Downregulation of Polo-like kinase-1 (PLK-1) expression is associated with poor clinical outcome in uveal melanoma patient

Introduction. Uveal melanoma (UM) is the most common primary eye tumour in adults. Distant metastases are seen in 50% of cases regardless of treatment, which contributes to high mortality rates. Polo-like kinase-1 (PLK-1) is a protein regulator of mitotic entry and cytokinesis. Increased PLK-1 expression has been shown in different tumours, which makes its inhibition a potential treatment target. To date, no study has been published to discuss the prognostic role of PLK-1 expression in patients with uveal melanoma. Material and methods. We assessed by immunohistochemistry PLK-1 expression in uveal melanoma cells collected in 158 patients treated by primary enucleation. We determined the correlation between PLK-1 levels evaluated by the immunoreactivity scale (IRS) method and detailed clinical as well as histological parameters. Additionally, we determined the association between PLK-1 expression levels and long-term prognosis. Results. Elevated PLK-1 expression in tumour cells, defined as IRS > 2, was observed in 70% (111/158) of cases, whereas low expression or no expression was seen in the remaining 30% (47/158) of patients. There was a significant correlation between low PLK-1 expression and a higher clinical tumour stage (pT, p = 0.04) as well as a higher AJCC prognostic stage group (p = 0.037). We observed an inverse correlation between PLK-1 expression and tumour cell pigment content (p = 0.0019). There was no correlation between PLK-1 expression and other histological parameters such as mitotic rate or histological subtype. The Kaplan-Meier’s analysis demonstrated that low PLK-1 expression was associated with significantly reduced overall survival (p = 0.0058). A similar trend, albeit not significant, was observed for disease-free survival (p = 0.088). Conclusions. Downregulated PLK-1 expression is a negative prognostic factor in uveal melanoma. It warrants further, multicentre research on prognostic role of PLK-1 expression and possibility of PLK-1 inhibition in uveal melanoma

The Leg-Tuck versus the Plank-Hold Relative to the Army Combat Fitness Test: Interactions with Body Composition, Strength and Sex.

In 2020 the U.S. Army replaced their older physical fitness test with the Army Combat Fitness Test (ACFT) to replicate modern battlefield demands. One component of the test, the leg-tuck (LTK) was found to disproportionately fail female soldiers. Following an independent review, the Army adopted the plank-hold (PLK), attempting to limit the influence of sex differences during the assessment. However, research regarding performance, relationships, and the influence of sex on the LTK versus the PLK is limited. PURPOSE: To determine relationships between the LTK, PLK, sex, body composition and abdominal and grip strength. METHODS: 49 physically active civilian college students (28 males, 21 females) were recruited as a surrogate population for Army personnel in this study. The following data were collected in one session: height; body mass (BM), body fat (BF%) and muscle mass percentage (MM%) measured via bioelectrical impedance analysis; combined grip strength (CGS) from both hands; the LTK; and the PLK. ACFT standards were utilized for the LTK and PLK for all participants and a 10-minute rest was provided between tests. Independent t-tests compared sexes in all variables (p\u3c.05). Partial correlations controlling for sex detailed relationships between the LTK and PLK and the other variables (p\u3c.05). Stepwise regression controlling for sex derived predictive relationships for the LTK and PLK. RESULTS: There were significant between-sex differences with males being taller, having greater BM, MM%, and performing better in CGS and the LTK. Females had greater BF%. There was no significant between-sex difference found in PLK performance. The LTK significantly correlated with PLK (r=.404), height (r=.546), BM (r=.343), BF% (r=-.639), MM% (r=.697) and CGS (r=.732). In addition to the relationship with the LTK, the PLK only correlated with BF% (r=-.295). Stepwise regression analysis showed LTK performance was predicted by sex (r2=.441), grip strength (r2=.595), and PLK performance (r2=.662). When controlling for sex, a significant predictive relationship was not produced for the PLK. CONCLUSION: Compared to the LTK, the PLK appeared to minimize the influence of sex and body composition on task performance in college-aged civilians. More research is needed on whether the PLK relates to Army job tasks

Aurora-A and Polo-Like Kinases are Important Diagnostic and Therapeutic Markers in Hodgkin Lymphoma and Mimics

Background: Aurora-A (AA) and Polo-like kinases (PLK) are mitotic kinases that regulate the G2/M phase of the cell cycle. It has been demonstrated that AA acts as an upstream regulator of PLK, mediating its phosphorylation in the presence of a cofactor named Bora. PLK is activated by AA to promote checkpoint recovery in mitosis. AA and PLK are implicated in the tumorigenesis of solid tumors, and, recently, in B- and T-cell non Hodgkin lymphomas (NHL). They play a key role in tumor proliferation and disease progression in highly aggressive B-cell NHL. They also serve as indicators of disease activity and are thus attractive potential therapeutic targets. Expression of AA and/or PLK has not yet been assessed in Classic Hodgkin Lymphoma (CHL) and its mimics. This study assesses AA and PLK expression in different CHL types, such as nodular sclerosis type, mixed cellularity type, and lymphocyte rich type, and their mimics: nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal B-cell lymphoma (PMBL).Design:We assessed 27 CHL cases, 16 NLPHL cases, and 8 PMBL cases for AA and PLK expression by immunohistochemistry. CHL cases included the following: 8 mixed cellularity CHL, 1 lymphocyte rich CHL, and 18 nodular sclerosis CHL. A mouse monoclonal AA-antibody (1:1000 dilution, Abcam, UK) and a PLK-antibody (1:500 dilution, Cell Signaling Technologies, USA) were used. Each case was semi-quantitatively graded for percentage of positive cells (\u3c50% vs. \u3e50%), for staining intensity (1-3+), and for localization (nuclear vs. cytoplasmic). Immunohistochemical analysis was performed independently by 2 pathologists (KMH and KVI). Statistical analysis was performed using Fisher\u27s exact test.Results:AA was expressed in 100% of CHL and NLPHL cases. AA stained predominantly cytoplasm of tumor cells in both NLPHL and CHL. PLK was expressed in 100% of NLPHL and 96% of CHL cases (1 mixed cellularity type CHL did not stain for PLK). PLK showed both nuclear and cytoplasmic staining for both NLPHL and CHL. In contrast, only 37% of PMBL cases were positive for AA and PLK (Table 1). In the CHL group, cases with more than 50% of tumor cells expressing PLK tended to present with higher stage and extranodal disease. In the NLPHL group, PLK correlated with higher stage (III-IV) disease at presentation (p=0.044). No statistically significant differences were found in either intensity or localization of AA or PLK within or between NLPHL and CHL cohorts.Aurora-A PositiveAurora-A NegativePLK PositivePLK NegativeClassic Hodgkin Lymphoma270261Nodular Lymphocyte Predominant Hodgkin Lymphoma160160Primary Mediastinal B-cell Lymphoma3535Table 1. AA and PLK positivity in CHL, NLPHL, and PMBL.AA was expressed in CHL but not PMBL (p=0.0002)PLK was expressed in CHL but not PMBL (p=0.0009)AA was expressed in NLPHL but not PMBL (p=0.0013)PLK was expressed in NLPHL but not PMBL (p=0.0013). Conclusion: AA and PLK are commonly expressed in CHL and NLPHL but not in PMBL. Thus, they are useful markers in the distinction of CHL or NLPHL from PMBL. PLK is a useful marker for the prognostication of NLPHL. AA and PLK are attractive potential therapeutic targets in the treatment of CHL and NLPHL. Additional studies are underway to characterize an array of hematopoietic lesions known to overlap with CHL.https://scholarlycommons.henryford.com/merf2019clinres/1027/thumbnail.jp

BUB-1 and CENP-C recruit PLK-1 to control chromosome alignment and segregation during meiosis I in C. elegans oocytes

Phosphorylation is a key post-translational modification that is utilised in many biological processes for the rapid and reversible regulation of protein localisation and activity. Polo-like kinase 1 (PLK-1) is essential for both mitotic and meiotic cell divisions, with key functions being conserved in eukaryotes. The roles and regulation of PLK-1 during mitosis have been well characterised. However, the discrete roles and regulation of PLK-1 during meiosis have remained obscure. Here, we used Caenorhabditis elegans (C. elegans) oocytes to show that PLK-1 plays distinct roles in meiotic spindle assembly and/or stability, chromosome alignment and segregation, and polar body extrusion during meiosis I. Furthermore, by a combination of live imaging and biochemical analysis we identified the chromosomal recruitment mechanisms of PLK-1 during C. elegans oocyte meiosis. The spindle assembly checkpoint kinase BUB-1 directly recruits PLK-1 to the kinetochore and midbivalent while the chromosome arm population of PLK-1 depends on a direct interaction with the centromeric-associated protein CENP-CHCP-4. We found that perturbing both BUB-1 and CENP-CHCP-4 recruitment of PLK-1 leads to severe meiotic defects, resulting in highly aneuploid oocytes. Overall, our results shed light on the roles played by PLK-1 during oocyte meiosis and provide a mechanistic understanding of PLK-1 targeting to meiotic chromosomes.</p

A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro.

Although novel agents effective against malignant mesothelioma (MM) have been developed, the prognosis of patients with MM is still poor. We generated a DNA-chimeric siRNA against polo-like kinase-1 (PLK-1), which was more stable in human serum than the non-chimeric siRNA. The chimeric PLK-1 siRNA inhibited MM cell proliferation through the induction of apoptosis. Next, we investigated the effects of zoledronic acid (ZOL) on MM cells, and found that ZOL also induced apoptosis in MM cells. Furthermore, ZOL augmented the inhibitory effects of the PLK-1 siRNA. In conclusion, combining a PLK-1 siRNA with ZOL treatment is an attractive strategy against MM

The expression of PLK-1 in cervical carcinoma: a possible target for enhancing chemosensitivity

<p>Abstract</p> <p>Background</p> <p>Polo-like kinase-1 (PLK-1) is reported to be upregulated in a variety of human tumors and is implicated in cell proliferation and survival. However, its importance in cervical carcinoma has not yet been fully elucidated.</p> <p>Methods</p> <p>We examined PLK-1 expression in cervical carcinoma tissues using immunohistochemical staining. Furthermore, we blocked PLK-1 expression in HeLa cells using specific siRNA and detected the cell cycle, cell proliferation and chemosensitivity using western blotting, MTT and flow cytometry.</p> <p>Results</p> <p>We provide evidence that expression of PLK-1 exists in human cervical carcinoma tissues and establish an association with tumor size. Furthermore, we show that PLK-1 knockdown by transfection of siRNA induces accumulation of HeLa cells in the G2/M cell cycle phase and enhances cisplatin-induced apoptosis.</p> <p>Conclusion</p> <p>Our results indicate that PLK-1 production in HeLa cells might be critical in determining whether cells survive or undergo apoptosis. Therefore, targeting PLK-1 might be a promising strategy for enhancing sensitivity to chemotherapeutic reagents in cervical carcinoma.</p

The RR Lyrae Period - K Luminosity relation for Globular Clusters: an observational approach

The Period - metallicity - K band luminosity (PLK) relation for RR Lyrae stars in 15 Galactic globular clusters and in the LMC globular cluster Reticulum has been derived. It is based on accurate near infrared (K) photometry combined with 2MASS and other literature data. The PLK relation has been calibrated and compared with the previous empirical and theoretical determinations in literature. The zero point of the absolute calibration has been obtained from the K magnitude of RR Lyr whose distance modulus has been measured via trigonometric parallax with HST. Using this relation we obtain a distance modulus to the LMC of (m-M)_0 = 18.54 \pm 0.15 mag, in good agreement with recent determinations based on the analysis of Cepheid variable stars.Comment: 6 pages, 4 figures, accepted for publication by MNRA

The homology of spaces of polynomials with roots of bounded multiplicity

Let P_{k, n}^l be the space consisting of monic complex polynomials f(z) of degree k and such that the number of n-fold roots of f(z) is at most l. In this paper, we determine the integral homology groups of P_{k, n}^l.Comment: This is the version published by Geometry & Topology Monographs on 25 February 200