OBJECTIVETo investigate the role of mesenchymal stem cells (BMSCs) in multiple myeloma (MM) bone marrow (BM) microenrivonment and their effect on myeloma cells survival and bortezomib induced apoptosis.

METHODSBMSCs were derived from BM of untreated myeloma patients (MM-BMSCs) and healthy donors (HD-BMSCs), respectively. The phenotype, proliferation time and cytokine secretion of MM-BMSCs were detected and compared with HD-BMSCs. Then BMSCs were co-cultured with myeloma cell line NCI-H929 and bortezomib in vitro. The NCI-H929 cells proliferation and bortezomib induced cell apoptosis were investigated.

RESULTSMM-BMSCs and HD-BMSCs were isolated successfully. The phenotype of MM-BMSCs was similar to that of HD-BMSCs. Expressions of CD73, CD105, CD44 and CD29 were positive, but those of CD31, CD34, CD45 and HLA-DR (< 1%) negative. The proliferation time of MM-BMSCs was longer than that of HD-BMSCs (82 h vs 62 h, P < 0.05). Moreover, over-expressions of IL-6 and VEGF in MM-BMSCs culture supernatant were detected as compared with that in HD-BMSCs [(188.8 ± 9.4) pg/ml vs (115.0 ± 15.1) pg/ml and (1497.2 ± 39.7) pg/ml vs (1329.0 ± 21.1) pg/ml, respectively]. MM- BMSCs supported survival of the myeloma cells NCI-H929 and protected them from bortezomib induced cell apoptosis.

CONCLUSIONSMM-BMSCs is benefit for myeloma cells proliferation and against cell apoptosis induced by bortezomib. Over-expression of IL-6 and VEGF maybe play a critical role in these effects.

Apoptosis ; drug effects ; Bone Marrow Cells ; cytology ; Bortezomib ; Humans ; Mesenchymal Stromal Cells ; metabolism ; Multiple Myeloma ; metabolism

OBJECTIVETo investigate the efficacy of imatinib in the treatment of chronic myeloid leukemia (CML) and analyse the treatment outcome and related factors.

METHODSNinety five CML patients were treated with imatinib in our hospital from May 2002 to May 2006. The outcomes and related factors were analysed.

RESULTS(1) One year after therapy, there were 95.5% of chronic phase (CP) patients achieved complete hematologic response (CHR). Fifty-two patients with complete cytogenetic dates were divided into primary-therapy group (n = 19) and secondary-therapy group (n = 33). The major cytogenetic responses (MCyR) at 6-, 12-, 18-, 24- and 30-months after therapy for the former group were 84.2%, 84.2%, 89.5%, 89.5% and 94.7%, and for the latter group were 36.4%, 39.4%, 39.4%, 39.4% and 39.4%, respectively (P < 0.01). The expected survival at 12-, 24-, 36- and 50-month after imatinib treatment for CP group was (98.1 +/-1.9)%, (87.8 +/- 7.1)%, (81.9 +/- 8.7)% and (81.9 +/- 8.7)%, respectively. (2) Twelve month after therapy, there are 70% of accelerated phase (AP) patients achieve CHR and 10% get MCyR. The expected survival at 12-, 24- and 36-month after imatinib treatment for AP group was (63.0 +/- 17.7)%, (15.8 +/- 14.3)% and (15.8 +/- 14.3)%, respectively. (3) Six month after therapy, 57.9% of blast crisis (BC) patients achieve CHR, with the expected survival at 12- and 24-month of (40.6 +/- 12.3)% and 0, respectively. (4) COX analysis CP group indicated that imatinib therapy administered for previously untreated was an independent favorable prognostic factor. Conclusion (1) Imatinib as a primary treatment for CP CML can significantly improve the survival time as compared with that AP or BC patients or with that used in previously treated patients. (2) Imatinib could induce hematologic, even cytogenetic response to a certain extent, in CP or BC patients and prolong the survival time.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo analyze the characteristics of cytogenetic aberration of adults with Philadelphia chromosome-positive (Ph+) and/or bcr-abl positive (bcr-abl+) acute lymphoblastic leukaemia (ALL), and investigate its influence on patients' outcomes.

METHODRetrospective analysis of 100 adult Ph+ ALL patients from January 1, 1996 to December 31, 2007 was carried out. The type, distribution and frequency of chromosome aberration were summarized, and compared among different subgroups.

RESULTS1) In all cases, 72 had chromosome aberrations, including 22 with sole Ph chromosome, 44 Ph+ with additional abnormalities, which included double Ph, monosomy 7, monosomy 20, trisomy 8 trisomy 21, 9p deletion and 22 deletion. 2) Patients with pseudodiploid and hyperdiploid had higher WBC count, and inferior outcome with lower rates of overall survival (OS) and relapse free survival (RFS). 3) Ph+ group also had higher WBC counts and inferior outcome with low OS and RFS rates. There was no statistic significance between sole Ph+ group and Ph plus additional aberrations group. 4) Patients with both abnormal and normal metaphase (AN) and with solely abnormal metaphase (AA) had higher WBC count, less frequent P190 occurrence and inferior outcome than those only normal metaphase (NN) group, whereas, there was no difference between AA and AN groups. 5) Double Ph chromosome had a lower frequency of P190 and inferior OS than non-double Ph group.

CONCLUSIONAdults with Ph+ ALL have complicated cytogenetic abnormalities, pseudodiploid and hyperdiploid indicate inferior outcome, and double Ph chromosome may be a unfavorable prognostic factor.

Adolescent ; Adult ; Chromosome Aberrations ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Prognosis ; Retrospective Studies ; Young Adult

Aim To investigate the effects of morphine preconditioning (MPC) on transient receptor potential vanilloid 1 (TRPV1) channel current in rat dorsal root ganglia (DRG) neurons and the phosphorylation (p) of TRPV1 and extracellular regulated protein kinases (ERK) in PC12 cells that sensitized by nerve growth factor (NGF). Methods DRG neurons isolated from T2-T8 segments of 10 days old SD rat or pheochromo-cytoma (PC12) cells were seeded into 24-well plates or 6-well plates, respectively, and randomly divided into 5 groups:control group (group C), NGF sensiti-zation group (group NGF), and morphine precondi-tioning groups (group MPC 0.3, group MPC 1.0 and group MPC 3.0). DRG neurons were identified by im-munofluorescent method with neuronal specific enolase (NSE). Cells were treated by morphine, NGF and capsaicin to simulate the effects of MPC on DRG neu-rons in T2-T8 segments during myocardial ischemia reperfusion injury (IRI). Afterwards, the inward cur-rent of DRG neurons induced by capsaicin in all groups were detected by whole cell recording; the expression and phosphorylation of TRPV 1 and ERK in PC12 cells were detected by Western blot. Results DRG neu-rons survived and grew nicely,and the staining of neu-ronal specific markers,NSE,was positive. In compar-ison with group C, the inward current of group NGF was enhanced (P <0.05), while MPC inhibited the enhancement (P <0.05). The relative expression of TRPV1,p-TRPV1 and p-ERK in group NGF was up-regulated when compared with group C (P <0.05).Moreover, the up-regulation was also suppressed by MPC (P <0.05). Conclusions MPC inhibits TR-PV1 channel current sensitized by NGF in neurocytes, and the mechanism might be associated with the down-regulation of TRPV1 p-TRPV1 and p-ERK expression.

OBJECTIVE: To investigate the effects of ulinastatin (UTI) on cerebral inflammatory response during cardiopulmonary bypass (CPB). METHODS: Twenty-four NYHA II-III patients (13 males and 11 females) aged 23-45 years, undergoing elective cardiac valve replacement under hypothermic CPB were randomly divided into 2 groups: ulinastatin group (Group U, n=12) and control group (Group C, n=12). In group U, UTI (1.2 x 10(4) U/kg) was given intravenously after the induction of anesthesia, 0.6 x 10(4) U/kg UTI was added to the priming solution, and 0.6 x 10(4) U/kg UTI was given about 5 min before the aortic decamping. In Group C, normal saline was given instead of UTI. Internal jugular vein was cannulated and the catheter was advanced retrogradely till jugular bulb. Blood samples were taken simultaneously from artery and jugular bulb after induction of anesthesia (T1), 60 min (T2) and 6 h (T3) after discontinuation of CPB for determination of TNFalpha, IL-6, IL-8 and IL-10. The juguloarterial gradients of these cytokines (deltaTNFalpha, deltaIL-6, deltaIL-8, and deltaIL-10) were calculated. RESULTS: In Group C, arterial levels of TNFalpha, IL-6, IL-8, IL-10 at T2 and T3, deltaTNFalpha, deltaIL-8 and deltaIL-10 at T2, deltaTNFalpha, deltaIL-6 and deltaIL-10 at T3 significantly increased (P < 0.01). deltaIL-8 increased at T3 (P < 0.05). In Group U, arterial levels of IL-6, IL-8, IL-10 at T2, arterial levels of IL-6, IL-8,IL-L-10 and deltaTNFalpha, deltaIL-8 at T3 significantly increased (P < 0.01). Arterial levels of TNFalpha at T2 and T3, deltaTNFalpha, deltaIL-10 at T2, deltaIL-6 at T3 increased (P < 0.05). Arterial levels of TNFalpha, IL-6 and deltaTNFalpha, deltaIL-8 at T2, arterial levels of TNFalpha and deltaIL-6 at T3 in Group U were lower than those in Group C (P < 0.05). Arterial levels of IL-6 at T3, IL-8 at T2 and T3 in Group U were significantly lower than those in Group C (P < 0.01). Arterial levels of IL-10 and deltaIL-10 at T3 in Group U were higher than those in Group C (P < 0.05). CONCLUSION Systemic and cerebral activation of inflammatory response during CPB can be alleviated by ulinastatin.
Adult ; Cardiopulmonary Bypass ; adverse effects ; Encephalitis ; etiology ; metabolism ; prevention & control ; Female ; Glycoproteins ; therapeutic use ; Heart Valve Prosthesis Implantation ; Humans ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Male ; Middle Aged ; Trypsin Inhibitors ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL).

METHODSFrom January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed.

RESULTSCR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002).

CONCLUSIONIM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.

Adolescent ; Adult ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Prospective Studies ; Recurrence ; Remission Induction ; Survival Rate ; Treatment Outcome ; Young Adult

Aim To investigate the effects of vitamin C (VC) on glycine receptor (GlyR) subtypes. Methods The HEK-293T cells were transfected with plasmids expressing different subtypes of GlyR. Then the cells were incubated with different concentrations of VC. The EC2 concentration of glycine-activated currents were recorded by patch clamp before or after incubation of VC. The effects of the sodium-dependent vitamin C transporter-type 2 ( SVCT2 ) inhibitor sulfinpyrazone on VC induced potentiation of GlyRs were also examined. The method of amino acid point mutation was used to explore the critical site for interaction between VC and GlyR. Results Ascorbic acid dose-dependently increased the currents mediated by GlyRal and GlyRa3, with a3 subunits being the most sensitive to VC. Ascorbic acid had no significant effect on the current mediated by the al subunit of GlyRs. Cell incubation with sulfinpyrazone did not affect the VC induced potentiation of GlyR function. The mutation of Ser296 at the third transmembrane domain of a3 GlyR significantly reduced the potentiation of VC on GlyR func-tion. Conclusions Ascorbic acid can enhance the function of GlyR al and a3 subunits, but not a2 sub- unit. Such enhancement is not likely to be an effect oc- curing inside cells. The Ser296 of GlyR plays a key role in the VC induced enhancement of GlyR function.

Objective::To study the protective effect and mechanism of Qidong Yixin oral liquid on doxorubicin-induced myocardial toxicity in mice. Method::Ninety male ICR mice were randomly divided into normal group, model(DOX) group, DOX+ Qidong Yixin oral liquid group (9.55, 23.88, 47.75 g·kg^-1) and high dose group (47.75 g·kg^-1) with 15 mice in each group. The normal group and model group were given pure water by gavage, and each dose group of Qidong Yixin oral liquid was given different doses of Qidong Yixin oral liquid once a day for 21 days. On the seventh day, normal saline was injected into the abdominal cavity of the normal group and the high dose group of Qidong Yixin oral liquid. Doxorubicin was injected into the abdominal cavity of the other groups (15 mg·kg^-1). After 21 days, the weight and heart weight of mice were weighed and cardiac index was calculated. Serum was taken for the detection of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST). Heart was taken for hematoxylin-eosin (HE) staining, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) in myocardial tissue were detected. The expression of nuclear factor NF-E2 related factor (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western blot. Result::Compared with normal group, adriamycin could significantly reduce the body weight of mice (P<0.01), increase the activities of LDH, CK and AST in serum(P<0.01), and decrease the activities of antioxidant enzymes (P<0.01). Compared with DOX group, high dose Qidong Yixin oral liquid could significantly increase the weight of mice (P<0.05, P<0.01), decrease the level of myocardial three enzymes(P<0.01), increase the activity of antioxidant enzymes(P<0.05, P<0.01), and increase the expression of Nrf2 and HO-1(P<0.01). Conclusion::Qidong Yixin oral liquid has a good protective effect on doxorubicin myocardial toxicity. Its mechanism may be related to activating Nrf2/HO-1 signaling pathway and alleviating oxidative stress injury.