ABSTRACT
Objective To analyze the clinical features,therapeutic effect and prognosis in patients with bone pain induced by malignant bone me?tastasis as well as the rationality of analgesic application,so as to improve the level of diagnosis and treatment for metastatic bone pain. Methods Totally 123 patients with pain due to malignant bone metastasis received antitumor therapy and analgesic therapy based on standardized three?step guidelines. Their clinical characteristics were retrospectively analyzed. Results The total pain relief rate was 85.4%and the pain was significantly relieved(P<0.05). The DUI value of each narcotic agent was close to 1 and the application of narcotic agents tended to be rational. The Kaplan?Meier survival analysis showed that patients with moderate pain had longer survival time than those with severe pain(P=0.015). The survival rate of patients with significant pain relief after treatment was higher than those unrelieved(P=0.021). The survival rate of patients without visceral me?tastasis was higher than those with visceral metastasis(P=0.000). The COX multivariate analysis indicated that the pain intensity and visceral me?tastasis were independent risk factors influencing patient prognosis. Conclusion Standard treatment can improve symptoms in most patients with bone metastasis and prolong survival time. Opioids have satisfactory analgesic effect for moderate to severe pain and the adverse reactions can be tol?erated.
ABSTRACT
Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC50 of 18.54 μM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.
Subject(s)
Animals , Humans , Rats , Apoptosis/drug effects , Arsenicals/pharmacology , Oxides/pharmacology , /antagonists & inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-cbl/pharmacology , Ubiquitin-Protein Ligases/pharmacology , Blotting, Western , Flow Cytometry , Signal Transduction/drug effects , Up-Regulation/drug effectsABSTRACT
<p><b>BACKGROUND</b>To study the diagnostic value of detection of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153) and cancer antigen 199 (CA199) in pleural fluid samples for lung cancer.</p><p><b>METHODS</b>Immunoprotein quantity of CEA, CA125, CA153 and CA199 was analyzed in pleural fluid and serum from patients with lung cancer (52 cases) and in pleural fluid from non cancerous patients (50 cases) by chemiluminescence.</p><p><b>RESULTS</b>The levels of CEA, CA125, CA153 and CA199 in pleural fluid of patients with lung cancer were significantly higher than those of non cancerous patients ( P < 0.01 or P < 0.05). In lung cancer patients, the levels of CEA, CA125, CA153 and CA199 in pleural fluid were obviously higher than those in serum ( P < 0.01 or P < 0.05). The sensitivity and the specificity of CEA+CA199 were 96.2% and 96.0%, respectively.</p><p><b>CONCLUSIONS</b>Detection of CEA, CA125, CA153 and CA199 in pleural fluid might be helpful for diagnosing lung cancer, and the optimal combination for assay is CEA+CA199.</p>