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1.
Sci Rep ; 14(1): 15402, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965305

RESUMO

The diagnosis of leukemia is a serious matter that requires immediate and accurate attention. This research presents a revolutionary method for diagnosing leukemia using a Capsule Neural Network (CapsNet) with an optimized design. CapsNet is a cutting-edge neural network that effectively captures complex features and spatial relationships within images. To improve the CapsNet's performance, a Modified Version of Osprey Optimization Algorithm (MOA) has been utilized. Thesuggested approach has been tested on the ALL-IDB database, a widely recognized dataset for leukemia image classification. Comparative analysis with various machine learning techniques, including Combined combine MobilenetV2 and ResNet18 (MBV2/Res) network, Depth-wise convolution model, a hybrid model that combines a genetic algorithm with ResNet-50V2 (ResNet/GA), and SVM/JAYA demonstrated the superiority of our method in different terms. As a result, the proposed method is a robust and powerful tool for diagnosing leukemia from medical images.


Assuntos
Algoritmos , Leucemia , Redes Neurais de Computação , Humanos , Leucemia/diagnóstico por imagem , Aprendizado de Máquina , Processamento de Imagem Assistida por Computador/métodos , Bases de Dados Factuais
2.
Sci Rep ; 14(1): 15625, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972881

RESUMO

Blood cancer has emerged as a growing concern over the past decade, necessitating early diagnosis for timely and effective treatment. The present diagnostic method, which involves a battery of tests and medical experts, is costly and time-consuming. For this reason, it is crucial to establish an automated diagnostic system for accurate predictions. A particular field of focus in medical research is the use of machine learning and leukemia microarray gene data for blood cancer diagnosis. Even with a great deal of research, more improvements are needed to reach the appropriate levels of accuracy and efficacy. This work presents a supervised machine-learning algorithm for blood cancer prediction. This work makes use of the 22,283-gene leukemia microarray gene data. Chi-squared (Chi2) feature selection methods and the synthetic minority oversampling technique (SMOTE)-Tomek resampling is used to overcome issues with imbalanced and high-dimensional datasets. To balance the dataset for each target class, SMOTE-Tomek creates synthetic data, and Chi2 chooses the most important features to train the learning models from 22,283 genes. A novel weighted convolutional neural network (CNN) model is proposed for classification, utilizing the support of three separate CNN models. To determine the importance of the proposed approach, extensive experiments are carried out on the datasets, including a performance comparison with the most advanced techniques. Weighted CNN demonstrates superior performance over other models when coupled with SMOTE-Tomek and Chi2 techniques, achieving a remarkable 99.9% accuracy. Results from k-fold cross-validation further affirm the supremacy of the proposed model.


Assuntos
Leucemia , Redes Neurais de Computação , Humanos , Leucemia/genética , Algoritmos , Neoplasias Hematológicas/genética , Aprendizado de Máquina Supervisionado , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Aprendizado de Máquina , Perfilação da Expressão Gênica/métodos
3.
Nat Commun ; 15(1): 5689, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38971796

RESUMO

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin ß2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.


Assuntos
Apoptose , Medula Óssea , Citarabina , Sistemas de Liberação de Medicamentos , Células-Tronco Hematopoéticas , Leucemia , Lipossomos , Animais , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Citarabina/farmacologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Medula Óssea/metabolismo , Apoptose/efeitos dos fármacos , Leucemia/tratamento farmacológico , Leucemia/patologia , Humanos , Diferenciação Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Antígenos CD18/metabolismo , Proliferação de Células/efeitos dos fármacos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo
4.
Zhonghua Yi Xue Za Zhi ; 104(27): 2477-2482, 2024 Jul 16.
Artigo em Chinês | MEDLINE | ID: mdl-38978372

RESUMO

Acute leukemia is the most common hematopoietic stem cell malignant tumor in children, which ranks in the top one of the incidence of tumor in children, it is a major disease that affects the growth and survival of children. With the continuous improvement of medical diagnosis and treatment and the extensive development of immunotherapy, the survival rate and quality of life of children with acute leukemia have been significantly improved. In recent years, three cooperative groups of childhood leukemia have been established in China, and a series of high-level research results have been published. In the future, efforts should be made to promote the process of standardization and homogenization in the diagnosis and treatment of children's acute leukemia, explore the monitoring targets of sensitive residual diseases, and find the best treatment for refractory/recurrent cases. Speeding up the clinical research of new drugs will be an urgent problem and development direction in the field of acute leukemia diagnosis and treatment in children.


Assuntos
Leucemia , Humanos , China , Criança , Leucemia/diagnóstico , Leucemia/terapia , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Imunoterapia , Qualidade de Vida
5.
Zhonghua Yi Xue Za Zhi ; 104(27): 2521-2528, 2024 Jul 16.
Artigo em Chinês | MEDLINE | ID: mdl-38978376

RESUMO

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Antígenos HLA , Leucemia , Humanos , Feminino , Masculino , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Prognóstico , Estudos Retrospectivos , Pré-Escolar , Criança , Leucemia/genética , Leucemia/terapia , Antígenos HLA/genética , Doença Enxerto-Hospedeiro/etiologia , Doadores de Tecidos , Teste de Histocompatibilidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
6.
Support Care Cancer ; 32(8): 512, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001992

RESUMO

INTRODUCTION: Skeletal muscle function is an important prognostically relevant indicator in patients with acute leukemia (AL), but skeletal dysfunction during chemotherapy is not well understood. This study aimed to investigate the factors that influence changes in skeletal muscle function from before the start of chemotherapy to before allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This was a retrospective cohort study that included 90 patients with AL who underwent chemotherapy before transplantation to perform allo-HSCT (men, 67.3%; median age, 53 years). The outcome measure was defined as changes in skeletal muscle function from before chemotherapy to before allo-HSCT, and was assessed by measuring the psoas muscle index (PMI) as skeletal muscle quantity and computed tomography values (CTV) as skeletal muscle quality using a computed tomography scanner. We examined the differences in PMI and CTV before chemotherapy and allo-HSCT, and the factors associated with changes in PMI. RESULT: The mean PMI for before chemotherapy and allo-HSCT were 4.6 ± 1.4 cm2/m2 and 4.0 ± 1.3 cm2/m2 and significant differences were observed (p < 0.001). However, the mean CTV before chemotherapy and allo-HSCT were 47.3 ± 4.5 HU and 47.4 ± 5.0 HU, respectively, and no significant differences were found (p = 0.798). In stepwise multiple regression analysis, age and sex were identified as factors related to changes in PMI (age, p = 0.019; sex, p = 0.001). CONCLUSION: We found that skeletal muscle quantity decreased during chemotherapy in patients with AL and was influenced by male sex and older age. TRIAL REGISTRATION NUMBER:   TRIAL REGISTRATION NUMBER: 34-096(11,243). Date of registration: September 11, 2023.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Músculo Esquelético , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Músculo Esquelético/fisiopatologia , Idoso , Tomografia Computadorizada por Raios X/métodos , Estudos de Coortes , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Músculos Psoas , Adulto Jovem , Leucemia/terapia , Leucemia/tratamento farmacológico , Transplante Homólogo/métodos , Doença Aguda , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem
7.
Sensors (Basel) ; 24(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39001200

RESUMO

Acute lymphoblastic leukemia, commonly referred to as ALL, is a type of cancer that can affect both the blood and the bone marrow. The process of diagnosis is a difficult one since it often calls for specialist testing, such as blood tests, bone marrow aspiration, and biopsy, all of which are highly time-consuming and expensive. It is essential to obtain an early diagnosis of ALL in order to start therapy in a timely and suitable manner. In recent medical diagnostics, substantial progress has been achieved through the integration of artificial intelligence (AI) and Internet of Things (IoT) devices. Our proposal introduces a new AI-based Internet of Medical Things (IoMT) framework designed to automatically identify leukemia from peripheral blood smear (PBS) images. In this study, we present a novel deep learning-based fusion model to detect ALL types of leukemia. The system seamlessly delivers the diagnostic reports to the centralized database, inclusive of patient-specific devices. After collecting blood samples from the hospital, the PBS images are transmitted to the cloud server through a WiFi-enabled microscopic device. In the cloud server, a new fusion model that is capable of classifying ALL from PBS images is configured. The fusion model is trained using a dataset including 6512 original and segmented images from 89 individuals. Two input channels are used for the purpose of feature extraction in the fusion model. These channels include both the original and the segmented images. VGG16 is responsible for extracting features from the original images, whereas DenseNet-121 is responsible for extracting features from the segmented images. The two output features are merged together, and dense layers are used for the categorization of leukemia. The fusion model that has been suggested obtains an accuracy of 99.89%, a precision of 99.80%, and a recall of 99.72%, which places it in an excellent position for the categorization of leukemia. The proposed model outperformed several state-of-the-art Convolutional Neural Network (CNN) models in terms of performance. Consequently, this proposed model has the potential to save lives and effort. For a more comprehensive simulation of the entire methodology, a web application (Beta Version) has been developed in this study. This application is designed to determine the presence or absence of leukemia in individuals. The findings of this study hold significant potential for application in biomedical research, particularly in enhancing the accuracy of computer-aided leukemia detection.


Assuntos
Aprendizado Profundo , Internet das Coisas , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Inteligência Artificial , Leucemia/diagnóstico , Leucemia/classificação , Leucemia/patologia , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
9.
Breastfeed Med ; 19(7): 539-546, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968405

RESUMO

Objective: The aim of this study was to test the hypothesis that the duration of breastfeeding in infancy reduces the risk of childhood leukemia or lymphoma, and modifies the risk of developing functional gastrointestinal disorders (FGIDs). Subjects and Methods: This case-control study involved the recruitment of children with lymphoid malignancy and functional gastrointestinal symptoms with healthy children as controls. Focused questionnaires were used to collect data on breastfeeding history and other key risk factors. Univariate and multivariate analyses were undertaken. Results: Of the 334 children with lymphoid malignancy, 65% were male. The control group included 334 age- and sex-matched participants. Most (n = 189; 56.6%) of the children with leukemia were <10 years of age. Differences between cases and controls included the duration of breastfeeding (p < 0.0001), mean birthweight (p < 0.001), maternal age (p < 0.001), paternal age (p < 0.001), birth order (p < 0.001), mean number of children (p < 0.001), BMI percentile (p = 0.042), and maternal smoking (p = 0.012). Breastfeeding duration of up to 6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for acute lymphoblastic leukemia (OR = 3.43, 95% confidence interval [CI] 2.37-4.98; p < 0.001), Hodgkin's lymphoma (OR = 1.58, 95% CI: 0.88-2.84, p = 0.120), Non-Hodgkin's lymphoma (OR = 2.14, 95% CI: 1.25-3.65, p = 0.005), and overall (OR = 1.95, 95% CI: 1.40-2.71, p < 0.001). Cases also differed from controls with regard to FGIDs, such as stomach ache (p < 0.001), dyspepsia (p < 0.001), early satiety (p = 0.017), bowel satisfaction (p < 0.001), bloating (p < 0.001), nausea (p = 0.005), vomiting (p = 0.039), constipation (p = 0.003), diarrhea (p = 0.010), gastrointestinal canal congestion (p =0.039), muscle aches pains (p = 0.008), fecal incontinence (p = 0.021), and indigestion (p = 0.003). A multivariate stepwise regression analysis revealed that maternal smoking (p < 0.001), formula feeding (p < 0.001), duration of breastfeeding (p < 0.001), birth order (p = 0.002), mother's age (p = 0.004) and the child's birthweight (p = 0.009) were predictors for leukemia. Further analysis showed that dyspepsia (p < 0.001), gastrointestinal tract canal congestion (p < 0.001), constipation (p = 0.009), diarrhea (p = 0.013), bowel satisfaction (p = 0.021), bloating (p = 0.022), duration of breastfeeding (p < 0.001), and stomach ache (p = 0.025) were significant predictors for developing FGID symptoms after adjusting for age, gender, and other confounding variables. Conclusion: This study confirmed that breastfeeding has some effect on reducing possible risk of childhood lymphoma and leukemia and FGID symptoms compared with healthy control children.


Assuntos
Aleitamento Materno , Gastroenteropatias , Humanos , Aleitamento Materno/estatística & dados numéricos , Feminino , Masculino , Estudos de Casos e Controles , Fatores de Risco , Criança , Fatores de Tempo , Gastroenteropatias/epidemiologia , Gastroenteropatias/prevenção & controle , Lactente , Pré-Escolar , Recém-Nascido , Inquéritos e Questionários , Leucemia/epidemiologia , Leucemia/prevenção & controle , Adolescente , Peso ao Nascer , Idade Materna
10.
Mol Biol Rep ; 51(1): 807, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39002036

RESUMO

BACKGROUND: Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis. Besides, insulin is known to activate the PI3K/Akt pathway, often disrupted in cancers, leading to enhanced cell survival and resistance to apoptosis. In light of the above-mentioned points, we examined the anti-cancer impact of antibiotics Ciprofloxacin (CP) and Salinomycin (SAL) and their combination on KG1-a cells in the presence and absence of insulin. METHODS: This was accomplished by exposing KG1-a cells to different doses of CP and SAL alone, in combination, and with or without insulin for 24-72 h. Cell viability was evaluated using the MTT assay. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR. RESULTS: CP and SAL demonstrated cytotoxic and notable pro-apoptotic impact on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, leading to G0/G1 cell cycle arrest and prevention of the PI3K-Akt signaling pathway. Our findings demonstrated that combination of CP and SAL promote apoptosis in the KG1-a cell line by down-regulating BIRC5 and Akt, as well as up-regulating Bax, p53, PTEN, and FOXO1. Additionally, the findings strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in the cells treated with CP and SAL. CONCLUSION: Our findings showed that the combined treatment of CP and SAL exhibit a strong anti-cancer effect on leukemia KG1-a cells. Moreover, it was discovered that the PI3K-Akt signaling can be a promising target in leukemia treatment particularly in hyperinsulinemia condition.


Assuntos
Apoptose , Sobrevivência Celular , Ciprofloxacina , Insulina , Piranos , Humanos , Ciprofloxacina/farmacologia , Apoptose/efeitos dos fármacos , Piranos/farmacologia , Linhagem Celular Tumoral , Insulina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Forkhead Box O1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Policetídeos de Poliéter
11.
Toxicol In Vitro ; 99: 105890, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38972516

RESUMO

Beauvericin (BEA), Enniatin B (ENN B), and Ochratoxin A (OTA) are mycotoxins produced by fungi species. Their main effect on several organs and systems is associated with chronic exposure going from immunotoxicity, estrogenic disorders, and renal failure to cancer (in animals and humans). OTA belongs to Group 1 according to the International Agency for Research in Cancer (IARC) and it has legislated limited values; not happening for BEA nor ENN B. Exposure to mixtures of mycotoxins occurs through food intake in daily consumption. The aim of this study was to evaluate the implication of BEA, ENN B, and OTA individually and combined in producing cytotoxicity in cells for immunological studies and cancer cell lines (human leukemia cells (HL-60), fresh human peripheral blood mononuclear cells (PBMCs), and human breast cancer (MDA-MB-231) cells). Cells were treated for 4 h and 24 h at different concentrations of BEA, ENN B, and OTA, respectively. Viability assays were carried out by flow cytometry using DAPI (4',6-diamindino-2-phenylindole, dihydrochloride) as a viability dye and the potential effects of synergism, addition, and antagonism were assessed through the Chou and Talalay method. Individual OTA treatment exerted the greatest cytotoxicity for PBMC cells (IC50 0.5 µM) while ENN B for HL-60 (IC50 0.25 µM) and MDA-MB-231 (IC50 0.15 µM). In binary combination [ENN B + OTA] resulted in exerting the greatest cytotoxicity for HL-60 and MDA-MB-231 cells; while [BEA + OTA] in PBMC cells. The triple combination resulted in being highly cytotoxic for PBMC cells compared to HL-60 and MDA-MB-231 cells. In summary, PBMC cells were the most sensible cells for all three mycotoxins and the presence of OTA in any of the combinations had the greatest toxicity causing synergism as the most common cytotoxic effect.


Assuntos
Neoplasias da Mama , Sobrevivência Celular , Depsipeptídeos , Leucócitos Mononucleares , Ocratoxinas , Humanos , Depsipeptídeos/toxicidade , Ocratoxinas/toxicidade , Leucócitos Mononucleares/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Leucemia/tratamento farmacológico
12.
Adv Exp Med Biol ; 1459: 405-430, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39017854

RESUMO

HOXA9, an important transcription factor (TF) in hematopoiesis, is aberrantly expressed in numerous cases of both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and is a strong indicator of poor prognosis in patients. HOXA9 is a proto-oncogene which is both sufficient and necessary for leukemia transformation. HOXA9 expression in leukemia correlates with patient survival outcomes and response to therapy. Chromosomal transformations (such as NUP98-HOXA9), mutations, epigenetic dysregulation (e.g., MLL- MENIN -LEDGF complex or DOT1L/KMT4), transcription factors (such as USF1/USF2), and noncoding RNA (such as HOTTIP and HOTAIR) regulate HOXA9 mRNA and protein during leukemia. HOXA9 regulates survival, self-renewal, and progenitor cell cycle through several of its downstream target TFs including LMO2, antiapoptotic BCL2, SOX4, and receptor tyrosine kinase FLT3 and STAT5. This dynamic and multilayered HOXA9 regulome provides new therapeutic opportunities, including inhibitors targeting DOT1L/KMT4, MENIN, NPM1, and ENL proteins. Recent findings also suggest that HOXA9 maintains leukemia by actively repressing myeloid differentiation genes. This chapter summarizes the recent advances understanding biochemical mechanisms underlying HOXA9-mediated leukemogenesis, the clinical significance of its abnormal expression, and pharmacological approaches to treat HOXA9-driven leukemia.


Assuntos
Regulação Leucêmica da Expressão Gênica , Proteínas de Homeodomínio , Nucleofosmina , Proto-Oncogene Mas , Humanos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Animais , Leucemia/genética , Leucemia/metabolismo , Leucemia/tratamento farmacológico , Leucemia/patologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
13.
Rom J Morphol Embryol ; 65(2): 203-208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39020534

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in childhood and rare in adults, while acute myeloid leukemia (AML) is less common in children and more common in older adults. The aim of the study was to present our experience for the diagnostic of leukemia by using the classic and molecular cytogenetic methods. The study was conducted between 2009 and 2019 within the Classic and Molecular Genetic Laboratory of the Oncohematology Department from the Louis Turcanu Emergency Hospital for Children, Timisoara, Romania. The study group included 337 children and adults, evaluated between 2009 and 2019. By using the conventional and molecular cytogenetic technique, the cytogenetic anomalies found were 35 numerical chromosomal abnormalities, 10 (9;22)(q34;q11) [four ALL, one AML, five chronic myeloid leukemia (CML)] translocations, nine (15;17)(q24;q21) translocations, three (14;14)(q11;q32) translocations, two (4;11)(q21;q23) translocations, one (1;14)(p32;q11) translocation, one (7;14)(qter;q11) translocation, one (8;21)(q22;q22) translocation, one (9;14)(p12;q32) translocation, seven rearrangements of the MLL gene and two rearrangements of the core-binding factor subunit beta∕myosin heavy chain 11 (CBFB∕MYH11) gene. The use of conventional and molecular cytogenetic analysis is one of the most important prognostic indicators in acute leukemia patients, allowing the identification of biologically distinct subtypes of disease and selection of appropriate treatment approaches.


Assuntos
Leucemia , Humanos , Romênia , Feminino , Masculino , Adulto , Criança , Adolescente , Pré-Escolar , Leucemia/genética , Leucemia/patologia , Leucemia/diagnóstico , Análise Citogenética/métodos , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Aberrações Cromossômicas , Lactente
15.
Sci Rep ; 14(1): 16636, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025941

RESUMO

In therapies, curcumin is now commonly formulated in liposomal form, administered through injections or creams. This enhances its concentration at the cellular level compared to its natural form ingestion. Due to its hydrophobic nature, curcumin is situated in the lipid part of the membrane, thereby modifying its properties and influencing processes The aim of the research was to investigate whether the toxicity of specific concentrations of curcumin, assessed through biochemical tests for the SK-N-SH and H-60 cell lines, is related to structural changes in the membranes of these cells, caused by the localization of curcumin in their hydrophobic regions. Biochemical tests were performed using spectrophotometric methods. Langmuir technique were used to evaluate the interaction of the curcumin with the studied lipids. Direct introduction of curcumin into the membranes alters their physicochemical parameters. The extent of these changes depends on the initial properties of the membrane. In the conducted research, it has been demonstrated that curcumin may exhibit toxicity to human cells. The mechanism of this toxicity is related to its localization in cell membranes, leading to their dysfunction. The sensitivity of cells to curcumin presence depends on the saturation level of their membranes; the more rigid the membrane, the lower the concentration of curcumin causes its disruption.


Assuntos
Membrana Celular , Curcumina , Neuroblastoma , Curcumina/farmacologia , Curcumina/química , Humanos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Linhagem Celular Tumoral , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Leucemia/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Interações Hidrofóbicas e Hidrofílicas
16.
PLoS One ; 19(7): e0304354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954710

RESUMO

BACKGROUND: Childhood leukemia (CL) is a major global concern, accounting for 33% of all new cancer cases and 31% of all cancer deaths in children aged 0-14 years. Our study aimed to analyze the global incidence and mortality rates of CL in 2020 and its relationship with the Human Development Index (HDI). MATERIAL AND METHODS: In this ecologic study, we analyzed the 2020 cancer incidence and mortality data for children aged 0-14 years from the GLOBOCAN Project. We calculated the Age-Standardized Incidence Rate (ASIR) and Age-Standardized Mortality Rate (ASMR) of CL per 100,000 individuals. Pearson's correlation coefficient was used to examine the association between childhood leukemia ASIR, ASMR, and the HDI, with a statistical significance threshold of P<0.05. RESULTS: In 2020, there were a total of 67,008 new cases of CL worldwide, with males accounting for 57.85%. The global ASIR for CL was 3.4 per 100,000 (3.9 in males, 3 in females). Additionally, there were 25,080 CL-related deaths, with males comprising 58.86%. The overall ASMR for CL was 1.3 (1.4 in males, 1.1 in females). We found a significant positive correlation (r = 0.405, P≤0.001) between the global ASIR and ASMR for CL. There was a strong positive correlation (r = 0.770, P = 0.001) between the HDI and childhood leukemia ASIR, but no significant association (r = 0.077, P = 0.337) was observed with ASMR. CONCLUSION: Our study reveals that CL remains a significant health burden worldwide. We identified a positive correlation between the ASIR of CL and the HDI, indicating a potential role of socioeconomic factors in CL incidence.


Assuntos
Saúde Global , Leucemia , Humanos , Criança , Lactente , Masculino , Pré-Escolar , Feminino , Incidência , Adolescente , Leucemia/epidemiologia , Leucemia/mortalidade , Recém-Nascido , Saúde Global/estatística & dados numéricos
17.
Adv Exp Med Biol ; 1459: 359-378, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39017852

RESUMO

ETS proto-oncogene 1 (ETS1) is a transcription factor (TF) critically involved in lymphoid cell development and function. ETS1 expression is tightly regulated throughout differentiation and activation in T-cells, natural killer (NK) cells, and B-cells. It has also been described as an oncogene in a range of solid and hematologic cancer types. Among hematologic malignancies, its role has been best studied in T-cell acute lymphoblastic leukemia (T-ALL), adult T-cell leukemia/lymphoma (ATLL), and diffuse large B-cell lymphoma (DLBCL). Aberrant expression of ETS1 in these malignancies is driven primarily by chromosomal amplification and enhancer-driven transcriptional regulation, promoting the ETS1 transcriptional program. ETS1 also facilitates aberrantly expressed or activated transcriptional complexes to drive oncogenic pathways. Collectively, ETS1 functions to regulate cell growth, differentiation, signaling, response to stimuli, and viral interactions in these malignancies. A tumor suppressor role has also been indicated for ETS1 in select lymphoma types, emphasizing the importance of cellular context in ETS1 function. Research is ongoing to further characterize the clinical implications of ETS1 dysregulation in hematologic malignancies, to further resolve binding complexes and transcriptional targets, and to identify effective therapeutic targeting approaches.


Assuntos
Proto-Oncogene Mas , Proteína Proto-Oncogênica c-ets-1 , Humanos , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Animais , Linfoma/genética , Linfoma/metabolismo , Linfoma/patologia , Transdução de Sinais , Regulação Leucêmica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia
18.
Mycoses ; 67(7): e13759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39012211

RESUMO

The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality.


Assuntos
Antifúngicos , Fusariose , Fusarium , Humanos , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Fusarium/isolamento & purificação , Idoso , Adulto , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Brasil/epidemiologia , Criança , Japão/epidemiologia , Pré-Escolar , Leucemia Mieloide Aguda/complicações , Estados Unidos/epidemiologia , Leucemia/complicações , Leucemia/microbiologia , Dermatomicoses/microbiologia , Dermatomicoses/epidemiologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia
19.
Integr Cancer Ther ; 23: 15347354241261356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872330

RESUMO

BACKGROUND: Among leukemia patients, sleep disruptions are prevalent and can profoundly affect their overall quality of life. Acupressure and foot reflexology, modalities rooted in traditional Chinese medicine, have garnered attention for their potential to address sleep disturbances and mitigate associated symptoms. METHODS: This research utilized a randomized controlled trial with a pretest-posttest design involving 102 leukemia patients admitted to Imam Khomeini Hospital in Urmia. Participants were randomly allocated to 3 groups: acupressure (n = 34), reflexology (n = 34), or control (n = 34). Prior to the intervention, patients completed a demographic survey and the Pittsburgh Sleep Quality Index (PSQI) for baseline assessments. Acupressure involved stimulation of the SP6 point twice daily for 10 minutes over 4 weeks, while reflexology entailed daily 10-minute sessions with sweet almond oil on the soles for the same duration. The control group received standard care without additional interventions. Following the 4-week intervention period, post-intervention evaluations were conducted using identical measurement tools. RESULTS: The findings underscored the efficacy of both acupressure and foot reflexology in significantly improving sleep quality within the intervention groups (P < .001). Initially, there were no notable differences in sleep quality among the 3 groups (P > .05). Subsequently, pairwise comparisons adjusted with Bonferroni corrections revealed significant disparities in sleep quality between the acupressure and reflexology groups compared to the control group (P < .001). However, post-intervention analysis indicated no statistically significant variance in enhancing sleep quality between the acupressure and foot reflexology groups (P < .05). CONCLUSION: This study demonstrates that acupressure and foot reflexology interventions can enhance sleep quality in individuals with leukemia. These findings support the effectiveness of these complementary modalities, offering targeted relief and relaxation. While these non-invasive therapies show promise in improving well-being, further research is needed to confirm and expand upon these results due to study limitations.


Assuntos
Acupressão , , Leucemia , Qualidade de Vida , Qualidade do Sono , Humanos , Acupressão/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Pé/fisiopatologia , Leucemia/complicações , Leucemia/terapia , Massagem/métodos , Transtornos do Sono-Vigília/terapia , Medicina Tradicional Chinesa/métodos , Resultado do Tratamento
20.
Br J Hosp Med (Lond) ; 85(6): 1-15, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38941971

RESUMO

Aims/Background Breast leukaemia (BL) is a rare breast malignancy that is treated differently from other malignant conditions. However, it is easily confused with other conditions; therefore, how to accurately diagnose is crucial. We retrospectively analysed the imaging findings of 13 patients to provide a diagnostic reference. Methods From January 2015 to April 2023, 13 patients with BL confirmed by biopsy who underwent imaging in Peking University People's hospital were retrospectively analysed. The imaging findings obtained via ultrasound (US), mammography (MMG), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) were analysed, and the detection rates of these methods for diagnosing BL were compared. Results Twenty-nine lesions were detected in the 13 patients. These patients presented with palpable masses or breast swelling several months after treatment for leukaemia, mainly involving the bilateral breasts. Ultrasonography was performed for 13 patients, and all lesions were detected. Most of the identified masses were hypoechoic and had indistinct boundaries, irregular shapes, no enhancement of the posterior echo, and no abundant blood flow. MMG was performed for five patients, revealing breast masses, architectural distortion, and no abnormalities. MRI was performed for four patients, and all lesions were detected; most of the lesions were hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging and diffusion-weighted imaging, with a decreased apparent diffusion coefficient and inhomogeneous enhancement. The enhancement curves were mostly inflow patterns. PET/CT was performed for four patients; two patients had hypermetabolism, and the other two had no obvious radioactive uptake. Conclusion Compared to MMG and PET/CT, US and MRI have higher detection rates. Furthermore, compared to MRI, US is inexpensive, convenient and efficient; therefore, it should be the first choice for diagnosing BL.


Assuntos
Neoplasias da Mama , Imageamento por Ressonância Magnética , Mamografia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Ultrassonografia Mamária , Leucemia/diagnóstico por imagem , Idoso
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