Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Clinical factors affecting the long-term survival of breast cancer patients.

OBJECTIVE: The average 5-year survival rate of breast cancer (BC) patients has been significantly prolonged with new therapeutic methods. However, their effects on BC patient long-term survival rates are unclear. Therefore, this study aimed to analyze the specific clinical factors that can affect BC long-term survival. METHODS: Here, we conducted a retrospective study and analyzed long-term survival using data of 3,240 BC patients from 1977 to 2005 from the Genotype-Tissue Expression (GTEx) database using the Kaplan-Meier method. RESULTS: Breast tumor size and stage were negatively correlated with long-term survival, but age showed no significant correlation. Estrogen receptor (ER) and progesterone receptor (PR) expression were each positively correlated with patient survival time, while ERBB2 receptor (HER2) expression was negatively correlated with survival time. Patients with high Nottingham prognostic index (NPI) values did not benefit from available therapies. Furthermore, breast-conserving surgery is more conducive to BC patient long-term survival than mastectomy. CONCLUSIONS: Early detection and breast-conserving surgery may support long-term survival for BC patients. Elevated expression of ER and PR were both associated with longer patient survival time, while positive expression of HER2 showed the opposite trend. The long-term survival rates of patients with high NPI values can potentially be increased.

A new indole alkaloid with HUVEC proliferation activities from Nauclea officinalis.

A new indole alkaloid, namely naucleofficine H (1), was obtained from the aqueous extract of Nauclea officinalis, together with four known alkaloids, vincosamide (2), strictosamide (3), angustoline (4) and pumiloside (5). Their structures were characterized by analyzing their physicochemical data including NMR, and HRMS. In addition, five compounds were tested for their proliferation activities. The expression of vascular endothelial growth factor (VEGF), extra-cellular signal-regulated protein kinase 1 and 2 (ERK) and phosphorylation of ERK 1/2 (p-ERK) were also detected in HUVEC treated withbioactive compounds using western blotting. The result showed that these compounds could promote HUVEC cell proliferation. Compounds 3 and 5 could up-regulate VEGF and p-ERK in HUVEC.

Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway.

BACKGROUND: Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. METHODS: In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. RESULTS: Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. CONCLUSION: Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique.

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next-generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3-internal tandem duplication (FLT3-ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPAdouble mutation . In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse-free survival (RFS), DNMT3A, FLT3-ITD, or RUNX1 mutation predicted a higher likelihood of remission-induction failure, whereas NRAS mutation or CEBPAdouble mutation predicted longer OS. Concurrent DNMT3A, FLT3-ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation-related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.

Single­cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction.

Single­cell RNA sequencing (scRNA­seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA­seq. Clustering methods were used to separate leukemia cells into different sub­populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT­rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA­seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.

[Investigation of PRAM1 Expression Features and Their Clinical Significance in AML via Gene Expression Microarray Database].

OBJECTIVE: To study the clinical phenotype and its prognostic value of PRAM1 in patients with acute myeloid leukemia(AML). METHODS: Based on the gene expression microarray platform of 486 AML cases, the PRAM1 expression phenotypes were summarized in all of AML subtypes. The PRAM1 expression features were explored in every differentiation stage of hematocytes through normal human stem cell chips and bone marrow gene expression microarray. The clinical drugs which could up-regulate PRAM1 expression in AML cell lines should be found out. RESULTS: The PRAM1 expression was the richest in the inv(16) AML and the lowest in the t(15;17)M3, almost the same in the other subtypes of AML. By the classification of molecular abnormalities, PRAM1 expression was more in the panel of CN-AML with CEBPAdm than the other two panels. Interestingly, high/low expression of PRAM1 could be re-classified in the CN-AML, and the EFS is statistically significant. It was proven again that PRAM1 is more expressed in the mature granulocytes. Finally, it was confirmed that decitabine and the chidamide could up-regulate PRAM1 expression in AML cell lines, and chidamide effect is better. CONCLUSION: PRAM1 expression is the lowest in t(15;17) M3 and the highest in inv(16) AML. The high expression of PRAM1 is a sign for favorable prognosis in the CN-AML. PRAM1 is more expressed in mature granulocytes, chidamide can up-regulate PRAM1 expression in AML cell lines.

Regulatory crosstalk between KLF5, miR-29a and Fbw7/CDC4 cooperatively promotes atherosclerotic development.

Atherogenesis is a chronic inflammatory process that involves complex interactions between endothelial dysfunction, lipid deposition and vascular smooth-muscle cell (VSMC) proliferation. However, the molecular mechanism is still unclear. We found that a pro-atherosclerotic factor (oxLDL) induced the expression of Krüppel-like factor 5 (KLF5), which in turn increased miR-29a expression levels. The increased miR-29a was retained within HASMCs and down-regulated Fbw7/CDC4 expression by targeting the 3´UTR of Fbw7/CDC4, subsequently increasing KLF5 stability by reducing the Fbw7/CDC4-dependent ubiquitination of KLF5, forming a positive feedback loop to enhance VSMC proliferation and promote atherogenesis. These results indicate a potentially important role for the oxLDL-activated feedback mechanism in VSMC proliferation and atherogenesis. Suppression of miR-29a may be an effective way to attenuate atherosclerosis. In conclusion, our data are the first to reveal that the regulatory crosstalk between KLF5, miR-29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development.

[Clinical Features and Prognosis of t(8;21) AML Patients in China: A Multicenter Retrospective Study].

OBJECTIVE: To summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China. METHODS: The factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression. RESULTS: The immune type of t(8;21) AML patients was mainly with HLA-DR+, CD117+, CD34+, MPO+, CD38+, CD13+ and CD33+ (>95%), part of them with CD19+ and CD56+; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×109/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×109/L(P<0.05). CONCLUSION: The clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×109/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.

[Research Progress of Ras/Raf/MEK/ERK Signaling Pathways in Leukemia-Review].

Ras/Raf/MEK/ERK signaling pathway plays an important role in the occurrence and development of leukemia. Using the inhibitors of key signaling components in the signaling pathway is new strategy for the treatment of leukemia. In recent years, the screening of these inhibitors and their in vitro and in vivo researches have become a hot spot in the field of treatment. In vivo and in vitro experiments and early clinical studies have shown that these inhibitors have good effect and application prospects in the treatment of leukemia. This review focuses on the recent advances of the role of Ras/Raf/MEK/ERK signaling pathway in the occurence, development and treatment of leukemia.

[A Retrospective Study of Ph Negative Adolescent and Young Adults with Acute B Lymphoblastic Leukemia in Two Centers].

OBJECTIVE: To analyze the therapeutic efficacy of different consolidation therapies after induction remission on Ph negative adolescent and young adults with acute B lymphoblastic leukemia, and to explore the effect of different risk factors on prognosis. METHODS: The treatment and efficacy of 80 Ph negative B-ALL in patients of 16-39 years old in the Hematology Department of 301(65 cases) and 309(15 cases) hospital from 1999 to 2016 are retrospectively analyzed. The patients received combined induction chemotherapy of 4 or 5 chemotherapeutic drugs (VDCLP/ VDLP/ DOLP/ IOLP). After remission patients received consolidation protocols of 3-5 cycls, and then received allo-HSCT or haploidentical HSCT. The median follow-up time was 29 (6-153) months. RESULTS: HSCT was carried out after CR1. The 5-year OS and EFS of allo-HSCT group(n=29) was (73±16)% and (67±17)%, respectively, while those of haploidentical-HSCT group(n=20) were (53±22)% and (53±22)%, respectively, and those of pediatric-inspired protocols(n=31) was (63±17)% and (50±18)%, respectively. The difference between OS and EFS in 3 group was not statistically significant(P>0.05). The re-remission rate of recurrent patients was (50±23)%. On the one side, the cumulative incidence of TRM of pediatric-inspired protocol was better than that of HSCT (P<0.05). On the other side, the cummulative incidence of relapse (CIR) of pediatric-inspired protocol was poorer than that of HSCT, yet without significant difference (P>0.05). The median remission time of CR2 in patients was 14(2-36) months. Univariate and multivariate analysis were performed in 65 patients, and showed an abnormal result of CD13 or CD33 positive, CD22 negative, indicating a poor prognosis(P<0.05). CONCLUSION: In the adolescent and young adult patients with Ph- B-ALL treated by pediatric-inspired protocols, the survival time is similar with that in allo-HSCT group. However, more prospective clinical studies of random control test(RCT) should be carried out.

MicroRNA-21 Regulates the Proliferation, Differentiation, and Apoptosis of Human Renal Cell Carcinoma Cells by the mTOR-STAT3 Signaling Pathway.

MicroRNA-21 (miRNA-21), a kind of short, noncoding RNAs, functioned as a tumor marker and was upregulated in renal cell carcinoma (RCC). However, the underlying mechanisms of miRNA-21 in RCC were uncertain. Therefore, the effects and mechanisms of miRNA-21 on the proliferation, differentiation, and apoptosis of cultured human RCC cells were further investigated in this study. After slicing miRNA-21 in RCC cells, the viability, mRNA expression of C/EBPα and PPARγ, caspase 3 activity, and protein expression of mTOR, STAT3, and pSTAT3 were determined. It was found that knockdown of miRNA-21 downregulated the optical density (OD) value of cells, inhibited mRNA expression of PPARγ and C/EBPα, and enhanced activity of caspase 3. Furthermore, protein expression of pSTAT3 was also decreased in the absence of miRNA-21. Notably, miRNA-21-changed proliferation, differentiation, and apoptosis of human RCC cells were partially regulated following the block of the mTOR-STAT3 signaling pathway by the mTOR inhibitor (XL388). It was indicated that miRNA-21 promoted proliferation and differentiation and decreased apoptosis of human RCC cells through the activation of the mTOR-STAT3 signaling pathway.

Comparison of Clinical Efficacy of Cytarabine with Different Regimens in Postremission Consolidation Therapy for Adult t(8;21) AML Patients: A Multicenter Retrospective Study in China.

BACKGROUND: The survival of patients with acute myeloid leukemia (AML) with t(8;21) was reported to be shorter in China than in other countries. PATIENTS: We analyzed the correlation between different cytarabine (Ara-c) regimens and outcome in 255 t(8;21) AML patients in China who received postremission consolidation chemotherapy only. RESULTS: The 5-year overall survival (OS) of the high-dose Ara-c group (HDAC; 2≤ Ara-c ≤3 g/m2), intermediate-dose Ara-c group (MDAC; 1.0≤ Ara-c <2.0 g/m2), low-dose Ara-c group (LDAC; 0.2< Ara-c <1.0 g/m2) and standard-dose Ara-c group (SDAC; 0.1≤ Ara-c ≤0.2 g/m2) were 65.3, 39.4, 25.2 and 27.9%, respectively (p = 0.003). In the HDAC group, but not in the MDAC group, the 5-year OS of patients who achieved 3-4 cycles of chemotherapy was superior to those who underwent 1-2 cycles (84.4 vs. 43.6%, p < 0.05), and the 3-year OS of patients who achieved an accumulated 36 g/m2 of Ara-c was significantly higher compared to those who did not (85.3 vs. 39.2%, p < 0.05). Multivariate analysis indicated that factors such as WBC >3.5 × 109/l, PLT ≤30 × 109/l, and extramedullary infiltration were associated with a poor prognosis. CONCLUSION: The survival of t(8;21) AML patients treated with high-dose Ara-c (≥2 g/m2) was superior to other dose levels in postremission consolidation chemotherapy. Patient survival was improved by 3-4 cycles of chemotherapy with an accumulated concentration of 36 g/m2 of Ara-c. WBC >3.5 × 109/l, PLT ≤30 × 109/l and extramedullary infiltration could be indicative of a poor clinical prognosis.

Prognostic Significance of Mixed-Lineage Leukemia (MLL) Gene Detected by Real-Time Fluorescence Quantitative PCR Assay in Acute Myeloid Leukemia.

BACKGROUND The overall prognosis of acute myeloid leukemia (AML) patients with mixed-lineage leukemia (MLL) gene-positivity is unfavorable. In this study, we evaluated the expression levels of the MLL gene in AML patients. MATERIAL AND METHODS We enrolled 68 MLL gene-positive patients out of 433 newly diagnosed AML patients, and 216 bone marrow samples were collected. Real-time fluorescence quantitative PCR (RQ-PCR) was used to precisely detect the expression levels of the MLL gene. RESULTS We divided 41 patients into 2 groups according to the variation of MRD (minimal residual disease) level of the MLL gene. Group 1 (n=22) had a rapid reduction of MRD level to ≤10^-4 in all samples collected in the first 3 chemotherapy cycles, while group 2 (n=19) had MRD levels constantly >10^-4 in all samples collected in the first 3 chemotherapy cycles. Group 1 had a significantly better overall survival (p=0.001) and event-free survival (p=0.001) compared to group 2. Moreover, the patients with >10^-4 MRD level before the start of HSCT (hematopoietic stem cell transplantation) had worse prognosis and higher risk of relapse compared to patients with ≤10^-4 before the start of HSCT. CONCLUSIONS We found that a rapid reduction of MRD level to ≤10^-4 appears to be a prerequisite for better overall survival and event-free survival during the treatment of AML. The MRD levels detected by RQ-PCR were basically in line with the clinical outcome and may be of great importance in guiding early allogeneic HSCT (allo-HSCT) treatment.

Correlations of Promoter Methylation in WIF-1, RASSF1A, and CDH13 Genes with the Risk and Prognosis of Esophageal Cancer.

BACKGROUND This study was designed to explore the correlations of promoter methylation in Wnt inhibitory factor-1 (WIF-1), ras-association domain family member 1A (RASSF1A), and Cadherin 13 (CDH13) genes with the risk and prognosis of esophageal cancer (EC). MATERIAL AND METHODS A total of 71 EC tissues from resection and 35 adjacent normal tissues were collected. Methylation status in the promoter region was detected by methylation- and non-methylation-specific primers. Corresponding mRNA levels were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Correlations between the methylations of these 3 genes and clinicopathologic characteristics were analyzed. Kaplan-Meier method and Cox regression model were used to investigate the relationships between WIF-1, RASSF1A, and CDH13 promoter methylations and the prognosis of EC. RESULTS Compared with adjacent normal tissues, the methylation frequencies of WIF-1, RASSF1A, and CDH13 genes were significantly higher but the mRNA levels of these 3 genes were significantly lower in EC tissues (all P<0.05). WIF-1 and CDH13 promoter methylations were associated with the degree of tumor differentiation and WIF-1 and RASSF1A promoter methylations were associated with age (all P<0.05). The survival rates of patients with WIF-1, RASSF1A, and CDH13 methylations were significantly lower than those of patients without methylation (all P<0.05). WIF-1, RASSF1A, and CDH13 promoter methylations were independent risk factors affecting the prognosis of EC (all P<0.05). CONCLUSIONS WIF-1, RASSF1A, and CDH13 promoter methylations are associated with EC. The methylation levels are negatively related with the prognosis in EC.

[Analysis of Clinical Characteristics in 10 Patietns with T Large Granular Lymphocytic Leukemia].

OBJECTIVE: To analyze the clinical manifestations and laboratory features of patients with T large granular lymphocytic leukemia (T-LGLL), so as to improve the understanding of this disease. METHODS: The clinical data of 10 patients with T-LGLL in General Hospital of Chinese PLA from October 2015 to March 2010 were analyzed retrospectively. RESULTS: Their median age at diagnosis was 51 years old. 9/10 (90%) patients showed symptoms of anemia, with a median Hb level of 82.5 g/L, 5/10 (50%) patients combined with autoimmune disorders and with a median Hb level of 77 g/L. 7/10 (70%) patients had splenomegaly, 2/10 (20%) patients had complex karyotype, 2/10 (20%) patients had gene mutations, the median age of 4 patients with complex karyotype and gene mutation was 49 years old, all of them suffered from splenomegaly. The immunophenotype of 6/10 patients was CD3+ CD4- CD8+ and that of 2/10 patients (20%) was CD3+ CD4- CD8-, that of another 2/10 (20%) was CD3+ CD4+ CD8-, the clinical features between different types of immunization were not statistically different. CONCLUSION: T-LGLL patients often are old men, combined with anemia and splenomegaly, often associated with autoimmune diseases; the patients with complex karyotype and gene mutation are younger and they are more with hepatosplenomegaly; the guide role of different immunotypes for clinical strategy is no significant.

Epigenetic Silencing of Eyes Absent 4 Gene by Acute Myeloid Leukemia 1-Eight-twenty-one Oncoprotein Contributes to Leukemogenesis in t(8;21) Acute Myeloid Leukemia.

BACKGROUND: The acute myeloid leukemia 1 (AML1)-eight-twenty-one (ETO) fusion protein generated by the t(8;21)(q22;q22) translocation is considered to display a crucial role in leukemogenesis in AML. By focusing on the anti-leukemia effects of eyes absent 4 (EYA4) gene on AML cells, we investigated the biologic and molecular mechanism associated with AML1-ETO expressed in t(8;21) AML. METHODS: Qualitative polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-PCR), and Western blotting analysis were used to observe the mRNA and protein expression levels of EYA4 in cell lines. Different plasmids (including mutant plasmids) of dual luciferase reporter vector were built to study the binding status of AML1-ETO to the promoter region of EYA4. Chromatin immunoprecipitation assay was used to study the epigenetic silencing mechanism of EYA4. Bisulfite sequencing was applied to detect the methylation status in EYA4 promoter region. The influence of EYA4 gene in the cell proliferation, apoptosis, and cell clone-forming ability was detected by the technique of Cell Counting Kit-8, flow cytometry, and clonogenic assay. RESULTS: EYA4 gene was hypermethylated in AML1-ETO+ patients and its expression was down-regulated by 6-fold in Kasumi-1 and SKNO-1 cells, compared to HL-60 and SKNO-1-siA/E cells, respectively. We demonstrated that AML1-ETO triggered the epigenetic silencing of EYA4 gene by binding at AML1-binding sites and recruiting histone deacetylase 1 and DNA methyltransferases. Enhanced EYA4 expression levels inhibited cellular proliferation and suppressed cell colony formation in AML1-ETO+ cell lines. We also found EYA4 transfection increased apoptosis of Kasumi-1 and SKNO-1 cells by 1.6-fold and 1.4-fold compared to negative control, respectively. CONCLUSIONS: Our study identified EYA4 gene as targets for AML1-ETO and indicated it as a novel tumor suppressor gene. In addition, we provided evidence that EYA4 gene might be a novel therapeutic target and a potential candidate for treating AML1-ETO+ t (8;21) AML.

Effects of Minimally Invasive Esophagectomy and Open Esophagectomy on Circulating Tumor Cell Level in Elderly Patients with Esophageal Cancer.

OBJECTIVE: To investigate the effects of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on circulating tumor cell (CTC) level of elderly patients with esophageal cancer (EC). METHODS: A total of 78 elderly EC patients who aged over 64 years were divided into the MIE group (n = 40) and the OE group (n = 38). CTC enrichment was performed through CD326 (EpCAM) immunomagnetic beads positive sorting, and then labeled by CK-PE and CD45. The quantity of CTCs was measured by multiparameter flow cytometry. Double antibody sandwich enzyme-linked immuno sorbent assay ELISA (DAS-ELISA) was used for detecting the levels of IL-6, IL-10, and IFN-γ. RESULTS: Among the 78 elderly EC patients, CTC level after the surgery was higher than that during the surgery, and CTC level during surgery was higher than that before the surgery (both P < 0.05). Postoperative CTC level in the MIE group was lower than that in the OE group, and the variation of CTC level from pre-operation to intra-operation in the MIE group was also lower than that in the OE group (both P < 0.05). Furthermore, there was significant difference in the incidences of intra-operative and postoperative complications between the MIE group and the OE group (17 cases vs. 31 cases, P < 0.05), and the CTC levels of the patients with complications in either group were significantly higher than the patients without complications (both P < 0.05). IL-6 and IL-10 levels significantly increased, while IFN-γ level decreased in both groups during the surgery and 3 days after the surgery compared to those before the surgery; 2 weeks after the surgery, IL-6 and IL-10 levels in the MIE group recovered to the pre-operative levels (all P < 0.05). However, in the OE group, IL-6 and IL-10 levels 2 weeks after the surgery were still significantly higher than those before the surgery (all P < 0.05); IFN-γ levels in both groups recovered to the pre-operative levels, with higher level in the MIE group than that in the OE group (P < 0.05). CONCLUSION: MIE helped to reduce the survival rate of tumor cells in peripheral blood at the early period of postoperation, and dynamic monitoring CTC level could be used to evaluate the prognosis of EC patients.

SUMOylation of KLF4 acts as a switch in transcriptional programs that control VSMC proliferation.

The regulation of vascular smooth muscle cell (VSMC) proliferation is an important issue due to its major implications for the prevention of pathological vascular conditions. The objective of this work was to assess the function of small ubiquitin-like modifier (SUMO)ylated Krϋppel-like transcription factor 4 (KLF4) in the regulation of VSMC proliferation in cultured cells and in animal models with balloon injury. We found that under basal conditions, binding of non-SUMOylated KLF4 to p300 activated p21 (p21(WAF1/CIP1))transcription, leading to VSMC growth arrest. PDGF-BB promoted the interaction between Ubc9 and KLF4 and the SUMOylation of KLF4, which in turn recruited transcriptional corepressors to the p21 promoter. The reduction in p21 enhanced VSMC proliferation. Additionally, the SUMOylated KLF4 did not affect the expression of KLF4, thereby forming a positive feedback loop enhancing cell proliferation. These results demonstrated that SUMOylated KLF4 plays an important role in cell proliferation by reversing the transactivation action of KLF4 on p21 induced with PDGF-BB.

[Retrospective Analysis of the Impact of Treatment on Prognosis in 44 Adolescents and Young Adult Patients with Acute Lymphoblastic Leukemia].

OBJECTIVE: To study the clinical characteristics and the impact of treatment on prognosis in 44 adolescents and young adult (AYA) patients with acute lymphoblastic leukemia. METHODS: Clinical data of 44 AYA ALL patients admitted in our hospital from September 1997 to April 2014 were analyzed retrospectively and the impact of treatment on overall survival (OS) and event free survival (EFS) were investigated. RESULTS: The median age of the patients at diagnosis was 23.7 (15-37) years and the male/female was 2.38:1. Out of them 88.6% of patients achieved complete remission (CR) after 1 course of induction chemotherapy, 35 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 6 patients received chemotherapy, 3 patients received autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy in CR1. The expected 3-year OS and EFS rates of all the 44 patients were 64.3% and 61.7% respectively. The expected 5-year OS and EFS rates were 55.4% and 56.6% respectively. Allo-HSCT was not superior to chemotherapy and auto-HSCT in all the 44 patients (P = 0.308 for OS and P = 0.291 for EFS). In allo-HSCT group, the treatment related mortality was 22.9%, and the differences of OS and EFS in standard risk and poor risk AYA ALL patients were no significant (P = 0.775 for OS and P = 0.817 for EFS). However, compared with chemotherapy and auto-HSCT, allo-HSCT could significantly improve the OS and EFS in standard risk AYA ALL (P = 0.0296 for OS and P = 0.0359 for EFS). CONCLUSION: Allo-HSCT as consolidation therapy may provide survival improvement for standard risk AYA ALL. However, further prospectively randomized clinical study is warranted to confirm whether allo-HSCT is an optimal treatment for AYA ALL, which is still controversial at present.