In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC is loss of intercellular adhesion. Although widely attributed to mutations in the CDH1 gene encoding E-cadherin, a significant percentage of diffuse GC do not harbor CDH1 mutations. We found that the expression of the actin-modulating cytoskeletal protein, gelsolin, is significantly higher in diffuse-type compared to intestinal-type GCs, using immunohistochemical and microarray analysis. Furthermore, in GCs with wild-type CDH1, gelsolin expression correlated inversely with CDH1 gene expression. Downregulating gelsolin using siRNA in GC cells enhanced intercellular adhesion and E-cadherin expression, and reduced invasive capacity. Interestingly, hepatocyte growth factor (HGF) induced increased gelsolin expression, and gelsolin was essential for HGF-medicated cell scattering and E-cadherin transcriptional repression through Snail, Twist and Zeb2. The HGF-dependent effect on E-cadherin was found to be mediated by interactions between gelsolin and PI3K-Akt signaling. This study reveals for the first time a function of gelsolin in the HGF/cMet oncogenic pathway, which leads to E-cadherin repression and cell scattering in gastric cancer. Our study highlights gelsolin as an important pro-disseminative factor contributing to the aggressive phenotype of diffuse GC.
There is currently no examination technique that allows direct measurement of supraorbital nerve conduction velocity and amplitude. Therefore, in this study we describe a novel nerve conduction technique that allows measurement of the supraorbital sensory nerve action potential (SNAP) distal to the supraorbital foramen. Supraorbital SNAPs were recorded bilaterally from 17 healthy volunteers using an antidromic technique. The SNAPs were consistently recordable over the site 6 cm lateral to the midline point that was marked 10 cm above the nasion. Measured parameters included peak latency (mean 2.3 ms, SD 0.3), amplitude (mean 14.6 μV; SD 10.5), and velocity (mean 51.3 m/s, SD 6.8). The mean percentage of interside difference in amplitude was 25.6% (SD 17.3). Cut-off values (97th percentile) were 2.7 ms (peak latency), 3.3 μV (amplitude), 41.9 m/s (conduction velocity), and 54.9% (interside difference in amplitude). Supraorbital SNAPs can be recorded in all normal subjects and used as a quantitative measure of the functioning large fibers in the nerve.
BackgroundThe combination of polycaprolactone and hyaluronic acid creates an ideal environment for wound healing. Hyaluronic acid maintains a moist wound environment and accelerates the in-growth of granulation tissue. Polycaprolactone has excellent mechanical strength, limits inflammation and is biocompatible. This study evaluates the safety and efficacy of bio-conjugated polycaprolactone membranes (BPM) as a wound dressing.Methods16 New Zealand white rabbits were sedated and local anaesthesia was administered. Two 3.0×3.0 cm full-thickness wounds were created on the dorsum of each rabbit, between the lowest rib and the pelvic bone. The wounds were dressed with either BPM (n=12) or Mepitel (n=12) (control), a polyamide-silicon wound dressing. These were evaluated macroscopically on the 7th, 14th, 21st, and 28th postoperative days for granulation, re-epithelialization, infection, and wound size, and histologically for epidermal and dermal regeneration.ResultsBoth groups showed a comparable extent of granulation and re-epithelialization. No signs of infection were observed. There was no significant difference (P>0.05) in wound size between the two groups. BPM (n=6): 8.33 cm2, 4.90 cm2, 3.12 cm2, 1.84 cm2; Mepitel (n=6): 10.29 cm2, 5.53 cm2, 3.63 cm2, 2.02 cm2; at the 7th, 14th, 21st, and 28th postoperative days. The extents of epidermal and dermal regeneration were comparable between the two groups.ConclusionsBPM is comparable to Mepitel as a safe and efficacious wound dressing.
Changes in cabin pressure can potentially cause expansion of any preexisting intracranial air resulting in tension pneumocephalus. The authors describe a 28-year-old man, who was involved in a motor vehicle accident complicated by multiple facial fractures and a dural tear while on his way to the airport. Instead of seeking medical attention after the accident, he proceeded with a 2-hour commercial flight. He did not suffer from any neurologic deterioration inflight, but upon presentation to our center, a computed tomography scan was done which revealed extensive pneumocephalus, for which he required intensive monitoring and subsequent surgery. Controversy still exists regarding whether it is safe to travel by air in patients with intracranial air. It is hoped that this patient will add to the discussion regarding the safety for air travel in patients with traumatic pneumocephalus.
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