Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child ; Cytarabine ; administration & dosage ; Daunorubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Mitoxantrone ; administration & dosage ; adverse effects ; Young Adult

Objective To summarize the diagnostic and therapeutic experience of a patient with chronic graft versus host disease (cGVHD) related polymyositis (PM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods A patient with acute lymphocytic leukemia in com- plete remission received sibling allo-HSCT,and cyclosporine and methotrexate were adopted to pre- vent GVHD.Results Eleven days after HSCT,WBC＞0.5?10~9/L,13 days after HSCT,PLT＞20?10~9/L;27 days after HSCT,chromosome analysis of bone marrow cells showed 99% donor type. Seventeen days after HSCT,Ⅰ~0 acute GVHD of skin occurred,and it was cured by intravenous injec- tion of dexamethasone and methotrexate.Eight months after HSCT,cGVHD of liver happened.Al- though treated by tacrolimus and azathioprine,enzymes of liver were still elevated.At last,tacrolimus combined with sirolimus were used,and enzymes of liver subsided gradually.However,the serum creatine phosphokinase (CK) began to rise from 9 U/L to 3010 U/L,and fatigue all over the patient occurred.Finally,the symptom relapsed,and disability involved with the origin of limbs appeared. The electromyogram and magnetic resonance imaging of concerned muscles confirmed the PM diagno- sis.Although treated with methylprednisolone and plasma exchange,the patient died due to asphyxia, while the CK as high as 21 010 U/L.Conclusion PM is a rare kind of manifestations of cGVHD. When the key muscle tissue was involved,the prognosis is poor.

In order to explore what role relative cytokines play in acute GVHD (aGVHD) of mice transplanted with H-2 haploidentical nonmyeloablative bone marrow, a murine model was established by using C57BL/6J mouse as donor and (C57BL/6J x BALB/C) F1 mouse as the recipient. The recipient mice were given CsA and mycophenolate mofetile (MMF) for prophylaxis of aGVHD. The expression levels of IL-2, INFgamma, IL-4 and IL-10 in the spleen were detected by semi-quantitative RT-PCR at different time points after transplantation. The results showed that the expression levels of these cytokines increased slightly in the group only received nonmyeloablative conditioning. The expression levels of IL-2 and INF-gamma elevated significantly after transplantation in group 2 (without aGVHD prophylaxis), peaked at day 21 and day 14 respectively, then dropped rapidly, returned to the basal levels at day 35. The study on kinetic pattern of expression of IL-2 and INF-gamma in group 3 (with aGVHD prophylaxis) gave a similar result to group 2, but the peak value of cytokine expression in group 3 was much lower than that in group 2. The expression of IL-4 in Group 2 and group 3 all peaked at day 14, but the peak value in group 3 was higher than that in group 2, and decreased slowly in group 3. The expression of IL-10 increased gradually after transplantation, peaked at day 14, decreased after day 21, elevated again until day 35. It is concluded that the expression levels of these cytokines in the spleen all increase after H-2 haploidentical nonmyeloablative bone marrow transplantation. CsA and MMF can reduce the incidence and severity of aGVHD by down-regulating the expression levels of IL-2 and INF-gamma.
Animals ; Bone Marrow Transplantation ; immunology ; methods ; Cyclosporine ; administration & dosage ; Cytokines ; genetics ; Gene Expression ; drug effects ; Graft vs Host Disease ; prevention & control ; H-2 Antigens ; genetics ; Interferon-gamma ; genetics ; Interleukin-2 ; genetics ; Kinetics ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To investigate the mechanism of losartan treating glomerulosclerosis and to observe the effect of losartan on the expressions of TGF-beta1, p-Smad2/3, and Smad7 in the renal tissues of 5/6 nephrectomized rats. METHODS: Male Wistar rats were randomly divided into a sham-operated group, a 5/6 nephrectomized model group, and a losartan treated group. The rats in the model group and the losartan treated group were performed 5/6 nephrectomy by the method with 2 procedures. Twelve weeks after of the operation, all rats were killed. The 24-hour urinary protein, serum creatinine, and urea nitrogen were detected. Pathological changes of the renal tissues were observed by HE and Masson staining, and the expressions of TGF-beta1, p-Smad2/3, and Smad7 were detected by immunohistochemical staining. RESULTS: The 24-hour urinary protein, serum creatinine, urea nitrogen, and the relative area of collagen in the renal tissues of the rats in the model group significantly increased (P<0.01), and losartan could reduce these indexes. The expressions of TGF-beta1 and p-Smad2/3 were just at a low level in the renal tissues of the rats in the sham-operated group, and were strongly positive in the model group; but losartan could decrease the expressions of TGF-beta1 and p-Smad2/3 (P<0.01). The expression of Smad7 in the model group was fewer than that in the sham-operated group (P<0.01), but losartan could improve the expression of Smad7 (P<0.01). CONCLUSION Losartan may implement its anti-glomerulosclerosis by affecting TGF-beta1, p-Smad2/3, and Smad7 of TGF-beta/Smads pathway of the renal tissues of 5/6 nephrectomized rats.
Animals ; Kidney ; drug effects ; metabolism ; Losartan ; pharmacology ; Male ; Nephrectomy ; methods ; Rats ; Signal Transduction ; drug effects ; Smad2 Protein ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

BACKGROUNDPeripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis after conventional chemotherapy. The place for high-dose chemotherapy and autologous stem cell transplantation (ASCT) in these patients is still not clear. In this study, we presented the outcomes of PTCL patients followed these treatments in our centre.

METHODSWe retrospectively analyzed the outcomes of 39 patients with PTCL received the two treatments between 1999 and 2010.

RESULTSThe 3-year overall survival (OS) of 61.9% and 3-year progression free survival (PFS) of 35.7% were observed in the 39 patient. Twenty-one patients received Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%. Eighteen patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%. Further analysis revealed that patients with elevated lactate dehydrogenase, at least 2 international prognostic index (IPI) points, and extranodal involvement had a poorer outcome compared with the control group.

CONCLUSIONThese findings might suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival benefit for patients with aggressive PTCL.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Dexamethasone ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Lymphoma, T-Cell, Peripheral ; drug therapy ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Vincristine ; therapeutic use ; Young Adult

Nuclear factor κB (NF-κB), including RelA, RelB, c-Rel, NF-κB1, and NF-κB2, plays a crucial role in immune response, inflammatory reaction, tumorigenesis, and development of peripheral lymphoid organs and lymphocytes. There are two NF-κB activation pathways: canonical pathway (classical pathway) and noncanonical pathway (alternative pathway). Previous studies focused on the effects of the canonical NF-κB pathway (mainly p50-RelA) in hematological malignancies. Recently, the noncanonical NF-κB pathway (mainly p52-RelB) is gradually taken importance in pathogenesis of hematological malignancies. Understanding the relations of the noncanonical pathway with hematological malignancies would provide a new therapeutic approach for these diseases. This review focuses on the noncanonical NF-κB signaling transduction pathway and its relation to hematologic malignancies.
Hematologic Neoplasms ; metabolism ; Humans ; NF-kappa B ; metabolism ; NF-kappa B p50 Subunit ; metabolism ; NF-kappa B p52 Subunit ; metabolism ; Signal Transduction

OBJECTIVETo evaluate the prevalence of c-kit and JAK2 gene mutations in protein tyrosine kinase (PTK) family in adult t(8;21) acute myeloid leukemia (AML) and their implications.

METHODSGenomic DNAs from 78 t(8;21) AML patients were screened for mutated c-kit (mutKIT) in exon 8 and 17 by PCR and sequencing. JAK2 V617F mutation screening was processed by allele-specific PCR.

RESULTS(1) Among 78 t(8;21) AML patients, 27 (34.6%) had muc-kit/JAK2 and 6 (7.7%) had JAK2 V617F, and none had both. (2) Peripheral WBC count was higher in mutKIT/JAK2 V617F patients than in wide-type c-kit/JAK2 (wtKIT/JAK2) patients \[(36.2 +/- 37.7) x 10(9)/L vs (21.7 +/- 21.1) x 10(9)/L\] (P < 0.05). There was no significant difference in hemoglobin level, platelet counts, percentage of blast cell in bone marrow, CD117 expression level, the age of onset and gender between the two groups. Peripheral WBC count was higher in mutKIT patients \[(38.8 +/- 40.7) x 10(9)/L\] than in wtKIT patients \[(22.0 +/- 20.4) x 10(9)/L\] (P < 0.05). (3) Complete remission (CR) rates between patients with mutkit/JAK2 V617F and with wtKIT/JAK2 were similar (69.6% vs 80.0%, P > 0.05), but the 2 year continuous CR (CCR) rate was lower in patients with mutKIT/JAK2 V617F (26.7% vs 56.1%, P < 0.05). However, there was no significant difference in OS between mutKIT/JAK2 V617F and wtKIT/JAK2 patients (34.8% vs 58.6%, P > 0.05).

CONCLUSIONSOccurrence of c-kit and JAK2 gene mutations especially c-kit mutation is common in t(8;21) AML patients, and is associated with higher WBC. These mutations confer higher relapse risk and predict poor prognosis.

Adolescent ; Adult ; Aged ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Gene Expression Regulation, Leukemic ; Humans ; Janus Kinase 2 ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; Translocation, Genetic ; Young Adult

OBJECTIVEWe aimed to perform a meta-analysis of clinical trials on the efficacy of autologous bone marrow-derived cells (BMCs) transfer for patients with chronic ischemic heart disease.

METHODSWe searched MEDLINE, EMBASE, and Cochrane database through September 2009. Eligible studies were randomized controlled trials of autologous BMCs infusion in patients with chronic ischemic heart disease. We gathered information about left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and death, and did a random-effect meta-analysis to obtain summary effect estimates for outcomes. The pooled analyses were performed and forest plots were generated with RevMan 5.0 software. Heterogeneity was assessed by meta-regression with STATA 10.0 software. Additionally, subgroup analysis was performed to compare the effect of intracoronary BMCs transfer with intramyocardial cell injection on LVEF.

RESULTSEleven trials with 490 participants were identified. There were 268 patients in BMCs group, and 222 in control group. In control group, the patients received saline injection or autologous plasma injection or no injection. BMCs transfer was performed via intracoronary transfer or intramyocardial injection. Compared with controls, BMCs transfer significantly improved LVEF by 4.63% (95%CI 2.42 to 6.84; P < 0.01). BMCs transfer was also associated with significant reductions in LVEDV (standardized mean difference -0.55, 95%CI -0.94 to -0.17, P = 0.005) and LVESV (standardized mean difference -0.45, 95%CI -0.73 to -0.17, P = 0.002). In addition, BMCs treatment was associated with a significant effect on death (OR 0.42, 95%CI 0.18 to 1.01, P = 0.05). Subgroup analysis indicated that intramyocardial cell injection was preferred due to its more significant improvement of LVEF than intracoronary cell therapy. Meta-regression suggested the existence of a negative association between baseline LVEF and LVEF change.

CONCLUSIONBMCs infusion is associated with a significant improvement in LVEF, and an attenuation of left ventricular remodeling.

Bone Marrow Transplantation ; Humans ; Myocardial Ischemia ; surgery ; Randomized Controlled Trials as Topic ; Transplantation, Autologous

OBJECTIVETo compare the angiogenesis in unstable and stable plaques and to investigate the potential role of neovessels in creating vulnerable sites for atherosclerotic plaques.

METHODSSpecimens of coronary arteries were obtained from 52 autopsy cases with acute coronary syndromes. Plaque morphology was studied by use of stained slides. 922 tissue blocks of late-stage lesions were classified into two groups: (1) unstable plaque (n = 153), the plaque was characterized by a large extracellular lipid core (more than 40% of the plaque area); (2) stable plaque (n = 769), lipid core less than 40% of the plaque area. Forty blocks were selected randomly from each group and serial sections were stained immunohistochemically with a polyclonal antibody against F VIII RAg. Computer-aided planimeter was used for quantitative analysis.

RESULTSIn unstable plaques, the occurrence of neovessels was more frequent and the neovessel density (number/mm(2)) was significantly increased as compared to that of stable plaques (frequency: 80.4% vs 66.6%, P < 0.01; shoulder: 22.16 +/- 19.96 vs 10.04 +/- 11.52, base: 21.68 +/- 20.44 vs 9.68 +/- 11.52, fibrous cap: 3.80 +/- 5.32 vs 1.48 +/- 2.28, P < 0.05). Most neovessels were located in the shoulder region and at the base of plaques.

CONCLUSIONSThese findings suggest that neovessels in coronary atherosclerotic plaques are closely associated with the decreased stabilization of the plaques.

Aged ; Aged, 80 and over ; Coronary Artery Disease ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Neovascularization, Pathologic ; pathology

OBJECTIVETo investigate the function of tumor necrosis factor receptor-associated factor 1 (TRAF1) and CD30-TRAF1 signaling in Hodgkin's lymphoma.

METHODSEndogenous and CD30 ligand-induced TRAF1 expression at mRNA and protein levels were examined by quantitative RT-PCR and Western blot analyses, respectively. RNA interference was performed to silence the expression of TRAF1 in L428 cells and examine its effect on cell survival. ELISA-based NF-kappaB family transcription factor activity assay was performed to quantify the kappaB DNA-binding activity in nuclear extracts. The expression of JunB was measured by Western blot.

RESULTSTRAF1 expression was detected at both mRNA and protein levels in B cell-derived lymphoma cell lines (L428 and KM-H2). CD30 activation via binding to CD30 ligand induced the TRAF1 expression, the relative mRNA expression was increased to 7.26 +/- 0.23 from 3.50 +/- 0.20, the relative protein expression was increased to 4.53 +/- 0.55 from 2.31 +/- 0.35. The apoptosis rate was increased to (27.7 +/- 5.8)% in TRAF1-silenced L428 cells compared to (5.7 +/- 1.2)% in control cells. The p50 and RelA DNA-binding activity were decreased in TRAF1-silenced L428 cells. The expression of JunB upon CD30 ligand stimulation was not changed in TRAF1-silenced L428 cells.

CONCLUSIONSTRAF1 is overexpressed in B cell-derived Hodgkin's lymphoma cells, which is regulated by CD30 signaling pathway. TRAF1 is a crucial molecule mediating the activation of the classical NF-kappaB activity, which further facilitates the anti-apoptosis.

Apoptosis ; Cell Line, Tumor ; Hodgkin Disease ; Humans ; NF-kappa B ; metabolism ; Signal Transduction ; genetics ; TNF Receptor-Associated Factor 1