ABSTRACT
Objective To explore short term curative effects and adverse reactions of two different kinds of intraperitoneal hyperthermic chemotherapy (IPHC) drugs in the treatment of advanced ovarian cancer after cytoreductive surgery.Methods 76 patients with advanced ovarian cancer in the Second Affiliated Hospital of Zhengzhou University from July 2013 to November 2015 were divided into two groups:single-drugs group of 36 patients (IPHC with 5-fluorouracil after cytoreductive surgery combined with intravenous chemotherapy),combined treatment group of 40 patients(IPHC with 5-fluorouracil and carboplatin after cytoreductive surgery combined with intravenous chemotherapy).Short term curative effects,postoperative clinical indicators and adverse reactions of chemotherapy in two groups were compared and analyzed.Results The CA125 effective rates in single-drugs and combined treatment group were 86.11％ and 95％,and the difference showed statistically significant differences (P ＞ 0.05).The ascites remission rates in single-drugs and combined treatment group were 97.22％ and 97.5％,and the difference between two groups showed no statistically significant differences (P ＞ 0.05).Adverse drug reactions showed statistical difference in distribution of the bone marrow,liver damage and gastrointestinal toxicity.No statistical difference were found between the two groups in terms of distribution of renal damage and cardiovascular system damage.Conclusion IPHC after cytoreductive surgery in the treatment of advanced ovarian cancer is an effective means as adjuvant chemotherapy.The short-term curative effect of combined treatment group is obvious and adverse reactions can be tolerated.IPHC can be applied according to the patient's specific clinical situation.
ABSTRACT
BACKGROUND: Chemoresistance remains a significant challenge in chronic myelogenous leukemia (CML) management, which is one of the most critical prognostic factors. Elucidation the molecular mechanisms underlying the resistance to chemoresistance may lead to better clinical outcomes. RESULTS: In order to identify potential protein targets involved in the drug-resistant phenotype of leukemia, especially the chronic myelogenous leukemia (CML), we used a high-resolution "ultra-zoom" 2DE-based proteomics approach to characterize global protein expression patterns in doxorubicin-resistant myelogenous leukemia cells compared with parental control cells. Ultra-high resolution of 2DE was achieved by using a series of slightly overlapping narrow-range IPG strips during isoelectric focusing (IEF) separation. A total number of 44 proteins with altered abundances were detected and identified by MALDI-TOF or LC-MS/MS. Among these proteins, enolase, aldolase, HSP70 and sorcin were up-regulated in doxorubicin-resistant myelogenous leukemia cell line, whereas HSP27 was down-regulated. Some of the results have been validated by Western blotting. Both enolase and aldolase were first reported to be involved in chemoresistance, suggesting that process of glycolysis in doxorubicin-resistant myelogenous leukemia cells was accelerated to some extent to provide more energy to survive chemical stress. Possible roles of most of the identified proteins in development of chemoresistance in myelogenous leukemia cells were fully discussed. The results presented here could provide clues to further study for elucidating the mechanisms underlying drug resistance in leukemia. CONCLUSIONS: As a whole, under the chemical stress, the doxorubicin-resistant myelogenous leukemia cells may employ various protective strategies to survive. These include: (i) pumping the cytotoxic drug out of the cells by P-glycoprotein, (ii) increased storage of fermentable fuel, (iii) sophisticated cellular protection by molecular chaperones, (iv) improved handling of intracellular calcium, (v) increased glucose utilization via increased rates of glycolysis. In the present study, proteomic analysis of leukemia cells and their drug resistant variants revealed multiple alterations in protein expression. Our results indicate that the development of drug resistance in doxorubicin-resistant myelogenous leukemia cells is a complex phenomenon undergoing several mechanisms.
