Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 114
Filtrar
1.
J Pediatr Hematol Oncol ; 46(5): e313-e316, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857191

RESUMO

In the most recent fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System, astroblastoma has been defined by molecular rearrangements involving the MN1 gene, with common partners being BEND2 or CXXC5 . Accordingly, this tumor entity is now known as "astroblastoma, MN1 -altered." However, gliomas with EWSR1::BEND2 fusions, devoid of MN1 fusion alterations, have recently been shown to exhibit astroblastoma-like histomorphologic features and reside in a distinct epigenetic subgroup based on DNA methylation studies similar to high-grade neuroepithelial tumor with MN1 alteration, which includes astroblastoma, MN1 altered tumors. This new epigenetically distinct subtype of astroblastoma containing EWSR1::BEND2 fusions lacks the required MN1 alteration and, thus, does not satisfy the current molecular classification of these lesions. Here, we describe a case of glioma with histologic features and DNA methylation profiling consistent with astroblastoma with a novel YAP1: : BEND2 fusion. This case and others further expand the molecular findings observable in astroblastoma-like tumors outside the constraints of MN1 alteration. Such cases of astroblastoma with EWSR1::BEND2 and YAP1::BEND2 fusions challenge the current molecular classification of astroblastoma based solely on an MN1 alteration.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Neuroepiteliomatosas , Proteínas de Fusão Oncogênica , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Masculino , Metilação de DNA , Fosfoproteínas/genética , Feminino
2.
Sci Rep ; 14(1): 14078, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890502

RESUMO

Ipomoea species have diverse uses as ornamentals, food, and medicine. However, their genomic information is limited; I. alba and I. obscura were sequenced and assembled. Their chloroplast genomes were 161,353 bp and 159,691 bp, respectively. Both genomes exhibited a quadripartite structure, consisting of a pair of inverted repeat (IR) regions, which are separated by the large single-copy (LSC) and small single-copy (SSC) regions. The overall GC content was 37.5% for both genomes. A total of 104 and 93 simple sequence repeats, 50 large repeats, and 30 and 22 short tandem repeats were identified in the two chloroplast genomes, respectively. G and T were more preferred than C and A at the third base position based on the Parity Rule 2 plot analysis, and the neutrality plot revealed correlation coefficients of 0.126 and 0.105, indicating the influence of natural selection in shaping the codon usage bias in most protein-coding genes (CDS). Genome comparative analyses using 31 selected Ipomoea taxa from Thailand showed that their chloroplast genomes are rather conserved, but the presence of expansion or contraction of the IR region was identified in some of these Ipomoea taxa. A total of five highly divergent regions were identified, including the CDS genes accD, ndhA, and ndhF, as well as the intergenic spacer regions psbI-atpA and rpl32-ccsA. Phylogenetic analysis based on both the complete chloroplast genome sequence and CDS datasets of 31 Ipomoea taxa showed that I. alba is resolved as a group member for series (ser.) Quamoclit, which contains seven other taxa, including I. hederacea, I. imperati, I. indica, I. nil, I. purpurea, I. quamoclit, and I. × sloteri, while I. obscura is grouped with I. tiliifolia, both of which are under ser. Obscura, and is closely related to I. biflora of ser. Pes-tigridis. Divergence time estimation using the complete chloroplast genome sequence dataset indicated that the mean age of the divergence for Ipomoeeae, Argyreiinae, and Astripomoeinae, was approximately 29.99 Mya, 19.81 Mya, and 13.40 Mya, respectively. The node indicating the divergence of I. alba from the other members of Ipomoea was around 10.06 Mya, and the split between I. obscura and I. tiliifolia is thought to have happened around 17.13 Mya. The split between the I. obscura accessions from Thailand and Taiwan is thought to have taken place around 0.86 Mya.


Assuntos
Composição de Bases , Genoma de Cloroplastos , Ipomoea , Filogenia , Ipomoea/genética , Ipomoea/classificação , Repetições de Microssatélites/genética , Análise de Sequência de DNA/métodos , Evolução Molecular , Uso do Códon
3.
Carbohydr Polym ; 334: 122043, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553239

RESUMO

Here, we prepared ionically crosslinked films using pectin extracted from agro-wastes, specifically ambarella peels (AFP) and jackfruit seed slimy sheath (JFS). Physiochemical properties of pectins, including moisture content, molecular weight (Mw), degree of esterification (DE), and galacturonic acid (GA), were analyzed. Optimal extraction was determined, i.e., citric acid concentration 0.3 M, time 60 min, solid/liquid ratio 1:25, and temperature 90 °C for AFP or 85 °C for JFS. Pectin yields under these conditions were 29.67 % ± 0.35 % and 29.93 ± 0.49 %, respectively. AFP pectin revealed Mw, DE, and GA values of 533.20 kDa, 67.08 % ± 0.68 %, and 75.39 ± 0.82 %, while JFS pectin exhibited values of 859.94 kDa, 63.04 % ± 0.47 %, and 78.63 % ± 0.71 %, respectively. The pectin films crosslinked with Ca2+, Cu2+, Fe3+, or Zn2+ exhibited enhanced tensile strength and Young's modulus, along with reduced elongation at break, moisture content, water solubility, water vapor permeability, and oxygen permeability. Structural analyses indicated metal ions were effectively crosslinked with carboxyl groups of pectin. Notably, the Cu2+-crosslinked film demonstrated superior water resistance, mechanical properties, and exhibited the highest antioxidant and antibacterial activities among all tested films. Therefore, the pectin films represent a promising avenue to produce eco-friendly food packaging materials with excellent properties.


Assuntos
Artocarpus , Pectinas , Artocarpus/química , Embalagem de Alimentos , Frutas/química , Íons/análise , Pectinas/química , Sementes
4.
Sci Rep ; 14(1): 3480, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347058

RESUMO

The ability to parse sound mixtures into coherent auditory objects is fundamental to cognitive functions, such as speech comprehension and language acquisition. Yet, we still lack a clear understanding of how auditory objects are formed. To address this question, we studied a speech-specific case of perceptual multistability, called verbal transformations (VTs), in which a variety of verbal forms is induced by continuous repetition of a physically unchanging word. Here, we investigated the degree to which auditory memory through sensory adaptation influences VTs. Specifically, we hypothesized that when memory persistence is longer, participants are able to retain the current verbal form longer, resulting in sensory adaptation, which in turn, affects auditory perception. Participants performed VT and auditory memory tasks on different days. In the VT task, Japanese participants continuously reported their perception while listening to a Japanese word (2- or 3-mora in length) played repeatedly for 5 min. In the auditory memory task, a different sequence of three morae, e.g., /ka/, /hi/, and /su/, was presented to each ear simultaneously. After some period (0-4 s), participants were visually cued to recall one of the sequences, i.e., in the left or right ear. We found that delayed recall accuracy was negatively correlated with the number of VTs, particularly under 2-mora conditions. This suggests that memory persistence is important for formation and selection of perceptual objects.


Assuntos
Percepção da Fala , Humanos , Rememoração Mental , Sinais (Psicologia) , Cognição , Fala , Memória de Curto Prazo , Percepção Auditiva
5.
J Biomed Opt ; 28(12): 126001, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38074217

RESUMO

Significance: Post-burn scars and scar contractures present significant challenges in burn injury management, necessitating accurate evaluation of the wound healing process to prevent or minimize complications. Non-invasive and accurate assessment of burn scar vascularity can offer valuable insights for evaluations of wound healing. Optical coherence tomography (OCT) and OCT angiography (OCTA) are promising imaging techniques that may enhance patient-centered care and satisfaction by providing detailed analyses of the healing process. Aim: Our study investigates the capabilities of OCT and OCTA for acquiring information on blood vessels in burn scars and evaluates the feasibility of utilizing this information to assess burn scars. Approach: Healthy skin and neighboring scar data from nine burn patients were obtained using OCT and processed with speckle decorrelation, Doppler OCT, and an enhanced technique based on joint spectral and time domain OCT. These methods facilitated the assessment of vascular structure and blood flow velocity in both healthy skin and scar tissues. Analyzing these parameters allowed for objective comparisons between normal skin and burn scars. Results: Our study found that blood vessel distribution in burn scars significantly differs from that in healthy skin. Burn scars exhibit increased vascularization, featuring less uniformity and lacking the intricate branching network found in healthy tissue. Specifically, the density of the vessels in burn scars is 67% higher than in healthy tissue, while axial flow velocity in burn scar vessels is 25% faster than in healthy tissue. Conclusions: Our research demonstrates the feasibility of OCT and OCTA as burn scar assessment tools. By implementing these technologies, we can distinguish between scar and healthy tissue based on its vascular structure, providing evidence of their practicality in evaluating burn scar severity and progression.


Assuntos
Cicatriz , Tomografia de Coerência Óptica , Humanos , Cicatriz/diagnóstico por imagem , Cicatriz/patologia , Tomografia de Coerência Óptica/métodos , Pele/irrigação sanguínea , Cicatrização , Neovascularização Patológica/patologia
6.
In Vivo ; 37(6): 2796-2802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905612

RESUMO

BACKGROUND/AIM: With the increasing use of marginal donors, it is important to identify factors for outcomes in kidney transplantation. The aim of the present study was to evaluate the influence of surgical complications for graft survival after kidney transplantation and identify risk factors for surgical complications. PATIENTS AND METHODS: We performed a retrospective cohort study by chart review of patients who underwent kidney transplantation at the Taichung Veterans General Hospital in the period from 2007 to 2018. RESULTS: Of the 433 patients who underwent kidney transplantation, 57 experienced surgical complications with an occurrence rate of 13.2%. The most common complications were vascular complications (n=31; 7.2%), followed by urologic (n=9; 2%) and wound (n=9; 2%) complications. From univariate analyses, risk factors for surgical complications were cold ischemia time, blood loss, operation time, number of vascular anastomoses and year of operation. From univariate and multivariate analyses, operation time was associated to surgical complications. Patients with surgical complications experienced worse both one-year and five-year death-censored graft and patient survival. CONCLUSION: Surgical complications were associated with higher risk of death-censored graft failure and mortality. Cold ischemia time, blood loss, operation time, number of vascular anastomoses and year of operation were risk factors for surgical complications. Efforts should aim to minimize surgical complications to improve both graft and patient survival.


Assuntos
Doenças Cardiovasculares , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Sobrevivência de Enxerto , Doenças Cardiovasculares/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia
7.
Lung Cancer ; 184: 107352, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37657238

RESUMO

OBJECTIVES: About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking. MATERIALS AND METHODS: We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort. RESULTS: We found sixteen nonsynonymous mutations harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22-26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182, miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients. CONCLUSION: Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Humanos , Sequenciamento do Exoma , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/genética , MicroRNAs/genética , Receptores ErbB/genética
8.
Oncol Lett ; 26(1): 284, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37274483

RESUMO

Patients with high-risk prostate cancer after prostatectomy have a particularly high chance of being diagnosed with biochemical recurrence (BCR). Patients with BCR have a greater risk of disease progression and mortality. The present retrospective observational study aimed to clarify the risk factors for the BCR of prostate cancer after radical prostatectomy in patients with high-risk and very high-risk prostate cancer. Patients diagnosed with prostate cancer who received radical prostatectomy in a single center from January 2009 to June 2020 were included in the study. Data from medical records were reviewed and the patients were followed up for ≥6 years. The primary outcome was BCR within 1 year after surgery. A total of 307 patients were included, with 187 in the high-risk group and 120 in the very high-risk group as classified by the National Comprehensive Cancer Network (NCCN) guidelines. Patients in the very high-risk group had a lower BCR-free survival rate compared with those in the high-risk group, with a high risk of BCR even if their PSA levels were initially undetectable after prostatectomy, and a high risk of postoperatively detectable PSA. In patients with undetectable PSA after prostatectomy, BCR was associated with the initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1). Postoperatively detectable PSA was associated with pathologic stage (T3bN0M0 and any N1) In conclusion, preoperative MRI imaging stage and PSA density are predictors for short-term BCR after prostatectomy. NCCN-defined high-risk patients with a high initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1) had a higher risk of BCR when compared with other patients with undetectable PSA, while those with pathologic stage (T3bN0M0 or any N1) displayed a higher risk of postoperatively detectable PSA. These findings may help urologists to identify patients for whom active therapeutic protocols are necessary.

9.
eNeuro ; 9(6)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36351819

RESUMO

Visual accuracy is consistently shown to be modulated around the time of the action execution. The neural underpinning of this motor-induced modulation of visual perception is still unclear. Here, we investigate with EEG whether it is related to the readiness potential, an event-related potential (ERP) linked to motor preparation. Across 18 human participants, the magnitude of visual modulation following a voluntary button press was found to correlate with the readiness potential amplitude measured during visual discrimination. Participants' amplitude of the readiness potential in a purely motor-task was also found to correlate with the extent of the motor-induced modulation of visual perception in the visuomotor task. These results provide strong evidence that perceptual changes close to action execution are associated with motor preparation processes and that this mechanism is independent of task contingencies. Further, our findings suggest that the readiness potential provides a fingerprint of individual visuomotor interaction.


Assuntos
Variação Contingente Negativa , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Percepção Visual , Potenciais Evocados , Desempenho Psicomotor
10.
J Neurosci ; 42(47): 8817-8825, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36223998

RESUMO

It is well known that recent sensory experience influences perception, recently demonstrated by a phenomenon termed "serial dependence." However, its underlying neural mechanisms are poorly understood. We measured ERP responses to pairs of stimuli presented randomly to the left or right hemifield. Seventeen male and female adults judged whether the upper or lower half of the grating had higher spatial frequency, independent of the horizontal position of the grating. This design allowed us to trace the memory signal modulating task performance and also the implicit memory signal associated with hemispheric position. Using classification techniques, we decoded the position of the current and previous stimuli and the response from voltage scalp distributions of the current trial. Classification of previous responses reached full significance only 700 ms after presentation of the current stimulus, consistent with retrieval of an activity-silent memory trace. Cross-condition classification accuracy of past responses (trained on current responses) correlated with the strength of serial dependence effects of individual participants. Overall, our data provide evidence for a silent memory signal that can be decoded from the EEG potential, which interacts with the neural processing of the current stimulus. This silent memory signal could be the physiological substrate subserving at least one type of serial dependence.SIGNIFICANCE STATEMENT The neurophysiological underpinnings of how past perceptual experience affects current perception are poorly understood. Here, we show that recent experience is reactivated when a new stimulus is presented and that the strength of this reactivation correlates with serial biases in individual participants, suggesting that serial dependence is established on the basis of a silent memory signal.


Assuntos
Potenciais Evocados Visuais , Percepção Visual , Adulto , Masculino , Humanos , Feminino , Percepção Visual/fisiologia , Viés , Potenciais Evocados
11.
Biomed Res Int ; 2022: 2832996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303584

RESUMO

Purpose: A non-invasive way of assessing post-transplant renal graft function has been needed. This study aimed to assess the micro-structural and micro-functional status of graft kidneys by using intravoxel incoherent motion- (IVIM-) diffusion-weighted imaging (DWI) to investigate delayed graft function (DGF) immediately after transplantation. Method: A prospective study was conducted on 37 patients, 14 with early graft function (EGF) and 23 with DGF (9 with complication, 14 without) who underwent IVIM-DWI, most often within 1-7 days after kidney transplantation. A total of 37 cases were collected and all the participants have been well-informed and signed their consents. In addition, the study conducted in this paper was approved by the Ethics Committee of Clinical Research, Taichung Veterans General Hospital (IRB number: CE14065). Using biexponential analysis of slow diffusion coefficient (D slow), fast diffusion coefficient (D fast), and perfusion fraction was performed. The apparent diffusion coefficient (ADC) was calculated by use of a monoexponential model. All parameters were measured from three different regions-of-interest (ROI), covering the entire renal parenchyma, cortex, and medulla. Results: D slow, perfusion fraction, and ADC were significantly higher in patients with EGF than DGF (all p values values <0.001). Especially, ADC measured from ROI covering the entire kidney parenchyma had the best cut-off value (1.93µm2/msec) with the highest area under the receiver operating characteristic curve (AUC 0.943) in differentiating EGF from DGF. For analysis of pair-wise differences, only the perfusion fraction values, measured from the ROI covering the renal cortex, were significantly higher in 14 DGF patients with no complications than in the 9 DGF patients with complications, with the best cut-off value of 12.3% and the AUC of 0.844. Conclusion: Noninvasive IVIM-DWI reliably differentiates DGF from EGF after kidney transplantation, and it may aid in identifying posttransplant complications and indications for renal biopsy.


Assuntos
Transplante de Rim , Humanos , Função Retardada do Enxerto/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Transplante de Rim/efeitos adversos , Estudos Prospectivos
13.
Eur J Neurosci ; 55(11-12): 3083-3099, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33559266

RESUMO

To maintain a continuous and coherent percept over time, the brain makes use of past sensory information to anticipate forthcoming stimuli. We recently showed that auditory experience of the immediate past is propagated through ear-specific reverberations, manifested as rhythmic fluctuations of decision bias at alpha frequencies. Here, we apply the same time-resolved behavioural method to investigate how perceptual performance changes over time under conditions of stimulus expectation and to examine the effect of unexpected events on behaviour. As in our previous study, participants were required to discriminate the ear-of-origin of a brief monaural pure tone embedded in uncorrelated dichotic white noise. We manipulated stimulus expectation by increasing the target probability in one ear to 80%. Consistent with our earlier findings, performance did not remain constant across trials, but varied rhythmically with delay from noise onset. Specifically, decision bias showed a similar oscillation at ~9 Hz, which depended on ear congruency between successive targets. This suggests rhythmic communication of auditory perceptual history occurs early and is not readily influenced by top-down expectations. In addition, we report a novel observation specific to infrequent, unexpected stimuli that gave rise to oscillations in accuracy at ~7.6 Hz one trial after the target occurred in the non-anticipated ear. This new behavioural oscillation may reflect a mechanism for updating the sensory representation once a prediction error has been detected.


Assuntos
Percepção Auditiva , Ritmo Teta , Estimulação Acústica/métodos , Encéfalo , Humanos , Ruído
14.
Int J Urol ; 29(1): 69-75, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34608678

RESUMO

OBJECTIVES: To investigate the significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. METHODS: Between January 2001 and December 2015, 548 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy in a single institution were included in this retrospective cohort study. Several clinicopathological characteristics and outcomes were explored. The crucial end-point was the diagnosis of contralateral upper tract recurrence after radical nephroureterectomy. RESULTS: Of the 548 patients, the median age was 68 years (range 24-93 years), and the median follow-up time after radical nephroureterectomy was 41 months (range 8-191 months). Contralateral upper tract recurrence occurred in 28 patients (5.1%). The median time period between radical nephroureterectomy and contralateral upper tract recurrence was 15.4 months (range 3.4-52.4 months). In the multivariate analysis, preoperative estimated glomerular filtration rate <30 mL/min/1.73 m2 (hazard ratio 3.08, P = 0.003) and tumor multifocality (hazard ratio 2.16, P = 0.043) were independent risk factors. CONCLUSION: Preoperative estimated glomerular filtration rate <30 and tumor multifocality are significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.


Assuntos
Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/cirurgia , Taxa de Filtração Glomerular , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Nefroureterectomia , Estudos Retrospectivos , Neoplasias Ureterais/epidemiologia , Neoplasias Ureterais/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto Jovem
15.
Theranostics ; 11(19): 9667-9686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646392

RESUMO

The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME. Methods: Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs in vitro and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics. In vivo patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs. Results: The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity in vitro and in vivo, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs. Conclusions: The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.


Assuntos
Reposicionamento de Medicamentos/métodos , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/fisiologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Proliferação de Células , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Detecção Precoce de Câncer , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/metabolismo , Preparações Farmacêuticas
16.
J Cardiovasc Magn Reson ; 23(1): 104, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34587984

RESUMO

BACKGROUND: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information. METHODS: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. RESULTS: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*. CONCLUSION: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.


Assuntos
Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio com Supradesnível do Segmento ST , Animais , Cães , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
17.
J Clin Invest ; 131(16)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34228648

RESUMO

Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the ß values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Epigenoma , Neoplasias Pulmonares/genética , Fumar/efeitos adversos , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibroblastos Associados a Câncer/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ilhas de CpG , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Fumar/genética , Fumar/metabolismo , Células Tumorais Cultivadas , Microambiente Tumoral/genética
18.
Diagnostics (Basel) ; 10(4)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260187

RESUMO

The purpose of this study was to identify the significant risk factors of urinary bladder recurrence (UBR) after nephroureterectomy (NUx) in patients with upper tract urothelial carcinoma (UTUC). A total of 550 patients diagnosed with UTUC between January 2001 and December 2015 were included in this retrospective study. The median age of our patients was 68 (range 24-93) and the median follow-up time after NUx was 40.3 months (range 8-191). The most important censored point of this study was the first episode of UBR. Of the 550 patients, UBR occurred in 164 patients (29.8%). One hundred and forty-two (86.6%) patients with UBR were identified within two years after NUx for UTUC, with the median time interval between NUx and UBR being 8.4 months (range 3-59.8). Through univariate analysis, the positive surgical margin (p = 0.049) and tumor multifocality (p = 0.024) were both significant prognostic factors for UBR-free survival after NUx in patients with UTUC. However, only tumor multifocality (p = 0.037) remained a significant prognostic factor by multivariate analysis. In conclusion, tumor multifocality is a significant risk factor of UBR after nephroureterectomy in patients with upper tract urothelial carcinoma.

19.
BMC Nephrol ; 21(1): 6, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906890

RESUMO

BACKGROUND: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies. METHODS: Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment. RESULTS: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. CONCLUSIONS: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.


Assuntos
Rejeição de Enxerto/imunologia , Fatores Imunológicos/uso terapêutico , Transplante de Rim , Rim/patologia , Adulto , Antibacterianos/uso terapêutico , Anticorpos , Soro Antilinfocitário/uso terapêutico , Biópsia , Bortezomib/uso terapêutico , Terapia Combinada , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Rim/mortalidade , Pessoa de Meia-Idade , Plasmaferese , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Rituximab/uso terapêutico , Análise de Sobrevida
20.
Asian J Surg ; 43(1): 257-264, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31324510

RESUMO

BACKGROUND/OBJECTIVES: To investigate the oncological and functional outcomes after partial nephrectomy for clinical stage T1 (cT1) renal cell carcinoma (RCC), and assess the association between excisional volume loss (EVL) and postoperative renal function. METHODS: We retrospectively reviewed 150 patients with cT1 RCC undergoing partial nephrectomy from 2002 to 2016. End-point evaluation was assessed by recurrence free survival (RFS), overall survival (OS), stage III and stage IV chronic kidney disease (CKD). Regression models were used to determine the risk factors of CKD after surgery. The relationship between EVL and renal function decline was evaluated using Spearman correlation method. RESULTS: Ninety patients with clinical stage T1a (cT1a) tumors and 60 patients with clinical stage T1b (cT1b) tumors were included. There were no differences in RFS, OS, and risk of stage III and stage IV CKD between the two groups. In Cox regression models, multivariate analysis showed that preoperative estimated glomerular filtration rate (eGFR) was an independent risk factor for developing stage III (hazard ratio 0.937, P < 0.001) and stage IV CKD (hazard ratio 0.929, P = 0.027). EVL was significantly associated with postoperative eGFR decrease. (Correlation Coefficient = 0.325, P = 0.003). CONCLUSIONS: Patients with cT1a and cT1b RCC have comparable oncological and functional outcome after partial nephrectomy, and preoperative eGFR is an independent factor to predict developing CKD. EVL has influence on the postoperative renal function decline.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Testes de Função Renal , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Rim/patologia , Rim/cirurgia , Nefrectomia/métodos , Recuperação de Função Fisiológica , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...