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1.
Clin Cancer Res ; 30(10): 2097-2110, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38457288

RESUMO

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de Cabeça e Pescoço , Terapia Neoadjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Pessoa de Meia-Idade , Feminino , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante/métodos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Adulto , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos
2.
JCO Clin Cancer Inform ; 8: e2300201, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38271642

RESUMO

PURPOSE: In artificial intelligence-based modeling, working with a limited number of patient groups is challenging. This retrospective study aimed to evaluate whether applying synthetic data generation methods to the clinical data of small patient groups can enhance the performance of prediction models. MATERIALS AND METHODS: A data set collected by the Cancer Registry Library Project from the Yonsei Cancer Center (YCC), Severance Hospital, between January 2008 and October 2020 was reviewed. Patients with colorectal cancer younger than 50 years who started their initial treatment at YCC were included. A Bayesian network-based synthesizing model was used to generate a synthetic data set, combined with the differential privacy (DP) method. RESULTS: A synthetic population of 5,005 was generated from a data set of 1,253 patients with 93 clinical features. The Hellinger distance and correlation difference metric were below 0.3 and 0.5, respectively, indicating no statistical difference. The overall survival by disease stage did not differ between the synthetic and original populations. Training with the synthetic data and validating with the original data showed the highest performances of 0.850, 0.836, and 0.790 for the Decision Tree, Random Forest, and XGBoost models, respectively. Comparison of synthetic data sets with different epsilon parameters from the original data sets showed improved performance >0.1%. For extremely small data sets, models using synthetic data outperformed those using only original data sets. The reidentification risk measures demonstrated that the epsilons between 0.1 and 100 fell below the baseline, indicating a preserved privacy state. CONCLUSION: The synthetic data generation approach enhances predictive modeling performance by maintaining statistical and clinical integrity, and simultaneously reduces privacy risks through the application of DP techniques.


Assuntos
Inteligência Artificial , Neoplasias Colorretais , Humanos , Teorema de Bayes , Estudos Retrospectivos , Hospitais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia
3.
Ann Dermatol ; 35(Suppl 2): S281-S286, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38061722

RESUMO

The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen®) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna®) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.

4.
J Gastric Cancer ; 23(4): 574-583, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37932224

RESUMO

PURPOSE: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. MATERIALS AND METHODS: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period. RESULTS: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. CONCLUSIONS: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

5.
Cell Rep Med ; 4(11): 101251, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37890486

RESUMO

Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Antibacterianos/administração & dosagem , Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia
6.
Biomolecules ; 13(7)2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37509167

RESUMO

Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Apigenina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Morte Celular , Apoptose , Proliferação de Células , Células Hep G2 , Linhagem Celular Tumoral , Receptores de Morte Celular
7.
BMC Cancer ; 23(1): 691, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481515

RESUMO

BACKGROUND: Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis. METHODS: This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate. DISCUSSION: This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Oxaliplatina , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como Assunto
8.
Clin Colorectal Cancer ; 22(3): 307-317, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37271592

RESUMO

BACKGROUND: Intensive surveillance of colon cancer by using the abdominopelvic computed tomography (AP-CT) is common in real world practice; however, it is still unclear whether high-frequency surveillance using AP-CT in patients with these risk factors is superior to that in the low-frequency surveillance. PATIENTS AND METHODS: We retrospectively reviewed 1803 patients with stage II-III colon cancer receiving curative surgery between January 1, 2005 to December 31, 2015. We evaluated the average scan-to-scan intervals of postoperative AP-CT testing and assigned patients with an interval of 5 to 8 and 9 to 13 months to the high-frequency (HF) and low-frequency (LF) groups, respectively. The cutoff value of preoperative and postoperative CEA levels was 5 ng/mL. We also applied propensity score matching (PSM) and inverse probability of treatment weighting to adjust clinicopathologic differences between the 2 groups. RESULTS: We matched 1:1 for each surveillance group yielding a cohort of 776 matched patients. After PSM, Baseline demographics were overall well balanced between 2 groups. Stage III (OR, 2.00; 95% Confidence interval [CI], 1.21-3.30) and postoperative CEA elevation (OR, 2.30; 95% CI, 1.08-4.92) were independent risk factors of recurrence in multivariate analyses. Patient in the HF group had more surgery plus chemo- or radiotherapy as postrecurrence treatment than patient in the LF group (46.2% vs. 23.1%, P = .017). This trend was retained after PSM, although it is not significant (44.4% vs. 23.1%, P = .060). However, survival outcomes of high-frequency AP-CT surveillance were not superior to those of low-frequency surveillance in all subgroups, including stage III (HR 0.99, 95% CI 0.40-2.47) and postoperative CEA elevation (HR 1.36, 95% CI 0.45-4.11). CONCLUSION: High-frequency AP-CT testing is associated with a higher proportion of surgery plus chemo- or radiotherapy as postrecurrence treatment, without improvement in 5-year overall survival.


Assuntos
Neoplasias do Colo , Humanos , Seguimentos , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/terapia , Neoplasias do Colo/patologia , Tomografia Computadorizada por Raios X
9.
Lung Cancer ; 180: 107213, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37104879

RESUMO

INTRODUCTION: Lazertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that provides a high level of selectivity for sensitizing and p.Thr790Met (T790M) EGFR mutations. We aimed to collect real-world data regarding the efficacy and safety of lazertinib. METHODS: This study included patients treated with lazertinib for T790M-mutated non-small cell lung cancer who had previously been treated with an EGFR-TKI. The primary outcome measure was progression-free survival (PFS). Additionally, this study evaluated overall survival (OS), time-to-treatment failure (TTF), duration of response (DOR), objective response rate (ORR) and disease control rate (DCR). Drug safety was also assessed. RESULTS: In a study of 103 patients, 90 received lazertinib as a second- or third-line therapy. The ORR and DCR were 62.1% and 94.2%, respectively. The median follow-up duration was 11.1 months, and the median PFS period was 13.9 (95% confidence interval [CI], 11.0-not reached [NR]) months. OS, DOR, and TTF had not yet been determined. In a subgroup of 33 patients with evaluable brain metastases, the intracranial DCR and ORR were 93.5% and 57.6%, respectively. The median intracranial PFS period was 17.1 (95% CI, 13.9-NR) months. Approximately 17.5% of patients had dose modification or discontinuation due to adverse events, with the most common being grade 1 or 2 paresthesia. CONCLUSIONS: The efficacy and safety of lazertinib were recapitulated in a real-world study reflecting routine clinical practice in Korea, showing durable disease control both systematically and intracranially, with manageable side effects.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores ErbB/genética , Inibidores de Proteínas Quinases/farmacologia , Mutação/genética , Compostos de Anilina/uso terapêutico
10.
Vet Radiol Ultrasound ; 64(2): 233-242, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36594223

RESUMO

An improved understanding of the CT characteristics for histologically confirmed primary intestinal tumors would be helpful for guiding prognosis and treatment plans in affected dogs. This retrospective, multi-center, analytical study aimed to evaluate the CT characteristics for the differentiation of adenocarcinoma, lymphoma, and spindle cell sarcoma (SCS) in dogs. Thirty-seven dogs who underwent contrast CT and histopathological examinations were included (adenocarcinomas, n = 11; lymphomas, n = 12; SCS, n = 14). Quantitative and qualitative CT parameters, including tumor morphology, contrast enhancement pattern, Hounsfield unit (HU) value, and presence or absence of intraabdominal lymphadenopathy, were evaluated for each included small intestine tumor CT case. Adenocarcinomas tended to show endophytic growth, intestinal obstruction, and a heterogeneous enhancement pattern. Lymphomas tended to show exophytic growth, contrast enhancement of the intestinal tumor mucosal layer, a homogeneous enhancement pattern, and the presence of lymphadenopathies in the abdominal cavity. SCSs tended to show lobulated growth, a large cystic portion within the tumor, a heterogeneous enhancement pattern, a large size with fat stranding sign, and lower HU values in postcontrast images. Cut-off values of the minimum diameter/fifth lumbar vertebral mid-body height (≥5.80; area under the curve [AUC] = 0.97, P < 0.001) and minimum HU value/HU value of the aorta (≤0.26; AUC = 0.96, P < 0.001) were derived to discriminate SCS from the two other tumor types. In conclusion, contrast CT characteristics may be useful in differentiating small intestinal adenocarcinomas, lymphomas, and SCSs in dogs.


Assuntos
Adenocarcinoma , Doenças do Cão , Linfadenopatia , Linfoma , Sarcoma , Cães , Animais , Estudos Retrospectivos , Linfoma/diagnóstico por imagem , Linfoma/veterinária , Tomografia Computadorizada por Raios X/veterinária , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/veterinária , Intestino Delgado/diagnóstico por imagem , Sarcoma/diagnóstico por imagem , Sarcoma/veterinária , Linfadenopatia/veterinária , Meios de Contraste , Doenças do Cão/diagnóstico por imagem
11.
J Vet Sci ; 23(6): e89, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36448435

RESUMO

It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.


Assuntos
Adenocarcinoma , Doenças do Cão , Doenças dos Roedores , Camundongos , Cães , Animais , Xenoenxertos , Camundongos Nus , Transplante Heterólogo/veterinária , Células-Tronco Neoplásicas , Biomarcadores , Adenocarcinoma/diagnóstico , Adenocarcinoma/veterinária , Doenças do Cão/diagnóstico
12.
Genomics Inform ; 20(3): e29, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36239106

RESUMO

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

13.
Cells ; 11(17)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36078142

RESUMO

Apigetrin (7-(ß-D-glucopyranosyloxy)-4',5-dihydroxyflavone), a glycoside bioactive dietary flavonoid derived from Taraxacum officinale and Teucrium gnaphalodes, is known to possess anticancer, antioxidant, and anti-inflammatory effects on numerous cancers. In the present study, we examined the effect of apigetrin in Hep3B hepatocellular cancer cell line (HCC). Apigetrin inhibited cell growth and proliferation of Hep3B cells, as confirmed by MTT and colony formation assay. We used apigetrin at concentrations of 0, 50, and 100 µM for later experiments. Of these concentrations, 100 µM of apigetrin showed a significant effect on cell inhibition. In apigetrin-treated Hep3B cells, cell cycle arrest occurred at the G2/M phase. Apoptosis and necroptosis of Hep3B cells treated with apigetrin were confirmed by Annexin V/propidium iodide (PI) staining and flow cytometry results. Morphological observation through 4',6-diamidino-2-phenylindole (DAPI) staining showed intense blue fluorescence representing chromatin condensation. Hematoxylin staining showed necroptotic features such as formation of vacuoles and swelling of organelles. Apigetrin increased reactive oxygen species (ROS) levels in cells, based on fluorescence imaging. Furthermore, the underlying mechanism involved in the apoptosis and necroptosis was elucidated through western blotting. Apigetrin up-regulated TNFα, but down-regulated phosphorylation of p-p65, and IκB. Apigetrin inhibited the expression of Bcl-xl but increased Bax levels. Up-regulation of cleaved PARP and cleaved caspase 3 confirmed the induction of apoptosis in apigetrin-treated Hep3B cells. Additionally, necroptosis markers RIP3, p-RIP3, and p-MLKL were significantly elevated by apigetrin dose-dependently, suggesting necroptotic cell death. Taken together, our findings strongly imply that apigetrin can induce apoptosis and necroptosis of Hep3B hepatocellular cancer cells. Thus, apigetrin as a natural compound might have potential for treating liver cancer.


Assuntos
Apigenina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , NF-kappa B/metabolismo , Necroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
14.
Foods ; 10(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34945625

RESUMO

The objectives of this study were to evaluate antioxidant capacity of hot water extract from red maple leaf with different extraction times (experiment I) and to determine their impacts on color, free anthocyanin content, and hardness of gelatin gels (experiment II). In experiment I, hot water extraction time (30, 60, 120, 180, and 360 min at 60 °C) was fixed as a main effect. The different extraction times had no impacts on total polyphenol content and DPPH radical scavenging activity (p > 0.05). However, extraction time for 360 min could decrease anthocyanin content as well as ferric reducing antioxidant power (p < 0.05). In experiment II, 6%, 18%, and 30% gelatin gels were prepared without/with red maple leaf extract (1000 mg/L). The red maple leaf extract significantly increased redness, yellowness, and hardness, but decreased free anthocyanin content. Such impacts were obviously observed at high gelatin concentration. Thus, red maple leaf extract could be a novel anthocyanin source for improving antioxidant capacity and reddish color of gelatin gels. However, the addition amount of red maple leaf extract may be limited in the development of senior-friendly jelly food for soft texture in that it could increase the hardness of the gelatin gel.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34444596

RESUMO

Occupational noise is known to be one of the most hazardous risk factors, frequently exceeding the exposure limit thus causing hearing loss and other health outcomes among many field workers in various industries and workplaces. This study aims to characterize the levels of occupational noise exposure during the daily working hours and break periods (sampling preparation and lunch break), identify work-related characteristics affecting the noise exposure levels when including or excluding the break periods and finally determine the most effective approach for occupational noise exposure assessment by using the Korean and U.S. OSHA's guidelines. A total of 1575 workers employed by a large shipbuilding company participated in this study, and the historical exposure datasets of noise dosimeters, collected from 2016 to 2018, were classified by characteristics. A threshold level (TL) for the noise dosimeter was set as a value of 80 dBA during the break periods, including the preparation time for sampling instruments and one hour for the lunch break. The shipbuilding workers were exposed to high levels of occupational noise during the break periods, especially for those working in heating, grinding, and power processes in the painting-related departments. Out of 1575 samples, most cases were related to the preparation time (N = 1432, 90.9%) and lunch break (N = 1359, 86.9%). During the break time, the levels of noise exposure were measured depending on task-specific characteristics. When including the break time, the noise levels increased by approximately 1 dBA during the break, combining 0.8 dBA in the lunch hours and 0.2 dBA for the preparation of the sampling instrument. When excluding the break time, the levels of noise exposure collected using a Korean Occupational Safety and Health Administration (KOSHA) guide tended to be underestimated compared to those using the U.S. OSHA method. When including the break times, the proportion of noise exposure levels exceeding the compliance exposure limit declined from 37.9% to 34.5%, indicating that the break times might affect the decrease in the noise exposure levels. Taken together, shipbuilding workers could possibly be exposed to much greater amounts of noise exposure during break times in the shipbuilding processes, and the noise exposure levels in the department of painting were high. Therefore, it is recommended that industrial hygienists collect exposure monitoring data of occupational noise one hour after their job tasks begin and then consecutively monitor the noise exposure levels for at least 6 h including the break periods for each day.


Assuntos
Ruído Ocupacional , Exposição Ocupacional , Humanos , Indústrias , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional/análise , República da Coreia , Estados Unidos , United States Occupational Safety and Health Administration
16.
J Environ Manage ; 285: 112110, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561728

RESUMO

Asbestos management in Korea has, to date, focused exclusively on dismantlement and removal; however, the effective management of asbestos in public facilities and rural dwellings is also critical. This study compares eight different asbestos stabilization treatments and their effectiveness in reducing asbestos fiber dispersion from weathered corrugated asbestos cement sheets (CACS) under different wind conditions. The effectiveness of the different asbestos stabilizers was assessed in order to identify the characteristics of fibers dispersed from treated CACS samples. The impact of wind speed on the concentration and composition of the dispersed fibers was also evaluated. For all wind speeds, the concentration of the fibers dispersed from the CACS samples that were treated with stabilizers decreased relative to the untreated CACS. These results show that asbestos concentrations were considerably reduced following stabilizer treatment and that treated CACS dispersed fewer asbestos fibers relative to untreated CACS. The results of this study will be useful for the development of strategies regarding the appropriate management of asbestos in public buildings.


Assuntos
Amianto , Amianto/análise , Materiais de Construção , Manufaturas , República da Coreia , Tempo (Meteorologia)
17.
Sci Rep ; 10(1): 20359, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230116

RESUMO

The Asbestos Injury Relief Act in Korea requires that asbestos exposure be assessed through clinical examination and chest computed tomography (CT). However, a more specific measurement of asbestos characteristics in the lung tissue may be appropriate. We aimed to investigate the asbestos burden and characterize asbestos fibers in patients with lung cancer and ultimately assess the relationship between occupational and environmental asbestos exposure and lung cancer in Korea. We evaluated 37 lung cancer patients (LCPs) from Busan. The factors affecting asbestos burden in LCPs were analyzed using a multiple regression analysis. History of asbestos exposure (environmental/occupational), male sex, and old age were the main factors affecting asbestos burden in lung tissues of LCPs. These factors had an approximate 37% adjusted coefficient of determination. There was a significant difference in the length of asbestos fibers (4.06-37.6 µm vs. 4.26-91.7 µm) and aspect ratio (4.5-151.9 vs. 5.6-735.6) between those who were occupationally exposed to asbestos and those who were environmentally exposed (P < 0.01). Therefore, both environmental/occupational exposure to asbestos should be strongly managed to reduce the risk of lung cancer, and exposure should be assessed according to the characteristics of asbestos fibers in the lung tissue.


Assuntos
Amianto/efeitos adversos , Asbestose/diagnóstico por imagem , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/diagnóstico por imagem , Exposição Ocupacional/efeitos adversos , Adulto , Fatores Etários , Idoso , Asbestose/epidemiologia , Asbestose/patologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , Tomografia Computadorizada por Raios X
18.
J Prev Med Public Health ; 52(4): 265-271, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31390690

RESUMO

OBJECTIVES: The Samsung Ombudsperson Commission was launched as an independent third-party institution following an agreement among Samsung Electronics, Supporters for Health and Right of People in Semiconductor Industry (Banolim in Korean, an independent NGO), and the Family Compensation Committee, in accordance with the industry accident prevention measure required by the settlement committee to address the issues related to employees who allegedly died from leukemia and other diseases as a result of working at Samsung's semiconductor production facilities. METHODS: The Commission has carried out a comprehensive range of activities to review and evaluate the status of the company's occupational accidents management system, as well as occupational safety and health risk management within its facilities. RESULTS: Based on the results of this review, termed a comprehensive diagnosis, the Commission presented action plans for improvement to strengthen the company's existing safety and health management system and to effectively address uncertain risks in this area going forward. CONCLUSIONS: The Commission will monitor the execution of the suggested tasks and provide advice and guidance to ensure that Samsung's semiconductor and liquid crystal display production lines are safer.


Assuntos
Acidentes de Trabalho/prevenção & controle , Eletrônica/organização & administração , Neoplasias/etiologia , Saúde Ocupacional/normas , Humanos , Neoplasias/epidemiologia , Exposição Ocupacional/efeitos adversos , República da Coreia/epidemiologia , Semicondutores/efeitos adversos
19.
Meat Sci ; 158: 107907, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31402198

RESUMO

The aim of this study was to determine the relationship between in vitro antioxidant capacity of soy sauces and its impact on lipid oxidation in raw and cooked beef patties during 10 days of refrigerated storage. Three commercial soy sauces were used: industrially fermented soy sauce (IS), traditionally fermented Korean soy sauce (KS), and mixed soy sauce (MS). In vitro antioxidant capacity, KS showed the highest total phenol content, whereas IS and MS had a higher Fe2+ chelating activity than KS (P < .05). Heat treatment decreased total phenol content but increased Fe2+ chelating activity of soy sauces (P < .001). In both raw and cooked beef patties, the addition of IS or MS caused a lower 2-thiobarbituric acid reactive substances (TBARS) level than KS throughout the overall storage period (P < .05). This preliminary study suggests that the Fe2+ chelating activity of soy sauce may be one of the major mechanisms in preventing lipid oxidation in meat products.


Assuntos
Antioxidantes/análise , Produtos da Carne/análise , Alimentos de Soja/análise , Animais , Bovinos , Fermentação , Armazenamento de Alimentos , Temperatura Alta , Quelantes de Ferro/análise , Oxirredução , Fenóis/análise , Substâncias Reativas com Ácido Tiobarbitúrico/análise
20.
Ann Work Expo Health ; 63(2): 197-217, 2019 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445617

RESUMO

This study aims to evaluate the accuracy, precision and conservatism of three models (ECETOC TRA 3.1, Stoffenmanager 7.0 and ART 1.5) by comparing model predictions and repeated exposure measurements in Korea. We collected the exposure measurements (n = 390) and detailed contextual information extracted from 10 survey reports published by Ministry of Employment and Labour in the mid-2000s. Using these three models, seven occupational health professionals predicted inhalation exposure to 10 solvents used for cleaning tasks in 51 situations at 33 companies in 15 industries. We applied four comparison approaches previously used by several European studies and calculated the lack of agreement (bias, relative bias, precision), Pearson correlation coefficients (r), level of conservatism, and residuals between the log-transformed predicted estimates and measured exposures on both individual and situation levels. The overall bias and precision were -0.53 ± 2.11 with ART, -1.32 ± 5.88 with Stoffenmanager, and -1.03 ± 8.88 with ECETOC TRA. Pearson correlation coefficients were significantly high in ART (r = 0.95) and Stoffenmanager (r = 0.82), but moderate in ECETOC TRA (r = 0.58). We found ART to be the most accurate model, and Stoffenmanager was the most balanced model in terms of good accuracy, high correlation, and medium conservatism in the model predictions. However, ECETOC TRA showed less accurate outcomes and lower level of conservatism but still had moderate correlations. We observed a systematic tendency to overestimate low exposures and underestimate higher exposures in all models, similar to previous studies. Therefore, our findings suggest that these European models can be used to predict occupational exposure to solvents in Korea.


Assuntos
Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Compostos Orgânicos/análise , Medição de Risco/métodos , Solventes/análise , Algoritmos , Viés , Humanos , Exposição por Inalação/análise , Modelos Biológicos , Saúde Ocupacional , República da Coreia
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