Sub-bandgap photoluminescence properties of multilayer h-BN-on-sapphire.

Two-dimensional hexagonal boron nitride (h-BN) materials have garnered increasing attention due to its ability of hosting intrinsic quantum point defects. This paper presents a photoluminescence (PL) mapping study related to sub-bandgap-level emission in bulk-like multilayer h-BN films. Spatial PL intensity distributions were carefully analyzed with 500 nm spatial resolution in terms of zero phonon line (ZPL) and phonon sideband (PSB) emission-peaks and their linewidths, thereby identifying the potential quantum point defects within the films. Two types of ZPL and PSB emissions were confirmed from the point defects located at the non-edge and edge of the films. Our statistical PL data from the non-edge- and edge-areas of the sample consistently reveal broad and narrow emissions, respectively. The measured optical properties of these defects and the associated ZPL peak shift and line broadening as a function of temperature between 77° and 300° K are qualitatively and quantitatively explained. Moreover, an enhancement of the photostable PL emission by at least a factor of ×3 is observed when our pristine h-BN was irradiated with a 532 nm laser.

An acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation.

Internalization of macromolecules and membrane into cells through endocytosis is critical for cellular growth, signaling and plasma membrane (PM) tension homeostasis. Although endocytosis is responsive to both biochemical and physical stimuli, how physical cues modulate endocytic pathways is less understood. Contrary to the accumulating discoveries on the effects of increased PM tension on endocytosis, less is known about how a decrease of PM tension impacts on membrane trafficking. Here, we reveal that an acute decrease of PM tension results in phosphatidic acid (PA) production, F-actin and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2]-enriched dorsal membrane ruffling and subsequent macropinocytosis in myoblasts. The PA production induced by decreased PM tension depends on phospholipase D2 (PLD2) activation via PLD2 nanodomain disintegration. Furthermore, the 'decreased PM tension-PLD2-macropinocytosis' pathway is prominent in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway that converts an acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P2-mediated processes.

Lipid biomarkers and Cancer risk - a population-based prospective cohort study in Taiwan.

BACKGROUND: Blood lipids are essential components for cellular growth. An inverse association between serum lipid levels and risk of cancer has led to a controversy among previous studies. The aim of this prospective cohort study was to investigate the association between blood lipids change and risk of cancer incidence. METHODS: A cohort of 4130 Taiwanese adults from the Taiwanese Survey on the Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia database underwent repeated examinations in 2002 and 2007. Six groups were established based on the combined baseline (lower/higher) and interval change (decreasing/stable/increasing) in plasma lipid levels. Multivariable Cox proportional hazard model was used to investigate the relationship between lipids change and all-cause cancer incidence. RESULTS: Two hundred and forty cancer events developed over a median follow-up of 13.4 years. Comparing these with individuals with decreasing lower-baseline lipid levels, cancer risk reduction was demonstrated in those with increasing lower-baseline total cholesterol (adjusted hazard ratio [aHR], 0.48; 95% confidence interval [CI], 0.27 to 0.85), low-density lipoprotein cholesterol (LDL-C; aHR, 0.56; 95% CI, 0.35 to 0.92), and non-high-density lipoprotein cholesterol (non-HDL-C) (aHR, 0.54; 95% CI, 0.31 to 0.92) levels. A decreased risk for cancer incidence also presented in participants with stable lower-baseline, decreasing and increasing higher-baseline LDL-C levels, and with decreasing and stable higher-baseline non-HDL-C levels. CONCLUSIONS: The interval decline in lower-baseline total cholesterol, LDL-C, and non-HDL-C levels was linked to a higher risk for all-cause cancer incidence. More attention to a potential cancer risk may be warranted for an unexplained fall in serum lipids.

Trend analysis of palliative care consultation service for terminally ill non-cancer patients in Taiwan: a 9-year observational study.

BACKGROUNDS: Early integration of palliative care for terminally ill non-cancer patients improves quality of life. However, there are scanty data on Palliative Care Consultation Service (PCCS) among non-cancer patients. METHODS: In this 9-year observational study Data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill non-cancer patients with 9 categories of diagnoses who received PCCS during 2011 to 2019 were enrolled. Trend analysis was performed to evaluate differences in categories of diagnosis throughout study period, duration of PCCS, patient outcomes, DNR declaration, awareness of disease by patients and families before and after PCCS. RESULTS: In total, 536 non-cancer patients received PCCS from 2011 to 2019 with an average age of 70.7 years. The average duration of PCCS was 18.4 days. The distributions of age, gender, patient outcomes, family's awareness of disease before PCCS, and patient's awareness of disease after PCCS were significantly different among the diagnoses. Organic brain disease and Chronic kidney disease (CKD) were the most prevalent diagnoses in patients receiving PCCS in 2019. For DNR declaration, the percentage of patients signing DNR before PCCS remained high throughout the study period (92.8% in 2019). Patient outcomes varied according to the disease diagnoses. CONCLUSION: This 9-year observational study showed that the trend of PCCS among non-cancer patients had changed over the duration of the study. An increasing number of terminally ill non-cancer patients received PCCS during late life, thereby increasing the awareness of disease for both patients and families, which would tend to better prepare terminally ill patients for end-of-life as they may consider DNR consent. Early integration of PCCS into ordinary care for terminally non-cancer patients is essential for better quality of life.

Therapeutic implications of circadian clocks in neurodegenerative diseases.

Circadian clocks, endogenous oscillators generating daily biological rhythms, have important roles in the nervous system to control diverse cellular processes-not only in the suprachiasmatic nucleus (SCN), where the master clocks reside to synchronize all circadian clocks in the body but also in other non-SCN areas. Accumulating evidence has shown relationships between circadian abnormalities (e.g., sleep disturbances and abnormal rest-activity rhythms) and disease progressions in various neurodegenerative diseases, including Alzheimer's (AD) and Parkinson's (PD) disease. Although circadian abnormalities were frequently considered as consequences of disease onsets, recent studies suggest altered circadian clocks as risk factors to develop neurodegenerative diseases via altered production or clearance rates of toxic metabolites like amyloid ß. In this review, we will summarize circadian clock-related pathologies in the most common neurodegenerative diseases in the central nervous system, AD and PD. Then, we will introduce the current clinical trials to rescue circadian abnormalities in AD and PD patients. Finally, a discussion about how to improve targeting circadian clocks to increase treatment efficiencies and specificities will be followed. This discussion will provide insight into circadian clocks as potential therapeutic targets to attenuate onsets and progressions of neurodegenerative diseases.

Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases.

With the advances in deep sequencing-based transcriptome profiling technology, it is now known that human genome is transcribed more pervasively than previously thought. Up to 90% of the human DNA is transcribed, and a large proportion of the human genome is transcribed as long noncoding RNAs (lncRNAs), a heterogenous group of non-coding transcripts longer than 200 nucleotides. Emerging evidence suggests that lncRNAs are functional and contribute to the complex regulatory networks involved in cardiovascular development and diseases. In this article, we will review recent evidence on the roles of lncRNAs in the biological processes of cardiovascular development and disorders. The potential applications of lncRNAs as biomarkers and targets for therapeutics are also discussed.

Factors associated with hospitalization for community-acquired pneumonia in home health care patients in Taiwan.

BACKGROUND: Pneumonia is a leading cause of hospitalization and death worldwide. However, studies focusing on risk factors of community-acquired pneumonia (CAP) in the home health care (HHC) population remain scarce. AIMS: This study aimed to evaluate risk factors associated with hospitalization for CAP among HHC patients in Taiwan. METHODS: This retrospective cross-sectional study extracted data from patients' electronic medical records between 1 January 2017 and 31 December 2017. Multiple logistic regression analyses were performed to explore factors associated with hospitalization for CAP. RESULTS: In total, 598 patients (men/women: 236/362) were included. One hundred ninety-nine patients (33.28%) were hospitalized for pneumonia. Inpatients showed a higher proportion of the following: male sex, functional impairment, hypoalbuminemia, anemia, nasogastric tube use, excessive polypharmacy, stroke, dementia, heart failure, chronic respiratory disease, and chronic liver disease. Furthermore, nasogastric tube use (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.88-4.82), anemia (OR 2.37, 95% CI 1.48-3.80), male sex (OR 2.14, 95% CI 1.43-3.20), chronic respiratory disease (OR 2.09, 95% CI 1.33-3.30), dementia (OR 1.94, 95% CI 1.27-2.97), heart failure (OR 1.69, 95% CI 1.11-2.56), and hypoalbuminemia (OR 1.57, 95% CI 1.03-2.40) significantly increased the risk of hospitalization for CAP. CONCLUSIONS: Our results revealed risk factors associated with hospitalization for CAP in HHC patients. In addition to chronic diseases, malnutrition is an important risk factor. Caregivers should make prompt assessments and take preventive measures for such patients.

IgG4-Related Disease Presenting as Cervical Lymphadenopathy.

Cervical lymph node enlargement as the first and sole manifestation of IgG4-related disease (IgG4-RD) is rare and is often difficult to distinguish from lymphoma. Here, we report a case of a 63-year-old man initially presenting with bilateral posterior neck masses. Ultrasonography revealed multiple matted, ovoid, homogenous, hypoechoic, and enlarged lymph nodes below the right parotid gland. In addition, there was heterogeneous echotexture with small and indistinct hypoechoic nodules over bilateral parotid and submandibular glands which suggested sclerosing sialadenitis. Pathology of the tissues obtained by core needle biopsy revealed reactive hyperplasia, but a diagnosis of lymphoma could not be excluded. Subsequently, excisional biopsy and serological tests were done. The diagnosis of IgG4-RD was confirmed due to marked elevation of serum IgG4 levels and pathological evidence of IgG+ and IgG4+ plasma cell infiltration in the lymph node specimen. The patient's neck masses subsided gradually after 1 week of oral steroid therapy. The differential diagnosis of IgG4-RD should always be considered when sclerosing sialadenitis is presented with cervical lymphadenopathy.

Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

PURPOSE: To assess the clinical roles of [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. METHODS: Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. RESULTS: PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001). CONCLUSIONS: Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.

Target disruption of ribosomal protein pNO40 accelerates aging and impairs osteogenic differentiation of mesenchymal stem cells.

pNO40/PS1D, a novel nucleolar protein, has been characterized as a core protein of eukaryotic 60S ribosome and at least two splicing forms of pNO40 mRNAs with alternative starting sites have been identified. Through production of knockout (ko) mice with either exon 2 (△E2), exon 4 (△E4) or △E2+E4 targeted disruption we identified a cryptic splicing product occurring in the ko tissues examined which in general cannot be observed in regular RT-PCR detection of wild-type (wt) animals. Among ko animals, △E4 null embryos exhibited prominent senescence-associated ß-galactosidase (SA-ß-gal) staining, a marker for senescent cells, in notochord, forelimbs and heart while bone marrow-derived mesenchymal stem cells (MSCs) from △E4 null mice developed accelerated aging and osteogenic differentiation defects compared to those from wt and other isoform mutant mice. Examination of the causal relationship between pNO40 deficiency and MSC-accelerated aging revealed △E4 null disruption in MSCs elicits high levels of ROS and elevated expression levels of p16 and Rb but not p53. Further analysis with iTraq identified CYP1B1, a component of the cytochrome p450 system, as a potential molecule mediating ROS generation in pNO40 deficient MSCs. We herein established a mouse model of MSC aging through pNO40-targeted depletion and demonstrated the effects of loss of pNO40 on bone homeostasis.

Utility of (18)F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy: a parallel study of a prospective randomized trial.

PURPOSE: The aim of this prospective study was to assess the usefulness of (18)F-FDG PET/CT performed before and during treatment for predicting treatment failure in patients with advanced squamous cell carcinoma of the uterine cervix treated with concurrent chemoradiotherapy (CCRT). METHODS: Patients with cervical squamous cell carcinoma, International Federation of Gynecology and Obstetrics stage III/IVA or positive pelvic or paraaortic lymph node (LN) metastasis without other distant metastasis on PET/CT entering a randomized trial of CCRT (AGOG 09-001) were eligible. PET/CT scans were performed at baseline, during week 3 of CCRT and 2 - 3 months after CCRT. PET/CT parameters were correlated with sites of failure and overall survival (OS). The resulting predictors developed from the study cohort were validated on two independent datasets using area under the curve values, sensitivities and specificities. RESULTS: With a median follow-up of 54 months for survivors, 20 (36 %) of the 55 eligible patients were proven to have treatment failure. Sites of failure were local in five, regional in 11, and distant in 11. Four predictors for local failure, three for regional failure, and four for distant failures were identified. After validation with two independent cohorts of 31 and 105 patients, we consider the following as clinically useful predictors: pretreatment metabolic tumour volume (MTV) and during-treatment cervical tumour MTV for local failure; during-treatment SUVnode (maximum standardized uptake value of LNs) for regional and distant failure, and during-treatment MTV for distant failure. During-treatment SUVnode (P = .001) and cervical tumour MTVratio (P = .004) were independent significant predictors of OS by stepwise Cox regression. CONCLUSION: PET/CT imaging before and during treatment is useful for predicting failure sites and OS, making tailored therapeutic modifications feasible with potential outcome improvement during primary therapy.

Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133-A Report From the Children's Oncology Group Bone Tumor Committee.

BACKGROUND: The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery. METHODS: Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan-Meier methodology. RESULTS: Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1). CONCLUSION: We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.

Levels of depressive symptoms may modify the relationship between the WHOQOL-BREF and its determining factors in community-dwelling older adults.

BACKGROUND: Depression is closely associated with quality of life (QOL) in older adults. Being elderly and exhibiting mild depressive symptoms may not lead to a depression diagnosis, but these attributes are clinically important. However, the extent to which these factors influence QOL and its determinants in older adults remains unclear. METHODS: Questionnaires were administered to people aged 65 years or older at community senior centers in Taiwan to collect socio-demographic information and to assess results from the brief version of the World Health Organization's Quality of Life instrument (WHOQOL-BREF), Modified Barthel Index (MBI), 15-item Geriatric Depression Scale (GDS), and Mini-Mental State Examination (MMSE). Levels of depressive symptoms were classified as no depressive symptoms (NDS), lower level of depressive symptoms (LLDS), and higher level of depressive symptoms (HLDS), corresponding to GDS = 0, 1≦GDS≦5, and GDS>5, respectively. Multiple linear regression analyses were conducted to assess associations between the WHOQOL-BREF and its covariates for different levels of depressive symptoms. RESULTS: A total of 454 older adults participated. The GDS and MBI scores significantly affected the WHOQOL-BREF physical and psychological domain scores in the LLDS group. Gender influenced the WHOQOL-BREF scores in the NDS group, and increased age demonstrated protective effects on the three domains in the HLDS group. Moreover, the association between the WHOQOL-BREF and its covariates varied for different levels of depressive symptoms. CONCLUSIONS: Treatment for depressive symptoms is of high priority, and early recognition of and appropriate intervention for mild depressive symptoms may improve community-dwelling older adults' QOLs.

High or low calcium intake increases cardiovascular disease risks in older patients with type 2 diabetes.

BACKGROUND: We investigated the effects of dietary calcium (Ca) and magnesium (Mg) intakes on cardiovascular disease risks in older patients with diabetes. METHODS: In this cross-sectional study, 197 patients with type 2 diabetes aged 65 years and above were recruited. The 24-h dietary recalls and 1-week self-reported typical dietary intake patterns were collected. The Ca and Mg intakes of <67% of the recommended dietary allowance (RDA), 67%-100% of RDA, and >100% of RDA were defined as low, moderate, and high Ca and Mg intakes, respectively. Anthropometric measurements were determined and biochemical analysis of blood and urine was performed. RESULTS: Our data indicated that 60.9% and 87.3% of our patients were Ca and Mg intakes below RDA, respectively. Patients whose Ca intake was high or low (81.2%) had significantly higher C-reactive protein (CRP) than those whose Ca intake was moderate (p = 0.043). Furthermore, patients whose Mg intake was low (87.3%) had significantly higher CRP than that of those who took adequate Mg (p = 0.025). The dietary Ca:Mg intake ratios were highly correlated with CRP, platelet counts, and red blood cell distribution (p < 0.05). A dietary Ca:Mg intake ratio of 2.0-2.5 was significantly correlated to lower CRP levels (p = 0.013). CONCLUSIONS: High or low calcium intake increases cardiovascular disease risks. We suggest that "moderate" intake of 402-600 mg Ca/day (approximately 67%-100% of Taiwan RDA for Ca) and adequate Mg intake (or meeting RDA for Mg) with Ca:Mg intake ratio of 2.0-2.5 are important for reducing cardiovascular disease risks in older patients with diabetes.

Protein binding reaction enhanced by bi-directional flow driven by on-chip thermopneumatic actuator.

A microfluidic immunoassay system was developed for the study of the enhancement of protein binding reaction. The system mainly consisted of a thermopneumatic actuator and a reaction chamber. Reagent was pre-installed in the on-chip reservoir and manipulated by the actuator. Such design could eliminate the external tubing connections in order to reduce the waste of reagent and improve the portability. The on-chip actuator could manipulate the reagent bi-directionally to induce vortexes in the chamber. Enhancement of protein binding reaction was demonstrated by the protein model pair, i.e., mouse IgG and anti-mouse IgG. By such bi-directional fluid motion, more binding opportunities between suspended protein and its surface-immobilized counterpart were generated to improve the performance of immunoassay. It showed that an 83.74 % enhancement of the binding reaction was achieved, compared with the static situation. As a whole, the proposed microfluidic system is highly integrated and can enhance the protein binding efficiency using such novel design. The developed system can be easily extended to multi-reagents immunoassay protocols and provides a useful platform for point-of-care applications.

Dose-Escalated Radiation Therapy as Primary Treatment for Residual Bladder Cancer After Transurethral Resection.

Purpose: The aim of this study was to determine whether escalating the local radiation dose can improve the outcome of residual bladder cancer after transurethral resection of bladder tumor without increasing treatment-related toxicity. Methods and Materials: The treatment plans and medical records of patients with bladder cancer treated with curative-intent radiation therapy between 2008 and 2020 were reviewed. Those who had residual tumors in the computed tomography simulation images were included. A cumulative radiation dose higher than 6600 cGy was defined as dose escalation. The effect of dose escalation on 3-year locoregional control, progression-free survival, and overall survival was evaluated. Results: A total of 149 patients with residual tumors were identified. The median follow-up period was 27.5 months. Among them, 51 patients received an escalated radiation dose, and 98 received a standard dose in the residual tumor area. Patients in the dose-escalation group had higher 3-year locoregional control (65.6% vs 27.8%; P < .001) and progression-free survival (42.6% vs 18.2%; P < .001) than the standard-dose group. Overall survival also showed a trend favoring the dose-escalation group (54.9% vs 36.2%; P = .059). In the multivariate analyses, the differences between the dose-escalation and standard-dose groups were significant in terms of locoregional control (hazard ratio, 0.32; CI, 0.18-0.59; P = <.001) and progression-free survival (hazard ratio, 0.51; CI, 0.32-0.82; P = .005). There was no statistical difference in acute and chronic treatment-related toxicities between the 2 groups. Conclusions: The outcome of residual bladder cancer after transurethral resection of bladder tumor could be improved by dose-escalated radiation therapy.

Desmethylclomipramine triggers mitochondrial damage and death in TGF-ß-induced mesenchymal type of A549 cells.

Lung cancer is the leading cause of cancer deaths, where the metastasis often causes chemodrug resistance and leads to recurrence after treatment. Desmethylclomipramine (DCMI), a bioactive metabolite of clomipramine, shows the therapeutic efficacy with antidepressive agency as well as potential cytostatic effects on lung cancer cells. Here, we demonstrated that DCMI effectively caused transforming growth factor (TGF)-ß1-mediated mesenchymal type of A549 cells to undergo mitochondrial death via myeloid cell leukemia-1 (Mcl-1) suppression and activation of truncated Bid (tBid). TGF-ß1 induced epithelial mesenchymal transition in A549 cells with the increase of fibronectin and decrease of E-cadherin, the activation of Akt/glycogen synthase kinase-3ß (GSK-ß)/Mcl-1 axis, and the hypo-responsiveness to cisplatin. DCMI initiated a dose-dependent cytotoxicity on TGF-ß1-mediated mesenchymal type of A549 cells through inactivating Akt/GSK-ß/Mcl-1 axis, in which mitochondria instability and caspase-9/3 activation also occurred concurrently. Pharmacological inhibition of caspase-8 and cathepsin B partly reversed tBid expression and mitochondrial damage to further attenuate DCMI-mediated cytotoxicity. Additionally, DCMI presented partial therapeutic effects in treating mesenchymal type of A549 tumor bearing nude mice through an acceleration of cancer cell death. Taken together, DCMI exerts antitumor effects via initiating the mechanisms of Akt/GSK-ß/Mcl-1 inactivation and cathepsin B/caspase-8-regulated mitochondrial death, which suggests its potential role in mesenchymal type of cancer cell therapy.

Centrosomal protein 55 (Cep55) stability is negatively regulated by p53 protein through Polo-like kinase 1 (Plk1).

Centrosomal protein 55 (Cep55), which is localized to the centrosome in interphase cells and recruited to the midbody during cytokinesis, is a regulator required for the completion of cell abscission. Up-regulation of Cep55 and inactivation of p53 occur in the majority of human cancers, raising the possibility of a link between these two genes. In this study we evaluated the role of p53 in Cep55 regulation. We demonstrated that Cep55 expression levels are well correlated with cancer cell growth rate and that p53 is able to negatively regulate Cep55 protein and promoter activity. Down-regulation of expression of Cep55 was accompanied by repression of polo-like kinase 1 (Plk1) levels due to p53 induction. Overexpression of Plk1 and knockdown of p53 expression both enhanced the post-translational protein stability of Cep55. BI 2356, a selective Plk1 inhibitor, however, prevented Cep55 accumulation in p53 knockdown cells while persistently keeping Plk1 levels elevated. Our results, therefore, indicate the existence of a p53-Plk1-Cep55 axis in which p53 negatively regulates expression of Cep55, through Plk1 which, in turn, is a positive regulator of Cep55 protein stability.