The effect of dexmedetomidine on expressions of inflammatory factors in patients with radical resection of gastric cancer.

OBJECTIVE: To investigate the effect of dexmedetomidine on the expressions of inflammatory factors, T-lymphocyte subgroups and nuclear factor kappa-B (NF-κB) in peripheral blood monocytes in the perioperative period of radical resection of gastric cancer. PATIENTS AND METHODS: We selected 74 patients who were admitted to our hospital for radical resection of gastric cancer between January 2012 and October 2015. All patients were randomly divided into the dexmedetomidine group and the control group. Within 15 min before anesthesia induction, patients in the dexmedetomidine group received the intravenous injection of dexmedetomidine, while the same volume saline in the control group. During the operation, the initial dosage in the dexmedetomidine group was set as 1 µg/kg followed by 0.2 µg/kg•h intravenous injection to the end of operation. Three time points were selected: 15 min before anesthesia induction (T0), 1 h before the end of operation (T1) and 24 h after operation (T2). At these time points, we detected the levels of serum inflammatory factors using enzyme-linked immune sorbent assay (ELISA), immunoturbidimetry, and flow cytometer, respectively. RESULTS: The levels of IL-1ß, IL-6, TNF-α, NF-κB and CRP at T1 and T2 were significantly elevated compared with the levels at T0, and the amplitude of elevation in the control group was significantly larger than that in the dexmedetomidine group. The expression levels of T-lymphocyte subgroup in patients in both groups were decreased at T1 (compared with the levels at T0), and the decreasing extent of the ratio of CD4+ to CD8+ in the control group was significantly larger than that in the dexmedetomidine group. Meanwhile, we found that the percentages of CD3+ and CD4+ at T1 and T2 in the control group were significantly lower than those in the dexmedetomidine group. CONCLUSIONS: Dexmedetomidine can effectively reduce the release of inflammatory factors in patients that received the radical resection of gastric cancer, and the anti-inflammation effect may be exerted through downregulating the expression of NF-κB. Besides, dexmedetomidine can also alleviate the reduction in subgroups of CD3+ and CD4+, thereby ameliorating the impaired immune functions.

No difference of complete or incomplete left-sided malignant colonic obstruction on both short- and long-term outcomes.

The impact of complete and incomplete colonic obstruction on the short- and long-term outcomes of malignant colorectal cancer has not yet been elucidated. The aim of this study was to investigate whether there was a difference in the impacts of the 2 types of obstruction on the short- and long-term outcomes of colorectal resection. This study included 224 colorectal cancer patients (162 patients with incomplete obstruction and 62 with complete obstruction) with left-sided malignant colonic obstruction who underwent surgical therapy between February 2007 and September 2012. The short- and long-term outcomes of surgical therapy were analyzed. No significant difference was found between the 2 groups with regard to short-term outcomes such as the curative resection rate (80.86 vs 70.97%, P = 0.109), hospital stay time (24.20 ± 16.01 vs 24.19 ± 12.06, P = 0.999), and the overall and respective complications (32.72 vs 46.77%, P = 0.051). Furthermore, no significant difference was found between the 2 groups with regard to long-term outcomes including the 1-, 3-, and 5-year survival rates (P = 0.089), recurrence rates (P = 0.711), and recurrence-free survival rates (P = 0.440). The 2 types of obstruction, i.e., complete and incomplete left-sided malignant colonic obstruction, had no impact on the short- and long-term outcomes of colorectal resection. Similar therapeutic methods can be used for treating both types of obstruction.

Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion.

Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on ß1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of ß1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on ß1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of ß1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.

Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert's syndrome in Taiwanese adults.

Gilbert's syndrome (GS) is caused by a reduction in the activity of hepatic bilirubin UDP-glucuronosyltransferase (UGT). This reduction is associated with UGT1A1*28 and UGT1A1*6 polymorphisms. Recent research also showed that carriage of UGT1A1*6 allele were significantly related with UGT1A7*3. Polymerase chain reaction-restriction fragment length polymorphism were utilized to determine UGT1A7 and UGT1A1 genes for 207 patients with GS and 207 gender/age-matched healthy controls. For the 207 healthy controls, linkage disequilibrium was observed between -57UGT1A7 and 622UGT1A7 loci (D' = 1.00 and r(2) = 1.00), -57UGT1A7 and 211UGT1A1 loci (D' = 0.72 and r(2) = 0.36), respectively. A dose-response effect for number of at-risk allele of UGT1A1 and risk for GS was noted (odds ratio (OR) = 8.19 for heterozygous UGT1A1*28 genotype; OR = 124.96 for homozygous UGT1A1*28 genotype; and p for trend <0.05). Patients with combined genotypes carrying UGT1A7 variant alleles and UGT1A1 variant alleles (including UGT1A1*28 and UGT1A1*6) are associated with increased risk of GS (OR = 13.96 for patients with combined genotype carrying at least one variant allele of UGT1A1 and UGT1A7). In conclusion, the -57UGT1A7 (T>G) is highly associated with UGT1A7*3 and moderately associated with 211UGT1A1 (G>A). Certain UGT1A1/UGT1A7 combined genotypes are risk factors of GS.

Structure-activity analysis of guanidine group in agmatine for brain agmatinase.

To identify a selective inhibitor of mammalian agmatinase, screening was performed on four analogues of agmatine with modifications directly to the guanidine group, six analogues with modifications to the carbon-amine chain, and one analogue with modifications at both ends of the molecule. Control compounds were aminoguanidine and 7-nitroindazole, known inhibitors of the three isoforms (i, e, n) of nitric oxide synthase (NOS), and arcaine, a known inhibitor of the glutamate NMDA receptor. These compounds were compared for inhibition of rat agmatinase and arginine decarboxylase (ADC) activities. Results were studied by ab initio Hartee-Fock descriptors based on optimized geometries and van der Waals radii. Linear correlations were obtained using various geometric and electronic descriptors of the carbon (C), nitrogen (N), and hydrogen (H) atoms in the guanidine moiety. The best fit equation for percent activity remaining of rat agmatinase was = 0.3225 D + 72.76 D1916 + 64.97 D1920 - 192.58 H21 - 253.09 (r = 0.89), where D is the calculated dipole moment, D1916 and D1920 are the N19-N16 and N19-N20 distances, respectively, and H21 is the charge on H21. This agmatinase equation is distinct from the equations fit for ADC, the three NOS isoforms, and inhibition of NMDA receptor binding.

A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the antitumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.