Effect of irradiated human lung fibroblasts on activation of canonical Wnt/β-catenin signaling pathway in mesenchymal stem cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of irradiated human lung fibroblasts (HLFs) on the canonical Wnt/β-catenin signaling pathway in human umbilical cord mesenchymal stem cells (HUMSCs).</p><p><b>METHODS</b>HUMSCs were cultured alone (single group) or co-cultured with HLFs exposed to 5Gy X-rays (co-culture group). The protein levels of GSK-3β, p-GSK-3β, FRAT1 and β-catenin in HUMSCs were examined by Western blotting 3 days after culture or co-culture. WISP-1 protein levels in conditioned medium were examined by ELISA.</p><p><b>RESULTS</b>The levels of p-GSK3β/GSK3β (0.15 ± 0.05), FRAT1 (0.48 ± 0.07) and β-catenin (0.50 ± 0.07) in co-cultured HUMSCs significantly decreased compared to those in single group (0.55 ± 0.05, 1.16 ± 0.13 and 2.39 ± 0.15, all P<0.05). The supernatant level of WISP-1 in co-culture group was significantly decreased [(602.23 ± 161.47) ng/mL], compared to the single group [(977.77 ± 110.56) ng/mL, P<0.05].</p><p><b>CONCLUSION</b>Irradiated HLFs attenuate the activation of canonical Wnt/β-catenin signaling pathway in HUMSCs in vitro.</p>

The clinical characteristics and prognostic analysis of 147 cases of diffuse large B-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the clinical features, pathogenesis, immunophenotype, different classification models and prognosis in Chinese patients with diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>A total of 147 patients with DLBCL who were treated with CHOP-like or R-CHOP were subjected to analysis. Standard two-step Envision method of immunohistochemical staining was used to assess the expression of CD10, Bcl-6, MUM1, FOXP1, GCET1, CD5, Bcl-2, Ki-67, then according to Hans algorithm, Choi algorithm and Molecular markers, we compared the differences of their prognoses.</p><p><b>RESULTS</b>(1) Kaplan-Meier univariate analysis of the clinical data of 147 DLBCL patients found that the 3-year overall survival (OS) rates were better in early stage (P=0.032), low IPI score (P=0.001), less than one extranodal involvement (P=0.014), and complete remission (P<0.01). The prognoses had no significant difference in terms of gender, age, LDH, B symptoms and treatment options (P value> 0.05). (2 )For Hans model, GCB group had 42 cases, the ABC group 85 cases; GCB were 47 cases, ABC 80 cases (according to Choi model). Choi model suggested GCB subtype showed much better prognosis than ABC subtype (P=0.047), while Hans model shed no statistically significant difference (P=0.285). (3) Ki-67 of 75% was found to significantly discriminate patients with good or bad prognosis. In R-CHOP group at the same time, low Ki-67 (P=0.017) and CD5-negative groups (P=0.012) were better. Cox proportional hazards regression model showed that IPI score (P=0.002) and Ki-67 (P=0.019) were independent adverse prognostic factors.</p><p><b>CONCLUSION</b>The Ann Arbor stage, IPI score, extranodal involvement status and Ki-67 were significantly associated with prognosis .Compared to Hans algorithm, Choi had an advantage to predict the different prognosis between subtypes, and ABC group had poor outcome. Finally, both Ki-67 and IPI score were independent adverse prognostic factors.</p>

Regulation of C-type natriuretic peptides and natriuretic peptide receptor-B expression in diabetic rats renal treated by Tongluo Recipe / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the expression of C-type natriuretic peptides (CNP) and natriuretic peptide receptor-B (NPR-B) receptor in diabetic rats renal cortex, and the regulation by Tongluo Recipe (TLR).</p><p><b>METHODS</b>Sixty male SD rats were divided into 3 groups: the normal control group, diabetic model group and diabetic TLR group. Each group was further divided into two subgroups of ten in each, according to 4-week or 12-week observation period. Streptozotocin (STZ)-induced diabetic rats were treated with TLR (1.0 g·kg(-1)·d(-1)) for 4 and 12 weeks, respectively. (1) The essential information was collected for comparing renal mass, serum creatinine and 24 h urine albumen on each group was calculated. (2) CNP mRNA and NPR-B mRNA were detected by realtime-polymerase chain reaction (PCR) on rats renal cortex. (3) Concentration of CNP on renal cortex or serum were analyzed by enzyme-linked immunosorbent assay (ELISA). (4) Pathological evaluation and NPR-B immunostaining for renal tissue were also performed.</p><p><b>RESULTS</b>(1) CNP and NPR-B mRNA levels were detected in each treated or untreated group, with slight elevated in untreated diabetes rats administrated with STZ after 4-week and CNP mRNA level remarkable elevated at 39.21 times higher than normal control group after 12 weeks, but NPR-B mRNA level showed a remarkably down-regulation at 98.07% after 12 weeks. CNP mRNA of TLR-treated group was also elevated after 12-week treatment, but less than untreated group. (2) Concentrations of CNP in renal cortex were obviously increased in treated or untreated diabetes rats, within these groups the treatment of TLR was found more significantly on prompting CNP concentration. Comparing to normal group, serum concentrations of CNP were also increased in treated or untreated diabetic groups, but there was no difference between these diabetic groups. (3) Renal lesions like glomerular volume increased are observed mostly in the relative early stage after 4 weeks. Although TLR treated group had no significant difference in their glomerular volume, the degrees of injury of glomerulus were ameliorated, as well as the NPR-B immunostaining enhanced in glomerulus. Weakly positive immunostaining of NPR-B are observed in glomerulus of normal control, and negative in glomerulus of untreated diabetes rats administrated with STZ after 12 weeks, whereas TLR-treatment groups showed a little enhancement.</p><p><b>CONCLUSION</b>CNP and NPR-B showed different characteristic on renal cortex at different pathological period in diabetes rats, and TLR regulated their expression.</p>

Influence of extract of Ginkgo biloba leaves tablets on the aquaporin-1 expression in isolated lung ischemia reperfusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The extract of Ginkgo biloba leaves tablets, ginaton, is widely used in treating ischemic cerebrovascular disease in the clinic. This study aimed to investigate the expression of aquaporin-1 (AQP-1) in rat lung with ischemia/reperfusion injury after pretreatment with ginaton, and whether the pretreatment with ginaton reduces the acute lung injury caused by ischemia/reperfusion injury.</p><p><b>METHODS</b>Adult Wistar rats were divided into two groups. Some rats were used as donors (n = 20), the others as recipients (n = 20). Left lungs of donor rats were used for the isolated lung reperfusion model, which perfused only with low potassium dextran (LPD) solution as group A (n = 10); the others were pretreated with ginaton before reperfusion as group C (n = 10). Right lung of donor rat without any treatment was used as a control group (group B and group D, n = 10 for each group). After the model was established, the expression of AQP-1 in the lung tissues was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction.</p><p><b>RESULTS</b>Immunohistochemical examination revealed that AQP-1 was expressed in endothelia. Immunoblotting demonstrated that the relative gray values of AQP-1 protein in groups A and C were 0.65±0.06, 0.88±0.11, respectively. The relative gray values of the mRNA expression in groups A and C were 0.30±0.08, 0.49±0.11, respectively. The expression of AQP-1 protein and mRNA in group C was significantly higher than in group A (P < 0. 05).</p><p><b>CONCLUSION</b>The pretreatment with ginaton can reduce the acute lung injury caused by ischemia/reperfusion.</p>

Large and giant medial sphenoid wing meningiomas involving vascular structures: clinical features and management experience in 53 patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Large and giant medial sphenoid wing meningiomas that are located deeply in the skull base where they are closely bounded by cavernous sinus, optic nerve, and internal carotid artery make the gross resection hard to achieve. Also, this kind of meningiomas is often accompanied by a series of severe complications. Therefore, it was regarded as a formidable challenge to even the most experienced neurosurgeons. This study aimed to investigate the clinical features and management experience of patients with large and giant medial sphenoid wing meningiomas.</p><p><b>METHODS</b>In this study, 53 patients (33 female and 20 male, mean age of 47.5 years) with large and giant medial sphenoid wing meningiomas were treated surgically between April 2004 to March 2012, with their clinical features analyzed, management experience collected, and treatment results investigated retrospectively.</p><p><b>RESULTS</b>In this study, gross total resection (Simpson I and II) was applied in 44 patients (83%). Fifty-three patients had accepted the routine computed tomography scan and magnetic resonance imaging scan as postoperative neuroradiological evaluation. Their performance showed surgical complications of vascular lesions and helped us evaluate patients' conditions, respectively. Meanwhile, the drugs resisting cerebral angiospasm, such as Nimodipine, were infused in every postoperative patient through vein as routine. As a result, 11 patients (21%) were found to have secondary injury of cranial nerves II, III, and IV, and nine patients got recovered during the long-term observing follow-up period. Temporary surgical complications of vascular lesions occurred after surgery, such as cerebral angiospasm, ischemia, and edema; 24 patients (45%) appeared to have infarction and dyskinesia of limbs. Overall, visual ability was improved in 41 patients (77%). No patient died during the process.</p><p><b>CONCLUSIONS</b>Microsurgical treatment may be the most effective method for the large and giant medial sphenoid wing meningiomas. The surgical strategy should focus on survival and postoperative living quality.</p>

The efficacy and safety analysis of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma (MM), who previously responded to bortezomib.</p><p><b>METHODS</b>Retrospective analysis of 76 MM patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to August 2011, received bortezomib retreatment when they relapsed or progressed.</p><p><b>RESULTS</b>The overall response rate (ORR) was 60.5%, among them 6.5% patients achieved CR, 5.8% patients achieved very good partial response (VGPR), 38.2% patients achieved PR. Then we further stratified all patients into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 84.6%, 73.1% and 43.2%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 7(1-39) and 5(1-14) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 16(2-64) and 8(1-28) months, respectively (P<0.05). Adverse events (AE) were identified in 88% patients during bortezomib retreatment, including neutropenia, diarrhea and thrombocytopenia, only 9.2%(7 patients) reached Ⅲ-Ⅳ grade of AE. Severe peripheral neuropathy occurred in only one patient.</p><p><b>CONCLUSION</b>Bortezomib retreatment regimen is demonstrated a higher response rate in patients who achieved deeper response in initial treatment, with no more adverse events.</p>

Busulfan, cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) as conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM).</p><p><b>METHODS</b>From September 2007 to September 2010, thirty-two ASCT-eligible patients with MM received high dose melphalan (HDM) as conditioning in our center. Median age was 53.5 (30-63) years. From October 2010 to October 2012, thirty-eight patients conditioned by BCV regimen (intravenous busulfan, total doses 9.6 mg/kg), whose median age was 54(35-64) years.</p><p><b>RESULTS</b>There were no statistical differences in clinical characteristics between the two groups, including myeloma isotype, Durie-Salmon staging, international staging system(ISS), and patients received the first line, second line or more than third line therapy. The median time to neutrophil and platelet engraftment were 10.5 vs 11 days (P=0.057) and 11 vs 12 days (P=0.100) in the BCV and HDM groups, respectively. The toxicity of two conditioning regimens had no significant difference. None of hepatic veno-occlusive disease and early transplant related mortality was observed. Although overall response rates showed no significant difference between two groups (P>0.05), the CR rates increased from 44.74% pre-ASCT to 63.18% post-ASCT in the BCV group, while 37.50% to 59.38% in the HDM group. During the median follow-up of 16 months (range 2-27) in BCV group, ten patients (26.32%) developed progressive disease and PFS at 12 months were 71.37%.</p><p><b>CONCLUSIONS</b>In this study, the dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) conditioning was demonstrated an effective and safety regimen for ASCT-eligible patients with MM. However, the long term observation is needed.</p>

Clinical and laboratory features of four cases with IgM multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the understanding of the clinical and laboratory features of the IgM multiple myeloma (MM).</p><p><b>METHODS</b>The clinical data of four cases of IgM MM patients were collected, their clinical and laboratory features were summarized and analyzed.</p><p><b>RESULTS</b>Four patients met the criteria of IgM MM. They were all male. The age at the diagnosis ranged from 54 to 69 years. The primary symptoms included bone pain, hyperviscosity and bleeding. Three cases had κ-chain and only one case had λ-chain. They were all staged ⅢA according to the Durie-Salmon staging system (DSS). One case stagedⅠand three cases staged Ⅱ according to the international staging system (ISS). The average value of IgM, hemoglobin, serum calcium, creatinine and the proportion of bone marrow plasma cells were 83.6 (52.9-111.0) g/L, 79.5 (61.0-105.0) g/L, 3.20(2.11-6.00) mmol/L, 104.3 (56.0-171.0) μmol/L and 0.558 (0.290-0.775), respectively. Bone destruction was found in 3 cases. Immunophenotypes of bone marrow plasma cells were analyzed in 3 patients. Results showed that these cells expressed CD38 and CD138, and did not express CD19, CD20 and CD117. Chromosome and fluorescence in situ hybridization (FISH) analysis were carried out in 4 cases and found that all of them had IgH translocations and 1q21 amplification, 2 cases had 13q and 17p deletion, and 3 cases had t(11;14). Three patients received bortezomib-based regimens as induction therapy and reached partial response (PR) - very good partial response (VGPR). Followed up to November 30, 2012, the median progress-free survival (PFS) and overall survival (OS) of the 4 cases were only 6.0 (2.5-7.0) months and 17.5 (2.5-27.0) months, respectively.</p><p><b>CONCLUSIONS</b>IgM MM is very rare and is no more than 0.5% in all types of MM. IgM MM have frequent t(11;14) and amp(1q21). Bortezomib-based regimens are effective for it, however, the disease progresses rapidly and has poor prognosis.</p>

Allogeneic peripheral blood stem cell transplantation from sibling donors for 10 patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from sibling donors for treatment of multiple myeloma (MM).</p><p><b>METHODS</b>Ten patients with MM received allo-PBSCT with conditioning consisting of fludarabine plus melphalan and cyclophosphamide mostly.CsA plus mycophenolate mofetil (MMF) and short-term MTX were applied to prevent graft versus host disease (GVHD) in 8 patients, FK506 plus short-term MTX in other 2 patients.</p><p><b>RESULTS</b>All patients engrafted successfully, the median time for ANC > 0.5 × 10(9)/L was 16 (12 - 24) days, and for BPC > 20 × 10(9)/L 23 (16 - 102) days. Five patients developed acute GVHD, and only one III-IV aGVHD. Of 9 patients, 7 developed chronic GVHD. The transplant-related mortality (TRM) at 100 days was 10% (1/10), mainly from heart and renal failure and severe infection. The 1-year expected overall survival (OS), 1-year disease-free survival (DFS) and relapse rate were 67.5%, 55.56% and 11.11% respectively. Up to now, 6 patients were still alive, of them 1 patient have survived over 99 months after allo-PBSCT.</p><p><b>CONCLUSION</b>Young MM patients having HLA-identical sibling donors well tolerated allo-PBSCT based on fludarabine to prolong their OS by reducing TRM, though further work is warranted.</p>

Exploration of early assessment of renal impairment in multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of serum cystatin C (Cys-C), urinary Cys-C, urinary retinol binding protein (RBP) and urinary neutrophil gelatinase-associated lipocalin (NGAL) in the early assessment of multiple myeloma (MM) and their characteristic changes in different pathological types of renal impairment.</p><p><b>METHODS</b>According to glomerular filtration rate (eGFR), the patients were divided into two groups, of which marked group A with normal renal function, the other marked group B with abnormal renal function. Sixty healthy subjects were chosen as control. Detection of the serum Cys-C, urinary RBP, urinary Cys-C, urinary NGAL, serum creatinine (Scr), urinary microalbumin (MAU) and urinary α1-microglobulin (α1-MG) were performed. Renal biopsy was carried out for patients who had abnormal serum Cys-C, urinary Cys-C, urinary RBP, urinary NGAL and were willing to accept further test.</p><p><b>RESULTS</b>Compared with healthy controls, the serum Cys-C, urinary RBP, urinary Cys-C, urinary NGAL of group A were significantly higher than that of healthy controls. Six group A patients received renal biopsy, and varying degrees of renal damage were discovered. The serum Cys-C, urinary RBP, urinary Cys-C and urinary NGAL positive rate were 66.7%, 66.7%, 66.7% and 83.3%, respectively. Of twenty-four cases received biopsy after abnormal examination results were shown, six turned out to be amyloidosis, twelve cast nephropathy (CN) and 6 monoclonal immunoglobulin deposition disease (MIDD). Compared with MIDD and amyloidosis, the urinary Cys-C and NGAL of the CN group are significantly higher (P < 0.05). Compared with CN and amyloidosis, urinary RBP of MIDD is significantly higher (P = 0.043). Compared with MIDD and CN, the MAU of amyloidosis is significantly higher (P = 0.006).</p><p><b>CONCLUSION</b>Compared with the conventional indicators, serum Cys-C, urinary Cys-C, RBP and NGAL are more sensitive in early assessment of MM patients with renal damage. The MAU is higher in amyloid, the urinary Cys-C and urinary NGAL are significantly elevated in CN, the urinary RBP is significantly elevated in MIDD.</p>

Clinical effects of autologous stem cell transplantation as consolidation treatment in 70 multiple myeloma patients: a case-controlled study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Autologous stem cell transplantation (ASCT) is a part of the standard induction therapy of multiple myeloma (MM). This case-controlled clinical trial aimed to further evaluate the therapeutic effects of ASCT as a consolidation therapy for MM and discuss factors influencing the prognosis.</p><p><b>METHODS</b>Clinical data of 70 patients diagnosed as MM who received ASCT as a consolidation therapy in our hospital between October 1998 and August 2010 were analyzed retrospectively (ASCT group). Other 70 MM patients receiving routine chemotherapy without ASCT (non-ASCT group) during the same period were used as controls. Differences in the degree and duration of remission, progression-free survival (PFS) and overall survival (OS) were compared to explore factors that may influence the prognosis.</p><p><b>RESULTS</b>The median follow-up period was 38 months (range 1 - 128 months). The complete response (CR) rate of ASCT group increased from 27.1% (19/70) before ASCT to 51.4% (36/70) after ASCT. The median PFS of ASCT group was significantly higher than non-ASCT group (45 months vs. 25 months, P < 0.001). The median OS of ASCT group was also significantly higher (55 months vs. 30 months, P = 0.016). Single-factor analysis showed that International Staging System (ISS) stage, very good partial response (VGPR) or better outcome were significantly correlated with PFS and OS (P < 0.001). Multi-factor analysis showed that whether or not VGPR or better outcome was achieved were independent factors influencing the disease prognosis.</p><p><b>CONCLUSION</b>Used as a consolidation therapy, ASCT can achieve better responses and higher OS and PFS of MM patients.</p>

Influence of metallothionein on kidney oxidation of diabetic rats / 第二军医大学学报

Objective: To study the effect of metallothionein (MT), a potent antioxidant, on the oxidative stress and NADPH oxidase in kidneys of diabetic rats. Methods: Male SD rats were assigned to the following 3 groups: normal control (NC, n=8), diabetes mellitus control (DM, n = 7), diabetes mellitus models treated with MT by lavage (10 g * kg-1 * d-1, DM+MT, n=8). Diabetes in DM group and DM+MT group was induced by intraperitoneal injection of streptozotacin (60 mg/ kg). At 4 weeks after initiating treatment, 24 h urinary protein (24 h UP) and kidney weight/ body weight (KW/BW) were determined in the 3 groups to assess the renal function of rats; malondialdehyde (MDA) was examined with visible spectrophotometry; NADPH oxidase subunits p47phox and p22phox, protein kinase C (PKC)-β, and Angiotensinogen (Ang) were examined by real-time PCR. Results: MDA, 24 h UP and KW/BW in DM group were significantly higher than those in NC group (P<0.05); expression of PKC-β, Ang, and NADPH oxidase subunits p22phox and p47phox mRNA were increased markedly in DM group compared with NC group (P<0.05, P<0.01). 24 h UP, KW/ BW and MDA were significantly lower in DM+MT group compared with DM group (P < 0.05); expression of p47phox, PKC-β and Ang mRNA were significantly decreased in DM+MT group compared with DM group (P<0.05), but the expression of p22phox mRNA in DM and DM+MT groups had no significant changes. Conclusion: MT may lower the oxidase stress on kidney tissues, inhibit the expression of PKC-β and Ang in the kidney, and decrease NADPH oxidase activity, excerting protective effect on the kidney of rats with diabetes mellitus.

Effect of Tongluo recipe on oxidative stress in kidneys of diabetic rats / 第二军医大学学报

Objective: To study the effect of two types of Tongluo recipe (ultrafine type and fine type) on the level of oxidative stress in kidneys of diabetic Sprague-Dawley rats. Methods: Experimental diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg) in male Sprague-Dawley rats. One week after streptozotocin injection rats with blood glucose higher than 16.7 mmol/L were taken as diabetics. The study included the following 4 groups: normal control(NC), diabetes mellitus control(DMC), diabetics treated with ultrafine Tongluo recipe (DM+UT, 1 g · kg-1 · d-1), and diabetics treated with fine Tongluo recipe (DM+FT, 1 g · kg-1 · d-1). Four weeks after treatment, 24 h urinary protein (24 h UP) and kidney weight/ body weight (KW/BW) were detected as renal function indices; malondialdehyde(MDA) and antioxidant enzymes was examined with colorimetry; and NADPH oxidase subunits p47phox and p22phox mRNA were studied with real-time PCR. Results: Compared with the NC group, DMC group had significantly higher MDA, 24 h UP, KW/BW, and glutathione peroxidase (GSH-Px) activity, and had significantly lower activity of total superoxide dismutase (TSOD). No significant difference was found in catalase(CAT) activity between the NC group and DMC group. Compared with the 2 Tongluo Recipe groups, the DMC group had significantly lower 24 h UP, KW/BW and MDA, and significantly higher activities of TSOD and GSH-Px, and no significant difference was found in their CAT activities. The effect of ultrafine type on 24 h UP, KW/BW, MDA, TSOD and GSH-Px was significantly greater than the fine type did. The expression of p47phox mRNA of NADPH oxidase in renal cortex group was significantly lower than that in the DMC group, and the latter was significantly higher than the 2 Tongluo of the NC recipe groups, and there was no significant difference between the 2 Tongluo recipe groups. There was no significant difference in p22phox mRNA expression between all the 4 groups. Conclusion: Tongluo recipe may improve the activities of antioxidant enzymes (including TSOD and GSH-Px), decrease p47phox expression, and therefore inhibit the oxidative stress in renal cortex of diabetic rats, reducing the early kidney injury.

Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM).</p><p><b>METHODS</b>The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis.</p><p><b>RESULTS</b>In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049).</p><p><b>CONCLUSION</b>The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.</p>

The role of human herpesvirus-8 infection in the pathogenesis of multiple myeloma / 中国实验血液学杂志

Multiple myeloma is a B-cell neoplasm characterized by abnormal proliferation and accumulation of monoclonal plasma cells in the bone marrow. Recently some laboratories have detected human herpesvirus-8 (HHV-8) DNA sequences in bone marrow dendritic cells from myeloma patients. It has been suggested that the cytokines expressed by HHV-8 gene, such as vIRF, vIL-8R and vIL-6, may play a role in the pathogenesis of multiple myeloma. However, the majority of European investigators failed to find evidence to confirm this observation. It remains unclear whether HHV-8 is consequentially associated with myeloma or only a regional opportunistic infection. Controversy still focuses on the role of specific HHV-8 strains involved in pathogenesis of multiple myeloma and causality between the