Human Papilloma Virus (HPV) status, P16INK4a and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer

OpenCAL++: An object-oriented architecture for transparent parallel execution of cellular automata models

Cellular Automata (CA) models, initially studied by John von Neumann, have been developed by numerous researchers and applied in both academic and scientific fields. Thanks to their local and independent rules, simulations of complex systems can be easily implemented based on CA modelling on parallel machines. However, due to the heterogeneity of the components - from the hardware to the software perspective-the various possible scenarios running parallelism in today’s architectures can pose a challenge in such implementations, making it difficult to exploit. This paper presents OpenCAL++, a transparent and efficient object-oriented platform for the parallel execution of cellular automata models. The architecture of OpenCAL++ ensures the modeller a fully transparent parallel execution and a strong ”separation of concerns” between the execution parallelism issues and the model implementation. The code implementing the Cellular Automata model remains the same whether the execution performs in a shared-, distributed-memory or a GPGPU context, irrespective of the optimizations adopted. To this aim, the object-oriented paradigm has been intensely exploited. As well as the OpenCAL++ architecture, we present the description of a simple Cellular Automata model implementation for illustrative purposes.This research was funded by the Italian “ICSC National Center for HPC, Big Data and Quantum Computing” Project, CN00000013 (approved under the Call M42C –Investment 1.4 – Avvisto “Centri Nazionali” – D.D. n. 3138 of 16.12.2021, admitted to financing with MUR Decree n. 1031 of 06.17.2022)Peer ReviewedPostprint (author's final draft

Adipocyte-derived extracellular vesicles promote breast cancer cell malignancy through HIF-1α activity.

Abstract Extracellular vesicles (EVs) are emerging key protagonists in intercellular communication between adipocytes and breast cancer (BC) cells. Here, we described a new mechanism by which EVs released by mature adipocytes promoted breast cancer cell malignancy "in vitro" and "in vivo". We found that adipocyte-derived EVs enhanced growth, motility and invasion, stem cell-like properties, as well as specific traits of epithelial-to-mesenchymal transition in both estrogen receptor positive and triple negative BC cells. Of note, adipocyte-derived EVs aid breast tumor cells in lung metastatic colonization after tail-vein injection in mice. These EV-mediated effects occur via the induction of HIF-1α activity, since they were abrogated by the use of the HIF-1α inhibitor KC7F2 or in cells silenced for HIF-1α expression. Moreover, using an "ex vivo" model of obese adipocytes we found that the depletion of EVs counteracted the ability of obese adipocytes to sustain pro-invasive phenotype in BC cells. Interestingly, EVs released by undifferentiated adipocytes failed to induce aggressiveness and HIF-1α expression. These findings shed new light on the role of adipocyte-derived EVs in breast cancer progression, suggesting the possibility to target HIF-1α activity to block the harmful adipocyte-tumor cell dialogue, especially in obese settings

Characterization of cancer stem cells (CSC) isolated from LI, a human glioblastoma (GBM) cell line

It is becoming increasingly clear that tumour development is due to a small fraction of mutated stem cells (CSC). Established cancer cell lines represent a good source of CSC with respect to tissue tumour samples because they do not contain any contaminating normal stem cells and it is easy to obtain large quantities of them. We isolated putative CSC via a non-adherent neurosphere (NS) assay from LI. Using a clonal assay, we selected from the primary NS two clones named F11 and D2. LI, F11 and D2 cells and these clones under differentiation were examined for expression of stem cell markers (CD133, Nestin, Musashi-1 and Sox-2), markers of differentiation (βIII-Tubulin and GFAP) and Ca2+-channels, by immunocytochemistry, western blot analysis and confocal Ca2+ imaging. Both F11 and D2 clones expressed higher levels of stem cell markers with respect to LI cells. Markers of differentiation were expressed at high levels in both LI cells and clones. The expression of Nestin, Sox-2, and βIII-Tubulin was down-regulated in clones under differentiation, whereas Musashi-1 was increased. LI, F11 and D2 cells did not exhibit Ca2+ signals following KCl-induced membrane depolarization, thus suggesting that they do not express functional voltage-dependent Ca2+-channels. Nevertheless, transient increases in intracellular Ca2+ levels were observed after cell exposure to ATP in both F11 and D2 during differentiation. The ATP treatment did not affect cell proliferation. The increased expression of stem cell markers and their decrease in cells under differentiation demonstrate the stem characteristics of clones we selected. The findings regarding expression of differentiation markers and of Ca2+-channels require further investigation. After a deeper characterization, both F11 and D2 could represent a good model to improve the knowledge on CSC and to identify new therapeutic approaches in GBM

Laser Interferometric sensor for Seismic Waves Measurement

Laser interferometry is one of the most sensitive methods for small displacement measurement for scientific and industrial applications, whose wide diffusion in very different fields is due not only to the high sensitivity and reliability of laser interferometric techniques, but also to the availability of not expensive optical components and high quality low-cost laser sources. Interferometric techniques have been already successfully applied also to the design and implementation of very sensitive sensors for geophysical applications. In this paper we describe the architecture and the expected theoretical performances of a laser interferometric velocimeter for seismic waves measurement. We analyze and discuss the experimental performances of the interferometric system, comparing the experimental results with the theoretical predictions and with the performances of a state-of the art commercial accelerometer. The results obtained are very encouraging, so that we are upgrading the system in order to measure the local acceleration of the mirrors and beam splitter of the velocimeter using an ad hoc designed monolithic accelerometers for low frequency direct measurement of the seismic noise