Alternatively spliced tissue factor synergizes with the estrogen receptor pathway in promoting breast cancer progression.

BACKGROUND: Procoagulant full-length tissue factor (flTF) and its minimally coagulant alternatively spliced isoform (asTF), promote breast cancer (BrCa) progression via different mechanisms. We previously showed that flTF and asTF are expressed by BrCa cells, resulting in autoregulation in a cancer milieu. BrCa cells often express hormone receptors such as the estrogen receptor (ER), leading to the formation of hormone-regulated cell populations. OBJECTIVE: To investigate whether TF isoform-specific and ER-dependent pathways interact in BrCa. METHODS: Tissue factor isoform-regulated gene sets were assessed using ingenuity pathway analysis. Tissues from a cohort of BrCa patients were divided into ER-positive and ER-negative groups. Associations between TF isoform levels and tumor characteristics were analyzed in these groups. BrCa cells expressing TF isoforms were assessed for proliferation, migration and in vivo growth in the presence or absence of estradiol. RESULTS: Ingenuity pathway analysis pointed to similarities between ER- and TF-induced gene expression profiles. In BrCa tissue specimens, asTF expression was associated with grade and stage in ER-positive but not in ER-negative tumors. flTF was only associated with grade in ER-positive tumors. In MCF-7 cells, asTF accelerated proliferation in the presence of estradiol in a ß1 integrin-dependent manner. No synergy between asTF and the ER pathway was observed in a migration assay. Estradiol accelerated the growth of asTF-expressing tumors but not control tumors in vivo in an orthotopic setting. CONCLUSION: Tissue factor isoform and estrogen signaling share downstream targets in BrCa; the concomitant presence of asTF and estrogen signaling is required to promote BrCa cell proliferation.

Tissue factor-integrin interactions in cancer and thrombosis: every Jack has his Jill.

Tissue factor (TF) is a 47 kDa membrane protein that initiates coagulation by binding to FVII(a) and FX(a) and is a risk factor for thrombosis in many disease states. In addition to its coagulant activity, TF also influences cancer progression by triggering signaling effects via a group of G-protein coupled receptors named protease-activated receptors (PARs). TF localizes to cytoskeletal structures in migrating cells, influences cytoskeleton reorganization and promotes migration. Recently, integrins, important mediators of cell motility, have emerged as important binding partners for TF and influence both TF coagulant and PAR-2-dependent signaling functions. Direct binding of TF to integrins also impacts processes such as cell migration and signaling independent of PAR-2. A recently discovered alternatively spliced, soluble TF isoform also ligates integrins to augment angiogenesis, thus fuelling cancer progression. To date, the literature describes a complex interplay between different integrin subunits and distinct TF isoforms, but our understanding of TF-integrin bidirectional regulation remains clouded. In this review, we aim to summarize the existing knowledge on integrin-TF interaction and speculate on its relevance to physiology and pathology.

The importance of measuring intraocular pressure using a tonometer in order to estimate the postmortem interval.

AIM: The purpose of this study is to evaluate postmortem eye changes and to investigate the relationship between these changes and time elapsed after death. MATERIAL AND METHOD: The eyes of 100 noncriminal cases who had died while being treated at Eskisehir Osmangazi University (ESOGU) hospital were evaluated for corneal turbidity and tache noire macroscopically, and also repeatedly evaluated by ophthalmoscope, pupilometer, and tonometer at intervals until removal from hospital. The postmortem time, corneal turbidity, development of tache noire, pupil size, intraocular pressure (IOP), and fundus findings were recorded. The relationship between these findings and the postmortem interval (PMI) was evaluated. RESULTS: No relationship between tache noire development and postmortem time (P > 0.05) was found. The corneal turbidity ratio increased significantly at 8 hours after decease (P < 0.01). No relationship between right-left pupil size and postmortem time (P > 0.05) was found. There was, however, a significant relationship between the fundus findings and postmortem time. Over time, the first optic disc becomes pale, then vascular clarity decreases and segmentation increases. The right and left IOP related significantly to postmortem time and decreased gradually as time passed (P < 0.05). Application of linear, exponential, and power equations showed that IOP can be used to estimate postmortem time by a 2 hour interval with a 95% probability. CONCLUSIONS: This study shows that corneal turbidity and IOP have a significant relationship with postmortem time and can be used to estimate a postmortem interval with other postmortem findings. This study provides data that would support the idea that such examination might be useful in estimating postmortem interval.

Simultaneous sudden infant death syndrome.

The simultaneous sudden deaths of twins rarely occur and therefore it has received limited attention in the medical literature. When the deaths of the twins meet the defined criteria for sudden infant death syndrome (SIDS) independently and take place within the same 24 h range it can be called as simultaneous SIDS (SSIDS). The case(s): Twin girls (3.5-month-old) were found dead by their mother in their crib, both in supine position. The infants were identical twins and delivered at a hospital by cesarean section. Both infants were healthy and did not have any serious medical history. Two days prior to the incident, the twins had received the second dose of oral polio, DPT and the first dose of hepatitis B vaccines and they had fever on the first day of the vaccination and been given teaspoonful of acetaminophen. Death scene investigation, judicial investigation, parental assessment, macroscopic and microscopic autopsy findings and the toxicological analysis did not yield any specific cause of death. The case(s) were referred to a supreme board composed of multidisciplinary medical professionals at the Institute of Forensic Medicine, Ministry of Justice, in Istanbul. The Board decided that the available data was consistent with SIDS. These SIDS case(s) are presented because twin SIDS are rare and this is the first time that a simultaneous twin SIDS have been reported in Turkey. Simultaneous SIDS cases have many implications regarding definition, diagnosis and medico-legal approach.