Is dual-energy absorptiometry accurate in the assessment of bone status of patients with chronic kidney disease?

Several patients with chronic kidney disease (CKD) have deteriorated bone status. Estimation of bone status using DXA has limitations especially in patients with CKD accompanying aortic calcifications. Quantitative CT and the trabecular bone score could be more accurate methods to estimate bone status for patients with CKD and vascular calcifications. INTRODUCTION: It remains unclear whether dual-energy absorptiometry (DXA) is appropriate for the assessment of bone status in patients with chronic kidney disease (CKD), a disease that impacts bone health. The aims of this study were to compare DXA and central quantitative computed tomography (cQCT) and to evaluate bone status in patients with pre-dialysis CKD. METHODS: This retrospective study included 363 healthy control subjects whose bone mineral density (BMD) was evaluated with DXA and 117 CKD patients whose BMD was evaluated using both cQCT and DXA. Diagnostic discordance was assessed between the lumbar spine (LS) and femur neck (FN) from DXA or between two modalities. The trabecular bone score (TBS) was extracted from DXA images. The volume of abdominal aortic calcification (AAC) was calculated using CT images from cQCT. RESULTS: Using LS DXA T-score, osteoporosis was less common in the CKD group than in controls. Patients with normal LS BMD using DXA were reclassified into osteopenia or osteoporosis using cQCT in CKD patients. Among discordant subjects between FN and LS in DXA, a higher BMD of LS was more common in CKD patients than in controls. CKD patients had lower TBS than controls despite having the same diagnosis using DXA. AAC volume negatively correlated with BMD from cQCT and with TBS but not with BMD from DXA. CONCLUSIONS: TBS and cQCT could accurately assess bone status in CKD patients since DXA may overestimate LS BMD, likely due to an increased AAC volume.

Galectin-3 stabilizes heterogeneous nuclear ribonucleoprotein Q to maintain proliferation of human colon cancer cells.

Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU.

Incidence of cancer among patients with systemic sclerosis in Korea: results from a single centre.

OBJECTIVE: The aim of this study was to determine whether the incidence of cancer has increased among patients with systemic sclerosis (SSc) in Korea. METHODS: The study subjects consisted of 112 patients who had been consecutively evaluated for at least 6 months between 1990 and 2007. We retrospectively reviewed their medical records, investigated the incidence rate of cancer and compared it with that of the Korea National Cancer Centre database. RESULTS: Nine out of 112 patients developed cancer (four males and five females). The average age at diagnosis of cancer was 56.4 years and the mean disease duration was 8.9 years. The standardized incidence ratio (SIR) for SSc patients was 4.2 [95% confidence interval (CI) 2.3-6.1], 3.7 for women (95% CI 1.2-6.2) and 6.4 for men (95% CI 1.6-11.2). Lung cancer was the most common cancer (n = 4), followed by oesophagus (n = 1), stomach (n = 1), liver (n = 1), pancreas (n = 1), and squamous cell carcinoma of unknown origin (n = 1). All patients who developed lung cancer were female and non-small cell carcinoma in origin. The SIR of lung cancer in female patients was 23.0 (95% CI 6.0-40.0). Two out of four lung cancer patients had concomitant interstitial lung disease (ILD); all were non-smokers. Treatment agents, autoantibodies, smoking, and lung involvement were not significantly different between SSc patients with or without cancer. CONCLUSION: The SIR of cancer was significantly higher in SSc patients, and especially in those who were male, than in the general population. Lung cancer was the most common cancer. Active surveillance for the detection of cancer should be performed in all SSc patients.

HOXB13 downregulates intracellular zinc and increases NF-κB signaling to promote prostate cancer metastasis.

Characteristically, prostate cancer (PCa) cells exhibit marked decrease in intracellular zinc; however, the mechanism responsible is not clearly understood. HOXB13 is involved in PCa progression and is overexpressed in castration-resistant PCa. DNA microarray analysis of LNCaP Pca cells showed that ZnT zinc output transporters were strikingly upregulated among androgen-independent HOXB13 target genes. Furthermore, exogenous HOXB13 caused intracellular zinc concentrations to fall in PCa cells, stimulated NF-κB-mediated signaling by reducing inhibitor of NF-κB alpha (IκBα) and enhanced the nuclear translocation of RelA/p65. Human prostate tumors also exhibited strong inverse correlation between the protein expressions of HOXB13 and IκBα. Consequently, HOXB13 stimulated PCa cell invasion, and this was inhibited by the suppression of ZnT4. In addition, studies in a PC3 orthotopic mouse model of PCa metastasis showed that HOXB13 is a strong metastatic stimulator. Taken together, these results show that HOXB13 promotes PCa invasion and metastasis by decreasing intracellular zinc levels, thus stimulating NF-κB signals, and suggest that HOXB13 acts as a modulator of intracellular zinc levels that promotes the malignant characteristics of PCa.

Targeting Gli transcription activation by small molecule suppresses tumor growth.

Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anticancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study, we identified an interaction between Gli proteins and a transcription coactivator TBP-associated factor 9 (TAF9), and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic small molecule, FN1-8, that efficiently interferes with Gli/TAF9 interaction and downregulate Gli/TAF9-dependent transcriptional activity. More importantly, FN1-8 suppresses cancer cell proliferation in vitro and inhibits tumor growth in vivo. Our results suggest that blocking Gli transactivation, an important control point of multiple oncogenic pathways, may be an effective anticancer strategy.

Research to improve extension ladder angular positioning.

A leading cause for extension ladder fall incidents is a slide-out event usually related to suboptimal ladder inclination. An improved ladder positioning method or procedure could reduce the risk of ladder stability failure and the related fall injury. The objective of the study was to comparatively evaluate the effectiveness of a multimodal angle indicator with other existing methods for extension ladder angular positioning. Twenty experienced and 20 inexperienced ladder users participated in the study. Four ladder positioning methods were tested in a controlled laboratory environment with 4.88 m (16 ft) and 7.32 m (24 ft) ladders in extended and retracted positions. The positioning methods included a no-instruction method, the current standard anthropometric method, and two instrumental methods - a bubble level indicator, and a multimodal indicator providing direct feedback with visual and sound signals. Performance measures included positioning angle and time. The results indicated that the anthropometric method was effective in improving the extension ladder positioning angle (p < 0.001); however, it was associated with considerable variability and required 50% more time than no-instruction. The bubble level indicator was an accurate positioning method (with very low variability), but required more than double the time of the no-instruction method (p < 0.001). The multimodal indicator improved the ladder angle setting as compared to the no-instruction and anthropometry methods (p < 0.001) and required the least time for ladder positioning among the tested methods (p < 0.001). An indicator with direct multimodal feedback is a viable approach for quick and accurate ladder positioning. The main advantage of the new multimodal method is that it provides continuous feedback on the angle of the device and hence does not require repositioning of the ladder. Furthermore, this indicator can be a valuable tool for training ladder users to correctly apply the current ANSI A14 standard anthropometric method in ladder angular positioning. The multimodal indicator concept has been further developed to become a hand-held tool in the form of a smart phone application.

Hipk2 cooperates with p53 to suppress γ-ray radiation-induced mouse thymic lymphoma.

A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53+/- and p53-/- mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2 Mb interval that contained only the gene encoding homeobox-interacting protein kinase 2 (Hipk2). More than 30% of radiation-induced tumors from both p53+/- and p53-/- mice showed heterozygous loss of one Hipk2 allele. Mice carrying a single inactive allele of Hipk2 in the germline were susceptible to induction of tumors by γ-radiation, but most tumors retained and expressed the wild-type allele, suggesting that Hipk2 is a haploinsufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of both Hipk2 and p53 confers strong sensitization to radiation-induced lymphoma. We conclude that Hipk2 is a haploinsufficient lymphoma suppressor gene.