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Induction of tumoricidal activity is one of the major functions of activated macrophages. Our previous study demonstrated that P388D1 murine macrophage-like cells secreted a plasmacytoma cytotoxic factor (PCF) that selectively killed certain tumor cell lines including MOPC-315 plasmacytoma in vitro. Our subsequent studies demonstrated that PCF killed MOPC-315 cells by induction of apoptosis. In this report, the involvement of Fas and Fas ligand (FasL) in PCF-induced apoptosis was investigated. Results suggest that expression of Fas mRNA time-dependently increased in PCF-treated cells and reached an optimal level after 36 h of treatment. The augmented effect of PCF on Fas mRNA expression was significantly reduced by the addition of CB7.C2, an anti-PCF monoclonal antibody. The expression of FasL mRNA was also induced by PCF and reached an optimal level at 24 h, but sharply decreased after 36 h of treatment. Caspase-3 is one of the proteolytic enzymes that can be activated by the Fas-FasL interaction. In our studies, the enzymatic activity of caspase-3 was significantly induced by PCF after 6 h of treatment and reached an optimal level at 12 h. The augmented effect of PCF on caspase activity was significantly reduced by the addition of CB7.C2 and the caspase-3-specific inhibitor, DEVD-fmk. Therefore, PCF-treated plasmacytoma cells might undergo apoptosis via interaction between Fas and FasL. 相似文献
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Sainz IM Isordia-Salas I Espinola RG Long WK Pixley RA Colman RW 《Cancer immunology, immunotherapy : CII》2006,55(7):797-807
Multiple myeloma (MM), a B-cell malignancy characterized by proliferation of monoclonal plasma cells remains incurable. Murine
plasma cell tumors share common features with human MM. We used two cell lines (B38 and C11C1) derived from P3X63Ag8 myeloma
cells. The new cell lines were implanted subcutaneously in the strain of origin (Balb/c mice) and used as a model to monitor
the effects of C11C1 monoclonal antibody (mAb) to kininogen (HK). We assessed their behavior by intraperitoneal and subcutaneous
implantation, by implanting them together and by treating B38–MM with purified mAb C11C1. We evaluated growth, microvascular
density (MVD), and cellular expression of urokinase-type plasminogen activator-receptor (uPAR), fibroblast growth factor-2
(FGF-2), vascular endothelial growth factor (VEGF), bradykinin-1 receptor (B1R), bradykinin-2 receptor (B2R) and HK. We found
that both MM-cell-lines are uPAR positive, that mAb C11C1 inhibits its own tumor growth in vivo, slows down B38-MM growth
rate when both MM are implanted together and when mAb C11C1 is injected intraperitoneally. MAb C11C1-treated-MM showed decreased
MVD and HK binding in vivo without FGF-2, B1R or B2R expression changes. We propose that the B38-extramedullary-myeloma-model
is a useful tool to study the interactions of this hematopoietic tumor and its environment and that mAb C11C1 may improve
the efficacy of conventional MM treatment with minimal side effects.
Financial support: NIH grants. R01 CA-083121-08 (R.W.C.) and T32 HL-07777-14 (R.W.C.) 相似文献
3.
目的:探讨免疫固定电泳(immunofixation electrophoresis,IFE)检测对浆细胞肿瘤相关肾损害的诊断价值。方法:回顾性分析我院肾病科665例住院患者的免疫固定电泳分型结果及检出M蛋白带的患者骨髓检查结果。结果:665例肾病科患者中检出44例单克隆免疫球蛋白带,检出率6.6%,其中IgG型24例(κ型6例,λ型18例),IgA型10例(κ型6例,λ型4例),IgM型2例(均为κ型),单纯轻链κ型2例,单纯轻链λ型6例;此44例患者经骨髓检查,38例确诊为多发性骨髓瘤(multiple myeloma,MM),2例确诊为巨球蛋白血症(waldenstrom macroglobulinemia,WM),骨髓涂片中骨髓瘤细胞比例均≥10%;骨髓瘤细胞10%的4例,诊断为意义未明单克隆免疫球蛋白血症(monoclonal gammopathy of un-determined significance,MGUS)。结论:免疫固定电泳检测可对浆细胞肿瘤相关肾损害提供重要的诊断和分型依据,值得临床应用。 相似文献
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Yang Y Groshong JS Matta H Gopalakrishnan R Yi H Chaudhary PM 《The Journal of biological chemistry》2011,286(32):27988-27997
Myeloma cells are dependent on IL6 for their survival and proliferation during the early stages of disease, and independence from IL6 is associated with disease progression. The role of the NF-κB pathway in the IL6-independent growth of myeloma cells has not been studied. Because human herpesvirus 8-encoded K13 selectively activates the NF-κB pathway, we have used it as a molecular tool to examine the ability of the NF-κB pathway to confer IL6 independence on murine plasmacytomas. We demonstrated that ectopic expression of K13, but not its NF-κB-defective mutant or a structural homolog, protected plasmacytomas against IL6 withdrawal-induced apoptosis and resulted in emergence of IL6-independent clones that could proliferate long-term in vitro in the absence of IL6 and form abdominal plasmacytomas with visceral involvement when injected intraperitoneally into syngeneic mice. These IL6-independent clones were dependent on NF-κB activity for their survival and proliferation but were resistant to dexamethasone and INCB018424, a selective Janus kinase 1/2 inhibitor. Ectopic expression of human T cell leukemia virus 1-encoded Tax protein, which resembles K13 in inducing constitutive NF-κB activation, similarly protected plasmacytoma cells against IL6 withdrawal-induced apoptosis. Although K13 is known to up-regulate IL6 gene expression, its protective effect was not due to induction of endogenous IL6 production but instead was associated with sustained expression of several antiapoptotic members of the Bcl2 family upon IL6 withdrawal. Collectively, these results demonstrate that NF-κB activation cannot only promote the emergence of IL6 independence during myeloma progression but can also confer resistance to dexamethasone and INCB018424. 相似文献
5.
Haimovich J Kukulansky T Weissman B Hollander N 《Cancer immunology, immunotherapy : CII》1999,47(6):330-336
Idiotypic determinants of immunoglobulins of malignant B lymphocytes and plasma cells are tumor-specific antigens and have
been used extensively in immunotherapy studies. The mechanisms involved in resistance to tumor challenge following idiotype
vaccination are poorly understood. Although a predominant role has been attributed to anti-idiotype antibodies, both humoral
and cellular immune responses are probably involved. Cell-mediated responses may be particularly effective against tumor cell
variants that do not express the idiotype on the cell surface and are therefore resistant to anti-idiotype antibodies but
continue to produce one of the original immunoglobulin polypeptides that may be processed and presented to T cells. In this
report we describe two experimental models of idiotype vaccination in which antibodies are unlikely to play a role, and hence
tumor immunity is attributed to cell-mediated responses. One model consists of the murine B lymphocyte tumor 38C-13 and its
idiotype-negative variant DB2, which has lost the idiotypic specificity of the parental 38C-13 cell line through the production
of a different light chain but expresses the original heavy chain. Vaccination of mice with the purified IgM of 38C-13 induced
resistance to 38C-13 tumor cells as well as to the variant cells. Although immunized mice produced high levels of anti-idiotype
antibodies that bound to 38C-13 cells, no binding of antibodies to DB2 cells occurred. The finding that idiotype-vaccinated
mice were resistant to idiotype-negative DB2 cells suggested that cellular mechanisms are involved in mediating resistance.
The second model consists of the two plasma cell line JLμs and JLμm, which produce IgM with an identical specificity. Whereas
one of them (JLμs) secretes the IgM, the other one(JLμm) can neither secrete nor deposit it on the cell surface. Immunization
against JLμs IgM followed by tumor challenge resulted in prolonged survival of both JLμs- and JLμm-challenged mice. Although
sera of immunized mice contained high levels of anti-idiotype antibodies, they did not react with the plasmacytoma cells.
Similarly to the results obtained in the 38C-13 experimental model, these results suggest that a non-antibody-mediated mechanism
was involved in the resistance of mice to tumor growth.
Received: 11 June 1998 / Accepted: 26 November 1998 相似文献
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《Reports of Practical Oncology and Radiotherapy》2020,25(3):389-395
BackgroundAlthough much studied in multiple myeloma, bone events (BE) can also cause important morbidity in bone plasmacytoma patients. To our knowledge, the effect of BE on overall survival (OS) and progression to multiple myeloma free-survival (MPFS) also has never been studied.Patients and MethodsFifty-nine patients treated from 2008 to 2017 were retrospectively assessed. All patients had histological proof of disease and were treated with radical radiotherapy (RT). Available clinical information for at least 6 months follow-up or until death had to be available. BE were described as one of the following events in the index bone: fractures, osteomyelitis, chronic pain, surgery or loss of limb function after RT.ResultsMean age at diagnosis was 57.3 years (18–80); most male (67.8%). Mean OS, bone event free-survival (BEFS), local progression-free survival (LPFS) and MPFS were 41, 36, 37 and 19 months, respectively. There were 15 deaths. BEFS (p = 0.008) and age>55y (p = 0.044) were associated with MPFS. Only BEFS correlated with OS (p = 0.029). BE was independently associated with both MPFS and OS in multivariate analysis.ConclusionBE and survival end-points were correlated. BE should be investigated in prospective trials. 相似文献
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