Serum galectin-3 concentrations in patients with ankylosing spondylitis.

OBJECTIVE: The aim of our study was to assess potential correlations between serum galectin-3 concentrations and Ankylosing Spondylitis Disease Activity (ASDAS) index in patients with ankylosing spondylitis (AS). METHODS: A total of 112 patients with AS were included, and 130 healthy subjects were considered as controls. We collected the detailed medical history, and ASDAS index was used to assess the disease severity in patients with AS. RESULTS: The serum galectin concentrations were higher in AS patients compared to the health groups (14.1 ± 9.6 vs 9.2 ± 3.7, P < 0.001). The correlation analysis showed that serum galectin concentrations were significantly positively correlated with C-reactive protein and erythrocyte sedimentation rate (r = 0.369, P < 0.001; r = 0.240, P = 0.011). In addition, the positively correlation of serum galectin-3 with global pain index (r = 0.238, P = 0.011) was observed in AS patients. A significant positively correlation between serum galectin and ASDAS index in AS patients was found (r = 0.367; P < 0.001). In multiple linear regression analysis, the results indicated that increased serum galectin still was correlated with ASDAS index (r = 0.322, P < 0.001) in patients with AS. CONCLUSIONS: Serum galectin concentrations were found to be correlated with ASDAS index in patients with AS.

[Case-control study on modified Weaver-Dunn surgery combined with clavical hook-plate internal fixation for the treatment of Tossy type III acromioclavicular dislocation].

OBJECTIVE: To compare therapeutic effects of clavicular hook-plate fixation and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation in treating Tossy type III acromioclavicular joint dislocation. METHODS: Forty-one patients with Tossy type III acromioclavicular dislocation treated by operation were retrospectively analysis from January 2012 to January 2014. The patients were divided into clavicular hook-plate fixation group (group A) and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation (group B) according to surgical procedures. In group A, there were 15 males and 6 females aged from 17 to 51 years old with an average of (31.60 ± 12.58) years old, preoperative Constant-Murley score was 40.25 ± 9.80, and treated with clavicular hook-plate fixation. In group B, there were 13 males and 7 females aged from 18 to 48 years old with an average of (29.40 ± 11.27) years old, preoperative Constant-Murley score was 41.45 ± 8.81, and treated with modified Weaver-Dunn surgery combined with clavicular hook-plate fixation. Operative time, blood loss, imaging changes before and after operation, postoperative complications were compared; Constant-Murley score at 3, 6 and 12 months after operation were evaluated. RESULTS: In group A, operative time was 40.50 ± 24.36) min, blood loss was (75.30 ± 30.36) ml; In group B, operative time was (60.10 ± 23.55) min, blood loss was (100.70 ± 40.12) ml. Twenty-one patients in group A were followed-up from 12 to 18 months with an average of (14.8 ± 3.1) months; 20 patients in group B were followed-up from 12 to 14 months with an average of (13.6 ± 1.5) months. There were no significant differences in operative time, blood loss and follow-up time between two groups. Complications were in six patients of group A and 3 patients of group B, and there were no significant meaning between two groups. At 6 months after operation, Constant-Murley score in group A was 88.85 ± 4.23, 92.15 ± 3.82 in group B; and had significant meaning between two groups (t = -2.56, P = 0.022 < 0.05). While there were no differences in Constant-Murley score in other times. CONCLUSION: Both of clavicular hook-plate fixation and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation are effective operative methods for the treatment of Tossy type III acromioclavicular dislocation. Clavicular hook-plate fixation has advantage of less trauma, while modified Weaver-Dunn surgery combined with clavicular hook-plate fixation could reconstruct coracoclavicular ligament more stronger, clavicular hook plate could take out earlier, also improve shoulder joint function earlier.

11-Phenyl-[b,e]-dibenzazepine compounds: novel antitumor agents.

A series of 11-phenyl-[b,e]-dibenzazepine compounds were synthesized and shown to be inhibitors of tumor cell proliferation with IC(50) values ranging from submicromolar to micromolar concentrations. Flow cytometric analyses of several active compounds demonstrated inhibition of cell cycle progression at the G(0)-G(1) phase transition resulting in G(0)-G(1) arrest.

NK cell activation and tumor infiltration are involved in the antitumor mechanism of Virulizin.

Previous studies have demonstrated antitumor efficacy of Virulizin in several human tumor xenograft models and a critical role for macrophages in the antitumor mechanism of Virulizin. Although there is growing support for an immune stimulatory mechanism of action for Virulizin, the details remain to be elucidated. The aim of this study was to determine whether infiltration of natural killer (NK) cells into xenografted tumors is altered by Virulizin treatment, and whether such alterations contribute to the antitumor activity of Virulizin. Immunohistochemical analysis demonstrated that xenografted tumors from Virulizin-treated mice had an increase in infiltration of F4/80(+) (macrophages) and NK1.1(+) (NK) cells. The increase in NK1.1(+) cell infiltration occurred at an early stage of Virulizin treatment, which correlated with an early sign of apoptosis. In addition, Virulizin resulted in an increase in the number of NK cells in the spleens, and NK cells isolated from the spleen exhibited increased cytotoxicity to tumor cells in vitro. In NK cell-deficient SCID-beige mice, the antitumor activity of Virulizin was compromised, providing additional support to the hypothesis that NK cells are necessary for inhibition of tumor growth by Virulizin. Finally, depletion of macrophages resulted in the loss of Virulizin-induced increase in NK1.1(+) cell infiltration into xenografted tumors, suggesting the involvement of macrophages in NK cell infiltration into tumors. Taken together, these results strongly support a mechanism in which Virulizin stimulates a sustained expansion and infiltration of NK cells and macrophages into tumors with subsequent activation of NK cells that is responsible for the observed antitumor activity.

Triaryl methane derivatives as antiproliferative agents.

Clotrimazole (CLT) 1, a synthetic anti-fungal imidazole derivative, inhibits tumor cell proliferation and angiogenesis. In the current study, flow cytometric analysis demonstrated that the decrease in tumor cell growth by CLT 1 was associated with inhibition of cell cycle progression at the G(1)-S phase transition, resulting in G(0)-G(1) arrest. A series of CLT 1 analogues has been generated in order to develop CLT 1 derivatives that are devoid of the imidazole moiety which is responsible for the hepatoxicity associated with CLT 1 while retaining CLT 1 efficacy. The majority of these analogues demonstrate in vitro antiproliferative activity ranging from submicromolar to micromolar concentrations.

NC381, a novel anticancer agent, arrests the cell cycle in G0-G1 and inhibits lung tumor cell growth in vitro and in vivo.

Although clotrimazole (CLT), an antifungal drug, inhibits tumor cell proliferation and angiogenesis, its clinical application is hampered by significant hepatotoxicity due to the presence of an imidazole moiety. In our attempts to develop CLT analogs that are devoid of imidazole and are as efficacious as CLT, one pharmacophore designated NC381 was generated and shown to inhibit tumor cell growth via a mechanism similar to that of CLT. In vitro, treatment of NCI-H460 nonsmall cell lung cancer (NSCLC) cells with NC381 inhibited growth in a time-dependent manner. Flow cytometric analysis demonstrated that the decrease in cell growth was associated with inhibition of cell cycle progression at the G(1)-S phase transition, resulting in G(0)-G(1) arrest. There was a concomitant inhibition of cyclin D1 expression and subsequent reduction in the formation of the cyclin D1-CDK4 complex. Consistent with a decrease in the cyclin D1-CDK4 complex, NC381 treatment resulted in significant inhibition of pRb phosphorylation. There also were changes in the activity of cell cycle-related proteins, including p16(Ink4) and p27(Kip1). Together, these results are consistent with a model in which NC381 arrests cell cycle progression via inhibition of the pathway that promotes exit from the G(1) phase of the cell cycle. Furthermore, the clinical applicability of NC381 was evaluated in an in vivo murine xenograft model of human NSCLC (NCI-H460). NC381 treatment resulted in significant inhibition of tumor growth. Given the poor prognosis and the limited treatment options available, the present results underscore the potential of NC381 in the treatment of human NSCLC.

Adenovirus-mediated ribonucleotide reductase R1 gene therapy of human colon adenocarcinoma.

Ribonucleotide reductase is the enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides for DNA synthesis. Ribonucleotide reductase is a multisubunit complex containing two polypeptides, R1 and R2. In addition to catalytic and allosteric regulatory functions, the R1 subunit appears to act as a novel tumor suppressor. Previous studies demonstrated that overexpression of mouse R1 resulted in suppression of tumorigenicity and metastatic potential, whereas expression of antisense RNA, complementary to R1 mRNA, increased anchorage-independent growth of ras-transformed NIH 3T3 cells. The current study investigated the potential of R1 gene therapy for human cancer using a recombinant adenovirus encoding the human R1 gene (rAd5-R1). Recombinant viruses were constructed by FLP-mediated site-specific recombination and demonstrated high infectivity of a human colon carcinoma cell line (Colo320 HRS), as assessed by expression of a viral encoded beta-Gal gene (rAd5-LacZ). R1mRNA and protein were overexpressed in Colo320 HRS cells infected with rAd5-R1 compared with untreated or rAd5-LacZ-infected cells. Infection with rAd5-R1 inhibited Colo320 HRS cell proliferation, in vitro, in a time- and dose-dependent manner. When Colo320 HRS cells were treated with rAd5-R1, before injection into CD-1 mice, there was complete inhibition of tumor growth compared with treatment with rAd5-LacZ. Furthermore, intratumoral injection of rAd5-R1 into Colo320 HRS tumor xenografts inhibited tumor growth in CD-1 mice compared with rAd5-LacZ treated mice (P = 0.0001). These results demonstrate gene-specific antitumor effects of R1 and suggest that rAd5-R1 gene therapy has the potential to improve currently available treatments for colon cancer.