Navegando por Palavras-chave "multiple myeloma"
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- ItemSomente MetadadadosAdvances in the treatment of multiple myeloma: the role of thalidomide(Taylor & Francis Ltd, 2003-01-01) Ribas, Christian [UNIFESP]; Colleoni, Gisele Wally Braga [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Multiple myeloma (MM) accounts for 1% of all malignancies and 10% of malignant hematological neoplasms. in spite of high-dose therapy with stem cell rescue, relapse and disease resistance are common events in the course of the disease. Thalidomide (Thal) has been successfully used in such situations and it's use has also been expanded to the up-front therapy and as adjuvant to stem cell transplantation. Here, we review the underlying concepts and current clinical data regarding Thal in the treatment of MM.
- ItemSomente MetadadadosBilateral central retinal vein occlusion associated with multiple myeloma(Karger, 2004-01-01) Aggio, F. B.; Cariello, A. J.; Almeida, MSS; Rodrigues, C. A.; Moraes, NSB de; Colleoni, GWB; Farah, M. E.; Universidade Federal de São Paulo (UNIFESP)Purpose: To report a case of simultaneous bilateral central retinal vein occlusion (CRVO) associated with multiple myeloma. Methods: A 65-year-old woman had sudden, painless loss of vision in both eyes for 20 days. Ophthalmologic examination revealed bilateral CRVO. Appropriate medical workup was conducted, and multiple myeloma was diagnosed as the underlying cause. Results: Clinical support and chemotherapy effectively controlled paraprotein production, leading to improvement of both systemic and ocular alterations. Conclusions: Many conditions have been noted to be associated with CRVO. Based on a Medline search, this is the first report of simultaneous bilateral CRVO as the first manifestation of multiple myeloma, illustrating the need for a primary care ophthalmologist to be involved in the basic assessment for associated underlying diseases in retinal disorders. Copyright (C) 2004 S. Karger AG, Basel.
- ItemSomente MetadadadosDiagnosis of chronic lymphoproliferative disorders by flow cytometry using four-color combinations for immunophenotyping: A proposal of the brazilian group of flow cytometry (GBCFLUX)(Wiley, 2017) Sales, M. M.; Ferreira, S. I. A. C. P.; Ikoma, M. R. V.; Sandes, A. F.; Beltrame, M. P.; Bacal, N. S.; Silva, M. C. A.; Malvezzi, M.; Lorand-Metze, I. G. H.; Orfao, A.; Yamamoto, M. [UNIFESP]BackgroundMultiparametric flow cytometry (MFC) is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purposes of the Brazilian Group of Flow Cytometry (GBCFLUX), the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country. Most laboratories in Brazil work with 4-fluorescence flow cytometers, which is why the GBCFLUX CLPD Committee has proposed 4-color monoclonal antibody (MoAb) panels. Methods/ResultsPanels for screening and diagnosis in B, T and NK lymphoproliferative disorders were developed based on the normal differentiation pathways of these cells and the most frequent phenotypic aberrations. Important markers for prognosis and for minimal residual disease (MRD) evaluation were also included. The MoAb panels presented here were designed based on the diagnostic expertise of the participating laboratories and an extensive literature review. ConclusionThe 4-color panels presented to aid in the diagnosis of lymphoproliferative neoplasms by GBCFLUX aim to provide clinical laboratories with a systematic, step-wise, cost-effective, and reproducible approach to obtain an accurate immunophenotypic diagnosis of the most frequent of these disorders. (c) 2016 International Clinical Cytometry Society
- ItemSomente MetadadadosEndocarditis due to glycopeptide-intermediate Staphylococcus aureus: case report and strain characterization(Elsevier B.V., 2003-02-01) Andrade-Baiocchi, S.; Tognim, MCB; Baiocchi, Otavio Carvalho Guimarães [UNIFESP]; Sader, H. S.; Universidade Federal de São Paulo (UNIFESP)We report a case of infective endocarditis due to vancomycin-intermediate Staphylococcus aureus (VISA) that did not respond to high doses of vancomycin. Initial vancomycin MIC of the last isolate recovered from blood was 8 1 mug/mL, but could be induced up to 32 mug/mL by consecutive growing with vancomycin. Clinical response was only accomplished when linezolid was included in therapy. (C) 2003 Elsevier Science Inc. All rights reserved.
- ItemSomente MetadadadosEstudos funcionais da expressão dos genes triap1 e hsp70 em linhagens celulares de mieloma múltiplo(Universidade Federal de São Paulo (UNIFESP), 2014-08-28) Alves, Veruska Lia Fook [UNIFESP]; Colleoni, Gisele Wally Braga Colleoni [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Some evidences suggest that heat shock protein 70 (HSP70) is overexpressed in many types of cancer, and that high expression of this chaperone is linked with increasing tumor grade and/or poor prognosis. The overexpression of HSP70 may provide a selective advantage for tumor cell survival, due in part, to their ability to inhibit cell death via APAF1 (apoptosis protease activating factor 1) and Caspase 9. The TP53 Regulated Inhibitor Of Apoptosis 1 (TRIAP1) gene can modulate apoptotic pathways by interaction with HSP70. Although there are several studies on the role of HSP70 gene in apoptosis and drug resistance, there is a lack of information about this gene in multiple myeloma (MM). Objectives: To analyze the importance of HSP70 and TRIAP1 as potential targets for MM therapy through: 1) stable silencing of HSP70 and TRIAP1 in MM cell lines; 2) evaluation of each gene silencing effect on cell cycle and apoptosis. Methods:. The expression of HSP70 and P53CSV genes in MM cell lines (U266, SKO-007, SK-MM2 and RPMI8226) was examined by quantitative real time PCR (qPCR). Cell lines were submitted to transduction with pLKO lentiviral vector containing short hairpin RNAs (shRNAs) for silencing the target genes (shRNAHSP70 and shRNATRIAP1). Lentiviral vectors with control sequences (scramble) were used to transduce the same cell lines. Apoptosis was assessed by flow cytometry after annexin V and propidium iodide (PI) staining. We also evaluated APAF1 and Caspase9 gene expression by qPCR and Caspase 9 and Caspase 3/7 protein activity. Results:. The cell lines RPMI8226 (without deletion of TP53 by FISH) and U266 (deletion of one allele of TP53 by FISH) were chosen for the transduction experiments because they showed significant levels of expression of HSP70 and TRIAP1. The efficiency of transduction, as measured in both cell lines transduced with the pLKO vector containing the GFP reporter gene, was 70%. RPMI8226 and U266 were submitted to three independent transductions, in triplicate, with the lentiviral vector containing the constructs pLKO shRNAHSP70, shRNATRIAP1 and shRNAscramble. We obtained the stable silencing of HSP70 and TRIAP1 in both MM cell lines. Silencing was confirmed by relative quantitative PCR and Western blotting (for HSP70 only). Inhibition of TRIAP1 increased the percentage of cells in late apoptosis and was accompanied by increased expression of Caspase9 in both MM cell lines. Furthermore, the inhibition of TRIAP1 resulted in accumulation of hypodiploid cells after 24 hours of transduction in U266 cell line. Inhibition of HSP70 showed no significant changes in the cell cycle in both MM cell lines. However, we observed an increment in late apoptosis after inhibition of this gene in the two cell lines and the results were confirmed by increased activity of Caspase3/7. Conclusion: Stable silencing of HSP70 and TRIAP1 in MM cell lines showed a strong impact of this method on the induction of late apoptosis, through APAF1/Caspase9 pathway, suggesting that inhibitors of both genes could be exploited as potential targets for the treatment of MM, helping patients whatever TP53 status assessed by FISH.
- ItemSomente MetadadadosIs there any relationship between gene expression of tumor antigens and CD4(+) T cells in multiple myeloma?(Future Medicine Ltd, 2014-05-01) Braga, Walter M. T.; Silva, Bruna R. da [UNIFESP]; Alves, Veruska L. F. [UNIFESP]; Bortoluzo, Adriana B.; Atanackovic, Djordje; Colleoni, Gisele W. B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Insper Inst Educ & Res; Univ Med Ctr Hamburg EppendorfAim: the present study aimed at correlating the expression of cancer/testis antigens (CTAs) with the expression of genes related to tumor-infiltrating T cells. Materials & methods: MAGE-C1/CT-7, MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE expression were evaluated in 46 bone marrow multiple myeloma (MM) aspirates by RT-PCR. Expression of FOXP3/CTLA4 and RORyt, as markers for Tregs and Th17 cells, respectively, was investigated by quantitative PCR. Results: MAGEC1/CT7 was expressed in 66% of MM samples. We did not find correlation between the presence of single CTA and expression of CTLA4 or RORyt neither expression of CD4(+) T-cell markers and the number of CTA simultaneously expressed in the tumor. However, we did observe a correlation between the percentage of plasma cells and the number of CTAs expressed in the patients' bone marrow. Conclusion: Although CTAs and immunomodulatory CD4(+) T cells represent potential targets for immunotherapy in MM, we did not find association among expression of such genes in MM.
- ItemSomente MetadadadosN-RAS and K-RAS gene mutations in Brazilian patients with multiple myeloma(Taylor & Francis Ltd, 2006-02-01) Ortega, Manoela M.; Faria, Rosa MD [UNIFESP]; Shitara, Edson S.; Assis, Angela M.; Albuquerque, Dulcinéia M.; Oliveira, José SR; Noguti, Maria Aparecida Eiko [UNIFESP]; Faria, Jose Roberto de [UNIFESP]; Costa, Fernando Ferreira [UNIFESP]; Lima, Carmen Silvia Passos; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)Point mutations affecting codons 12, 13 (exon 1) and 61 (exon 2) of the N-RAS gene and codons 12 and 13 (exon 1) of the K-RAS gene are identified in approximately 30.0% and 10.0%, respectively, of multiple myeloma (MM) patients living in the northern hemisphere. To date, there are no reports about the prevalence of RAS gene mutations in MM Brazilian patients, and this comprised the aim of the present study. DNA from bone marrow aspirates of 252 patients with MM (139 males and 113 females; aged 59.33 +/- 11.95 years) were investigated for whole exons 1 and 2 of the N-RAS gene and whole exon 1 of the K-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Fifty-three out of 252 (21.03%) MM patients presented RAS mutations. Heterozygous mutations at codons 4, 10 (exon 1), 61 and 65 (exon 2) of the N - RAS gene were identified in seven out of 252 (2.78%) patients. K-RAS heterozygous mutations at codons 7, 12, 13 (exon 1) were seen in 46 out of 252 (18.25%) patients. To the best of our knowledge, the mutation at codon 7 of K-RAS gene is reported for the first time in MM. Taken together, these results suggest that Brazilian MM patients are characterized by: (i) a low prevalence of RAS mutation and (ii) RAS mutations located at distinct regions of the critical codons of the N - RAS and K-RAS genes.
- ItemSomente Metadadadosp16 gene methylation lacks correlation with angiogenesis and prognosis in multiple myeloma(Elsevier B.V., 2005-05-26) Ribas, C.; Colleoni, GWB; Felix, R. S.; Silva, MRR; Caballero, O. L.; Brait, M.; Bordin, J. O.; Universidade Federal de São Paulo (UNIFESP); Ludwig Inst Canc ResMethylation of p16 gene is a relatively frequent molecular finding in multiple myeloma (MM), but its clinical implication is disputable. Cell cycle regulators are now recognized as active in the control of angiogenesis, which is an integral component of pathogenesis and a target for new treatment modalities of this disease. On such background, we focused on determining whether loss of p16 function by methylation could be associated with increased angiogenesis and VEGF expression, and the prognostic relevance of p16 methylation in 50 untreated, newly diagnosed MM patients. Thirty-one percent (13/42) of 42 patients assessable for p16 gene methylation showed to be methylation-positive. High-angiogenesis was present in 73% of cases, but methylation of the p16 gene did not associate with angiogenesis or with VEGF expression. Also, p16 methylation did not show prognostic relevance or correlation with the clinical and laboratory parameters of prognostic significance in univariate analysis. PI 6 immunoexpression presented only a faint agreement with the molecular study. Therefore, p 16 methylation seems to have no correlation with angiogenesis and VEGF expression, neither with overall and event-free survival in MM patients. Besides, P16 immunohistochemistry seems inadequate to substitute the molecular study of methylation in this type of tumor cells. Additional studies are needed to clarify the correspondence between the epigenetic alteration of the p16 gene and its protein immunexpression, and the clinical relevance of p16 methylation in MM patients. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
- ItemSomente MetadadadosPrognostic significance of vascular endothelial growth factor immunoexpression in the context of adverse standard prognostic factors in multiple myeloma(Blackwell Munksgaard, 2004-11-01) Ribas, C.; Colleoni, GWB; Silva, MRR; Carregoza, M. J.; Bordin, J. O.; Universidade Federal de São Paulo (UNIFESP)Objectives: Vascular endothelial growth factor (VEGF) acts in several steps of multiple myeloma (MM) pathogenesis and it is an important mediator of tumor angiogenesis. the aim of this study was to examine the prognostic significance of VEGF immunoexpression in the context of standard prognostic factors present in a cohort of advanced MM patients. Methods: Fifty untreated MM patients were enrolled from May 2000 to December 2002. Bone marrow sections were subjected to morphologic assessment and immunohistochemical studies with antibodies against CD34 and VEGF. Angiogenesis was measured by microvessel density (MVD) and stratified into high (MVD greater than or equal to 20) and low angiogenesis status (MVD < 20). VEGF immunoreactivity was examined on the basis of intensity and percentage of positive plasma cells (PC). Results: Ninety-four percent of patients presented advanced disease at diagnosis. Median PC marrow infiltration was 80%. Twelve percent of patients presented plasmablastic morphology. Low angiogenesis was present in 27% of patients, while high angiogenesis was present in 73%. Twenty-nine percent of patients had VEGF < 10% and 71% had VEGF greater than or equal to 10%. Weak-intensity VEGF was observed in 34% of cases, while 37% had moderate/strong VEGF intensity. Although VEGF had prognostic impact on overall survival (OS) and event-free survival (EFS) in univariate analysis, multivariate analysis identified only plasmablastic morphology and elevated serum lactate dehydrogenase (LDH) level as independent prognostic factors to predict OS (P = 0.04 and P = 0.02, respectively). With regard to EFS, although VEGF showed statistical trend to influence survival (P = 0.08), the parameters of independent prognostic value were also plasmablastic morphology (P = 0.01) and elevated LDH level (P = 0.01). Conclusion: Our findings underline the frequent expression of VEGF in advanced-stage MM and the greater prognostic information of simple and readily available factors, namely plasmablastic morphology and elevated LDH. Moreover, despite the absence of prognostic importance in multivariate analysis, VEGF and its receptors remain promising therapeutic targets in MM.
- ItemAcesso aberto (Open Access)Proteasome and heat shock protein 70 (HSP70) inhibitors as therapeutic alternative in multiple myeloma(Impact Journals Llc, 2017) Pereira Eugenio, Angela Isabel [UNIFESP]; Fook-Alves, Veruska Lia [UNIFESP]; de Oliveira, Mariana Bleker [UNIFESP]; Fernando, Rodrigo Carlini [UNIFESP]; Zanatta, Daniela B.; Strauss, Bryan Eric; Regis Silva, Maria Regina [UNIFESP]; Porcionatto, Marimelia Aparecida [UNIFESP]; Braga Colleoni, Gisele Wally [UNIFESP]HSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment. Bioluminescence imaging was used to follow tumor response. Treatment with bortezomib showed similar to 60% of late apoptosis in RPMI8226-LUC-PURO (without additional benefit of VER155008 in this cell line). However, U266-LUC-PURO showed similar to 60% of cell death after treatment with VER155008 (alone or with bortezomib). RPMI8226-LUC-PURO xenograft presented tumor reduction by bioluminescence imaging after treatment with bortezomib, VER155008 or drug combination compared to controls. Treatment with bortezomib, alone or combined with VER155008, showed inhibition of tumor growth assessed by bioluminescence imaging after one week in both RPMI8226-LUC-PURO and U266-LUC-PURO cell lines when compared to controls. In conclusion, our study shows that the combination of proteasome and HSP70 inhibitors induced cell death in tumor cells in vitro (late apoptosis induction) and in vivo (inhibition of tumor growth) with special benefit in U266-LUC-PURO, bearing 17p deletion.
- ItemSomente MetadadadosUnderstanding myeloma cancer stem cells(Future Medicine Ltd, 2013-12-01) Pascutti, Fabio [UNIFESP]; Cunha, Lucas Leite [UNIFESP]; Rizzatti, Edgar Gil; Colleoni, Gisele W. B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Grp Fleury