Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma

Gastric Cancer - Around 10% of gastric carcinomas (GC) contain Epstein–Barr virus (EBV) DNA. We characterized the GC-specific antibody response to this common infection, which may provide a...     

CT comparison of primary snoring and obstructive sleep apnea syndrome: role of pharyngeal narrowing ratio and soft palate-tongue contact in awake patient

Soft palate-tongue contact and automatically calculated pharyngeal narrowing ratio (PNR), defined as a ratio between the airway cross-section at the hard palate level and the narrowest cross-section from the hard palate to the epiglottis, could assist in earlier identification of potential obstructive sleep apnea syndrome (OSA) patients even on awake individuals. Parameters were studied on carotid CTA images from 67 consecutively included awake Caucasians who were later classified by second independent physician into the primary snorers (SNORE, n = 34) or obstructive sleep apnea syndrome patient (OSA, n = 33) group according to the clinical examination, laboratory testing and a full-night video polysomnography (PSG) in the sleep laboratory. Imaging and clinical data were statistically compared between groups. The odd’s ratio calculation showed a 2.95 (P = 0.0354) higher risk for OSA development in snoring person with a PNR greater than 8.6. The loose-contact subgroup among OSA patients showed significantly (P = 0.002) higher values of AHI in contrast to the in-contact subgroup. Authors didn’t have any financial relationship concerning presented study.     

Melatonin induces pro‐apoptotic signaling pathway in human pancreatic carcinoma cells (PANC‐1)

Abstract: Pancreatic cancer is a highly lethal disease with a poor prognosis for long‐term survival rate at all stages of invasiveness. It responds poorly to radio‐ and chemotherapy because the tumor cells are resistant to apoptosis. Melatonin has been reported to inhibit pancreatic cancer growth in experimental studies in animals but the effect of melatonin on cultured human pancreatic carcinoma cells has not been tested. Moreover, we have recently shown that melatonin stimulates production of two major anti‐apoptotic heat shock proteins, HSP27 and HSP 90, in pancreatic carcinoma cells. This study investigated the changes in intrinsic pathway of apoptosis at the mitochondrial level and cascade of caspases in human pancreatic carcinoma cells (PANC‐1) cells subjected to melatonin and/or luzindole. Melatonin (10^?8–10^?12 m ), the nonselective melatonin receptor antagonist, luzindole (10^?8–10^?12 m ) or a combination of both agents were added to PANC‐1 cell cultures. Cells were harvested, and the cytoplasmic proteins were isolated after 24 and 48 hr of incubation and analyzed employing co‐immunoprecipitation and western blot. Administration of melatonin to the PANC‐1 cells resulted in the stimulation of Bcl‐2/Bax and caspase‐9 proteins levels. The strongest signal of these pro‐apoptotic factors was observed at the low concentration (10^?12 m ) of melatonin. Pretreatment with luzindole alone and prior to the addition of melatonin reversed the stimulatory effect of this indoloamine on Bcl‐2/Bax and caspase‐9 proteins expression in PANC‐1 cells. This is the first study to demonstrate a pro‐apoptotic effect of low (physiological) concentration of melatonin on the pancreatic carcinoma cells. In conclusion, melatonin induced pro‐apoptotic pathways in human pancreatic carcinoma, probably by interaction with the Mel‐1 A/B receptors.     

Tumor‐associated autoantibody signature for the early detection of gastric cancer

Autoantibodies against tumor‐associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display‐based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage–antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero‐positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150‐feature microarray was tested with sera from 100 patients with GC and 100 cancer‐free controls, and then the top‐ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45‐autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.     

Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells

We have previously described the oncolytic adenovirus, Ad(CgA-E1A-miR122), herein denoted Ad5(CgA-E1A-miR122) that selectively replicates in and kills neuroendocrine cells, including freshly isolated midgut carcinoid cells from liver metastases. Ad5(CgA-E1A-miR122) is based on human adenovirus serotype 5 (Ad5) and infects target cells by binding to the coxsackie-adenovirus receptor (CAR) and integrins on the cell surface. Some neuroendocrine tumor (NET) and neuroblastoma cells express low levels of CAR and are therefore poorly transduced by Ad5. However, they often express high levels of somatostatin receptors (SSTRs). Therefore, we introduced cyclic peptides, which contain four amino acids (FWKT) and mimic the binding site for SSTRs in the virus fiber knob. We show that FWKT-modified Ad5 binds to SSTR? on NET cells and transduces midgut carcinoid cells from liver metastases about 3-4 times better than non-modified Ad5. Moreover, FWKT-modified Ad5 overcomes neutralization in an ex vivo human blood loop model to greater extent than Ad5, indicating that fiber knob modification may prolong the systemic circulation time. We conclude that modification of adenovirus with the FWKT motif may be beneficial for NET therapy.