Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments.

Elaborated Reaction Pathway of Photothermal Catalytic CO Conversion with H O on Gallium Oxide-Decorated and -Defective Surfaces.

Ga O -decorated and -defective surface models based on anatase TiO have been established. The thermodynamic reaction pathways, including protonation, deoxygenation and hydroxylation steps, during CO conversion with H O to C products were calculated. The calculation results demonstrate that a Ga O cocatalyst enhances the selective adsorption of CO and slightly weakens the competitive adsorption of H O.

Total Chemical Synthesis of Correctly Folded Disulfide-Rich Proteins Using a Removable O-Linked β--Acetylglucosamine Strategy.

Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. Our strategy comprises the introduction of simple O-linked β--acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates.

Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia.

Identifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo.

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma].

Objective: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

Methods: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL).

Wu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways.

The kinase FLT3 internal tandem duplication (FLT3-ITD) is related to poor clinical outcomes of acute myeloid leukemia (AML). FLT3 inhibitors have provided novel strategies for the treatment of FLT3-ITD-positive AML. But they are limited by rapid development of acquired resistance and refractory in monotherapy.

Effects and long-term follow-up of using umbilical cord blood-derived mesenchymal stromal cells in pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis after unrelated cord blood transplantation.

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 10 /kg once a week until the symptoms improved.

[Efficacy Analysis of Unrelated Cord Blood Transplantation for High-Risk Refractory AML1-ETO Positive Myeloid Leukemia].

Objective: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).

Methods: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.

Overexpression of Fbxo6 inactivates spindle checkpoint by interacting with Mad2 and BubR1.

The spindle assembly checkpoint prevents chromosome mis-segregation during mitosis by delaying sister chromatid separation. Several F-box protein members play critical roles in maintaining genome stability and regulating cell cycle progress via ubiquitin-mediated protein degradation. Here, we showed that Fbxo6 critically regulated spindle checkpoint and chromosome segregation.

Characterization of naturally occurring pentacyclic triterpenes as novel inhibitors of deubiquitinating protease USP7 with anticancer activity in vitro.

Deubiquitinating protease USP7 is a promising therapeutic target for cancer treatment, and interest in developing USP7 inhibitors has greatly increased. In the present study, we reported a series of natural pentacyclic triterpenes with USP7 inhibitory activity in vitro. Among them, both the ursane triterpenes and oleanane triterpenes were more active than the lupine triterpenes, whereas ursolic acid was the most potent with IC of 7.

Double vs. single cord blood transplantation in adolescent and adult hematological malignancies with heavier body weight (≥50 kg).

Background: Double-unit cord blood transplantation (CBT) can be used to overcome the limitation of single-unit CBT with low cell content for adults and larger adolescents. However, whether double-unit CBT is superior to single-unit CBT remains controversial.

Methods: We reviewed the medical records of 228 consecutive hematological malignancies who received CBT between November 2005 and December 2013.

Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells.

Synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-Me) has been shown as a promising agent against ovarian cancer. However, the underlying mechanism is not well understood. Here, we demonstrate that CDDO-Me directly interacts with Hsp90 in cells by cellular thermal shift assay.

Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells.

Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells.

Ikaros inhibits proliferation and, through upregulation of Slug, increases metastatic ability of ovarian serous adenocarcinoma cells.

The transcription factor Ikaros was originally found to function as a key regulator of lymphocyte differentiation. In this study, we provide the first evidence that Ikaros is expressed at higher levels in ovarian cancer tissues compared with normal ovarian tissues and is significantly associated with high FIGO stage and low differentiation state in ovarian serous adenocarcinoma. To this end, we transfected IK1 (full length of Ikaros) into the SKOV3 ovarian cancer cell line and examined cell biological behaviors including proliferation, migration and invasion.

Proteomic identification of common SCF ubiquitin ligase FBXO6-interacting glycoproteins in three kinds of cells.

FBOX6 ubiquitin ligase complex is involved in the endoplasmic reticulum-associated degradation pathway by mediating the ubiquitination of glycoproteins. FBXO6 interacts with the chitobiose in unfolded N-glycoprotein, pointing glycoproteins toward E2 for ubiquitination. Although the glycoprotein-recognizing mechanism of FBXO6 is well documented, its bona fide interacting glycoproteins are largely unknown.

Ikaros is degraded by proteasome-dependent mechanism in the early phase of apoptosis induction.

Ikaros is an important transcription factor involved in the development and differentiation of hematopoietic cells. In this work, we found that chemotherapeutic drugs or ultraviolet radiation (UV) treatment could reduce the expression of full-length Ikaros (IK1) protein in less than 3h in leukemic NB4, Kasumi-1 and Jurkat cells, prior to the activation of caspase-3. Etoposide treatment could not alter the mRNA level of IK1 but it could shorten the half-life of IK1.

PU.1 directly regulates retinoic acid-induced expression of RIG-G in leukemia cells.

RIG-G is a retinoic acid- or interferon-induced gene with potential anti-proliferation function. However, the mechanism underlying ATRA-induced RIG-G induction is not completely understood. Here, we demonstrate that ATRA up-regulates the expression of PU.

[Early antigen diagnosis of invasive fungal infection in patients with hematological malignancies and patients receiving hematopoietic stem cell transplantation].

This study was purposed to evaluate the sensitivity and specificity of G/(1, 3-β-D glucan)/GM (galactomannan) combined detection for early diagnosis of invasive fungal disease (IFD), determine the GM positive cut-off value, and investigate the change of diagnostic level before and after G/GM test and the relation of GM value with therapeutic effect. The ELISA with double antibody sandwich was used to detect the serum levels of G and G/M. The results showed that according to determined GM positive cut-off value, the sensitivity, specificity, positive and negative predictive value of G/GM combined detection were 100%, 65.

Pharicin B stabilizes retinoic acid receptor-α and presents synergistic differentiation induction with ATRA in myeloid leukemic cells.

All-trans retinoic acid (ATRA), a natural ligand for the retinoic acid receptors (RARs), induces clinical remission in most acute promyelocytic leukemia (APL) patients through the induction of differentiation and/or eradication of leukemia-initiating cells. Here, we identify a novel natural ent-kaurene diterpenoid derived from Isodon pharicus leaves, called pharicin B, that can rapidly stabilize RAR-α protein in various acute myeloid leukemic (AML) cell lines and primary leukemic cells from AML patients, even in the presence of ATRA, which is known to induce the loss of RAR-α protein. Pharicin B also enhances ATRA-dependent the transcriptional activity of RAR-α protein in the promyelocytic leukemia-RARα-positive APL cell line NB4 cells.

Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function.

In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in leukemia and solid tumor-derived cells identified by their morphology, DNA content and mitotic marker analyses. Pharicin A-induced mitotic arrest is associated with unaligned chromosomes, aberrant BubR1 localization and deregulated spindle checkpoint activation.

[Functional defect of partial homing receptor on human cord blood hematopoietic stem/progenitor cells].

This study was aimed to investigate the function defect of partial homing receptor on cord blood hematopoietic stem cells (CBHSC) and explore efficacy and feasibility of intervention in vitro. The expression and activity of active groups in P, E-selectin ligands on CD34+ cells from cord blood, bone marrow and peripheral blood were detected by flow cytometry; meanwhile the expression of active groups in selectin ligands on CD34+ cells treated by fucosyl transferase in vitro was determined by flow cytometry. The results indicated that the expression levels of CD26 on the surface of stem/progenitor cells (CD34+) from cord blood, bone marrow and peripheral blood were (7.

Synergistic mitosis-arresting effects of arsenic trioxide and paclitaxel on human malignant lymphocytes.

The treatment outcome of acute lymphoblastic leukemia (ALL) has improved steadily over the last 50 years. However, the cure rates are unlikely to be raised further with current therapies. Since increasing the dosage of chemotherapeutic agents could also elevate toxicity, a solution to how one could achieve maximum therapeutic effect with the minimum dosage possible is imminent.

Defects in chromosome congression and mitotic progression in KIF18A-deficient cells are partly mediated through impaired functions of CENP-E.

KIF18A, a molecular motor, is an essential component in the regulation of orderly chromosome congression by attenuation of the kinetochore oscillation amplitude at the midzone during mitosis in vertebrate cells. Here we report that KIF18A depletion resulted in mitotic arrest which was accompanied by the presence of unaligned chromosomes in HeLa cells. This resembles the phenotype induced by an impaired function of CENP-E, also a mitotic kinesin essential for the formation of the mitotic spindles.