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1.
J Extracell Biol ; 3(1): e133, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38938678

RESUMO

Extracellular vesicles (EVs) secreted by human-induced pluripotent stem cells (hiPSCs) have great potential as cell-free therapies in various diseases, including prevention of blood-brain barrier senescence and stroke. However, there are still challenges in pre-clinical and clinical use of hiPSC-EVs due to the need for large-scale production of a large quantity. Vertical-Wheel bioreactors (VWBRs) have design features that allow the biomanufacturing of hiPSC-EVs using a scalable aggregate or microcarrier-based culture system under low shear stress. EV secretion by undifferentiated hiPSCs expanded as 3-D aggregates and on Synthemax II microcarriers in VWBRs were investigated. Additionally, two types of EV collection media, mTeSR and HBM, were compared. The hiPSCs were characterized by metabolite and transcriptome analysis as well as EV biogenesis markers. Protein and microRNA cargo were analysed by proteomics and microRNA-seq, respectively. The in vitro functional assays of microglia stimulation and proliferation were conducted. HiPSCs expanded as 3-D aggregates and on microcarriers had comparable cell number, while microcarrier culture had higher glucose consumption, higher glycolysis and lower autophagy gene expression based on mRNA-seq. The microcarrier cultures had at least 17-23 fold higher EV secretion, and EV collection in mTeSR had 2.7-3.7 fold higher yield than HBM medium. Microcarrier culture with mTeSR EV collection had a smaller EV size than other groups, and the cargo was enriched with proteins (proteomics) and miRNAs (microRNA-seq) reducing apoptosis and promoting cell proliferation (e.g. Wnt-related pathways). hiPSC-EVs demonstrated the ability of stimulating proliferation and M2 polarization of microglia in vitro. HiPSC expansion on microcarriers produces much higher yields of EVs than hiPSC aggregates in VWBRs. EV collection in mTeSR increases yield compared to HBM. The biomanufactured EVs from microcarrier culture in mTeSR have exosomal characteristics and are functional in microglia stimulation, which paves the ways for future in vivo anti-aging study.

2.
Glob Health Sci Pract ; 12(3)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38834532

RESUMO

In sanitation policies, "improved sanitation" is often broadly described as a goal with little rationale for the minimum standard required. We conducted a secondary analysis of data collected as part of a cluster randomized controlled trial in rural Ethiopia. We compared the performance of well-constructed and poorly constructed pit latrines in reducing child diarrhea. In addition, we explored whether having a well-constructed household latrine provides indirect protection to neighbors if cluster-level coverage reaches a certain threshold. We followed up children aged younger than 5 years (U5C) of 906 households in rural areas of the Gurage zone, Ethiopia, for 10 months after community-led total sanitation interventions. A study-improved latrine was defined as having all the following: pit of ≥2 m depth, slab of any material, drop-hole cover, wall, roof, door, and handwashing facilities (water and soap observed). U5C in households with a study-improved latrine had 54% lower odds of contracting diarrhea than those living in households with a latrine missing 1 or more of the characteristics (adjusted odds ratio [aOR]=0.46; 95% confidence interval [CI]=0.27, 0.81; P=.006). Analyses were adjusted for child age and sex, presence of improved water for drinking, and self-reported handwashing at 4 critical times. The odds of having diarrhea among those with an improved latrine based on the World Health Organization/UNICEF Joint Monitoring Program (JMP) definition (i.e., pit latrines with slabs) were not substantially different from those with a JMP-unimproved latrine (aOR=0.99; 95% CI=0.56, 1.79; P=.99). Of U5C living in households without a latrine or with a study-unimproved latrine, those in the high-coverage villages were less likely to contract diarrhea than those in low-coverage villages (aOR=0.55; 95% CI=0.35, 0.86; P=.008). We recommend that academic studies and routine program monitoring and evaluation should measure more latrine characteristics and evaluate multiple latrine categories instead of making binary comparisons only.


Assuntos
Diarreia , População Rural , Saneamento , Banheiros , Humanos , Etiópia , Diarreia/prevenção & controle , Diarreia/epidemiologia , Pré-Escolar , População Rural/estatística & dados numéricos , Masculino , Feminino , Lactente , Estudos Longitudinais , Características da Família
3.
Haematologica ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38841794

RESUMO

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

4.
Sci Rep ; 14(1): 8517, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609396

RESUMO

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Perfil Genético , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Medição de Risco
5.
Hematology ; 29(1): 2324417, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38433437

RESUMO

OBJECTIVES: This study aimed to evaluate the prognostic significance of the revised European LeukemiaNet (ELN)-2022 risk stratification model for 123 elderly acute myeloid leukemia (AML) patients treated with decitabine chemotherapy. RESULTS: Based on the ELN-2022 risk stratification, 15 (12.2%), 51 (41.5%), and 57 (46.3%) patients were classified as having favorable, intermediate, and high-risk AML, respectively. In comparison with the ELN-2017 risk stratification, the ELN-2022 risk stratification re-assigned 26 (21.1%) and three (2.4%) patients to the adverse and favorable risk groups, respectively. Survival analysis revealed distinctive overall survival (OS) outcomes among the ELN-2022 risk groups (6-month OS rate: 73.3%, 52.9%, and 47.7% for favorable, intermediate, and adverse risk, respectively; P = 0.101), with a parallel trend observed in the event-free survival (EFS) (6-month EFS rate: 73.3%, 52.9%, and 45.6% for favorable, intermediate, and adverse risk, respectively; P = 0.049). Notably, both OS and EFS in the favorable risk group were significantly superior in comparison to that of the adverse risk group (OS: P = 0.040, EFS: P = 0.030). Although the ELN-2022 C-index (0.559) was greater than the ELN-2017 C-index (0.539), the result was not statistically significant (P = 0.059). Based on the event net reclassification index, we consistently observed significant improvements in the ELN-2022 risk stratification for overall survival (0.21 at 6 months). CONCLUSION: In conclusion, the revised ELN-2022 risk stratification model may have improved the risk classification of elderly AML patients treated with hypomethylating agents compared to the ELN-2017 risk stratification model.


Assuntos
Leucemia Mieloide Aguda , Idoso , Humanos , Decitabina/uso terapêutico , Prognóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Intervalo Livre de Progressão , Medição de Risco
7.
Heliyon ; 10(6): e27892, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524535

RESUMO

Despite major advances in therapeutic platforms, most patients with multiple myeloma (MM) eventually relapse and succumb to the disease. Among the novel therapeutic options developed over the past decade, genetically engineered T cells have a great deal of potential. Cellular immunotherapies, including chimeric antigen receptor (CAR) T cells, are rapidly becoming an effective therapeutic modality for MM. Marrow-infiltrating lymphocytes (MILs) derived from the bone marrow of patients with MM are a novel source of T cells for adoptive T-cell therapy, which robustly and specifically target myeloma cells. In this review, we examine the recent innovations in cellular immunotherapies, including the use of dendritic cells, and cellular tools based on MILs, natural killer (NK) cells, and CAR T cells, which hold promise for improving the efficacy and/or reducing the toxicity of treatment in patients with MM.

8.
Sci Rep ; 14(1): 4308, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383681

RESUMO

The fall armyworm (FAW) Spodoptera frugiperda is a severe economic pest of multiple crops globally. Control of this pest is often achieved using insecticides; however, over time, S. frugiperda has developed resistance to new mode of action compounds, including diamides. Previous studies have indicated diamide resistance is a complex developmental process involving multiple detoxification genes. Still, the mechanism underlying the possible involvement of microRNAs in post-transcriptional regulation of resistance has not yet been elucidated. In this study, a global screen of microRNAs (miRNAs) revealed 109 known and 63 novel miRNAs. Nine miRNAs (four known and five novel) were differentially expressed between insecticide-resistant and -susceptible strains. Gene Ontology analysis predicted putative target transcripts of the differentially expressed miRNAs encoding significant genes belonging to detoxification pathways. Additionally, miRNAs are involved in response to diamide exposure, indicating they are probably associated with the detoxification pathway. Thus, this study provides comprehensive evidence for the link between repressed miRNA expression and induced target transcripts that possibly mediate diamide resistance through post-transcriptional regulation. These findings highlight important clues for further research to unravel the roles and mechanisms of miRNAs in conferring diamide resistance.


Assuntos
Inseticidas , MicroRNAs , Animais , Spodoptera/genética , MicroRNAs/genética , Diamida/farmacologia , Inseticidas/farmacologia , Regulação da Expressão Gênica , Resistência a Inseticidas/genética , Larva
9.
Ann Hematol ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38267559

RESUMO

The outcomes of patients with myeloma after exposed to penta-classes are extremely poor. Selinexor is the first approved exportin inhibitor for those patients, but intractable toxicities may limit its use. This retrospective study evaluated the real-world efficacy and safety of selinexor plus dexamethasone (XD) and involved 48 patients with multiple myeloma, who were treated from November 2020 to October 2022. Their median age was 64 years, and the median number of prior lines of therapy was 6. The overall response rate was 25%, and the median progression-free survival (PFS) was 2.1 months (95% confidence interval (CI), 1.7-2.5). Patients on a reduced initial dose, delayed treatment, and dose reduction had better PFS. After XD treatment failure, 17 patients received subsequent therapy and had a median PFS of 2.4 months. The median overall survival was 4.6 months (95% CI, 2.3-6.9). Among the patients, 12 (25%) and 17 (35%) experienced dose reduction and delayed treatment, respectively. Our data show that the real-world efficacy of XD treatment in heavily pretreated patients was modest and that improving treatment adherence through reducing initial doses or delaying treatments may improve patient outcomes.

10.
Biosens Bioelectron ; 248: 115987, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38176256

RESUMO

Point-of-care testing (POCT) for low-concentration protein biomarkers remains challenging due to limitations in biosensor sensitivity and platform integration. This study addresses this gap by presenting a novel approach that integrates a metal-enhanced fluorescence (MEF) biosensor within a capillary flow-driven microfluidic cartridge (CFMC) for the ultrasensitive detection of the Parkinson's disease biomarker, aminoacyl-tRNA synthetase complex interacting multi-functional protein 2 (AIMP-2). Crucial point to this approach is the orientation-controlled immobilization of capture antibody on a nanodimple-structured MEF substrate within the CFMC. This strategy significantly enhances fluorescence signals without quenching, enabling accurate quantification of low-concentration AIMP-2 using a simple digital fluorescence microscope with a light-emitting diode excitation source and a digital camera. The resulting platform exhibits exceptional sensitivity, achieving a limit of detection in the pg/mL range for AIMP-2 in human serum. Additionally, the CFMC design incorporates a capillary-driven passive sample transport mechanism, eliminating the need for external pumps and further simplifying the detection process. Overall, this work demonstrates the successful integration of MEF biosensing with capillary microfluidics for point-of-care applications.


Assuntos
Técnicas Biossensoriais , Técnicas Analíticas Microfluídicas , Humanos , Microfluídica , Técnicas Biossensoriais/métodos , Técnicas Analíticas Microfluídicas/métodos , Imunoensaio/métodos , Biomarcadores , Ouro
11.
Korean J Intern Med ; 39(2): 327-337, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38268194

RESUMO

BACKGROUND/AIMS: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. METHODS: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. RESULTS: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2-3, and 4-5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). CONCLUSION: The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.


Assuntos
Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Prognóstico , Fluordesoxiglucose F18 , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/tratamento farmacológico , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons
12.
Clin Lymphoma Myeloma Leuk ; 24(2): e50-e57.e2, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37973459

RESUMO

BACKGROUND: Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM). METHODS: We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM. RESULTS: The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death. CONCLUSION: Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.


Assuntos
Hepatite B , Mieloma Múltiplo , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Antígenos de Superfície da Hepatite B/farmacologia , Antígenos de Superfície da Hepatite B/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Antivirais/uso terapêutico , Ativação Viral , Vírus da Hepatite B , República da Coreia/epidemiologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico
13.
Cytotherapy ; 26(3): 242-251, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38142382

RESUMO

BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.


Assuntos
Neoplasias de Cabeça e Pescoço , Células Matadoras Naturais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Modelos Animais de Doenças , Linhagem Celular Tumoral , Camundongos Endogâmicos NOD , Camundongos SCID , Células Matadoras Naturais/metabolismo , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-38082768

RESUMO

In purpose of screening arrhythmia, wearable adhesive patch-type electrocardiographs that can measure electrocardiogram continuously for 14 days have been replacing the 24-hour Holter monitor. The reason for that is the patch-type electrocardiograph being smaller and lighter than the Holter monitor, making it more convenient for patients to coexist with in their daily lives. However, this type of electrocardiograph generates a lot of noise signals due to movements during various physical activities and extended wear time.While analyzing electrocardiograms automatically using software, noise signals make the analysis difficult and they may be misclassified as arrhythmia signals. These misclassified signals require a lot of effort and time from clinical technicians to reclassify them as noise. To resolve this problem, this study hypothesized that a deep learning algorithm could be used to screen noise signals. We used 7,467 noise signals and 15,638 ECG signals collected from arrhythmia patients and healthy people. The signals were divided into 10 seconds segments and labeled by cardiologists. We split the data into training and test datasets, ensuring no patient overlap.A hybrid noise classification model, Squeeze and Excitation - Residual Network - Vision Transformer (SE-ResNet-ViT) was developed using the training and validation datasets with an 8:2 ratio. We evaluated the performance of the model using a test dataset. The best F1 score was 0.964. The proposed model can effectively screen for noise signals and potentially reducing the time and effort required by clinical technicians.


Assuntos
Adesivos , Dispositivos Eletrônicos Vestíveis , Humanos , Eletrocardiografia , Arritmias Cardíacas/diagnóstico , Eletrocardiografia Ambulatorial
15.
Ergonomics ; : 1-10, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039103

RESUMO

Subacromial pain syndrome (SAPS) is the most common upper-extremity musculoskeletal problem among workers. In this study, a machine learning model was built to predict and classify the presence or absence of SAPS in assembly workers with shoulder joint range of motion (ROM) and muscle strength data using support vector machine (SVM). Permutation importance was used to determine important variables for predicting workers with or without SAPS. The accuracy of the support vector classifier (SVC) polynomial model for classifying workers with SAPS was 82.4%. The important variables in model construction were internal rotation and abduction of shoulder ROM and internal rotation of shoulder muscle strength. It is possible to accurately perform SAPS classification of workers with relatively easy-to-obtain shoulder ROM and muscle strength data using this model. In addition, preventing SAPS in workers is possible by adjusting the factors affecting model building using exercise or rehabilitation programs.Practitioner summary: This study aimed to create a machine learning model that can predict and classify SAPS using shoulder ROM and muscle strength and identify the variables that are of high importance in model construction. This model could be used to predict or classify workers' SAPS and manage or prevent SAPS.

16.
Front Oncol ; 13: 1209110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965454

RESUMO

Introduction: Pegylated granulocyte colony-stimulating factor (G-CSF) has been widely used for preventing febrile neutropenia in various types of cancer treatment. In the present study, we prospectively evaluated the safety and efficacy of pegfilgrastim as a primary prophylaxis of febrile neutropenia and infection among patients with relapsed refractory multiple myeloma (RRMM) treated with pomalidomide-based regimens. Methods: Thirty-three patients with RRMM who received pomalidomide and dexamethasone (Pd) with or without cyclophosphamide (PCd) were enrolled in this study. Twenty-eight patients were treated with PCd and 5 patients were treated with Pd. All patients were given pegfilgrastim subcutaneously with a single administration performed on the first day of each cycle as primary prophylaxis until the fourth cycle. Results: The median age of the patients was 75 (range 56-85), and the median prior line of therapy was 2 (range 2-6). Seventeen patients (51.5%) had any grade of neutropenia and 20 (60.6%) had any grade of thrombocytopenia before starting pomalidomide treatment. During the 4 cycles of treatment, grade 3 or more neutropenia occurred in 17 patients (51.5%), and 4 (12.1%) experienced grade 3 or more febrile neutropenia. Grade 3 or more infections occurred in 5 patients (15.2%). Interestingly, the patients with markedly increased ANC of more than 2 x 109/L compared to baseline ANC after 7 days of pegfilgrastim at 1st cycle of treatment showed a significantly lower incidence of grade 3-4 neutropenia. The most common adverse event of pegfilgrastim was fatigue, and all the adverse events caused by pegfilgrastim were grade 1 or 2. And there was no significant change in the immune cell population and cytokines during the administration of pegfilgrastim. Discussion: Considering that this study included elderly patients with baseline neutropenia, pegylated G-CSF could be helpful to prevent severe neutropenia, febrile neutropenia, or infection in patients with RRMM.

17.
Front Oncol ; 13: 1275076, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023191

RESUMO

Major advances in the treatment of multiple myeloma (MM) have been achieved by effective new agents such as proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies. Despite significant progress, MM remains still incurable and, recently, cellular immunotherapy has emerged as a promising treatment for relapsed/refractory MM. The emergence of chimeric antigen receptor (CAR) technology has transformed immunotherapy by enhancing the antitumor functions of T cells and natural killer (NK) cells, leading to effective control of hematologic malignancies. Recent advancements in gene delivery to NK cells have paved the way for the clinical application of CAR-NK cell therapy. CAR-NK cell therapy strategies have demonstrated safety, tolerability, and substantial efficacy in treating B cell malignancies in various clinical settings. However, their effectiveness in eliminating MM remains to be established. This review explores multiple approaches to enhance NK cell cytotoxicity, persistence, expansion, and manufacturing processes, and highlights the challenges and opportunities associated with CAR-NK cell therapy against MM. By shedding light on these aspects, this review aims to provide valuable insights into the potential of CAR-NK cell therapy as a promising approach for improving the treatment outcomes of MM patients.

18.
Zookeys ; 1173: 61-69, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564108

RESUMO

A new species of the family Issidae (Hemiptera, Auchenorrhyncha, Fulgoroidea), Dentatissuslongispinosussp. nov., is described from the Korean Peninsula. Morphological information is presented with photographs based on male and female specimens. A key to species of the genus Dentatissus is also provided.

19.
Zootaxa ; 5284(3): 593-600, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37518719

RESUMO

The third fossil record of a deraeocorine species, preserved as an inclusion in late Lower Miocene, Burdigalian amber from Hispaniola (Dominican Republic) is presented with a description of Electroderaeous crassicornis gen. and sp. nov. based on a well-preserved specimen.

20.
Ann Hematol ; 102(8): 2233-2240, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392367

RESUMO

Despite the development of effective agents for multiple myeloma (MM), the management of patients with high-risk MM (HRMM) is challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is regarded as upfront treatment for transplant-eligible patients with HRMM. In the present study, we retrospectively investigated the efficacies of two conditioning regimens for upfront ASCT in newly diagnosed patients with MM and high-risk features: high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL). In total, 221 patients underwent ASCT between May 2005 and June 2021; among these 221 patients, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS; not reached vs. 53.2 months; P = 0.091, median PFS; not reached vs. 31.7 months; P = 0.062). Additionally, multivariate analysis revealed that BUMEL was significantly associated with PFS (hazard ratio = 0.37, 95% confidence interval = 0.15-0.89, P = 0.026). We compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than very good partial response (VGPR) to frontline therapy, median PFS was significantly longer in the BUMEL group than in the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011). These findings indicate that BUMEL may be an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics; BUMEL may be more appropriate than HDMEL for patients with less than VGPR to frontline therapy.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Melfalan , Mieloma Múltiplo/tratamento farmacológico , Bussulfano , Estudos Retrospectivos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Condicionamento Pré-Transplante , Transplante de Células-Tronco
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