Advances in the mechanism of small nucleolar RNA and its role in DNA damage response.

Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.

Small Nucleolar RNA, C/D Box 16 (SNORD16) Acts as a Potential Prognostic Biomarker in Colon Cancer.

Colon cancer (CC) is considered one of the most common and lethal malignancies occurring both in male and female. Its widespread prevalence demonstrates the need for novel diagnostic and prognostic biomarkers for CC. Emerging evidence has shown that small nucleolar RNAs play critical roles in tumor development. In this study, we investigated the expression profile and functions of SNORD16 in CC. Our data showed that SNORD16, rather than its host gene (RPL4), was upregulated in CC cell lines. Compared to matched adjacent normal tissues, CC tissues showed higher SNORD16 expression levels, and no correlation was found between SNORD16 and RPL4. Patients with high SNORD16 expression levels had a worse prognosis, and multivariate analysis showed the high SNORD16 expression was an independent prognostic factor for CC. In vitro gain- and loss-of-function studies revealed that SNORD16 can promote cell growth, proliferation, migration, and invasion of CC cells by inhibiting apoptosis. These results suggested that SNORD16 has an oncogenic role in CC and might be a novel diagnostic and prognostic biomarker for CC.

Single-Component Bismuth Nanoparticles as a Theranostic Agent for Multimodal Imaging-Guided Glioma Therapy.

Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo. In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.

Treatment of acute myeloid leukemia by directly targeting both leukemia stem cells and oncogenic molecule with specific scFv-immunolipoplexes as a deliverer.

Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the suppression of normal hematopoiesis, chemotherapy is currently the most used method to treat AML. The standard chemotherapy results in a more than 50% complete remission rate in AML patients. However, treatment with drugs such as anthracyclines is associated with severe side effects and a high incidence of relapse, the long-term survival of AML is poor. The success of the treatment of acute promyelocytic leukemia with all trans retinoic acid and chronic myeloid leukemia with imatinib mesylate (Gleevec) has led to increased efforts to look for agents for AML targeted therapy. But, most of presented targeted therapy agents do only direct some oncogenic molecules involved in the leukemogenesis of AML, their anti-leukemic efficacy is unsatisfied. Thus, novel therapeutic approaches are required. In recent years, a leukemia stem cells (LSCs) origin for AML has been demonstrated, and some unique immunophenotype and specific molecular features of LSCs have also been identified. With the technique development of Immunoliposomes (antibody-coupled liposomes) and the recombination of the variable regions of heavy and light chains and their integration into a single polypeptide that offer the possibility of using single-chain antibody variable region fragments (scFv) for targeting purposes, here we put the hypothesis that treatment of AML by targeting both LSCs and oncogenic molecule participated in AML pathogenesis, with LSCs-specific scFv-immunolipoplexes as a deliverer, might be possible. If successfully using this approach in practice, LSCs might be selectively eradicated and AML might be cured.

[Relation between the expression of sIL-2R and the relapse in patients with acute lymphoblastic leukemia].

OBJECTIVE: To explore the relation of the serum level of sIL-2R in relapse patients with acute lymphoblastic leukemia (ALL). METHODS: With ELISA, we determined the levels of sIL-2R of 48 patients with ALL after their first diagnoses, complete remission 1 and relapse. The levels of sIL-2R of 30 patients from complete remission 1 to relapse were monitored. RESULTS: The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the control. The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the complete remission 1 group. However, the difference between the complete remission 1 and the control had no statistical significance. When we determined the levels of sIL-2R dynamically, we found that after complete remission, the levels of sIL-2R decreased, however, before one month of hematological relapse, the levels of sIL-2R increased. CONCLUSION: Monitor of the level of sIL-2R can predict impending relapse of patients with ALL and is helpful to early diagnosis of relapse.

[Chimeric Ad5F35 adenoviral vector-mediated expression of mutant IκBα induces apoptosis of leukemia cells].

Constitutive activation of nuclear transcription factor-κB (NF-κB) exists in a variety of leukemia, and induction of apoptosis through blocking NF-κB activation may be an alternative strategy for leukemia treatment. The aim of this study was to investigate the inducing effect of modified adenovirus 5-based adenovirus vector (i.e. chimeric Ad5F35 Vec)-mediated expression of mutant IκBα (IκBαDN) on apoptosis of HL-60 cells. The recombinant Ad5F35-IκBαDN Vec carrying IκBαDN cDNA which deleted the first 1-70 amino acids coding sequences at 5' terminal of human IκBα was transfected into HL-60 cells. The apoptosis, NF-κB DNA binding activity, the expressions of IκBα, cIAP-2 and xIAP in HL-60 cells were detected by DNA binding assay, flow cytometry, real-time quantitative polymerase chain reaction and Western blot respectively. The results showed that apoptosis rates were 22.53 ± 2.999%, 6.08 ± 2.464% and 4.86 ± 1.366% for Ad5F35-IκBαDN Vec-infected or blank vector of Ad5F35-EGFP Vec-transfected and untransfected HL-60 cells respectively, which showed a significant difference between Ad5F35-IκBαDN Vec-transfected and untransfected cells (p < 0.001) and between Ad5F35-IκBαDN Vec-transfected and Ad5F35-EGFP Vec-transfected cells (p < 0.001, p < 0.002), while NF-κB DNA binding activity was decreased, the truncated IκBα was expressed, and IκBα mRNA expression was up-regulated, but the expression of cIAP-2 and xIAP mRNA was down-regulated after transduction for 48 hours. It is concluded that the chimeric Ad5F35 Vec can effectively mediate the expression of IκBαDN cDNA in HL-60 cells, leading to the inhibition of NF-κB DNA binding activity and inducing apoptosis of HL-60 cells.

[Effect of acetyl-11-keto-ß-boswellic acid on proliferation, apoptosis and cell cycle of human acute myeloid leukemia cell line HL-60].

The aim of this study was to investigate the effect of 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) on the proliferation, apoptosis and cell cycle of human acute myeloid leukemia (AML) cell line HL-60. HL-60 cells were treated by AKBA at various concentrations. The inhibitory effects of AKBA on the proliferation of HL-60 were analyzed by MTT assay. Morphologic changes of HL-60 cells were observed by fluorescence microscopy with Hochest33342 staining. Cell apoptosis rate was determined by flow cytometry with Annexin-V-FITC/PI double staining. The cell cycle was measured by flow cytometry with PI staining. The results showed that AKBA inhibited the proliferation of HL-60 and the apoptosis rate of HL-60 cells was gradually enhanced when AKBA dose increased. AKBA changed the cell cycle of HL-60, resulting in cell increase at G(1) phase and decrease at S phase. It is concluded that the AKBA has anti-proliferation and apoptosis-inducing effects on HL-60 cells, that seems a promising therapeutical approach for AML.

[Effect of diallyl disulfide on the expression and secretion of VEGF in HL-60 cells].

OBJECTIVE: To investigate the proliferation inhibition of human leukemic cell line HL-60 and the expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein in HL-60 cells treated with diallyl disulfide (DADS). METHODS: MTT was used to test the cell growth, semi-quantitative RT-PCR and ELISA to study the expression of VEGF mRNA and secretion of VEGF protein. RESULTS: DADS significantly inhibited proliferation of HL-60 cell and the inhibiting effects showed a dose (r > 0.9, P < 0.01) and time-dependent( r > 0.7, P < 0.01) manner. The expression of VEGF mRNA and secretion of VEGF protein could be down regulated by 0.625, 1.250, and 2.500 microg/mL DADS in HL-60 cells for 24,48 and 72 hours exposure and the effects also showed dose -dependence(r > 0.9, P < 0.01). The growth inhibition rates of DADS in HL-60 cells at three dosages for 24 hours were (8.19 +/- 3.34)%, (16.79 +/- 2.07)% and (21.30 +/- 2.72)%, those for 48 hours were (11.93 +/- 3.93)%, (22.81 +/- 2.31)% and (30.74 +/- 2.03)%, for 72 hours were (16.68 +/- 2.37)%, (28.54 +/- 3.26)% and (36.59 +/- 2.37)% respectively, The difference between the DADS-treated and untreated HL-60 cells was statistically significant (P < 0.01). There were also statistically significant differences among the three groups of different dosages (P < 0.01). CONCLUSION: DADS can effectively inhibit the proliferation of HL-60 cells. DADS probably exerts its anti-leukemia effects by reducing the expression of VEGF mRNA and secretion of VEGF protein in HL-60 cells.

[CD34(+)/CD123(+) cell sorting from the patients with leukemia by Midi MACS method].

The aim of this study was to sort the CD34(+)/CD123(+) cells from the bone marrow cells of patients with acute myeloid leukemia (AML) by Midi MACS method. Firstly, the bone marrow mononuclear cells (BMMNC) were isolated from the patients with AML with Ficoll Paque, CD34(+) cells were then isolated by Midi MACS method followed by the isolation of CD34(+)/CD123(+) cells from the fraction of CD34(+) cells. The enrichment and recovery of CD34(+) and CD34(+)/CD123(+) cells were assayed by FACS technique. The results showed that the enrichment of CD34(+) cells was up to 98.73%, its average enrichment was 95.6%, and the recovery of CD34(+) was 84.6%, its average recovery was 51% after the first round sorting, by the second round sorting, the enrichment of CD34(+)/CD123(+) cells was up to 99.23%, its average enrichment was 83%. With regard to BMMNCs before sorting, the recovery of CD34(+)/CD123(+) was 34%. But, on the CD34(+) cells obtained by the first round sorting, its recovery was 56%. In conclusion, these results confirmed that the method of Midi MACS sorting can be applied to sort CD34(+)/CD123(+) cells from the bone marrow cells of AML patients, which give rise to the similar enrichment and recovery of the sorted cells with that of literature reported by the method of FACS.

[Advances of study on activation of nuclear factor kappaB in hematological malignancies and its mechanism--review].

The nuclear factor kappa B(NF-kappaB) plays a crucial role in inflammatory, immune response, embryo development, cell proliferation and apoptosis, cell cycle control as well as tumorgenesis. In recent years, a variety of investigations have demonstrated that NF-kappaB was closely associated with the pathogenesis of hematological malignancies such as leukemia, lymphoma and multiple myeloma. Nowadays, increasingly attention has been paid to the studies on the activation and its mechanism of NF-kappaB in the hematogenic malignancies. So that, in this article, progress on these aspects is reviewed.

[Clinical significance and expression of vascular endothelial growth factor in serum of patients with acute leukemia].

OBJECTIVE: To determine the serum vascular endothelial growth factor (VEGF) level in patients with acute leukemia and to elucidate the relation of its level with the carcinogenesis or relapse of acute leukemia and its clinical significance. METHODS: The VEGF levels in the serum and leukemic cell cultured supernatants were measured by sandwich ELISA in 88 acute leukemia patients and 30 healthy individuals. RESULTS: The pre-chemotherapeutic serum and supernatant VEGF level in newly diagnosed or relapsed patients with acute leukemia were significantly higher than those in healthy subjects (P < 0.01). The serum VEGF level was correlated with the count of blast cells in bone marrow or peripheral blood of patients with acute leukemia (P < 0.05). CONCLUSION: The pretherapeutic serum VEGF level of patients with acute leukemia appears to be a predictor of the carcinogenesis or relapse of acute leukemia and reflects the tumor burden of acute leukemia.

[Clinical significance of the detection of the sL-selectin level in patients with acute leukemia].

OBJECTIVE: To study the relationship between the episode and state of acute leukemia and the level of soluble L-selectin (sL-selectin) in the plasma and cerebrospinal fluid. METHODS: With a sandwich enzyme-linked immunosorbent assay (ELISA), the levels of sL-selectin in the plasma of 40 patients with acute leukemia and in the cerebrospinal fluid of 28 patients with acute lymphoblastic leukemia were measured, and compared with 20 controls. RESULTS: The levels of sL-selectin were significantly higher in the patients with untreated and therapy-resistant acute leukemia or leukemia relapse than those in the complete remission patients and the controls (P < 0.001). The levels of SL-selectin were related to the clinical course of acute leukemia. CONCLUSION: Monitoring the sL-selectin level may be useful for evaluating leukemia activity, in particular for the detection of leukemia relapse and meningeal infiltration.

[Study on expression of cell surface L-selectin and soluble L-selectin in patients with acute leukemia].

To study the relationship between the level of the soluble L-selectin (sL-selectin) in plasma and surface L-selectin expression on leukemic cells and episode and state of illness in acute leukemia patients, the plasma level of sL-selectin was measured by a sandwich enzyme-linked immunosorbent assay, and the expressions of surface L-selectin and its gene (lyam-1) were detected by immunohistochemistry and RT-PCR. The results showed that the levels of sL-selectin were significantly higher in untreated and therapy-resistant acute leukemia patients, and expression of L-selectin mRNA and cell surface L-selectinin in untreated and NR patients were significantly lower than that in CR patients and control group (P < 0.05). The plasma levels of sL-selectin were significantly increased in patients with splenomegaly and hepatomegaly (extramedullary infiltration). The levels of sL-selectin were related to the clinical course of the acute leukemia patients. A significant correalation existed between expressions of L-selectin mRNA and surface L-selectin in acute leukemia patients (gamma = 0.782, P < 0.05). It is concluded that expression of L-selectin gene was down-regulated in level of mRNA and protein in acute leukemia patients and both changes were highly correlated. Monitoring of the plasma level of sL-selectin is possibly useful for early diagnosis of relapse and extramedullary infiltration in acute leukemia.