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1.
Methods Mol Biol ; 2261: 151-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33420989

RESUMO

Cancer cells secrete membranous extracellular vesicles (EVs) which contain specific oncogenic molecular cargo (including oncoproteins, oncopeptides, and RNA) into their microenvironment and the circulation. As such, EVs including exosomes (small EVs) and microvesicles (large EVs) represent important circulating biomarkers for various diseases, including cancer and its progression. These circulating biomarkers offer a potentially minimally invasive and repeatable targets for analysis (liquid biopsy) that could aid in the diagnosis, risk stratification, and monitoring of cancer. Although their potential as cancer biomarkers has been promising, the identification and quantification of EVs in clinical samples remain challenging. Like EVs, other types of circulating biomarkers (including cell-free nucleic acids, cf-NAs; or circulating tumor cells, CTCs) may represent a complementary or alternative approach to cancer diagnosis. In the context of multiple myeloma (MM), a systemic cancer type that causes cancer cells to accumulate in the bone marrow, the specific role for EVs as biomarkers for diagnosis and monitoring remains undefined. Tumor heterogeneity along with the various subtypes of MM (such as non-secretory MM) that cannot be monitored using conventional testing (e.g. sequential serological testing and bone marrow biopsies) render liquid biopsy and circulating tumor-derived EVs a promising approach. In this protocol, we describe the isolation and purification of EVs from peripheral blood plasma (PBPL) collected from healthy donors and patients with MM for a biomarker discovery strategy. Our results demonstrate detection of circulating EVs from as little as 1 mL of MM patients' PBPL. High-resolution mass spectrometry (MS)-based proteomics promises to provide new avenues in identifying novel markers for detection, monitoring, and therapeutic intervention of disease. We describe biophysical characterization and quantitative proteomic profiling of disease-specific circulating EVs which may provide important implications for the development of cancer diagnostics in MM.


Assuntos
Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/isolamento & purificação , Exossomos/metabolismo , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue , Proteômica , Espectrometria de Massas em Tandem , Métodos Analíticos de Preparação de Amostras , Estudos de Casos e Controles , Cromatografia Líquida , Exossomos/ultraestrutura , Humanos , Biópsia Líquida , Gamopatia Monoclonal de Significância Indeterminada/patologia , Mieloma Múltiplo/ultraestrutura , Proteólise
2.
Anticancer Res ; 40(10): 5437-5443, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988865

RESUMO

BACKGROUND: Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor A (VEGFA), and has been reported to be overexpressed in several malignancies. Since angiogenesis plays an important role in pathogenesis of multiple myeloma (MM) and the role of NRP1 in MM has not been studied yet, we characterized the expression of NRP1 in this disease. MATERIALS AND METHODS: The expression level of NRP1 was measured in 140 patients newly diagnosed with MM and 28 healthy controls by flow cytometry and quantitative reverse transcriptase polymerase chain reaction. RESULTS: Expression of NRP1 was significantly reduced on plasma cells (median=2.05%) compared to that on B-cells (median=10.05%, p<0.0001) in bone marrow of patients with MM. In MM, the expression of NRP1 was high on plasmacytoid dendritic cells (median=85.85%) and low on regulatory T-cells (median=0.6%). CONCLUSION: In MM, NRP1 is regulated differentially as compared to other B-cell malignancies at both the RNA and protein level.


Assuntos
Mieloma Múltiplo/genética , Neovascularização Patológica/genética , Neuropilina-1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Linfócitos B/metabolismo , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Neovascularização Patológica/sangue , Neovascularização Patológica/patologia , Neuropilina-1/sangue , Transdução de Sinais/genética
3.
Ann Hematol ; 99(8): 1813-1822, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32607596

RESUMO

Infection is associated with great morbidity and mortality in patients with multiple myeloma (MM), but evidence for invasive fungal infections (IFIs) is lacking. We aimed to investigate risk factors for IFI in MM patients and to determine its impact on patients' survival. We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan between January 2002 and October 2018. MM was diagnosed according to the International Myeloma Working Group criteria. IFI was defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. All risk factors of IFI in MM patients were estimated using Cox regression models in the univariate and multivariate analyses. Of the 623 patients recruited, 22 (3.5%) were diagnosed with proven or probable IFI. Light chain disease (adjusted hazard ratio [HR] 6.74, 95% confidence interval [CI] 2.10-21.66), hemoglobin less than 8 g/dl (adjusted HR 3.34, 95% CI 1.32-8.42), serum albumin < 3.5 g/dl (adjusted HR 3.24, 95% CI 1.09-9.68), and having received allogeneic stem cell transplantation (allo-SCT) (adjusted HR 5.98, 95% CI 1.62-22.03) were significantly associated with IFI in the multivariate analysis. Contracting IFI was in turn associated with early mortality (adjusted HR 11.60, 95% CI 1.26-106.74). Light chain disease, anemia, hypoalbuminemia, and receiving allo-SCT were independent predictors of IFI in MM patients. The early mortality risk is much higher in those encountering IFI. Physicians must be aware of the rare but potentially lethal infections.


Assuntos
Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/terapia , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Feminino , Humanos , Infecções Fúngicas Invasivas/sangue , Infecções Fúngicas Invasivas/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Fatores de Risco
5.
Ann Hematol ; 99(8): 1779-1791, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32594218

RESUMO

The Revised International Staging System (R-ISS) was introduced as a powerful prognostic system to stratify patients with newly diagnosed multiple myeloma (NDMM). The serum-free light chain (sFLC) has been developed as a valuable marker to monitor multiple myeloma (MM) progression and response. Therefore, it is imperative to combine R-ISS and sFLC prognostic factors as modified R-ISS (MR-ISS) to better stratify patients into homogeneous survival subgroups, especially to further distinguish the high-risk MM patients who are likely to experience rapid progression or relapse. A total of 595 patients with NDMM were studied retrospectively. We performed the K-adaptive partitioning in 595 NDMM patients to define the MR-ISS classification: stage I includes R-ISS stage I and sFLC ratio < 80 (n = 66); stage III includes R-ISS stage III with sFLC ratio ≥ 80 (n = 87); stage II includes all the remaining conditions (n = 442). The median OS was not reached for MR-ISS stage I, 48.67 months for stage II, and 21.13 months for stage III. A significant OS difference of MR-ISS stage I and III patients has a particularly superior and inferior outcome compared with R-ISS stage I and III, respectively, which showed the similar results in PFS analysis. Validation of results was performed in an independent cohort. Our data indicate that the MR-ISS provides an improved prognostic power compared with R-ISS.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo , Proteínas de Neoplasias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
6.
Hematol Oncol ; 38(4): 523-530, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594534

RESUMO

High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is applied for consolidation in myeloma and relapsing lymphoma patients. Vitamin D (VitD) exerts effects during hematopoietic stem cell proliferation, differentiation and interactions with the immune system. VitD deficiency is frequent in patients with hematological malignancies, but its prognostic relevance after ASCT remains unclear. We investigated the effect of VitD serum levels in patients with lymphomas and myeloma at ASCT on progression-free (PFS) and overall survival (OS). The cohort (n = 183) was divided into two groups: 81 (44%) had VitD levels >52 nmol/L and 102 (56%) ≤52 nmol/L at ASCT. VitD levels >52 nmol/L were associated with better PFS (P = 0.0194) and OS (P = 0.011). Similarly, when evaluating myeloma patients alone, patients with lower VitD levels (≤52 nmol/L) had inferior PFS (P = 0.0412) and OS (P = 0.049). Finally, the multivariate analysis was consistent that varying VitD levels were significantly associated with OS (P = 0.0167), also when stratifying patients in groups with VitD levels > versus ≤52 nmol/L (P = 0.0421). Our data suggest that reduced serum VitD levels in myeloma and lymphoma patients undergoing HDCT/ASCT are associated with inferior outcome. Optimizing VitD levels before ASCT may be warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mieloma Múltiplo/mortalidade , Deficiência de Vitamina D/fisiopatologia , Vitamina D/sangue , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Suíça/epidemiologia , Transplante Autólogo , Adulto Jovem
7.
Ann Hematol ; 99(9): 2159-2171, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32591878

RESUMO

Increasing knowledge of long non-coding RNAs (lncRNAs) has shown that they can be used as circulating tumor markers. Also, considerable evidences have revealed that lncRNAs have important roles in tumor diagnosis and prognosis. The lncRNA CCAT2 has manifested its carcinogenic effect in a variety of tumors, but the serum expression level and clinical value in multiple myeloma (MM) remain to be explored. In our study, the expression of lncRNA CCAT2 is upregulated in the serum and bone marrow of MM patients by using quantitative real-time polymerase chain reaction (qRT-PCR). The high expression level of CCAT2 in the serum of MM patients correlated with International Scoring System (ISS) stages, renal dysfunction, serum ß2-microglobulin (ß2-MG) concentration, and light chain (κ and λ) concentrations. Area under the curve (AUC) of CCAT2 in serum is 0.899. Besides, the sensitivity and specificity were 85.80% and 83%, respectively. Furthermore, combination of CCAT2, IgA, HGB, and ß2-MG significantly improved the MM diagnostic sensitivity and AUC. Here, our present investigation indicates that serum circulating CCAT2 may serve as a potential tumor marker for diagnosis and prognosis of MM.


Assuntos
Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , RNA Longo não Codificante/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Distribuição Aleatória
8.
Ann Hematol ; 99(8): 1907-1915, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32444892

RESUMO

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoglobulinas/sangue , Mieloma Múltiplo , Adulto , Idoso , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
9.
Am J Med Sci ; 360(2): 206-207, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32387118

Assuntos
Fraturas por Compressão/etiologia , Fraturas Espontâneas/etiologia , Plasmocitoma/complicações , Fraturas da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Descompressão Cirúrgica , Dexametasona/administração & dosagem , Progressão da Doença , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas Espontâneas/diagnóstico por imagem , Humanos , Fraturas do Úmero/etiologia , Fraturas do Úmero/cirurgia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Laminectomia , Lenalidomida/administração & dosagem , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/tratamento farmacológico , Plasmocitoma/diagnóstico por imagem , Plasmocitoma/patologia , Plasmocitoma/cirurgia , Tomografia por Emissão de Pósitrons , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X
10.
Ann Hematol ; 99(6): 1331-1339, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382775

RESUMO

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.


Assuntos
Filgrastim/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Análise Custo-Benefício , Feminino , Filgrastim/economia , Mobilização de Células-Tronco Hematopoéticas/economia , Mobilização de Células-Tronco Hematopoéticas/tendências , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/economia , Polietilenoglicóis/economia , Transplante Autólogo/economia , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Resultado do Tratamento
11.
J Cancer Res Ther ; 16(1): 88-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362614

RESUMO

Introduction: The impact of rapid reduction in paraprotein levels, with induction chemotherapy in myeloma, on treatment outcomes is less clear. There are very few studies in transplant ineligible patients treated with novel agents, correlating an early reduction in paraprotein with survival duration. Methods: In this retrospective analysis of newly diagnosed multiple myeloma, ineligible for stem cell transplant, paraprotein levels at baseline and 3 months were noted with percentage reduction. Survival analysis was performed with Kaplan-Meier curves and Cox proportional hazard model. Results: Among a total of 121 patients, 42 (35%), 29 (24%), and 50 (41%) had paraprotein reduction of 100%, 90%-99%, and <90%, respectively from baseline levels at 3 months. Patients with complete disappearance of paraprotein (100% reduction) when compared against those with <100% reduction at 3 months had a trend toward higher overall survival (OS) (3-year OS of 81% vs. 69%, hazard ratio [HR] = 0.54, P = 0.182). However, the progression-free survival (PFS) was significantly higher when these two groups were compared (median PFS of 51 vs. 17 months, HR = 0.33, P ≤ 0.001). When patients with ≥90% reduction were compared with <90% reduction at 3 months, there was significant improvement in both OS and PFS (3-year OS of 80% vs. 48%, HR = 0.24, P = 0.001, median PFS of 38 vs. 14 months, HR = 0.13, P < 0.001). Conclusions: Achieving a faster and deeper reduction in paraprotein as early as 3 months could lead to significant improvement in PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Quimioterapia de Indução/métodos , Mieloma Múltiplo/mortalidade , Paraproteínas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
12.
J Cancer Res Ther ; 16(1): 98-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362616

RESUMO

Context: The fluctuations of proteins in multiple myeloma (MM) are well-known markers for checking the status of the patients. Aims: The objective of this study was to examine three proteins that have an important role in disease progression. Subjects and Methods: The study was performed with two groups: 30 MM stage I patients' (14 females/16 males; aged 60.83 ± 12.38 years) as case group and 40 healthy individuals (18 females/22 males; aged 57.65 ± 6.43 years) as control group. Both groups have been matched in gender and age. Bone sialoprotein (BSP), osteopontin (OPN), and ß2-microglobulin (ß2M) were measured with an enzyme-linked immunosorbent assay. Results: Serum BSP levels of MM-I patients was significantly higher than that of healthy controls (29.24 ± 5.57 vs. 20.89 ± 3.67, P = 0.001). OPN levels of MM-I patients were significantly lower than that of healthy individuals (12.03 ± 3.45 vs. 19.35 ± 4.67, P = 0.001). ß2M levels of patients and controls were similar (1.49 ± 0.67 vs. 1.29 ± 0.55, P = 0.193). Conclusions: The results suggested that myeloma cells may affect the production of BSP and OPN, which possibly contributes to osteoclastic bone resorption in MM-I patients. Their levels may be a useful biomarker for assessing bone destruction in MM-I patients and distinguishing MM-I from healthy individuals.


Assuntos
Biomarcadores Tumorais/sangue , Sialoproteína de Ligação à Integrina/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Osteopontina/sangue , Microglobulina beta-2/sangue , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Ann Hematol ; 99(6): 1251-1255, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32307566

RESUMO

Secretion of monoclonal immunoglobulins (MIg) detected in the serum and/or urine is one of the typical features of multiple myeloma (MM). However, some patients secrete MIg in quantities below "measurable" (termed oligosecretory MM) and others have no detectable MIgs by standard serum and urine immunofixation (termed non-secretory MM). In a cohort of 852 consecutive patients with active myeloma, we identified 100 (11.7%) patients with oligo/non-secretory MM, including 20 (2.3%) with non-secretory MM. Compared to patients with secretory MM, these were younger, less anemic, and had less often renal dysfunction and less extensive bone marrow infiltration. Presence and extent of bone disease were similar, however, hypercalcemia was less common and more often is ISS (International Staging System)-1 and, in those with available FISH (Fluoresense In Situ Hybridization) , high-risk cytogenetics were less common. FLCs (Free Light Chains) were available in 17 patients with non-secretory MM: only 3 had normal FLC ratio; the others had abnormal ratio and 9/14 had involved FLC ≥ 100 mg/L. The 4-year OS for patients with oligo/non-secretory disease was 64% vs 58% for secretory MM. In multivariate analysis, oligo/non-secretory disease was not an independent prognostic factor per se. Thus, 12% of MM patients present with oligo/non-secretory disease at diagnosis and have different biologic characteristics but similar outcome to other MM patients.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Imunoglobulina M/sangue , Imunoglobulina M/urina , Mieloma Múltiplo/sangue , Mieloma Múltiplo/urina , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Resultado do Tratamento
15.
Anticancer Res ; 40(3): 1443-1449, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132041

RESUMO

BACKGROUND/AIM: Although numerous cytokines influence proliferation and progression of multiple myeloma (MM), a relevant action in the onset of the disease also seems to be played by the oxidative state. PATIENTS AND METHODS: In the present study we evaluated the concentrations of interleukin-8 (IL-8) and soluble receptor of advanced glycation end products (sRAGE) in patients with MM, assessing the existing variations with respect to a control group and the possible existence of correlations between these molecules and the biological variables or the presence of a correlation between IL-8 and sRAGE. The study was conducted on 33 patients affected by MM compared to 39 healthy subjects. RESULTS: IL-8 and sRAGE levels were significantly higher in MM patients compared to healthy subjects. sRAGE and IL-8 evidence no significant linear correlation. Furthermore, IL-8 was significantly increased in both sexes, but we found a slight variation for females compared to males. CONCLUSION: IL-8 could play an important role in the onset of MM and the progression of bone disease, while the increased sRAGE values would seem to have a protective action in MM patients. Further studies on animal models may clarify the real impact of introducing modulation of IL-8 and sRAGE levels.


Assuntos
Antígenos de Neoplasias/sangue , Interleucina-8/sangue , Proteínas Quinases Ativadas por Mitógeno/sangue , Mieloma Múltiplo/sangue , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Masculino , Mieloma Múltiplo/patologia
16.
Ann Clin Lab Sci ; 50(1): 151-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32161026

RESUMO

OBJECTIVE: Capillary electrophoresis of serum proteins demonstrates occasional distortions. Distortions or peaks in the gamma, beta, and alpha-2 zones may represent monoclonal gammopathy. In this study, we investigated if such distortions are associated with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma. METHODS: Consecutive serum protein electrophoresis results were reviewed and immunofixation studies were recommended on specimens exhibiting distortions or distinct peaks in the gamma, beta or alpha-2 zones. RESULTS AND DISCUSSION: Of the 471 cases, we observed distortions in 101 cases. In the immunofixation studies, 17.8% of cases had a diagnosis of MGUS, but none contained multiple myeloma. CONCLUSIONS: We conclude that distortions in serum capillary electrophoresis may be associated with MGUS, but not multiple myeloma.


Assuntos
Proteínas Sanguíneas/análise , Eletroforese Capilar/métodos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo/diagnóstico , Proteínas Sanguíneas/metabolismo , Diagnóstico Diferencial , Humanos , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue
20.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069933

RESUMO

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase; polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (> 30 vs. ≤30 years, HR 4.71, 95%CI [2.40-9.27]; p < 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.


Assuntos
Doença de Gaucher/sangue , Imunoglobulinas/sangue , Paraproteinemias/sangue , Adulto , Estudos de Coortes , Feminino , Doença de Gaucher/complicações , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/patologia , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Paraproteinemias/complicações , Paraproteinemias/tratamento farmacológico , Paraproteinemias/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , gama-Globulinas/administração & dosagem
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