Background: Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells. Aims: To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. Methods: CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays.Results: Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p,0.001) and cytoplasmic (p,0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p,0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility. Conclusions: Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.
Background: The standard treatment for acute pancreatitis (AP) still remains based on supportive care. The searching for a drug that could alter the outcomes of this disease is a challenge. Some experimental studies report that previous inhibition of Cox-2 (the inflammatory isoform of cyclooxygenase) can ameliorate the histologic changes of the pancreas and the pulmonary lesion caused by systemic releasing of cytokines and others inflammatory mediators. The aim of this study is to evaluate the Cox-2 inhibition as a treatment for experimental acute pancreatitis. Material and Methods: Sixty Wistar male rats (240-260 g) were divided in two main groups: Group I (n = 30) -animals with taurocholate-induced acute pancreatitis treated with parecoxib (40 mg/Kg). Group II (n = 30) -animals with taurocholate-induced acute pancreatitis that received saline. AP was induced by retrograde injection of sodium taurocholate (2.5 %) into the main pancreatic duct. The Cox-inhibitor (parecoxib) was injected through penis dorsal vein immediately after AP induction. The parameters evaluated were histology, 72-hours mortality rate and serum levels of amylase, interleukin-10 (IL-10) and interleukin-6 (IL-6). Results: Serum levels of IL-6 and IL-10 were lower than in control group. Amylase serum levels and 72-hours mortality rate remained unchanged. Histologic evaluation was also unaltered, except for fat necrosis, which was worse in the parecoxib rats. Conclusion: Inhibition of Cox-2 might decrease the systemic release of at least two cytokines, but has a poor effect on mortality rate and on direct pancreas injury caused by taurocholate. .Purpose: In our previous communications, we reported the efficacy of genistein in augmenting the effects chemotherapeutic agents such as cisplatin and gemcitabine in pancreatic cancer cells in vitro (S.Banerjee et.al., APA-2004; AACR-2005). Here we report mechanism based evidence for the observed beneficial effect in vivo in SCID mice bearing orthotopically implanted pancreatic cancer cells. Background & Aims: Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Recent data suggests that genetic variation in functional gene polymorphisms of Glutathione S-Transferase theta-1 (GSTT-1*A) may help explain varying biological responses to AP. Our aim was to determine whether the GSTT-1*A polymorphism affects the severity of AP. Methods: 91 consecutive patients with AP (19 severe) and 268 controls were evaluated. The GSTT-1*A functional genotype was evaluated by polymerase chain reaction amplification, and restriction fragment length polymorphism.Results: The functional GSTT-1*A polymorphism was not significantly different in SAP (15 of 19; 78.9%) as compared to MAP (61 of 72; 84.7%; p = 0.54) and controls (228 of 268; 85.1%; p = 0.66). The functional GSTT-1*A genotype was not associated with elevated peak serum CRP (11.9 mg/dl vs 7.3 mg/dl; p = 0.19), IL-6 (74 vs 60; p = 0.9), APACHE II scores (7 vs 9; p = 0.26) or 48 hour Ranson sco...
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