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1.
Radiology ; 312(3): e231525, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39254451

RESUMO

Background There are insufficient data comparing resorbable microspheres (RMs) with permanent trisacryl gelatin microspheres (TAGMs) for uterine artery embolization (UAE). Purpose To compare therapeutic efficacy and clinical outcomes in participants with symptomatic fibroids after UAE with RMs or TAGMs. Materials and Methods This randomized controlled trial included participants undergoing UAE for symptomatic fibroids at a single institution (from May 2021 to May 2023). Participants were randomized one-to-one to undergo UAE with either RMs or TAGMs. Numeric rating scale pain scores and cumulative fentanyl consumption were assessed for 24 hours after undergoing UAE. Anti-Mullerian hormone was measured to assess effects of UAE on ovarian function. MRI was performed before and 3 months after UAE to evaluate fibroid necrosis and uterine artery recanalization. Repeated variables such as pain were analyzed using Mann-Whitney U test with post hoc Bonferroni correction. Results Sixty female participants (mean age, 45.7 years ± 3.6 [SD]) completed the study, with 30 in each group. No evidence of a difference in pain scores was observed between groups (P > .99). Moreover, there was no evidence of a difference in the total fentanyl consumption at 24 hours after UAE between groups (median: RMs, 423 [IQR, 330-530] vs TAGMs, 562 [IQR, 437-780]; P = .15). Serum anti-Mullerian hormone 3 months after UAE showed no evidence of a difference between groups (RMs vs TAGMs, 0.71 ng/mL ± 0.73 vs 0.49 ng/mL ± 0.45, respectively; P = .09). No evidence of a difference in the rate of complete necrosis of the dominant fibroid was observed between groups (97% [29 of 30] for both groups; P > .99). The rate of uterine artery recanalization was higher in RM versus TAGM groups (70% [21 of 30] vs 17% [five of 30], respectively; P < .001). Conclusion UAE with RMs, compared with UAE with TAGMs, showed no evidence of a difference in terms of therapeutic effectiveness or postprocedural pain scores in participants with symptomatic fibroids. Clinical trial registration no. NCT05086770 © RSNA, 2024 See also the editorial by Spies in this issue.


Assuntos
Resinas Acrílicas , Gelatina , Leiomioma , Embolização da Artéria Uterina , Humanos , Feminino , Embolização da Artéria Uterina/métodos , Gelatina/uso terapêutico , Pessoa de Meia-Idade , Leiomioma/terapia , Leiomioma/diagnóstico por imagem , Resinas Acrílicas/uso terapêutico , Adulto , Microesferas , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico por imagem , Resultado do Tratamento , Medição da Dor
2.
Cancers (Basel) ; 16(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39001548

RESUMO

Head and neck cancers (HNC) are frequently associated with neurodegeneration. However, the association between HNC and Parkinson's disease (PD) remains unclear. This study aimed to clarify the relationship between HNC and subsequent PD. This retrospective study used data from a nationally representative cohort. Patients with HNC were identified based on the presence of corresponding diagnostic codes. Participants without cancer were selected using 4:1 propensity score matching based on sociodemographic factors and year of enrollment; 2296 individuals without HNC and 574 individuals with HNC were included in the study. Hazard ratios (HR) for the incidence of PD in patients with HNC were calculated using 95% confidence intervals (CI). The incidence of PD was 4.17 and 2.18 per 1000 person-years in the HNC and control groups, respectively (adjusted HR = 1.89, 95% CI = 1.08-3.33). The HNC group also showed an increased risk of subsequent PD development. The risk of PD was higher in middle-aged (55-69 years) patients with HNC and oral cavity cancer. Our findings suggest that middle-aged patients with HNC have an increased incidence of PD, specifically those with oral cavity cancer. Therefore, our findings provide new insights into the development of PD in patients with HNC.

3.
Tomography ; 10(7): 1031-1041, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39058049

RESUMO

BACKGROUND: There is little information regarding the size measurement differences in gallbladder (GB) polyps performed by different radiologists on abdominal ultrasonography (US). AIM: To reveal the differences in GB polyp size measurements performed by different radiologists on abdominal US. METHODS: From June to September 2022, the maximum diameter of 228 GB polyps was measured twice on abdominal US by one of three radiologists (a third-year radiology resident [reader A], a radiologist with 7 years of experience in abdominal US [reader B], and an abdominal radiologist with 8 years of experience in abdominal US [reader C]). Intra-reader agreements for polyp size measurements were assessed by intraclass correlation coefficient (ICC). A Bland-Altman plot was used to visualize the differences between the first and second size measurements in each reader. RESULTS: Reader A, reader B, and reader C evaluated 65, 77, and 86 polyps, respectively. The mean size of measured 228 GB polyps was 5.0 ± 1.9 mm. Except for the case where reader A showed moderate intra-reader agreement (0.726) for polyps with size ≤ 5 mm, all readers showed an overall high intra-reader reliability (reader A, ICC = 0.859; reader B, ICC = 0.947, reader C, ICC = 0.948), indicative of good and excellent intra-reader agreements. The 95% limit of agreement of reader A, B, and C was 1.9 mm of the mean in all three readers. CONCLUSIONS: GB polyp size measurement on abdominal US showed good or excellent intra-reader agreements. However, size changes of approximately less than 1.9 mm should be interpreted carefully because these may be within the measurement error.


Assuntos
Pólipos , Radiologistas , Ultrassonografia , Humanos , Pólipos/diagnóstico por imagem , Pólipos/patologia , Ultrassonografia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Idoso , Adulto , Variações Dependentes do Observador , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/patologia , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/patologia , Abdome/diagnóstico por imagem , Abdome/patologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia
4.
Nat Genet ; 56(7): 1446-1455, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38969834

RESUMO

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel-Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL's coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype-phenotype relationships across complete genes.


Assuntos
Alelos , Carcinoma de Células Renais , Edição de Genes , Neoplasias Renais , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor Von Hippel-Lindau , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Humanos , Edição de Genes/métodos , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Linhagem Celular Tumoral , Predisposição Genética para Doença , Mutação
5.
Cancers (Basel) ; 16(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38792008

RESUMO

Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50-1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer.

6.
Cancers (Basel) ; 16(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611030

RESUMO

Although cancer and ischemic heart disease (IHD) frequently manifest in the same individual, the risk of IHD events in cancer, especially head and neck cancer (HNC), remains unclear. We aimed to examine the incidence and risk of IHD events in patients with HNC using a population-based cohort dataset in South Korea (2002-2013). Through rigorous propensity score matching, we compared data from 2816 individuals without HNC and 704 individuals with HNC. Key independent variables were matched between groups, and the Charlson Comorbidity Index was used to match comorbidities. The Kaplan-Meier method depicted the cumulative probability of IHD throughout the follow-up period for both the study and control groups. The overall IHD incidence was significantly higher (19.93) in patients with HNC than in those without HNC (14.81), signifying an augmented IHD risk in the HNC cohort. Subsequent temporal analysis revealed a significant surge in IHD risk commencing 4 years after HNC diagnosis and persisting throughout the follow-up period. Subgroup analysis revealed an increased IHD risk in men with HNC and patients with cancers affecting the oral and sinonasal regions. This retrospective cohort study provides valuable scientific insights into the nuanced relationship between HNC and IHD, underscoring the need for tailored monitoring protocols and specialized care for susceptible individuals.

7.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612663

RESUMO

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.


Assuntos
Imunidade Inata , Pólipos Nasais , Humanos , Animais , Camundongos , Linfócitos , Inflamação/tratamento farmacológico , Citocinas , Poeira , Mucosa Nasal , Material Particulado/toxicidade
8.
Ultrasound Q ; 40(2): 132-135, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38470608

RESUMO

ABSTRACT: This study aimed to assess the detection rate of small (<10 mm) pancreas cyst and intrareader reliability for cyst size measurements on transabdominal ultrasonography (US). From 2020 to 2022, 194 pancreas cysts in 173 patients, incidentally detected on computed tomography or magnetic resonance imaging, were evaluated on US by 1 of 2 radiologists (readers 1 and 2). Intrareader agreements of cyst size measurements on US were assessed by intraclass correlation coefficient (ICC). Bland-Altman plot was used to visualize the differences between the first and second size measurements in each reader. In this study, readers 1 and 2 evaluated 86 cysts in 76 patients and 108 cysts in 97 patients, respectively. Most of the cysts (191 of 194) were located in the nontail portion of the pancreas. Overall detection rate of pancreas cysts by US was 92.3% (179 of 194). The mean size of measured 179 pancreas cysts was 4.7 ± 1.5 mm. The readers showed excellent intrareader agreements (ICC = 0.925 and 0.960) for cyst size measurements, except for the cysts with size ≤5 mm, where both readers showed good intrareader agreements (ICC = 0.848 and 0.873). The 95% limits of agreement of readers 1 and 2 were 13.8% and 14.9% of the mean, respectively. Therefore, transabdominal US could be a reliable follow-up imaging modality for small (<10 mm) nontail pancreas cysts incidentally detected on computed tomography or magnetic resonance imaging, especially for the cysts with size between 5 and 10 mm. Size changes of the pancreas cysts approximately less than 15% may be within the measurement error.


Assuntos
Pâncreas , Cisto Pancreático , Ultrassonografia , Humanos , Cisto Pancreático/diagnóstico por imagem , Ultrassonografia/métodos , Feminino , Masculino , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Idoso , Adulto , Tomografia Computadorizada por Raios X/métodos , Variações Dependentes do Observador , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Idoso de 80 Anos ou mais
9.
Cancers (Basel) ; 16(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38539417

RESUMO

An increased risk of cancer among patients with rheumatoid arthritis (RA) has been reported. However, the risk of RA events among patients with head and neck cancer (HNC) is unknown. Therefore, we investigated the incidence and risk of RA among patients with HNC. This study was based on a cohort dataset. Overall, 2824 individuals without HNC and 706 patients with HNC were selected using propensity score matching. The overall RA event rate was 12.19 for patients with HNC and 7.60 for those without HNC. A significantly increased risk of developing RA was also observed among patients with HNC. The risk of developing RA over time was relatively high within the first year after HNC diagnosis; further, it increased significantly during the follow-up period. Moreover, middle-aged male patients with HNC exhibited an increased risk of developing RA compared with the controls; however, no significant difference was noted among female patients or other age groups. Notably, subgroup analysis according to cancer subtype revealed that only oral cancer survivors had an increased risk of developing RA. These results underscore the importance of vigilant monitoring by clinicians to promptly identify the onset of RA in patients with HNC.

10.
Front Oncol ; 14: 1349632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352890

RESUMO

Purpose: The purpose of this study is to elucidate the patterns of recurrence of hepatocellular carcinoma and to analyze factors that can predict recurrence after complete response to radioembolization. Materials and methods: A total of 289 consecutive patients who underwent radioembolization for the treatment of hepatocellular carcinoma at a single tertiary center were retrospectively reviewed. Baseline characteristics were collected and compared between the group showing complete response and the group showing noncomplete response. Data on recurrence status, time to recurrence, and the patterns of recurrence among the patients who showed radiologic complete response were collected. The group that maintained complete response and the group that experienced recurrence were compared, and the risk factors affecting recurrence were evaluated by logistic regression analysis. Results: The complete response rate was 24.9% (73/289). Age, sex, tumor markers, maximum tumor diameter, multiplicity, presence of vascular invasion, and target radiation dose were significantly different between the complete response and noncomplete response groups. The recurrence rate after complete response was 38.4% (28/73), and 67.9% (19/28) of recurrences occurred by 8 months after complete response. Eight patients who underwent resection/transplantation after complete response experienced no recurrence. Multiple tumors and a lower target radiation dose were independent risk factors of recurrence after complete response in the multivariate logistic regression. Conclusion: Hepatocellular carcinoma recurrence following complete response after radioembolization is not uncommon and frequently occurs within 1 year after complete response. Multiple tumors and a lower target radiation dose may be risk factors for recurrence.

11.
Cancers (Basel) ; 15(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38067220

RESUMO

Patients with head and neck cancer (HNC) often experience cognitive impairment. However, the relationship between cancer and Alzheimer's disease (AD) remains unclear. We aimed to elucidate the relationship between patients with HNC and their subsequent AD development. This retrospective study used data from a nationwide representative cohort sample, the Korean National Health Insurance Service Cohort. The cancer group was defined based on the presence of diagnostic codes for HNC (C00-C14 and C30-C32). After matching the independent variables with a propensity score of 4:1, a total of 2304 people without HNC and 576 with HNC were enrolled in this study. Hazard ratios (HRs) of AD incidence (per 1000 person-years) and 95% confidence intervals (CIs) in HNC patients were calculated. The incidence of AD was 14.92 in HNC patients and 9.77 in non-cancer patients. Additionally, the HNC group was found to have a higher risk of developing AD compared with the non-cancer group. Female and middle-aged HNC patients had a higher risk of developing AD events compared with other subgroups. Surprisingly, during the observation period, the risk of developing AD was relatively high within the first year after HNC diagnosis. In conclusion, our study suggests that HNC and AD are positively correlated.

12.
Allergy Asthma Immunol Res ; 15(5): 647-658, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37827981

RESUMO

PURPOSE: Several studies have reported a possible link between chronic rhinosinusitis (CRS) and rheumatoid arthritis (RA). However, it remains unclear whether CRS could influence the risk of developing RA. Therefore, in this study, we focused on examining the association between CRS and RA. METHODS: A total of 14,867 individuals with CRS and 14,867 without CRS were enrolled after 1:1 propensity score match from a nationwide longitudinal cohort database in South Korea. RA incidence was assessed using person-years at risk, and the hazard ratio (HR) was examined using the Cox proportional hazards model. RESULTS: The incidence of RA (per 1,000 person-years) was 6.51 for those with CRS, 6.55 for those with CRS without nasal polyps (CRSsNP), and 5.96 for those with CRS with nasal polyps (CRSwNP). We found that CRS individuals had a significantly increased risk of subsequent RA development with an adjusted HR of 1.41, regardless of the phenotype (adjusted HR was 1.42 in CRSsNP and 1.37 in CRSwNP patients). Moreover, the risk of developing RA over time was relatively higher within the first 4 years after the diagnosis of CRS. CONCLUSIONS: Our nationwide population-based cohort study suggests that CRS may be associated with a subsequent increase in RA events, regardless of the phenotype. Therefore, physicians should consider RA risk when diagnosing and treating CRS patients.

13.
J Belg Soc Radiol ; 107(1): 77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781476

RESUMO

Objectives: To identify the factors associated with Baker's cyst rupture on MRI. Material and methods: From January 2021 to December 2022, a total of 441 knee MRI examinations in 441 patients (mean age: 47.7 ± 13.8 years) with Baker's cyst were included in this study. Patients were classified into two groups: those with ruptured vs. unruptured Baker's cysts. On knee radiograph, osteoarthritis grade was assessed based on Kellgren-Lawrence grade. On MRI, combined structure injuries, alignment type between semimembranosus tendon and medial head of gastrocnemius tendon, amount of joint effusion, presence of septation, maximal diameters of cyst, and cyst volume were evaluated. Receiver operating characteristic (ROC) analysis was performed to assess the predictive performances of imaging factors for cyst rupture. Results: There were 146 patients with Baker's cyst rupture and 295 patients without rupture. Patients with cyst rupture showed significantly longer maximal transverse diameter (25.8 ± 6.8 mm vs. 21.6 ± 5.8 mm, p = 0.035) and larger volume (13.3 ± 6.2 cm3 vs. 9.9 ± 5.1 cm3, p = 0.012) than those without rupture. On ROC analysis, maximal transverse diameter of cyst ≥ 22.2 mm (sensitivity = 64.4%, specificity = 54.9%) and cyst volume ≥ 10.9 cm3 (sensitivity = 71.2%, specificity = 58.3%) were the cutoff values for predicting rupture of cyst, respectively. The cyst volume showed significantly higher area under the curve (AUC) than maximal transverse diameter (0.726 vs. 0.642, p = 0.002). Conclusion: Longer transverse diameter and larger volume of Baker's cyst could be predictive imaging parameters for cyst rupture.

14.
Polymers (Basel) ; 15(18)2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37765638

RESUMO

The interfacial adhesion between carbon fibers (CFs) and a thermoplastic matrix is an important aspect that should be improved in manufacturing CF-reinforced thermoplastics with high strength and rigidity. In this study, the effects of a two-step surface treatment comprising electrochemical oxidation and silane treatment of the CF surface on the mechanical properties of CF/maleic anhydride-grafted polypropylene (MAPP) composites were confirmed. The surface characteristics of the treated CFs were analyzed via scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The tensile testing of a single CF and interfacial adhesion of the samples before and after the surface treatment were analyzed using a single-fiber testing machine and a universal testing machine. After the silane treatment, the roughness of the CF surface increased due to the formation of a siloxane network. In addition, the interfacial shear strength increased by ∼450% compared to that of the untreated CFs due to the covalent bond between the -NH2 end group of siloxane and MAPP. This two-step surface treatment, which can be performed continuously, is considered an effective method for improving the mechanical interface strength between the CF and polymer matrix.

15.
Cancer Imaging ; 23(1): 85, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700359

RESUMO

BACKGROUND: 18Fluorine-Fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities. Although the usefulness of 18F-FDG PET has been reported in several endocrine diseases, studies on pituitary disease are extremely limited. To evaluate whether dexamethasone (DEX) suppression can improve 18F-FDG PET for the localization of adrenocorticotropic hormone-secreting adenomas in the pituitary gland in Cushing's disease (CD). METHODS: We included 22 patients with CD who underwent PET imaging before and after DEX administration. We compared the success rates of PET before and after DEX suppression, magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus sampling (BIPSS). We determined the final locations of adenomas based on intraoperative multiple-staged resection and tumor tissue identification using frozen sections. Standardized uptake value (SUV) were analyzed to confirm the change of intensity of adenomas on PET. RESULTS: Twenty-two patients were included (age at diagnosis: 37 [13-56] years), and most were women (90.91%). Pituitary adenomas compared to normal pituitaries showed increased maximum SUV after DEX suppression but without statistical significance (1.13 versus. 1.21, z=-0.765, P = 0.444). After DEX suppression, the mean and maximum SUV of adenomas showed a positive correlation with nadir cortisol levels in high-dose DEX suppression test (Rho = 0.554, P = 0.007 and Rho = 0.503, P = 0.017, respectively). In reference sites, mean SUV of cerebellum was significantly decreased (7.65 vs. 6.40, P = 0.006*), but those of the thalamus and gray matter was increased after DEX suppression (thalamus, 8.70 vs. 11.20, P = 0.010*; gray matter, 6.25 vs. 7.95, P = 0.010*). CONCLUSION: DEX suppression did not improve 18F-FDG PET/CT localization in patients with CD.


Assuntos
Neoplasias Hipofisárias , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Hormônio Adrenocorticotrópico , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Dexametasona
16.
Cell Commun Signal ; 21(1): 219, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612584

RESUMO

BACKGROUND: Megakaryocytes (MKs) are platelet precursors, which arise from hematopoietic stem cells (HSCs). While MK lineage commitment and differentiation are accompanied by changes in gene expression, many factors that modulate megakaryopoiesis remain to be uncovered. Replication initiation determinant protein (RepID) which has multiple histone-code reader including bromodomain, cryptic Tudor domain and WD40 domains and Cullin 4-RING E3 ubiquitin ligase complex (CRL4) recruited to chromatin mediated by RepID have potential roles in gene expression changes via epigenetic regulations. We aimed to investigate whether RepID-CRL4 participates in transcriptional changes required for MK differentiation. METHODS: The PCR array was performed using cDNAs derived from RepID-proficient or RepID-deficient K562 erythroleukemia cell lines. Correlation between RepID and DAB2 expression was examined in the Cancer Cell Line Encyclopedia (CCLE) through the CellMinerCDB portal. The acceleration of MK differentiation in RepID-deficient K562 cells was determined by estimating cell sizes as well as counting multinucleated cells known as MK phenotypes, and by qRT-PCR analysis to validate transcripts of MK markers using phorbol 12-myristate 13-acetate (PMA)-mediated MK differentiation condition. Interaction between CRL4 and histone methylation modifying enzymes were investigated using BioGRID database, immunoprecipitation and proximity ligation assay. Alterations of expression and chromatin binding affinities of RepID, CRL4 and histone methylation modifying enzymes were investigated using subcellular fractionation followed by immunoblotting. RepID-CRL4-JARID1A-based epigenetic changes on DAB2 promoter were analyzed by chromatin-immunoprecipitation and qPCR analysis. RESULTS: RepID-deficient K562 cells highly expressing MK markers showed accelerated MKs differentiation exhibiting increases in cell size, lobulated nuclei together with reaching maximum levels of MK marker expression earlier than RepID-proficient K562 cells. Recovery of WD40 domain-containing RepID constructs in RepID-deficient background repressed DAB2 expression. CRL4A formed complex with histone H3K4 demethylase JARID1A in soluble nucleus and loaded to the DAB2 promoter in a RepID-dependent manner during proliferation condition. RepID, CRL4A, and JARID1A were dissociated from the chromatin during MK differentiation, leading to euchromatinization of the DAB2 promoter. CONCLUSION: This study uncovered a role for the RepID-CRL4A-JARID1A pathway in the regulation of gene expression for MK differentiation, which can form the basis for the new therapeutic approaches to induce platelet production. Video Abstract.


Assuntos
Núcleo Celular , Histonas , Proteínas de Ciclo Celular , Diferenciação Celular , Cromatina , Domínio Tudor
17.
Res Sq ; 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37461562

RESUMO

Background Megakaryocytes (MKs) are platelet precursors, which arise from hematopoietic stem cells (HSCs). While MK lineage commitment and differentiation are accompanied by changes in gene expression, many factors that modulate megakaryopoiesis remain to be uncovered. Replication origin binding protein (RepID) which has multiple histone-code reader including bromodomain, cryptic Tudor domain and WD40 domains and Cullin 4-RING ubiquitin ligase complex (CRL4) recruited to chromatin mediated by RepID have potential roles in gene expression changes via epigenetic regulations. We aimed to investigate whether RepID-CRL4 participates in transcriptional changes required for MK differentiation. Methods The PCR array was performed using cDNAs derived from RepID-proficient or RepID-deficient K562 erythroleukemia cell lines. Correlation between RepID and DAB2 expression was examined in the Cancer Cell Line Encyclopedia (CCLE) through the CellMinerCDB portal. The acceleration of MK differentiation in RepID-deficient K562 cells was determined by estimating cell sizes as well as counting multinucleated cells known as MK phenotypes, and by qRT-PCR analysis to validate transcripts of MK markers using phorbol 12-myristate 13-acetate (PMA)-mediated MK differentiation condition. Interaction between CRL4 and histone methylation modifying enzymes were investigated using BioGRID database, immunoprecipitation and proximity ligation assay. Alterations of expression and chromatin binding affinities of RepID, CRL4 and histone methylation modifying enzymes were investigated using subcellular fractionation followed by immunoblotting. RepID-CRL4-JARID1A-based epigenetic changes on DAB2 promoter were analyzed by chromatin-immunoprecipitation and qPCR analysis. Results RepID-deficient K562 cells highly expressing MK markers showed accelerated MKs differentiation exhibiting increases in cell size, lobulated nuclei together with reaching maximum levels of MK marker expression earlier than RepID-proficient K562 cells. Recovery of WD40 domain-containing RepID constructs in RepID-deficient background repressed DAB2 expression. CRL4A formed complex with histone H3K4 demethylase JARID1A in soluble nucleus and loaded to the DAB2 promoter in a RepID-dependent manner during proliferation condition. RepID, CRL4A, and JARID1A were dissociated from the chromatin during MK differentiation, leading to euchromatinization of the DAB2 promoter. Conclusion This study uncovered a role for the RepID-CRL4A-JARID1A pathway in the regulation of gene expression for MK differentiation, which can form the basis for the new therapeutic approaches to induce platelet production.

18.
Cancers (Basel) ; 15(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37444613

RESUMO

Several studies have shown that head and neck cancer is associated with an increased risk of stroke incidence. However, investigations of the association between the two diseases based on a matching cohort dataset are still limited. Therefore, we identified the incidence and risk of stroke in patients with head and neck cancer using a nationwide population-based cohort dataset. A total of 5248 individuals without cancer and 1312 with cancer were enrolled from the dataset after a 4:1 propensity score matching. We found that the incidence of overall stroke (per 1000 person years) was 19.29 for those with head and neck cancer, consisting of 17.32 as ischemic type and 2.74 as hemorrhagic type. Additionally, patients with head and neck cancer had a significantly increased risk of overall and ischemic stroke development but not hemorrhagic stroke. Moreover, the risk of stroke development over time was relatively high within the first year after the diagnosis of head and neck cancer. However, in the subgroup analysis, oral cavity cancer survivors showed an increased risk of both ischemic and hemorrhagic strokes. Therefore, our nationwide population-based cohort study suggests that clinicians should closely monitor patients with head and neck cancers for the early detection of stroke.

19.
PLoS One ; 18(7): e0289225, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37494372

RESUMO

OBJECTIVE: To evaluate the precipitating factors and symptoms of primary spontaneous pneumomediastinum (PSPM) and to assess the factors related with recurrent spontaneous pneumomediastinum (RSPM). METHODS: From 2010 to 2021, 237 PSPM patients were included in this retrospective study. Clinical information including in-hospital periods, morbidity, mortality, presenting symptoms, precipitating events, smoking, and asthma history was obtained. The patients with smoking history were subdivided into "ex-smoker" or "current smoker". The severity of asthma was categorized into "mild intermittent", "mild persistent", "moderate persistent", or "severe persistent". During follow-up, patients with RSPM were classified into "recurrence" group and the others were into "no recurrence" group. Multivariate regression analysis was used to elucidate the associated factors with RSPM. RESULTS: The mean age of study patients (men: women = 222: 15) was 23.4 years and mean period of hospital stay was 7.5 days. There was no mortality and morbidity. Most frequent symptom and precipitating factor were acute chest pain (n = 211, 89.0%) and cough (n = 72, 30.4%), respectively. RSPM occurred in 11 patients (4.6%). The proportion of patients with smoking (72.8% vs. 37.1%, p = 0.010) or asthma (81.8% vs. 39.8%, p<0.001) was significantly higher in "recurrence" group than "no recurrence" group. On multivariate analysis, asthma was the only factor associated with RSPM (mild intermittent/persistent, OR = 7.092, p = 0.047; moderate persistent, OR = 8.000, p = 0.011). CONCLUSION: PSPM is a benign disease with no morbidity and mortality. Asthma may be the associated factor with RSPM; thus, despite the low rate of recurrence, patients with asthma should be informed about the chance of RSPM.


Assuntos
Asma , Enfisema Mediastínico , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Estudos Retrospectivos , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/complicações , Asma/complicações , Asma/epidemiologia , Asma/diagnóstico , Dor no Peito/complicações , Tosse/complicações
20.
J Vasc Interv Radiol ; 34(9): 1565-1574, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37302472

RESUMO

PURPOSE: To evaluate the feasibility and safety of robot-assisted transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using a new coaxial microcatheter driving controller-responder robot (CRR) system. MATERIALS AND METHODS: A single-center prospective pilot study approved by the institutional review board was conducted using this CRR developed after analyzing 20 cases of conventional TACE procedures from May to October 2021. The study included 10 patients with HCCs: 5 (median age, 72 years; range, 64-73 years) underwent robot-assisted TACE, and 5 (median age, 57 years; range, 44-76 years) underwent conventional TACE for comparison. The feasibility and safety of robot-assisted TACE were evaluated by assessing the technical success, procedure time, adverse event rate, radiation dose, and early tumor response. RESULTS: The entire TACE procedure was divided into 30 steps, of which 8 could be robotized. In robot-assisted TACE, technical success was achieved in 4 (80%) of 5 patients. No procedure-related adverse event was observed. The median procedure time was 56 minutes. At the 1-month follow-up, 3 of the 4 patients showed a complete or partial response after robot-assisted TACE. The median radiation doses for the operator and patients were 0.4 and 2,167.5 µSv in robot-assisted TACE and 53.2 and 2,989.7 µSv in conventional TACE, respectively. CONCLUSIONS: Robot-assisted TACE using a new CRR system was feasible and safe for the treatment of HCC and could remarkably decrease radiation exposure for the operators.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Robótica , Humanos , Idoso , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Estudos Retrospectivos
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