Peptides of the Constant Region of Antibodies Display Fungicidal Activity

Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents

Pancreatic Ductal Adenocarcinoma Associated with Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP), in contrast to other benign chronic pancreatic diseases, can be cured with immunosuppressant drugs, thus the differentiation of AIP from pancreatic cancer is of particular interest in clinical practice. There is the possibility that some patients with AIP may develop pancreatic cancer, and this possibility contributes to increasing our difficulties in differentiating AIP from pancreatic cancer. We herein report the case of a 70-year-old man in whom pancreatic adenocarcinoma and AIP were detected simultaneously. We must carefully monitor AIP patients for the simultaneous presence of pancreatic cancer, even when a diagnosis of AIP is confirmed

Estimating Floodplain Populations and Assessing Flood Risk and Flood Mitigation in Puerto Rico

This project performed floodplain population estimates and created population density maps for the municipalities of Bayamon, Catano, and Guaynabo. Our methods included the use of ArcGIS software to display aerial photographs, Census block data and FIRM data in the form of maps. A short survey was conducted to understand residents' flood experiences and awareness, as well as their trust in a catastrophe modeling system and flood alerts. The survey data were analyzed using SPSS, allowing us to make correlations between flooding experiences and preparedness among floodplain communities. These data will be used by the Planning Board to make population estimates for the rest of Puerto Rico and to better allocate resources for flood mitigation and prevention

Retroperitoneal lymphangioma: A report of 2 cases and a review of the literature regarding the differential diagnoses of retroperitoneal cystic masses

Cystic lymphangioma is a type of benign tumor originating from the lymph vessels. The tumor commonly occurs in childhood, in the head or neck regions, and retroperitoneal localization and presentations in adulthood are rare. Determining a pre-operative diagnosis is often challenging, and in the majority of cases, a diagnosis is only possible subsequent to the histological examination of the surgical specimen. A radical resection is the recommended treatment for cystic lymphangioma, and recurrence is usually due to an incomplete excision of the mass. The present study reports 2 cases of cystic lymphangioma, localized in the pancreatic gland and duodenal wall respectively, which were treated with surgical resection. The study also briefly reviews the literature regarding the differential diagnosis of retroperitoneal cystic masses

Metastatic pancreatic cancer: is gemcitabine still the best standard treatment?

Pancreatic ductal adenocarcinoma is the fourth cause of death in the Western world. Surgery remains the only treatment offering an advantage in terms of overall survival (5-year survival range, 15-25%), but unfortunately only 10-20% of patients present resectable disease at the time of diagnosis. Hence chemotherapy, possibly combined with radiation therapy, remains the only treatment option aimed at palliation of symptoms and ensuring a better quality of life. Notwithstanding the efforts to find more effective therapies for the treatment of pancreatic cancer, significant results have not yet been achieved. Increasing interest has focused on integrated treatments, i.e. chemotherapy combined with targeted therapies, and a better selection of patients. This study examines the principal clinical trials that will help give clinicians an overview of the progress made in the systemic therapy for advanced pancreatic cancer patients in recent years

Anti-Biofilm Properties of Saccharomyces cerevisiae CNCM I-3856 and Lacticaseibacillus rhamnosus ATCC 53103 Probiotics against G. vaginalis

Bacterial vaginosis (BV) is characterized by the presence of a polymicrobial biofilm where Gardnerella vaginalis plays a key role. Previously, we demonstrated that Saccharomyces cerevisiae CNCM (French National Collection of Cultures of Microorganisms) I-3856 is helpful in resolving experimental simulated BV in mice. In this study, we analyzed its capacity to affect G. vaginalis biofilms and to potentiate the activity of standard antimicrobial agents. We also investigated the anti-biofilm activity of Lacticaseibacillus rhamnosus GG (ATCC 53103), a well-known strain for its intestinal healthy benefits. Biofilm biomass was assessed by crystal violet staining, and G. vaginalis viability was assessed by a colony forming unit (CFU) assay. Here, for the first time, we demonstrated that S. cerevisiae CNCM I-3856 as well as L. rhamnosus GG were able (i) to significantly inhibit G. vaginalis biofilm formation, (ii) to markedly reduce G. vaginalis viability among the biomass constituting the biofilm, (iii) to induce disaggregation of preformed biofilm, and (iv) to kill a consistent amount of bacterial cells in a G. vaginalis preformed biofilm. Furthermore, S. cerevisiae CNCM I-3856 strongly potentiates the metronidazole effect on G. vaginalis biofilm viability. These results suggest that S. cerevisiae CNCM I-3856 as well as L. rhamnosus GG could be potential novel therapeutic agents against bacterial vaginosis

Circulating programmed death ligand-1 (cPD-L1) in non-smallcell lung cancer (NSCLC)

Background: This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients' clinical responses and survival outcome. Methods: Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher's test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p-value. Results: Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort (p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to nonchemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months (p = 0.062) and 8.8 vs 9.3 months (p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant (p = 0.063). Conclusions: This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations

Mutational burden of resectable pancreatic cancer, as determined by whole transcriptome and whole exome sequencing, predicts a poor prognosis

Despite the genomic characterization of pancreatic cancer (PC), marked advances in the development of prognosis classification and novel therapeutic strategies have yet to come. The present study aimed to better understand the genomic alterations associated with the invasive phenotype of PC, in order to improve patient selection for treatment options. A total of 30 PC samples were analysed by either whole transcriptome (9 samples) or exome sequencing (21 samples) on an Illumina platform (75X2 or 100X2 bp), and the results were matched with normal DNA to identify somatic events. Single nucleotide variants and insertions and deletions were annotated using public databases, and the pathogenicity of the identified variants was defined according to prior knowledge and mutation-prediction tools. A total of 43 recurrently altered genes were identified, which were involved in numerous pathways, including chromatin remodelling and DNA damage repair. In addition, an analysis limited to a subgroup of early stage patients (50% of samples) demonstrated that poor prognosis was significantly associated with a higher number of known PC mutations (P=0.047). Samples from patients with a better overall survival (>25 months) harboured an average of 24 events, whereas samples from patients with an overall survival of <25 months presented an average of 40 mutations. These findings indicated that a complex genetic profile in the early stage of disease may be associated with increased aggressiveness, thus suggesting an urgent requirement for an innovative approach to classify this disease

State of the art biological therapies in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a five-year survival rate of approximately 5%. Several target agents have been tested in PDAC, but almost all have failed to demonstrate efficacy in late phase clinical trials, despite the better understanding of PDAC molecular biology generated by large cancer sequencing initiatives in the past decade. Eroltinib (a small-molecule tyrosine-kinase inhibitor of epidermal growth factor receptor) plus gemcitabine is the only schedule with a biological agent approved for advanced pancreatic cancer, but it has resulted in a very modest survival benefit in unselected patients. In our work, we report a summary of the main clinical trials (closed and ongoing) that refer to biological therapy evaluation in pancreatic cancer treatment