Abstract Mastitis is one of the most impacting diseases in dairy farming, and its sensitive and specific detection is therefore of the greatest importance. The clinical evaluation of udder and mammary secretions is typically combined with the milk Somatic Cell Count (SCC) and often accompanied by its bacteriological culture to identify the causative microorganism. In a constant search for improvement, several non-enzymatic milk proteins, including milk amyloid A (M-SAA), haptoglobin (HP), cathelicidin (CATH), and lactoferrin (LF), have been investigated as alternative biomarkers of mastitis for their relationship with mammary gland inflammation, and immunoassay techniques have been developed for detection with varying degrees of success. To provide a general overview of their implementation in the different dairy species, we carried out a systematic review of the scientific literature using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Our review question falls within the type “Diagnostic test accuracy questions” and aims at answering the diagnostic question: “ Which are the diagnostic performances of mastitis protein biomarkers investigated by immunoassays in ruminant milk?” . Based on 13 keywords combined into 42 searches, 523 manuscripts were extracted from three scientific databases. Of these, 33 passed the duplicate removal, title, abstract, and full-text screening for conformity to the review question and document type: 78.8% investigated cows, 12.1% sheep, 9.1% goats, and 6.1% buffaloes (some included more than one dairy species). The most frequently mentioned protein was M-SAA (48.5%), followed by HP (27.3%), CATH (24.2%) and LF (21.2%). However, the large amount of heterogeneity among studies in terms of animal selection criteria (45.5%), index test (87.9%), and standard reference test (27.3%) resulted in a collection of data not amenable to meta-analysis, a common finding illustrating how important it is for case definitions and other criteria to be standardized between studies. Therefore, results are presented according to the SWiM (Synthesis Without Meta-analysis) guidelines. We summarize the main findings reported in the 33 selected articles for the different markers and report their results in form of comparative tables including sample selection criteria, marker values, and diagnostic performances, where available. Finally, we report the study limitations and bias assessment findings.
Abstract Background: Pancreatic cancer (PC) is one of the most lethal cancers and there is an urgent need to find out new therapeutic approaches. Deregulated signaling through ErbB-1 and ErbB-2, members of the epidermal growth factor receptor family, frequently occurs in PC. However, attempts aiming at inhibiting ErbB-1 and ErbB-2 have revealed only a modest impact on disease outcome. A growing body of evidence suggests that ErbB-3 and its ligand NRG-1β are key players in driving oncogenic signaling and resistance to targeted therapy in PC. We have recently developed a novel humanized ErbB-3 antibody, named EV20, which displayed a potent antitumor activity by promoting receptor downregulation in vitro and in vivo. Here we hypothesized that targeting of ErbB-3 with EV20 would enhance the therapeutic effect of ErbB-2 inhibitors in PC. Materials and Methods: Three different PC cell lines (BxPC-3, HPAF II and SW1990) were chosen based on their metastatic origin, genetic background (KRAS status) and responsiveness to erlotinib. The expression of ErbB-1, ErbB-2 and ErbB-3 was analyzed by FACS and WB. The effects of trastuzumab, cetuximab, EV20 and their combinations on NRG-1β-induced activation of the ErbB3/PI3K/Akt axis, cell proliferation, and in vivo tumor growth were evaluated by standard procedures. Results: ErbB-1 was overexpressed by all the cell lines, whereas the expression levels of ErbB-2 and ErbB-3 were moderate in HPAFII cells and low in BxPC-3 and SW1990 cells. NRG-1β was more effective than EGF (an ErbB-1 ligand) in activating ErbB-3 downstream signaling, which was not inhibited by cetuximab, despite a high ErbB-1 expression in the cells. Conversely, inhibition of ErbB-2 and/or ErbB-3 resulted in a marked suppression of NRG-1β-driven Akt activation. Finally, EV20 in combination with trastuzumab exerted a superior antitumor activity compared to single agent alone in terms of cell proliferation and growth of PC xenografts in nude mice. Conclusions: Dual targeting of ErbB-2 and ErbB-3 could represent a newer therapeutic approach in PC. Note: This abstract was not presented at the meeting. Citation Format: Gianluca Sala, Reza Ghasemi, Emily Capone, Ilario Giovanni Rapposelli, Sara Traini, Cosmo Rossi, Pier Giorgio Natali, Stefano Iacobelli. Dual targeting of ErbB-2 and ErbB-3: A new potential strategy for the treatment of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5437. doi:10.1158/1538-7445.AM2014-5437
Few data exist regarding the long-term effectiveness of golimumab in ulcerative colitis. No data have been reported on real-world continuous clinical response.This study aimed to describe the long-term outcomes in a large cohort of patients on golimumab who had ulcerative colitis.Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long-term persistence on golimumab therapy.A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naïve to anti-tumour necrosis factor alpha agents. The median duration of golimumab therapy was 52 weeks (range: 4-142 weeks). The cumulative probability of maintaining golimumab treatment was 47.3% and 22.5% at 54 and 108 weeks, respectively. Biological-naïve status (odds ratio [OR] = 3.02, 95% confidence interval [CI]: 1.44-6.29; p = 0.003) and being able to discontinue steroids at Week 8 (OR = 3.32, 95% CI: 1.34-8.30; p = 0.010) and Week 14 (OR = 2.94, 95% CI: 1.08-8.02; p = 0.036) were associated with longer persistence on therapy. At Week 54, 65/124 (52.4%) postinduction responders were in continuous clinical response. A continuous clinical response was associated with a lower likelihood of golimumab discontinuation throughout the subsequent year of therapy (p < 0.01). Overall, 40 (23.1%) patients were in clinical remission at the last follow-up visit. Twenty-six adverse events were recorded, leading to golimumab withdrawal in 9.2% of patients.Biological-naïve status and not requiring steroids at Weeks 8 and 14 seem to be associated with a longer persistence on golimumab therapy in ulcerative colitis.
Bluetongue (BT) is non-contagious, vector-borne viral disease of domestic and wild ruminants, transmitted by midges (Culicoides spp.) and is caused by Bluetongue virus (BTV). BTV is the type species of the Orbivirus genus within the Reoviridae family and possesses a genome consisting of 10 double-stranded RNA segments encoding 7 structural and 4 nonstructural proteins. Viral Protein 7 (VP7) is the major sera group-specific protein and is a good antigen candidate for immunoenzymatic assays for the BT diagnosis. In our work, BTV-2 recombinant VP7 (BTV-2 recVP7), expressed in Spodoptera frugiperda (Sf9) cells using a baculovirus system, was produced and purified by affinity chromatography from the supernatant of infected cell culture. The use of the supernatant allowed us to obtain a high quantity of recombinant protein with high purity level by an easy one-step procedure, rather than the multistep purification from the pellet. RecVP7-BTV2 was detected using a MAb anti-BTV in Western blot and it was used to develop an immunoenzymatic assay.
