The novel antitumor compound clinopodiside A induces cytotoxicity via autophagy mediated by the signaling of BLK and RasGRP2 in T24 bladder cancer cells.

In the study, we investigated the anti-cancer effect of clinopodiside A and the underlying mechanisms using T24 bladder cancer cells as an experimental model. We found that the compound inhibited the growth of the bladder cancer cells in vitro and in vivo in a in a concentration- and dose-dependent manner, respectively, which showed a combinational effect when used together with cisplatin. In the bladder cancer cells, clinopodiside A caused autophagy, which was mediated by the signaling of BLK and RasGRP2, independently. Inhibition of the autophagy by chemical inhibitor 3-methyladenine or by the inhibition of the signaling molecules attenuated the cytotoxicity of clinopodiside A. Further analyses showed that clinopodiside A acted in synergism with cisplatin which itself could trigger both autophagy and apoptosis, which occurred with concomitant enhancements in autophagy and the cisplatin-evoked apoptosis. In conclusion, our results suggest that clinopodiside A inhibits the growth of the bladder cancer cells via BLK- and RasGRP2-mediated autophagy. The synergistic effect between clinopodiside A and cisplatin is attributed to the increases in autophagy and autophagy-promoted apoptosis. Clinopodiside A is a promising investigational drug for the treatment of cancer, at least blabber, which can be used alone or in combination with clinical drug(s).

The association of preoperative atrial fibrillation with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients.

OBJECTIVE: The purpose of this study was to assess the fibrinolytic status after cardiopulmonary bypass in rheumatic valvular heart disease patients, and detect the associated factors of post-cardiopulmonary bypass hyperfibrinolysis. METHODS: According to the fibrinolytic status after cardiopulmonary bypass, 203 rheumatic valvular heart disease patients were divided into two groups: hyperfibrinolysis group (H group, n = 78) and non-hyperfibrinolysis group (NH group, n = 125). The demographic characteristics, operative variables, and postoperative follow-ups were compared between these two groups. RESULTS: The incidence of hyperfibrinolysis was 38.4% after cardiopulmonary bypass. Patients in the H group had a significant higher incidence of preoperative atrial fibrillation than patients in the NH group (92.3% vs. 55.2%, P < 0.01). Furthermore, postoperative daily drainage (655.3 ±â€¯131.5 ml vs. 535.4 ±â€¯161.4 ml, P < 0.01), transfusion volume of fresh frozen plasma (621.8 ±â€¯220.2 ml vs. 455.2 ±â€¯208.5 ml, P < 0.01), and red blood cells (5.9 ±â€¯2.2 u vs. 4.7 ±â€¯2.8 u, P < 0.01) was greater in the H group than in the NH group. Moreover, the logistic regression analysis revealed that preoperative atrial fibrillation was associated with post-cardiopulmonary bypass hyperfibrinolysis (OR = 19.691, 95% CI = 6.849-56.612; P < 0.05). CONCLUSION: Preoperative artial fibrillation is associated with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients.

[Plaque excision plus autologous perididymal patch grafting for Peyronie's disease].

OBJECTIVE: To investigate the clinical effect of plaque excision plus autologous perididymal patch grafting in the treatment of Peyronie's disease. METHODS: This study included 10 patients with Peyronie's disease received in our Department of Urology between January 2013 and December 2015, who had failed to respond to over 12 months of expectant drug therapy and remained stable for more than 6 months, none able to perform sexual intercourse due to penile curvature (>60°). All the patients underwent plaque excision plus autologous perididymal patch grafting. RESULTS: Postoperative follow-up ranged from 6 to 24 months. All the patients achieved normal penile erection, without testicular atrophy, torsion or necrosis at the surgery side and all were satisfied with the surgical results without complaining about obvious penile shortening. CONCLUSIONS: Plaque excision plus autologous perididymal patch grafting is a safe, simple, economic and effective method for the treatment of Peyronie's disease.

Effects of disodium cantharidinate on dendritic cells of patients with bladder carcinoma.

The present study explored the effects of disodium cantharidinate (DC) on the peripheral blood-derived dendritic cells of patients with bladder carcinoma. The peripheral blood mononuclear cells from the 15 cases of urinary bladder carcinoma of middle and advanced stage were separated, and dendritic cells were prepared. The morphological changes of dendritic cells were observed. Flow cytometry was used to detect the expression levels of CD1a and CD83 on dendritic cell surface. MTT assay was utilized to measure the proliferation ability of allogeneic lymphocyte stimulated by DC. Annexin V-FITC/propidium iodide (PI) double staining flow cytometry method was carried out to detect cell apoptosis after treatment with DC. The changes in caspase-3 and PARP expression levels were investigated by western blot method. The high-dose DC resulted in a significant increase in the expressions of dendritic cell phenotyptic molecules CDla and CD83 as compared to control group. In addition, the proliferation index of allogenic lymphocyte stimulated by DC was significantly higher than that of control group. Moreover, MTT assay showed significant inhibition of the growth of BIU-87 cells. After 24 h of DC treatment, double staining flow cytometry confirmed the ability of DC to induce cell apoptosis. Further, western blot method showed a significant elevation of caspase-3 and PARP protein expression after DC treatment. In conclusion, DC treatment could induce dendritic cell maturation of patient with carcinoma of urinary bladder and promote its functional changes. Furthermore, DC was able to inhibit the proliferation of cell BIU-87 and also has the ability to induce cell apoptosis.

The antitumor effect of the novel cancer-specific adenovirus Ad-VEGFR on bladder cancer in vitro and in vivo.

Bladder cancer is one of the most common cancers. Approaches that block tumor angiogenesis are a new therapeutic strategy for locally advanced or metastatic BC. VEGF/VEGFR signaling has been obviously and negatively correlated with the progression and invasion of cancer. In this study, we constructed the recombinant adenovirus vAd-VEGFR-3 to investigate its antitumor effector in vitro/vivo. First, we used the recombinant adenovirus vAd-VEGFR-3 to infect bladder cancer cells and then collected the cell culture supernatant to treat human umbilical vein endothelial cells (HUVECs). The proliferation, migration and apoptosis of HUVECs were respectively detected by MTT, transwell and Annexin V-FITC/PI double staining. In addition, mouse bladder mucosa was injured by trypsin, and the orthotopic transplantation model of human bladder cancer was successfully constructed to clarify the anti-tumor effect of Ad-VEGFR in vivo. The results showed that Ad-VEGFR could inhibit the cancer's proliferation and migration, while promoting the apoptosis of HUVECs in vitro. Moreover, Ad-VEGFR could significantly promote the apoptosis of bladder cancer cells and then prevent tumor growth in vivo. In addition, it also down-regulated the expression levels of CD31, an endothelial cell marker which is closely related to the angiogenesis. Taken together, it suggests that the infection of adenovirus-carrying VEGFR in bladder cancer cells may inhibit blood vessel formation and prevent tumor progression.

Genetic polymorphisms of CYP1A1 and risk of leukemia: a meta-analysis.

The associations between CYP1A1 polymorphisms and risk of leukemia have been studied extensively, but the results have been inconsistent. Therefore, in this study, we performed a meta-analysis to clarify associations of three CYP1A1 polymorphisms (T3801C, A2455G, and C4887A) with the risks of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Medline, EMBASE, and China National Knowledge Infrastructure databases were searched to collect relevant studies published up to April 20, 2015. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated to quantify the associations. Overall, 26 publications were included. Finally, T3801C was associated with an increased risk of AML in Asians under the dominant model. For A2455G, the risk of ALL was increased among Caucasians in the recessive model and the allele-contrast model; A2455G was also associated with an increased risk of CML among Caucasians under the recessive model, dominant model, and allele-contrast model. For C4887A, few of the included studies produced data. In conclusion, the results suggest that Asians carrying the T3801C C allele might have an increased risk of AML and that Caucasians with the A2455G GG genotype might have an increased risk of ALL. Further investigations are needed to confirm these associations.

[The impact of ischemic postconditioning on the tumor necrosis factor-α/IL-6/signal transducers and activators of transcription-3 signal pathway of liver regeneration].

OBJECTIVE: To investigate the impact of the ischemic postconditioning on the tumor necrosis factor (TNF)-α/IL-6/signal transducers and activators of transcription (STAT)-3 signal pathway of liver regeneration. METHODS: Ninety healthy clean grade male Sprague-Dawley rats weighting 230 to 280 g were selected and assigned into three groups randomly: group I subtotal hepatectomy (SH), group II ischemia reperfusion (IR), group III ischemic postconditioning (IPO). The left and middle liver was resected, and the remnant liver was treated as followed: the blood flow was not blocked in SH group, but blocked 30 minutes in IR group, then reperfused; IPO groups received three cycles of 30 s-30 s intermittent interruptions of blood flow at onset of reperfusion. At 1, 6, 12, 24, 48 h after reperfusion, the serum TNF-α, IL-6 was detected and the mRNA of cyclinD1, Cdk4, STAT-3 was assayed by real-time PCR as well as the protein expression of cyclinD1 and Cdk4 by Western blot. RESULTS: Compared with SH group, the expression of IL-6 declined at each set time point in IR group (t = 5.076 to 8.334, P = 0.000), but the content of TNF-α increased in early stage (1 to 12 h) (t = 2.972 to 7.215, P = 0.000 - 0.014). The expression of STAT-3, cyclinD1 and Cdk4 mRNA and protein of cyclinD1 and Cdk4 at 24 and 48 h after reperfusion were lower in IR group than in SH group (t = 2.857 to 6.684, P = 0.000 to 0.017). However, there was a significant decrease in TNF-α from 1 to 12 h after reperfusion (t = 2.995 to 4.112, P = 0.002 to 0.017), but a significant increase in IL-6 in IPO group than in IR group (t = 2.458 to 3.543, P = 0.005 to 0.034). The expression of STAT-3, cyclinD1, Cdk4 mRNA and protein of cyclinD1 and Cdk4 at 24 and 48 h after reperfusion were all increased in IPO group in comparison with in IR group (t = 2.383 to 6.803, P = 0.000 to 0.038). CONCLUSIONS: The ischemic postconditioning could promote the remnant liver regeneration after subtotal hepatectomy with ischemia reperfusion injury. Its mechanism relates with the activation of the TNF-α/IL-6/STAT-3 signal pathway of and the cyclinD1-Cdk4 complex which enhances the proliferation of hepatocyte.