Anti-tumour effects of xanthone derivatives and the possible mechanisms of action.

To explore the potential anti-tumour activities of xanthone derivatives, 26 hydroxylxanthones and benzoxanthones and their structurally modified analogues were examined for potential cytotoxic activities against eight human cancer cell lines. Most of the xanthone derivatives exhibited a higher degree of cytotoxicity on HepG2 cells than on the other seven cancer cell lines. Compound 24 (1,3,7-Trihydroxy-12H-benzo[b] xanthen-12-one) showed the highest degree of cytotoxicity of the tested compounds against HepG2 cells and demonstrated good tumour specificity by exhibiting a much higher degree of cytotoxicity against HepG2 cells than against normal liver cells (L02). Several valuable structure-activity relationships were derived from the cytotoxicity data. In addition, we found that compound 24 could downregulate the expression of the Mcl-1 protein, induce changes in the mitochondrial membrane potential and induce apoptosis in HepG2 cells via the mitochondrial pathway. Compound 24 was also shown to inhibit topoisomerase (topo) II activity and downregulate the levels of both topo II mRNA and protein in HepG2 cells. The present results suggest that due to its potent cytotoxicity and good tumour selectivity, compound 24 may be exploited as a potential lead compound in the development of a new anti-tumour agent with specific activity against liver cancer.

Anti-tumor activity and mechanisms of a novel vascular disrupting agent, (Z)-3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410).

Vascular disrupting agents (VDAs) have emerged as a new kind of anti-cancer drug in recent years. Structural modification of an active parent compound is an effective approach to developing new agents with more activity and fewer adverse reactions. In our study, six synthesized stilbene derivatives were screened for their cytotoxic activity against human tumor cells, and their mechanisms of action were investigated. The MTT assay was used to determine the anti-proliferative activity of these compounds. Polymerization of tubulin was detected by a tubulin assembly assay, and the cellular microtubule network was observed by immunocytochemical analyses. Cell-cycle distribution was detected by flow cytometry. A nude mouse model with xenografted colon cancer was used to demonstrate the in vivo anti-tumor activity, and microvessel density (MVD) was determined by immunohistochemistry. The expression levels of protein and mRNA were detected by Western blot and RT-PCR, respectively. Among the six newly synthesized compounds, (Z)-3,4',5-trimethoxylstilbene-3'-O-phosphate disodium (M410) showed potent cytotoxic activity toward proliferating tumor cells and exhibited a similar cytotoxicity against multi-drug resistant (MDR) tumor cells. M410 inhibited bovine brain tubulin polymerization in a way similar to that of colchicine. In proliferating human umbilical vein endothelial cells (HUVECs), 20 nM of M410 induced cellular tubulin depolymerization within 4 h, which led to M phase arrest. Systemic administration of M410 at nontoxic doses in nude mice resulted in inhibition of tumor growth of human colon cancer LoVo xenografts. The tumor vessel density also decreased after M410 treatment, as determined by immunohistochemical staining for CD31. M410 downregulated hypoxia-inducible factor-1 alpha (HIF-1α) expression, reduced nuclear HIF-1α, and downregulated vascular endothelial cell growth factor (VEGF) mRNA. Our results indicate that M410 is a potent microtubule inhibitor that is cytotoxic, angiogenesis inhibiting and vascular targeting.

Serum levels of procalcitonin as a biomarker for differentiating between sepsis and systemic inflammatory response syndrome in the neurological intensive care unit.

We explored the value of procalcitonin (PCT) to differentiate sepsis from systemic inflammatory response syndrome (SIRS), and determine sepsis severity in the neurological intensive care unit (NICU). Blood samples were measured for C-reactive protein (CRP) and PCT levels upon NICU admission, on the day of diagnosis of SIRS or sepsis, and at 3 and 7 days after diagnosis. We found that there were significant differences in serum levels of CRP and PCT as well as Glasgow Coma Scale (GCS) score upon admission between the SIRS and sepsis groups (p<0.05). CRP and white blood cell levels were not significantly different when attempting to differentiate sepsis severity (p>0.05). Multiple comparisons showed that significant differences in serum PCT levels were observed between sepsis and severe sepsis groups, as well as sepsis and septic shock groups (p<0.05). We obtained the highest sensitivity and specificity for SIRS and sepsis with cut-off values of 2 ng/mL for PCT, 44 mg/dL for CRP, and 4 for the GCS. There were no differences in CRP and PCT levels between cerebrovascular disease and non-cerebrovascular disease groups (p>0.05). No differences were found between viral and bacterial meningitis groups (p>0.05). PCT levels are valuable in discriminating sepsis from SIRS and determining sepsis severity in critically ill patients with neurological disease.

[Tracheal stent implantation for the treatment of tumor-induced acute airway stenosis].

BACKGROUND & OBJECTIVE: Tumor-induced acute airway stenosis is a medical emergency. Metal airway stent implantation can relieve dyspnea of patients suffering from this symptom and provide time for their further treatment. This study was to investigate the clinical application, efficacy, and complication management of tracheal stent implantation for the treatment of tumor-induced acute airway stenosis. METHODS: Nickel-titanium (Ni-Ti) alloy stent implantation was performed under the guidance of fiber-optic bronchoscopy in 52 patients with tumor-induced acute airway stenosis. RESULTS: Stent implantation was successful in all 52 patients. Dyspnea in all patients was significantly relieved. Values of arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and Karnofsky performance status (KPS) changed from (7.74+/-0.99) kPa, (5.37+/-0.39) kPa, and (68.85+/-8.08) preoperatively to (11.12+/-0.61) kPa, (4.58+/-0.30) kPa, and (84.62+/-5.03) postoperatively (P<0.01). The three-year survival rate was higher in lymphoma group than in lung cancer or esophageal cancer group. Postoperative complications were properly managed in all cases after symptomatic treatments. CONCLUSIONS: Tracheal stent implantation is an effective palliative treatment for acute dyspnea caused by local tumor compression or tumor invasion of large airways. It can rescue patients at risk for airway obstruction, improve the quality of life in terminal cancer patients, and provide further treatment opportunities for them.

[Effect of Coriolus versicolor polysaccharide B on membrane glycosaminoglycans and cellular glutathione changes in RAW264.7 macrophages exposed to angiotensin II].

OBJECTIVE: To investigate the effect of Coriolus versicolor polysaccharide B (CVP-B) on increased membrane glycosaminoglycans (GAG) expression and intracellular glutathione (GSH) of RAW264.7 macrophages exposed to angiotensin II (Ang II). METHODS: The plasma membrane of RAW264.7 macrophages exposed to Ang II treatment was isolated by ultracentrifugation, and the membrane GAG expression was analyzed using 1, 9-dimethylmethylene blue (DMMB) spectrophotometric assay for sulfated GAG. The intracellular reduced GSH was determined using fluorophotometry. RESULTS: The GAG content in the macrophage membranes increased by up to 54% following cell exposure to 1.0 micromol/L Ang II, whereas in presence of 1.0 micromol;/L Ang II, CVP-B at 1, 10, and 50 microg/ml decreased the GAG content by 13%, 43% (P<0.01), and 52% (P<0.01), respectively. The macrophage GSH activity decreased by 69% following incubation with 1.0 micromol;/L Ang II for 24 h, and CVP-B treatment at 1, 10, and 50 microg/ml in presence of 1.0 micromol;/L Ang II resulted in significant increment of GSH activity by 31%(P<0.05), 104% (P<0.01), and 168% (P<0.01), respectively. CONCLUSION: These data provide the first evidence that CVP-B inhibits elevated GAG expression in RAW264.7 macrophage membrane induced by Ang II.

[Postoperative complications in lung cancer patients with moderate pulmonary hypofunction].

BACKGROUND & OBJECTIVE: With the development of surgery treatment for lung cancer, the importance of preoperative pulmonary function assessment evoked more and more attention. This research was set to analyze postoperative complications of lung cancer patients with moderate pulmonary hypofunction, and explore associated factors. METHODS: Statistic t test and Chi(2) test were used to compare postoperative complications of 31 patients with moderate pulmonary hypofunction and 62 patients with normal pulmonary function (control group), logistic regression was performed to find associated factors. RESULTS: In the 31 patients with moderate pulmonary hypofunction, hypoxemia (41.9%), arrhythmia or cardiac dysfunction (25.8%), pulmonary inflammation (25.8%) were common postoperative complications; incidence of severe complications, such as respiratory failure, and cardiac failure, was 9.2%; in-hospital mortality was 3.2%. In control group, the occurrence rates were 16.1%, 8.1%, 9.6%, and 3.2%, accordingly, no in-hospital death occurred. Regression analysis showed that age and resection range associated with the occurrence of postoperative complications. CONCLUSIONS: compared with control group, incidences of common postoperative complications in patients with moderate pulmonary hypofunction are remarkably increased, but severe complications and in-hospital mortality are not significantly high. Patients with older age and larger resection range have a high risk of develop complications.