Sorin Hostiuc

The epithelial to mesenchymal transition in pancreatic cancer: A systematic review

BACKGROUND/OBJECTIVES The present article summarizes and analyzes the current knowledge about the role of the epithelial to mesenchymal transition (EMT) in the systemic invasiveness of pancreatic cancer. METHOD An electronic search of PubMed/MEDLINE, EMBASE, and the Web of Science was used to identify relevant original articles and reviews. RESULTS The EMT represents a key step during normal embryogenesis. However, increasing evidence reveals its essential role in the local progression and metastasis of pancreatic cancer. Areas of interest are the cross-linking between cells undergoing the EMT and pancreatic cancer stem cells, and the correlation between the EMT and chemoresistance to standard therapies. During carcinogenesis, malignant pancreatic cells at the primary site acquire the ability to undergo the EMT, a transformation associated with increased mobility. The reverse process at secondary sites, the mesenchymal to epithelial transition (MET), has devastating consequences, allowing neoplastic epithelial cells to invade surrounding tissues and spread to distant sites. Consequences of the EMT are the loss of E-cadherin expression and the acquisition of mesenchymal markers including fibronectin or vimentin. Detailed knowledge of the molecular processes underlying the EMT has opened possibilities for new therapeutic agents. These include an EMT approach for patients with early cancers, to prevent invasion and dissemination, and anti-MET therapy for patients with established metastasis. CONCLUSIONS The current literature shows a strong correlation between the EMT and the systemic aggressiveness of pancreatic tumors. Individualized therapy, targeting the process of EMT and its cross-linking with cancer stem cells, may increase survival of patients with pancreatic cancer.

The human trigeminal ganglion: c-kit positive neurons and interstitial cells.

OBJECTIVES The presence of c-kit positive neurons in sensory ganglia has been verified in various species but not in humans. Our aim has been to identify whether human primary trigeminal neurons label with c-kit/CD117 and thus, whether data gathered in animal studies can be extrapolated to humans. We also intended to establish whether, and which non-neuronal cells also label with c-kit in the trigeminal ganglion. METHODS Human adult trigeminal ganglia from eight cadavers were processed for immunohistochemistry on paraffin embedded samples using monoclonal antibodies for CD117/c-kit, and three additional trigeminal ganglia were used for transmission electron microscopy (TEM). To evaluate which neuronal type (A or B) was labeled with c-kit, we evaluated the same neurons on adjacent sections labeled with antibodies for neurofilaments (NF). RESULTS c-kit has labeled trigeminal neurons (TNs), mast cells and interstitial cells (ICs) within the trigeminal ganglion. c-kit+TNs were NF-and thus were strongly presumed to be nociceptive, as such neurons are known to be NF-poor. c-kit+ICs with long and moniliform processes intermingled with the satellite glial cells (SGCs) of the neuronal envelopes. TEM evaluations confirmed this mixed composition of the neuronal envelopes and demonstrated that the perineuronal ICs are in fact interstitial Cajal-like cells (ICLCs) and/or telocytes. CONCLUSIONS c-kit+TNs were objectified in humans and strongly presumed to be nociceptive. TNs envelopes mostly consist of SGCs, but are also combined with ICLCs/telocytes.

Extrahepatic and Intrahepatic Human Portal Interstitial Cajal Cells

Portal interstitial cells of Cajal (PICCs), acting as vascular pacemakers, were previously only identified in nonhumans. Moreover, there is no evidence available about the presence of such cells within the liver. The objective of the study is to evaluate whether or not PICCs are identifiable in humans and, if they are, whether or not they are following the scaffold of portal vein (PV) branches within the liver. We obtained extrahepatic PVs and liver samples from six adult human cadavers, negative for liver disease, in accordance with ethical rules. They were stained with hematoxylin‐eosin (HE) and Giemsa, and then we performed immunohistochemistry on formalin‐fixed paraffin‐embedded specimens for CD117/c‐kit, a marker of the Cajals cells. Immune labeling was also performed for S‐100 protein, desmin, glial fibrillary acidic protein (GFAP), neurofilaments, α‐smooth muscle actin (α‐SMA), and CD34. c‐kit‐Positive PICCs were identified within the extrahepatic PV, in portal spaces, and septa. On adjacent sections, these PICCs were negative for all the other antibodies used. In conclusion, our study confirms the presence of extrahepatic PICCs on humans, which may act as a possible intrinsic pacemaker in the human PV. However, the intrahepatic PICCs, which were evidenced here for the first time, are in need for further experimental studies to evaluate their functional role. A promising further direction of the study is the PICCs role in the idiopathic portal hypertension. Anat Rec, 2011.

Informed consent in posthumous sperm procurement

IntroductionAssisted reproductive technologies are increasingly more present in our everyday life: from classical sperm/egg donation or in vitro fertilization to newer, more controversial methods such as surrogate motherhood, male pregnancies or posthumous sperm procurement. Every year, new concepts are emerging in this field and the medical world is not always prepared to deal with them.Material and methodThe greatest problem of using posthumous sperm procurement as an assisted reproductive method resides in analyzing consent related. An extensive research of the scientific literature revealed eight possible situations which we will present and analyze in this article.ResultsBy analyzing consent related issues we present a decision making algorithm for posthumous sperm procurement.

Subsets of telocytes: Myocardial telocytes

Telocytes (TCs) are morphologically defined as small-sized cells with long, thin, moniliform processes called telopodes (Tps). Numerous papers imply that TCs are a distinctive cell type, and that transmission electron microscopy (TEM) is the gold standard tool for their identification. We aimed to reproduce previous studies on myocardial TCs to check their validity. For this purpose we performed an immunohistochemical study on human cardiac samples from six autopsied donor cadavers, using antibodies against CD10, CD31, CD34, CD146, Ki67, alpha-smooth muscle actin (α-SMA), Platelet-Derived Growth Factor Receptor-alpha (PDGFRα) and laminin. Additionally we performed a TEM study on cardiac samples from three human autopsied donor cadavers and five adult Sprague-Dawley rats. We found endothelial cells (ECs), cords, and filopodia-projecting endothelial tip cells (ETCs) that expressed CD10, CD31, CD34, CD146, and PDGFR-α. Often, endothelial cells closely neighbored the sarcolemmal basal laminae. Endothelial progenitor cells, as well as nascent capillaries, were CD31+/CD34+. Proliferative endothelial cells expressed Ki67. In larger vessels we found pericytes that expressed CD146 and α-SMA; scarce α-SMA-expressing spindle-shaped cells lining cardiomyocytes were suggestive of a pericytic role in angiogenic sprout guidance. The TEM study showed that endothelial tubes are almost exclusively found in the narrow myocardial interstitia. ECs that built them up appeared identical to the cells that previous TEM studies have suggested to be myocardial telocytes. A subset of stromal cells with TC-like phenotype and telopodes-like processes actually seem to configure blood vessels, and therefore belong to the endothelial lineage. This study shows that data presented in previous studies on myocardial telocytes is not enough to allow the reproducibility of the results. At least a subset of cells considered to be TCs might belong to the endothelial lineage.

Complex Ebstein's Malformation: Defining Preoperative Cardiac Anatomy and Function

Ebsteins malformation is a congenital malformation of the tricuspid valve and right ventricle, with a highly variable morphology, and clinical presentation, accounting for less than 1% of all congenital heart diseases, and about 40% of congenital malformations of the tricuspid valve.

Nestin immune labeling in human adult trigeminal ganglia

Nestin labels neuroepithelial stem cells and endothelial cells in newly formed blood vessels. The aim of the study was to investigate the immunolocalization of nestin in human adult trigeminal ganglia. Autopsy samples from eight human adult cadavers were paraffin embedded, and immunostained with anti-nestin antibody. Satellite glial cells (SGCs) and intraganglionic microvessels were positively labeled with nestin, which is usually expressed in endothelial cells of newly formed blood vessels. Nestin-positive SGCs have been previously reported in rat trigeminal ganglia. Our study is the first to identify them in human trigeminal ganglia. Further studies are needed to evaluate if the nestin phenotype of SGCs relates to the functional plasticity of these cells or to glial and/or neuronal remodeling in adults. Intrinsic angiogenesis in the adult trigeminal ganglion should be further checked as to whether it relates to a normal vascular remodeling or if it represents an overlooked determinant of trigeminal neuralgia.

Endocardial Tip Cells in the Human Embryo – Facts and Hypotheses

Experimental studies regarding coronary embryogenesis suggest that the endocardium is a source of endothelial cells for the myocardial networks. As this was not previously documented in human embryos, we aimed to study whether or not endothelial tip cells could be correlated with endocardial-dependent mechanisms of sprouting angiogenesis. Six human embryos (43–56 days) were obtained and processed in accordance with ethical regulations; immunohistochemistry was performed for CD105 (endoglin), CD31, CD34, α-smooth muscle actin, desmin and vimentin antibodies. Primitive main vessels were found deriving from both the sinus venosus and aorta, and were sought to be the primordia of the venous and arterial ends of cardiac microcirculation. Subepicardial vessels were found branching into the outer ventricular myocardium, with a pattern of recruiting α-SMA+/desmin+ vascular smooth muscle cells and pericytes. Endothelial sprouts were guided by CD31+/CD34+/CD105+/vimentin+ endothelial tip cells. Within the inner myocardium, we found endothelial networks rooted from endocardium, guided by filopodia-projecting CD31+/CD34+/CD105+/ vimentin+ endocardial tip cells. The myocardial microcirculatory bed in the atria was mostly originated from endocardium, as well. Nevertheless, endocardial tip cells were also found in cardiac cushions, but they were not related to cushion endothelial networks. A general anatomical pattern of cardiac microvascular embryogenesis was thus hypothesized; the arterial and venous ends being linked, respectively, to the aorta and sinus venosus. Further elongation of the vessels may be related to the epicardium and subepicardial stroma and the intramyocardial network, depending on either endothelial and endocardial filopodia-guided tip cells in ventricles, or mostly on endocardium, in atria.

Immunolocalization of 200 kDa neurofilaments in human cardiac endothelial cells.

Neurofilaments usually associated with neural tissues are the type IV family of intermediate filaments. Nestin, which is a type VI intermediate filament, is a well known marker of endothelial cells in newly formed blood vessels and is developmentally and structurally related to type IV intermediate filaments. We aimed to determine whether or not cardiac endothelial cells (ECs) label with antibodies for neurofilaments (200 kDa, Novocastra-Leica, clone RT97), as is already known for nestin. We used cardiac samples (sinoatrial nodes/right atrial walls) from cadavers of normal and diabetic donors (6 normal adults, 10 type II diabetic adults, 1 child) for neurofilament immune labeling. Positive labeling of endothelial cells, microvascular and endocardial, was obtained in all samples. As this is the first such evidence, we can only presume that the neurofilament positive labeling of endothelial cells may be due to interactions of nestin and neurofilaments. Further studies are needed to evaluate the hypothesis we reached and, in order to explore whether or not neurofilament antibodies can qualify as markers of angiogenesis.

Extralevator vs conventional abdominoperineal resection for rectal cancer—A systematic review and meta-analysis

BACKGROUND The aim of this study was to compare the short-term morbidity and long-term oncologic benefits of extralevator abdominoperineal excision (ELAPE) with conventional abdominoperineal resection (CAPR) for patients with rectal cancer. METHODS Electronic search of the Cochrane Library, MEDLINE, EMBASE, Korean Journal, and J-EAST database from 2007 until August 2015 was carried out. We considered randomized controlled trials and nonrandomized comparative studies comparing ELAPE with CAPR to be eligible, if they included patients with rectal cancers. RESULTS A total of 1 randomized controlled trials and 10 nonrandomized comparative studies met the inclusion criteria, involving 1,736 patients in the ELAPE group and 1,320 in the CAPR group. The ELAPE was associated with a significantly lower intraoperative perforation rate. There were no differences regarding the circumferential margin involvement, R0 resections, and local recurrence rate. There was less blood loss in ELAPE patients. CONCLUSIONS The ELAPE significantly lowered the intraoperative perforation rate, with no benefits regarding circumferential resection margin involvement and local recurrence rate.