RESUMO
BACKGROUND: The aim of this study was to identify the optimal equation that accurately estimates the glomerular filtration rate (GFR) and the chronic kidney disease (CKD) stage in the Chinese population. METHODS: A total of 1296 Chinese patients aged 18-65 years old were enrolled in this study. The estimated GFRs (eGFRs) calculated separately by three Diet in Renal Disease (MDRD) equations and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were compared with the reference GFR (rGFR) measured by the 99Tcm-DTPA renal dynamic imaging method. RESULTS: By Bland-Altman analysis, eGFRcys and eGFRscr_cys performed similarly, showing the tightest limits of agreement among the six equations. They also achieved the first and second highest 30% and 50% accuracies. Using a combination of the serum creatinine and cystatin C levels (eGFRscr_cys) could improve the bias (-0.3 for eGFRscr_cys) of the equation and achieve the highest diagnostic accuracy for renal insufficiency (AUC60, 0.953; P < 0.05, except for eGFR_MDRD). All equations predicted stage 3 CKD with moderate accuracy (49.7-51.4%) and stage 5 CKD with good accuracy (90.2-96.4%). For stage 1 CKD, eGFRcys showed a higher percentage of misclassification than the other equations. All equations seemed to perform poorly at predicting stage 2 and 4 CKD, as compared to the other CKD stages. eGFRscr_cys was the best-performing equation in terms of accurate classification of the CKD stage based on the overall performance (kappa value, 0.423). CONCLUSION: For a Chinese population, the CKD-EPIscr_cys equation seems more suitable for estimating the GFR than the other equations. Each equation had its own advantages in predicting different CKD stages.
Assuntos
Povo Asiático/genética , Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
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
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.
Assuntos
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
OBJECTIVE: To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19). METHODS: The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes. RESULTS: A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform. CONCLUSION: SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.
Assuntos
COVID-19 , Proteínas Relacionadas à Folistatina , Sistema Hematopoético , Preparações Farmacêuticas , Biologia Computacional , Humanos , SARS-CoV-2Assuntos
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
OBJECTIVE: To screen new candidate molecular-targeted anti-leukemia compounds with potential functions of targeted up-regulating ID4 gene expression. METHODS: Promoter region of ID4 gene including the upstream - 3000 bp sequence of transcriptional start site and message RNA sequence were fished out. Online promoter analysis tools of TESS and Genomax were used to search possible sequence of transcriptional start site and message RNA sequence were fished out. Online promoter analysis tools of TESS and Genomax were used to search possible cis-acting structure from human transcription factor database. The activity of related drugs with potential effects upon ID4 gene expression was analyzed using SAGE database. GEO database was applied to search the gene expression profiling regulated by ID4 gene. Finally, similar analysis between gene expression profiling by ID4 and genome-wide profiling regulated by 163 known drugs or active compounds was manipulated to screen the drugs and candidate compounds with similar gene expression profiling with ID4 gene. MOLT4 cell line was treated with the above candidate active compounds to investigate the ID4 gene expression by RT-PCR assay. RESULTS: ID4 gene had a type II promoter with a typical TATA box in upstream -45 bp of transcription start site. The 1300 bp-length promoter of ID4 gene contained a few cis-acting structures classified into two function types, i. e. positive regulatory type, including transcription factors Spl and c-Myb, cAMP, glucocorticoid receptor (GR) and estrogen receptor (ER), and negative regulatory type, including Wilms tumor-1 (WT1) and early growth response-2 (EGR2). The similarity of gene expression profiling was identified between cAMP and ID4 gene. ID4 gene expression was induced in MOLT4 cell line after treatment with calcium dibutyryladenosine cyclophosphate at the concentration of 0.1 mmol/L. CONCLUSION: The comprehensive bioinformatic analysis, based upon the combination of regulatory sequence prediction of promoter, similarity analysis of gene expression profiling and literature review, can be considered as a practical tool in screening the candidate drugs with the activity of targeted regulating functional genes. Calcium dibutyryladenosine cyclophosphate can induce ID4 gene expression in leukemic cells.
Assuntos
Biologia Computacional , Proteínas Inibidoras de Diferenciação/genética , Linhagem Celular Tumoral , Humanos , RNA Mensageiro/genética , Sequências Reguladoras de Ácido Nucleico , Análise de Sequência de DNA , Regulação para CimaRESUMO
OBJECTIVE: To investigate the prognosis-related miRNA histological features and clinical significance of lung adenocarcinoma. METHODS: Using The Cancer Genome Atlas (TCGA) data, the miRNA expression profile data of human lung adenocarcinoma were searched for differential analysis, and the prognosis-related miRNAs were screened by Cox risk regression model. The targeted miRNAs were predicted by mirwalk analysis platform, KEGG functional enrichment analysis, and finally, predict the function of prognosis-related miRNAs. RESULTS: A total of 46 differential miRNAs in lung adenocarcinoma were screened, including 19 up-regulated and 27 down-regulated. Six prognostic-related miRNAs were screened by Cox survival analysis, namely hsa-mir-21, hsa-mir-142, hsa-mir-200a high expression, hsa-mir-101, hsa-let-7c, hsa-mir-378e low expression, hsa-mir-21 and hsa-mir-378e were associated with poor prognosis in patients with lung adenocarcinoma, and the survival time was shortened significantly (P<0.05, AUC=0.618). KEGG analysis showed that the above prognosis-related miRNA targeting regulatory genes were related with immune response pathways, miRNA and cancer pathways, metabolic pathways and so on. CONCLUSIONS: Hsa-mir-21 and hsa-mir-378e are associated with poor prognosis of lung adenocarcinoma, and may be used as a molecular marker for prognosis of lung adenocarcinoma after further clinical verification.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Biomarcadores Tumorais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs , PrognósticoRESUMO
Penicillium marneffei infection in human immunodeficiency virus (HIV)-negative patients is addressed far less often. In this article, a small cohort of HIV-negative patients who disseminated P. marneffei infection was included. Sites of infection were found from blood culture, as subcutaneous nodules, or from lymph node biopsy. Fever, rash, swollen lymph nodes, anaemia and weight loss were common characteristics in most infected patients. The signs and symptoms are diverse and create challenges for accurate diagnosis. This paper will assist our understanding of this disease and contribute to an appropriate regime of therapy, thus improving the health of P. marneffei-positive patients.
Assuntos
Antifúngicos/uso terapêutico , Gerenciamento Clínico , Micoses/diagnóstico , Micoses/tratamento farmacológico , Penicillium/isolamento & purificação , Idoso , Sangue/microbiologia , Estudos de Coortes , Feminino , Humanos , Linfonodos/microbiologia , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/patologia , Tela Subcutânea/microbiologiaRESUMO
OBJECTIVE: The co-occurrence of blue rubber bleb nevus syndrome (BRBNS) and ventricular septal defects is rare. Here we present a case of BRBNS in a 15-year-old boy who was born with multiple cavernous hemangiomas and a ventricular septal defect. Examinations revealed the presence of hemangioma lesions in the subcutaneous and mucosal tissues as well as in the cerebrum, nasopharynx, tongue, esophagus, gastric body, sigmoid colon and adrenal gland. Combined imaging modalities played an important role in the diagnosis of hemangioma lesions.
Assuntos
Neoplasias Gastrointestinais/complicações , Comunicação Interventricular/complicações , Hemangioma Cavernoso , Nevo Azul/complicações , Neoplasias Cutâneas/complicações , Adolescente , Hemangioma , Humanos , MasculinoRESUMO
Amifostine is a cytoprotective drug that was initially used to control and treat nuclear radiation injury and is currently used to provide organ protection in cancer patients receiving chemotherapy. Clinical studies have also found that amifostine has some efficacy in the treatment of cytopenia caused by conditions such as myelodysplastic syndrome and immune thrombocytopenia, both of which involve megakaryocyte maturation defects. We hypothesized that amifostine induced the differentiation of megakaryocytes and investigated this by exposing the human Dami megakaryocyte leukemia cell line to amifostine (1 mmol/L). After 12 days of amifostine exposure, optical microscopy showed that the proportion of Dami cells with diameters >20 µm had increased to 24.63%. Transmission electron microscopy identified the development of a platelet demarcation membrane system, while flow cytometry detected increased CD41a expression and decreased CD33 expression on the Dami cell surface. Ploidy analysis found that the number of polyploid cells with >4N DNA content increased to 27.96%. We did not detect any elevation in the mRNA or protein levels of megakaryocytic differentiation-associated transcription factors GATA-binding factor 1 (GATA-1) and nuclear factor, erythroid 2 (NF-E2), but nuclear import assay revealed an increased nuclear translocation of these proteins. These findings indicate that amifostine induced the differentiation of Dami cells into mature megakaryocytes via a mechanism involving increased nuclear translocation of the transcription factors, NF-E2 and GATA-1.
Assuntos
Amifostina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Progenitoras de Megacariócitos/citologia , Células Progenitoras de Megacariócitos/efeitos dos fármacos , Megacariócitos/citologia , Megacariócitos/efeitos dos fármacos , Biomarcadores , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citoproteção , Humanos , Imunofenotipagem , Megacariócitos/metabolismo , Poliploidia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
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.
Assuntos
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.
Assuntos
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
The function of immune system degenerates in an aging-dependent manner and this results in immunosenescence. Human immune system includes two parts: genetic/innate immunity and adaptive immunity. The former is involved in monocytes, nature killer cells, and dendritic cells, the later is involved in acquired B and T lymphocytes. During the aging of immunity system, the both parts of immunity are damaged to some degree. Generally, innate immunity seems well-retained and the acquired immunity is degenerative seriously with aging. Immunocyte senescence is closely related to the elderly decreased ability to control infectious disease, cancer and to their generally poor response to vaccination. This review summarized the research progress on immunosenescence characteristics in aged phase.
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Envelhecimento/imunologia , Formação de Anticorpos , Imunidade Celular , Fatores Etários , Formação de Anticorpos/imunologia , Senescência Celular , Humanos , Imunidade Celular/imunologia , Ativação LinfocitáriaRESUMO
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.
Assuntos
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.
Assuntos
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
Objective of this study was to perform bioinformatics analysis of the characteristics of gene expression profiling regulated by amifostine and predict its novel potential biological function to provide a direction for further exploring pharmacological actions of amifostine and study methods. Amifostine was used as a key word to search internet-based free gene expression database including GEO, affymetrix gene chip database, GenBank, SAGE, GeneCard, InterPro, ProtoNet, UniProt and BLOCKS and the sifted amifostine-regulated gene expression profiling data was subjected to validity testing, gene expression difference analysis and functional clustering and gene annotation. The results showed that only one data of gene expression profiling regulated by amifostine was sifted from GEO database (accession: GSE3212). Through validity testing and gene expression difference analysis, significant difference (p < 0.01) was only found in 2.14% of the whole genome (460/192000). Gene annotation analysis showed that 139 out of 460 genes were known genes, in which 77 genes were up-regulated and 62 genes were down-regulated. 13 out of 139 genes were newly expressed following amifostine treatment of K562 cells, however expression of 5 genes was completely inhibited. Functional clustering displayed that 139 genes were divided into 11 categories and their biological function was involved in hematopoietic and immunologic regulation, apoptosis and cell cycle. It is concluded that bioinformatics method can be applied to analysis of gene expression profiling regulated by amifostine. Amifostine has a regulatory effect on human gene expression profiling and this action is mainly presented in biological processes including hematopoiesis, immunologic regulation, apoptosis and cell cycle and so on. The effect of amifostine on human gene expression need to be further testified in experimental condition.
Assuntos
Amifostina/farmacologia , Biologia Computacional , Perfilação da Expressão Gênica/métodos , Expressão Gênica/efeitos dos fármacos , Humanos , Análise em Microsséries , Anotação de Sequência MolecularRESUMO
OBJECTIVE: To evaluate the accuracy of sentinel lymph node mapping(SLM) in patients with rectal cancer by single-photon emission computed tomography (SPECT-CT) lymphoscintigraphy and carbon nanoparticles suspension injection. METHODS: Twelve patients with clinical T(1-2)N(0)M(0) rectal cancer were selected and locally injected with technetium-(99m)sulfur-colloid and carbon nanoparticles suspension by endoscope one day before surgery, followed by SPECT-CT scanning 1, 3 and 5 hours later. Radioactive isotope(RI) uptake of each sentinel node(SN) basin with location preoperatively determined by SPECT-CT was postoperatively calculated using gamma probe. Nodes with the highest RI uptake, the number of which was also pre-determined by SPECT-CT, was defined as SNs. Immunohistochemical cytokeratin staining was performed for all the SNs and non-SNs. RESULTS: The rate of sentinel node detection was 91.7%(11/12) with at least one SN(1-3) per patient. Ten cases showed metastasis-negative in SNs as well as all the resected regional nodes by immunohistochemical cytokeratin staining. Only one patient had positive nodes in both SN and non-SNs. The accuracy of SLM was 100%. CONCLUSION: SPECT-CT lymphoscintigraphy and carbon nanoparticles suspension injection can effectively detect the anatomic location and number of sentinel nodes, and improve the accuracy of SLM for rectal cancer.