|Tumour-associated trypsin inhibitor TATI is a prognostic marker in colorectal cancer. |
Selja Koskensalo,Jaana Hagström,Johanna Louhimo,Ulf-Håkan Stenman,Caj Haglund
The tumour-associated trypsin inhibitor TATI is expressed together with trypsin in many cancer forms, and an elevated serum level associates with poor prognosis. TATI can reduce tissue destruction by inhibiting trypsin and other proteinases, and in some cancer forms, its high tissue expression is associated with favourable prognosis. We analyzed the prognostic values of TATI, trypsinogen-1 and trypsinogen-2 immunoexpression from tissue array blocks constructed from surgical specimens of 592 colorectal cancer patients.
|Paneth cell hyperplasia and metaplasia in necrotizing enterocolitis. |
Patrycja J Puiman,Nanda Burger-Van Paassen,Maaike W Schaart,Adrianus C J M De Bruijn,Ronald R De Krijger,Dick Tibboel,Johannes B Van Goudoever,Ingrid B Renes
Paneth cell dysfunction has been suggested in necrotizing enterocolitis (NEC). The aim of this study was to i) study Paneth cell presence, protein expression, and developmental changes in preterm infants with NEC and ii) determine Paneth cell products and antimicrobial capacity in ileostomy outflow fluid. Intestinal tissue from NEC patients (n = 55), preterm control infants (n = 22), and term controls (n = 7) was obtained during surgical resection and at stoma closure after recovery. Paneth cell abundance and protein expression were analyzed by immunohistochemistry. RNA levels of Paneth cell proteins were determined by real-time quantitative RT-PCR. In ileostomy outflow fluid, Paneth cell products were quantified, and antimicrobial activity was measured in vitro. In acute NEC, Paneth cell abundance in small intestinal tissue was not significantly different from preterm controls. After recovery from NEC, Paneth cell hyperplasia was observed in the small intestine concomitant with elevated human alpha-defensin 5 mRNA levels. In the colon, metaplastic Paneth cells were observed. Ileostomy fluid contained Paneth cell proteins and inhibited bacterial growth. In conjunction, these data suggest an important role of Paneth cells and their products in various phases of NEC.
|Proinflammatory and proliferative responses of human proximal tubule cells to PAR-2 activation. |
Vesey, DA; Kruger, WA; Poronnik, P; Gobé, GC; Johnson, DW
American journal of physiology. Renal physiology
Despite the abundant expression of protease-activated receptor (PAR)-2 in the kidney, its relevance to renal physiology is not well understood. A role for this receptor in inflammation and cell proliferation has recently been suggested in nonrenal tissues. The aims of this study were to demonstrate that human proximal tubule cells (PTC) express functional PAR-2 and to investigate whether its activation can mediate proinflammatory and proliferative responses in these cells. Primary human PTC were cultured under serum-free conditions with or without the PAR-2-activating peptide SLIGKV-NH2 (up to 800 microM), a control peptide, VKGILS-NH2 (200 microM), or trypsin (0.01-100 nM). PAR-2 expression (RT-PCR), intracellular Ca2+ mobilization (fura-2 fluorimetry), DNA synthesis (thymidine incorporation), fibronectin production (ELISA, Western blotting), and monocyte chemotactic protein (MCP)-1 secretion (ELISA) were measured. Trypsinogen expression in kidney and PTC cultures was determined by immunohistochemistry and Western blotting. In the kidney PTC were the predominant cell type expressing PAR-2. SLIGKV-NH2, but not VKGILS-NH2, stimulated a rapid concentration-dependent mobilization of intracellular Ca2+ and ERK1/2 phosphorylation and, by 24 h, increases in DNA synthesis, fibronectin secretion, and MCP-1 secretion. These delayed responses appeared to be independent of ERK1/2. Trypsin produced similar rapid but not delayed responses. Trypsinogen was weakly expressed by PTC in the kidney and in culture. In summary, PTC are the main site of PAR-2 expression in the human kidney. In PTC cultures SLIGKV-NH2 initiates proinflammatory and proliferative responses. Trypsinogen expressed within the kidney has the potential to contribute to PAR-2 activation in certain circumstances.
|Experience with an automated microwave-assisted rapid tissue processing method: validation of histologic quality and impact on the timeliness of diagnostic surgical pathology. |
Morales, AR; Nassiri, M; Kanhoush, R; Vincek, V; Nadji, M
American journal of clinical pathology
We studied the effect of a fully automated microwave-assisted rapid tissue processor (RTP) on histologic examination and on the turnaround time for surgical pathology reports. A quality assurance program reviewed the histologic sections obtained by the rapid processing method for the last 3 calendar years. In addition, the histologic results from this method were compared blindly with those obtained from the conventional overnight tissue processing (CTP) method by 9 pathologists with different levels of experience. The surgical pathology turnaround times for 1 year of use of the RTP were compared with the last year for CTP. We found that the RTP reproducibly yielded histologic material comparable in quality to CTP. The turnaround time for surgical pathology reports was improved substantially, and, in particular, same-day reporting was achieved in approximately 55% of cases compared with fewer than 1% before use of the RTP. Moreover, use of the RTP enhanced safety by eliminating formalin and xylene from the procedure.