Expression of a-Tocopherol-Associated protein (TAP) is associated with clinical outcome in breast cancer patients

Background

The role of vitamin E in breast cancer prevention and treatment has been widely investigated, and the different tocopherols that comprise this nutrient have been shown to have divergent associations with cancer outcome. Our previous studies have shown that α-Tocopherol-associated protein (TAP), a vitamin E binding protein, may function as a tumor suppressor-like factor in breast carcinogenesis. The current study addresses the association of TAP expression with breast cancer clinical outcomes.

Methods

Immunohistochemical stain for TAP was applied to a tissue microarray from a breast cancer cohort consisting of 271 patients with a median follow-up time of 5.2 years. The expression of TAP in tumor cells was compared with patient’s clinical outcome at 5 years after diagnosis. The potential role of TAP in predicting outcome was also assessed in clinically relevant subsets of the cohort. In addition, we compared TAP expression and Oncotype DX scores in an independent breast cancer cohort consisting of 71 cases.

Results

We demonstrate that the expression of TAP was differentially expressed within the breast cancer cohort, and that ER+/PR?±?tumors were more likely to exhibit TAP expression. TAP expression was associated with an overall lower recurrence rate and a better 5-year survival rate. This association was primarily in patients with ER+ tumors; exploratory analysis showed that this association was strongest in patients with node-positive tumors and was independent of stage and treatment with chemotherapy. TAP expression in ER/PR negative or triple negative tumors had no association with clinical outcome. In addition, we did not observe an association between TAP expression and Oncotype DX recurrence score.

Conclusions

The significant positive association we found for α-Tocopherol-associated protein with outcome in breast cancer may help to better define and explain studies addressing α-tocopherol’s association with cancer risk and outcome. Additionally, further studies to validate and extend these findings may allow TAP to serve as a breast-specific prognostic marker in breast cancer patients, especially in those patients with ER+ tumors.

     

Randomized clinical trial of a quality improvement intervention in nursing homes

PURPOSE: The purpose of the study was to determine if simply providing nursing facilities with comparative quality performance information and education about quality improvement would improve clinical practices and subsequently improve resident outcomes, or if a stronger intervention, expert clinical consultation with nursing facility staff, is needed. DESIGN AND METHODS: Nursing facilities (n = 113) were randomly assigned to one of three groups: workshop and feedback reports only, workshop and feedback reports with clinical consultation, and control. Minimum Data Set (MDS) Quality Indicator (QI) feedback reports were prepared and sent quarterly to each facility in intervention groups for a year. Clinical consultation by a gerontological clinical nurse specialist (GCNS) was offered to those in the second group. RESULTS: With the exception of MDS QI 27 (little or no activity), no significant differences in resident assessment measures were detected between the groups of facilities. However, outcomes of residents in nursing homes that actually took advantage of the clinical consultation of the GCNS demonstrated trends in improvements in QIs measuring falls, behavioral symptoms, little or no activity, and pressure ulcers (overall and for low-risk residents). IMPLICATIONS: Simply providing comparative performance feedback is not enough to improve resident outcomes. It appears that only those nursing homes that sought the additional intensive support of the GCNS were able to effect enough change in clinical practice to improve resident outcomes significantly.     

Validation of the Childhood Health Assessment Questionnaire in the juvenile idiopathic myopathies. Juvenile Dermatomyositis Disease Activity Collaborative Study Group

OBJECTIVE: To examine the validity of the Childhood Health Assessment Questionnaire (CHAQ) in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS: One hundred fifteen patients were enrolled in a multicenter collaborative study, during which subjects were assessed twice, 7-9 months apart. Physical function was measured using the CHAQ. Internal reliability was assessed using adjusted item-total correlations and item endorsement rates. Construct validity was assessed by comparing predicted and actual correlations of the CHAQ with other measures of physical function and disease activity. Responsiveness was assessed by calculating effect size (ES) and standardized response mean (SRM) in a group of a priori defined "improvers." RESULTS: Item-total correlations were high (rs range = 0.35-0.81), suggesting all items were related to overall physical function. Manual muscle testing and the Childhood Myositis Assessment Scale correlated moderate to strongly with the CHAQ (r = -0.64 and -0.75, both p < 0.001). Moderate correlations were also seen with the physician global assessment of disease activity (rs = 0.58, p < 0.001), parent global assessment of overall health (rs = -0.65, p < 0.001), Steinbrocker function class (rs = 0.69, p < 0.001), and global skin activity (rs = 0.40, p < 0.001), while global disease damage and skin damage had low correlations (rs = 0.13 and 0.07, p > or =0.17). Responsiveness of the CHAQ was high, with ES = 1.05 and SRM = 1.20. CONCLUSION: In this large cohort of patients with juvenile IIM, the CHAQ exhibited internal reliability, construct validity, and strong responsiveness. We conclude that the CHAQ is a valid measure of physical function in juvenile IIM, appropriate for use in therapeutic trials, and potentially in the clinical care of these patients.     

In vivo transformation of mouse conventional CD8alpha+ dendritic cells leads to progressive multisystem histiocytosis

Division and proliferation of dendritic cells (DCs) have been proposed to contribute to homeostasis and to prolonged antigen presentation. Whether abnormal proliferation of dendritic cells causes Langerhans cell histiocytosis (LCH) is a highly debated topic. Transgenic expression of simian virus 40 (SV40) T antigens in mature DCs allowed their transformation in vivo while maintaining their phenotype, function, and maturation capacity. The transformed cells were differentiated splenic CD8 alpha-positive conventional dendritic cells with increased Langerin expression. Their selective transformation was correlated with higher steady-state cycling compared with CD8 alpha-negative DCs in wild-type and transgenic mice. Mice developed a DC disease involving the spleen, liver, bone marrow, thymus, and mesenteric lymph node. Surprisingly, lesions displayed key immunohistologic features of Langerhans cell histiocytosis, including expression of Langerin and absence of the abnormal mitoses observed in Langerhans cell sarcomas. Our results demonstrate that a transgenic mouse model with striking similarities to aggressive forms of multisystem histiocytosis, such as the Letterer-Siwe syndrome, can be obtained by transformation of conventional DCs. These findings suggest that conventional DCs may cause some human multisystem LCH. They can reveal shared molecular pathways for human histiocytosis between humans and mice.     

Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

Background  

Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications.