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BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
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Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.
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Artemisia , Rinite Alérgica , Humanos , Alérgenos , Pólen/efeitos adversos , Rinite Alérgica/terapia , Rinite Alérgica/etiologia , Taurina , Metabolômica , Imunoterapia , Resultado do Tratamento , Dessensibilização Imunológica/efeitos adversosRESUMO
BACKGROUND AIMS: Currently available treatment methods for advanced plasmacytoma include surgery, chemotherapy, radiotherapy, immunomodulatory agents, hematopoietic stem cell transplantation and donor lymphocyte infusion. We report a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old Asian man with multiple bone lesions, in whom autologous cytokine-induced killer (CIK) cells were administered in an effort to eliminate residual tumor lesions. METHODS: CIK cells were infused monthly for 21 courses. RESULTS: The patient has survived 63 months since the first hospital visit without disease progression for 40 months. CONCLUSIONS: This case represents the first report of autologous CIK cell immunotherapy used successfully to suppress multiple solitary plasmacytomas and resolve bone lesions.
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Neoplasias Ósseas/terapia , Vacinas Anticâncer , Células Matadoras Induzidas por Citocinas/transplante , Transplante de Células-Tronco Hematopoéticas , Imunoterapia/métodos , Plasmocitoma/terapia , Idoso , Povo Asiático , Neoplasias Ósseas/imunologia , Células Matadoras Induzidas por Citocinas/imunologia , Intervalo Livre de Doença , Humanos , Masculino , Plasmocitoma/imunologia , Transplante AutólogoRESUMO
This study aimed to develop effective adsorbents for capturing radioactive iodine in nuclear power waste gas. Two zinc metal-organic frameworks (Zn-MOFs) were synthesized and found to have favorable properties such as a large surface area, thermal stability, surface rich in π-electron-containing nitrogen, and redox potential. Adsorption experiments revealed maximum capacities of 1.25 and 1.96 g g-1 for the MOFs at 75 °C, with the pseudo-second-order kinetic model fitting the data well. The Langmuir equation provided a better fit in cyclohexane, with maximum adsorption amounts of 249 and 358 mg g-1 for Zn-MOF-1 and Zn-MOF-2, respectively. The MOFs were also stable during six cycles of adsorption and desorption. Furthermore, electron transfer occurred due to the synergistic adsorption of Zn, N, and O atoms, resulting in the conversion of some iodine to polyiodide. Zn-MOF-2 exhibited better chemisorption than Zn-MOF-1 due to a smaller highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap. Notably, it was discovered that N-containing radicals had stronger interactions with iodine compared to radicals without N. These findings provide valuable insights into MOF synthesis and environmental protection.
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AIMS: This case series aimed to evaluate the effects of treatment for allergic rhinitis (AR) in AR-diagnosed children with previous diagnosis of tic disorders/attention-deficit/hyperactivity disorders (TD/ADHD) but unresponsive to behavioral or medical treatment. MATERIALS AND METHODS: Between July 2016 and June 2021, children diagnosed with AR in our hospital were enrolled. All were diagnosed with TD/ADHD refractory to behavioral or medical treatment. The demography and clinical information were collected from medical records. The outcomes were visual analogue scale (VAS) for AR severity, Yale Comprehensive Tic Severity Scale (YGTSS) for TD symptoms, and Attention-Deficit Hyperactivity Screening Scale (SNAP-IV) for ADHD symptoms. RESULTS: A total of 27 children (18 boys, 9 girls) were included, with a mean age 7.4 ± 2.9 years (3 - 17 years). They had undergone behavioral or medical treatment of TD/ADHD for 3.6 ± 1.9 years but without significant improvement in TD/ADHD symptoms. After 2-6 months of systematic treatment for AR, VAS was decreased to 0.4 ± 0.1 from 0.8 ± 0.2, YGTSS to 3.5 ± 0.7 from 6.8 ± 1.4, and SNAP-IV to 0.4 ± 0.1 from 0.6 ± 0.2 (all p < 0.001). No recurrence of TD/ADHD symptoms was reported during a mean follow-up of 2.4 ± 1.1 years (0.5 - 5 years). CONCLUSION: AR treatment improves TD/ADHD outcomes in children with difficult-to-treat TD/ADHD. In TD/ADHD children who are unresponsive to behavioral or drug treatment and have AR-related symptoms, AR examination and treatment are recommended for better prognosis.
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BACKGROUND: Allergic rhinitis (AR) is a common allergic disease globally and its prevalence is increasing year by year. This study aimed to analyze the prevalence and risk factors of self-reported AR among the Chinese National Railway train crew in the China Railway Beijing Group.METHODS: This prospective questionnaire study surveyed 1511 randomly recruited train crewmembers from 20 cities in the China National Railway network, and 494 reported having AR. A structured questionnaire was tailored, designed, and delivered electronically to all subjects. Prevalence of and risk factors for AR were analyzed based on self-reported results.RESULTS: The prevalence of self-reported AR among train crewmembers was 32.6%. Among respondents, 86.03% worked in passenger cars and 64.6% reported having worse AR symptoms while on trains. AR frequencies were 40.15% perennially and 59.85% seasonally. Among the Total Nasal Symptoms Scores (TNSS), significant differences were found between rhinorrhea and sneezing and between nasal itching and sneezing. The Rhino-Conjunctivitis Quality of Life Questionnaire (RQLQ) showed significant correlations between all seven sections. TNSS was significantly associated with the RQLQ. Scores of both the TNSS and RQLQ showed that the severity of AR symptoms (rp = 0.103) and the impact on quality of life (rp = 0.113) correlated significantly with seniority.CONCLUSIONS: The prevalence of self-reported AR among train crew working in passenger cars is higher than that of the general Chinese population. The severity of AR symptoms and the impact on quality of life are associated with seniority, meaning the number of years working on trains.Yu R-L, Ning H-Y, Lan T-F, He H, Zheng C-B, Wang X-Y, Wang H-T, Wang X-Y. Self-reported allergic rhinitis prevalence and risk factors in employees of the China National Railway. Aerosp Med Hum Perform. 2023; 94(11):821-826.
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Qualidade de Vida , Rinite Alérgica , Humanos , Prevalência , Estudos Prospectivos , Rinite Alérgica/epidemiologia , Fatores de Risco , Autorrelato , EspirroRESUMO
The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3 × 10(9)) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum ß2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients.
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Células Matadoras Induzidas por Citocinas/transplante , Neoplasias Hematológicas/cirurgia , Imunoterapia Adotiva , Síndromes Mielodisplásicas/cirurgia , Terapia de Salvação , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/transplante , Comorbidade , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Interferon gama/farmacologia , Interleucina-2/farmacologia , Interleucina-2/uso terapêutico , L-Lactato Desidrogenase/sangue , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Síndromes Mielodisplásicas/tratamento farmacológico , Projetos Piloto , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Timopentina/farmacologia , Timopentina/uso terapêutico , Resultado do Tratamento , Microglobulina beta-2/análiseRESUMO
Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs. Methods: Artemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders. Results: Artemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT. Conclusion: Serum LTA4H may be a potential biomarker for early prediction of an effective AIT.
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Biomarcadores , Dessensibilização Imunológica , Epóxido Hidrolases/sangue , Adolescente , Adulto , Alérgenos/imunologia , Criança , Cromatografia Líquida , Tomada de Decisão Clínica , Dessensibilização Imunológica/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Prognóstico , Proteômica/métodos , Rinite Alérgica Sazonal/sangue , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/terapia , Espectrometria de Massas em Tandem , Resultado do Tratamento , Fluxo de Trabalho , Adulto JovemAssuntos
Amifostina/administração & dosagem , Azacitidina/análogos & derivados , Células Matadoras Induzidas por Citocinas/transplante , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Idoso de 80 Anos ou mais , Azacitidina/administração & dosagem , Células Cultivadas , Terapia Combinada/métodos , Decitabina , Gerenciamento Clínico , Progressão da Doença , Quimioterapia Combinada , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Síndromes Mielodisplásicas/diagnóstico , Transplante AutólogoRESUMO
This study was purposed to evaluate the effectiveness and safety of autologous cytokine induced killer (CIK) cells combined with chemotherapy in treatment of elderly patients with acute myeloid leukemia. Peripheral blood mononuclear cells (PBMNC) were isolated from 5 elderly patients with acute myeloid leukemia, and then augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. The autologous CIK cells thus obtained were infused back to individual patients, 28 days as one cycle. The changes in cellular immune function, incidence of infection, independence of hematoglobin or blood transfusion, and progression of disease were observed and assessed before and after therapy. The results showed that the 46 cycles of CIK cell infusion were performed for 5 patients, no adverse reaction was observed in these patients. The percentages of CD3(+), CD3(+)CD8(+) and CD3(+)CD56(+) increased significantly (P < 0.05), The therapy of CIK could significantly reduce the incidence of infection (P < 0.05) and shorten the time of high fever in AML patients (P < 0.05). CIK also could reduce the volume of erythrocyte infusion to maintenance hematoglobin level (P < 0.05). We found that although CIK could not change the outcome of AML, the combination of CIK and chemotherapy could control patients' condition and prolong their survival during the development and end stage of AML. It is concluded that autologous CIK cells combined with chemotherapy is safe and efficacious for the elderly patients with acute myeloid leukemia.
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Células Matadoras Induzidas por Citocinas , Leucemia Mieloide Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , MasculinoRESUMO
BACKGROUND: In recent years, a number of randomized controlled trials (RCTs) have reported on lenalidomide as a treatment for multiple myeloma (MM). Herein, we report results of a meta-analysis of RCTs examining the efficacy and safety of lenalidomide for MM. PATIENTS AND METHODS: Databases were searched using the terms "lenalidomide or revlimid AND multiple myeloma."RCTs evaluating initial or maintenance therapeutic outcomes were included. Main outcome measures were response rates, progression-free survival (PFS), overall survival, and adverse events. RESULTS: Seven trials were included (Nâ=â192-614 participants). Lenalidomide doses and treatment regimens differed between trials. Complete response (CR) and very good partial response (VGPR) risk ratios (RR) favored lenalidomide over placebo (CRâ=â2.54, 95% confidence interval [CI]â=â1.29-5.02; VGPRâ=â2.82, 95% CIâ=â1.30-6.09). The PFS hazard ratio favored lenalidomide over placebo (0.37, 95% CIâ=â0.33-0.41). For adverse events, neutropenia, deep vein thrombosis (DVT), infection, and hematologic cancer RR favored placebo over lenalidomide (neutropenia: 4.74, 95% CIâ=â2.96-7.57; DVT: 2.52; 95% CI: 1.60-3.98; infection: 1.98; 95% CI: 1.50-2.62; hematologic cancer: 3.20; 95% CI: 1.28-7.98). CONCLUSIONS: Lenalidomide is an effective treatment for MM; however, treatment-related adverse events must be considered and appropriate adjustments and/or prophylactic treatment should be initiated where possible.
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Mieloma Múltiplo/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Talidomida/análogos & derivados , Intervalo Livre de Doença , Humanos , Lenalidomida , Segunda Neoplasia Primária , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
The purpose of this study was to explore the clinicopathological features, therapy and prognostic factors of elderly patients with non-Hodgkin's lymphoma (NHL). The clinical data including general clinical characteristics, pathological features, chemotherapy selection and treatment response of 30 patients with NHL in our hospital from January 2003 to December 2012 were analyzed retrospectively. The survival was analyzed by using Kaplan-Meier methods, and the prognosis was evaluated by COX regression multivariate analysis model. The clinical parameters selected include age, Ann Arbor stage, international prognostic index (IPI), B symptom and lactate dehydrogenase (LDH) levels. The results showed that all the patients suffered from underlying disease, and the cardiovascular disease (hypertension, coronary heart disease, arrhythmia) is the most common, and minority (8/30) combined with secondary tumor, the 63% (19/30) cases had B symptoms at diagnosis. only 2 cases were diagnosed as T-cell lymphoma; the 93% (28/30) cases combined with B-cell lymphoma, 57% (17/28) of them combined with diffuse large B-cell lymphoma. Ann-Arbor stage ≤ IIwas 37% (11/30);10(37%) patient's IPI score was ≤ 2, and 67% (20/30) was scored 3-5; 13(43%) patient's serum LDH level was abnormal. Modified R-CHOP chemotherapy was given individually on the basis of clinical features. The patients achieved complete remission, partial remission, stable disease, or progressive disease accounted for 14 (46.7%), 13 (43.3%), 1 (3.3%), and 2 (6.7%), respectively; the total reaction rate was 90% after 4 cycles of chemotherapy; the overall survival (OS) rate at 1 and 2 years was 73.3% and 43.3%, and progression-free survival (PFS)rate at 0.5 and 1 years was 62.2% and 54.9%; multivariate analysis by COX regression showed that B symptoms and Ann-Arbor stage were independent factors (P = 0.014, 0.039; RR = 6.678, 4.939, respectively) affecting the OS of elderly NHL, and IPI score affected PFS independently. It is concluded that elderly patients with NHL usually are of late stage at newly diagnosis and have suffered from underlaying diseases. Besides strengthening supportive treatment, modified R-CHOP chemotherapy should be given individually according to different prognosis. B symptoms and Ann-Arbor stage >II are indicators for poor prognosis of elderly NHL.
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Linfoma não Hodgkin/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Acute tumor lysis syndrome (ATLS) is a recognized complication of the treatment of malignant lymphomas and is associated with significant morbidity and mortality. However, there have been few reports of the occurrence of ATLS in patients treated with rituximab. This study reports 2 patients with high-grade diffuse large B-cell non-Hodgkin's lymphoma who presented high tumor load, were sensitive to treatment and had multiple risk factors for ATLS. Both patients developed ATLS after treatment with rituximab and, despite aggressive supportive therapy, died of multiple organ failure. These cases illustrate that ATLS can occur after treatment with rituximab and that a high index of suspicion is necessary for the prompt diagnosis of ATLS.
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Anticorpos Monoclonais Murinos/efeitos adversos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/etiologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Rituximab , Resultado do TratamentoRESUMO
BACKGROUND: Human xenograft models, resulting from orthotopic transplantation (implantation into the anatomically correct site) of histologically intact tissue into animals, are important for investigating local tumor growth, vascular and lymphatic invasion at the primary tumor site and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We used surgical orthotopic transplantation to establish a nude mouse model of primary hepatic lymphoma (PHL), HLBL-0102. We performed orthotopic transfer of the HLBL-0102 tumor for 42 generations and characterized the tumor cells. The maintenance of PHL characteristics were supported by immunohistochemical and cytogenetic analysis. We also report the antitumor effect of Cantide, an antisense phosphorothioate oligonucleotide against hTERT, on the growth of HLBL-0102 tumors. We showed a significant, dose-dependent inhibition of tumor weight and serum LDH activity in the orthotopically transplanted animals by Cantide. Importantly, survival was prolonged in Cantide-treated HLBL-0102 tumor-bearing mice when compared to mock-treated mice. CONCLUSIONS/SIGNIFICANCE: Our study provided the basis for the development of a clinical trial protocol to treat PHL.
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Neoplasias Hepáticas/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Oligonucleotídeos Fosforotioatos/farmacologia , Telomerase/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Linfoma de Células B/enzimologia , Linfoma de Células B/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Transplante de Neoplasias , Telomerase/metabolismo , Transplante HeterólogoRESUMO
This study was purposed to evaluate the safety and curative effect of autologous cytokine induced killer cells (CIK) combined with low-dose IL-2 regimen containing immune enhancement of thymic peptide on elderly patients with B-cell chronic lymphocytic leukemia (B-CLL). Thymic peptide α1 was subcutaneously given as the immunoenhancement agent at a dose of 1.6 mg/d, 14 days as one cycle. Peripheral blood mononuclear cells (PBMNC) from 5 patients with B-CLL were isolated once a week to induce ex vivo CIK cells through culture in the context of interferon (IFN)-γ, interleukin (IL)-2 and anti-CD3 monoclonal antibody. The PBMNC were separated from patients before and after 14 days as one cycle of thymic peptide α1 administration. Parameters of amplification ability, effector cells quantity, lymphocyte subgroups percentage and antitumor cytotoxicity were compared before and after thymic peptide administration. The 5 patients were treated with CIK cells combined with low-dose IL-2 regimen immediately after injection of thymic peptide α1. The CIK cells plus low-dose IL-2 regimen containing thymic peptide enhancement was defined as: thymic peptide α1 1.6 mg/d was subcutaneously administered once every other day; (4 - 6) ×10(9) of CIK cells were transfused followed by IL-2 subcutaneous administration of 1 mU/d on days 1-10, 28 days as one cycle. Clinical evaluation parameters including cellular immunity function, CLL related biomarkers, disease state and infectious frequency and degree were investigated before and after CIK cells infusion puls IL-2. The results showed that the amount of amplified CIK cells, the percentage and amplification times of effector cells and antitumor cytotoxicity more significantly increased after thymic peptide α1 treatment than before its use (P < 0.05). The total 46 cycles of CIK cells infusion plus IL-2 were completed in the 5 CLL patients. No adverse reaction was observed. After treatment of CIK cells plus IL-2, the general conditions of 5 CLL patients were to different extent improved. Simultaneously, percentages of CD3(+), CD3(+)CD8(+), and CD3(+)CD56(+) cells in peripheral blood remarked by raised (P < 0.05), the serum level of ß2 microglobulin was significantly declined (P < 0.05), and the frequency and degree of infection was also decreased (P < 0.05). Following CIK cells plus IL-2 therapy, the transformation of disease state from partial remission (PR) to complete remission was seen in 3 patients, from stable disease (SD) to PR in 1 patient, and from progress of disease to SD in 1 patient. It is concluded that the regimen of autologous CIK cells combined with low-dose IL-2 containing immune enhancement of thymic peptide is safety and effective for the treatment of elderly patients with B-CLL.
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Células Matadoras Induzidas por Citocinas/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Timosina/imunologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , MasculinoRESUMO
To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from nine elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients; infusion was repeated every 4 weeks for 32 weeks (eight cycles). Patients were assessed for changes in lymphocyte subgroup, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL), and survival. Prior to CIK infusion, two patients were in complete remission and seven patients were in partial remission. After autologous CIK cell transfusions, the proportion of CD3+, CD3+CD8+, and CD3+CD56+ cells were significantly increased compared with baseline (P < 0.05); whereas serum levels of ß2-microglobulin and LDH were significantly decreased (P < 0.05). The lymphoma symptoms were reduced and QOL was improved (P < 0.05) in all patients. All patients achieved complete remission at study endpoint. No adverse reactions were reported. Autologous CIK cell immunotherapy is safe and efficacious for the treatment of elderly patients with diffuse large B-cell lymphoma.
Assuntos
Células Matadoras Induzidas por Citocinas/transplante , Imunoterapia , Linfoma Difuso de Grandes Células B/terapia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Complexo CD3/imunologia , Complexo CD3/metabolismo , Antígeno CD56/metabolismo , Antígenos CD8/metabolismo , Células Cultivadas , Células Matadoras Induzidas por Citocinas/imunologia , Feminino , Humanos , Interferon gama/farmacologia , Interleucina-2/farmacologia , L-Lactato Desidrogenase/sangue , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Macroglobulinas/análise , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Transplante Autólogo , Resultado do TratamentoRESUMO
BACKGROUND: The pathophysiology and etiology of chronic rhinosinusitis with nasal polyps (CRSwNP) are poorly understood. Although a potential role of staphylococcal enterotoxins (SE) in the pathogenesis of CRSwNP has been detected, additional studies are needed on the impact of SE on nasal epithelial cells. The purpose of this study was to evaluate the impact of Staphylococcus aureus enterotoxin B (SEB) on proinflammatory cytokine/chemokine releases in primary human nasal epithelial cells (HNEC) of subjects with and without CRSwNP and the inhibitory effect of glucocorticoid on it. METHODS: Epithelial cells of NP and inferior turbinate (IT) were cultured serum free under stimulus of SEB, and interleukin (IL)-1beta, respectively. Furthermore, the inhibitory effect of glucocorticoid on the proinflammatory response was investigated by addition of dexamethasone. In situ hybridization and Western immunoblot assays were used to investigate the proinflammatory impact of SEB on IL-5 and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels and protein production in HNEC. RESULTS: Results indicate (1) stimulation of HNEC with SEB resulted in increased IL-5 and GM-CSF expression, which could be suppressed by dexamethasone (p < 0.05), and SEB at concentrations of 1-100 ng/mL effectively promoted IL-5 and GM-CSF release by HNEC (p < 0.05); (2) patients with CRSwNP showed a significantly increased expression of IL-5 and GM-CSF in HNEC than patients without CRSwNP (p < 0.05); and (3) the expression of IL-5 and GM-CSF was significantly up-regulated under the stimulus of SEB compared with IL-1beta (p < 0.05). CONCLUSION: SEB acts as a superantigen and exhibits a dramatic proinflammatory impact on HNEC, which can be inhibited by the addition of glucocorticoid.
Assuntos
Dexametasona/farmacologia , Enterotoxinas/farmacologia , Células Epiteliais/efeitos dos fármacos , Glucocorticoides/farmacologia , Mucosa Nasal/patologia , Rinite/patologia , Sinusite/patologia , Western Blotting , Doença Crônica , Enterotoxinas/antagonistas & inibidores , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Hibridização In Situ , Interleucina-5/antagonistas & inibidores , Interleucina-5/biossíntese , Interleucina-5/genética , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/etiologia , Pólipos Nasais/patologia , RNA Mensageiro/genética , Rinite/tratamento farmacológico , Rinite/etiologia , Sinusite/tratamento farmacológico , Sinusite/etiologia , Staphylococcus aureus/imunologiaRESUMO
OBJECTIVE: To evaluate the effects of Staphylococcus aureus enterotoxin B (SEB) on proinflammatory cytokine/chemokine releases in primary human nasal epithelial cell (HNEC). METHODS: Epithelial cells of nasal polyps (NP) and inferior turbinate (IT) were cultured without serum under stimulus of SEB 1, 10, 100 ng/ml, IL-1beta 20 ng/ml and SEB 10 ng/ml + dexamethasone 13 ng/ml for 12,24 and 48 h, respectively. The expression of IL-5 and Granulocyte-macrophage colony stimulating factor (GM-CSF) mRNA derived from epithelial cells was detected by in situ hybridization. RESULTS: (1) The expression of IL-5 and GM-CSF mRNA was time and dose-dependent, and reached to a peak under SEB 10 ng/ml for 24 h (P < 0.05). The mRNA expressed more intensively in epithelial cells from NP than IT (P < 0.05). (2) The expression of IL-5 and GM-CSF mRNA increased less under the stimulus of IL-1beta than SEB 10 ng/ml (P < 0.05). (3) The mRNA level of IL-5 and GM-CSF decreased under the stimulus of SEB + dexamethasone 13 ng/m when compared with the stimulus of SEB 10 ng/ml (P < 0.05). CONCLUSION: SEB showed proinflammatory effects on HNEC.
Assuntos
Enterotoxinas/farmacologia , Células Epiteliais/metabolismo , Mucosa Nasal/metabolismo , Células Cultivadas , Dexametasona/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-5/metabolismo , Mucosa Nasal/citologia , Mucosa Nasal/patologia , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of glucocorticoid on tissue remodeling of nasal mucosa from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) after endoscopic surgery. METHODS: Nasal mucosa obtained from 30 cases of CRSwNP during nasal endoscopic surgery were considered as preoperation group. These patients were equally divided into two groups after surgery, ie. glucocorticoid group and contrast group. Uncinate process mucosa samples from 6 patients during septoplasty were considered as normal control group. Epithelial damage and expressions of transforming growth factor-beta1 (TGF-beta1) and collagen III were studied by light microscopy and immunohistochemistry. RESULTS: In nasal mucosa samples of preoperation group, epithelial damage showed 90% (27/30) of stage 3 and 10% (3/30) of stage 2; TGF-beta1 positive cells and collagen III positive basement membrane with more than 20 microm were seen in 87% (26/30) and 97% (29/30) of samples, respectively. No significant difference was observed in morphology of nasal mucosa and expressions of TGF-beta1 and collagen III between glucocorticoid group and contrast group at 1th month after surgery. At 3th month after surgery, epithelial damage displayed 53% (8/15) of stage 3, 33% (5/15) of stage 2 and 14% (2/15) of stage 1 in contrast group; however, 93% (14/15) of stage 0 and 7% (1/15) of stage 1 in glucocorticoid group. The difference of epithelial damage between two groups was significant (Uc = 4.481, P < 0.05). The amount of TGF-beta1 positive cell was markedly higher in contrast group than in glucocorticoid group (t = 2.32, P < 0.05). The thickness of basement membrane was above 20 microm in 67% of contrast group (10 cases) and 27% of glucocorticoid group (4 cases); the difference between the two groups was significant (P < 0.05). CONCLUSIONS: Tissue remodeling is present in nasal mucosa of CRSwNP after endoscopic surgery. Early and appropriate administration of glucocorticoid plays an important role in inhibition of tissue remodeling and prevention of relapse. Postoperative follow-up should not be less than 3 month.