Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

<p>Abstract</p> <p>Background</p> <p>Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75^NTRneurotrophin receptor. Trk receptors promote cell survival and differentiation while p75^NTRinduces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75^NTR-induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75^NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue.</p> <p>Methods</p> <p>Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75^NTRand phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined.</p> <p>Results</p> <p>Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75^NTRreceptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor grade-dependent manner (p < 0.05). Interestingly, a statistically significant (p < 0.05) reverse relationship between Trk receptors LIs and pc-Jun/pJNK LIs was noted in some glioblastomas multiforme.</p> <p>Conclusion</p> <p>In the context of astrocytomas, Trk receptors (TrkA, TrkB, TrkC) expression may promote tumor growth independently of grade. Furthermore, activation of JNK pathway may contribute to progression towards malignancy. Considering the fact that regional tumor heterogeneity may be a limiting factor for immunohistochemical studies, the significance of the reverse relationship between Trk receptors and pc-Jun/pJNK LIs with respect to biological behavior of human astrocytomas requires further evaluation.</p

Achaiki Iatriki : official publication of the medical society of western Greece and Peloponnesus

In the current issue, the editorial by Cauchi et al. argues for eco-friendly measures in endoscopy and emphasies the role of healthcare providers in reducing waste. The editorial adeptly employs the three Rs (Reduce, Reuse, Recycle) framework to tackle waste management, offering practical solutions. The editorial by Milionis et al. focuses on the reverse cascade screening for paediatric familial hypercholesterolaemia (FH), which is an upcoming tool for public health. Advantages, practices, and challenges regarding FH are thoroughly discussed. Lastly, the editorial by Fousekis et al. presents the main aspects of a chronic immune-mediated cutaneous disease, dermatitis herpetiformis (DH), which constitutes an extraintestinal manifestation of celiac disease, including its diagnosis, pathogenesis, and management. Moreover, this issue includes three review articles. The review article by Krontira et al. discusses the evolving data on the epidemiology, diagnostic approach and appropriate management of foreign body and caustic substance ingestion, based on updated guidelines published by gastroenterological and endoscopic societies. The review by Halliasos et al. provides data on the clinical presentation, diagnosis, and management of metastatic acute spinal cord compression, focusing on the importance of a multidisciplinary team approach, including spine surgeons, radiation oncologists, medical oncologists, palliative care clinicians, physiotherapists, and psychologists. Lastly, the review by Schinas et al. outlines the potential of immune modulation in the treatment of infections and the need for individualised approaches in the modern world of personalised medicine by examining some of the key strategies and immune-based therapies being developed to combat infectious diseases.peer-reviewe

DISTRIBUTION OF SEX STEROID HORMONE RECEPTORS, HORMONE-INDUCED PROTEINS AND ANGIOGENESIS IN CENTRAL NERVOUS SYSTEM NEOPLASMS. AN IMMUNOHISTOCHEMICAL STUDY

TO ACCESS A POSSIBLE SEX STEROID HORMONE DEPENDENCE OF CENTRAL NERVOUS SYSTEM NEOPLASMS WE HAVE IMMUNOHISTOCHEMICALLY EXAMINED 159 BRAIN TUMORS USING A STREPTARIDIN/PEROXIDASE METHOD AND MONOCLONAL ANTIBODIES FOR ESTROGEN RECEPTOR (ER), PROGESTERONE RECEPTOR (PGR) AND HORMONE-INDUCED PROTEINS PS2, HSP27 AND CKBB. FURTHERMORE, THE ANGIOGENESIS OF THESE NEOPLASMS WAS STUDIED. STRONG PGR-IMMUNOREACTIVITY WAS OBSERVED IN MENINGIOMAS AND POORLY DIFFERENTIATED ASTROCYTIC NEOPLASMS. ALL NEOPLASMS WERE NEGATIVE FOR ESTROGEN RECEPTOR AND ESTROGEN-REGULATED PROTEIN PS2. STRONG HSP27-IMMUNOREACTIVITY WAS OBSERVED IN POORLY DIFFERENTIATED ASTROCYTIC NEOPLASMS CONTRASTING WITH THE WELL DIFFERENTIATED NEOPLASMS. LOW HSP27-IMMUNOREACTION WAS FOUND IN MENINGIOMAS. A HIGLY PERCENTAGE (82%) OF ASTROCYTIC NEOPLASMS WERE RECOGNIZED TO BE HIGHLY VASCULAR WHILE 58% OF MENINGIOMAS WERE HIGHLY VASCULAR.ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ ΕΙΝΑΙ Η ΜΟΡΦΟΛΟΓΙΚΗ ΕΚΤΙΜΗΣΗ ΤΗΣ ΠΙΘΑΝΟΤΗΤΑΣ ΕΞΑΡΤΗΣΕΩΣ ΑΠΟ ΤΑ ΟΙΣΤΡΟΓΟΝΑ ΚΑΙ/Η ΤΗΝ ΠΡΟΓΕΣΤΕΡΟΝΗ ΤΩΝ ΝΕΟΠΛΑΣΜΑΤΩΝ ΤΟΥ ΚΕΝΤΡΙΚΟΥ ΝΕΥΡΙΚΟΥ ΣΥΣΤΗΜΑΤΟΣ. ΕΠΙΠΛΕΟΝ, ΜΕΛΕΤΗΘΗΚΕ Η ΠΑΡΟΥΣΙΑ ΝΕΑΓΓΕΙΩΣΗΣ. ΑΝΑΖΗΤΗΘΗΚΕ Η ΠΑΡΟΥΣΙΑ ΥΠΟΔΟΧΕΩΝ ΟΙΣΤΡΟΓΟΝΩΝ ΚΑΙ ΠΡΟΓΕΣΤΕΡΟΝΗΣ ΚΑΘΩΣ ΚΑΙ ΤΩΝ ΠΡΩΤΕΙΝΩΝ PS2, HSP27 ΚΑΙ CKBB Η ΠΑΡΟΥΣΙΑ ΤΩΝ ΟΠΟΙΩΝ ΘΕΩΡΕΙΤΑΙ ΟΤΙ ΕΠΑΓΕΤΑΙ ΑΠΟ ΤΙΣ ΓΕΝΕΤΙΚΕΣ ΣΤΕΡΟΕΙΔΕΙΣ ΟΡΜΟΝΕΣ, ΣΕ ΤΟΜΕΣ ΠΑΡΑΦΙΝΗΣ ΜΟΝΙΜΟΠΟΙΗΜΕΝΩΝ ΣΕ ΦΟΡΜΑΛΙΝΗ ΙΣΤΩΝ ΑΠΟ 159ΑΣΘΕΝΕΙΣ ΜΕ ΝΕΟΠΛΑΣΜΑΤΑ ΤΟΥ ΚΕΝΤΡΙΚΟΥ ΝΕΥΡΙΚΟΥ ΣΥΣΤΗΜΑΤΟΣ. ΕΦΑΡΜΟΣΤΗΚΕ Η ΑΝΟΣΟΙΣΤΟΧΗΜΙΚΗ ΜΕΘΟΔΟΣ ΤΗΣ ΒΙΟΤΙΝΗΣ-ΣΤΡΕΠΤΑΒΙΔΙΝΗΣ/ΥΠΕΡΟΞΕΙΔΑΣΗΣ ΚΑΙ ΧΡΗΣΙΜΟΠΟΙΗΘΗΚΑΝ ΜΟΝΟΚΛΩΝΙΚΑ ΑΝΤΙΣΩΜΑΤΑ. ΤΑ ΜΗ ΔΙΑΦΟΡΟΠΟΙΗΜΕΝΑ ΑΣΤΡΟΚΥΤΤΑΡΙΚΑ ΝΕΟΠΛΑΣΜΑΤΑ ΕΜΦΑΝΙΣΑΝ ΜΕΓΑΛΥΤΕΡΗ ΑΝΟΣΟΘΕΤΙΚΟΤΗΤΑ ΓΙΑ ΤΟΝ ΥΠΟΔΟΧΕΑ ΠΡΟΓΕΣΤΕΡΟΝΗΣ ΚΑΙ ΤΗ HSP 27 ΣΕ ΣΧΕΣΗ ΜΕ ΤΑ ΚΑΛΑ ΔΙΑΦΟΡΟΠΟΙΗΜΕΝΑ. ΣΤΑ ΜΗΝΙΓΓΙΩΜΑΤΑ ΠΑΡΑΤΗΡΗΘΗΚΕ ΥΨΗΛΗ ΕΚΦΡΑΣΗ ΤΟΥ ΥΠΟΔΟΧΕΑ ΠΡΟΓΕΣΤΕΡΟΝΗΣ ΕΝΩ Η ΑΝΟΣΟΑΝΤΙΔΡΑΣΗ ΓΙΑ ΤΗ HSCP 27 ΗΤΑΝ ΑΣΘΕΝΗΣ. ΕΚΦΡΑΣΗ ΤΟΥ ΥΠΟΔΟΧΕΑ ΑΣΤΡΟΓΟΝΩΝ ΚΑΘΩΣ ΚΑΙ ΤΗΣ PS2 ΔΕΝ ΤΑΥΤΟΠΟΙΗΘΗΚΕ ΣΕ ΚΑΝΕΝΑ ΝΕΟΠΛΑΣΜΑ ΤΗΣ ΜΕΛΕΤΗΣ. ΥΨΗΛΗ ΝΕΟΑΓΓΕΙΩΣΗ ΑΝΙΧΝΕΥΘΗΚΕ ΣΤΑ ΑΣΤΡΟΚΥΤΤΑΡΙΚΑ ΝΕΟΠΛΑΣΜΑΤΑ ΕΝΩ ΜΙΚΡΟΤΕΡΗ ΝΕΟΑΓΓΕΙΩΣΗ ΠΑΡΑΤΗΡΗΘΗΚΕ ΣΤΑ ΜΗΝΙΓΓΙΩΜΑΤΑ

Transient receptor potential (TRP) channels in human colorectal cancer: evidence and perspectives

Colorectal cancer (CRC) is one of the leading causes of death in the civilized world. Transient receptor potential channels (TRPs) are a heterogeneous family of cation channels that play an important role in gastrointestinal physiology. TRPs have been linked with carcinogenesis in the colon and their role as potential therapeutic targets and prognostic biomarkers is under investigation

Immunoexpression patterns for Hypoxia-inducible Factor-1α and von Hippel-Lindau protein, in relation to Hsp90, of human brain tumors

The pathogenesis of many tumors, including brain tumors, has been associated with hypoxia, which induces the transcriptional activity of Ηypoxia-inducible Factor-1α (HIF-1α). HIF-1α is normally degradated by the von Hippel-Lindau protein (pVHL) but, in hypoxia, pVHL/HIF-1α interaction is inhibited resulting in the nuclear accumulation of HIF-1α. Hsp90 (Heat shock protein 90), as a chaperone protein, plays a critical role for both stabilization of HIF-1α and degradation of pVHL. The aim of this study was to estimate immunohistochemically the expression levels of HIF-1α and pVHL, in relation to Hsp90, in different types of human brain tumors (42 gliomas, 9 medulloblastomas, and 38 meningiomas) using specific antibodies. The tumors were further divided into two groups according to the age of patients (≥19 years old or <19 years old). Nuclear, for HIF-1α, and cytoplasmic, for pVHL and Hsp90, localization was detected in a high percentage of tumor cells in the majority of tumors. In astrocytomas, a significant, grade-dependent relationship for HIF-1α immunoexpression was observed (p<0.05). Furthermore, there was a significant correlation between pVHL and Hsp90 immunoexpression (p<0.01). The group of ≥19 years old patients with glioblastomas (WHO grade IV) demonstrated significantly increased immunoexpression for HIF-1α compared to pVHL (p<0.0001) and Hsp90 expression (p<0.01). In medulloblastomas, a significant correlation of HIF-1α with Hsp90 immunoexpression (p<0.05) was found. In meningiomas, no significant correlation for the expression of the three proteins was detected (p≥0.05). These results indicate that HIF1α/pVHL/Hsp90 interactions may be implicated in biology of different types of brain tumors through different signaling mechanisms

Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis

The Transient Receptor Potential (TRP) family of selective and non-selective ion channels is well represented throughout the mammalian gastrointestinal track. Several members of the Transient Receptor Potential Vanilloid (TRPV) subfamily have been identified in contributing to modulation of mobility, secretion and sensitivity of the human intestine. Previous studies have focused on the detection of TRPV mRNA levels in colon tissue of patients with inflammatory bowel disease (IBD) whereas little information exists regarding TRPV channel expression in the colonic epithelium. The aim of this study was to evaluate the expression levels of TRPV1, TRPV2, TRPV3 and TRPV4 in mucosa epithelial cells of colonic biopsies from patients with ulcerative colitis (UC) in comparison to colonic resections from non-IBD patients (control group). Immunohistochemistry, using specific antibodies and quantitative analyses of TRPV-immunostained epithelial cells, was performed in semi-serial sections of the samples. TRPV1 expression was significantly decreased whereas TRPV4 expression was significantly increased in the colonic epithelium of UC patients compared to patients in the control group (p &lt; 0.05). No significant difference for TRPV2 and TRPV3 expression levels between UC and control specimens was detected (p &gt; 0.05). There was no correlation between TRPV channel expression and the clinical features of the disease (p &gt; 0.05). Further investigation is needed to clarify the role of TRPV channels in human bowel inflammatory response

Grade IV tumor (glioblastoma multiforme) exhibiting strong nuclear (arrows) and cytoplasmic immunostaining of pJNK and strong cytoplasmic immunostaining of TrkB (b) and TrkC (c) neurotrophin receptors, ×400

<p><b>Copyright information:</b></p><p>Taken from "Neurotrophin receptors expression and JNK pathway activation in human astrocytomas"</p><p>http://www.biomedcentral.com/1471-2407/7/202</p><p>BMC Cancer 2007;7():202-202.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2180182.</p><p></p

Strong TrkA granular cytoplasmic immunostaining in giant cells of glioblastoma multiforme (grade IV), ×400

<p><b>Copyright information:</b></p><p>Taken from "Neurotrophin receptors expression and JNK pathway activation in human astrocytomas"</p><p>http://www.biomedcentral.com/1471-2407/7/202</p><p>BMC Cancer 2007;7():202-202.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2180182.</p><p></p