Spontaneous immunogenicity of ribosomal P0 protein in patients with benign and malignant breast lesions and delay of mammary tumor growth in P0-vaccinated mice

A common carboxyl-terminal epitope (C-22 P0) of the ribosomal P proteins (P0, P1 and P2) was shown to elicit autoantibodies in systemic lupus erythematosus (SLE) and in head and neck cancer patients. In this report we provide evidence for the in vivo immunogenicity of the P0 protein in breast cancer patients. Using recombinant P proteins, we demonstrated that sera from breast carcinoma patients (8/75) displayed significant reactivity to P0 protein when compared with healthy donor sera (0/45). Four out of the eight sera showed simultaneous reactivity to all P proteins. Breast benign tumor (3/17) and mammary hyperplasia (3/17) patient sera also showed significant reactivity to P proteins, thus suggesting that the occurrence of P protein autoantibodies might reveal mammary cell cycle dysregulation. Patient sera reacting with all P proteins recognized C-22 P0. Anti-P0 autoantibodies did not correlate with prognostic parameters of breast carcinomas. High level expression of C-22 P0 was found in mammary carcinomas compared with normal adjacent epithelium and benign lesions. To determine the antitumor activity of P0 as an immunogen, BALB-neuT transgenic mice displaying age-related breast cancer progression were vaccinated using xenogeneic P0 at the stage of mammary atypical hyperplasia. P0 vaccination significantly delayed the onset of mouse mammary tumors that overexpressed C-22 P0. Sera from P0 vaccinated mice recognized C-22 P0. Evidence for immunity to the P0 protein, its overexpression in carcinomas and its peculiar surface localization on cancer cells, along with its antitumor activity as an immunogen might be relevant for the use of P0 protein in monitoring cancer progression and in planning immunotherapeutic strategies

Determination of the (3x3)-Sn/Ge(111) structure by photoelectron diffraction

At a coverage of about 1/3 monolayer, Sn deposited on Ge(111) below 550 forms a metastable (sqrt3 x sqrt3)R30 phase. This phase continuously and reversibly transforms into a (3x3) one, upon cooling below 200 K. The photoemission spectra of the Sn 4d electrons from the (3x3)-Sn/Ge(111) surface present two components which are attributed to inequivalent Sn atoms in T4 bonding sites. This structure has been explored by photoelectron diffraction experiments performed at the ALOISA beamline of the Elettra storage ring in Trieste (Italy). The modulation of the intensities of the two Sn components, caused by the backscattering of the underneath Ge atoms, has been measured as a function of the emission angle at fixed kinetic energies and viceversa. The bond angle between Sn and its nearest neighbour atoms in the first Ge layer (Sn-Ge1) has been measured by taking polar scans along the main symmetry directions and it was found almost equivalent for the two components. The corresponding bond lengths are also quite similar, as obtained by studying the dependence on the photoelectron kinetic energy, while keeping the photon polarization and the collection direction parallel to the Sn-Ge1 bond orientation (bond emission). A clear difference between the two bonding sites is observed when studying the energy dependence at normal emission, where the sensitivity to the Sn height above the Ge atom in the second layer is enhanced. This vertical distance is found to be 0.3 Angstroms larger for one Sn atom out of the three contained in the lattice unit cell. The (3x3)-Sn/Ge(111) is thus characterized by a structure where the Sn atom and its three nearest neighbour Ge atoms form a rather rigid unit that presents a strong vertical distortion with respect to the underneath atom of the second Ge layer.Comment: 10 pages with 9 figures, added reference

Infection by high-risk human papillomaviruses, epithelial-to-mesenchymal transition and squamous pre-malignant or malignant lesions of the uterine cervix: a series of chained events?

: Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally activated when the epithelium is chronically exposed to pathogens: this event deeply alters the tissue and eventually contributes to the development of diseases. Among the many of them is uterine cervical squamous cell carcinoma (SCC), the most frequent malignancy of the female genital system. SCC, whose onset is associated with the persistent infection of the uterine cervix by high-risk human papillomaviruses (HR-HPVs), often relapses and/or metastasizes, being resistant to conventional chemo- or radiotherapy. Given that these fearsome clinical features may stem, at least in part, from the exacerbated and long-lasting EMT occurring in the HPV-infected cervix; here we have reviewed published studies concerning the impact that HPV oncoproteins, cellular tumor suppressors, regulators of gene expression, inflammatory cytokines or growth factors, and the interactions among these effectors have on EMT induction and cervical carcinogenesis. It is predictable and desirable that a broader comprehension of the role that EMT inducers play in SCC pathogenesis will provide indications to flourish new strategies directed against this aggressive tumor

The natural history of ankylosing spondylitis in the 21st century

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects the axial skeleton and evolves in stiffnes followed by ankylosis and disability. However, it may be difficult to exactly establish the natural history of the disease and the influence of risk factors of progression, since most patients are treated with various pharmacologic or non-pharmacologic agents, which may potentially influence the natural progression of the disease. In this context, we report here a very interesting case of a 40 year old man, presented to our outpatient clinic, 28 years after the onset of AS. Previously for personal reasons, did not choose not to undergo any treatment. This case allows us to evaluate the natural radiological progression of the disease and the influence of predictive risk factors

Polished stone axes from Varna/Nössingbühel and Castelrotto/Grondlboden, South Tyrol (Italy)

A collection of polished stone axes from a late Neolithic site and an Early Bronze Age hill fort in South Tyrol (Italy) have been analysed through a multi-analytical approach, mainly based on non-destructive techniques (i.e. Raman spectroscopy, X-ray fluorescence and prompt gamma activation analysis) to identify the raw materials used in the same area during different periods and compare them with those in use in the surrounding territories. The analytical results suggest raw material exploitation strategies based on local or close sedimentary, metamorphic and magmatic rocks. Most of the artefacts are made from antigoritic serpentinite, whose origin is probably from Hohe Tauern (Austria) or related secondary deposits. These data confirm the importance of such raw material for the production of polished stone axes during recent prehistory and integrate the present knowledge about the distribution of antigoritic artefacts in north-eastern Italy and neighbouring countries

Laboratory findings in psoriatic arthritis.

Psoriatic arthritis (PsA) has been classically defined as an inflammatory arthritis associated with psoriasis. However, in comparison with other relevant inflammatory arthropathies, in which a definite diagnosis is frequently possible only by means of laboratory investigations, in PsA true laboratory diagnostic markers are lacking. Some markers are utilised more to differentiate other diseases than to characterise PsA. For example in polyarticular PsA, which may be in some cases indistinguishable from RA, the rheumatoid factor (RF) or the more specific and recently introduced antibodies to cyclic citrullinated peptides (anti-CCP), may be useful to better identify RA. However, RF was found in 5% to 13% of patients with PsA, and anti-CCP may be observed in almost similar percentage. The determination of ESR and/or CRP is frequently disappointing in PsA, since they are both elevated in only half of the patients with PsA. However, ESR and/or CRP are included in the most utilised response criteria for RA, such as ACR and DAS, and, in addition are also considered reliable in the assessment of PsA. Furthermore, elevated levels of ESR have been proposed as one of the best predictors of damage progression and, in addition, a low ESR seems protective, while an ESR >15 mm/h is one of the factors associated with an increased mortality in PsA. The synovial fluid (SF) effusion is much higher in PsA, in comparison with other arthropathies. When available, SF analysis may offer additive information useful for the diagnosis, such as the increased number of leukocytes, which underlines the inflammatory nature of the effusion even in a patient with normal serum levels of acute phase response. We found that elevated IL-1 levels in SF of patients with early disease (<6 months), may be predictive of an evolution in polyarticular form at follow-up. This observation is in keeping with the crucial role that inflammatory cytokines play in PsA, probably related to a genetic predisposition. The recent introduction in PsA of anti-TNF-α agents and the demonstration of their efficacy in the management of many clinical disease expressions including peripheral arthropathy, axial involvement, enthesopathy and skin manifestations, have stimulated the research also in the field of the possible laboratory markers. Key words: Psoriatic arthritis, laboratory investigations arthriti

Antiproliferative properties of papaver rhoeas ovule extracts and derived fractions tested on HL60 leukemia human cells

Papaver rhoeas plant is common in many regions worldwide and contributes to the landscape with its red flower. In the present study we first carried out morphological investigation by optical and scanning electron microscopy of the ovules within the ovary. After ovules’ isolation we prepared extracts to test possible cytotoxic activities on HL60 leukemia human cells and investigated the extracts using thin-layer chromatography (TLC) and gas-chromatography/mass spectrometry (GC-MS). P. rhoeas ovules showed an elongated, round shape and the presence of ordered sculptures on the ovule surface. The ovule extracts showed cytotoxic activity on HL60 human cells mainly found in some TLC-isolated spots. Compounds consisting of active spots were identified by GC-MS investigations. Our findings on the P. rhoeas ovule compounds open perspectives for further investigations of TLC-isolated spots on other human cancer cell lines

Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active immunization with rat Neu or human ErbB receptors

Employing the transgenic BALB-neuT mouse tumor model, we explored the in vivo biologic relevance of immunocompetent epitopes shared among the four ErbB receptors. The outcome of neu-mediated tumorigenesis was compared following vaccination with isogeneic normal rat ErbB2/Neu (LTR-Neu) or xenogeneic human ErbB receptors (LTR-EGFR, LTR-ErbB2, LTR-ErbB3 and LTR-ErbB4), each recombinantly expressed in an NIH3T3 murine cell background. Vaccination using rat LTR-Neu at the stage of atypical hyperplasia potently inhibited neu-mediated mammary tumorigenesis. Moreover, all human ErbB receptors specifically interfered with tumor development in BALB-neuT mice. Relative increase in tumor-free survival and reduction in tumor incidence corresponded to structural similarity shared with the etiologic neu oncogene, as rat orthologue LTR-Neu proved most effective followed by the human homologue LTR-ErbB2 and the other three human ErbB receptors. Vaccination resulted in high titer specific serum antibodies, whose tumor-inhibitory effect correlated with cross-reactivity to purified rat Neu extracellular domain in vitro. Furthermore, a T cell response specific for peptide epitopes of rat Neu was elicited in spleen cells of mice immunized with LTR-Neu and was remotely detectable for discrete peptides upon vaccination with LTR-ErbB2 and LTR-EGFR. The most pronounced tumor inhibition by LTR-Neu vaccination was associated with leukocyte infiltrate and tumor necrosis in vivo, while immune sera specifically induced cytotoxicity and apoptosis of BALB-neuT tumor cells in vitro. Our findings indicated that targeted inhibition of neu oncogene-mediated mammary carcinogenesis is conditional upon the immunization schedule and discrete immunogenic epitopes shared to a variable extent by different ErbB receptors