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Purpose: As a cyclin-independent atypical CDK, the role of CDK5 in regulating cell proliferation in gastric cancer remains unknown.Experimental Design: Expression of CDK5 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was measured by Western blotting, immunohistochemistry, and realtime PCR. The subcellular translocation of CDK5 was monitored during gastric cancer cell proliferation. The role of nuclear CDK5 in gastric cancer tumorigenic proliferation and ex vivo xenografts was explored. Furthermore, by screening for compounds in the PubChem database that disrupt CDK5 association with its nuclear export facilitator, we identified a small molecular (NS-0011) that inhibits gastric cancer cell growth.Results: CDK5 level was significantly decreased in the majority of gastric tumor tissues, and the reduction of CDK5 correlated with the severity of gastric cancer based on tumor and lymph node metastasis and patient 5-year fatality rate. Nuclear localization of CDK5 was found to be significantly decreased in tumor tissues and gastric cancer cell lines, whereas exogenously expression of nucleus-targeted CDK5 inhibited the proliferation and xenograft implantation of gastric cancer cells. Treatment with the small molecule NS-0011, which increases CDK5 accumulation in the nucleus, suppressed both cancer cell proliferation and xenograft tumorigenesis.Conclusions: Our results suggest that low CDK5 expression is associated with poor overall survival in patients with gastric cancer, and nuclear accumulation of CDK5 inhibits the proliferation and tumorigenicity of human gastric cancer cells.

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Background. We developed a novel procedure for spleenpreserving No. 10 lymph node (LN) dissection, which is difficult and advocates for patients with advanced proximal gastric cancer, except those with direct tumor extension to the spleen or definite LN metastasis at the splenic hilum. Methods. The surgeon reveals the splenic vessels (SVs), and the assistant pulls up the lymphatic fatty tissue on the surface of the lower lobar vessels of the spleen (LLVSs). The surgeon then exposes the left gastroepiploic vessels (LGEVs), completely separating the LLVSs from the LGEV roots. After tracking the SV termini, the No. 11d LNs are carefully dissected and the upper lobar vessels of the spleen are exposed from their roots to the upper pole of the spleen. During this process, 2-4 branches of the short gastric vessels are skeletonized and divided at their roots. The LNs behind the SVs in front of Gerota's fascia are then dissected. The above procedure was performed on 118 consecutive patients with stage cT2-3 disease. Results. Mean operation time was 20.4 ± 6.0 min (range 13-41 min), mean blood loss was 13.6 ± 4.0 ml (range 10-40 ml), and mean times to first flatus, fluid diet, and soft diet were 3.3 ± 1.2 days (range 2-8 days), 4.8 ± 1.6 days (range 3-14 days), and 8.1 ± 4.1 days (range 6-20 days), respectively. A mean 44.6 ± 17.3 LNs (range 22-103) were retrieved, including a mean 3.0 ± 2.4 (range 0-11) splenic hilar area LNs. At a median follow-up of 9 months, no patients had died or experienced recurrent or metastatic disease.Conclusions. This procedure is feasible and simplifies complicated laparoscopic No. 10 LN dissection.