OBJECTIVETo investigate the effect of apatinib, a small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, on the proliferation of human acute myeloid leukemia HL-60 cells and explore the possible mechanism.

METHODSMTT assay was used to assess the cytotoxicity of apatinib in HL-60 cells. The apoptosis and cell cycle changes of the cells in response to apatinib treatment were analyzed by flow cytometry, and Western blotting was used to assay P-Akt and P-Erk1/2 expressions in the cells.

RESULTSApatinib significantly inhibited the proliferation of HL-60 cells in vitro with an IC(50) of 4.96∓0.32 µmol/L. Apatinib treatment significantly increased the apoptotic rate of the cells in a dose-dependent manner, but produced no significant effect on the cell cycle (P>0.05). Western blotting showed that the expressions of P-Akt and P-Erk1/2 decreased in HL-60 cells after a 48-h apatinib treatment.

CONCLUSIONApatinib inhibits the proliferation of HL-60 cells by inducing cell apoptosis probably through the mechanism of inhibiting the expressions of the Akt/Erk1/2 signal transduction pathway.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; HL-60 Cells ; Humans ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyridines ; chemistry ; pharmacology

Objective To explore the present condition of endemic arsenism, the implementation of control measures and the effect of the monitored county (Tongyu County) and the monitoring spot (Baiyintuhai Village) in 2006 and 2007. Methods According to the National Survey Scheme of Endemic Arsenism, the progress of anti-arsenic water in Tongyu, and the management and running of all engineering projects and the arsenic content in water were surveyed. The patients with endemic arsenism in Tongyu were generally surveyed. The arsenic content of the improved drinking water in Tongyu and the arsenic in urine of children aged 8-12 and adults over 18 years of age were determinted. The causes of resident death in the monitoring spot from the year of 2006 and 2007 were investigated. Arsenic content of drinking water and the urine of local residents was examined with "Model AFS-930 Double-Channel Atomic Fluorescence Spectrometer". Results There were 30 endemic arsenism areas, 157 areas with high arsenic content and all population of 57 576 in Tongyu. Six areas had improved water till 2006, where 20.0% of water had improved, and six water-improving projects were all running normally, benefiting a population of 1670. Eight high arsenic areas changed water, in a rate of 5.09%. Eight water-improving projects were functioning well, benefiting a population of 4350. Until 2007, 28 areas had improved water in Tongyu, accounting for 93.33%. These 28 projects were well running, covering a population of 7980. One hundred and fouty-eight high arsenic areas had changed water, reaching a rate of 94.27%. One hundred and fouty-eight projects changedg water were running normally, benefiting a population of 46 214. In the surveyed spots, arsenic content was between 0.004 mg/L and 0.005 mg/L in 2006 and between 0.010 mg/L and 0.021 mg/L in 2007, all in the normal range to the time being. The arsenic contents in urine of the children aged 8-12 in the monitoring spots were determinted, averaging at 0.024 mg/L in 15 samples, fluctuating between 0.005 mg/L and 0.048 mg/L in 2006. The average content in urine from adults was 0.019 mg/L in 53 samples, fluctuating between 0.005 mg/L and 0.087 mg/L in 2007. The arsenic contents in urine were all in the normal range in 2006 and 2007. In 2006 14 endemic arsenism patients, all in light symptoms, had been checked out, the morbidity being 6.19%. In 2007, 17 patients who were all in light symptoms were identified in a rate of 6.94%. There was no significant difference of morbidity between the two years(χ2=0.1059, P>0.05). Two patients died, unrelating with drinking high arsenic water in 2006 and 2007. Conclusions The prevention and control measures are well implemented in Tongyu. The water-improving projects are functioning well. The condition of endemic arsenism is slight and hasn't changed so much in these two years. The arsenic contents in urine of children and adults within the normal range, showing that improving water can control the occurrence and the development of endemic arsenism.

OBJECTIVETo establish a rat model of oral mucositis (OM) induced by busulfan and cyclophosphamide (BUCY) conditioning regimen of hematopoietic stem cell transplantation (HSCT).

METHODSIn the model group, busulfan (6.0 mg.kg(-1).d(-1) x 4 d) and cyclophosphamide (120 mg.kg(-1).d(-1) x 2 d) were administered by intra-stomach perfusion and intraperitoneal injection, respectively. The left cheek mucosa were irritated by superficial scratching on day 6. The oral mucosal score (OMS) was assessed daily. Animals were sacrificed on day 7, 10, 13, 16 and 18. The samples of blood, bone marrow, and the oral mucosa were harvest to evaluate the clinical and histological changes.

RESULTSThe incidence of oral mucositis in model group was as high as 80.00% with a survival rate of 73.33%. The initial lesion on the oral mucosa was noted on day 7 with red spot and edema, and then progressive mucositis was characterized by large areas of ulcer formation. The duration of oral mucositis was 8 to 10 days. A continuous weight loss, white blood cell count decrease and bone marrow suppression occurred in the process of oral mucositis.

CONCLUSIONSAn animal model of conditioning regimen-induced oral mucositis was successfully established.

Animals ; Busulfan ; toxicity ; Cyclophosphamide ; toxicity ; Disease Models, Animal ; Feasibility Studies ; Hematopoietic Stem Cell Transplantation ; Male ; Mouth Mucosa ; pathology ; Rats ; Rats, Sprague-Dawley ; Stomatitis ; chemically induced ; etiology ; pathology ; Transplantation Conditioning ; adverse effects

In recent years,accumulating evidence shows that phosphatase of regenerating liver-3(PRL-3)is closely implicated in tumor progression,especially in the stages of invasion and metastasis of various solid tumors, inclu-ding colorectal cancer,gastric cancer and breast cancer.However,the study of PRL-3 in hematological malignancies is rel-atively lagged,but there are some advances in leukemia and myeloma,in which PRL-3 up-regulation is tightly associated with poor prognosis,while the underlying mechanism of signal transduction is gradually explored.In this review,we sum-marized the recent advances of PRL-3 in hematological malignancies such as acute myeloid leukemia,multiple myeloma and chronic myeloid leukemia,as well as the molecular mechanism of PRL-3 in pathogenesis.

Objective:To investigate the effect of IL-34 on the phenotype of monocyte derived dendritic cells in RA,and to speculate the role of IL-34 in the differentiation of myeloid dendritic cells.Methods:The peripheral blood of RA patients was collected to harvest PBMC by Ficoll density gradient centrifugation and cultured for 4h.Adherent cells were stimulated with GM-CSF+IL-4,IL-4, IL-4+IL-34 for 3 days,and then the expression of CD83,CD86 and CD14 was tested by flow cytometry.In addition,the cells stimulated by GM-CSF and IL-4 were added by TNF-α with or without IL-34 for another four days.The expression of CD83,CD86 and/or CD14 was detected by flow cytometry.Results:(1)The expression of CD83 and CD86 on immature DC induced by IL-34+IL-4 was upregulated compared with IL-4 alone(P<0.01),but no difference of the CD14 levels between the two groups(P>0.05).The levels of CD86 and CD14 induced by IL-34+IL-4 were slightly decreased compared with GM-CSF+IL-4 stimulation(P<0.05),but no difference of CD83 expression between the two groups(P>0.05).(2)The expression of CD83 and CD86 stimulated by GM-CSF+IL-4+IL-34 was lower than the GM-CSF+IL-4+TNF-α group(P<0.05),but no difference compared with GM-CSF+IL-4 group(P>0.05). (3)The CD83 expression induced by GM-CSF+IL-4+TNF-α+IL-34 was lower than GM-CSF+IL-4+TNF-α group(P<0.05),but there was no difference of CD86 and CD14 expression between the two groups(P>0.05).Conclusion:IL-34 played roles in the process of immature DC differentiation,but the effect was slightly weaker than that of GM-CSF.IL-34 did not effect the phenotype change of mature DC,but involved in the maintainence of immature DC.

OBJECTIVETo investigate the efficacy of Yunnan Baiyao (YNBY)as an adjuvant treatment of active ulcerative colitis.

METHODSA total of 221 patients with active ulcerative colitis were randomized into YNBY group (78 cases) and control group (143 cases). The patients were followed up for 26 weeks and time of remission and serological data (WBC, HGB, PLT, and CRP) were recorded.

RESULTSThe patients receiving YNBY as an adjuvant therapy had a median remission time of 9 weeks (95% CI: 8.293-9.707), significantly shorter than that of 13 weeks (95% CI: 11.855-14.145) in the control patients (P<0.001). According to the extent of the lesion, both YNBY group and control group were classified into E1, E2 and E3 subgroups, and the median remission time was 7 versus 11 weeks in E1 subgroups (P=0.09), 10 versus 13 weeks in E2 subgroups (P=0.04), and 9 versus 14 weeks in E3 subgroups (P<0.001). According to the disease severity, the patients in YNBY group and control group had a median remission time of 9 versus 10 weeks in mild cases (P=0.568), 9 versus 14 weeks in moderate cases (P<0.001), and 11 versus 20 weeks in severe cases (P=0.001). According to the standard treatment received, the median remission time in YNBY group and control group was 9 versus 12 weeks in those receiving mesalazine (P<0.001), 9 versus 13 weeks in those receiving corticosteroid (P=0.001), and 7 versus 14 weeks in those receiving infliximab (P=0.04). Cox proportional hazards regression analysis showed that YNBY was a protective factor for disease remission. The remission time was shortened by 2.283 times (95% CI: 1.69-3.070, P<0.001) in patients having YNBY as an adjuvant treatment compared to the control group.

CONCLUSIONPatients with active ulcerative colitis can benefit from YNBY as an adjuvant treatment, which shortens the time of disease remission, relieves the symptoms and improves the quality of life of the patients.

OBJECTIVETo study the differential expression of four TRAIL receptors on bone marrow mononuclear cells (BMMNC) from multiple myeloma (MM) patients and myeloma cell line KM3 cells, to compare their altered expressions after chemotherapy and to explore the mechanisms by which TRAIL selectively kills tumor cells.

METHODSSemi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to investigate the expression of four TRAIL receptors on BMMNCs in 23 MM patients, KM3 cells and 15 controls, and the changes of their expression pattern after chemotherapy and after incubation of KM3 cells with sub-clinical concentration of doxorubicin.

RESULTSDR4 and DR5 were highly expressed on KM3 cells with no expression of DcR1 and DcR2. Expressions of DR4 and DR5 on BMMNCs from MM patients were higher and expression of DcR1 and DcR2 were lower than that of controls (P < 0.05). The expression of DR5 on MM and KM3 cells was up-regulated after chemotherapy and exposure to doxorubicin (P < 0. 05).

CONCLUSIONSThe expressions of four TRAIL receptors on myeloma cells and normal controls were different, which might account for the selective killing effect of TRAIL on MM cells. Up-regulated DR5 on KM3 cells after incubating with doxorubicin and after chemotherapy suggests the cytotoxic agents might enhance the apoptosis of MM cells.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cells, Cultured ; Doxorubicin ; pharmacology ; Female ; Flow Cytometry ; Gene Expression ; drug effects ; Humans ; Leukocytes, Mononuclear ; cytology ; drug effects ; metabolism ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; genetics ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effect of the escharectomy during burn shock stage on expression of glucose translator-4 (GLUT4) mRNA in skeletal muscle and adipose tissue.

METHODS30% TBSA scalded rats were employed. Escharectomy were conducted at 8 h, 24 h, 168 h after burns respectively. Insulin, glucagon, cortisol and glucose levels in serum were analyzed. RT-PCR were employed to analyze GLUT4 mRNA expression in skeletal muscle and adipose tissue.

RESULTSGlucagon, cortisol and glucose levels in serum were declined in groups which escharectomy were conducted during burn shock stage. GLUT4 mRNA expression in both skeletal muscle and adipose tissue were downregulated after burns and escharectomy conducted during burn shock stage made it restored to near normal.

CONCLUSIONGLUT4 mRNA expression will declined after major burns in skeletal muscle and adipose tissue. Escharectomy during shock stage could make it upregulated, which will be helpful to improve glucose metabolism and hypermetabolism after major burns.

Adipose Tissue ; metabolism ; Animals ; Blood Glucose ; Burns ; physiopathology ; surgery ; Gene Expression ; Glucagon ; blood ; Hydrocortisone ; blood ; Insulin ; blood ; Male ; Monosaccharide Transport Proteins ; genetics ; Muscle, Skeletal ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Shock, Traumatic ; physiopathology

OBJECTIVETo investigate the correlation of prolactin receptor (PRL-R) expression to estrogen receptor (ER) and progesterone receptor (PR) expressions in primary breast cancer.

METHODSFor 130 female patients with breast cancer (median age 46 years), PRL-R expression in the primary tumor was detected by immunohistochemistry, and the correlation between PRL-R and ER/PR expressions was analyzed statistically.

RESULTSPRL-R positivity in the primary tumor was found in 89 of the patients (68.5%), and the positivity rate for PRL-R was positively correlated to ER expression (P<0.05). Further stratification of the patients according to the CerbB-2 status revealed such a correlation only in CerbB-2-positive patients (P<0.05). In the patient cohort, no significant correlation was found in the positivity rate between PRL-R and PR expressions (P>0.05), but in CerbB-2-positive patients, the positivity rate of PRL-R showed a positive correlation to PR expression (P<0.05).

CONCLUSIONThe positive correlations in positivity rate between the PRL-R and ER/PR expressions are found only in CerbB-2 positive patients with breast cancer, and the expressional status of CerbB-2 affects the correlation between PRL-R and ER/PR expression in breast cancer.

Adult ; Aged ; Breast Neoplasms ; metabolism ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; genetics ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Receptors, Prolactin ; metabolism

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
Antineoplastic Combined Chemotherapy Protocols ; Bortezomib/therapeutic use* ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Multiple Myeloma/therapy* ; Retrospective Studies ; Stem Cell Transplantation ; Transplantation, Autologous ; Treatment Outcome