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1.
Rev. clín. esp. (Ed. impr.) ; 220(2): 109-114, mar. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-186420

RESUMO

Introducción: El síndrome hemofagocítico (SHF) es un trastorno inmunológico grave caracterizado por una inflamación descontrolada con fracaso multiorgánico. Puede estar desencadenado por infecciones víricas, bacterianas, fúngicas o parasitarias. Se describe nuestra experiencia de SHF asociado a infecciones y se estima su incidencia local. Material y método: Estudio retrospectivo observacional de SHF asociado a infecciones en adultos atendidos en el Servicio de Patología Infecciosa de un hospital universitario durante 5años y revisión de las series publicadas en Europa. Resultados: En 2 mujeres con enfermedad de Crohn, el SHF se asoció a infección por citomegalovirus y a leishmaniosis visceral (mieloma múltiple 1, tumor sólido 2, sin enfermedad evidente 1) en 4 pacientes (3 hombres). Fallecieron 2 enfermos. La incidencia estimada fue 0,58/100.000/año. Las series publicadas son heterogéneas. Conclusiones: El SHF asociado a infecciones debe de ser más frecuente de lo descrito. El entorno geográfico puede influir en las infecciones desencadenantes (en nuestro medio, debe buscarse Leishmania)


Background: Haemophagocytic syndrome (HPS) is a severe immunological disorder characterised by uncontrolled inflammation and multiple organ failure. HPS can be triggered by viral, bacterial, fungal and parasitical infections. We report our experience with infection-related HPS and estimate its local incidence. Material and method: We conducted an observational retrospective study of infection-associated HPS in patients treated in the Department of Infectious Diseases of a university hospital within a 5-year period, as well as a review of the published series in Europe. Results: HPS was associated with infection by cytomegalovirus in 2 women with Crohn's disease and was associated with visceral leishmaniosis in 4 patients (3 men, 1 woman; 1 case of multiple myeloma; 2 cases of solid tumours; 1 case of no apparent disease). Two patients died, and the estimated incidence rate was 0.58/100,000 inhabitants/year. The published series are mixed. Conclusions: Infection-related HPS must be more common than reported. The geographical environment can influence the triggering infections (in our environment, Leishmania should be considered)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Idoso , Linfo-Histiocitose Hemofagocítica/diagnóstico , Insuficiência de Múltiplos Órgãos/diagnóstico , Etoposídeo/uso terapêutico , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Infecções por Citomegalovirus/diagnóstico , Leishmaniose/diagnóstico , Mieloma Múltiplo/complicações , Doença de Crohn/complicações , Resultado do Tratamento
2.
Wiad Lek ; 73(1): 203-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32124836

RESUMO

The objective of our study was to interpret and discuss atypical multiple myeloma case. The article describes the case of clinical observation of a patient K, in which manifestations of chronic kidney disease and circulatory failure prevailed in clinical picture of the disease. The authors recommended an X-ray examination of skull and pelvic bones as a screening method suitable for elderly people with symptoms of chronic renal insufficiency and chronic bone and muscle pain resistant to treatment.


Assuntos
Diagnóstico Diferencial , Mieloma Múltiplo , Osso e Ossos , Humanos , Radiografia
5.
Zhonghua Nei Ke Za Zhi ; 59(2): 161-164, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32074693

RESUMO

A 49-year-old woman was admitted to hospital with intermittent dizziness and fatigue for 7 years. The symptoms were aggravated and accompanied by bone pain for more than 4 months. She was referred to our hospital. Laboratory tests and imaging findings suggested that acquired Fanconi Syndrome (FS) was associated with smoldering multiple myeloma (MM). Renal biopsy and electron microscopy confirmed the diagnosis of proximal light chain tubular disease (LCPT). LCPT causes proximal tubular dysfunction, which is characterized by the cytoplasmic crystal deposition usually kappa monoclonal light chain in the proximal tubule. MM with FS and LCPT is less common in clinical practice because it is difficult to diagnose. This is a typical case focusing on the differential diagnosis of monoclonal gammopathy of renal significance(MGRS) such as LCPT and plasma cells diseases.


Assuntos
Anemia , Tontura/etiologia , Síndrome de Fanconi/etiologia , Fadiga/etiologia , Nefropatias/complicações , Mieloma Múltiplo , Paraproteinemias/complicações , Proteinúria , Síndrome de Fanconi/diagnóstico , Feminino , Humanos , Cadeias kappa de Imunoglobulina , Nefropatias/diagnóstico , Pessoa de Meia-Idade , Paraproteinemias/diagnóstico
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 165-170, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027271

RESUMO

OBJECTIVE: To explore the expression of Blimp1, ATF4 and CHOP in bone marrow mononuclear cells from patients with multiple myeloma as well as the effect of aspirin on their expression. METHODS: Sixty untreated patients with multiple myeloma and 30 patients with relatively normal bone marrow were selected. Mononuclear cells from the bone marrow fluid were separated using Ficoll separation solution. CD138+ plasma cells were sorted by immunomagnetic beads method. RT-PCR was used to detect the expression levels of Blimp1, ATF4 and CHOP mRNA in U266 cells cultured in vitro. The cells were divided into blank control group, negative control group (no-loaded virus transfection) and positive experimental group [LV-Blimp1-RNAi (40051-2) transfection] by lentivirus transfection. RT-PCR was used to detect the expression of Blimp1, ATF4 and CHOP mRNA in cells of different groups. U266 cells were stimulated in vitro with different concentrations of aspirin solution (0, 0.5 mmol/L, 2.5 mmol/L, 5.0 mmol/L) for 24, 48 h and 72 h, respectively. The ability of cell proliferation in different groups was measured by CCK-8. U266 cells were stimulated with different concentrations of aspirin for 48 hours. And the mRNA expression of Blimp1, ATF4 and CHOP was detected by RT-PCR. RESULTS: Compared with plasma cells in normal group, the expression of Blimp1 mRNA in CD138+ plasma cells of MM patients significantly increased (8.040±1.878), and the mRNA expression levels of ATF4 and CHOP significantly decreased (0.735±0.089; 0.837±0.062) (P<0.05). U266 cells were cultured in vitro. Compared with the blank control group and the negative control group, the mRNA expression level of Blimp in the positive experimental group was significantly down-regulated after infection with LV-Blimp1-RNAi (40051-2) lentiviral expression vector (0.637±0.021). ATF4 and CHOP mRNA expression levels were significantly increased (1.452 ± 0.027; 1.721 ± 0.038) (P<0.05). The proliferation of U266 cells decreased after stimulation with aspirin. In the range of (0.5-5) mmol/L, aspirin could significantly inhibit the proliferation of U266 cells. The inhibition effect of aspirin was increased along with prolongation of time and increase of concentrations. After aspirin stimulation of different concentrations for 48 hours, the expression level of Blimp1 in U266 cells decreased with increasing of drug concentration, while the expression levels of ATF4 and CHOP increased with increasing of drug concentration. CONCLUSION: Inhibition of Blimp1 expression in multiple myeloma cells can promote the expression of ATF4 and CHOP. Aspirin can inhibit the proliferation activity of myeloma cells by down-regulating Blimp1 expression in myeloma cells and up-regulating ATF4 and CHOP expression, therefore plays an anti-tumor rote.


Assuntos
Fator 4 Ativador da Transcrição/genética , Mieloma Múltiplo , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose , Aspirina , Linhagem Celular Tumoral , Proliferação de Células , Ciclofosfamida , Doxorrubicina , Humanos , Mieloma Múltiplo/genética , Prednisona , Vincristina
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 171-176, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027272

RESUMO

OBJECTIVE: To investigate the inhibitory effect of adiponectin receptor agonist AdipoRon on proliferation of myeloma cell lines and its possible mechanism. METHODS: The myeloma cell lines Sp2/0-Ag14 and MPC-11 were treated with different concentration of AdipoRon. The cell proliferation was detected by CCK-8. Western blot was used to determine the protein level of the signaling pathway. RT-PCR was used to quantify the mRNA copy number of adiponectin receptor AdipoR1 and AdipoR2 in the bone marrow cells from 21 patients with multiple myeloma (MM). Twenty-three normal bone marrow samples were served as control. RESULTS: AdipoRon significantly inhibited the proliferation of MM cell lines Sp2/0-Ag14 and MPC-11 in a concentration-dependent and time-dependent manner. Western blot showed that AdipoRon induced an increase of the expression levels of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. AdipoRon upregulated p-AMPK and its downstream p-ACC in MPC-11. In addition, AdipoRon upregulated LC3-II/LC3-I level and down-regulated the protein level of p62. The expression level of AdipoR1 in MM cells was significantly higher than that in normal controls, and the expression level of AdipoR2 in MM cells was significantly lower than that in normal controls. CONCLUSION: Adiponectin receptors are expressed differentially between MM patients and normal subjects. AdipoRon, an adiponectin receptor agonist, can inhibit myeloma cell proliferation and induce apoptosis, and AMPK/autophagy pathway may be one of its mechanisms.


Assuntos
Autofagia , Mieloma Múltiplo , Proteínas Quinases Ativadas por AMP , Apoptose , Proliferação de Células , Humanos , Piperidinas , Receptores de Adiponectina , Transdução de Sinais
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 185-190, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027274

RESUMO

OBJECTIVE: To investigate the expression and clinical significance of long non-coding RNA PRAL in patients with multiple myeloma(MM). METHODS: Clinical data of 60 MM patients and 60 healthy people with the same age(as controls) were selected. Real time-quantitative fluorescence PCR (RT-qPCR) was used to determine the expression levels of serum LncRNA PRAL in the patients and controls, and the relationship of its expression with the clinicopathological characteristics and prognosis of patients was analyed. RESULTS: LncRNA PRAL expression in MM patients was significantly lower than that in healthy people (F=13.294, P<0.001). LncRNA PRAL expression correlated with D-S staging and ISS staging in MM patients. PAD efficacy was significantly improved in MM patients with high expression of LncRNA PRAL, and median survival time was significantly prolonged (P<0.05). CONCLUSION: LncRNA PRAL expression decreases in MM patients, while MM patients with high expression of LncRNA PRAL can obtain better therapeutic efficacy and longer survival time.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Prognóstico , RNA Longo não Codificante , Reação em Cadeia da Polimerase em Tempo Real
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 191-195, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027275

RESUMO

OBJECTIVE: To analyzed the prognostic value of serum free light chain kappa/lambda ratio detection combined with immunofixation electrophoresis in multiple myeloma (MM) patients. METHODS: 72 patients with MM treated in our hospital from January 2017 to December 2018 were selected. Serum free light chain kappa/lambda ratio (sFLCR) and immune typing were detected respectively. The clinical characteristics and survival time were compared among patients. COX regression was used to analyze the factors influencing prognosis. RESULTS: 38 patients showed high sFLCR, and 34 showed low sFLCR. Compared with the low sFLCR group, the DS stage of patients in high sFLCR group elevated, the levels of ß2-MG and Scrwere increased, and Hb decreased, all the differences were statistically significant (P<0.05). Among 72 patients, there were 40 cases of IgG type (55.56%), 27 cases of IgA type (37.50%) and 5 cases of IgM type (6.94%). Compared with IgG and IgA patients, the serum calcium and creatinine in IgM patients were increased significantly, while Hb decreased significantly (P<0.05). The median survival time was 19.2 months in 21 patients with IgG type and high sFLCR; 24.0 months in 19 patients with IgG type and low sFLCR; 15.0 months in 12 patients with IgA type and high sFLCR; 16.7 months in 15 patients with IgA type and low sFLCR; 6.0 months in 5 patients with IgM type and high sFLCR,respectively. DS stage, M protein typing and sFLCR correlated with prognosis of patients (P<0.05). CONCLUSION: The serum free light chain kappa/lambda ratio combined with immunofixation electrophoresis is valuable for the prognostic evaluation of patients with multiple myeloma.


Assuntos
Mieloma Múltiplo , Eletroforese , Humanos , Cadeias Leves de Imunoglobulina , Cadeias kappa de Imunoglobulina , Cadeias lambda de Imunoglobulina , Prognóstico
10.
Med Lav ; 111(1): 63-73, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32096774

RESUMO

OBJECTIVE: We carried out a systematic review and meta-analysis of epidemiologic studies on the association between occupational exposure to glyphosate and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). METHODS: We conducted a systematic search of the literature, and identified 18 relevant publications, from which we extracted results from seven non-overlapping studies of NHL and three of MM. We performed random-effects meta-analyses for ever-exposure to glyphosate, dose-response, and risk of specific NHL subtypes. RESULTS: The meta-relative risk (RR) of NHL was 1.03 (95% confidence interval [CI] 0.86-1.21), that of MM was 1.04 (95% CI 0.67-1.41). The meta-RR of NHL for highest category of exposure was 1.49 (95% CI 0.37-2.61; 3 studies). The meta-RR for diffuse large B-cell lymphoma (DLBCL) was 1.31 (95% CI 0.93-1.75); that for follicular lymphoma was 0.82 (95% CI 0.93-1.70), and that for chronic lymphocytic leukemia was 0.85 (95% CI 0.20-1.49). There was indication of publication bias for studies on NHL. CONCLUSIONS: Our meta-analysis provided no overall evidence of an increased risk for both NHL and MM in subjects occupationally exposed to glyphosate. In secondary analyses we detected a small increase in risk for the category with highest level of exposure as well as for DLBCL. The evidence of publication bias suggests caution in the interpretation of the results.


Assuntos
Glicina/análogos & derivados , Linfoma não Hodgkin , Mieloma Múltiplo , Exposição Ocupacional , Glicina/toxicidade , Humanos , Linfoma não Hodgkin/epidemiologia , Mieloma Múltiplo/epidemiologia , Fatores de Risco
11.
Sheng Wu Gong Cheng Xue Bao ; 36(1): 122-132, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32072787

RESUMO

Signaling lymphocyte activation family 7 (SLAMF7/CS1) is a cell surface glycoprotein that is highly expressed in multiple myeloma cells. CS1 is a sensitive and specific biomarker for multiple myeloma. CAR-T cell immunotherapy is a new method for the treatment of multiple myeloma. CS1 CAR-T cell immunotherapy has good effect on relapsed refractory multiple myeloma. To detect the expression efficiency of CS1 CAR on CS1 CAR-T cells and to find an auxiliary means to CAR-T cell immunotherapy, we prepared a CS1-Fc fusion protein. First, the extracellular domain of CS1 was amplified from the existing plasmid by PCR and ligated with human IgG1-Fc fragment by overlap extension PCR. The recombinant fragment was ligated into pMH3 eukaryotic expression vector. After restriction enzyme digestion and DNA sequencing, the pMH3-CS1-Fc-his recombinant plasmid was successfully constructed. The recombinant plasmid was transfected into Chinese hamster ovary cell (CHO-S) by liposome. The expression of the CS1-Fc fusion protein in CHO-S cells was identified by flow cytometry after G418 pressure screening. Next, the CS1-Fc fusion protein was purified by nickel column. Western-blot analysis showed that molecular weight of the fusion protein was about 70 kDa was identified by Western blotting. The CS1-Fc fusion protein couldeffectively detect the expression rate of CS1 CAR and promote the activation, proliferation andcytokines secretion of the CS1 CAR-T cells. The results will lay the experimental foundation for the in vitro detection and potentiation of CAR-T cells in multiple myeloma treated with CS1 CAR-T cell.


Assuntos
Eucariotos , Mieloma Múltiplo , Animais , Células CHO , Cricetinae , Cricetulus , Humanos , Proteínas Recombinantes de Fusão , Proteínas Recombinantes
12.
Rinsho Ketsueki ; 61(1): 20-26, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32023597

RESUMO

We retrospectively evaluated the efficacy of pomalidomide/cyclophosphamide/dexamethasone (PCd) treatment in seven patients with extramedullary disease (EMD). Three of the seven patients achieved VGPR (very good partial response) with PCd therapy. We handled a patient complicated with secondary plasma cell leukemia, which was completely cured with PCd regimen and succeeded to autologous stem cell transplantation. In addition, there were no severe infections during the treatment period. This is the first report demonstrating the efficiency and tolerability of PCd treatment for EMD.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Ciclofosfamida , Dexametasona , Humanos , Mieloma Múltiplo/tratamento farmacológico , Recidiva , Estudos Retrospectivos , Talidomida/análogos & derivados , Transplante Autólogo
13.
Instr Course Lect ; 69: 625-640, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017756

RESUMO

It is important to review the physics of current MRI developments in nontraumatic spinal imaging and their specific applications for assessing the bone marrow. Techniques include chemical shift imaging and its use in differentiating aggressive from benign lesions and in confirming the presence of diffuse red marrow conversion, which may mimic diffuse marrow infiltration in metastatic disease. The principles of dynamic contrast MRI and its uses in multiple myeloma and discriminating between postoperative change/scarring versus recurrence in soft-tissue tumors warrant discussion. The basic physics of diffusion-weighted imaging (DWI) in bone marrow pathologies are distinguished from the principles of DWI as applied to solid organs, and DWI is used in the staging of multiple myeloma and in differentiating between benign versus malignant compressive vertebral fractures. The orthopaedic surgeon should be knowledgeable about whole-body MRI principles and its uses in staging multiple myeloma and sarcoma. Knowledge about PET-MRI principles and its limitations as well as its potential use in assessing the subchondral bone plate and bony remodeling is also important. This technique may play a role in the future for predicting progression to osteoarthritis.


Assuntos
Medula Óssea/anormalidades , Anormalidades Musculoesqueléticas/diagnóstico por imagem , Coluna Vertebral , Humanos , Imagem por Ressonância Magnética , Mieloma Múltiplo , Recidiva Local de Neoplasia , Fraturas da Coluna Vertebral
14.
Zhonghua Xue Ye Xue Za Zhi ; 41(1): 10-15, 2020 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-32023748

RESUMO

Objective: To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination. Results: Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively. Conclusions: Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.


Assuntos
Mieloma Múltiplo , Aberrações Cromossômicas , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Prognóstico , Estudos Retrospectivos
16.
Ann Hematol ; 99(3): 581-589, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31965271

RESUMO

Patients always have different responses to the same treatment due to the heterogeneity of multiple myeloma (MM). However, the relationship between monoclonal protein (M-protein) reduction rates during treatment and survival prognosis in MM patients remains controversial. We retrospectively analyzed 198 newly diagnosed MM patients who received regular bortezomib-based chemotherapy for at least 2 cycles and subsequent autologous stem cell transplantation (ASCT) plus continuous maintenance. The relationship between the early M-protein reduction rates and survival prognosis was evaluated. This study is the first to divide patients into three patterns, namely, A, B, and C, according to the M-protein reduction rate during the first two therapy cycles. The results showed that pattern B patients with progressive reduction in M-protein had better progression-free survival (PFS) and overall survival (OS) than did pattern A or C patients with precipitating or slow M-protein reduction (75.33 ± 18.81 versus 41.23 ± 9.13 or 26.60 ± 6.67 months; P < 0.001; 117.33 ± 18.44 versus 71.00 ± 10.06 or 39.73 ± 24.10 months; P = 0.003, respectively). In addition, biological analysis showed that pattern A + C patients had higher international staging system (ISS) stage III proportions (P = 0.008) and lactate dehydrogenase (LDH) elevations (P = 0.044) than pattern B patients. Furthermore, pattern A + C was a significant independent adverse parameter for PFS and OS (HR = 2.62, P = 0.001; HR = 2.15, P = 0.022, respectively). Thus, our results demonstrate that pattern A + C indicates an inferior survival prognosis in MM.


Assuntos
Bortezomib/administração & dosagem , Imunoglobulinas/sangue , Mieloma Múltiplo , Proteínas do Mieloma/metabolismo , Transplante de Células-Tronco , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Taxa de Sobrevida
18.
DNA Cell Biol ; 39(3): 368-378, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31971825

RESUMO

Nuclear protein 1 (NUPR1) is a stress-related small molecule and plays important roles in various tumors, including multiple myeloma (MM). Autophagy is essential for maintaining cellular homoeostasis in response to stress and, together with apoptosis, determines cell fate. Previous studies indicate that NUPR1 is involved in cancer progression of MM, but the underlying mechanisms have not been elucidated. In this study, we confirmed that NUPR1 and basal autophagy markers were highly expressed in the bone marrow of MM patients. The overexpression of NUPR1 was correlated with staging (both by Revised International Staging System [RISS] and Durie-Salmon [D-S] Staging System), levels of hemoglobin and calcium, and bone marrow plasma cell ratio in the MM patients. NUPR1 silencing reduced autophagy activities and induced apoptosis in U266 and RPMI 8226. We further observed a decrease in NUPR1 silencing-induced apoptosis in the presence of rapamycin, while an increase in apoptosis after chloroquine and 3-methyladenine treatment. Analysis of the mechanism indicated that PI3K/AKT/mTOR pathway was involved in autophagy-mediated apoptosis upon NUPR1 knockdown. In summary, our results demonstrate that NUPR1 silencing suppresses autophagy activities and induces autophagy-mediated apoptosis in MM cells through the PI3K/AKT/mTOR pathway, which exhibits potential as a treatment strategy for MM.


Assuntos
Apoptose , Autofagia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/genética , Transdução de Sinais , Adenina/análogos & derivados , Adenina/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Cloroquina/farmacologia , Inativação Gênica , Humanos , Mieloma Múltiplo/genética , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
Expert Opin Ther Pat ; 30(3): 159-162, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944149

RESUMO

Introduction: KIR is an inhibitory receptor expressed by natural killer cells that suppress the immune response against tumor cells. There is a great need to discover and develop new therapies focused on inhibiting the action of KIR and consequently improving the immune response in the various types of cancer. Authors of US9879082 and US2018208652 patents propose a method to eradicate cancer that utilizes anti-KIR antibody.Areas covered: US9879082 and US2018208652 patents describe an anti-KIR antibody, a pharmaceutical composition that contains it, and their application for cancer treatment, particularly, multiple myeloma and acute myeloid leukemia. Anti-KIR antibody is used to a dosage of 0.0003-3 mg antibody/kg patient weight, and is suspended in an isotonic solution consisting of sodium phosphate, sucrose, NaCl, and polysorbate 80.Expert opinion: The results of the clinical trials only support trials regarding the pharmacokinetic, pharmacodynamic, safety, and tolerability. In addition, these results demonstrate that treatment with the anti-KIR antibody can induce an antitumor response in cancer patients.


Assuntos
Anticorpos/administração & dosagem , Imunoterapia/métodos , Receptores KIR/antagonistas & inibidores , Animais , Anticorpos/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Patentes como Assunto , Receptores KIR/imunologia
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