Effect of BAFF/APRIL mRNA expression induced by glucocorticoid and bortezomib in multiple myeloma cells in vitro / 中国实验血液学杂志

The study was purposed to detect BAFF/APRIL gene expression changes in bone marrow mononuclear cells (BMMNC) and myeloma cell line U266 after interference with glucocorticoid and bortezomib. After separation of BMMNC from 7 patients with multiple myeloma, BAFF/APRIL mRNA expression in BMMNC and U266 cell line was detected by real-time PCR after treated with dexamethasone 100, 200 µg/ml, methylprednisolone 100, 200 µg/ml, bortezomib 0.1 µg/ml alone and dexamethasone or methylprednisolone combined with bortezomib respectively for 48 hours. The results showed that U266 cells and BMMNC of untreated MM patients highly expressed BAFF/APRIL genes. When dexamethasone, methylprednisolone or bortezomib was added to U266 cells or BMMNC alone, BAFF/APRIL gene expression decreased as compared with the blank control (p < 0.01). The inhibiting effect of bortezomib to BAFF/APRIL expression was obviously strong(p < 0.05). When dexamethasone or methylprednisolone combined with bortezomib, the BAFF/APRIL gene expression further decreased compared with dexamethasone or methylprednisolone alone (p < 0.01). As compared with the group of methylprednisolone combined with bortezomib, BAFF/APRIL gene expression decreased in dexamethasone combined with bortezomib with a statistically significant difference (p < 0.05). It is concluded that the expression of BAFF/APRIL gene is down-regulated after bing treated with glucocorticoids and bortezomib, which suggests that besides the glucocorticoid receptor and proteasomes targets, BAFF/APRIL and their receptor sites may be new targets of glucocorticoids and bortezomib.

Clinical analysis of histocytic necrotizing lymphadenitis / 中南大学学报(医学版)

OBJECTIVE@#To understand the clinical features and histopathology of histocytic necrotizing lymphadenitis (HNL) so as to better recognize the disease.@*METHODS@#The clinical features, histopathology, and diagnosis of 10 patients admitted to our hospital were retrospectively analyzed.@*RESULTS@#The clinical features of these 10 cases included: young females were the majority; lymphadenopathy and fever were the most common clinical manifestations; some cases were accompanied by connective tissue diseases. Histopathologic examination showed distinctive necrosis and around the necrotic foci, variable proliferations of histocytes but generally without infiltration of neutrophils.@*CONCLUSION@#HNL has some typical histopathological alterations and relatively fine prognosis,but it tends to be misdiagnosed as lymphoma or lymphoid tuberculosis and may be accompanied by other diseases.

Specific cell immune response mediated by dendritic cells in multiple myeloma patients in vitro / 中南大学学报(医学版)

OBJECTIVE@#To explore KM3 multiple myeloma (MM) cell line specific cytotoxic T lymphocyte (CTL) response in vitro mediated by autologous dendritic cells (DCs) aroused by KM3 cells' lysates and acid-eluted peptides.@*METHODS@#Monocytes were isolated from the peripheral blood of healthy individuals and MM patients, and were cultured in serum medium with IL-4, GM-CSF, and TNF-alpha to generate DCs. These DCs were pulsed by KM3 cells' lysates or the acid-eluted peptides, then incubated with autologous T lymphocytes for 3 days to induce KM3 cell antigen specific CTL. MTT assay was performed to examine the specific KM3 cells' lysing ability of CTL.@*RESULTS@#DCs were generated in peripheral blood monocytes cultured in the serum medium containing GM-CSF, IL-4, and TNF-alpha. Autologous T lymphocytes induced by IL-2 and DCs pulsed with KM3 cells' lysates or the acid-eluted peptides showed strong killing effect on KM3 cells.@*CONCLUSION@#The DCs pulsed by KM3 cells' lysates or the acid-eluted peptides incubated with autologous T lymphocytes can induce KM3 cell antigen specific CTL.

Clinical significance of serum vascular endothelial growth factor and interleukin-6 in multiple myeloma / 中南大学学报(医学版)

OBJECTIVE@#To investigate the clinical significance of the changes of vascular endothelial growth factor ( VEGF ) and interleukin-6 ( IL-6 ) level in multiple myeloma (MM), solid tumor following bone metastasis.@*METHODS@#Thirty- seven MM patients, including 7 in Stage I , 8 in Stage II , 22 in Stage III, 8 solid tumor with bone metastasis patientsly, and 17 healthy controls were enrolled in this study. The serum VEGF and IL-6 levels were determined by ELISA.@*RESULTS@#Serum VEGF and IL-6 concentrations in patients with MM and solid tumor were significantly higher than those of the healthy controls (P <0.01 ), and the VEGF level was higher in MM than in solid tumor with bone metastasis. There was significant difference in VEGF and IL-6 levels in various clinical stages of MM. VEGF levels in Stage II were significantly higher than in Stage I (P < 0.05 ) and IL-6 levels in Stage II were significantly higher than in Stage I (P < 0.05). The levels of IL-6 showed great difference according to bone lesion scores (P < 0.05). There was a positive correlation between IL-6 and serum calcium or C-reactive protein( P <0.01) , and there was a positive correlation between VEGF and serum Cr or urinary Bene-Jones protein lambda (P < 0.01 ). The IL-6 levels had significant differences between patients with the normal serum CRP, serum calcium, and beta2-MG and patients with abnormal ones (P < 0.05). VEGF levels showed significant differences between the patients with normal serum Cr, serum calcium Bene-Jones protein lambda, and urinary Bene-Jones protein lambda and patients with abnormal ones (P < 0.05).@*CONCLUSION@#Serum VEGF and IL-6 levels are helpful to diagnose the clinical stages, and understand bone lesion and serevity of MM.

Clinical phenotypes, ALK1 gene mutation and level of related plasma proteins in Chinese hereditary hemorrhagic telangiectasia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>We determined the diagnosis of hereditary hemorrhagic telangiectasis (HHT) in a suspected HHT family, identified ALK1 gene mutation and established a gene diagnosis method of HHT. The level of related plasma proteins (transforming growth factor beta and thrombomodulin) were also analyzed.</p><p><b>METHODS</b>Bleeding history and family history were collected; Dilatant nasal mucosal capillaries in proband were observed under nasal cavity endoscope; exons 3, 7, 8 of ALK1 gene in proband and her family members were amplified with polymerase chain reaction (PCR), and the PCR products were analyzed. Using enzyme-linked immunosorbent assay (ELISA), plasma TGF-beta1 and TGF-beta2 concentrations were measured. Plasma thrombomodulin (TM) level was detected by Western blotting.</p><p><b>RESULTS</b>Of all family members, four had epstaxis, two had evident telangiectases on skin or mucosa. Gene screening results showed that C to T substitution at position 1231 in exon 8 of ALK1 gene (CGG-->TGG) existed in proband, her affected brother and their father. The mutation did not exist in proband's sister-in-law and nephew. Plasma TGF-beta1 concentrations in the affected HHT was 20,538, 17,194, 13,131 pg/ml, while that of normal control and unaffected family members was 15,950, 20,297, 12,836 pg/ml, respectively. Plasma TGF-beta2 in HHT patients was 14,502, 9550, 10,592 and that of normal controls 8579, 20,297, 7680 pg/ml respectively. Level of plasma TM was in HHT subjects significantly lower than in normal subjects.</p><p><b>CONCLUSIONS</b>Chinese HHT individuals have mutant ALK1 gene, a C1231T variation on exon 8 of ALK1 is responsible for HHT clinical phenotypes in this family. ALK1 gene analysis, together with special clinical phenotypes and family history, provides a reliable method in diagnosing HHT. In affected HHT subjects, plasma TGFbeta levels were not obviously different from those of normal subject; while plasma TM concentration was significantly lower than that in normal subjects. The significance and mechanism remain to be elucidated.</p>