Veterans Administrative Medical Center

Louisville, KY, United States

Veterans Administrative Medical Center

Louisville, KY, United States
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Wu Y.-Y.,Tri Service General Hospital | Wu Y.-Y.,A-Life Medical | Chao T.-Y.,Taipei Medical University | Liu H.-Y.,Tri Service General Hospital | And 7 more authors.
Journal of B.U.ON. | Year: 2015

Purpose: The mechanism of cancer cachexia remains unclear and inflammatory cytokines may play a role in its development. Interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-a (TNFα) are known to be associated with cancer cachexia. Tartrate-resistant acid phos-phatase 5a (TRACP5α) is proposed to be related to chronic inflammation. In this study we hypothesize that TRACP5α is a chronic inflammatory marker that is correlated with cancer cachexia. Methods: Fifty-five cancer patients with and without cancer cachexia were enrolled from January 2009 to December 2012. Body mass index (BMI) was measured and serum total cholesterol, triglycerides and albumin were examined to evaluate the nutritional status. IL-6, CRP and TRACPSα protein activity were evaluated. Results: Inflammatory markers including IL-6, and CRP were significantly elevated in patients with cancer cachexia (ρ=0.0075 and 0.0021, respectively). Patients with cachexia also had higher CRP/albumin ratio (ρ =0.0265). TRACP5α activity, TRACP5α protein and their combinations with albumin were increased in the cancer cachexia groups but without significant difference. There were good correlations between IL-6, CRP, and BMI. Patients with higher TRACP5α activity had shorter survival (ρ=0.004). Conclusion:TRACP5α may be a promising chronic inflammatory marker and may play a prognostic role in cancer cachexia. Further large-scale prospective studies are warranted to confirm its role in the cancer cachexia process.

Yao N.-S.,Tri Service General Hospital | Wu Y.-Y.,Tri Service General Hospital | Janckila A.J.,Veterans Administrative Medical center | Ku C.-H.,National Defense Medical Center | And 6 more authors.
Clinica Chimica Acta | Year: 2011

Background: Diagnosis and follow-up of bone metastasis (BMet) in non-small cell lung cancer (NSCLC) patients usually rely on symptoms and image studies. A serum marker of bone resorption may improve the quality of treatment in such patients. Tartrate-resistant acid phosphatase 5b (TRACP5b) is a specific marker for osteoclasts and we proposed it can be used as a marker of BMet in NSCLC patients. Methods: In November 2002 till August 2008 serum samples were obtained from 141 newly diagnosed stage IIIA, IIIB or IV NSCLC patients and 41 normal subjects. All patients received baseline bone scintinography examination and evaluation of clinical symptoms as a standard of BMet diagnosis. Patients were divided into 2 groups by having BMet (Group I, n= 72) or not (Group II, n= 69). An in-house immunoassay using a TRACP-specific monoclonal antibody, 14G6, was used to measure the serum TRACP5b activity at pH 6.1. Results: The mean serum TRACP5b activities of Group I, Group II and normal subjects were 3.50. ±. 2.23. U/l, 2.09. ±. 0.72. U/l and 2.33. ±. 0.52. U/l, respectively. After adjusting for age, stage, gender, and histology in a generalized linear model, Group I has significantly higher TRACP5b activity than Group II (p<. 0.001). The receiver operating characteristic analysis established a cutoff value of 2.551. U/l to identify BMet in NSCLC patients with a sensitivity of 63.9% and a specificity of 76.8%. TRACP5b activity declined in patients who responded to treatment (p= 0.047), and elevated in patients who developed new BMet (p= 0.05). Conclusions: Serum TRACP5b activity test is a potentially useful adjunct in diagnosing and monitoring BMet in NSCLC. Further study is warranted to establish its real value in diagnosis and monitoring of BMet in NSCLC patients. © 2010 Elsevier B.V.

Wu Y.-Y.,Tri Service General Hospital | Janckila A.J.,Veterans Administrative Medical center | Ku C.-H.,National Defense Medical Center | Yu C.-P.,Tri Service General Hospital | And 6 more authors.
BMC Cancer | Year: 2010

Background: Serum tartrate-resistant acid phosphatase 5b (TRACP 5b) activity is a marker of osteoclast number and is elevated in breast cancer (BC) patients with extensive bone metastasis, which might in turn reflect the tumour burden. We tested the hypothesis that baseline serum TRACP 5b activity and its interval change are potential prognostic markers of survival in BC patients with bone metastasis.Methods: We analyzed the data from previous prospective studies. A total of 100 patients with newly diagnosed bone metastasis were included. Cox proportional regression model was used to evaluate the correlation between the overall survival time (OS) and baseline serum TRACP 5b activity and its interval changes. The least significant change (LSC) of TRACP 5b was calculated from data obtained from 15 patients with early BC.Results: Estrogen receptor status (Hazard Ratio (HR) = 0.397; p = 0.003) and visceral metastasis (HR = 0.492; p = 0.0045) were significantly correlated with OS. The OS was significantly shorter in those patients with higher baseline TRACP 5b activity based on a cut-off value to delineate the highest tertile (HR = 3.524; p < 0.0001). Further analysis demonstrated that among patients in the highest tertile, OS was significantly longer in those patients who had achieved a decrease of serum TRACP 5b activity greater than the LSC (38.59%) (p = 0.0015).Conclusions: We found that TRACP 5b activity and its interval change after treatment bore a prognostic role in BC patients with bone metastasis and a high baseline serum TRACP 5b activity. Further prospective phase II study is necessary to confirm these results. © 2010 Wu et al; licensee BioMed Central Ltd.

Wu Y.-Y.,Tri Service General Hospital | Janckila A.J.,Veterans Administrative Medical Center | Slone S.P.,University of Louisville | Perng W.-C.,Tri Service General Hospital | And 2 more authors.
Journal of the Formosan Medical Association | Year: 2014

Background/Purpose: Tartrate-resistant acid phosphatase (TRACP) 5a is expressed strongly in inflammatory macrophages (MΦ). Serum TRACP5a is elevated in rheumatoid arthritis patients with extra-articular manifestations of rheumatoid nodules, in a percentage of patients with end-stage chronic kidney disease, and may be a risk marker for acute myocardial infarction. This proof-of-concept study was undertaken in patients with sarcoidosis to further substantiate our hypothesis that TRACP5a protein is a biomarker for macrophages in other chronic inflammatory diseases. Methods: Immunohistochemical staining for TRACP5a and CD68 was performed in tissues of 19 patients with sarcoidosis. We also measured circulating TRACP5a protein and other inflammation biomarkers including interkeukin-6, angiotensin-converting enzyme, and C-reactive protein in 13 patients. Twenty healthy age-matched nonsmoking individuals were used as the reference group. Results: All sarcoidosis tissues showed strong staining for TRACP5a and CD68 in the non-caseating granulomatous lesions and localized specifically to MΦ, multinucleate giant cells, and epithelioid MΦ. Serum TRACP5a protein was elevated significantly in active sarcoidosis patients compared with the control group, and levels fluctuated with disease activity in one patient studied longitudinally. Conclusion: TRACP5a protein is expressed abundantly in the granulomatous tissues and may be elevated in a significant proportion of sarcoidosis patients. These findings further support our hypothesis that serum TRACP5a is derived from systemic inflammatory MΦ and thereby may be a biomarker of inflammation for sarcoidosis and also reflect its disease activity. © 2012.

Chen Y.-G.,Tri Service General Hospital | Janckila A.,Veterans Administrative Medical Center | Chao T.-Y.,Taipei Medical University | Yeh R.-H.,Tri Service General Hospital | And 5 more authors.
Medicine (United States) | Year: 2015

Infiltrating neutrophils, lymphocytes, macrophages, and cytokines constitute a state of chronic inflammation within the tumor microenvironment. Tartrate-resistant acid phosphatase 5a (TRACP5a) protein, a novel product of activated macrophage, is postulated to be a biomarker for systemic inflammatory burden in states of chronic inflammation. We aimed to investigate the clinical significance of TRACP5a expression in tumor-infiltrating macrophages and serum TRACP5a in patients with metastatic breast cancer (BC). We retrospectively analyzed the clinical data from 34 BC patients with confirmed skeletal/visceral metastasis upon or during first-line palliative treatment. Patients were stratified into 3 groups based on the therapeutic responses and follow-up disease course. The association ofTRACP5a protein with other inflammatory and cancer biomarkers was assessed among the clinically distinct group of patients. Higher TRACP5a protein was significantly correlated with earlier disease progression and survival (P=0.0045) in comparison to other inflammatory markers, CRP or IL-6. Patients with higher serum TRACP5a level and shorter survival and treatment refractoriness also had more TRACP+ tumor-infiltrating macrophages. Our data support a hypothesis that serum TRACP5a protein can potentially be a predictive and prognostic marker to evaluate disease progression and therapeutic response in BC patients with bone/visceral metastasis. The associations between overall survival and TRACP expression by macrophages require further prospective investigation. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

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