Due to the poor prognosis of pancreatic cancer, novel diagnostic modalities for early diagnosis and new therapeutic strategy are urgently needed. Recently, microRNA-21 (miR-21) was reported to be strongly overexpressed in pancreatic cancer as well as in other solid cancers. We investigated the functional roles of miR-21, which have not been fully elucidated in pancreatic cancer. miR-21 expression was assessed in pancreatic cancer cell lines (14 cancer cell lines, primary cultures of normal pancreatic epithelial cells and fibroblasts, and a human normal pancreatic ductal epithelial cell line) and pancreatic tissue samples (25 cancer tissues and 25 normal tissues) by quantitative real-time reverse transcription-PCR amplification. Moreover, we investigated the proliferation, invasion, and chemoresistance of pancreatic cancer cells transfected with miR-21 precursor or inhibitor. miR-21 was markedly overexpressed in pancreatic cancer cells compared with nonmalignant cells, and miR-21 in cancer tissues was much higher than in nonmalignant tissues. The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor. These data suggest that miR-21 expression is increased in pancreatic cancer cells and that miR-21 contributes to the cell proliferation, invasion, and chemoresistance of pancreatic cancer.
This observational study strictly adjusted for confounding factors has provided evidence to suggest that LG is oncologically comparable to OG for locally advanced gastric cancer. The validity of this result will be examined in ongoing randomized trials.
Recently, we reported a novel ultrasound technique to assess the biomechanical properties of the oesophagus in humans. To investigate whether the oesophageal sensation induced by oesophageal distension correlates with wall tension, wall stress or wall strain, we studied 20 healthy subjects using a manometry catheter equipped with a high-compliance bag and a high-frequency intraluminal ultrasound probe. Oesophageal distensions were performed by injecting 1-20 mL water into the bag for 20-30 s. Subjects scored the nature (heartburn or chest pain) and severity of sensation in response to distension, before and after atropine (15 microg kg(-1), i.v.). Ultrasound images of oesophagus were digitized and measurements were made to calculate oesophageal wall tension, stress and strain during distensions. Subjects experienced mostly heartburn, not chest pain, in response to oesophageal distension. Oesophageal wall strain and bag pressures correlated best with the oesophageal sensation. Atropine reduced bag pressure but did not affect the distension induced heartburn and chest pain. We conclude that heartburn is a common sensation in response to oesophageal distension in normal subjects. A strong correlation between wall strain and oesophageal sensation suggests that the wall stretch is the stimulus for nociceptive mechanoreceptors of the oesophagus.
The effect of atropine, a smooth muscle relaxant, has often been determined as a change of compliance in the gastrointestinal (GI) tract. There are reports that atropine increases, decreases or has no effect on the compliance of the oesophagus in isovolumic distension studies (Barish et al. 1984;Richter et al. 1986;Paterson, 1991;Paterson et al. 1991a;Mayrand & Diamant, 1993;Mayrand et al. 1994). The compliance, however, is not an accurate measure of the wall stiffness. The elastic modulus, which is determined from the stress-strain relationship, is a more accurate measure of the wall stiffness. It has not been possible, however, to measure stress and strain in vivo in humans because previous methods could not measure wall thickness, luminal radius and pressure simultaneously. We recently developed a novel ultrasound technique that can measure all of the above-mentioned parameters simultaneously, in real time. Therefore, our technique allows accurate measurement of loading and deformation and subsequent computation of stress, strain and elastic modulus of the human oesophagus in vivo.The oesophagus consists of several layers, mucosa, submucosa and muscularis propria. The latter consists of circumferential and longitudinal muscle fibres. The muscle layer has both passive and active properties consistent with the Hill's three elements model and the non-muscle tissue has only passive properties. The active contraction of the muscle can be described by a combination of 'contractile element' in series with an 'elastic element'. The passive component can be described by a 'parallel element'. The goals of our study were to determine: (1) the effect of atropine on the stress-strain properties of the human oesophagus under isovolumic and isobaric test conditions, and (2) the active and passive components of the wall stress properties of the human oesophagus. Effect of atropine on the biomechanical properties of the oesophageal wall in humansTorahiko Takeda*, Ghassan Kassab †, Jianmin Liu*, Toshinaga Nabae* and Ravinder K. Mittal* Recently, we reported a novel ultrasound technique to assess biomechanical properties of the oesophagus in human subjects. In the present study, we use the technique, in combination with atropine, to determine the active and passive biomechanical properties of the oesophagus in normal healthy humans. A manometric catheter equipped with a high-compliance bag and a high-frequency intraluminal ultrasonography probe was used to record pressure and oesophageal geometry. Oesophageal distensions with either isovolumic (5-20 ml water) or with isobaric (10-60 mmHg) technique were performed. Intra-bag pressure and ultrasound images of the oesophagus were recorded simultaneously. Following injection of atropine (15 mg kg _1 , I.V.), the oesophageal distensions were repeated. The oesophageal wall compliance, circumferential wall tension, stress, strain and elastic modulus were calculated. Atropine resulted in an increase in the oesophageal wall compliance during isobaric distension, but no change in complia...
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