Experiment research of focused ultrasound combined with drug and microbubble for treatment of central nervous system leukemia.

It has been shown that low frequency ultrasound in the presence of microbubble can effectively open the blood brain barrier (BBB) to allow the drugs to be delivered into the brain with an increased concentration. We aim to apply this method to increase the efficacy of Cytarabine (Ara-c) to treat central nervous system leukemia (CNSL). In the present study, we validated this ultrasound contrast agent Sonovue® targeting treatment via in vivo and in vitro experiments. The results showed that Sonovue® combined with Cytarabine could significantly inhibit K562 cell (chronic myeloid leukemia cell line) proliferation. In the animal experiments, it has been shown that high dose Ara-c chemotherapy could prevent and cure CNSL effectively and the drug concentration in the brain was much higher compared with low dose Ara-c chemotherapy group. We certified that under ultrasound exposure Sonovue® combined with low dose Cytarabine achieved an effective drug concentration in the rat brain, and brain tissue had no significant damage. Further animal experiments will be conducted to confirm these results in a leukemia animal model, considering the blood brain barrier is destroyed at different levels by leukemia cells. We hope this method will reduce the side effects of high-dose Cytarabine and improve the clinically high recurrence and poor prognosis of the central nervous system leukemia.

[Effects of DNMT3A gene mutations on prognosis of patients with acute myeloid leukemia: a meta-analysis].

OBJECTIVE: To evaluate the effects of DNMT3A gene mutation on prognosis of patients with acute myeloid leukemia (AML) by a meta-analysis. METHODS: Methods of Cochrane systematic review was followed by 7 databases,including PubMed, Embase, Ovid, CNKI, CBM, WanFang Data and VIP, were searched for peer-reviewed articles related to DNMT3A gene mutations and prognosis of patients with AML.Then manual retrieval was applied into literature references. After the evaluation of quality and extract of clinical trialliterature data, Stata 11.0 was employed to perform meta-analysis. RESULTS: Seven randomized controlled trials involving 1493 cases were included in the meta-analysis. The prognosis of patients with DNMT3A mutations and without DNMT3A mutations was compared. There was no statistically significant difference in complete remission(CR) rate (OR=1.034, 95%CI: 0.596~1.796, P=0.905 between two groups, but the overall survival (OS（HR=1.990, 95%CI: 1.463~2.510, P=0.000 and disease free survival (DFS) (HR= 2.840, 95%CI: 1.063~4.613, P=0.002) of patients without DNMT3A mutations were longer than those with DNMT3A mutation. CONCLUSION: DNMT3A gene mutation is an independent risk factor of poor prognosis of patients with acute myeloid leukemia.

[WT1 gene expression difference in leukemia and non-leukemia and its clinical significance].

This study was aimed to investigate the expression level of Wilms' tumor 1( WT1) gene in hematologic neoplasm (leukemia, multiple myeloma and lymphoma) patients and its clinical significance. Real-time quantitative polymerase chain reaction (RQ-PCR) was used to detect the copy number of WT1 gene and reference gene (ALB) in bone marrow cells of 228 patients with hematologic neoplasm in our hospital. The gene expression level was determined by using the ratio of the copy number of WT1 gene and reference gene. The results showed that the WT1 expression level between male and female patients was not statistically significantly different (P > 0.05). All the patients were divided into 3 groups: the group aged under 19, the group aged between 19-50, and the group aged over 50; the WT1 expression level among the three groups were not statistically significantly different (P > 0.05) . The above-mentioned patients were redivided into the groups aged under 45 and over 45, the difference between them was not statistically significant (P > 0.05). The difference of WT1 expression level between newly diagnosed patients and treated patients with hematologic neoplasm was statistically significant (P < 0.01), but no statistically significant difference of WT1 expression was found (P > 0.05) at each stage within 3 years after treatment, however, among them the difference between newly diagnosed leukemia patients and treated leukemia patients was very statistically significant (P < 0.01), while the difference between newly diagnosed and treated non-leukemia patients was not statistically significant (P > 0.05). The expression difference of WT1 between leukemia and non-leukemia patients was very statistically significant (P < 0.01), the difference between the newly diagnosed leukemia and non-leukemia patients also was very statistically significant (P < 0.01). The difference of WT1 expression between treated leukemia and non-leukemia patients was not statistically significant (P > 0.05). It is concluded that the WT1 expression level in leukemia patients can be a reliable marker to evaluate the prognosis of newly diagnosed leukemia and the curative effect for minimal residual disease. No WT1 expression difference has been found before and after treatment among the patients with non-leukemia, such as multiple myeloma and lymphoma, therefore, which should be furtherly explored.

[Research progress on drug-loaded microbubble targeting treatment of central nervous system leukemia].

Central nervous system leukemia (CNS-L) is a fatal complication with low remission, high relapse and high death rates in leukemia. Because the existence of blood brain barrier (BBB) hinders drug from going into CNS, therefore it is urgent that to develop a new drug delivery system by which drug can highly and effectively go through BBB. Searching home and abroad literatures from December 2012 to February 2014 found a scheme which may effectively treat the CNSL, that is, ultrasonic microbubbles loading Ara-C, which changes the cell membrane permeability and increases the intercellular space by cavitation effect so as to make the Ara-C through the BBB for therapy. This review focuses on the present status of CNSL treatment and the progress of treating CNSL with ultrasonic microbubbles loading drug.

[Clinical investigation of Q-T prolongation in hepatic cirrhosis].

OBJECTIVE: To investigate the relationship between the prolonged corrected QT interval (Q-Tc) and the severity and prognosis of patients with hepatic cirrhosis. METHODS: Electrocardiography was conducted on 126 patients with hepatic cirrhosis, 86 males and 40 females, aged (62 +/- 16), 38 of Child-Pugh grade A, 64 of grade B, and 24 of grade C, and 126 sex- and aged-matched healthy persons as controls. Peripheral blood samples were collected to undergo the examination of prothrombin time, and serum albumin, total bilirubin, potassium, calcium, ALT, AST, gamma glutamyl transferase, and alkaline phosphatase. The relationship between the Q-Tc and other parameters were analyzed. Twenty cirrhotic patients underwent liver transplantation. RESULTS: The Q-Tc value of the cirrhosis patients was (421 +/- 38) ms, significantly longer than that of the controls (386 +/- 25) ms. The Q-Tc prolongation rate of the cirrhosis patients was 46.93% (58/126), significantly higher than that of the controls (1.58%, 2/126, P < 0.01). The Q-Tc prolongation rates of the patients of Child-Pugh grade B and C were 56.89% and 59.60% respectively, both significantly higher than that of the patients of grade A (21.05%, both P < 0.01). Linear regression analysis showed that Q-Tc was positively correlated with the Child-Pugh score. Q-Tc was not significantly correlated with the biochemical indicators mentioned above. The prolonged Q-Tc became normal in 17 of the 20 patients undergoing liver transplantation and became shorter in 3 cases one year after the operation. CONCLUSION: Q-Tc prolongation exits in hepatic cirrhosis and the Q-Tc prolongation rate increases along with the severity of disease. After liver transplantation the prolonged Q-Tc may recover to normal Q-Tc prolongation can be used to assess the severity and prognosis of hepatic cirrhosis.