Role of Chemokine Network in the Development and Progression of Ovarian Cancer: A Potential Novel Pharmacological Target

Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development

THE CASE OF THE ORATORY OF SAN ROCCO IN SORAGNA (PARMA): FROM ABANDONMENT TO HEALTH FACILITY. AN INTEGRATED RESTORATION PROCESS

It’s well known that the identification of the most appropriate use for historical heritage, is a fundamental instrument of conservation, which in maintenance, even before in “restoration intervention”, find the first guarantee of success. In this paper, the participated restoration process which involved the abandoned convent of San Rocco in Soragna (Parma) is presented, with the aim of showing the application of “integrated conservation process” principles to an interesting episode of cultural heritage. Starting from historical and structural analysis of this really compromised and damaged structure, the project of reuse is presented, which, starting from a deep interaction between social and functional aspects, gathering local and social needs, has led to the creation of a territorial health structure, a small-size health facility, thus becoming a response to the municipality’s needs, making the most of the historical vocation of the building. Moreover, the adopted approach counterposes with the current tendency of multiplying interventions by proposing a diversification of uses instead: higher flexibility of spaces, and functions operating at different times of day will lead to a more effective and extended functioning of the complex, resulting in an overall better use (and, thus) preservation of the building in the long-term

Primary Cultures from Human GH-secreting or Clinically Non-functioning Pituitary Adenomas

Pituitary adenomas are among the more frequent intracranial tumors usually treated with both surgical and pharmacological\u2013based on somatostatin and dopamine agonists\u2013approaches. Although mostly benign tumors, the occurrence of invasive behaviors is often detected resulting in poorer prognosis. The use of primary cultures from human pituitary adenomas represented a significant advancement in the knowledge of the mechanisms of their development and in the definition of the determinants of their pharmacological sensitivity. Moreover, recent studies identified also in pituitary adenomas putative tumor stem cells representing, according to the current hypothesis, the real cellular targets to eradicate most malignancies. In this protocol, we describe the procedure to establish primary cultures from human pituitary adenomas, and how to select, in vitro expand, and phenotypically characterize putative pituitary adenoma stem cells

Diurnal and semidiurnal cyclicity of Radon (222Rn) in groundwater, Giardino Spring, Central Apennines, Italy

Understanding natural variations of Rn (222Rn) concentrations is the fundamental prerequisite of using this radioactive gas as a tracer, or even precursor, of natural processes, including earthquakes. In this work, Rn concentrations in groundwater were continuously measured over a seven-month period, during 2017, in the Giardino Spring, Italy, together with groundwater levels in a nearby well installed into a fractured regional aquifer. Data were processed to reduce noise, and then analyzed to produce the Fourier spectra of Rn concentrations and groundwater levels. These spectra were compared with the spectrum of tidal forces. Results showed that diurnal and semidiurnal cycles of Rn concentrations, and filtered oscillations of groundwater levels, in the nearby well, are correlated with solar and luni-solar components of tidal forces, and suggested no correlation with the principal lunar components. Therefore, influencing factors linked to solar cycles, such as daily oscillations of temperature and atmospheric pressure, and related rock deformations, may have played a role in Rn concentrations and groundwater levels. An open question remains regarding the correlation, which is documented elsewhere, of Rn concentrations and groundwater levels with the lunar components of the solid Earth tides

Polynucleotide: Adenosine glycosidase is the sole activity of ribosome-inactivating proteins on DNA

Polynucleotide: adenosine glycosidases (PNAG) are a class of plant and bacterial enzymes commonly known as ribosome-inactivating proteins (RIP). They are presently classified as rRNA N-glycosidases in the enzyme nomenclature [EC 3.2.2.22]. Several activities on nucleic acids, other than depurination, have been attributed to PNAG: in particular modifications induced in circular plasmids, including linearisation and topological changes, and cleavage of guanidinic residues. Here we describe a chromatographic procedure to obtain nuclease-free PNAG by dye-chromatography onto Procion Red derivatized Sepharose®. Highly purified enzymes depurinate extensively pBR322 circular, supercoiled DNA at neutral pH and exhibit neither DNase nor DNA glycolyase activities, do not cause topological changes, and adenine is the only base released from DNA and rRNA, even at very high enzyme concentrations. A scanning force microscopy (SFM) study of pBR322 treated with saporin-S6 confirmed that (i) this PNAG binds extensively to the plasmid, (ii) the distribution of the bound saporin-S6 molecules along the DNA chain is markedly variable, (iii) plasmids already digested with saporin-S6 do not appear fragmented or topologically modified. The observations here described demonstrate that polynucleotide:adenosine glycosidase is the sole enzymatic activity of the four ribosome-inactivating proteins gelonin, momordin I, pokeweed antiviral protein from seeds and saporin-S6. These proteins belong to different families, suggesting that the findings here described may be generalized to all PNAG

Anomalous Weak Values and the Violation of a Multiple-measurement Leggett-Garg Inequality

Quantum mechanics presents peculiar properties that, on the one hand, have been the subject of several theoretical and experimental studies about its very foundations and, on the other hand, provide tools for developing new technologies, the so-called quantum technologies. The nonclassicality pointed out by Leggett-Garg inequalities has represented, with Bell inequalities, one of the most investigated subject. In this letter we study the connection of Leggett-Garg inequalities with a new emerging field of quantum measurement, the weak values. In particular, we perform an experimental study of the four-time correlators Legget-Garg test, by exploiting single and sequential weak measurements performed on heralded single photons. We show violation of a four-parameters Leggett-Garg inequality in different experimental conditions, demonstrating an interesting connection between Leggett-Garg inequality violation and anomalous weak values

Experimental Evidence and Clinical Implications of Pituitary Adenoma Stem Cells

Pituitary adenomas, accounting for 15% of diagnosed intracranial neoplasms, are usually benign and pharmacologically and surgically treatable; however, the critical location, mass effects and hormone hypersecretion sustain their significant morbidity. Approximately 35% of pituitary tumors show a less benign course since they are highly proliferative and invasive, poorly resectable, and likely recurring. The latest WHO classification of pituitary tumors includes pituitary transcription factor assessment to determine adenohypophysis cell lineages and accurate designation of adenomas, nevertheless little is known about molecular and cellular pathways which contribute to pituitary tumorigenesis. In malignant tumors the identification of cancer stem cells radically changed the concepts of both tumorigenesis and pharmacological approaches. Cancer stem cells are defined as a subset of undifferentiated transformed cells from which the bulk of cancer cells populating a tumor mass is generated. These cells are able to self-renew, promoting tumor progression and recurrence of malignant tumors, also conferring cytotoxic drug resistance. On the other hand, the existence of stem cells within benign tumors is still debated. The presence of adult stem cells in human and murine pituitaries where they sustain the high plasticity of hormone-producing cells, allowed the hypothesis that putative tumor stem cells might exist in pituitary adenomas, reinforcing the concept that the cancer stem cell model could also be applied to pituitary tumorigenesis. In the last few years, the isolation and phenotypic characterization of putative pituitary adenoma stem-like cells was performed using a wide and heterogeneous variety of experimental models and techniques, although the role of these cells in adenoma initiation and progression is still not completely definite. The assessment of possible pituitary adenoma-initiating cell population would be of extreme relevance to better understand pituitary tumor biology and to identify novel potential diagnostic markers and pharmacological targets. In this review, we summarize the most updated studies focused on the definition of pituitary adenoma stem cell phenotype and functional features, highlighting the biological processes and intracellular pathways potentially involved in driving tumor growth, relapse, and therapy resistance