a survival and growth advantage using a NFκB survival pathway. Targeting PNI might help detain local spread of the tumor and influence survival.
Aneurysmal bone cyst of the rib.
Authors: S Sabanathan, K Chen, C S Robertson, F D Salama
Journal: Thorax (1984)

Aneurysmal bone cysts are uncommon lesions, especially in the ribs. Four patients with aneurysmal bone cysts of the rib are presented and previously reported cases reviewed. A brief discussion of the clinical manifestations, pathology, aetiology, and current treatment of aneurysmal bone cyst is also included.
Proteolytic enzyme treatment reduces glomerular immune deposits and proteinuria in passive Heymann nephritis.
Authors: M Nakazawa, S N Emancipator, M E Lamm
Journal: The Journal of Experimental Medicine (1986)

We investigated the effect of proteolytic enzyme treatment on the course of passive Heymann nephritis (PHN). PHN was induced by intravenous injection of Heymann antibody into Sprague Dawley rats. Protease-treated rats received intraperitoneal chymopapain and subtilisin. In rats given subnephritogenic doses of Heymann antibody (5 or 10 mg, insufficient to cause proteinuria), glomerular immune deposits were assessed by immunofluorescence and electron microscopy. In rats given 5 mg Heymann antibody and treated with protease in the heterologous phase of the disease (days 1-7), fewer animals were positive for rabbit IgG and rat IgG, as determined by immunofluorescence on day 12, compared with controls (p less than 0.01). Rats given 10 mg Heymann antibody and treated on days 1-5 were less frequently positive for rabbit IgG on day 5 than controls (p less than 0.05). When treatment was given on days 6-12 (autologous phase), fewer rats had glomerular rabbit and rat IgG compared with controls (p less than 0.025). Protease treatment of rats given nephritogenic doses of Heymann antibody (greater than or equal to 40 mg, causing proteinuria) did not result in significant differences in immunofluorescence deposits. However, protease treatment significantly reduced the number of electron dense deposits at all doses of antibody (p less than 0.01). Furthermore, rats given 60 mg Heymann antibody followed by enzyme treatment in the heterologous phase (days 1-7) or throughout the autologous phase (days 6-18) had significantly reduced protein excretion during the autologous phase compared with control rats (p less than 0.05). After onset of significant proteinuria on day 15 in rats given 40 mg Heymann antibody and treated from day 15 until day 25, there was significantly less (p less than 0.05) proteinuria on days 21-22 and 24-25 than in control rats; thus, enzymes could reverse proteinuria. In normal rats, administration of proteases did not have significant effects on urinary protein excretion, serum creatinine, or renal morphology, nor did protease affect anti-rabbit IgG antibody production in rats injected with Heymann antibody. The overall results indicate that proteolytic enzyme treatment can prevent or remove glomerular immune deposits and can prevent or reverse proteinuria.
Foot pronation is not associated with increased injury risk in novice runners wearing a neutral shoe: a 1-year prospective cohort study
Authors: Rasmus Oestergaard Nielsen, Ida Buist, Erik Thorlund Parner, Ellen Aagaard Nohr, Henrik Sørensen, Martin Lind, Sten Rasmussen
Journal: British Journal of Sports Medicine (2013)

Objective To investigate if running distance to first running-related injury varies between foot postures in novice runners wearing neutral shoes. Design A 1-year epidemiological observational prospective cohort study. Setting Denmark. Participants A total of 927 novice runners equivalent to 1854 feet were included. At baseline, foot posture on each foot was evaluated using the foot-posture index and categorised into highly supinated (n=53), supinated (n=369), neutral (n=1292), pronated (n=122) or highly pronated (n=18). Participants then had to start running in a neutral running shoe and to use global positioning system watch to quantify the running distance in every training session. Main outcome measure A running-related injury was defined as any musculoskeletal complaint of the lower extremity or back caused by running, which restricted the amount of running for at least 1 week. Results During 1 year of follow-up, the 1854 feet included in the analyses ran a total of 326 803 km until injury or censoring. A total of 252 participants sustained a running-related injury. Of these, 63 were bilateral injuries. Compared with a neutral foot posture, no significant body mass index-adjusted cumulative risk differences (RD) were found after 250 km of running for highly supinated feet (RD=11.0% (−10% to 32.1%), p=0.30), supinated feet (RD=−1.4% (−8.4% to 5.5%), p=0.69), pronated feet (RD=−8.1% (−17.6% to 1.3%), p=0.09) and highly pronated feet (RD=9.8% (−19.3% to 38.8%), p=0.51). In addition, the incidence-rate difference/1000 km of running, revealed that pronators had a significantly lower number of injuries/1000 km of running of −0.37 (−0.03 to −0.70), p=0.03 than neutrals. Conclusions The results of the present study contradict the widespread belief that moderate foot pronation is associated with an increased risk of injury among novice runners taking up running in a neutral running shoe. More work is needed to ascertain if highly pronated feet face a higher risk of injury than neutral feet.
Effects of petrissage massage on fatigue and exercise performance following intensive cycle pedalling
Authors: R Ogai, M Yamane, T Matsumoto, M Kosaka
Journal: British Journal of Sports Medicine (2008)

Petrissage is assumed to influence circulation as well as interstitial drainage of both superficial and deep tissues. To study its effect it was applied between consecutive bouts of supramaximal exercise performed by the lower leg muscles.Subjects were 11 healthy female students actively engaged in sports. Exercise bouts of ergometer cycling at loads determined individually (0.075 kp x body weight (kg)) for 5 s repeated eight times at intervals of 20 s had to be performed twice on an experimental day with 35 min intermittent bed rest. Each subject was investigated on two occasions with a minimum interval of 1 week, once without (control, CO) and once with 10 min petrissage (massage, MA) of the exercising lower leg during the bed rest phase. Effects of exercise bouts on blood lactate, muscle stiffness and perceived lower limb fatigue and their recovery before and after the second exercise bout were determined.For the first exercise bouts total power did not differ between MA and CO. Courses of blood lactate did not differ between MA and CO. However, recovery from measured muscle stiffness (p<0.05) and perceived lower limb fatigue (p<0.05) were more pronounced and total power during the second exercise bout was enhanced (p<0.01) in MA as compared with CO subjects.Petrissage improved cycle ergometer pedalling performance independent of blood lactate but in correlation with improved recovery from muscle stiffness and perceived lower limb fatigue.
A critical appraisal of overdiagnosis: estimates of its magnitude and implications for lung cancer screening
Authors: J M Reich
Journal: Thorax (2008)

The magnitude of overdiagnosis is a critical and unresolved issue in lung cancer (LC) screening:(1) its contribution to the increase in survival constitutes specious evidence of benefit;(2) overdiagnosed individuals who undergo resection will experience a reduction in life expectancy, partially or completely offsetting the benefit received by others in whom earlier intervention proves curative.Critical analysis of studies in opposition and support of the view that LC screening imposes a substantial burden of overdiagnosis.Approximately 25%, possibly more, of radiographically (chest x ray) diagnosed LC appears to be overdiagnosed. Based on the observed tumour volume doubling time of low dose CT identified small malignant pulmonary nodules, CT will markedly augment lead time, increasing exposure to competing lethal morbidities, thereby increasing overdiagnosis.To reduce all-cause mortality, CT screening will need to reduce LC mortality by an amount that exceeds the increase in mortality attributable to surgery and loss of pulmonary reserve in persons who are overdiagnosed or pathologically understaged (ie, with occult micrometastases). Presently, there is no evidence that CT screening will achieve any reduction in LC mortality.
The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection
Authors: Judy J. Chang, Alexander J. V. Thompson, Kumar Visvanathan, Stephen J. Kent, Paul U. Cameron, Fiona Wightman, Paul Desmond, Stephen A. Locarnini, Sharon R. Lewin
Journal: Hepatology (2007)

Hepatitis B virus (HBV)-specific T cells play a key role in clearance of the virus and in the pathogenesis of liver disease. Peripheral blood (n = 25) and liver biopsies (n = 19) were collected from individuals with chronic untreated HBV infection. Whole blood, cultured peripheral blood mononuclear cells (PBMCs), and cultured liver-infiltrating lymphocytes (LILs) were each stimulated with an overlapping peptide library to the whole HBV genome. The expression of T helper 1 (Th1) cytokines [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 2 (IL-2)] and interleukin 10 (IL-10) was analyzed by intracellular cytokine staining and flow cytometry. In ex vivo whole blood, more lymphocytes produced Th1 cytokines than IL-10. When comparing cultured LILs with cultured PBMCs, we found a significantly higher magnitude of CD8+ T cells from the liver producing IL-10 ( P = 0.044), primarily in hepatitis B e antigen positive (HBeAg+) individuals. A positive correlation resulted between the magnitude of HBV-specific TNF-α+ CD4+ T cells in the liver and the degree of liver inflammation and fibrosis ( P = 0.002 and P = 0.006, respectively). Conclusion: The differences in cytokine production from HBV-specific T cells in blood and liver may explain the capacity for HBV to persist in the absence of significant hepatic destruction and highlights the balance between cytokine-mediated viral control and liver damage.
Acute regulation of human lymphocyte insulin receptors. Analysis by the glucose clamp.
Authors: J H Helderman
Journal: Journal of Clinical Investigation (1984)

The T lymphocyte insulin receptor model has been used to explore the regulation of insulin receptor appearance in that lymphocytes do not bear the insulin receptor in the circulation and thus are not amenable to regulation by virtue of ligand binding. Such cells synthesize insulin receptors when stimulated by antigen in vivo or in vitro. In these studies, the glucose clamp technique was employed to isolate perturbations in plasma glucose and plasma insulin as potential mediators of the regulation of the mitogen-induced T lymphocyte insulin receptor. Nondiabetic, normal weight individuals volunteered for 10 hyperglycemic clamp studies and nine euglycemic clamp studies with five individuals studied by both protocols. Hyperglycemia and hyperinsulinemia were created by the hyperglycemic clamp (basal plasma glucose was increased from 89 +/- 2 mg/dl to 230 +/- 2 mg/dl and an insulin of 99 +/- 8 microU/ml was reached). Blood was removed for isolation of T lymphocytes at 0, 1, 3, and 4 h of the clamped condition. After 1 h of hyperglycemia accompanied by an elevated plasma insulin, T cell insulin binding fell from 9.9 +/- 0.9 pg/10(6) lymphocytes to 8.5 +/- 0.9 pg/10(6), and reached a nadir of 19 +/- 4% at the conclusion of the clamp. Scatchard analysis of binding data from two of the subjects who underwent the hyperglycemic clamp demonstrated a reduction of the number of binding sites per cell without a change in the affinity of ligand for receptor. To separate the effects of glucose and insulin and the manner in which insulin is provided, the 4-h euglycemic clamp was performed in which fasting plasma glucose was maintained (95 +/- 2 mg/dl) while constant hyperinsulinemia was created (80 +/- 3 microU/ml). Insulin binding to activated, cultured T lymphocytes demonstrated a similar fall in insulin binding. Scatchard analysis of three additional studies again revealed a reduction in receptor number to approximately 40% of base line. These studies reveal that T cell insulin receptor regulation is achieved by hyperinsulinemia independent of the glucose level achieved. The reduction in insulin binding and receptor number could not be accounted for by variations in the strength of lectin stimulation, the time course of lectin response, or by the stress of the clamp itself. The effect of the clamp was specific for the lymphocyte insulin receptor in that the clamp had little effect on the interleukin II receptor activation marker. Acute changes in plasma insulin by the glucose clamp technique are perceived by the T lymphocyte and displayed in tissue culture by an alteration in lectin-induced insulin receptors. One can conclude that rapid changes in ambient in vivo insulin concentrations can regulate the synthesis of T lymphocyte insulin receptors generated in vitro.
New Strategies in Metastatic Prostate Cancer: Targeting the Androgen Receptor Signaling Pathway
Authors: Gerhardt Attard, Juliet Richards, Johann S. de Bono
Journal: Clinical Cancer Research (2011)

Recent data report that abiraterone acetate, a specific inhibitor of CYP17 that is key to androgen and estrogen synthesis, improves survival in metastatic castration-resistant prostate cancer (CRPC), confirming the continued dependency of CRPC on the androgen receptor (AR) signaling pathway. MDV3100 is a novel antagonist of AR that is also in phase III clinical trials. In addition, several other agents targeting the AR axis are undergoing evaluation in early clinical studies. CRPC patients progress on these therapies with an increasing prostate specific antigen (PSA), suggesting that repeated therapeutic interventions targeting the AR signaling axis could induce secondary responses and achieve prolonged clinical benefit for a subgroup of patients. These exciting results are good news for patients but introduce a number of treatment paradigm dilemmas for physicians. Clinical studies evaluating the ideal sequence of administration of these new agents, best timing for initiation, combination strategies, discontinuation beyond progression and after commencement of subsequent therapies, and coordination with other treatments have not been done. Predictive biomarkers could allow patient selection for a specific treatment, but in their absence, most physicians will rely on a trial of treatment with a preferred agent and substitute for an alternative therapy on objective progression. Current data suggest that the response rate to drugs targeting the AR ligand-binding domain decreases with each treatment, but we hypothesize that a significant proportion of CRPC remains dependent on the AR axis and, therefore, novel strategies for disrupting AR signaling merit evaluation.
Outcomes Among African-Americans and Caucasians in Colon Cancer Adjuvant Therapy Trials: Findings From the National Surgical Adjuvant Breast and Bowel Project
Authors: J. J. Dignam, L. Colangelo, W. Tian, J. Jones, R. Smith, D. L. Wickerham, N. Wolmark
Journal: JNCI Journal of the National Cancer Institute (1999)

African-Americans generally have lower survival rates from colon cancer than Caucasian Americans. This disparity has been attributed to many sources, including diagnosis at later disease stage and other unfavorable disease features, inadequate treatment, and socioeconomic factors. The randomized clinical trial setting ensures similarity in disease stage and a uniform treatment plan between blacks and whites. In this study, we evaluated survival and related end points for African-American and Caucasian patients with colon cancer participating in randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine whether outcomes were less favorable for African-Americans.The study included African-American (n = 663) or Caucasian (n = 5969) patients from five serially conducted, randomized clinical trials of the NSABP. We compared recurrence-free survival, disease-free survival (recurrence, new primary cancer, or death), and survival (death from any cause) between blacks and whites by using statistical modeling to account for differences in patient and disease characteristics between the groups. Statistical tests were two-sided.Dukes' stage and number of positive lymph nodes were remarkably similar between African-American and Caucasian patients in each trial. Over all trials combined, an 8% (95% confidence interval [CI] = -6% to 25%; P =.27) excess risk of colon cancer recurrence that was not statistically significant was observed for blacks. A greater disparity in survival was seen, with blacks experiencing a statistically significant 21% (95% CI = 6%-37%; P =.004) greater risk of death. Treatment efficacy appeared similar between the groups.While the overall survival prognosis was less favorable for African-Americans compared with Caucasians in these trials, other outcomes measured were considerably more similar than those seen in the population at large, suggesting that earlier detection and adjuvant therapy could appreciably improve colon cancer prognosis for African-Americans. Continued investigations into causes of the deficits noted are warranted.
Thirty Years of Multiple Sequence Codes
Authors: Edward N. Trifonov
Journal: Genomics Proteomics & Bioinformatics (2011)

An overview is presented on the status of studies on multiple codes in genetic sequences. Indirectly, the existence of multiple codes is recognized in the form of several rediscoveries of Second Genetic Code that is different each time. A due credit is given to earlier seminal work related to the codes often neglected in literature. The latest developments in the field of chromatin code are discussed, as well as perspectives of single-base resolution studies of nucleosome positioning, including rotational setting of DNA on the surface of the histone octamers.
CD8 + ve Cells in the Lungs of Smokers with Chronic Obstructive Pulmonary Disease
Authors: MARINA SAETTA, SIMONETTA BARALDO, LAURA CORBINO, GRAZIELLA TURATO, FAUSTO BRACCIONI, FEDERICO REA, GIORGIO CAVALLESCO, GIUSEPPE TROPEANO, CRISTINA E. MAPP, PIERO MAESTRELLI, ADALBERTO CIACCIA, LEONARDO M. FABBRI
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Previous studies have shown an increased number of inflammatory cells and, in particular, CD8 + ve cells in the airways of smokers with chronic obstructive pulmonary disease (COPD). In this study we investigated whether a similar inflammatory process is also present in the lungs, and particularly in lung parenchyma and pulmonary arteries. We examined surgical specimens from three groups of subjects undergoing lung resection for localized pulmonary lesions: nonsmokers (n = 8), asymptomatic smokers with normal lung function (n = 6), and smokers with COPD (n = 10). Alveolar walls and pulmonary arteries were examined with immunohistochemical methods to identify neutrophils, eosinophils, mast cells, macrophages, and CD4 + ve and CD8 + ve cells. Smokers with COPD had an increased number of CD8 + ve cells in both lung parenchyma (p < 0.05) and pulmonary arteries (p < 0.001) as compared with nonsmokers. CD8 + ve cells were also increased in pulmonary arteries of smokers with COPD as compared with smokers with normal lung function (p < 0.01). Other inflammatory cells were no different among the three groups. The number of CD8 + ve cells in both lung parenchyma and pulmonary arteries was significantly correlated with the degree of airflow limitation in smokers. These results show that an inflammatory process similar to that present in the conducting airways is also present in lung parenchyma and pulmonary arteries of smokers with COPD.
Serum Proteomic Profiles Suggest Celecoxib-Modulated Targets and Response Predictors
Authors: Zhen Xiao, Brian T. Luke, Grant Izmirlian, Asad Umar, Patrick M. Lynch, Robin K. S. Phillips, Sherri Patterson, Thomas P. Conrads, Timothy D. Veenstra, Peter Greenwald, Ernest T. Hawk, Iqbal U. Ali
Journal: Cancer Research (2004)

Abstract Cyclooxygenase-2 is a valid target for cancer prevention and treatment. This has been shown in preclinical and clinical cancer prevention studies by using a cyclooxygenase-2 inhibitor, celecoxib. When used in a randomized cancer prevention clinical trial on patients with the inherited autosomal dominant condition, familial adenomatous polyposis, celecoxib proved efficacious. However, a remarkable heterogeneity in patients’ responses to the chemopreventive effects of celecoxib was observed. Proteomic profiling of sera from these patients identified several markers, the expression of which was specifically modulated after treatment with celecoxib. A decision tree algorithm identified classifiers for response to celecoxib with relatively high sensitivity but moderate to low specificity. In particular, a spectral feature at m/z 16,961.4 was identified as a strong discriminator between response and nonresponse to celecoxib at the highest dose.