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1.
Sci Rep ; 14(1): 20338, 2024 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223155

RESUMEN

Preclinical drug efficacy and tumor microenvironment (TME) investigations often utilize humanized xenograft mouse models, yet these models typically fall short in replicating the intricate TME. We developed a humanized liver metastasis (LM) model by transplanting human peripheral blood mononuclear cells (PBMCs) and assessed it against the conventional subcutaneous (SC) xenograft model, focusing on immune cell dynamics post-transplantation and immunotherapy response. NOD-scid IL2Rgammanull(NSG) were inoculated with PBMCs to create humanized models. We induced SC and LM models using HCT116 cells, to investigate and compare the distributions and transformations of immune cell subsets, respectively. Both models were subjected to anti-PD-L1 therapy, followed by an analysis the TME analysis. The LM model demonstrated enhanced central tumor infiltration by tumor-infiltrating lymphocytes (TILs) compared to the peripheral pattern of SC model. TIL subpopulations in the LM model showed a progressive increase, contrasting with an initial rise and subsequent decline in the SC model. Post-anti-PD-L1 therapy, the LM model exhibited a significant rise in central and effector memory T cells, a response absents in the SC model. Our study highlights differential TME responses between SC and LM models and introduces a robust humanized LM model that swiftly indicates the potential efficacy of immunotherapies. These insights could streamline the preclinical evaluation of TME-targeting immunotherapeutic agents.


Asunto(s)
Neoplasias Hepáticas , Linfocitos Infiltrantes de Tumor , Ratones Endogámicos NOD , Ratones SCID , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Ratones , Microambiente Tumoral/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Leucocitos Mononucleares/inmunología , Modelos Animales de Enfermedad , Células HCT116 , Inmunoterapia/métodos
2.
Ther Adv Med Oncol ; 16: 17588359231225029, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38288157

RESUMEN

Purpose: This study aimed to investigate clinical practices and factors related to the outcomes of T-DM1 use in patients with HER2-positive metastatic breast cancer (mBC). Methods: We included patients with HER2-positive mBC who received T-DM1 as a palliative therapy between August 2017 and December 2018. The safety and outcomes of T-DM1, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) for mortality or progression to HER2-positive mBC. Results: In total, 824 patients were enrolled during the study period. The mean age of patients was 58 years, and 516 (62.6%) patients relapsed after curative treatment. Excluding a history of endocrine therapy, 341 (41.4%) patients previously received none or first-line chemotherapy, 179 (21.7%) received second-line therapy, and 303 (36.9%) received third-or later-line chemotherapy before T-DM1 therapy. During a median follow-up of 16.8 months, the ORR was 35%, the median PFS was 6.6 months, and the median OS was not reached. The clinical factors associated with the hazard of progression were age (<65 years), poor performance status (⩾2), advanced line of palliative chemotherapy (⩾2), prior pertuzumab use, and treatment duration of palliative trastuzumab (<10 months). Common grade 3-4 adverse events were thrombocytopenia (n = 107, 13.2%), neutropenia (n = 23, 2.8%), anemia (n = 21, 2.6%), and elevated liver enzyme (n = 20, 2.5%). Hypokalemia (⩽3.0 mmol/L) and any-grade bleeding events occurred in 25 (3.1%) and 94 (22.6%) patients, respectively. Conclusion: This is the first nationwide real-world study of T-DM1 use in patients with HER2-positive mBC in Korea. The effectiveness and toxicity profiles of T-DM1 in real-world practice were comparable to those in randomized trials. Moreover, patient factors and previous anti-HER2 therapy could predict the outcomes of T-DM1 therapy.

3.
J Psychosom Res ; 177: 111562, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38113795

RESUMEN

AIM: We investigated the impact of sleep disturbance on immune status in colorectal cancer (CRC) patients with consideration of the moderating role of circadian clock gene polymorphisms. METHODS: A prospective longitudinal study design was used to collect information regarding sleep disturbance. Blood samples for immunologic assays were obtained the day before the first (baseline) and last cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical sleep disturbance was compared between the two-time points using the Pittsburgh Sleep Quality Index (PSQI) global score. We analysed single-nucleotide polymorphisms in rs2278749, rs3749474, rs2291738, rs17031614, and rs2287161. The dependent variables included changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two-time points. The results were analysed using moderated regression analysis; the p-values were adjusted using the false discovery rate. RESULTS: Among the 104 patients, no significant dyadic associations were observed between changes in lymphocyte percentages and the PSQI global score. However, the moderated regression analysis revealed five significant associations (rs2287161 with CD8+, rs2278749 and rs2291738 with CD19+, and rs17031614 with CD4+ and CD16/56+ lymphocytes). The inclusion of each interaction resulted in a significant increase (5.7-10.7%) in the variance explained by changes in lymphocyte percentage. CONCLUSION: Patients with specific circadian gene allele types may be more susceptible to immune dysregulation when experiencing sleep disturbances. Considering that sleep disturbance is a modifiable factor that can impact immune regulation, it is essential to prioritise the management of sleep disturbances in CRC patients receiving FOLFOX chemotherapy.


Asunto(s)
Neoplasias Colorrectales , Subgrupos Linfocitarios , Humanos , Estudios Longitudinales , Estudios Prospectivos , Fluorouracilo/uso terapéutico , Oxaliplatino/uso terapéutico , Polimorfismo de Nucleótido Simple , Leucovorina/uso terapéutico , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/genética , Sueño
4.
Front Cardiovasc Med ; 10: 1285233, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37900575

RESUMEN

Despite significant advancements in systemic anticancer therapies, cardiac tamponade remains a serious and potentially life-threatening complication in metastatic breast cancer (MBC). However, there is a paucity of comprehensive research investigating alternative management approaches, such as pericardiocentesis and anti-inflammatory therapy (AIT), to effectively address cardiac tamponade and mitigate the risk of heart failure arising from constrictive physiology (CP) in patients with MBC when traditional systemic anticancer drugs fail to yield favorable outcomes. Herein, we describe two cases of MBC with cardiac tamponade that occurred despite the administration of effective systemic anticancer drugs. In each case, pericardial effusion was detected in a patient who was undergoing palliative anticancer therapy for human epidermal growth factor receptor 2 (HER2)-positive MBC. The patients in these cases were successfully treated with pericardiocentesis and AIT (prednisolone and colchicine) for subsequent CP without substitution with their systemic anticancer drugs. Cardiac tamponade and CP are regarded as signs of advanced cancer and are associated with a worse clinical outcome in general; however, they can still be treated with an effective anticancer drug, pericardiocentesis, and management of CP by cardiooncology specialists.

5.
Cell Death Discov ; 9(1): 122, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37041137

RESUMEN

Transforming growth factor-ß-activated kinase 1 (TAK1), which is highly expressed and aberrantly activated in triple-negative breast cancer (TNBC), plays a pivotal role in metastasis and progression. This makes it a potential therapeutic target for TNBC. Previously, we reported lectin galactoside-binding soluble 3 binding protein (LGALS3BP) as a negative regulator of TAK1 signaling in the inflammatory response and inflammation-associated cancer progression. However, the role of LGALS3BP and its molecular interaction with TAK1 in TNBC remain unclear. This study aimed to investigate the function and underlying mechanism of action of LGALS3BP in TNBC progression and determine the therapeutic potential of nanoparticle-mediated delivery of LGALS3BP in TNBC. We found that LGALS3BP overexpression suppressed the overall aggressive phenotype of TNBC cells in vitro and in vivo. LGALS3BP inhibited TNF-α-mediated gene expression of matrix metalloproteinase 9 (MMP9), which encodes a protein crucial for lung metastasis in TNBC patients. Mechanistically, LGALS3BP suppressed TNF-α-mediated activation of TAK1, a key kinase linking TNF-α stimulation and MMP9 expression in TNBC. Nanoparticle-mediated delivery enabled tumor-specific targeting and inhibited TAK1 phosphorylation and MMP9 expression in tumor tissues, suppressing primary tumor growth and lung metastasis in vivo. Our findings reveal a novel role of LGALS3BP in TNBC progression and demonstrate the therapeutic potential of nanoparticle-mediated delivery of LGALS3BP in TNBC.

6.
Cell Death Discov ; 7(1): 65, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33824294

RESUMEN

Galectin 3-binding protein (LGALS3BP, also known as 90K) is a multifunctional glycoprotein involved in immunity and cancer. However, its precise role in colon inflammation and tumorigenesis remains unclear. Here, we showed that Lgals3bp-/- mice were highly susceptible to colitis and colon tumorigenesis, accompanied by the induction of inflammatory responses. In acute colitis, NF-κB was highly activated in the colon of Lgals3bp-/- mice, leading to the excessive production of pro-inflammatory cytokines, such as IL-6, TNFα, and IL-1ß. Mechanistically, Lgals3bp suppressed NF-κB through the downregulation of TAK1 in colon epithelial cells. There was no significant difference in the pro-inflammatory cytokine levels between wild-type and Lgals3bp-/- mice in a chronic inflammatory state, during colon tumorigenesis. Instead, Lgals3bp-/- mice showed elevated levels of GM-CSF, compared to those in WT mice. We also found that GM-CSF promoted the accumulation of myeloid-derived suppressor cells and ultimately increased colon tumorigenesis in Lgals3bp-/- mice. Taken together, Lgals3bp plays a critical role in the suppression of colitis and colon tumorigenesis through the downregulation of the TAK1-NF-κB-cytokine axis. These findings suggest that LGALS3BP is a novel immunotherapeutic target for colon inflammation and tumorigenesis.

7.
Support Care Cancer ; 29(1): 397-407, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32372177

RESUMEN

PURPOSE: A caregiver's prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers' prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers. METHODS: This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers' awareness of the prognosis. RESULTS: Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients' QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients' prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024). CONCLUSION: Caregivers' prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.


Asunto(s)
Cuidadores/psicología , Depresión/epidemiología , Neoplasias/mortalidad , Neoplasias/terapia , Calidad de Vida/psicología , Adulto , Afecto , Anciano , Concienciación , Depresión/psicología , Emociones , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Neoplasias/psicología , Pronóstico , Estudios Prospectivos , Encuestas y Cuestionarios
8.
Cancer Sci ; 111(9): 3268-3278, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32533590

RESUMEN

Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and antiapoptosis through activation of RAS/RAF/ERK and PI3K/AKT pathways, which are also known as major molecular bases of colon cancer carcinogenesis related with epidermal growth factor receptor (EGFR) signaling. However, the interaction between FGFR4 and EGFR signaling in regard to colon cancer progression is unclear. Here, we investigated a potential cross-talk between FGFR4 and EGFR, and the effect of anti-EGFR therapy in colon cancer treatment. To explore the biological roles of FGFR4 in cancer progression, RNA sequencing was carried out using FGFR4 transfected colon cell lines. Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3. This result was also shown in in vivo study and the cooperative interaction between EGFR and FGFR4 promoted tumor growth. In addition, FGFR4 overexpression reduced cetuximab-induced cytotoxicity and the combination of FGFR4 inhibitor (BLU9931) and cetuximab showed profound antitumor effect compared to cetuximab alone. Clinically, we found the positive correlation between FGFR4 and AREG expression in tumor tissue, but not in normal tissue, from colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide the novel mechanism of FGFR4 in connection with EGFR activation and the combination of FGFR4 inhibitor and cetuximab could be a promising therapeutic option to achieve the optimal response to anti-EGFR therapy in colon cancer.


Asunto(s)
Anfirregulina/genética , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Línea Celular Tumoral , Cetuximab/farmacología , Neoplasias del Colon/patología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
9.
Oncol Lett ; 20(1): 921-930, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32566021

RESUMEN

Early [stage I and II (T2N0M0)] laryngeal cancer types are currently recommended to be treated with a single modality, consisting of definitive radiation therapy or larynx-preserving surgery. Although the treatment outcomes of stage I are good, the frequency of successful outcomes decreases with T2N0M0. Therefore, the present study investigated the treatment outcomes of different treatment methods in T2N0M0 laryngeal cancer. In total, 83 patients with previously untreated T2N0M0 laryngeal squamous cell carcinoma were enrolled. Patients were grouped by treatment method: Radiation therapy (RT; 27 patients); chemoradiotherapy (CRT; 46 patients) with cisplatin base; and surgery-based therapy (SBT; ten patients). The recurrence rates of the RT, CRT and SBT groups were 44.4, 19.6 and 50%, respectively. Moreover, the local control rates of the RT, CRT and SBT groups were 55.6, 87.0 and 80%, respectively. The CRT group had a significantly lower recurrence rate and higher local control rate compared with the RT group (P<0.05). In the survival analysis, overall and disease-specific survival rate did not differ significantly among the treatment groups. However, 3- and 5-year disease-free survival rates (DFS) of the RT group were both 55%, those of the SBT group were both 50% and those of the CRT group were both 80%. Furthermore, the DFS was significantly higher in CRT group compared with the other groups (P=0.02). Using multivariate analysis with Cox regression, it was found that the treatment method was the most important factor for DFS and had a significant impact in the CRT group. In addition, in patients with glottic cancer with anterior commissure and subglottic invasion, the CRT group had significantly improved DFS compared with the RT group, whereas there was no significant difference between the two groups in patients without subglottic invasion. According to National Cancer Institution Common Toxicity Criteria (version 5.0), more patients had toxicity in the CRT group compared with the RT group. However, in the RT and CRT groups, no patients demonstrated mortality due to toxicity, and treatment-related toxicities were manageable. Collectively, although definitive conclusions could not be established, due to the limitations of this retrospective study, the results suggest that CRT had a positive impact on the local control and DFS rates with manageable toxicity in patients with T2N0M0 laryngeal cancer.

10.
Sci Rep ; 10(1): 9549, 2020 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-32533084

RESUMEN

Background The clinical features and therapeutic strategies for gastric cancer with positive peritoneal washing cytology but without visible gross peritoneal metastasis have not been defined. The aim of this study was to evaluate the effect and clinical prognostic value of postoperative chemotherapy in gastric cancer patients with positive peritoneal washing cytology without gross peritoneal metastasis who underwent radical D2 gastrectomy in terms of disease-free survival (DFS) and overall survival (OS). Materials and Methods Intraoperative peritoneal washing cytology was performed in 285 patients who underwent radical D2 gastrectomy between April 2004 and May 2016. Of them, 88 patients with positive cytology but without gross peritoneal metastasis were included in the study. In total, 64 patients received postoperative chemotherapy, whereas 24 patients underwent surgery only. Results Most gastric cancer patients with positive cytology without gross peritoneal metastasis demonstrated pT4 and/or pN3 disease. Postoperative chemotherapy improved DFS and OS compared to surgery only in gastric cancer patients with positive cytology without gross peritoneal metastasis (median DFS 11.63 vs. 6.98 months, p < 0.001; median OS 25.50 vs. 12.11 months, p < 0.001). In multivariate analyses of gastric cancer patients with positive cytology without gross peritoneal metastasis, no chemotherapy was the strongest clinical factor for poorer DFS (hazard ratio [HR] 3.76, p < 0.001) or OS (HR 4.37, p < 0.001). Conclusion Postoperative chemotherapy improves the survival outcome compared to surgery alone in gastric cancer patients with positive peritoneal washing cytology but without visible gross peritoneal metastasis who underwent radical D2 gastrectomy.


Asunto(s)
Neoplasias Peritoneales/patología , Peritoneo/patología , Neoplasias Gástricas/patología , Citodiagnóstico/métodos , Supervivencia sin Enfermedad , Femenino , Gastrectomía/métodos , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Lavado Peritoneal/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
11.
Am J Hosp Palliat Care ; 37(11): 904-912, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32052654

RESUMEN

BACKGROUND: Accurate awareness of the prognosis is an important factor in the treatment decision of patients with advanced cancer; however, prognostic disclosure is still subject to debate because it can reduce patient's satisfaction and increase depression. AIM: The purpose of this study is to assess whether patients' prognostic awareness is associated with decreased quality of life (QoL) or increased depressive mood in patients with advanced cancer. DESIGN AND PARTICIPANTS: In this cohort study, 386 patients with advanced cancer were recruited across 3 periods from December 2016 to August 2018. The outcome of this study was a change in QoL and depression according to the patients' prognostic awareness at baseline, 3 months, and 6 months. RESULTS: This study found significant differences in changes of QoL based on patients' prognostic awareness. From baseline to 3 months, emotional functioning (P = .039), pain (P = .042), existential well-being (P = .025), and social support (P = .038) subscale scores improved significantly more in those with lack of prognostic awareness. Over 6 months, the group without prognostic awareness improved significantly in terms of physical functioning (P = .037), emotional functioning (P = .002), nausea/vomiting (P = .048), and constipation (P = .039) subscale scores and existential well-being scores (P = .025). No significant difference between the groups was found in terms of depression. CONCLUSION: Accurate prognostic awareness may pose harm and may provide no additional benefits in terms of QoL and mood among patients with advanced cancer for a short period of time.


Asunto(s)
Neoplasias , Calidad de Vida , Afecto , Estudios de Cohortes , Humanos , Pronóstico
12.
Cancer Sci ; 111(2): 513-527, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31789476

RESUMEN

The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Irinotecán/administración & dosificación , Leucovorina/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pueblo Asiatico , Determinación de Punto Final , Femenino , Fluorouracilo/uso terapéutico , Humanos , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Liposomas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Análisis de Supervivencia , Resultado del Tratamiento
13.
Support Care Cancer ; 28(6): 2959-2967, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31768736

RESUMEN

PURPOSE: Little has been determined regarding the association between patients' and families' illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers. METHODS: Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results. RESULTS: Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients' illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC. CONCLUSION: Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.


Asunto(s)
Planificación Anticipada de Atención , Comprensión , Neoplasias/terapia , Prioridad del Paciente , Cuidado Terminal , Planificación Anticipada de Atención/estadística & datos numéricos , Directivas Anticipadas/psicología , Directivas Anticipadas/estadística & datos numéricos , Anciano , Cuidadores/psicología , Estudios de Cohortes , Comprensión/fisiología , Progresión de la Enfermedad , Familia/psicología , Femenino , Cuidados Paliativos al Final de la Vida/psicología , Cuidados Paliativos al Final de la Vida/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/patología , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Cuidados Paliativos/estadística & datos numéricos , Prioridad del Paciente/psicología , Prioridad del Paciente/estadística & datos numéricos , Estudios Prospectivos , República de Corea/epidemiología , Cuidado Terminal/psicología , Cuidado Terminal/estadística & datos numéricos
14.
Commun Biol ; 2: 406, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31701034

RESUMEN

Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17ß-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. Analysis of mammary gland RNA revealed that PBDEs both augmented E2-facilitated gene expression and modulated immune regulation. Through single-cell RNA sequencing (scRNAseq) analysis, E2 was found to induce Pgr expression in both Esr1+ and Esr1- luminal epithelial cells and Ccl2 expression in Esr1+ fibroblasts. PBDEs promote the E2-AREG-EGFR-M2 macrophage pathway. Our findings support that E2 + PBDE increases the risk of developing breast cancer through the expansion of estrogen-responsive luminal epithelial cells and immune modulation.


Asunto(s)
Disruptores Endocrinos/toxicidad , Estradiol/toxicidad , Éteres Difenilos Halogenados/toxicidad , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Animales , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Receptor alfa de Estrógeno/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Retardadores de Llama/toxicidad , Perfilación de la Expresión Génica , Humanos , Glándulas Mamarias Animales/patología , Ratones , Ratones Endogámicos BALB C , Ovariectomía , RNA-Seq , Receptores de Progesterona/metabolismo , Análisis de la Célula Individual
15.
Support Care Cancer ; 27(10): 3921-3926, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31309297

RESUMEN

While recently extending that research, however, we discovered that 236 members of the general population were mistakenly duplicated by the investigating agency (Word Research) and 1241 were reported rather than 1005. Here, we present corrections and discuss the relevant data.

16.
J Cancer Res Clin Oncol ; 145(8): 2157-2166, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31273512

RESUMEN

PURPOSE: Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer. METHODS: We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, > 0.1-0.25; and LNR 3, > 0.25), and their disease-free survival (DFS) was evaluated. RESULTS: The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR > 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P < 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR > 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011). CONCLUSIONS: The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.


Asunto(s)
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Conducta de Elección , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Gastrectomía , Ganglios Linfáticos/patología , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Capecitabina , Quimioterapia Adyuvante/clasificación , Cisplatino/uso terapéutico , Terapia Combinada , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Gastrectomía/métodos , Humanos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oxaloacetatos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Tegafur/uso terapéutico , Uracilo/uso terapéutico
17.
J Pain Symptom Manage ; 57(4): 774-782, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30593911

RESUMEN

CONTEXT: To respect a patient's wish for end-of-life care, "the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life" was enacted in South Korea in 2016. Current understanding of people who would be involved in advance care planning (ACP) is crucial to disseminate it systematically. OBJECTIVES: The objective of this study was to investigate awareness and attitudes toward ACP in South Korea. METHODS: A multicenter, nationwide cross-sectional study was conducted, a survey regarding ACP among four groups that would have different positions and experiences: 1001 cancer patients, 1006 family caregivers, 928 physicians, and 1241 members of the general public. RESULTS: A total of 15% of the general population, 33% of the patients and caregivers, and 61% of the physicians had knowledge of advance directives. More than 64% of the general population, above 72% of the patients and caregivers, and 97% of the physicians were willing to do so when the disease status was aggravated or terminal. The possibility for changing the plan, uncertainty as to whether directives would actually be followed, and psychological discomfort were common reasons for not wanting to engage in ACP. Routine recommendations for a specific medical condition, heightened accessibility, and health insurance support were common factors that could help facilitate ACP. CONCLUSION: Our findings suggest that strategies for promoting ACP should reflect different perspectives among the general public, patients, family caregivers, and physicians. Public advocacy, resources for approaching and integrating ACP into routine health care, as well as systematic support provisions are needed.


Asunto(s)
Planificación Anticipada de Atención , Directivas Anticipadas/psicología , Actitud del Personal de Salud , Actitud Frente a la Salud , Cuidadores/psicología , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prioridad del Paciente , Encuestas y Cuestionarios , Cuidado Terminal/psicología
18.
Palliat Support Care ; 17(3): 300-305, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-29806573

RESUMEN

OBJECTIVE: Depressive symptoms are common in bereaved caregivers; however, there have been few prospective studies using a structured interview. This study investigated the prevalence and preloss predictors of major depressive disorder (MDD) in bereaved caregivers of patients in a palliative care unit. METHOD: This prospective cohort study collected caregiver sociodemographic and psychological data before the death of a palliative care unit patient, including MDD, care-burden, coping style, and hopeful attitude. Postloss MDD was assessed 6 and 13 months after death, and a multivariate logistic regression analysis was conducted to identify its predictors.ResultOf 305 caregivers contacted, 92 participated in this study. The prevalence of preloss MDD was 21.8%; the prevalences of postloss MDD were 34.8% and 24.7% at 6 and 13 months, respectively. Preloss MDD predicted postloss MDD at 6 months (odds ratio [OR] = 5.38, 95% confidence interval [CI95%] = 1.29, 22.43); preloss nonhopeful attitude and unemployment status of caregivers predicted postloss MDD at 13 months (OR = 8.77, CI95% = 1.87, 41.13 and OR = 7.10, CI95% = 1.28, 39.36, respectively).Significance of resultsApproximately 35% of caregivers suffered from MDD at 6 months postloss, but the prevalence of MDD decreased to about 25% at 13 months. Preloss MDD significantly predicted postloss MDD at 6 months, whereas hopeful attitude and unemployment at baseline were significantly associated with postloss MDD at 13 months.


Asunto(s)
Aflicción , Cuidadores/psicología , Trastorno Depresivo Mayor/etiología , Prevalencia , Adaptación Psicológica , Anciano , Estudios de Cohortes , Trastorno Depresivo Mayor/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Estudios Prospectivos , Psicometría/instrumentación , Psicometría/métodos , República de Corea/epidemiología , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Factores de Tiempo
19.
BMJ Open ; 8(9): e020519, 2018 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-30206075

RESUMEN

OBJECTIVES: This study determined attitudes of four groups-Korean patients with cancer, their family caregivers, physicians and the general Korean population-towards five critical end-of-life (EOL) interventions-active pain control, withdrawal of futile life-sustaining treatment (LST), passive euthanasia, active euthanasia and physician-assisted suicide. DESIGN AND SETTING: We enrolled 1001 patients with cancer and 1006 caregivers from 12 large hospitals in Korea, 1241 members of the general population and 928 physicians from each of the 12 hospitals and the Korean Medical Association. We analysed the associations of demographic factors, attitudes towards death and the important components of a 'good death' with critical interventions at EoL care. RESULTS: All participant groups strongly favoured active pain control and withdrawal of futile LST but differed in attitudes towards the other four EoL interventions. Physicians (98.9%) favoured passive euthanasia more than the other three groups. Lower proportions of the four groups favoured active euthanasia or PAS. Multiple logistic regression showed that education (adjusted OR (aOR) 1.77, 95% CI 1.33 to 2.36), caregiver role (aOR 1.67, 95% CI 1.34 to 2.08) and considering death as the ending of life (aOR 1.66, 95% CI 1.05 to 1.61) were associated with preference for active pain control. Attitudes towards death, including belief in being remembered (aOR 2.03, 95% CI 1.48 to 2.79) and feeling 'life was meaningful' (aOR 2.56, 95% CI 1.58 to 4.15) were both strong correlates of withdrawal of LST with the level of monthly income (aOR 2.56, 95% CI 1.58 to 4.15). Believing 'freedom from pain' negatively predicted preference for passive euthanasia (aOR 0.69, 95% CI 0.55 to 0.85). In addition, 'not being a burden to the family' was positively related to preferences for active euthanasia (aOR 1.62, 95% CI 1.39 to 1.90) and PAS (aOR 1.61, 95% CI 1.37 to 1.89). CONCLUSION: Groups differed in their attitudes towards the five EoL interventions, and those attitudes were significantly associated with various attitudes towards death.


Asunto(s)
Actitud , Cuidadores/psicología , Neoplasias/psicología , Médicos/psicología , Cuidado Terminal/métodos , Actitud Frente a la Muerte , Estudios Transversales , Escolaridad , Eutanasia Activa , Eutanasia Pasiva , Femenino , Humanos , Masculino , Inutilidad Médica , Persona de Mediana Edad , Neoplasias/terapia , Manejo del Dolor , Prioridad del Paciente , República de Corea , Suicidio Asistido , Privación de Tratamiento
20.
Oncol Lett ; 15(5): 6571-6577, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29731856

RESUMEN

The present study was conducted to investigate the prognostic significance of p16 (also known as cyclin-dependent kinase inhibitor 2A) in the treatment of induction chemoradiotherapy for advanced hypopharyngeal squamous cell carcinoma (HPSCC). Patients who were treated with at least two cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced HPSCC were reviewed in the study. The staining results were analyzed to examine the association between the chemotherapy response and the survival outcome. A total of 45 patients were enrolled for the present study; the majority had received induction chemotherapy with docetaxel, cisplatin, and 5-FU. Following induction chemotherapy, 17 patients (37.8%) exhibited a complete response and 28 patients (62.2%) exhibited a partial response. There were 11 patients (24.4%) with p16-positive immunohistochemical stains and 30 patients (66.7%) with p53-positive immunohistochemical stains. There was no significant difference in chemotherapy response, overall survival, or progression-free survival time between groups with p16-positive and p16-negative stains. Low p53 expression and chemotherapy response were not associated with each other. High p16 expression did not correlate with low p53 expression. In this study, p16 was not determined to predict the chemotherapy response for HPSCC. High p16 expression did not correlate with survival incidence for patients with HPSCC.

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