Hormonal therapy as an adjuvant to radical radiotherapy for locally advanced prostate cancer.
Explore the source record for details and available documents.
Antineoplastic Agents, Hormonal↗
Biomedical subjects
C Parker
Publications and source records attributed to C Parker.
Active surveillance: an individualized approach to early prostate cancer.
Explore the source record for details and available documents.
Humans↗
The COPE index--a first stage assessment of negative impact, positive value and quality of support of caregiving in informal carers of older people.
Data was collected in five countries from informal carers of older people (n = 577) via a common protocol. Carers completed: (1) a 17-item version of the Carers of Older People in Europe (COPE) Index, an assessment of carers' perceptions of their role : (2) a questionnaire on demographic and caregiving circumstances : and (3) three instruments included for the criterion validation of the COPE Index (the General Health Questionnaire, the Hospital Anxiety and Depression Scale, and the World Health Organization Quality of Life-BREF). Principal Component Analysis of the COPE Index was followed by internal consistency analysis of emergent components. Scales derived by summing items loading on the components were analyzed for their association with the criterion measures. Two components, negative impact and positive value, emerged consistently across countries. A third component, quality of support was less consistent across countries. Scales derived from the negative impact and positive value components were internally consistent and significantly associated with the criterion validity measures. These two scales and four items drawn from the quality of support component were retained in the final COPE Index. While further testing is required, the COPE Index has current utility in increasing understanding of the role perceptions of carers of older people.
Affect↗
Lung cancer * 8: Management of malignant mesothelioma.
Explore the source record for details and available documents.
Analgesics↗
Vaccination of ewes for prevention of vertical transmission of Neospora caninum.
OBJECTIVE: To evaluate the immunologic response of a killed tachyzoite vaccine against Neospora caninum and its effectiveness in preventing vertical transmission of N caninum in sheep. ANIMALS: 40 Dorset ewes seronegative for N caninum. PROCEDURE: Group-A ewes (n = 20) were vaccinated on days 1 and 126 with a killed N caninum tachyzoite preparation in a commercially available adjuvant. Group-B ewes (n = 20) were sham vaccinated. Blood samples were collected from ewes every 2 weeks and a recombinant ELISA (rELISA) was used to determine serum antibody titers against N caninum. During pregnancy, ewes were challenged with live N caninum tachyzoites. Precolostral serum was collected from lambs and tested for antibodies against N caninum by use of an indirect fluorescence antibody test and the rELISA. Tissue specimens from stillborn lambs or lambs that died within 2 weeks of birth were collected and examined for N caninum antigen and DNA by use of immunohistochemistry and polymerase chain reaction assay, respectively. RESULTS: Serum antibody titers against N caninum were significantly higher in group-A ewes, compared with group B ewes, following vaccination. Serum antibodies against N caninum were detected in 100% (33/33) of group-B lambs and 75% (18/24) of group-A lambs. In tissue specimens, N caninum DNA was detected in 9 of 11 group-B lambs and 0 of 10 group-A lambs. Histologically, N caninum tachyzoites were observed in 4 group-A lambs and 3 group-B lambs. CONCLUSIONS AND CLINICAL RELEVANCE: The killed tachyzoite vaccine against N caninum stimulated a humoral immune response in sheep and provided partial protection against vertical transmission.
Animals↗
The prognostic significance of the tumour infiltrating lymphocyte count in stage I testicular seminoma managed by surveillance.
The degree of lymphocytic infiltration is a significant determinant of outcome for a variety of malignancies, but its role in seminoma is unknown. 150 men with stage I testicular seminoma presenting between 1981 and 1993 were managed by surveillance following orchidectomy. The presence of tumour infiltrating lymphocytes (TILs) in each case was classified as high, intermediate or low. At a median follow-up of 9.4 years, 30 of the 150 men developed recurrent seminoma. On univariate analysis, the risk of relapse was associated with age < or =33 years (P=0.002), tumour diameter >6 cm (P=0.03), lymphatic or vascular invasion (P=0.04), tumour invasion of rete testis (P=0.05), and lower TIL count (P=0.02). On multivariate analysis, statistically significant predictors of risk of relapse were age < or =33 years (hazard ratio (HR) 4.6 (95% confidence intervals (CI): 1.7-12.2)) and tumour diameter >6 cm (HR 2.8 (CI: 1.2-6.5)). Lower TIL count was of borderline statistical significance (HR 1.8 (CI: 0.96-3.44)). The functional role of the lymphocytic infiltrate in testicular seminoma warrants further study.
Adult↗
Surveillance in stage I testicular seminoma - risk of late relapse.
INTRODUCTION: Surveillance is an alternative to adjuvant radiotherapy for stage I testicular seminoma. We present the long-term results of seminoma surveillance, with emphasis on quantifying the risk of late relapse beyond 5 years. METHODS: From 1981 to 1993, of 431 men with stage I testicular seminoma, 203 were managed by surveillance following radical orchidectomy. The surveillance protocol comprised a combination of clinical examination, CT scans of abdomen and pelvis, chest x-rays and serum markers, at defined intervals. RESULTS: At a median follow-up of 9.2 years, 35 men have relapsed. Five of the relapses occurred more than 5 years after orchidectomy (at 5.1, 6.9, 7.3, 7.3, and 9.0 years). The actuarial risk of relapse at 5 and 10 years was 15% (standard error [SE] 1.1%) and 18% (SE 1.8%) respectively. One hundred sixty one men were free of relapse at 5 years, and have been followed beyond this point for a median of 4.3 years. The actuarial risk of relapse between 5 and 10 years was 4% (SE 0.5%). CONCLUSIONS: These results demonstrate that there is a small but clinically significant risk of relapse more than 5 years after orchidectomy for stage I seminoma. These data support the need for long term surveillance.
Adult↗
E-cadherin as a prognostic indicator in primary breast cancer.
Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal antibody HECD-1 (Zymed Laboratories Inc.). In normal epithelial cells E-CD was strongly expressed at cell-cell boundaries. 66% of the breast cancers examined had reduced intensity of E-CD expression with 74% having significant reductions in the proportion of E-CD-positive tumour cells. Using a combined intensity/proportion score, significant associations were found between E-CD expression and tumour type (P </= 0.001). ER status (P = 0.026) and histological grade (P = 0.031). Expression of E-CD was not found to be related to recurrence, distant metastases, lymph node stage, vascular invasion, primary tumour size, prognostic group or survival. Thus E-CD expression in human breast cancer appears to have minimal prognostic value, but may have a role as a phenotypic marker.
Adult↗
Immunolocalization of UDP-glucose:glycoprotein glucosyltransferase indicates involvement of pre-Golgi intermediates in protein quality control.
The UDP-glucose:glycoprotein glucosyltransferase (GT) is a protein folding sensor and glycosyltransferase that constitutes an important component of the protein quality control machinery. With the use of quantitative immunogold electron microscopy, we established the subcellular distribution of GT in rat liver and pancreas and Drosophila melanogaster salivary gland as well as cell lines and correlated it with that of glucosidase II, calreticulin, and pre-Golgi intermediate markers. Labeling for GT, as well as for glucosidase II and calreticulin, was found in the endoplasmic reticulum (ER), including nuclear envelope and pre-Golgi intermediates located between ER and Golgi apparatus, and in the cell periphery. In the rough ER, labeling for GT was inhomogeneous, with variously sized labeled and unlabeled cisternal regions alternating, indicative of a meshwork of quality control checkpoints. Notably, labeling intensity for GT was highest in pre-Golgi intermediates, corresponding to twice that of rough ER, whereas the Golgi apparatus exhibited no specific labeling. These results suggest that protein quality control is not restricted to the ER and that the pre-Golgi intermediates, by virtue of the presence of GT, glucosidase II, and calreticulin, are involved in this fundamental cellular process.
Animals↗
Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release.
BACKGROUND: Moderate red wine consumption is inversely associated with coronary ischemia, and both red wine and purple grape juice (PGJ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events. Acute cardiac events are also associated with decreased platelet-derived nitric oxide (NO) release. In this study, the effects of PGJ and PGJ-derived flavonoids on platelet function and platelet NO production were determined. METHODS AND RESULTS: Incubation of platelets with dilute PGJ led to inhibition of aggregation, enhanced release of platelet-derived NO, and decreased superoxide production. To confirm the in vivo relevance of these findings, 20 healthy subjects consumed 7 mL. kg(-1). d(-1) of PGJ for 14 days. Platelet aggregation was inhibited after PGJ supplementation, platelet-derived NO production increased from 3.5+/-1.2 to 6.0+/-1.5 pmol/10(8) platelets, and superoxide release decreased from 29.5+/-5.0 to 19.2+/-3.1 arbitrary units (P<0.007 and P<0.05, respectively). alpha-Tocopherol levels increased significantly after PGJ consumption (from 15.6+/-0.7 to 17.6+/-0.9 micromol/L; P<0.009), and the plasma protein-independent antioxidant activity increased by 50.0% (P<0.05). Last, incubation of platelets with select flavonoid fractions isolated from PGJ consistently attenuated superoxide levels but had variable effects on whole-blood aggregation, platelet aggregation, and NO release. CONCLUSIONS: Both in vitro incubation and oral supplementation with PGJ decrease platelet aggregation, increase platelet-derived NO release, and decrease superoxide production. These findings may be a result of antioxidant-sparing and/or direct effects of select flavonoids found in PGJ. The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products, independent of alcohol consumption, in cardiovascular disease.
Adult↗
Mapping the molecular interface between the sigma(70) subunit of E. coli RNA polymerase and T4 AsiA.
Bacteriophage T4 antisigma protein AsiA (10 kDa) orchestrates a switch from the host and early viral transcription to middle viral transcription by binding to the sigma(70) subunit of E. coli RNA polymerase. The molecular determinants of sigma(70)-AsiA complex formation are not known. Here, we used combinatorial peptide chemistry, protein-protein crosslinking, and mutational analysis to study the interaction between AsiA and its target, the 33 amino acid residues-long sigma(70) peptide containing conserved region 4.2. Many region 4.2 amino acid residues contact AsiA, which likely completely occludes the DNA-binding surface of region 4.2. Though none of region 4.2 amino acid residues is singularly responsible for the very tight interaction with AsiA, sigma(70) Lys593 and Arg596 which lie outside the putative DNA recognition element of region 4.2, contribute the most. In AsiA, the first 20 amino acid residues are both necessary and sufficient for interactions with sigma(70). Our results clarify details of sigma(70)-AsiA interaction and open the way for engineering AsiA derivatives with altered specificities.
Amino Acid Sequence↗
Egg contamination by Salmonella serovar enteritidis following vaccination with Delta-aroA Salmonella serovar typhimurium.
The efficacy of an aroA Salmonella serovar typhimurium modified live vaccine to decrease internal egg contamination after oral challenge of hens with egg-contaminating Salmonella serovar enteritidis was assessed. Challenge was with a mixed phenotype of S. enteritidis that had virulence characteristics previously associated with enhanced oral invasiveness and egg contamination in chickens. Immunized birds had fewer positive ovary/oviduct pools and lower cfu g(-1) cecal contents than did non-immunized birds, but the differences were not significant. The number of positive intestinal (duodenum, jejunum, ileum) and organ (spleen, kidney, liver) pools following challenge from each treatment group were equivalent. Most importantly, immunization did not decrease egg contamination. These results suggest that the ability of modified live vaccines to reduce internal egg contamination by S. serovar enteritidis can be assessed using characterized strains for challenge.
Animals↗
PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.
In papillary renal cell carcinomas the TFE3 transcription factor becomes fused to the PSF and NonO pre-mRNA splicing factors and most commonly to a protein of unknown function designated PRCC. In this study we have examined the ability of the resulting PRCC-TFE3 and NonO-TFE3 fusions to activate transcription from the plasminogen activator inhibitor-1 (PAI-1) promoter. The results show that only fusion to PRCC enhanced transcriptional activation, indicating that the ability to enhance the level of transcription from endogenous TFE3 promoters is not a consistent feature of TFE3 fusions. In investigations of the normal function of PRCC we observed that PRCC expressed as a green fluorescent fusion protein colocalizes within the nucleus with Sm pre-mRNA splicing factors. It was also found that endogenous PRCC is coimmunoprecipitated by antibodies that recognize a variety of pre-mRNA splicing factors including SC35, PRL1 and CDC5. Association with the cellular splicing machinery is therefore, a common feature of the proteins that become fused to TFE3 in papillary renal cell carcinomas.
Adult↗
Soluble adhesion molecules and unstable coronary artery disease.
Leukocyte adhesion and transendothelial migration, prerequisites in the development of atherosclerosis, are largely mediated by adhesion molecules. In addition, unstable coronary syndromes usually involve platelet activation and thrombus formation at the site of atherosclerotic plaque. Therefore, we compared plasma levels of soluble P-selectin, a measurement of platelet activation, as well as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with atherosclerosis undergoing coronary angiography (n=76). Soluble P-selectin levels, as measured by ELISA, were significantly elevated in patients with unstable (n=44) vs stable (n=32) atherosclerotic disease (73.0 +/- 2.5 ng/ml vs 52.3 +/- 3.0 ng/ml, respectively, P<0.01). By logistic regression analysis, plasma level of soluble P-selectin was an independent predictor of an unstable coronary syndrome (OR 4.2, CI 1.4-12.9, P<0.01). Soluble E-selectin level, a marker of endothelial activation, was associated with extent of atherosclerosis but did not correlate with disease stability. Interestingly, soluble P-selectin was inversely correlated with plasma levels of the antioxidant alpha-tocopherol (R=-0.443, P<0.001), a known inhibitor of platelet function. In summary, amongst the soluble adhesion molecules, only P-selectin is significantly increased in patients with unstable coronary syndromes. This study suggests that platelet activation persists in patients with unstable coronary syndromes despite concurrent aspirin therapy. In addition, the beneficial effects of alpha-tocopherol in patients with cardiovascular disease may be related to inhibition of platelet function.
Aged↗
A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer.
New therapeutic alternatives are needed to improve outcomes in patients with androgen-independent prostate cancer (AIPC). For several years, researchers at the National Cancer Institute have been interested in elucidating the importance of angiogenesis in the pathogenesis of prostate cancer and in identifying inhibitors of this process. Thalidomide has been shown to inhibit the ability of tumors to recruit new blood vessels. In a recent phase II trial of thalidomide in AIPC, 28% of patients achieved a prostate-specific antigen (PSA) decrease of >40%. The taxane docetaxel also produces PSA and measurable disease responses when used as monotherapy or as a component of combination chemotherapy for AIPC. Thus, based on the single-agent activity of thalidomide and docetaxel, we initiated a randomized phase II study of weekly docetaxel with or without thalidomide, 200 mg at bedtime, in patients with chemotherapy-naive metastatic AIPC. Docetaxel, 30 mg/m(2) intravenously, was administered every 7 days for 3 weeks, followed by a 1-week rest period. Both regimens have been well tolerated among the first 59 treated patients, with a near absence of grade (3/4) myelosuppression. Fatigue, hyperglycemia, and pulmonary toxicity were seen in both groups. Thrombotic events have been seen in the combination arm. Thirty-five percent (6 of 17) of the patients receiving docetaxel alone and 53% (19 of 36) of those receiving docetaxel and thalidomide have had a PSA decrease of at least 50%. Combining a cytotoxic agent with an angiogenesis inhibitor is a promising area of investigation for prostate cancer management.
Adenocarcinoma↗
Salvage radiotherapy for PSA failure after radical prostatectomy.
BACKGROUND AND PURPOSE: Prostate-specific antigen (PSA) failure after radical prostatectomy is a common clinical scenario, and there is no consensus on how it should be managed. Salvage radiation to the prostatic bed is a potentially curative treatment option, and is the subject of this review. Patient selection, and the efficacy and toxicity of treatment will be discussed, and recommendations made for current practice and future studies. METHODS: An English language MEDLINE search was performed, limited to the years 1989-2000, using the MeSH headings 'prostatic neoplasms' and 'radiotherapy'. The 660 abstracts identified were reviewed, and articles concerning patient selection for, or outcome of, post-operative radiation to the prostatic bed selected. After exclusion of articles concerning adjuvant, rather than salvage, radiation, this left a total of 22 case series, including 1062 patients for the review of treatment efficacy. RESULTS AND CONCLUSIONS: The quality of the evidence makes it difficult to form a judgment regarding the efficacy of salvage radiation following radical prostatectomy, particularly in men with a PSA level in the range 0.01-0.2 ng/ml. Salvage radiation may be more effective given earlier rather than later. These considerations have important consequences for the interpretation of current trials of adjuvant radiation following radical prostatectomy.
Bone Neoplasms↗
Use of diabetes preventive care and complications risk in two African-American communities.
BACKGROUND: We examined levels of diabetes preventive care services and glycemic and lipid control among African Americans with diabetes in two North Carolina communities. METHODS: Cross-sectional, population-based study of 625 African-American adults with diagnosed diabetes. Participants had a household interview to determine receipt of preventive care services including glycosylated hemoglobin (HbA(1c)), blood pressure, lipid, foot, dilated eye, and dental examinations; diabetes education; and health promotion counseling. A total of 383 gave blood samples to determine HbA(1c) and lipid values. RESULTS: Annual dilated eye, foot, and lipid examinations were reported by 70% to 80% of the population, but only 46% reported HbA(1c) tests. Rates of regular physical activity (31%) and daily self-monitoring of blood glucose (40%) were low. Sixty percent of the population had an HbA(1c) level >8% and one fourth had an HbA(1c) level >10%. Half of the population had a low-density lipoprotein value >130 mg/dL. Lack of insurance was the most consistent correlate of inadequate care (odds ratio [OR]=2.3; 95% confidence interval [CI]=1.3-3.9), having HbA(1c) >9.5% (OR=2.1, 95% CI=1.1-4.2), and LDL levels >130 mg/dL (OR=2.1; 95% CI=1.0-4.5). CONCLUSIONS: Levels of diabetes preventive care services were comparable to U.S. estimates, but glycemic and lipid control and levels of self-management behaviors were poor. These findings indicate a need to understand barriers to achieving and implementing good glycemic and lipid control among African Americans with diabetes.
Adolescent↗
SB-272183, a selective 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptor antagonist in native tissue.
A novel compound, SB-272183 (5-Chloro-2, 3-dihydro-6-[4-methylpiperazin-1-yl]-1[4-pyridin-4-yl]napth-1-ylaminocarbonyl]-1H-indole), has been shown to have high affinity for human 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors with pK(i) values of 8.0, 8.1 and 8.7 respectively and is at least 30 fold selective over a range of other receptors. [(35)S]-GTPgammaS binding studies showed that SB-272183 acts as a partial agonist at human recombinant 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors with intrinsic activities of 0.4, 0.4 and 0.8 respectively, compared to 5-HT. SB-272183 inhibited 5-HT-induced stimulation of [(35)S]-GTPgammaS binding at human 5-HT(1A) and 5-HT(1B) receptors to give pA(2) values of 8.2 and 8.5 respectively. However, from [(35)S]-GTPgammaS autoradiographic studies in rat and human dorsal raphe nucleus, SB-272183 did not display intrinsic activity up to 10 microM but did block 5-HT-induced stimulation of [(35)S]-GTPgammaS binding. From electrophysiological studies in rat raphe slices in vitro, SB-272183 did not effect cell firing rate up to 1 microM but was able to attenuate (+)8-OH-DPAT-induced inhibition of cell firing to give an apparent pK(b) of 7.1. SB-272183 potentiated electrically-stimulated [(3)H]-5-HT release from rat and guinea-pig cortical slices at 100 and 1000 nM, similar to results previously obtained with the 5-HT(1B) and 5-HT(1D) receptor antagonist, GR127935. Fast cyclic voltammetry studies in rat dorsal raphe nucleus showed that SB-272183 could block sumatriptan-induced inhibition of 5-HT efflux, with an apparent pK(b) of 7.2, but did not effect basal efflux up to 1 microM. These studies show that, in vitro, SB-272183 acts as an antagonist at native tissue 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗