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1.
Neural Regen Res ; 20(1): 107-115, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38767480

RESUMO

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields, including neurology and neuroscience. High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern, which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, epilepsy, and traumatic brain injury. Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern, such as glycyrrhizin, ethyl pyruvate, and neutralizing anti-high-mobility group box 1 antibodies, are commonly used to target high-mobility group box 1 activity in central nervous system disorders. Although it is commonly known for its detrimental inflammatory effect, high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders. In this narrative review, we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern, its downstream receptors, and intracellular signaling pathways, how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system, and clues on how to differentiate the pro-regenerative from the pro-inflammatory role. Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

2.
Eur J Cancer ; 208: 114194, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38968872

RESUMO

INTRODUCTION: This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. METHODS: Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0-1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. RESULTS: In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1-7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3-4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0-8.1) and median overall survival was 11.4 months (95 % CI, 9.8-15.5). CONCLUSION: NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen.

3.
MethodsX ; 13: 102781, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38978971

RESUMO

Oligodendrocytes (OLs) are glial cells responsible for the formation of myelin sheaths in the central nervous system. The characteristic features of the oligodendrocyte lineage, ranging from proliferative and migratory oligodendrocyte progenitor cells (OPC) to myelinating mature OLs, can be observed in vitro cultures of OL lineage cells. Here, we introduce a method for analyzing the spatial distribution of OPCs, which reflects their capacity for proliferation and migration, and the morphological complexity of mature OLs, which reflects their capacity for myelin formation, from immunostaining images of in vitro OL cultures. Through the methods described, we have demonstrated the tendency for OPCs to cluster in an environment with epidermal growth factor (EGF), and the differing morphological complexity of mature OLs according to culture medium and duration of differentiation.•The proliferative and migratory characteristics of OPCs can be evaluated by analyzing their spatial distribution.•The myelin-forming capacity of mature OLs can be measured by analyzing their morphological complexity.•Image-based analyses may be a substitute for more convoluted experiments to assess OL function.

4.
Cancer Res Treat ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38993093

RESUMO

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from 6 available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion: Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

5.
Heliyon ; 10(8): e29359, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38655345

RESUMO

Oligodendrocytes (OL) are myelin-forming glial cells in the central nervous system. In vitro primary OL culture models offer the benefit of a more readily controlled environment that facilitates the examination of diverse OL stages and their intricate dynamics. Although conventional methods for primary OL culture exist, their performance in terms of simplicity and efficiency can be improved. Here, we introduce a novel method for primary OL culture, namely the E3 (easy, efficient, and effective) method, which greatly improves the simplicity and efficiency of the primary OL culture procedure using neonatal rodent brains. We also provided the optimal media composition for the augmentation of oligodendrocyte progenitor cell (OPC) proliferation and more robust maturation into myelin-forming OLs. Overall, E3 offers an undemanding method for obtaining primary OLs with high yield and quality. Alongside its value as a practical tool, in vitro characteristics of the OL lineage additionally identified during the development of the E3 method have implications for advancing research on OL physiology and pathophysiology.

6.
Curr Oncol ; 31(4): 2278-2288, 2024 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-38668072

RESUMO

Background: Accurate detection of axillary lymph node (ALN) metastases in breast cancer is crucial for clinical staging and treatment planning. This study aims to develop a deep learning model using clinical implication-applied preprocessed computed tomography (CT) images to enhance the prediction of ALN metastasis in breast cancer patients. Methods: A total of 1128 axial CT images of ALN (538 malignant and 590 benign lymph nodes) were collected from 523 breast cancer patients who underwent preoperative CT scans between January 2012 and July 2022 at Hallym University Medical Center. To develop an optimal deep learning model for distinguishing metastatic ALN from benign ALN, a CT image preprocessing protocol with clinical implications and two different cropping methods (fixed size crop [FSC] method and adjustable square crop [ASC] method) were employed. The images were analyzed using three different convolutional neural network (CNN) architectures (ResNet, DenseNet, and EfficientNet). Ensemble methods involving and combining the selection of the two best-performing CNN architectures from each cropping method were applied to generate the final result. Results: For the two different cropping methods, DenseNet consistently outperformed ResNet and EfficientNet. The area under the receiver operating characteristic curve (AUROC) for DenseNet, using the FSC and ASC methods, was 0.934 and 0.939, respectively. The ensemble model, which combines the performance of the DenseNet121 architecture for both cropping methods, delivered outstanding results with an AUROC of 0.968, an accuracy of 0.938, a sensitivity of 0.980, and a specificity of 0.903. Furthermore, distinct trends observed in gradient-weighted class activation mapping images with the two cropping methods suggest that our deep learning model not only evaluates the lymph node itself, but also distinguishes subtler changes in lymph node margin and adjacent soft tissue, which often elude human interpretation. Conclusions: This research demonstrates the promising performance of a deep learning model in accurately detecting malignant ALNs in breast cancer patients using CT images. The integration of clinical considerations into image processing and the utilization of ensemble methods further improved diagnostic precision.


Assuntos
Axila , Neoplasias da Mama , Aprendizado Profundo , Metástase Linfática , Tomografia Computadorizada por Raios X , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Feminino , Metástase Linfática/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Adulto , Idoso
7.
BMC Ophthalmol ; 24(1): 128, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519990

RESUMO

BACKGROUND: Retinal vascular occlusions, including retinal vein occlusion and retinal artery occlusion, are common causes of visual impairment. In order to evaluate the national medical burden and help improve ophthalmic health care policy planning, we investigated the incidence of retinal vascular occlusive diseases from 2011 to 2020 in Korea. METHODS: This study is a nationwide population-based retrospective study using data from the Korea national health claim database of the Health Insurance Review and Assessment (HIRA) service. We identified retinal vascular occlusive diseases registered from January 1, 2009, to December 31, 2020, according to the retinal vascular occlusion code (H34) and its sub-codes from international classification of disease, tenth revision diagnosis code. We used data from the entire Korean population based on the 2015 census of the population in Korea to calculate standardized incidence rates. RESULTS: We identified 348,775 individuals (male, 161,673 [46.4%]; female, 187,102 [53.6%]) with incident retinal vascular occlusion (H34), 10,451 individuals (males, 6,329 [60.6%]; females, 4,122 [39.4%]) with incident central retinal artery occlusion (H34.1), and 252,810 individuals (males, 114,717 [45.4%]; females, 138,093 [54.6%]) with incident retinal vein occlusion (H34.8) during the 10-year study period. The weighted mean incidence rate of retinal vascular occlusion was 70.41 (95% CI, 70.18-70.65) cases/100,000 person-years. The weighted mean incidence rate of central retinal artery occlusion was 2.10 (95% CI, 2.06-2.14) cases/100,000 person-years. The weighted mean incidence rate of retinal vein occlusion was 50.99 (95% CI, 50.79-51.19) cases/100,000 person-years. CONCLUSION: The total retinal vascular occlusion and retinal vein occlusion showed a decreasing trend until 2020. However, the central retinal artery occlusion decreased until 2014 and remained stable without a significant further decline until 2020. The incidence of total retinal vascular occlusion and retinal vein occlusion was higher in females than in males, while the incidence of central retinal artery occlusion was higher in males. All retinal vascular occlusive diseases showed an increasing incidence with older age; the peak age incidence was 75-79 years for total retinal vascular occlusion and retinal vein occlusion, and 80-85 years for central retinal artery occlusion.


Assuntos
Oclusão da Artéria Retiniana , Oclusão da Veia Retiniana , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Incidência , Oclusão da Veia Retiniana/diagnóstico , Estudos de Coortes , Oclusão da Artéria Retiniana/diagnóstico , República da Coreia/epidemiologia , Fatores de Risco
8.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339049

RESUMO

Although conventional combination chemotherapies for advanced gastric cancer (GC) increase survival, such therapies are associated with major adverse effects; more effective and less toxic treatments are required. Combinations of different anti-cancer drugs, for example, paclitaxel plus ramucirumab, have recently been used as second-line treatments for advanced GC. This study evaluated how copy number variations of the MET gene, MET mutations, and MET gene and protein expression levels in human GC cells modulate the susceptibility of such cells to single-agent (tepotinib, ramucirumab, or paclitaxel) and doublet (tepotinib-plus-paclitaxel or ramucirumab-plus-paclitaxel treatment regimens. Compared with ramucirumab-plus-paclitaxel, tepotinib-plus-paclitaxel better inhibited the growth of GC cells with MET exon 14 skipping mutations and those lacking MET amplification but containing phosphorylated MET; such inhibition was dose-dependent and associated with cell death. Tepotinib-plus-paclitaxel and ramucirumab-plus-paclitaxel similarly inhibited the growth of GC cells lacking MET amplification or MET phosphorylation, again in a dose-dependent manner, but without induction of cell death. However, tepotinib alone or tepotinib-plus-ramucirumab was more effective against c-MET-positive GC cells (>30 copy number variations) than was ramucirumab or paclitaxel alone or ramucirumab-plus-paclitaxel. These in vitro findings suggest that compared with ramucirumab-plus-paclitaxel, tepotinib-plus-paclitaxel better inhibits the growth of c-MET-positive GC cells, cells lacking MET amplification but containing phosphorylated MET, and cells containing MET mutations. Clinical studies are required to confirm the therapeutic effects of these regimens.


Assuntos
Piperidinas , Proteínas Proto-Oncogênicas c-met , Piridazinas , Pirimidinas , Ramucirumab , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Variações do Número de Cópias de DNA , Paclitaxel , Fosforilação , Neoplasias Gástricas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo
9.
Biosensors (Basel) ; 13(11)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37998137

RESUMO

Surface-enhanced Raman spectroscopy (SERS) is an effective technique for biosensing, enabling label-free detection of biomolecules with enhanced sensitivity. There is a tremendous probability of signal failure in Raman frequencies because of the scattering of the Raman radiation in liquids, effective SERS improvement is required to reduce this issue when considering liquid specimens. We examined a liquid bacterial sample, investigating the electrostatic interactions of the bacterial samples with gold nanorods (AuNRs) and graphene. We established a voltage-gated 3D graphene functionalized with an AuNR-based device on the silicon substrate for SERS measurements when the applied voltage ranges from 0 to 3 V. Moreover, AuNRs density-susceptible bacterial sample analysis with varied concentrations of bacterial samples has also been described. Using bacterial SERS analysis, the bacterial components amide II (1555-1565 cm-1) and amide III (1250-1350 cm-1) have been discovered for both bacteria, Gram-positive, Listeria monocytogenes and Gram-negative, Salmonella typhi. Our fabricated device affords an interesting label-free, rapid, and reproducible bacterial sample analysis based on the density of the AuNRs when functionalizing flake-like 3D graphene, which can help facilitate label-free bacteria sensing platforms.


Assuntos
Grafite , Nanopartículas Metálicas , Nanotubos , Grafite/química , Ouro/química , Nanotubos/química , Análise Espectral Raman/métodos , Bactérias , Amidas , Nanopartículas Metálicas/química
10.
J Vasc Access ; : 11297298231193525, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37615157

RESUMO

PURPOSE: This study aimed to compare the complication rates of non-absorbable suture (NAS) and n-butyl-2-cyanoacrylate (NBCA) skin adhesive for skin closure during totally implantable venous access devices (TIVADs) implantation. METHODS: Between March 2020 and February 2021, 586 consecutive patients who underwent TIVAD implantation were retrospectively analyzed. Two groups of patients suture with NAS (n = 299) or NBCA (n = 287) were followed up for 18 months to compare the occurrence of infection, thrombosis, and non-thrombotic malfunction. A total of 364 cases were extracted using propensity score matching in a 1:1 ratio. Mean TIVADs maintenance days were analyzed using Kaplan-Meier survival analysis. RESULTS: Nineteen cases of complications occurred (0.294/1000 catheter-days) in the NAS group and 17 cases (0.210/1000 catheter-days) in the NBCA group. The difference in the complication rates between the two groups was not statistically significant (p = 0.725) after propensity score matching. Mean TIVADs maintenance days were 627.3 days in NAS group and 697.6 days in NBCA group. There was no statistically significant difference in the number of TIVADs maintenance days between the two groups (p = 0.081). CONCLUSION: In TIVADs implantation, skin closure using NBCA showed no difference in the occurrence of infectious complications compared with conventional non-absorbable skin suture.

11.
Sci Total Environ ; 898: 165468, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37451459

RESUMO

Distribution of arsenic (As) in the environment can occur through various paths, depending on the interrelationship between soil and surface water, and groundwater. This study aimed to identify the origins and pathways of As among various potential origins in soil and water systems using two-dimensional reactive transport models (2D RTMs) and to evaluate the contribution of each origin to the geochemical distribution of As in the study area, which included a reservoir, two streams, and two abandoned mines. The 2D RTMs were prepared by combining hydraulic and geochemical reactive models. The MODFLOW-2005 package was used to simulate the water flow in the study area. The geochemical reaction and distribution of As were simulated using Geochemist's Workbench. The concentration of As in the reservoir was ∼50 µg/L, while that in the soils collected around the mine X and Y was 15.0-1853.2 mg/kg (median: 126.1 mg/kg) and 3.6-1629.2 mg/kg (median: 60.9 mg/kg), respectively. Hydraulic and geochemical input data were derived from field surveys and laboratory experiments. Based on the geochemical and hydrogeological input data, 2D RTMs determined that 32.0 kg of As accumulated into the reservoir over 18 years through surface water, which is from mines X (2.7 kg) and Y (29.3 kg). Hence, mine Y would be the primary origin of As to the reservoir. Based on 2D RTM, 2.4 kg of As entered the reservoir via groundwater (DO <0.1 mg/L). Also, precipitation of sulfide minerals (e.g., orpiment; As2S3) influences As dispersion and contribution under subsurface conditions. These modeling results suggest that 2D RTMs could be a new approach for identifying and assessing the contribution of potential As origins in soil and water system.

12.
Medicine (Baltimore) ; 102(27): e34161, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37417629

RESUMO

Fluorescein angiography is a crucial examination in ophthalmology to identify retinal and choroidal pathologies. However, this examination modality is invasive and inconvenient, requiring intravenous injection of a fluorescent dye. In order to provide a more convenient option for high-risk patients, we propose a deep-learning-based method to translate fundus photography into fluorescein angiography using Energy-based Cycle-consistent Adversarial Networks (CycleEBGAN) We propose a deep-learning-based method to translate fundus photography into fluorescein angiography using CycleEBGAN. We collected fundus photographs and fluorescein angiographs taken at Changwon Gyeongsang National University Hospital between January 2016 and June 2021 and paired late-phase fluorescein angiographs and fundus photographs taken on the same day. We developed CycleEBGAN, a combination of cycle-consistent adversarial networks (CycleGAN) and Energy-based Generative Adversarial Networks (EBGAN), to translate the paired images. The simulated images were then interpreted by 2 retinal specialists to determine their clinical consistency with fluorescein angiography. A retrospective study. A total of 2605 image pairs were obtained, with 2555 used as the training set and the remaining 50 used as the test set. Both CycleGAN and CycleEBGAN effectively translated fundus photographs into fluorescein angiographs. However, CycleEBGAN showed superior results to CycleGAN in translating subtle abnormal features. We propose CycleEBGAN as a method for generating fluorescein angiography using cheap and convenient fundus photography. Synthetic fluorescein angiography with CycleEBGAN was more accurate than fundus photography, making it a helpful option for high-risk patients requiring fluorescein angiography, such as diabetic retinopathy patients with nephropathy.


Assuntos
Retina , Humanos , Angiofluoresceinografia/métodos , Estudos Retrospectivos , Fundo de Olho , Retina/patologia , Fluoresceínas
13.
J Clin Oncol ; 41(27): 4394-4405, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37364218

RESUMO

PURPOSE: Trastuzumab-containing chemotherapy is the recommended first-line regimen for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. We evaluated the safety and efficacy of trastuzumab combined with ramucirumab and paclitaxel as second-line treatment for HER2-positive G/GEJ cancer. PATIENTS AND METHODS: Patients with HER2-positive advanced G/GEJ cancer who progressed after first-line treatment with trastuzumab-containing chemotherapy were enrolled from five centers in the Republic of Korea. Patients were administered a 28-day cycle of trastuzumab (once on days 1, 8, 15, and 22: 2 mg/kg followed by 4 mg/kg loading dose), ramucirumab (once on days 1 and 15: 8 mg/kg), and paclitaxel (once on days 1, 8, and 15: dose level 1, 80 mg/m2; or dose level -1, 70 mg/m2). Phase II was conducted with the recommended phase II dose (RP2D). Primary end points were determination of RP2D during phase Ib and investigator-assessed progression-free survival (PFS) in patients treated with RP2D. RESULTS: Dose-limiting toxicity at dose level 1 was not documented during phase Ib, and a full dose combination was selected as the RP2D. Among 50 patients with a median follow-up duration of 27.5 months (95% CI, 17.4 to 37.6), median PFS and overall survival were 7.1 months (95% CI, 4.8 to 9.4) and 13.6 months (95% CI, 9.4 to 17.7), respectively. Objective response rate was 54% (27 of 50, including one complete response), and disease control rate was 96% (48 of 50). Loss of HER2 expression was observed in 34.8% (8 of 23) patients after first-line treatment, and no definite association between HER2 expression and the outcome was revealed. Safety profiles were consistent with previous reports. CONCLUSION: Trastuzumab combined with ramucirumab and paclitaxel showed appreciable efficacy with manageable safety profiles in patients with previously treated HER2-positive G/GEJ cancer.


Assuntos
Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Trastuzumab , Paclitaxel , Intervalo Livre de Doença , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Junção Esofagogástrica/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ramucirumab
15.
Nano Lett ; 23(13): 6269-6275, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37099317

RESUMO

Tailoring the electrical properties of one-dimensional (1D) van der Waals (vdW) materials is desirable for their applications toward electronic devices by exploiting their unique characteristics. However, 1D vdW materials have not been extensively investigated for modulation of their electrical properties. Here we control doping levels and types of 1D vdW Nb2Pd3Se8 over a wide energy range by immersion in AuCl3 or ß-nicotinamide adenine dinucleotide (NADH) solutions, respectively. Through spectroscopic analyses and electrical characterizations, we confirm that the charges were effectively transferred to Nb2Pd3Se8, and the dopant concentration was adjusted to the immersion time. Furthermore, we make the axial p-n junction of 1D Nb2Pd3Se8 by a selective area p-doping using the AuCl3 solution, which exhibits rectifying behavior with an Iforward/Ireverse of 81 and an ideality factor of 1.2. Our findings could pave the way to more practical and functional electronic devices based on 1D vdW materials.

16.
Oncologist ; 28(9): e823-e834, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37036671

RESUMO

BACKGROUND: Loss of PTEN function leads to increased PI3Kß signaling. AZD8186, a selective PI3Kß/δ inhibitor, has shown anti-tumor activity in PTEN-deficient preclinical models. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed in advanced gastric cancer with PTEN loss. METHODS: In the phase Ib dose-escalation, subjects with advanced solid tumors received oral AZD8186 (60 mg or 120 mg; twice daily (BID); 5 days on/2 days off) plus intravenous paclitaxel (70 mg/m2 or 80 mg/m2; days 1, 8, and 15) every 4 weeks. In the phase II part, MRGC patients with PTEN loss or PTEN/PIK3CB gene abnormality were enrolled and received recommended phase II dose (RP2D) of AZD8186 plus paclitaxel. Primary endpoints were to determine maximum tolerated dose (MTD) and RP2D in phase Ib and 4-month progression-free survival (PFS) rate in phase II. RESULTS: In phase Ib, both MTD and RP2D were determined at paclitaxel 80 mg/m2 and AZD8186 120 mg BID. In phase II, 18 patients were enrolled [PTEN loss (n = 18) and PIK3CB mutation (n = 1)]. The 4-month PFS rate was 18.8% (3 of 16 evaluable patients) and further enrollment stopped due to futility. CONCLUSION: Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.ClinicalTrials.gov Identifier: NCT04001569.


Assuntos
Paclitaxel , Neoplasias Gástricas , Humanos , Compostos de Anilina/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cromonas/farmacologia , Dose Máxima Tolerável , Paclitaxel/farmacologia , Proteínas Repressoras , Neoplasias Gástricas/tratamento farmacológico
17.
J Gastric Cancer ; 23(1): 3-106, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36750993

RESUMO

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

18.
J Gastric Cancer ; 23(1): 3-106, 20230131. tab
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1436360

RESUMO

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.


Assuntos
Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/diagnóstico por imagem , Endoscopia Gastrointestinal , Anticarcinógenos/uso terapêutico
19.
Adv Mater ; 35(43): e2204775, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35819877

RESUMO

Continuous industrial development has increased the demand of energy. Inevitably, the development of energy sources is steadily progressing using various methods. Rather than establishing a new energy source, a system for storing waste heat generated by industry has now been accepted as a useful strategy. Among such systems, the hydration and dehydration reactions of MgO/Mg(OH)2  are eco-friendly, have relatively low toxicity and risk, and have a large reserves. Therefore, it is a promising candidate for a heat-storage system. In this study, ultrahigh-porosity particles are used to maximize the heat-storage efficiency of pure MgO. Due to its large surface area, the heat storage rate is 90.3% of the theoretical value and the reaction rate is very high. In addition, as structural collapse, likely to be caused by volume changes between reactions, is blocked as the porous region is filled and emptied, the cycle stability is secured. Ultrahigh-porosity MgO microparticles can be used to build eco-friendly heat-storage systems.

20.
Polymers (Basel) ; 14(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36501618

RESUMO

The rapid advancement of electrical and telecommunication facilities has resulted in increasing requirements for the development of electromagnetic interference (EMI) shielding composites. Accordingly, an experimental study was conducted to evaluate the EMI shielding performance of carbon nanomaterial (CNM)-embedded carbon-fiber-reinforced polymer (CFRP) or glass-fiber-reinforced polymer (GFRP) composites. Nine combinations of CNMs and carbon or glass fibers were used to fabricate the composites. The synergistic effects of CNMs on the EMI shielding performance were systematically investigated. The results indicated that plate-type CNMs (i.e., graphene and graphite nanoplatelets) have more prominent effects than fiber-type CNMs (carbon nanofibers). The composites fabricated with CFRP afforded higher EMI shielding than the GFRP-based composites. Among the eighteen samples, 3% CNT-GNP in CFRP composites, which included plate-typed CNM, exhibited the best EMI shielding performances, showing 38.6 dB at 0.7 GHz. This study helps understand the shielding performance of CNM-embedded CFRP and GFRP composites in electrical and telecommunication facilities.

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