Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of pancreatic ductal adenocarcinoma (PDAC) involves multi-stage development of molecular aberrations affecting signaling pathways that regulate cancer growth and progression. This study was performed to gain a better understanding of the abnormal signaling that occurs in PDAC compared with normal duct epithelia.</p> <p>Methods</p> <p>We performed immunohistochemistry on a tissue microarray of 26 PDAC, 13 normal appearing adjacent pancreatic ductal epithelia, and 12 normal non-PDAC ducts. We compared the levels of 18 signaling proteins including growth factor receptors, tumor suppressors and 13 of their putative downstream phosphorylated (p-) signal transducers in PDAC to those in normal ductal epithelia.</p> <p>Results</p> <p>The overall profiles of signaling protein expression levels, activation states and sub-cellular distribution in PDAC cells were distinguishable from non-neoplastic ductal epithelia. The ERK pathway activation was correlated with high levels of ^S2448p-mTOR (100%, p = 0.05), ^T389p-S6K (100%, p = 0.02 and ^S235/236p-S6 (86%, p = 0.005). Additionally, ^T389p-S6K correlated with ^S727p-STAT3 (86%, p = 0.005). Advanced tumors with lymph node metastasis were characterized by high levels of ^S276p-NFκB (100%, p = 0.05) and ^S9p-GSK3β (100%, p = 0.05). High levels of PKBβ/AKT2, EGFR, as well as nuclear ^T202/Y204p-ERK and ^T180/Y182p-p38 were observed in normal ducts adjacent to PDAC compared with non-cancerous pancreas.</p> <p>Conclusion</p> <p>Multiple signaling proteins are activated in pancreatic duct cell carcinogenesis including those associated with the ERK, PKB/AKT, mTOR and STAT3 pathways. The ERK pathway activation appears also increased in duct epithelia adjacent to carcinoma, suggesting tumor micro-environmental effects.</p

Notch 1 Receptor, Delta 1 Ligand and HES 1 Transcription Factor are Expressed in the Lining Epithelium of Periapical Cysts (Preliminary Study)

Periapical cyst is a chronic inflammatory disorder of periradicular tissues. The precise pathological mechanisms involved in periapical cyst enlargement remain unclear. Notch signaling is an evolutionarily conserved pathway with a regulatory role in cell fate decisions during development and in carcinogenesis. To date, there are no published data available on the expression of Notch signaling components in periapical cysts or any other jaw cyst. In this immunohistochemical study we have examined the expression of the receptor Notch 1, the ligand Delta 1 and the transcription factor HES 1 in the epithelium of well defined periapical cysts. Immunostaining reaction of Notch 1, Delta 1 and HES 1 was observed in the cytoplasm and/or the cytoplasmic membrane and occasionally in the nucleus in the majority of epithelial cells of all periapical cysts. The present observations indicate that Notch pathway is active in the epithelium of periapical cysts. It can be speculated that activation of epithelial cells of periapical cysts is associated with activation of Notch pathway and imply involvement of this pathway in periapical cyst growth and expansion

Implementation of a real-time reference and calibration grid platform for improved screening – mapping in Pap test slides

Cervical cancer screening based on the Papanicolaou (Pap) test is a widely applied but not always efficient practice for detecting Human Papillomavirus (HPV) mediated lesions, partially due to a non-systematic and inadequate screening process. Our aim was to introduce an inexpensive easy-to-use direct screening platform for improved detection of abnormal cells indicative of underlying cervical neoplasia as well as persisting HPV infection. By employing a novel, efficient technique of laser-based micromachining, we achieved the fabrication of spatial grids on commercially available coverslips allowing visual segmentation of the slide for efficient screening. Abnormal and formerly diagnosed as negative for intraepithelial lesion or malignancy (NILM) Pap test slides (n = 200) were analyzed by conventional and grid-based screening. Grid-based microscopy led to a more reliable diagnosis compared to the conventional by identifying an increased number of abnormal cells (P = 0.001). It decreased borderline ASCUS, AGC diagnosis, increasing LSIL, HSIL and in situ AdenoCa detection rates closely related with biopsy (P = 0.015; kappa = 0.978). Concerning the set of NILM diagnoses in rapid re-screening, the method upgraded six cases (n = 6) to LSIL (P = 0.001). The proposed technical solution offers a calibration and orientation visual aid during the on-site screening process providing significant advantages compared to expensive digital imaging techniques. © 2016 Japanese Society of Pathology and John Wiley &amp; Sons Australia, Lt

Molecular landscape in laryngeal chondrosarcoma

[No abstract available

Large dermoid cyst of the spermatic cord presenting as an incarcerated hernia: A rare presentation and literature review

Dermoid cyst of the spermatic cord is a very rare clinical entity with only a few cases reported in the literature so far. We herein describe an extremely rare case of a large dermoid cyst of the spermatic cord measuring 8.5 × 5 × 5 cm in a young patient who presented with clinical manifestations of an incarcerated inguinal hernia. After the cyst excision, a diVuse direct hernia became apparent and a Lichtenstein polypropylene mesh repair was performed. Direct hernia was likely the result of chronic pressure on the inguinal Xoor maintained by the large cyst. We conclude that although very rare, dermoid cyst of the spermatic cord should be considered as a part of the diVerential diagnosis in patients presenting with an irreducible inguinal mass of a long course. © Springer-Verlag 2009

Mathematical modeling for Delta and Omicron variant of SARS-CoV-2 transmission dynamics in Greece

A compartmental, epidemiological, mathematical model was developed in order to analyze the transmission dynamics of Delta and Omicron variant, of SARS-CoV-2, in Greece. The model was parameterized twice during the 4th and 5th wave of the pandemic. The 4th wave refers to the period during which the Delta variant was dominant (approximately July to December of 2021) and the 5th wave to the period during which the Omicron variant was dominant (approximately January to May of 2022), in accordance with the official data from the National Public Health Organization (NPHO). Fitting methods were applied to evaluate important parameters in connection with the transmission of the variants, as well as the social behavior of population during these periods of interest. Mathematical models revealed higher numbers of contagiousness and cases of asymptomatic disease during the Omicron variant period, but a decreased rate of hospitalization compared to the Delta period. Also, parameters related to the behavior of the population in Greece were also assessed. More specifically, the use of protective masks and the abidance of social distancing measures. Simulations revealed that over 5,000 deaths could have been avoided, if mask usage and social distancing were 20% more efficient, during the short period of the Delta and Omicron outbreak. Furthermore, the spread of the variants was assessed using viral load data. The data were recorded from PCR tests at 417 Army Equity Fund Hospital (NIMTS), in Athens and the Ct values from 746 patients with COVID-19 were processed, to explain transmission phenomena and disease severity in patients. The period when the Delta variant prevailed in the country, the average Ct value was calculated as 25.19 (range: 12.32–39.29), whereas during the period when the Omicron variant prevailed, the average Ct value was calculated as 28 (range: 14.41–39.36). In conclusion, our experimental study showed that the higher viral load, which is related to the Delta variant, may interpret the severity of the disease. However, no correlation was confirmed regarding contagiousness phenomena. The results of the model, Ct analysis and official data from NPHO are consistent