Abstract. Microtubule affinity-regulating kinases (MARKs; MARK1, MARK2, MARK3 and MARK4) act directly downstream of LKB1, the multitasking tumor-suppressor kinase, and thereby mediate its biological effects. Current understanding of the function of MARKs is greatly restricted to regulation of cell polarity. However, whether or how MARKs contribute to cellular growth control remains largely unknown. In the present study, we utilized an inducible lentiviral expression system that allows rapid MARK expression in LKB1-deficient HeLa cells, and characterized additional functions of MARKs: overexpression of MARK2 in HeLa cells resulted in a decrease in cell growth, inhibition of colony formation and arrest in G1 cell cycle phase, with AMPK as the putative downstream effector upregulating the expression of p21 and p16. MARK2 was found to play a role in F-actin reorganization and to contribute to reversal of epithelial-mesenchymal transition (EMT) as exemplified in the case of HeLa cells that exhibited phenotypic changes, reduced cell migration and invasion. Our findings unveil the coordinated regulation of cell growth and EMT mediated by MARK2, and also provide new insights into the mechanisms underlying the anti-metastatic activity of MARK2.

The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer.

In this study, dry‐cured Spanish mackerel ( Scomberomorus niphonius , DCSM) was prepared via three different methods (hot‐air drying, cold‐air drying, and sun drying). The content of 4‐hydroxy‐2‐hexenal (HHE) and 4‐hydroxy‐2‐nonenal (HNE) derived from lipid oxidation in whole processes was investigated by HPLC‐MS/MS. The changes in fatty acid composition were detected by GC‐MS, and the degree of lipid oxidation was evaluated by the levels of acid values (AV), peroxide values (POV), and thiobarbituric acid‐reactive substances (TBARS). The results showed that the drying process significantly accelerated lipid oxidation in DCSM. The contents of HHE and HNE were significantly increased after processing. The content of HHE was higher by 18.44‐, 13.45‐, and 16.32‐folds compared with that of HNE after three different processes, respectively. The HHE and HNE contents fluctuated upward during the hot‐air and cold‐air drying process. However, the contents of HHE and HNE increased time‐dependent during the sun drying process, with the highest values of 86.33 ± 10.54 and 5.29 ± 0.54 mg/kg fish among the three different processes. Besides, there was a significant positive correlation between HHE contents and n‐3 fatty acids content in hot‐air drying and sun drying processes (Pearson's r = .991/.996), and HNE occurrence was closely related to n‐6 fatty acid content in sun drying process (Pearson's r = .989). Regression analysis indicated that the content of HHE and TOTOX TBA values in DCSM showed good linear relationships ( R 2 value = .907), which suggested that the content of HHE could be used to estimate the oxidative deterioration of dry‐cured fish products.

Background: This study intends to compare the short-term effects and long-term survival of gastric cancer patients who underwent delta-shaped anastomosis (DA) and Billroth I reconstructions after laparoscopic distal gastrectomy.Methods: We retrospectively collected data from 257 patients with gastric cancer who underwent laparoscopic distal gastrectomy between January 2013 and December 2017. Patients were classified into 2 groups according to the reconstruction method used: the DA group (n=91) and the Billroth I group (n=166).The clinical data, short-term efficacy, and long-term results were compared between the 2 groups.Results: The operation time (P<0.001) and the post-operative length of hospital stay (P<0.001) were shorter in the DA group than in the Billroth I group. The time to the first oral intake of a soft diet after surgery was earlier in the DA group than in the Billroth I group (P=0.014). Kaplan-Meier (log-rank test) analysis showed no significant difference in the 5-year survival rates between the 2 groups for patients at the same pathological stage. Multivariate analysis showed that abnormal carcinoembryonic antigen (CEA) (P=0.006), chemotherapy (P<0.001), T stage (P<0.001), and N stage (P<0.001) were independent prognostic factors for survival.Conclusions: DA and Billroth I are feasible and safe reconstruction methods of the digestive tract after gastric cancer. DA is the recommended reconstruction method for laparoscopic distal gastrectomy.

BackgroundImatinib is the first-line adjuvant treatment for gastrointestinal stromal tumors (GISTs). Considering that some studies have suggested that imatinib (IM) plasma trough levels (Cmin) change with time, the aim of this study is to assess the changes in IM Cmin in patients with GIST in a long-term study and to elucidate the relationships between clinicopathological features and IM Cmin.MethodsIn 204 patients with intermediate- or high-risk GIST who were taking IM, IM Cmin was analyzed. Patient data were grouped according to the duration of medication (A: 1–3 months, B: 4–6 months, C: 7–9 months, D: 10–12 months, E: ≤12 months, F: 12&lt;–≤36 months, G: &gt;36 months). The correlation between IM Cmin at different time stages and clinicopathological characteristics was assessed.ResultsStatistically significant differences were observed between Groups A, C, and D (P = 0.049 and 0.01, respectively). In Group E, IM Cmin correlated with sex (P = 0.049) and age (P = 0.029) and negatively correlated with body weight, height, and body surface area (P = 0.007, 0.002, and 0.001, respectively). In Groups F and G, IM Cmin was significantly higher in non-gastric operation patients than in patients with gastrectomy (P = 0.002, 0.036) and was significantly higher in patients with the primary sites of others than in the stomach (P &lt; 0.001, = 0.012). In addition, IM Cmin was much higher in patients with mutation sites other than KIT exon 11 in Group F (P = 0.011).ConclusionThis is the first study of IM Cmin during the long-term treatment of patients with intermediate- or high-risk GIST. IM Cmin was the highest for the first 3 months and then declined, and long-term administration of IM showed a relatively stable plasma trough level. The IM Cmin correlated with different clinical characteristics at different durations of medication. This meant that future “trough level–clinicopathological characteristics” analyses should be time-point-specific. We also need to formulate time-specific medication monitoring plans in clinical practice to study disease progression caused by the occurrence of drug resistance.