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Background:The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods:Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1–3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results:About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions:Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC.

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

, et al.. One dose of a porcine circovirus 2 subunit vaccine induces humoral and cell-mediated immunity and protects against porcine circovirus-associated disease under field conditions. Veterinary Microbiology, Elsevier, 2011, 149 (3-4) Please cite this article as: Martelli, P., Ferrari, L., Morganti, M., De Angelis, E., Bonilauri, P., Guazzetti, S., Caleffi, A., Borghetti, P., One dose of a porcine circovirus 2 subunit vaccine induces humoral and cell-mediated immunity and protects against porcine circovirus-associated disease under field conditions, Veterinary Microbiology (2010Microbiology ( ), doi:10.1016Microbiology ( /j.vetmic.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 This study investigated the efficacy of a one-dose porcine circovirus 2 (PCV2) subunit 22 vaccine based on the PCV2 Cap protein expressed in a baculovirus system on two different farms at 23 which a history of porcine circovirus-associated disease (PCVD) was present. Morbidity, mortality, 24 average daily weight gain, carcass weight, PCV2 load in serum and vaccine immunogenicity were 25 assessed. Serology to porcine reproductive and respiratory syndrome virus (PRRSV) and 26Mycoplasma hyopneumoniae was performed. A double-blind, randomised, and controlled field trial 27 was performed distributing 818 piglets between two treatment groups. At inclusion (weaning at 21 28 ± 3 days of age), 408 animals (group B) received a 2-mL intramuscular dose of Porcilis PCV between 12 and 26 weeks of age when viremia and the specific disease occurred) as well as carcass 38 weight at slaughter age (+4.5 kg). These effects were associated with virologic and clinical 39 protection from the immunogenicity of the vaccine measured as activation of both a humoral and a 40 cellular immune response. 41 42

The Central Nervous (CNS) and Immune Systems (IS) are the two major adaptive systems which respond rapidly to numerous challenges that are able to compromise health. The defensive response strictly linking innate to acquired immunity, works continuously to limit pathogen invasion and damage. The efficiency of the innate response is crucial for survival and for an optimum priming of acquired immunity. During infection, the immune response is modulated by an integrated neuro-immune network which potentiates innate immunity, controls potential harmful effects and also addresses metabolic and nutritional modifications supporting immune function. In the last decade much knowledge has been gained on the molecular signals that orchestrate this integrated adaptive response, with focus on the systemic mediators which have a crucial role in driving and controlling an efficient protective response. These mediators are also able to signal alterations and control pathway dysfunctions which may be involved in the persistence and/or overexpression of inflammation that may lead to tissue damage and to a negative metabolic impact, causing retarded growth. This review aims to describe some important signalling pathways which drive bidirectional communication between the Immune and Nervous Systems during infection. Particular emphasis is placed on pro-inflammatory cytokines, immunomodulator hormones such as Glucocorticoids (GCs), Growth hormone (GH), Insulin-like Growth Factor-1 (IGF-1), and Leptin, as well as nutritional factors such as Zinc (Zn). Finally, the review includes up-to-date information on this neuroimmune cross-talk in domestic animals. Data in domestic animal species are still limited, but there are several exciting areas of research, like the potential interaction pathways between mediators (i.e. cytokine-HPA regulation, IL-6-GCS-Zn, cytokines-GH/IGF-1, IL-6-GH-Leptin and thymus activity) that are or could be promising topics of future research in veterinary medicine.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

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Various solutes were tested to see if they could modify the responses of SV-3T3 cells to hyperosmotic (0.5 osM) conditions, which cause an inhibition of general cell protein synthesis and of the rate of cell proliferation, coupled with an induction of amino acid transport activity. The added solutes were glycerol, proline, taurine, betaine, dimethylglycine and sarcosine. Of these, betaine produced the most dramatic and consistent effects. Addition of 10-25 mM-betaine to the hyperosmotic medium largely prevented the 90% inhibition of cell proliferation that occurred in its absence. Whether it was added initially or after the cells were exposed to hyperosmotic medium, 25 mM-betaine also converted a 50% recovery of the rate of protein synthesis into 100%. Similarly, the same concentrations of betaine prevented a 30% decrease in cell volume and decreased the induction of amino acid transport via system A by 73%. Lower concentrations of betaine produced smaller but still significant changes in these functional responses. With chick-embryo fibroblasts, under identical hyperosmotic conditions, 25 mM-betaine completely counteracted a 75% inhibition of the rate of protein synthesis. At present it is not clear how betaine modulates these effects of hyperosmolarity on cell functions.