The balance of Polo-like kinase 1 in tumorigenesis

Polo-like kinase 1 (Plk1) belongs to a family of conserved serine/threonine kinases with a polo-box domain, which have similar but non-overlapping functions in the cell cycle progression. Plk1 plays a key role to ensure the normal mitosis. Interestingly, overexpression of Plk1 is associated with tumor development and could serve as a prognostic marker for many cancers. Due to Plk1 overexpression, several Plk1 inhibitors have been developed and tested for the cancer treatment. However, in a recent study, it has been suggested that down-regulation of Plk1 could also induce aneuploidy and tumor formation in vivo. Therefore, a normal level of Plk1 is important for mitosis. And caution should be taken when Plk1 inhibitors are used in the clinical trial and their side effects including tumorigenesis should be carefully evaluated

Latent analysis of unmodified biomolecules and their complexes in solution with attomole detection sensitivity

The study of biomolecular interactions is central to an understanding of function, malfunction and therapeutic modulation of biological systems, yet often involves a compromise between sensitivity and accuracy. Many conventional analytical steps and the procedures required to facilitate sensitive detection, such as the incorporation of chemical labels, are prone to perturb the complexes under observation. Here we present a 'latent' analysis approach that uses chemical and microfluidic tools to reveal, through highly sensitive detection of a labelled system, the behaviour of the physiologically relevant unlabelled system. We implement this strategy in a native microfluidic diffusional sizing platform, allowing us to achieve detection sensitivity at the attomole level, determine the hydrodynamic radii of biomolecules that vary by over three orders of magnitude in molecular weight, and study heterogeneous mixtures. We illustrate these key advantages by characterizing a complex of an antibody domain in the solution phase and under physiologically relevant conditions.We would like to thank the ERC, BBSRC, Wellcome Trust, Newman Foundation, Winston Churchill Foundation, and Elan Pharmaceuticals for financial support. E.D.G was supported by the MRC (G1002272)

Early-stage cervical cancer: agreement between ultrasound and histopathological findings with regard to tumor size and extent of local disease

Objectives To determine the agreement between ultrasound and histological examination of the cervix in patients with early stage cervical cancer with regard to tumor size and local extent of the disease. Methods Eighteen patients with histologically proven cervical cancer Stage IB1-IIA according to traditional clinical staging (FIGO 1988) who were scheduled for radical surgery underwent a standardized transvaginal ultrasound examination. The maximum tumor length, anteroposterior tumor diameter, tumor width, tumor area, depth of cervical stroma invasion, and the minimal thickness of tumor-free cervical stroma on sagittal and transverse planes through the cervix were measured, and the local extent of the disease within the parametria and vagina were evaluated. The surgical specimens were examined using a specifically devised method of histopathological examination. The results of the ultrasound and histopathological examinations were compared. Results Limits of agreement were wide and the intra-class correlation coefficient (ICC) was low (0.51-0.58) for three of the four measurements taken to represent the minimal depth of tumor-free cervical stroma, i.e. the results of the measurements taken posteriorly and laterally. However, the limits of agreement were narrower and the ICC values were higher (0.74-0.92) for the depth of cervical stroma invasion and for the tumor size measurements. Histological examination revealed parametrial cancer infiltration in four patients, which was detected during ultrasound examination, with no false-positive results. Conclusions Transvaginal sonography is acceptably accurate for evaluation of tumor size and depth of cervical stroma invasion in clinical practice. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd

Correlation of sonographic characteristics and pathomorphological findings in cases of early-stage cervical cancer: preliminary results.

Objectives: To correlate the sonographic two-dimensional (2D) gray-scale features with pathological findings in early-stage invasive cervical cancer. Methods: Eighteen patients with biopsy-confirmed invasive cervical carcinoma (stages IB1 IIA according to FIGO staging) who underwent surgery were enrolled in the study. Transvaginal 2D gray-scale sonography was performed in all of them at the Hospital of Kaunas University of Medicine prior to hysterectomy. The largest diameters of tumor mass, tumor shape, tumor area, as well as the deepest cervical stromal invasion and the largest thickness of tumorfree cervical stroma in sagittal and axial planes were correlated with their pathomorphological equivalents using Pearson correlation coefficients. Toshiba NICE and Canvas X Scientific Edition software packages were employed for the analysis and correlation of sonographic and pathomorphological images. The interobserver variability was evaluated by having two blinded sonologists interpret each examination and calculating kappa statistics. The intraobserver variability was assayed in nine patients at 24-h intervals. Results: At 2D gray-scale analysis 15 patients (83%) showed detectable tumor masses. The largest diameters of the tumor mass (maximum length, depth and width) measured at sonographic and pathomorphological examinations correlated well (R = 0.87, R = 0.89 and R = 0.76, respectively). The largest tumor area measured in both sagittal and axial planes also showed a strong correlation (R = 0.78 and R = 0.84, respectively). Poor correlation was seen in the deepest cervical stromal invasion (R = 0.14). A discrepancy of more than 10% of the tumor shape in the sagittal plane seen during sonography and pathomorphological examination occurred in seven cases (47%). Conclusions: Two-dimensional gray-scale sonography is accurate in the assessment of early-stage cervical cancer. This method should be considered in all patients with early-stage cervical cancer scheduled for radical treatment

Early-stage cervical cancer: agreement between ultrasound and histopathological findings with regard to tumor size and extent of local disease.

OBJECTIVES: To determine the agreement between ultrasonographic and histological examination of the cervix in patients with early stage cervical cancer with regard to tumor size and local extent of the disease. METHODS: Eighteen patients with histologically proven cervical cancer stage IB1-IIA according to traditional clinical staging (FIGO 1988) and scheduled for radical surgery underwent a standardized transvaginal ultrasound examination: the maximum tumor length, anterior-posterior tumor diameter, tumor width, tumor area, depth of cervical stroma invasion, and the minimal thickness of tumor free cervical stroma on sagittal and transverse planes through the cervix were measured, and the local extent of the disease into the parametria and vagina was evaluated. The surgical specimens were examined using a dedicated method of histopathological examination. The results of the ultrasound and histopathological examinations were compared. RESULTS: Limits of agreement were wide and the Inter-Class Correlation Coefficient (Inter-CC) was low (0.51 to 0.58) for three of the four measurements taken to represent the minimal depth of tumor free cervical stroma, i.e. the results for the measurements taken posteriorly and laterally. The limits of agreement were smaller and the Inter-CC values were higher (0.74 - 0.92) for the depth of cervical stroma invasion and for the tumor size measurements. Histological examination revealed parametrial cancer infiltration in four patients. All these cases were detected at ultrasound examination with no false positive results