RESUMO
Leukemia is a kind of hematopoietic stem cell malignant clonal disease. Drug therapy is the core treatment strategy for leukemia, but the current therapeutic drugs have defects such as low bioavailability, large adverse reactions and inconvenient intravenous administration. Targeted therapy can combine drugs with specific carcinogenic sites on cells to kill cancer cells and avoid damage to normal cells, which has gradually become the mainstream method of leukemia treatment. In addition, nanomedicine delivery systems can significantly improve drug efficacy through controlled size and targeted optimization of drug delivery by modification strategies. Therefore, the targeted treatment of leukemia based on nanomaterials has great research value and application prospect. This paper gives an overview of the current therapeutic strategies for leukemia, and then reviews the cutting-edge targeted therapeutic nanomaterials for leukemia, including organic nanomaterials (mainly carbon-based nanomaterials, lipid materials, polymers, etc.) and inorganic nanomaterials (mainly noble metal nanoparticles, magnetic nanoparticles, hollow mesoporous materials, etc.). The challenges and prospects for the future development of targeted nanomaterials in the treatment of leukemia are also briefly reviewed.
RESUMO
Myelodysplastic syndromes (MDS) encompass a collection of clonal hematopoietic malignancies distinguished by the depletion of peripheral blood cells. The treatment of MDS is hindered by the advanced age of patients, with a restricted repertoire of drugs currently accessible for therapeutic intervention. In this study, we found that ES-Cu strongly inhibited the viability of MDS cell lines and activated cuproptosis in a copper-dependent manner. Importantly, ferroptosis inducer IKE synergistically enhanced ES-Cu-mediated cytotoxicity both in vitro and in vivo. Of note, the combination of IKE and ES-Cu intensively impaired mitochondrial homeostasis with increased mitochondrial ROS, MMP hyperpolarized, down-regulated iron-sulfur proteins and declined oxygen consumption rate. Additionally, ES-Cu/IKE treatment could enhance the lipoylation-dependent oligomerization of the DLAT. To elucidate the specific order of events in the synergistic cell death, inhibitors of ferroptosis and cuproptosis were utilized to further characterize the basis of cell death. Cell viability assays showed that the glutathione and its precursor N-acetylcysteine could significantly rescue the cell death under either mono or combination treatment, demonstrating that GSH acts at the crossing point in the regulation network of cuproptosis and ferroptosis. Significantly, the reconstitution of xCT expression and knockdown of FDX1 cells have been found to contribute to the tolerance of mono treatment but have little recovery impact on the combined treatment. Collectively, these findings suggest that a synergistic interaction leading to the induction of multiple programmed cell death pathways could be a promising approach to enhance the effectiveness of therapy for MDS.
Assuntos
Cobre , Sinergismo Farmacológico , Ferroptose , Síndromes Mielodisplásicas , Ferroptose/efeitos dos fármacos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/metabolismo , Humanos , Animais , Cobre/química , Cobre/metabolismo , Piperazinas/farmacologia , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Imidazóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismoRESUMO
OBJECTIVE: Nasopharyngeal carcinoma (NPC) remains a challenging cancer to treat. This study investigates the molecular mechanisms of Hedyotis diffusa Willd (HDW) combined with Andrographis paniculata (AP) in treating NPC. METHODS: Key compounds and target genes in HDW and AP were analyzed using network pharmacology. Protein-protein interaction (PPI) networks were constructed with STRING and visualized using Cytoscape. MCODE identified critical clusters, while DAVID facilitated GO and KEGG analyses. In vivo and in vitro experiments evaluated HDW-AP effects on NPC, including tumor volume, weight, Ki-67 expression, cell apoptosis, migration, invasion, cell cycle distribution, and DNA damage. RESULTS: The database identified 495 NPC-related genes and 26 compounds in the HDW-AP pair, targeting 165 genes. Fifty-eight potential therapeutic genes were found, leading to 18 key targets. KEGG analysis revealed a significant impact on 78 pathways, especially cancer pathways. Both in vivo and in vitro tests showed HDW-AP inhibited NPC cell proliferation, migration, invasion, and induced apoptosis. Mechanistically, this was achieved through AKT1 downregulation and VEGFA upregulation. CONCLUSION: The combination of HDW and AP targets 16 key genes to impede the development of NPC, primarily by modulating AKT1 and VEGFA pathways.
Assuntos
Hedyotis , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas Proto-Oncogênicas c-akt , Fator A de Crescimento do Endotélio Vascular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos Nus , Apoptose/efeitos dos fármacos , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Andrographis/química , Proliferação de Células/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacos , Sinergismo Farmacológico , Mapas de Interação de Proteínas , Carcinogênese/efeitos dos fármacos , Andrographis paniculata , Regulação para Baixo , MasculinoRESUMO
Background: Despite significant advances in tumor immunotherapy, hepatocellular carcinoma (HCC) remains a malignancy with a challenging prognosis. The increasing research emphasizes the crucial role of ubiquitination in tumor immunotherapy. However, the establishment of prognostic signatures based on ubiquitination-related genes (UbRGs) and their role in immunotherapy are still lacking in HCC. Methods: We employed datasets from TCGA and GEO for transcriptome differential expression analysis and single-cell RNA sequencing analysis. Applying weighted gene co-expression network analysis, cox regression, lasso, selection and visualization of the most relevant features, and gradient boosting machine, we identified hub UbRGs as a gene signature to develop a prognostic model. We evaluated the predictive utility concerning clinical characteristics as well as its role in the immune landscape and immunotherapy potential. Additionally, western blotting, reverse transcription-quantitative PCR, and immunofluorescence were employed to detect the expression and sub-localization of hub genes. Results: Three hub UbRGs (BOP1, CDC20, and UBE2S) were identified as a gene signature. In particular, the high-risk group exhibited notable characteristics, including higher tumor mutation burden, enrichment in immune-related pathways, up-regulation immune checkpoint, and higher immunity scores. Treatment response to immunotherapy varied based on the expression of PD-1 and CTLA-4. Furthermore, single-cell data analysis revealed heterogeneous expression of hub UbRGs across different cell subtypes, while cytological experiments provided additional confirmation of the high expression of hub UbRGs in HCC. Conclusion: Our study provides valuable insights into the identification of novel ubiquitination-related biomarkers with potential applications for prognosis, immunotherapy prediction, and drug sensitivity in HCC.
RESUMO
Recent years have witnessed increasing studies on the effect of epigenetic silencing of genes in the progression of chronic lymphocytic leukemia (CLL). This study investigates whether the nucleotide binding oligomerization domain containing 2 (NOD2) participates in the cell apoptosis and drug resistance of CLL cells. Cells were treated with adriamycin (ADR), etoposide, aclacinomycin and daunorubicin. After treatment, drug resistance and cell proliferation were examined to detect the inhibitory effect of ADR on cell proliferation; flow cytometry to identify ADR accumulation, the cell cycle distribution and apoptosis after transfection, and rhodamine 123 accumulation and efflux tests to assess P-glycoprotein (P-gp) function. NOD2 silencing or inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway suppressed the multidrug resistance level in CLL, the inhibition rate, and cell proliferation caused by ADR at concentrations of approximately 0.25-1.5 µmol/L. Greater accumulation of ADR was observed in the CLL-AAT cell line than in the CLL-AAT/A02 cell line, but NOD2 silencing or inhibition of the NF-κB signaling pathway further increased the accumulation of ADR drugs in the CLL-AAT cell line and inhibited the drug efflux pump function of P-gp. Additionally, NOD2 silencing or NF-κB signaling pathway inhibition increased the apoptotic rate. The results of this study indicate that NOD2 promotes cell apoptosis and reduces the drug resistance of CLL by inhibiting the NF-κB signaling pathway.
Assuntos
Leucemia Linfocítica Crônica de Células B , NF-kappa B , Humanos , NF-kappa B/metabolismo , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Apoptose , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Proteína Adaptadora de Sinalização NOD2/farmacologiaRESUMO
PURPOSE: This paper intended to study RBPMS-AS1 in lung cancer (LC) radiosensitivity. MATERIALS AND METHODS: LC cells were transfected with RBPMS-AS1 overexpression plasmid and miR-19a-3p mimic and treated with radiation. PTEN, AKT, p-AKT, RBPMS-AS1, and miR-19a-3p expressions were detected via Western blot and qRT-PCR. The localization of RBPMS-AS1 in cells was determined through fluorescence in situ hybridization assay. The targeting relationships of RBPMS-AS1 and miR-19a-3p/miR-19a-3p and PTEN were determined through RIP and dual luciferase reporter analysis. Cell survival, viability, and apoptosis were assessed through colony formation, CCK-8, and flow-cytometry assays. RESULTS: RBPMS-AS1 was downregulated in LC and mainly distributed in cytoplasm. RBPMS-AS1 targeted miR-19a-3p in LC cells. Radiation suppressed LC cell survival, viability, and induced apoptosis, as overexpressed RBPMS-AS1 performed the similar effects and enhanced those effects induced by radiation. MiR-19a-3p mimic reversed the effect of overexpressed RBPMS-AS1 on enhancing radiation-induced LC cell apoptosis. MiR-19a-3p targeted PTEN and miR-19a-3p mimic reversed the effect of overexpressed RBPMS-AS1 on PTEN and phosphorylation of AKT in LC cells. CONCLUSION: Overexpressed RBPMS-AS1 sponged miR-19a-3p to increase cell radiosensitivity in LC via regulating PTEN/AKT axis.
Assuntos
Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hibridização in Situ Fluorescente , Linhagem Celular , Tolerância a Radiação/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Proliferação de Células , Linhagem Celular Tumoral , Apoptose/genética , Proteínas de Ligação a RNA , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Background: With the unveiling of new mechanisms and the advent of new drugs, the prognosis of diffuse large B-cell lymphoma (DLBCL) becomes promising, but some patients still progress to the relapse or refractory stage. Necroptosis, as a relatively novel programmed cell death, is involved in the development of multiple tumors. There are no relevant studies on the prognostic significance of necroptosis in DLBCL to date. Methods: We identified the differential necroptosis-related genes (NRGs) by comparing the DLBCL and normal control in GSE12195 and GSE56315 datasets. TCGA DLBC and GSE10846 containing clinical information and microarray expression profiling were merged as the entire cohort. We performed consensus clusters based on NRGs and two clusters were obtained. Kaplan-Meier (K-M) survival analysis, GSVA, GO, KEGG, and ssGSEA were used to analyze the survival, function, and immune microenvironment between two clusters. With LASSO and proportional hazard model construction, we identified differentially expressed genes (DEGs) between NRG clusters, calculated the risk score, established a prognostic model, and validated its value by calibration and ROC curves. The entire cohort was divided into the training and test cohort, and GSE87371 was included as an external validation cohort. K-M, copy number variation, tumor mutation burden, and drug sensitivity were also analyzed. Results: We found significant differences in prognosis between the two NRG clusters. Cluster A with a poor prognosis had a decreased expression of NRGs and a relatively suppressed immune microenvironment. GSVA analysis indicated that cluster A was related to the downregulation of the TGF-ß signaling pathway and the activation of the Notch signaling pathway. The risk score had an accurate predictive ability. The nomogram could help predict the survival probability of DLBCL patients in the entire cohort and the external validation cohort. The area under the curve (AUC) of the nomogram, risk score, and International Prognostic Index was 0.723, 0.712, and 0.537, respectively. γ/δ T cells and Macrophage 1 cells decreased while Macrophage 2 cells and Natural Killer resting cells increased in the high-risk group. In addition, the high-risk group was more sensitive to the PI3K inhibitor and the PDK inhibitor. Conclusion: We explored the potential role of necroptosis in DLBCL from multiple perspectives and provided a prognostic nomogram for the survival prediction of DLBCL. Necroptosis was downregulated and was correlated with an immunosuppressed tumor microenvironment and poor prognosis in DLBCL. Our study may deepen the understanding and facilitate the development of new therapy targets for DLBCL.
RESUMO
Hairy and enhancer of split homolog-1 (HES1), regulated by the Notch, has been reported to play important roles in the immune response and cancers, such as leukemia. In this study, we aim to explore the effect of HES1-mediated Notch1 signaling pathway in chronic lymphocytic leukemia (CLL). Reverse transcription quantitative polymerase chain reaction and Western blot assay were conducted to determine the expression of HES1, Notch1, and PTEN in B lymphocytes of peripheral blood samples of 60 CLL patients. We used lentivirus-mediated overexpression or silencing of HES1 and the Notch1 signaling pathway inhibitor, MW167, to detect the interaction among HES1, Notch1, and PTEN in CLL MEC1 and HG3 cells. MTT assay and flow cytometry were employed for detection of biological behaviors of CLL cells. HES1 and Notch1 showed high expression, but PTEN displayed low expression in B lymphocytes of peripheral blood samples of patients with CLL in association with poor prognosis. HES1 bound to the promoter region of PTEN and reduced PTEN expression. Overexpression of HES1 activated the Notch1 signaling pathway, thus promoting the proliferation of CLL cells, increasing the proportion of cells arrested at the S phase and limiting the apoptosis of CLL cells. Collectively, HES1 can promote activation of the Notch1 signaling pathway to cause PTEN transcription inhibition and the subsequent expression reduction, thereby promoting the proliferation and inhibiting the apoptosis of CLL cells.
Assuntos
Leucemia Linfocítica Crônica de Células B , Apoptose , Proliferação de Células , Humanos , Leucemia Linfocítica Crônica de Células B/genética , PTEN Fosfo-Hidrolase/genética , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismoRESUMO
Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.
RESUMO
Non-small cell lung cancer (NSCLC), a commonly diagnosed lung cancer, is characterized by a high incidence of metastatic spread to the brain, which adversely impacts prognosis. The present study aimed to assess the value of combined dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in predicting the treatment outcomes of whole-brain radiotherapy (WBRT) and gefitinib in brain metastases from non-small cell lung cancer (NSCLC) from the perspectives of response rate and short- and long-term efficacy. These results suggested that the indicators measured by DCE-MRI combined with DWI can be used as key imaging-derived markers that predicted the efficacy of WBRT combined with gefitinib in NSCLC patients with brain metastases. Specifically, patients with higher ΔADCmid and ΔADCpost values showed better treatment outcomes. ROC curve analysis indicated ADCpost, ΔADCpost, ΔADCpost (%), and tumor regression rate as the best predictors of efficacy of WBRT combined with gefitinib in these patients. The short-term and long-term effects noted were also significant. Taken together, the findings of this study reveal that tumor regression rate, ADCpost, ΔADCpost, and ΔADCpost (%) can be used as important imaging indicators that predict the therapeutic effect of WBRT combined with gefitinib in NSCLC patients with brain metastases.
RESUMO
BACKGROUND: Duodenal adenocarcinoma (DA) with skin metastasis as initial manifestation is clinically rare. In this study, we report a rare case of skin metastasis of DA. CASE PRESENTATION: An 84-year-old male patient developed multiple ecchymoses on the trunk and lower extremities. Physical examination showed that the ecchymosis was dark red and had a hard texture, but showed no bulging, rupture, or tenderness. The skin biopsy implied skin metastatic adenocarcinoma. After an endoscopic duodenal biopsy, the patient was finally diagnosed with DA with skin metastasis. The patient received two courses of oral treatment of Tegafur (40 mg, bid d1-d14). However, the patient stopped taking Tegafur because of its poor effect and received Chinese medicine as a replacement treatment. Unfortunately, he was lost to follow-up. CONCLUSIONS: Early diagnosis of DA metastasis is of significant importance as prognosis of these patients is poor.
RESUMO
BACKGROUND Acute myeloid leukemia (AML) is associated with a high relapse rate and poor prognosis. This study aimed to use weighted gene coexpression network analysis (WGCNA) of gene coexpression networks to identify candidate prognostic biomarker genes in patients with AML and to investigate the expression of these genes in the human U937 cell line in vitro. MATERIAL AND METHODS RNA-seq data were retrieved from the Cancer Genome Atlas (TCGA) and included bone marrow samples and survival data of patients with AML (N=151), patients who did not relapse after treatment (N=119), and patients with relapse (N=40). Differentially expressed genes were identified, WGCNA was used to detect functional modules, and survival analysis was performed. The Cell Counting Kit-8 (CCK-8) assay investigated the proliferation of U937 cells transfected with short hairpin RNAs (shRNAs), shCRIP1, shHIST1H1C, and shHIST1H1E. RNA-seq analysis identified gene expression following CRIP1 knockdown. RESULTS Eighty-two genes were associated with both relapse and prognosis in patients with AML. There were two prognosis-related gene modules in the coexpression network. In the coexpression network, the histone cluster 1 H1 family member gene, HIST1H1C had the maximum relapse fold change, HIST1H1E had the lowest survival p-value, and the cysteine-rich intestinal protein 1 (CRIP1) gene had the most edge numbers and was significantly associated with poor prognosis (P=0.0165786). RNA-seq data showed that there was a significant difference in gene expression after CRIP1 knockdown in U937 cells. CONCLUSIONS WGCNA of gene coexpression networks identified CRIP1 as a potential prognostic biomarker gene in patients with AML.
Assuntos
Proteínas de Transporte/genética , Perfilação da Expressão Gênica/métodos , Proteínas com Domínio LIM/genética , Leucemia Mieloide Aguda/genética , Proteínas de Transporte/metabolismo , Proliferação de Células , China , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes/genética , Humanos , Proteínas com Domínio LIM/metabolismo , Masculino , Prognóstico , RNA Longo não Codificante/genética , RNA Interferente Pequeno , Recidiva , Células U937RESUMO
Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway.
Assuntos
MicroRNAs/metabolismo , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-raf/metabolismo , Animais , Antagomirs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-raf/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismoRESUMO
INTRODUCTION: Angioimmunoblastic T-cell lymphoma (AITL) is a kind of rare peripheral T cell lymphoma, which usually has acute onset at old age. MATERIALS AND METHODS: Here we report a case of relapsed refractory AITL, which has achieved obvious curative effect after treatment with chidamide. RESULTS: Initially, the patient received 7 courses of treatment with recombinant human endostatin (endostar)+CHOP. The patient achieved complete remission, but suffered from recurrence later. After changing chemotherapy regimens, the outcome was still not satisfactory, and the patient developed systemic skin infiltration and rashes. After 2 courses of chemotherapy with chidamide (30âmg) twice a week + intravenous injections with cyclophosphamide (0.1âg) twice every other day + thalidomide (50âmg) every night, the patient began with the oral intake of chidamide, and the therapeutic effect was satisfactory, with diminishing systemic rashes and shrunken lymph nodes. DISCUSSION AND CONCLUSIONS: Chidamide has good therapeutic effect in the treatment of AITL, which provides a novel therapeutic strategy for relapsed refractory AITL. However, more cases are still needed to further validate its efficacy.
Assuntos
Aminopiridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/patologia , Pessoa de Meia-IdadeRESUMO
We investigated the ability of support vector machines (SVM) to analyze minimal residual disease (MRD) in flow cytometry data from patients with acute myeloid leukemia (AML) automatically, objectively and standardly. The initial disease data and MRD review data in the form of 159 flow cytometry standard 3.0 files from 36 CD7-positive AML patients in whom MRD was detected more than once were exported. SVM was used for training with setting the initial disease data to 1 as the flag and setting 15 healthy persons to set 0 as the flag. Based on the two training groups, parameters were optimized, and a predictive model was built to analyze MRD data from each patient. The automated analysis results from the SVM model were compared to those obtained through conventional analysis to determine reliability. Automated analysis results based on the model did not differ from and were correlated with results obtained through conventional analysis (correlation coefficient c = 0.986, P > 0.05). Thus the SVM model could potentially be used to analyze flow cytometry-based AML MRD data automatically, objectively, and in a standardized manner.
Assuntos
Leucemia Mieloide Aguda/diagnóstico , Máquina de Vetores de Suporte , Adolescente , Adulto , Idoso , Antígenos CD7/análise , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Adulto JovemRESUMO
The long non-coding RNA, HOX transcript antisense intergenic RNA (HOTAIR), has been indicated to have involvement in a number of cancers, however, its role in acute myeloid leukemia (AML) is unknown. The present study aimed to investigate the pattern of HOTAIR expression in AML and to evaluate its clinical significance in tumor progression. Quantitative polymerase chain reaction was performed to examine the HOTAIR expression in mononuclear cells from the bone marrow (BM) or peripheral blood specimens of 85 patients with newly diagnosed AML. The association of HOTAIR expression with the clinicopathological factors and prognosis of AML patients was statistically analyzed. The expression of HOTAIR was significantly upregulated in the AML patients compared with the healthy controls (mean expression value, 3.87±0.29 vs. 1.28±0.09; P<0.001), and markedly decreased in the patients post-treatment compared with pre-treatment (4.76±0.47 vs. 2.81±0.27; P<0.001). Moreover, high levels of HOTAIR were associated with higher white blood cell and BM blast counts (P<0.001 and P=0.001, respectively), and lower hemoglobin and platelet counts (P=0.007 and 0.001, respectively). Patients with a high level of HOTAIR expression had relatively poor overall survival (OS; 20.5 vs. 32.1 months, P=0.001) and relapse-free survival (21.5 vs. 33.6 months, P=0.001) times compared with those with a low level of HOTAIR expression. These data demonstrated that HOTAIR expression was upregulated in newly diagnosed AML patients and was associated with leukemic burden, and DFS and OS times. HOTAIR may represent a biomarker of a poor prognosis and is a potential therapeutic target for AML treatment.
RESUMO
An efficient preparative separation method for Sphallerocarpus gracilis stems and leaves polyphenols (SGslP) was established in this study. An X-5 macroporous adsorption resin was selected for the purification of the SGslP, and the polyphenol content of the purified SGslP (PSGslP) was increased 5.11-fold from 8.29% to 42.38% after one treatment run. The chemical composition of the PSGslP was analyzed by HPLC-MS/MS, and the predominant compounds were found to be luteolin-7-glucoside, acacetin-7-acetyglycoside and its isomers. In addition, the PSGslP was evaluated in vitro to determine the DNA damage-protective activity and inhibitory effects of α-amylase and α-glucosidase. The results indicated that the PSGslP exhibited significant protective activities against both ROO⢠and â¢OH radical-induced DNA damage. Moreover, the PSGslP exerted a dose-dependent inhibition effect on α-glucosidase but no inhibitory effect on α-amylase. These findings indicate that the Sphallerocarpus gracilis stems and leaves are good natural sources of antioxidants and are potent inhibitors of α-glucosidase activity and are potential anti-diabetic inhibitor.
Assuntos
Apiaceae/química , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Caules de Planta/química , Polifenóis/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Polifenóis/isolamento & purificaçãoRESUMO
OBJECTIVE: To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen. METHODS: A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively. RESULTS: The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P > 0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P = 0.848) and progression-free survival (median 22 months versus 25 months; P = 0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%, P = 0.015). CONCLUSIONS: The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/efeitos adversos , Demografia , Dexametasona/efeitos adversos , Feminino , Humanos , Injeções Subcutâneas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Talidomida/efeitos adversos , Resultado do TratamentoRESUMO
The effect of three processing units (blanching, enzyme liquefaction, pasteurisation) on chemical composition and antimicrobial activity of carrot juice essential oil was investigated in this paper. A total of 36 compounds were identified by GC-MS from fresh carrot juice essential oil. The main constituents were carotol (20.20%), sabinene (12.80%), ß-caryophyllene (8.04%) and α-pinene (6.05%). Compared with the oil of fresh juice, blanching and pasteurisation could significantly decrease the components of the juice essential oil, whereas enzyme liquefaction had no considerable effect on the composition of juice essential oil. With regard to the antimicrobial activity, carrot juice essential oil could cause physical damage and morphological alteration on microorganisms, while the three different processing units showed noticeable differences on the species of microorganisms, the minimum inhibitory concentration and minimum bactericidal concentration. Results revealed that the carrot juice essential oil has great potential for application as a natural antimicrobial applied in pharmaceutical and food industries.
Assuntos
Anti-Infecciosos/química , Daucus carota/química , Óleos Voláteis/química , Anti-Infecciosos/farmacologiaRESUMO
Adiponectin, a member of adipokines, is a functional ligand for Adiponectin Receptor-1 (AdipoR1) and Adiponectin Receptor-2 (AdipoR2), and has been found to be linked to the risk of CML. Imatinib has undoubtedly revolutionised the management and outcome of chronic myeloid leukemia (CML), however imatinib resistance has been recognized as a major problem in CML therapy. In this study, we first established imatinib-resistant K562 CML cells, and then evaluated the effect of Adiponectin in reversing imatinib resistance. The data presented here demonstrated that Adiponectin was able to reverse K562 resistance to imatinib in vitro and in vivo. Additional data with molecular approaches suggested that the reversion of Adiponectin in imatinib resistance signals through AdipoR1 but not AdipoR2 to downregulate Bcr-Abl expression and effect in imatinib-resistant K562 CML cells. Taken together, our data showed that Adiponectin can reverse imatinib resistance in CML, and to a certain extent elucidate the mechanism of Adiponectin reversing imatinib resistance that may provide a new and promising approach in imatinib resistance management in CML therapy.