Effects of Decitabine Combined with Bortezomib on the Proliferation of Mantle Cell Lymphoma Cell Lines and Its Underling Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms.@*METHODS@#Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively.@*RESULTS@#Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells.@*CONCLUSION@#The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.

Expression of PEDF and VEGF in corneal neovascularization after corneal alkali burn / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the effect of human amniotic homogenate extract on corneal neovascularization after corneal alkali burn in the process of pigment epithelium derived factor (PEDF) and vascular endothelial growth factor (VEGF) expression and the effect of corneal neovascularization.METHODS: Totally 32 patients with corneal alkali burn were selected from June 2015 to June 2016 in Foshan,and were randomly divided into Group A and Group B,with a total of 37 eyes.Group A of 17 cases,with a total of 19 eyes,were treated with 40mg/L human amniotic homogenate extract;Group B (n=15),and 18 eyes,treated with 3g/L prednisolone eye drops.In the treatment of 1,4,7,14,21 and 28d at different time points,we observed the growth of corneal neovascularization,and detected the expression of PEDF and VEGF during angiogenesis.RESULTS: Group A of patients in the use of human amniotic homogenate extract after the treatment,the expression level of PEDF was significantly higher than that in Group B(P=0.001),after 28d treatment,the expression level of PEDF reached 0.721±0.314.While patients in Group B the expression level of PEDF was only 0.538±0.253.Two groups had significant difference between the expression level of PEDF (P<0.05).The expression level of VEGF in Group A was lower than in Group B at different time points in the test.After the treatment of 28d patients in the Group A,the expression level of VEGF was 0.152±0.020,in Group B the expression level of VEGF was0.302±0.031.Two groups of patients with VEGF expression level between the differences were statistically significant (P<0.05).The patients number in Group A with corneal neovascularization was significantly lower than that in Group B,the difference was statistically significant (P<0.05).CONCLUSION: Human amniotic homogenate extract can increase the expression of PEDF in corneal neovascularization after corneal alkali burn,inhibit the expression of VEGF and the proliferation of corneal neovascularization.

Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis of Randomized Controlled Trials / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lenalidomide has emerged as an important treatment for patients with multiple myeloma (MM). However, its role in the management of MM is still controversial and requires further clarification. The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.</p><p><b>METHODS</b>We searched the electronic databases including: PubMed, EMBASE and the Cochrane Center Register of Controlled Trials. Seven randomized clinical trials were identified, which included a total of 2357 patients with MM who received lenalidomide-containing, noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy. The outcomes included overall response (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, and different types of treatment-related adverse events. We calculated the risk ratios (RRs) as well as their 95% confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.</p><p><b>RESULTS</b>For patients with previously untreated MM, OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group. For relapsed or refractory MM patients, lenalidomide-containing regimens significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate. With regard to MM patients after autologous stem cell transplantation, lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate. In terms of toxicities, lenalidomide therapy has a higher rate of Grade 3-4 grade cytopenias, infection, deep-vein thrombosis, and diarrhea. Furthermore, the incidence of second primary malignancies was significantly higher in the lenalidomide group.</p><p><b>CONCLUSIONS</b>The lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM. However, when physicians choose to use the lenalidomide as maintenance therapy, whether the benefits outweigh the risks should be taken into account.</p>

Combined treatment with urea injection and surgical procedure for the scrotal vein malformation in teenagers / 中华整形外科杂志

<p><b>OBJECTIVE</b>To discuss the treatment of the scrotal vein malformation in teenagers and clinical efficacy.</p><p><b>METHODS</b>32 cases with the local and diffuse scrotal vein malformation were retrospectively analyzed. 31 cases underwent local injection with 40% urea before resection. The urea was injected locally into tumor through multi-points within 30 seconds, 2-6 ml every time, one time a day. The injection was performed for 5-12 days. The treatment was refused in one case. The therapeutic effect and cosmetic result were recorded.</p><p><b>RESULTS</b>The tumors were removed radically in 28 cases including one operation in 25 cases and secondary operation in 3 cases. The patients were followed up for 1-3 years with no recurrence. Cosmetic result with bilaterally symmetric scrotum was satisfactory. The tumors in 3 severe cases were partially resected with improvement.</p><p><b>CONCLUSIONS</b>Combined treatment with urea injection and surgical procedure can effectively treat the scrotal vein malformation with satisfactory result.</p>

Surgical treatment of cervical giant cystic lymphangioma in children / 中华整形外科杂志

<p><b>OBJECTIVE</b>To discuss the radical treatment of cervical giant cystic lymphangioma in Children and cosmetic result.</p><p><b>METHODS</b>Twenty-five children with cervical giant cystic lymphangioma were retrospectively analyzed. The diameter of all the tumors was more than 10 cm. 24 cases underwent resection. The complication, therapeutic effect and cosmetic result were recorded.</p><p><b>RESULTS</b>The tumors were all removed radically in all the cases. The patients were followed up for 1-5 years with no recurrence. Cosmetic result was satisfactory in 22 cases. Secondary operation was performed in 2 cases with satisfactory result. Complications included 5 cases of lymph leakage, 2 cases of poor wound healing, 1 case of infection and 2 cases of tongue edema.</p><p><b>CONCLUSIONS</b>The cervical giant cystic lymphangioma in children can be resected radically with satisfactory result.</p>

Analysis of outocome of pirarubicin-based combination chemotherapy regimen in the treatment of newly diagnosed acute myeloid leukemia-a prospective, open, randomized and multicenter clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the effectiveness and side effects of two chemotherapy regimens [pirarubicin + cytarabine (TA) and daunorubicin + cytarabine (DA)] in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>From Oct 2006 to Jul 2009, there were 207 newly diagnosed AML patients randomized into DA or TA group from 72 centers all over the country. The aim of this clinical trial is to observe and evaluate complete remission rate (CR), total remission rate (TRR), and side effect after one or two circles of therapy.</p><p><b>RESULTS</b>In 198 evaluable patients, 126 cases in TA group and 72 in DA group were evalvable, with a ratio of 1.75:1. CR was 69.8% and TRR (CR + PR) was 81.8% in TA group and 63.9%, 80.9% in DA group, correspondingly (P > 0.05). For patients with subtype M(2), CR (77.1%) in TA group was higher than that in DA (60%). There was no difference in side effect between the two groups.</p><p><b>CONCLUSION</b>There is no difference of the effect between TA and DA chemotherapy for newly diagnosed AML patients. But for subtype M(2), TA is more efficacy. And there is no difference in side effect between the two regimens.</p>

Expression of c-fes gene in leukemia cells and its clinical significance / 中国实验血液学杂志

This study was purposed to investigate the expression of c-fes gene in leukemia patients and its clinical significance. The expression of c-fes mRNA in bone marrow cells from 121 cases of acute and chronic leukemia patients, and the expression of c-fes mRNA in peripheral blood mononuclear cells of 20 normal persons were detected by real time-quantitative reverse transcription polymerase chain reaction (RQ-PCR). The results showed that the level of c-fes mRNA in AML patients was higher than that in normal controls [(48.017 +/- 57.170) x 10(-3) vs (0.152 +/- 0.398) x 10(-3)] (p < 0.0001); but there was no significant differences of level of c-fes mRNA between samples of ALL and normal controls(0.047 +/- 0.068) x 10(-3) vs(0.152 +/- 0.398) x 10(-3) (p>0.05); the level of c-fes mRNA in CML patients was higher than that in normal persons (21.605 +/- 24.818) x 10(-3) vs (0.152 +/- 0.398) x 10(-3) (p < 0.0001). The positive expression rate of c-fes gene in CML-CP patients (80%) was higher than that in CML-AP patients (66.7%) and CML-BP (28.6%) patients. In AML patients, c-fes gene was expressed higher in M(2) (80.77%) and M(3) (92.86%) patients. The remission rate of AML (except M(3))patients who had expression of c-fes gene was 81.08%, which was higher than that of patients with no expression of c-fes gene (40.00%). It is concluded that c-fes gene expression was found in myeloid leukemias, whereas low or no expression in lymphocytic leukemias. The differentiation of myelocytic cells may be related to c-fes gene. All AML (except M(3))patients with high level of c-fes mRNA may get good prognosis.

Expressions of cyclin E2 and survivin in acute leukemia and their correlation / 中国实验血液学杂志

Cyclin E2 is present in solid tumors, while its expression and clinical value in acute leukemia is unknown. This study was aimed to investigate the expression of cyclin E2 and survivin gene in bone marrow cells from patients with acute leukemia and their relationship. Reverse transcription polymerase chain reaction was used for detection of the expression of cyclin E2 and survivin mRNA in 84 adult patients with acute leukemia which included 16 cases of relapse, 60 cases of de novo acute leukemia, 8 cases of continuously complete remission, and 20 normal persons as controls. The results showed that (1) positive expression of cyclin E2 (70.24%) in acute leukemia patients was significantly higher than that (0%) in controls, positive expression of survivin (72.62%) in acute leukemia patients was higher than that (30%) in control. (2) the expression of cyclin E2 positively correlated with that of survivin in acute leukemia patients. (3) remission rate in cyclin E2-positive patients (55.81%) was lower than that (88.24%) in cyclin E2-negative patients, the rate of cyclin E2 expression in relapse group was the highest among the three groups; while that in continuously complete remission group was the lowest among the three groups. (4) positive rate of cyclin E2 expression (59.32%) in patients with acute myelocytic leukemia was lower than that (96%) in patients with acute lymphocytic leukemia, no correlation between cyclin E2 expression and white blood cell counts of patients was found. It is concluded that the overexpression of cyclin E2 has been confirmed for the first time to positively correlate with the expression of the survivin in acute leukemia patients, and implicate the poor prognosis. Cyclin E2 may be used as a marker for examination of minimal residual disease.

Expressions of cyclin B1 and p21cipl in adult acute leukemia and their correlation / 中国实验血液学杂志

Cyclin B1, a positive regulator, controls mitosis occurrence, plays an important role in cell proliferation. To investigate the clinical significance of cyclin B1, the expression of cyclin B1 in acute leukemia (AL) patients was measured; the expression of cyclin B1 and p21(cipl), and their cell cycle distribution were assayed by flow cytometry in 136 adult patients with newly diagnosed AL, 10 continuous complete remission (CCR) AL and 17 normal controls; the mRNA of cyclin B1 and p21(cipl), and the proliferation cell nuclear antigen (PCNA) in patients and normal controls were detected with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The results showed that the expression of cyclin B1 in newly diagnosed AL patients was significantly higher than that in normal controls. For the relapsed AL patients, the cyclin B1 expression was also higher than that in normal controls, but lower than that in newly diagnosed cases, there was no significant difference between the remission cases and normal controls, nor difference between CCR AL patients and normal controls. All patients with high cyclin B1 expression had an unscheduled expression manner, that cyclin B1 protein appeared in G(1) phase, and in some case it even higher than that of G(2) phase. The response rate (partial remission + complete remission) and survival rate in the cyclin B1 high expressed patients were higher than that of cyclin B1 low expressed patients. The relapse rate in cyclin B1 high expressed patients was higher than that in cyclin B1 normally expressed patients. The survival rate in cyclin B1 high expressed patients was higher than that in cyclin B1 low expression patients. A negative correlation between the expression of cyclin B1 and p21(cipl) was observed. Additionally, cyclin B1 protein expression was generally correlated with proliferation index (PI) and proliferation cell nuclear antigen (PCNA). It is concluded that this study demonstrates for the first time cyclin B1 overexpression and abnormally distribution in cell cyclin of newly diagnosed AL patients. It was considered that cyclin B1 may play an important role in leukemic pathogeneses and can be one of the factors influencing the prognosis of AL patients.

Expression of cyclin g2 mRNA in patients with acute leukemia and its clinical significance / 中国实验血液学杂志

To evaluate the expression of cyclin G2 mRNA in patients with acute leukaemia (AL) and its clinical value, the expression of cyclin G2, G1 and P53 mRNA in the bone marrow from 74 AL patients and 10 normal individuals as control were detected with reverse transcription polymerase chain reaction (RT-PCR). The positive segment of cyclin G2 was analyzed by DNA sequencing. The results showed that (1) the positive rate and the expressing level of cyclin G2 in AL patients (52.7%, 0.552 +/- 0.498) were significantly lower than those in normal control (100%, 1.953 +/- 0.675) (P < 0.01); (2) among new diagnosed AL patients, the complete remission (CR) rate (69.2%) in the positive cyclin G2 patients was higher than that (40%) in negative cyclin G2 patients (P < 0.05); (3) the positive rate of cyclin G2 (43.6%) in resistance group was significantly higher than that (68.6%) in sensitive group (P < 0.01); (4) following-up for 14.3 month (11 - 18.5 month) in 28 AL patients with CR, there were 10 relapsed in 11 AL patients with low expression level of cyclin G2 (90.9%); and 7 relapsed in 17 AL patients with high expression (41.2%), and there was significant difference (P < 0.05). In conclusion, the expression of cyclin G2 in AL patients was higher than that in normal control, the abnormal expression of cyclin G2 might be a prognostic marker of CR in AL patients.

Clinical significance of the expression of DNA methyltransferase genes (DNMT) in acute leukemia patients / 中国实验血液学杂志

To investigate the relationship between the expression of DNMT and clinical prognosis in adult patients with acute leukemia (AL), the mRNA expressions of DNMT, p15(INK4B), mdr1 were measured in 72 AL patients and 20 normal controls by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR); the ratio of p15 CpG land methylation was measured in 56 AL patients and 14 normal controls by methylation-specific PCR (MSP-PCR). The results showed that all three DNMT mRNA expressions in AL patients were significantly higher than that in normal controls (P < 0.01). When the internal control was changed into PCNA, a kind of cell proliferation marker gene, the difference still showed a statistic significance. All three DNMT genes were significantly expressed and positively correlated with AL patients, showing high synergistic expression, and there was a negative correlation between the levels of p15, mdr1 gene expression and DNMT. The complete remission (CR) rate in AL patients with the positive expression of all DNMT genes was significantly higher than that of AL patients with partially positive or negative expression (P < 0.01) of DNMT genes. In 56 AL patients, the P15I(NK4B) was completely methylated in 55.4% (31 of 56), partly methylated in 21.4% (12 of 56) and all 14 cases of normal controls were not methylated. It is concluded that DNMT genes are abnormally high expressed in adult AL patients, which lead to methylation-silence of tumor suppressor genes by CpG land hypermethylation, the AL patients with high expression of DNMT are more sensitive to chemotherapy, which may be a good prognostic factor for AL patients.

Growth and gene expression of leukemia cell after treated with methylation inhibitor 5-aza-2'-deoxycytidine / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of demethylation therapy of leukemia by 5-aza-2'-deoxycytidine (5-aza-CdR).</p><p><b>METHODS</b>By using MTT test, NBT reduction reaction and DNA agarose gel electrophoresis, changes in proliferation, differentiation and apoptosis were observed in K562, HL-60 and fresh leukemia cells after treated with 5-aza-CdR. The mRNA expressions of DNMTs, p15, p53 and bcl-2 were measured by RT-PCR. The status of p15(INK4B) gene methylation was examined by methylation-specific PCR (MSP-PCR).</p><p><b>RESULTS</b>The growth inhibition of K562, HL-60 and fresh leukemia cells displayed a dose and time-dependent manner after treated by 5-aza-CdR. The differentiation-inducing ability on HL-60 cells was obvious at 0.5 micromol/L of 5-aza-CdR. The up-regulation of p15 mRNA and p53 mRNA expression and down-regulation of bcl-2 mRNA expression were obvious as compared with the control, but the DNMTs expression was not significantly different from the control. The methylation status of p15 gene in fresh leukemia cells decreased gradually with increasing concentration of 5-aza-CdR.</p><p><b>CONCLUSION</b>The proliferation of leukemia cells was obviously inhibited by 5-aza-CdR, its mechanism maybe related to the up-regulation of p15 and p53 genes and down-regulation of bcl-2 gene. The decrease of p15 gene methylation was associated with the competitive inhibition of 5-aza-CdR.</p>

Relationship between resistance to chemotherapy and expression of breast cancer resistance protein (BCRP) gene in patients with acute leukemia / 中国实验血液学杂志

In order to investigate the relationship between the expression of breast cancer resistance protein (BCRP) gene and drug resistance in patients with acute leukemia (AL), semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of BCRP mRNA in AL patients and 15 normal subjects. Beta(2)-microglobin (beta(2)-MG) was used as positive reference. BCRP/beta(2)-MG ratio >or= 0.5 was defined as BCRP mRNA positive. The results showed that the positive percentage of BCRP gene expression in newly diagnosed group was 37.6%. The first complete remission rate was 79.3% and 31.6% in BCRP mRNA negative and BCRP mRNA positive patients respectively. The difference was significant (P = 0.001). The expression levels of BCRP mRNA in drug resistance group and drug sensitive group were 0.962 +/- 0.426 and 0.315 +/- 0.296 respectively (P = 0.0001). The expression level of BCRP mRNA in relapsed/refractory group was significantly higher than that in newly diagnosed group (P = 0.0025). The expression level of BCRP gene in normal individuals and long-term survival group was very low and correlated with FAB subtypes. It is concluded that high expression of BCRP mRNA leads to clinical drug resistance and is an unfavorable factor for prognosis of AL patients except acute promyelocytic leukemia.

Expression of survivin, Fas, bcl-2 and bax in bone marrow cells from acute myeloid leukemia patients and its clinical significance / 中国实验血液学杂志

<p><b>UNLABELLED</b>To study the clinical significance of the expression of antiapoptosis gene, survivin and bcl-2, and proapoptosis gene, Fas and bax, in acute myeloid leukemia (AML), RT-PCR was used to examine the expression of survivin and flow cytometry (FCM) to detect the expression of Fas, bcl-2, bax and bcl-2/bax ratio in 68 cases of AML. The results demonstrated that: (1) The positivity of survivin mRNA expression was significantly higher in AML compared to control (70.6% vs 30%, P < 0.05). (2) The expression of Fas and bcl-2 in AML before treatment was significantly higher than that in control (P < 0.001), but the bax expression did not (P > 0.05). (3) The survivin-positive AML cases showed a significantly lower Fas and higher bcl-2 expression in comparison with survivin-negative ones (P < 0.01 and P < 0.001, respectively), but the bax did not (P > 0.01). (4) Survivin-positive AML cases had a lower CR rate as compared with survivin-negative cases (64.6% vs 90%, P < 0.05). (5) The survivin-positive CR cases showed a decreased expression of Fas and bcl-2 after treatment in comparison with pretreatment expression (P < 0.001), but the bax expression remained unchanged before and after therapy. The survivin-positive NR cases showed a significantly decreased Fas and increased bcl-2 expression as compared with pretreatment expression (P < 0.001). bcl-2/bax ratio was also significantly higher in NR cases.</p><p><b>IN CONCLUSION</b>70.6% AML cases showed positive for survivin expression with a lower CR rate, the survivin-positive AML showed a low Fas with high bcl-2 expression and bcl-2/bax ratio as compared to the survivin-negative cases.</p>

Blastic natural killer cell leukemia--one case report and review of literature / 中华血液学杂志

<p><b>OBJECTIVE</b>To report a case of blastic natural killer cell leukemia with an aggressive clinical course.</p><p><b>METHODS</b>The characteristics of blastic NK cell leukemia and its treatment were discussed with review of literatures.</p><p><b>RESULTS</b>After combination chemotherapy and spinal cord segmental radiotherapy, the patient entered hematological remission, but the extramedullary lesion remained unchanged.</p><p><b>CONCLUSION</b>Blastic NK cell leukemia has an aggressive clinical course with poor response to treatment and unfavorable prognosis.</p>

The clinical significance of cyclin B1 expression in adult acute leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of cyclin B1 expression in adult acute leukemia (AL) patients.</p><p><b>METHODS</b>The expression of cyclin B1 and p21 and their cell cycle distribution were measured by flow cytometry in 85 adult patients with de novo AL, 10 continuous complete remission (CCR) AL and 17 normal controls (NC). The mRNAs of cyclin B1, p21 cip1 and proliferation cell nuclear antigen (PCNA) in patients and NCs were measured with semi-quantity reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Cyclin B1 protein expression in de novo AL patients was significantly higher than that in NC (P < 0.001). It was higher in relapsed patients than in NC (P < 0.05) but was lower than in de novo AL (P < 0.01). There was no difference between the remission cases and NC (P = 0.21), and between CCR patients and NC (P > 0.05). The cyclin B1 overexpression ratio was higher than that of NC. A negative correlation between the expression levels of cyclin B1 and P21 was observed (r = -0.266, P < 0.05). The cyclin B1 protein expression level was positively correlated with its mRNA level. The expression of cyclin B1 was positively correlated with proliferation index (PI) levels, and with PCNA levels (rPI = 0.7314, rPCNA = 0.7152). Remission rate was higher in high cyclin B1 expression patients than in normal cyclin B1 expression patients (P < 0.01), so did the relapse rate (P < 0.01). Patients with higher cyclin B1 expression had higher survival rate.</p><p><b>CONCLUSION</b>Cyclin B1 was overexpressed and abnormally distributed in cell cycle phases in de novo AL patients. Overexpression of cyclin B1 might be a favorable prognostic factor for patients with AL.</p>