Using the Actor-Partner Interdependence Model to explore the psychological impact of COVID-19 on anxiety in dyads of patients with cancer and caregivers.

BACKGROUND: Delineating the compound psychological effect of the pandemic on cancer care, and the interdependency across cancer patient-caregiver dyads have yet to be explored. This study examines the levels of psychological impact of COVID-19 on patient-caregiver dyads anxiety, and the interdependent associations between their COVID-19 and cancer concerns, and risk perceptions. METHOD: There were 352 patients and caregivers (patient-caregiver dyads, N = 176) included in this study (43.2% spousal dyads). Generalized Anxiety Disorder-7 and questionnaires regarding risk perception, perceived confidence in healthcare system, COVID-19, and cancer-related concerns were administered. Actor-Partner Interdependence Model (APIM) analyses were used to determine the interdependent effects. Indirect effects were tested using mediation pathway analyses. RESULTS: Patients reported significantly higher levels of risk perceptions and anxiety than their caregivers (p < 0.01). Anxiety rates (GAD-7 ≥ 10) were also significantly higher (26.7% vs 18.2%, p < 0.01). Dyads' anxiety, "general COVID-19 concerns," "cancer-related concerns," and risk perceptions were correlated (ps < 0.01). APIM showed only actor effects of general COVID-19 concerns, cancer-related COVID-19 concerns, and risk perceptions on anxiety (ßs = 0.19-0.53, ps < 0.01). No partner effects were observed. Similar results were found in the composite APIM. Indirect effects of the patient/caregiver's variables on their partner's anxiety were observed in the mediation analyses. CONCLUSION: Concerns about COVID-19 and cancer care could be indirectly associated in patient-caregiver dyads and need to be proactively addressed. As pandemic evolves into endemicity, engagement with patients and caregivers should strive to be sensitive to their differential needs and messages should be tailored to the informational needs of each.

Stability of Pattern Formation in Systems with Dynamic Source Regions.

We explain the principles of gene expression pattern stabilization in systems of interacting, diffusible morphogens, with dynamically established source regions. Using a reaction-diffusion model with a step-function production term, we identify the phase transition between low-precision indeterminate patterning and the phase in which a traveling, well-defined contact zone between two domains is formed. Our model analytically explains single- and two-gene domain dynamics and provides pattern stability conditions for all possible two-gene regulatory network motifs.

Update on the Recommendations on Breast Cancer Screening by the Cancer Expert Working Group on Cancer Prevention and Screening.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

Low-level laser therapy for carpal tunnel syndrome: systematic review and network meta-analysis.

BACKGROUND: Splinting is recommended by various organisations as a non-surgical first-line treatment for carpal tunnel syndrome (CTS), despite the limited evidence supporting its effectiveness. Previous studies on the effectiveness of low-level laser therapy (LLLT) have reported mixed results, and this systematic review aimed to resolve this controversy. OBJECTIVE: To perform a network meta-analysis (NMA) for evaluating the effectiveness of LLLT compared with other conservative treatments for CTS. METHODS: Eighteen electronic databases were searched for potential randomised controlled trials (RCTs). RCTs evaluating LLLT or other non-surgical treatments as an add-on to splinting were included. Included RCTs measured at least one of the following three outcomes with validated instruments: pain, symptom severity and functional status. RESULTS: Six RCTs (418 patients) were included. NMA suggested that LLLT plus splinting has the highest probability (75%) of pain reduction, compared with sham laser plus splinting (61%), ultrasound plus splinting (57%) and splinting alone (8%). However, while LLLT plus splinting is significantly more effective than sham laser plus splinting for pain reduction, the magnitude is not clinically significant (Visual Analogue Scale mean difference -0.53cm, 95% confidence interval -1.01 to -0.05cm; P=0.03, I2=25%). The effect of LLLT plus splinting on symptom severity and functional status was not superior to splinting alone. CONCLUSION: The use of LLLT in addition to splinting for the management of CTS is not recommended, as LLLT offers limited additional benefits over splining alone in terms of pain reduction, reduction of symptom severity or improved functional status. PROSPERO for systematic reviews and meta-analyses registration number CRD42017082650.

iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates.

Young-onset Parkinson's disease (YOPD), defined by onset at <50 years, accounts for approximately 10% of all Parkinson's disease cases and, while some cases are associated with known genetic mutations, most are not. Here induced pluripotent stem cells were generated from control individuals and from patients with YOPD with no known mutations. Following differentiation into cultures containing dopamine neurons, induced pluripotent stem cells from patients with YOPD showed increased accumulation of soluble α-synuclein protein and phosphorylated protein kinase Cα, as well as reduced abundance of lysosomal membrane proteins such as LAMP1. Testing activators of lysosomal function showed that specific phorbol esters, such as PEP005, reduced α-synuclein and phosphorylated protein kinase Cα levels while increasing LAMP1 abundance. Interestingly, the reduction in α-synuclein occurred through proteasomal degradation. PEP005 delivery to mouse striatum also decreased α-synuclein production in vivo. Induced pluripotent stem cell-derived dopaminergic cultures reveal a signature in patients with YOPD who have no known Parkinson's disease-related mutations, suggesting that there might be other genetic contributions to this disorder. This signature was normalized by specific phorbol esters, making them promising therapeutic candidates.

Thoracic kyphosis assessment in postmenopausal women: an examination of the Flexicurve method in comparison to radiological methods.

The Flexicurve ruler is an alternative method to radiographs for measuring thoracic kyphosis (curvature), but it is not certain that it is comparable. This study shows that Flexicurve can estimate radiographic vertebral centroid angles with less error than Cobb angles but that its accuracy would be inadequate for most clinical purposes. INTRODUCTION: The Flexicurve ruler provides a non-radiological method of measuring thoracic kyphosis (TK) that has moderately strong correlations with the gold-standard radiographic Cobb angle method, while consistently underestimating the TK angle. Cobb angles can include measurement errors that may contribute to poor agreement, particularly in older populations. The vertebral centroid angle could be a better radiographic reference method for the validation of Flexicurve. Using two separate radiographic measurements of TK, we examined the validity of Flexicurve. We aimed to ascertain the level of agreement between measures and to empirically explore reasons for between-method differences. METHODS: TK angles determined using Flexicurve and radiographic Cobb and vertebral centroid methods were compared using data from 117 healthy postmenopausal women (mean (SD) age 61.4 (7.0) years). Bland and Altman plots were used to assess differences between methods. Age, bone mineral density and body mass index were examined as characteristics that might explain any differences. RESULTS: Flexicurve angles were scaled prior to analysis. There was no statistically significant difference between angles produced by Flexicurve and vertebral centroid methods (MD - 2.16°, 95%CI - 4.35° to 0.03°) although differences increased proportionally with TK angles. Flexicurve angles were significantly smaller than radiographic Cobb angles and depending on the scaling method used, systematic error ranged between - 2.48° and - 5.19°. Age accounts for some of the differences observed (R2 < 0.08, p < 0.005). CONCLUSIONS: TK measured using the Flexicurve shows better agreement with the radiographic vertebral centroid method, but inaccuracy of the Flexicurve increases with increasing angle of kyphosis.

Teleological explanation and positive emotion serially mediate the effect of religion on well-being.

OBJECTIVE: Previous research has demonstrated a robust relationship between religion and well-being, and it has been proposed that positive emotions are important mediators of this effect. Yet the mechanism via which religion promotes positive emotions has not been widely studied. We sought to examine whether teleological explanations of daily events and resulting positive emotions serially mediated the effects of religion on well-being. METHOD: These hypotheses were tested over three studies involving full-time and part-time university students in Singapore. In Study 1, participants completed measures of religiousness and well-being, and explained and described three recent personally significant events and their resulting emotions. Studies 2 and 3 adopted an ecological momentary assessment approach to measure teleological explanations, resulting emotions, and well-being in almost real time. RESULTS: In Study 1, teleological explanations and positive emotions serially mediated the effects of religiousness on well-being. In Study 2, momentary teleological explanations of daily events mediated the positive relationship between religiousness and momentary positive emotions. In Study 3, serial mediation of the relationship between religiousness and momentary well-being by momentary teleological explanations and positive emotions was observed. CONCLUSIONS: These results provide evidence of the importance of teleological explanations of daily events in religious enhancement of well-being.

A facile method to functionalize gold nano-tripods with high suspension stability in an aqueous environment.

Here we aim to develop a facile emulsion-based method to prepare tripod gold nanoparticles (AuNPs) with high suspension stability in an aqueous environment. A gyroid-structured polymer template formed by the hydrolysis of a degradable block copolymer, polystyrene (PS)-b-poly(l-lactide), is used for the fabrication of AuNPs. Also, a successful emulsification of dichloromethane (DCM) in the aqueous phase is developed by using thiolated polyethylene glycol (PEG-SH) as the stabilizer. Subsequently, the nanohybrids of PS/Au can be fabricated by templated electroless plating, and then selectively dissolving in the DCM dispersive phase. Most interestingly, a dedicated process for the simultaneous release of the tripod AuNPs from the dissolution of PS associated with PEG-SH at the interface of the emulsion is achieved, giving PEG-SH-functionalized tripod AuNPs dispersed in the aqueous phase, which significantly improves the suspension stabilization of tripod AuNPs. The in situ temperature-programmed electrospray-differential mobility analysis provides a quantitative, statistical analysis of mobility diameter, dynamic shape factor, polydispersity, and colloidal stability.

Symptoms of Anxiety and Depression in Obese Singaporeans: a Preliminary Study.

BACKGROUND: Obesity is a major component of metabolic syndrome and an independent risk factor for various chronic diseases. It is also closely associated with mental illness, and the interaction is complex and multifactorial. This study aimed to estimate the prevalence of anxiety and depressive symptoms among obese Singaporeans. METHODS: Cross-sectional data of 36 male and 47 female obese Singaporeans who had been referred to the weight management clinic of National University Hospital, Singapore, between January 2010 and November 2011 were collected. Obesity was classified according to criteria of the World Health Organization. The extents of anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale. RESULTS: In obese Singaporeans attending the weight management clinic, the prevalence of anxiety symptoms was higher than that of depressive symptoms (28% vs 11%). There was no major socioeconomic difference between obese patients with and without anxiety, or with and without depressive symptoms. CONCLUSION: In obese Singaporeans, anxiety symptoms may be more common than depressive symptoms. Weight management programmes should incorporate anxiety management as part of standard treatment. Early detection and pharmacological and psychological interventions should be implemented.

Incidence, recurrence and comorbidity of anxiety disorders in four major developmental stages.

BACKGROUND: Anxiety disorders are common in childhood, adolescence, and adulthood, and frequently comorbid with other mental disorders. OBJECTIVE: The main aim of the present study was to examine the incidence, recurrence and comorbidity rates of anxiety disorders across four developmental periods, namely, during childhood (5 - 12.9 years), adolescence (13 - 17.9 years), emerging adulthood (18 - 23.9 years), and adulthood (24 - 30 years). METHOD: Eight hundred and sixteen participants from a large community sample were interviewed twice during adolescence, at age 24, and at age 30. They completed self-report measures of psychosocial functioning and semi-structured diagnostic interviews during adolescence and adulthood. RESULTS: The result showed first incidence of anxiety disorders to be significantly higher in childhood and adulthood than in adolescence and emerging adulthood. Female gender was associated with first incidence, but not with recurrence. Significant comorbidity was found between anxiety disorders and major depressive disorder (MDD) across the four developmental periods. The comorbidity between anxiety and substance use disorders (SUD) was significant in childhood, emerging adulthood and adulthood, but not in adolescence. The presence of anxiety disorders during childhood and adolescence significantly increased the probability of having an anxiety disorder during emerging adulthood. LIMITATIONS: The participants are ethically and geographically homogenous. CONCLUSION: Incidence and recurrence rates of anxiety disorders differed across four diverse developmental periods. The magnitude of comorbidity between anxiety disorders and MDD was comparable across periods.

Methodological quality of systematic reviews on treatments for depression: a cross-sectional study.

AIMS: Depression is one of the most common mental disorders and identifying effective treatment strategies is crucial for the control of depression. Well-conducted systematic reviews (SRs) and meta-analyses can provide the best evidence for supporting treatment decision-making. Nevertheless, the trustworthiness of conclusions can be limited by lack of methodological rigour. This study aims to assess the methodological quality of a representative sample of SRs on depression treatments. METHODS: A cross-sectional study on the bibliographical and methodological characteristics of SRs published on depression treatments trials was conducted. Two electronic databases (the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects) were searched for potential SRs. SRs with at least one meta-analysis on the effects of depression treatments were considered eligible. The methodological quality of included SRs was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. The associations between bibliographical characteristics and scoring on AMSTAR items were analysed using logistic regression analysis. RESULTS: A total of 358 SRs were included and appraised. Over half of included SRs (n = 195) focused on non-pharmacological treatments and harms were reported in 45.5% (n = 163) of all studies. Studies varied in methods and reporting practices: only 112 (31.3%) took the risk of bias among primary studies into account when formulating conclusions; 245 (68.4%) did not fully declare conflict of interests; 93 (26.0%) reported an 'a priori' design and 104 (29.1%) provided lists of both included and excluded studies. Results from regression analyses showed: more recent publications were more likely to report 'a priori' designs [adjusted odds ratio (AOR) 1.31, 95% confidence interval (CI) 1.09-1.57], to describe study characteristics fully (AOR 1.16, 95% CI 1.06-1.28), and to assess presence of publication bias (AOR 1.13, 95% CI 1.06-1.19), but were less likely to list both included and excluded studies (AOR 0.86, 95% CI 0.81-0.92). SRs published in journals with higher impact factor (AOR 1.14, 95% CI 1.04-1.25), completed by more review authors (AOR 1.12, 95% CI 1.01-1.24) and SRs on non-pharmacological treatments (AOR 1.62, 95% CI 1.01-2.59) were associated with better performance in publication bias assessment. CONCLUSION: The methodological quality of included SRs is disappointing. Future SRs should strive to improve rigour by considering of risk of bias when formulating conclusions, reporting conflict of interests and authors should explicitly describe harms. SR authors should also use appropriate methods to combine the results, prevent language and publication biases, and ensure timely updates.

Who Wants to Be an Intrapreneur? Relations between Employees' Entrepreneurial, Professional, and Leadership Career Motivations and Intrapreneurial Motivation in Organizations.

This paper reports an empirical study conducted to examine the relationship between employees' Entrepreneurial, Professional, and Leadership (EPL) career motivations and their intrapreneurial motivation. Using data collected from 425 working adults in the research/innovation and healthcare settings, we develop a self-report measure of employee intrapreneurial motivation. We also adapt an existing self-report measure of E, P, and L career motivations (previously developed and used with university students) for use with working adult organizational employees. Confirmatory factor analysis indicate that E, P, and L motivations and intrapreneurial motivation can be measured independently and reliably, while regression analyses show that the employees' E, P, and L motivations all contribute to explaining variance in their intrapreneurial motivation. Individuals with high E, P, and L motivational profiles are also found to have the highest intrapreneurial motivation scores, while those low on E, P, and L motivations have the least intrapreneurial motivation. Our findings suggest that the potential for intrapreneurship is not unique to only entrepreneurial employees. Instead, one can find intrapreneurs among employees with strong leadership and professional motivations as well. We discuss the findings in the context of generating more research to address the challenges of talent management in the 21st century knowledge economies where there is greater career mobility and boundarylessness in the workforce.

Biosynthesis of 1α-hydroxycorticosterone in the winter skate Leucoraja ocellata: evidence to suggest a novel steroidogenic route.

The present study explores the ability of intracellular bacteria within the renal-inter-renal tissue of the winter skate Leucoraja ocellata to metabolize steroids and contribute to the synthesis of the novel elasmobranch corticosteroid, 1α-hydroxycorticosterone (1α-OH-B). Despite the rarity of C1 hydroxylation noted in the original identification of 1α-OH-B, literature provides evidence for steroid C1 hydroxylation by micro-organisms. Eight ureolytic bacterial isolates were identified in the renal-inter-renal tissue of L. ocellata, the latter being the site of 1α-OH-B synthesis. From incubations of bacterial isolates with known amounts of potential 1α-OH-B precursors, one isolate UM008 of the genus Rhodococcus was seen to metabolize corticosteroids and produce novel products via HPLC analysis. Cations Zn2+ and Fe3+ altered metabolism of certain steroid precursors, suggesting inhibition of Rhodococcus steroid catabolism. Genome sequencing of UM008 identified strong sequence and structural homology to that of Rhodococcus erythropolis PR4. A complete enzymatic pathway for steroid-ring oxidation as documented within other Actinobacteria was identified within the UM008 genome. This study highlights the potential role of Rhodococcus bacteria in steroid metabolism and proposes a novel alternative pathway for 1α-OH-B synthesis, suggesting a unique form of mutualism between intracellular bacteria and their elasmobranch host.

Global Prevalence of Elder Abuse: A Meta-analysis and Meta-regression.

OBJECTIVE: Elder abuse is increasingly recognised as a global public health and social problem. There has been limited inter-study comparison of the prevalence and risk factors for elder abuse. This study aimed to estimate the pooled and subtype prevalence of elder abuse worldwide and identify significant associated risk factors. METHODS: We conducted a meta-analysis and meta-regression of 34 population-based and 17 non-population-based studies. RESULTS: The pooled prevalences of elder abuse were 10.0% (95% confidence interval, 5.2%-18.6%) and 34.3% (95% confidence interval, 22.9%-47.8%) in population-based studies and third party- or caregiver-reported studies, respectively. Being in a marital relationship was found to be a significant moderator using random-effects model. CONCLUSIONS: This meta-analysis revealed that third parties or caregivers were more likely to report abuse than older abused adults. Subgroup analyses showed that females and those resident in non-western countries were more likely to be abused. Emotional abuse was the most prevalent elder abuse subtype and financial abuse was less commonly reported by third parties or caregivers. Heterogeneity in the prevalence was due to the high proportion of married older adults in the sample. Subgroup analysis showed that cultural factors, subtypes of abuse, and gender also contributed to heterogeneity in the pooled prevalence of elder abuse.

Clonal evolution of colorectal cancer in IBD.

Optimizing the management of colorectal cancer (CRC) risk in IBD requires a fundamental understanding of the evolutionary process underpinning tumorigenesis. In IBD, clonal evolution begins long before the development of overt neoplasia, and is probably accelerated by the repeated cycles of epithelial wounding and repair that are characteristic of the condition. Here, we review the biological drivers of mutant clone selection in IBD with particular reference to the unique histological architecture of the intestinal epithelium coupled with the inflammatory microenvironment in IBD, and the unique mutation patterns seen in IBD-driven neoplasia when compared with sporadic adenomas and CRC. How these data can be leveraged as evolutionary-based biomarkers to predict cancer risk is discussed, as well as how the efficacy of CRC surveillance programmes and the management of dysplasia can be improved. From a research perspective, the longitudinal surveillance of patients with IBD provides an under-exploited opportunity to investigate the biology of the human gastrointestinal tract over space and time.

C9orf72 is required for proper macrophage and microglial function in mice.

Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression of C9orf72 is seen in expansion carriers, suggesting that loss of function may play a role in disease. We found that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease. Instead, C9orf72 null mice developed progressive splenomegaly and lymphadenopathy with accumulation of engorged macrophage-like cells. C9orf72 expression was highest in myeloid cells, and the loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 ALS but not sporadic ALS human patient tissue. Thus, C9orf72 is required for the normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in C9orf72 expansion carriers.

Tumor-induced lymph node alterations detected by MRI lymphography using gadolinium nanoparticles.

Contrast-enhanced MRI lymphography shows potential to identify alterations in lymph drainage through lymph nodes (LNs) in cancer and other diseases. MRI studies have typically used low molecular weight gadolinium contrast agents, however larger gadolinium-loaded nanoparticles possess characteristics that could improve the specificity and sensitivity of lymphography. The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection. Mice bearing B16-F10 melanoma footpad tumors were imaged to assess tumor-induced alterations in lymph drainage through tumor-draining popliteal and inguinal LNs versus contralateral uninvolved drainage. Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective. All of the contrast agents distributed in foci around the cortex and medulla of tumor-draining popliteal LNs, while they were restricted to the cortex of non-draining LNs. Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage. These characteristics of tumor-induced lymph drainage could be useful for diagnosis of LN pathology in cancer and other diseases. The preferential uptake of nanoparticle contrasts into tumor-draining LNs could also allow selective targeting of therapies to tumor-draining LNs.

Childhood intermittent exotropia from a different angle: does severity affect quality of life?

BACKGROUND: Few studies have explored the relationship between health-related quality of life (HRQOL) and clinical severity of childhood intermittent exotropia (IXT) measured by angle of deviation, control and stereoacuity. METHODS: Sixty-eight consecutive children aged 5-17 years with childhood IXT who attended the paediatric eye clinic were recruited. One accompanying parent was recruited concurrently. Child, parent and proxy (parent about the child) HRQOL was measured using the IXT questionnaire (IXTQ). Angle of deviation, control and stereoacuity of the children were measured and correlated with IXTQ scores using Spearman's correlation coefficient and paired t test for differences in child and proxy IXTQ mean scores. RESULTS: The mean age of the children was 9.0±2.6 years. Child HRQOL was not correlated to any strabismus measurements. Poorer parent HRQOL was correlated with poorer distance control (surgery subscale, r=-0.24 p=0.049), poorer near control (surgery subscale, r=-0.30, p=0.013), poorer office near control (mean, r=-0.24, p=0.047; psychological subscale, r=-0.27, p=0.025; surgery subscale, r=-0.28, p=0.020) and larger angle of deviation (psychological subscale, r=-0.30, p=0.013). Poorer proxy HRQOL was correlated with poorer home control (r=-0.28, p=0.022) and larger angle of deviation (r=0.33, p=0.0061). CONCLUSIONS: It is difficult to predict child HRQOL based on clinical measurements. However, parent HRQOL tends to be worse with poorer control and larger angle of deviation. Perhaps HRQOL should be routinely assessed in clinic alongside clinical measurements in order to tailor management appropriately.

Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70-90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.