Current standard of care for muscle-invasive urothelial cell carcinoma (UCC) is surgery along with perioperative platinum-based chemotherapy. UCC is sensitive to cisplatin-based regimens, but ...acquired resistance eventually occurs, and a subset of tumors is intrinsically resistant. Thus, there is an unmet need for new therapeutic approaches to target chemotherapy-resistant UCC. Yes-associated protein (YAP) is a transcriptional co-activator that has been associated with bladder cancer progression and cisplatin resistance in ovarian cancer. In contrast, YAP has been shown to induce DNA damage associated apoptosis in non-small cell lung carcinoma. However, no data have been reported on the YAP role in UCC chemo-resistance. Thus, we have investigated the potential dichotomous role of YAP in UCC response to chemotherapy utilizing two patient-derived xenograft models recently established. Constitutive expression and activation of YAP inversely correlated with in vitro and in vivo cisplatin sensitivity. YAP overexpression protected while YAP knockdown sensitized UCC cells to chemotherapy and radiation effects via increased accumulation of DNA damage and apoptosis. Furthermore, pharmacological YAP inhibition with verteporfin inhibited tumor cell proliferation and restored sensitivity to cisplatin. In addition, nuclear YAP expression was associated with poor outcome in UCC patients who received perioperative chemotherapy. In conclusion, these results suggest that YAP activation exerts a protective role and represents a pharmacological target to enhance the anti-tumor effects of DNA damaging modalities in the treatment of UCC.
Summary
Nasal cytology is an easy, cheap, non‐invasive and point‐of‐care method to assess nasal inflammation and disease‐specific cellular features. By means of nasal cytology, it is possible to ...distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non‐allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time‐course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non‐allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic‐mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non‐invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.
Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects ...and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.
Two commercial organosilicons, Hydrophase.sup.®, a monomeric dispersion, and Disboxan 450.sup.®, an oligomeric dispersion, were studied in pure form and applied on acrylic paint replicas. Their ...physico-chemical characteristics, coating properties, and interaction with acrylic paint replicas were evaluated by TG, DSC, FTIR, and contact angle measurements. Hydrophase.sup.® showed a higher interaction when used on the top of acrylic paint replicas than Disboxan 450.sup.®. No appreciable modification was detected after two years of natural ageing.
To cite this article: Heffler E, Nebiolo F, Asero R, Guida G, Badiu I, Pizzimenti S, Marchese C, Amato S, Mistrello G, Canaletti F, Rolla G. Clinical manifestations, co-sensitizations, and ...immunoblotting profiles of buckwheat-allergic patients. Allergy 2011; 66: 264-270. ABSTRACT: Background: Buckwheat allergy is a rare food allergy in Europe and North America, whereas it is often described and studied in Asia. The aim of this study was to describe a series of patients with proven buckwheat allergy evaluated in an Italian allergy clinic. Co-sensitization to other food and inhalant allergens and immunoblotting profiles of buckwheat-allergic patients were studied. Methods: Patients with suspected buckwheat allergy who attended the allergy clinic between January 1, 2006, and September 30, 2008, were evaluated. All patients underwent skin prick tests for a standard panel of inhalant and food allergens, prick-by-prick with buckwheat flour, buckwheat-specific IgE determinations, and double-blind placebo-controlled food challenge (DBPCFC) with buckwheat flour. Immunoblotting with buckwheat flour extract was performed on sera from buckwheat-allergic patients. Results: Among 72 patients with suspected buckwheat allergy, 30 (41.7%) were sensitized to buckwheat and 24 had a positive DBPCFC. The mean buckwheat IgE level was 6.23 kUA/l (range, 0.16 to >100 kUA/l). Several IgE-binding proteins were identified and grouped into three patterns: a 16-kDa band in patients with predominantly gastrointestinal symptoms with grass and wheat flour co-sensitization, a 25-kDa band in patients with predominantly cutaneous symptoms and a low frequency of co-sensitization, and a 40-kDa band in patients with anaphylaxis and a low frequency of co-sensitization. Conclusions: Buckwheat allergy is an emerging food allergy in Italy. We identified three distinct patterns of clinical and laboratory characteristics, suggesting that specific allergens could be more frequently associated with clinical manifestations of different severity.
Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in ...non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3% of them were atopic. Mean prevalence of buckwheat sensitization was 3.6% with significant difference between Northern (4.5%), Central (2.2%) and Southern (2.8%) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.
Whether peripheral inflammatory molecules can be considered markers of dementia is still an open issue. We have investigated the presence of circulating cytokines and the ability of blood cells to ...release them in response to an inflammatory stimulus in patients with different types of dementia and in age-matched controls. A significant increase in circulating interleukin-1β in moderate Alzheimer and in multiinfarct (145 and 224 times control concentration, respectively) dementia and in circulating tumor necrosis factor-α concentration in multiinfarct dementia patient group (156%) were found. Tumor necrosis factor-α and interleukin-6 released from blood cells after exposure to lipopolysaccharide were significantly reduced in moderate Alzheimer (60%, both cytokines) and multiinfarct patients (71 and 50%, respectively), while interleukin-10 was decreased only in multiinfarct patients (61%). The results show that patients with Alzheimer disease or multiinfarct dementia have an upregulation of circulating cytokines and a downregulation of cytokines released by blood cells.
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