Zebrafish patient-derived xenografts identify chemo-response in pancreatic ductal adenocarcinoma patients

It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predic-tiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice

Mustelus canis,the smooth dogfish shark as a model for immunoprivileged sites in yolk sac placentation and sperm storage

Placental viviparity and sperm storage make their first appearance in the vertebrate line in Chondrichthyes, the oldest extant jawed vertebrates. Although viviparity is advantageous for nourishment and growth of the offspring, it involves an immunological risk for sperm containing paternal antigens and the placenta containing fetal antigens. The placental smoothhound shark, Mustelus canis, has yolk sac placentation and stores sperm throughout the year in sperm storage tubules (SST) of the terminal zone (TZ) in the oviducal gland (OG) in the female. This animal has been used as a model to examine the uteroplacental complex and SST. Techniques used were transmission electron microscopy and immunohistochemistry to investigate the tissue expression of the cytokines interlukin 1 (IL-1) α, IL-1 β, its specific membrane receptor, IL-1 receptor type I (IL-1R tI) and macrophage migration inhibitory factor (MIF). In addition the uteroplacental complex has been profiled as to the diversity of its glycosylation, which was found to be as complex as that found in both reptilian and mammalian placenta. Immunostaining of the uteroplacental complex for IL-1 α, IL-1 β, IL-R tI revealed by binding leucocytes of both the mother and fetus. Yolk sac endoderm was also positive for all the epitopes studied while ectoderm was positive only for IL-1 α. Immunoreactivity in the uterine endometrium was obtained for IL-1 α and its receptor while the egg envelope was always negative. Placenta and SST were positive for MIF and IL-1 receptor. The present findings on the expression of the interleukin system and MIF in the uteroplacental complex and SST suggest that these cytokines are involved in evolutionarily conserved immunological mechanisms that anticipate the presence of paternal and fetal antigens in maternal tissues

Chemoenzymatic synthesis and antimicrobial activity evaluation of monogalactosyl diglycerides

Monogalactosyl diglycerides with medium to long fatty acid acyl chains, were prepared and examined for antimicrobial activity against Gram positive, Gram negative bacteria and fungi. The study of their in vitro antimicrobial activity confirms the significant activity of some monogalactosyl diacylglycerol analogues and establishes for the galactose series that the 1,2-disubstitution and the octanoyl chain are the proper structural features for the maximum activity