High expression of anti-apoptotic protein Bcl-2 is a good prognostic factor in colorectal cancer: Result of a metaanalysis

AIM To systematically evaluate the prognostic-predictive capability of Bcl-2 in colorectal cancer(CRC).METHODS A systematic literature search was conducted using Pub Med,Web of Science and EMBASE databases. Any eligible study must meet the following criteria:(1) bcl-2 expression was evaluated in human CRC tissues by immunohistochemistry;(2) assessment of the relationships between bcl-2 expression and overall survival(OS),disease free survival(DFS),recurrent free survival(RFS) or clinic-pathological characteristics of CRC was included;(3) sufficient information was provided to estimate the hazard ratio(HR) or odds ratio and their 95% confidence intervals(CIs); and(4) the study was published in English. The impact of Bcl-2 expression on survival of CRC patients were evaluated through this meta-analysis.RESULTS A total of 40 eligible articles involving 7658 patients were enrolled in our final analysis. We drew the conclusion that Bcl-2 high expression was significantly correlated with favorable OS(pooled HR = 0.69,95%CI: 0.55-0.87,P = 0.002) and better DFS/RFS(pooled HR = 0.65,95%CI: 0.50-0.85,P = 0.001). Additionally,the subgroup analysis suggested that Bcl-2 overexpression was significantly associated withprognosis(OS) especially in patients came from Europe and America but not Asian and patients who did not receive any adjuvant therapy before surgery. Finally,our present results indicated that expression of bcl-2 protein was associated with high differentiation grade and A/B Ducks' stage. CONCLUSION Bcl-2 high expression was significantly correlated with favorable OS and better DFS/RFS. Hence,we propose that Bcl-2 may be a valuable prognostic-predictive marker in CRC.

Secretion of nerve growth factor,brain-derived neurotrophic factor,and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

The present study co-cultured human embryonic olfactory ensheathJng cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7-10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid （10%, 20% and 30%） in the growth medium caused a decrease of neurotrophic factor secretion Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.

Local low-dose X-ray radiation promotes homing of mesenchymal stem cells to the injured mouse spinal cord

BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.

Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report

BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

Research progress of follicular cytotoxic T cells in human immunodeficiency virus infection

Recently, a new type of CD8^+ T cell subset, namely, the CXCR5^+ CD8^+ T cell subset(also called the follicular cytotoxic T cell(TFC) subgroup), has been discovered around B cell follicles. The discovery has aroused widespread interest.However, the processes and mechanisms of TFCs taking part in the immune response of the germinal center and their specific roles must still be clearly identified. This paper reviews domestic and foreign studies on factors regulating the phenotype,physiological functions, maturity, and differentiation of TFCs and roles and clinical significance these cells in human immunodeficiency virus infection. Our review has shown good application prospects for TFCs. We believe that further studies on TFCs can provide another tool for cytotherapy of controlling or curing chronic viral infections or tumors.

The Analysis of Anemia in Chronic Heart Failure

objectives To demonstrate the phenomena and explore the causes of anemia in patients with chronic heart failure （CHF）. Methods To observe the phenomena of anemia in patients with CHF, a total of 276 patients with CHF were included in this retrospective study. The clinical characteristics of the patients are： mean age 69.2± 11.0 years; male 151, female 125; NYHA Ⅲ and Ⅳ 115（41.7%）. Results ①Among the 276 patients with CHF, 81 （29.4%）had anemia （Mean hemoglobulin concentration 101.5±13.0 g/L）.② Patients with Anemia were more likely to be female and to have greater NYHA （ Ⅲ or Ⅳ ） （P 〈 0.05）, higher serum creatinine, as well as lower serum albumin and low-density lipoprotein levels （P 〈 0.01 ）. ③ A weak negative correlation was also noted between the level of NYHA and hemoglobulin. ④ There was no significant difference in age, the primary cardiac etiology of the CHF, the history of diabetes, left ventricular end diastolic diameter, and left ventricular ejection fraction between CHF patient with and without anemia. Conclusions The prevalence of anemia is high among patients with CHF. The anemia patients with CHF tend to be female, have greater cardiac and renal functional impairment, but with lower serum albumin and LDL that suggests some degree of malnutrition.

CONSTRUCTION AND SIGNIFICANCE OF DIRECTIONAL cDNA EXPRESSION LIBRARY FROM HUMAN MYELOMA CELL

Objective To construct human myeloma cell cDNA expression library as to screen myeloma tumor antigen. Methods Total RNA and purified mRNA were extracted from human myeloma cell line HMy2. First and second strand cDNA were synthesized through reverse transcription. After blunting, the cDNA fragments were ligated with EcoR I adapters. Then the cDNAs were digested by Xho I, and smaller than 400bp were removed by Sephacryl-S400 spin column, the remaining were ligated with λZAP vector. The recombinants were packaged in vitro, and a small portion of packaged phage was used to infect E.coli XL1-Blue-MRF for titration. The recombinants were examined by color selection. In order to evaluate the size of cDNA inserts and the diversity of library, the pBK-CMV phagemid were excised from the ZAP express vector by using ExAssist helper phage with XLOLR strain , and then the pBK-CMV phagemid were digested by Xho I and EcoR I. Results The HMy2 cell line cDNA library consisting of 1.58×10 6 recombinant bacteriophages was constructed with the recombinant ratio 99.6%. The average length of the recombinant exogenous inserts was about 1.7kb.Conclusion The constructed cDNA library are deserved to screen target clones.

Shp2,a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia

Shp2 ，由 PTPN11 基因编码了为人，是包含二N终端 Src 相同的无所不在地表示的蛋白质酷氨酸磷酸酶 2 ( SH2 )领域( N-SH2 ， C-SH2 ，分别地)，一个催化蛋白质酷氨酸磷酸酶( PTP )领域，并且C终端与 tyrosyl 磷酸化地点和一个prolyl富有的主题跟踪。我们 Shp2 的生物函数的理解的进步清楚地证明了 Shp2 不仅在正常造血的房间和另外的哺乳动物的房间的生物学，而且在白血病和另外的肿瘤的开发起一个重要作用。最最近，当第一 proto-oncogenethat 编码蛋白质酷氨酸磷酸酶， PTPN11 基因坚定地被建立了。在造血的系统，最如果 Shp2 的并非所有功能是充当一个积极部件，那为通过表明包含英皇家空军之阶级最低之兵， Akt 和 STAT5 的小径的规定的造血的房间的增长或幸存是必要的。

Berbamine selectively induces apoptosis of human acute promyelocytic leukemia cells via survivin-mediated pathway

Background Currently, resistance and relapse are still major problems in acute promyelocytic leukemia （APL） cases. Thus, new agents that override the resistance are crucial to the development of curative therapies for APL. In this study, we investigated the effects of berbamine on the proliferation of APL cell line NB4 and its possible mechanisms. Methods NB4 cells were treated with berbamine at different concentrations （0-64 μg/ml） for 72 hours. MTT assay was used to determine proliferation inhibition of NB4 cells. Cell apoptosis was evaluated by both flow cytometry （FCM） and morphological examination. PML/RAR-α and survivin mRNAs were measured by nested-RT-PCR and RT-PCR, respectively. Activated-caspase 3 was determined by FCM. Results Berbamine greatly inhibited the proliferation of NB4 cells in dose- and time-dependent manners, and its IC50 value was 3.86 μg/ml at 48 hours. Both morphological observations and FCM results showed that berbamine induced apoptosis of NB4 cells with concomitant increase of activated caspase-3 and decrease of survivin mRNA. After treatment with berbamine at 8 μg/ml for 48 hours, the percentage of apoptotic cells increased from 2.83% to 58.44% （P〈0.01）, and the percentage of cells with activated-caspase 3 elevated from 2.06% to 70.89% （P〈0.01）, whereas, level of survivin mRNA was reduced to 38.24% of control （P〈0.01）. However, no significant change was observed in PML/RAR-α mRNA.Conclusions Berbamine induces caspase-3-dependent apoptosis of leukemia NB4 cells via survivin-mediated pathway, suggesting that berbamine may be a novel potential agent against APL with a mechanism distinct from that of all-trans retinoic acid （ATRA） and arsenic trioxide （ATO）.

Fibrinogen and P-selectin expression in atherosclerosis model of Sprague Dawley rat

Background Platelet P-selectin plays an important role in inflammation and contributes to thrombosis and hemostasis. Fibrinogen may take part in inflammation, thrombosis, and hemostasis via enhancement of platelet P-selectin expression. This study aimed to discover the correlation between them in atherosclerosis model of Sprague Dawley （SD） rat. Methods Diet-induced atherosclerosis SD rats were adopted as experimental models. The blood from the common abdominal aorta of the rats was obtained to measure the biochemical characteristics and for the check of flow cytometry. Then the aortas were separated carefully, taken out, put into 10% （w/v） neutral formalin for later use. Then fibrinogen and P-selectin expression were detected by flow cytometry and immunohistochemistry. Results SD rats were induced to atherosclerosis model by high fat diet and vitamin D2 injected. It was discovered that the binding of fibrinogen and the expression of P-selectin on the platelet increase in atherosclerosis model （Group H） than in that in the control group （Group Z）, there were closely interrelated. High levels of fibrinogen and P-selectin express on the artery of atherosclerosis rat model. Conclusions Fibrinogen and P-selectin are concerned with atherosclerosis. Fibrinogen can interact with P-selectin in order to contribute to the development of atherosclerosis, high levels of fibrinogen and P-selectin can be regarded as risk factors for markers of atherosclerosis.

Effect of Artemisinin Combined with Glucocorticoid on the Expressions of Glucocorticoid Receptor α mRNA,Glucocorticoid Receptor β mRNA and P300/CBP Protein in Lupus Nephritis Mice

Objective：To investigate the therapeutic effects and mechanisms of using artemisinin（Art） combined with glucocorticoid（GC） to treat lupus nephritis（LN） mice.Methods：Forty hybrid female mice were randomly and equally divided into four groups with the method of random number table：control group,model group,prednisone group administrated with 6.45 mg/（kg·d） prednisone suspension,and Art＋prednisone group administrated with 150 mg/（kg·d） Art suspension and 3.225 mg/（kg·d） prednisone suspension.A mice model of LN was established by injection with living lymph cell suspension.The changes of urine protein/24h,the expressions of GC receptorα（GRα） mRNA,GC receptorβ（GRβ） mRNA in peripheral blood mononuclear cells（PBMCs）,and transcriptional coactivator P300/CBP protein in renal tissue were measured.Results： Compared with the model group,the treatment groups had significant decrease in urine protein/24 h,and renal pathological lesion（P0.01）.In the same groups,the expression of transcriptional coactivator P300/CBP protein in renal tissue and GRαmRNA were significantly increased,and GRβmRNA expression was significantly decreased（P0.01）.And the Art＋prednisone group has a better therapeutic effect than the prednisone group （P0.01）.Conclusions：Art has therapeutic sensitization effects on GC in the LN mice.The underlying mechanism could be correlated with the effect of Art on the increase of the expressions of GRαmRNA and transcriptional coactivator P300/CBP protein in renal tissue and on the decrease of the expression of GRβmRNA in PBMCs.

Clinical Study of Trilogy Detoxicating Therapy Combined with Routine Western Medicine on Patients with Chronic Renal Failure

Objective： To investigate the mechanism of Trilogy Detoxicating Therapy in treating patients with chronic renal failure （CRF）. Methods： A total of 142 patients were assigned to the Trilogy Detoxicating Therapy group （the treatment group, 82 patients） and the Western medicine treatment group （the control group, 60 patients）. All of the patients were treated with NovoNorm 1 mg and metformin hydrochloride tablets 0.15 g thrice per day for lowering the blood glucose, as well as Perindopril 4 mg twice daily for lowering blood pressure, recombinant human erythropoietin 2 000 U and a hypodermic injection thrice a week for rectifying anemia, 30 days as one course of treatment, and all patients were treated for two courses. Patients in the treatment group were treated with the Trilogy Detoxicating Therapy [dispersing the five-zang （脏） organs, expelling toxins through colonic dialysis and skin dialysis fumigation] in addition to the aforementioned drugs. Parameters observed and recorded in the study included renal function [serum creatinine （SCr）, blood urea nitrogen （BUN）], blood lipids [triglyceride （TG）, total cholesterol （TC）, low-density lipoprotein C （LDL-C）, high-density lipoprotein C （HDL-C）], plasma total protein （TP）, hemoglobin （Hb）, serum interleukin-6 （IL-6）, and tumor necrosis factor-α （TNF-α） before and after the treatment. Results： After two courses of treatment, the levels of SCr, BUN, TG, TC, LDL-C, serum IL-6 and TNF-α decreased significantly, meanwhile HDL-C increased in the treatment group （P〈0.05 or P〈0.01）. In contrast, no obvious changes of the above mentioned items occurred in the control group. In both groups, the levels of TP and Hb were significantly elevated （P〈0.05 or P〈0.01）, but the changes were more obvious in the treatment group （P〈0.01）. Conclusion： Trilogy Detoxicating Therapy played a therapeutic role on patients with CRF possibly through lowering the levels of blood lipids, serum IL-6 and TNF- α.

Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells

Background Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 （CXCR4） and extracellular matrix metalloproteinase inducer （EMMPRIN） had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated. Methods A co-culture system between SHI-1 cells and bone marrow stromal cells （BMSCs） is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 1：10 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 （MMP-2, MMP-9）, tissue inhibitor of metalloproteinase 2 （TIMP-2）, and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 （SDF-1） in serum free supernatant was measured by ELISA. Results Both SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the co- culture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant. Conclusion The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.

Study on Effect of Yishen Capsule (益肾胶囊) in Preventing Recurrence of Chronic Glomerulonephritis

Objective： To observe the effect of Yishen Capsule （益肾胶囊, YSC） on preventing the recurrence of chronic glomerulonephritis （CGN） and to explore its mechanism preliminarily. Methods： CGN patients were assigned to the treated group （61 cases） and the control group （48 cases） and all of them were orally administered with 4 mg of Perindopril twice a day, but 3 capsules of YSC, thrice a day, were given additionally to patients in the treated group. The therapeutic course for both groups was 18 months. The recurrence rate of CGN at the 6th, 12th, and 18th month in the two groups was observed and compared, and the changes of 24-h urinary protein quantity and T-lymphocyte subsets before and after treatment were observed as well. Results： （1） Comparison of recurrence rate between the two groups showed insignificant difference at the 6th month, but it did show significant difference at the 12th and the 18th month, which was significantly decreased in the treated group than in the control group （P〈0.05, P〈0.01）; （2） The 24-h urinary protein quantity at the 18th month decreased significantly in both groups （P〈0.05, P〈0.01）, but in the treated group was more significant （P〈0.01）; （3） T-lymphocyte subsets showed no obvious change in the control group after treatment （P〉0.05）, while in the treated group, it showed significant increase in CD3, CD4 and CD4/CD8 （P〈0.05 or P〈0.01） and significant decrease in CD8 （P〈0.05）, and also the difference after treatment in T-lymphocyte subsets between the two groups was significant （P〈0.05 or P〈0.01）. Conclusion： YSC has marked effects in reducing the recurrence of CGN and in decreasing urinary protein, and its mechanism might be related with its function in regulating the ratio of T-lymphocyte subsets to enhance the immunity of patients.

HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression

Diffuse large B-cell lymphoma(DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%-15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog(MYC) and/or B-cell lymphoma-2(BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL;however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase(HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.

Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic,leading to millions of infections and hundreds of thousands of human deaths.The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses,although the viral proteins responsible for this immune evasion are not clear.In this study,we identified SARS-CoV-2 structural proteins,accessory proteins,and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways.In particular,the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways.Viral accessory protein 0RF3a had the unique ability to inhibit STING,but not the RLR response.On the other hand,structural protein N was a unique RLR inhibitor.0RF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-KB signaling.3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling.Diverse vertebrate STINGs,including those from humans,mice,and chickens,could be inhibited by 0RF3a and 3CL of SARS-CoV-2.The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo.Since evasion of host innate immune responses is essential for the survival of all viruses,our study provides insights into the design of therapeutic agents against SARS-CoV-2.

Up-regulation of TIMP-2 expression promotes SHI-1 leukemic cells proliferation and infiltration in immunodeficiency mice

Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro. Methods A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-I. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-traated nu/nu mice to investigate the infiltration ability feature in vitro. Results The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over- expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice. Conclusion Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.

Etoposide,dexamethasone,and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma:A randomized phase III study

Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and safety of reduced-intensity,non-intravenous etoposide,dexamethasone,and pegaspargase(ESA)with sandwiched radiotherapy.This multicenter,randomized,phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China.Patients were randomly assigned(1:1)to receive ESA(pegaspargase 2,500 IU/m^(2)intramuscularly on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4)or MESA(methotrexate 1 g/m^(2)intravenously on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4,and pegaspargase 2,500 IU/m^(2)intramuscularly on day 5)regimen(four cycles),combined with sandwiched radiotherapy.