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Zhai K.,Sun Yat Sen University | Chang L.,Sun Yat Sen University | Zhang Q.,Cancer Hospital of Gansu Province | Liu B.,Sun Yat Sen University | And 2 more authors.

During a survey of control region (D-loop) sequence variances in 142 cervical cancer (CC) patients and 136 controls, all Chinese women, including both HPV-positive (human papillomavirus) and HPV-negative subjects, we determined that the C150T polymorphism increased the CC risk in a case-control study (OR=3.0, 95% CI=1.8-5.0, P<0.05). HPV-positive individuals were more likely to carry the C150T polymorphism than HPV-negative controls (OR=5.8, 95% CI=2.6-13.2, P=2.3×10-5). HPV-positive CC patients were more likely to carry the C150T polymorphism than HPV-negative controls (OR=4.9, 95% CI=2.6-9.3, P=9.9×10-7). In all subjects, an increased risk of HPV infection was also associated with the C150T polymorphism (OR=4.5, 95% CI=2.5-8.1, P=6.6×10-7). However, no significant difference in the frequency of other alleles was found at the variable sites in D146, D152, D310 and D514. These results indicated that the C150T polymorphism increased the risk of HPV infection and CC progression. Additionally, we assessed the association of mtDNA copy number with CC risk or the C150T polymorphism in 45 CC patients and 43 controls. There was no significant association of mtDNA copy number with CC risk or the C150T polymorphism. To the best of our knowledge, this is the first report to suggest that mtDNA C150T polymorphism was positively associated with HPV infection and subsequent CC risk among Chinese women. © 2011 Elsevier B.V. and Mitochondria Research Society. Source

Zhang X.,Lanzhou University | Qiao H.,Lanzhou University | Zhang T.,Cancer Hospital of Gansu Province | Shi Y.,Lanzhou University | Ni J.,Lanzhou University
Advanced Powder Technology

Isoliquiritigenin (ISL) has various pharmacological effects. Our previous studies demonstrated that the oral bioavailability of ISL was low and the concentration-time profiles of ISL exhibited double peaks after oral administration in rat, but the underlying mechanisms remained unknown. The objective of this study was to clarify the gastrointestinal (GI) absorptive characteristics of ISL using in situ intestinal perfusion model as well as explain double peaks phenomenon after oral administration and to evaluate the potential of using nanostructured lipid carrier (NLC) as an oral delivery carrier for poorly water soluble drugs. The results showed that the absorption percent in the stomach for 2 h was less than 10%, the absorption process of intestine was first-order process with passive diffusion mechanism, and the main absorptive segment was colon. Isoliquiritigenin-loaded nanostructured lipid carrier (ISL-NLC) could enhance oral absorption of ISL. The reason for the Double Peak Phenomenon following oral administration in ISL plasma concentrations versus time profiles is Variability of Absorption within different regions of the gut, very low absorption from the stomach, jejunum, duodenum and ileum compared with the absorption from the colon. A pharmacokinetic study was conducted in rats after a single dose oral administration of ISL at 20 mg/kg in the form of either ISL-NLC or isoliquiritigenin solution (ISL-Sol). The AUC (0∼) values were 5.43 ± 0.67 μg h mL-1 and 29.60 ± 2.88 μg h mL-1 after administration of the ISL-Sol and ISL-NLC, respectively. The relative bioavailability of ISL-NLC to isoliquiritigenin was 545%. Our studies provide evidence that NLC are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, ISL. © 2014 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder. Source

Su L.,Lanzhou University | Deng Y.,Cancer Hospital of Gansu Province | Zhang Y.,Lanzhou University | Li C.,Lanzhou University | And 5 more authors.
Toxicology Mechanisms and Methods

This study determined whether nickel sulfate (Ni)-induced reproductive damage occurs via apoptosis and oxidative stress and to examine the expression of Bax and c-kit and their effects on Ni exposure. The study also explored the protective effects of grape seed proanthocyanidin extract (GSPE) against Ni toxicity in the testes. Wistar rats were treated with normal saline, Ni alone (1.25, 2.5, and 5 mg/kg/day), and Ni (2.5 mg/kg/day) plus GSPE (50 and 100 mg/kg/day). After 30 days, Ni significantly decreased sperm motility and the percentage of S-phase cells and enhanced testicular apoptosis in the 2.5 and 5 mg groups. The levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and nitric oxide (NO) significantly increased. The decreased activity of glutathione peroxidase and catalase in the Ni groups showed that Ni could increase oxidative stress, especially at 2.5 and 5 mg. Western blot analysis showed that the expression of Bax protein and c-kit increased in 2.5 and 5 mg Ni groups compared with controls. Conversely, these changes were partially attenuated in rats simultaneously administered GSPE, especially in the 100 mg group. These results demonstrate the following: (1) Ni exhibits reproductive toxicity in rats by decreasing sperm at concentrations of 2.5 and 5 mg; (2) intratesticular apoptosis, oxidative stress, and c-kit overexpression play pivotal roles in reproductive damage induced by Ni; and (3) GSPE enhances sperm motility by down-regulating c-kit expression and offsetting the apoptosis and oxidative stress induced by Ni by directly decreasing MDA and NO, scavenging H2O2, and down-regulating Bax expression. © 2011 Informa Healthcare USA, Inc. Source

Zhang F.,Lanzhou University of Technology | Zeng Y.L.,Lanzhou University of Technology | Zhang X.G.,Lanzhou University of Technology | Chen W.J.,Lanzhou University of Technology | And 2 more authors.
European Journal of Gynaecological Oncology

Overexpression of extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN CD147) has been implicated in the growth and survival of malignant cells. However, its presence and role in cervical cancer cells has not been well-studied. In the present study, small interfering RNA(siRNA) was designed and synthesized to breakdown the expression of CD147. The present data demonstrated that 24 and 48 hours after transfecting CD147 siRNA, both the CD147 mRNA and protein expression were significantly inhibited as determined by quantitative real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. Meanwhile, simultaneous silencing of CD147 resulted in distinctly increasing MMP-9, VEGF, and MDR-1. Further studies demonstrated decreased CD147 expression, resulted in G1/S phase transition with flow cytometry analysis, as well as the resistance of the cells to 5-FU. These findings provide further evidence that CD147 may become a promising therapeutic target for human cervical cancer and a potential chemotherapy-sensitizing agent. Source

Ji H.,Cancer Hospital of Gansu Province | Li L.,Maternal and Child Health Hospital of Gansu Province | Guo Q.,Institute for Disease Control and Prevention | Ren J.,Cancer Hospital of Gansu Province | And 2 more authors.
Chinese Journal of Clinical Oncology

Objective: To evaluate the significance of the matrix metalloproteinase-2 (MMP-2) and cytokeratin 19 (CK19) expressions in the pelvic lymph nodes of patients with early stage cervical cancer. Methods: Immunohistochemical staining and light microscopy were used to detect the expression of MMP-2 and CK19 in 902 lymph nodes from 64 patients. A routine pathological examination was performed to confirm lymph node metastasis. Results: In the relapse group, 11 of 477 patients had CK19-positive lymph nodes (2.3%); from 8 of 32 patients (25%), 8 were MMP-2 positive (1.7%) from 32 patients in 6 (18.8%), the results of the two test targets are in good agreement. In the group without recurrence, the 425 lymph nodes from 32 patients showed negative CK19 and MMP-2 expression (0/425). The difference between the two protein expressions was statistically significant. CK19 and MMP-2 expression, pathological type, and tissue differentiation were all correlated (P < 0.05). Of the 32 patients in the relapse group, 25 survived while 7 died from cancer. A total of 6 cases exhibited positive CK-19 and MMP-2 expression in the pelvic lymph nodes, indicating that micrometastases, postoperative recurrence, and metastasis were correlated (P < 0.05). Conclusion: Compared to traditional histopathological staining, immunohistochemical staining can improve the detection rate for micrometastases. The high MMP-2 expression, CK19 invasion, cervical cancer metastasis, and early cervical cancer detection can be used as biological indicators of lymph node metastasis. Source

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