Human Papillomavirus in Endometrial Adenocarcinomas: Infectious Agent or a Mere “Passenger”?

Aims. To investigate the possible association of human papillomavirus (HPV) with endometrial hyperplasias and neoplasia. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas? Methods. Twenty-five endometrial adenocarcinomas of the endometrioid cell type, with and without squamous differentiation, and twenty-four endometrial hyperplasias of various forms (simple, complex, and atypical) were analyzed for the presence of type 16 and 18 HPV by the polymerase chain reaction (PCR). The results were related to histopathological features of the tumour, and the patients' age, and prognosis. Results. Six of 25 endometrial adenocarcinomas were HPV 16-positive (24%), and 5 of 25 (20%) were HPV 18-positive. Simple endometrial hyperplasias was associated somewhat more commonly with HPV 16 and 18 (2/8 and 1/8 cases, resp.) than hyperplasias progressing to endometrial adenocarcinomas, namely, atypical endometrial hyperplasia (1/8 and 0/8 cases, resp.). None of the positive cases in the series, whether hyperplastic or neoplastic, demonstrated cytological evidence of HPV infection. There was no relation between HPV-positive cases and squamous differentiation, depth of myometrial invasion, lymphatic involvement, lymphocytic response, patients' age, or prognosis. Conclusion. It appears that the presence of HPV in the endometrium, as detected by PCR, does not play any role in the initiation or prognosis of endometrial adenocarcinoma

Autophagosome proteins LC3A, LC3B and LC3C have distinct subcellular distribution kinetics and expression in cancer cell lines

LC3s (MAP1-LC3A, B and C) are structural proteins of autophagosomal membranes, widely used as biomarkers of autophagy. Whether these three LC3 proteins have a similar biological role in autophagy remains obscure. We examine in parallel the subcellular expression patterns of the three LC3 proteins in a panel of human cancer cell lines, as well as in normal MRC5 fibroblasts and HUVEC, using confocal microscopy and western blot analysis of cell fractions. In the cytoplasm, there was a minimal co-localization between LC3A, B and C staining, suggesting that the relevant autophagosomes are formed by only one out of the three LC3 proteins. LC3A showed a perinuclear and nuclear localization, while LC3B was equally distributed throughout the cytoplasm and localized in the nucleolar regions. LC3C was located in the cytoplasm and strongly in the nuclei (excluding nucleoli), where it extensively co-localized with the LC3A and the Beclin-1 autophagy initiating protein. Beclin 1 is known to contain a nuclear trafficking signal. Blocking nuclear export function by Leptomycin B resulted in nuclear accumulation of all LC3 and Beclin-1 proteins, while Ivermectin that blocks nuclear import showed reduction of accumulation, but not in all cell lines. Since endogenous LC3 proteins are used as major markers of autophagy in clinical studies and cell lines, it is essential to check the specificity of the antibodies used, as the kinetics of these molecules are not identical and may have distinct biological roles. The distinct subcellular expression patterns of LC3s provide a basis for further studies

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Insulin/IGF and Sex Hormone Axes in Human Endometrium and Associations with Endometrial Cancer Risk Factors

Given an ordered set of points and an ordered set of geometric objects in the plane, we are interested in finding a non-crossing matching between point-object pairs. In this paper, we address the algorithmic problem of determining whether a non-crossing matching exists between a given point-object pair. We show that when the objects we match the points to are finite point sets, the problem is NP-complete in general, and polynomial when the objects are on a line or when their size is at most 2. When the objects are line segments, we show that the problem is NP-complete in general, and polynomial when the segments form a convex polygon or are all on a line. Finally, for objects that are straight lines, we show that the problem of finding a min-max non-crossing matching is NP-complete. © 2012 Elsevier B.V.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Amifostine protects mouse liver against radiation-induced autophagy blockage

Background/Aim: Amifostine is the only selective normal tissue cytoprotector, approved for the protection against platinum toxicities and radiotherapy-induced xerostomia. Free radical scavenger and DNA repair activities have been attributed to the drug. Materials and Methods: We investigated the effect of amifostine on autophagy, lysosomal biogenesis and lipophagy of normal mouse liver exposed to clinically relevant doses of radiation. Results: The study provides evidence that ionizing radiation blocks autophagy activity and lysosomal biogenesis in normal mouse liver. Amifostine, protects the liver autophagic machinery and induces lysosomal biogenesis. By suppressing autophagy, ionizing radiation induces lipid droplet accumulation, while pre-treatment with amifostine protects lipophagy and up-regulates the TIP47 protein and mRNA levels, showing a maintenance of lipid metabolism in the liver cells. Conclusion: It is concluded that amifostine, aside to DNA protection activity, exerts its cytoprotective function by preventing radiation-induced blockage of autophagy, lysosomal biogenesis and lipophagy

No relationship between thymidine phosphorylase (TP, PD-ECGF) expression and hypoxia in carcinoma of the cervix

The expression of hypoxia-regulated genes promotes an aggressive tumour phenotype and is associated with an adverse cancer treatment outcome. Thymidine phosphorylase (TP) levels increase under hypoxia, but the protein has not been studied in association with hypoxia in human tumours. An investigation was made, therefore, of the relationship of tumour TP with hypoxia, the expression of other hypoxia-associated markers and clinical outcome. This retrospective study was carried out in patients with locally advanced cervical carcinoma who underwent radiotherapy. Protein expression was evaluated with immunohistochemistry. Hypoxia was measured using microelectrodes and the level of pimonidazole binding. There was no relationship of TP expression with tumour pO2 (r=−0.091, P=0.59, n=87) or pimonidazole binding (r=0.13, P=0.45, n=38). There was no relationship between TP and HIF-1α, but there was a weak borderline significant relationship with HIF-2α expression. There were weak but significant correlations of TP with the expression of VEGF, CA IX and Glut-1. In 119 patients, the presence of TP expression predicted for disease-specific (P=0.032) and metastasis-free (P=0.050) survival. The results suggest that TP is not a surrogate marker of hypoxia, but is linked to the expression of hypoxia-associated genes and has weak prognostic power