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1.
Breast Cancer Res Treat ; 197(3): 479-488, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36515748

RESUMEN

PURPOSE: This study evaluated radiosensitivity and the tumor microenvironment (TME) to identify characteristics of breast cancer patients who would benefit most from radiation therapy. METHODS: We analyzed 1903 records from the Molecular Taxonomy of Breast Cancer International Consortium cohort using the radiosensitivity index and gene expression deconvolution algorithms, CIBERSORT and xCell, that estimates the TME composition of tumor samples. In this study, patients were stratified according to TME and radiosensitivity. We performed integrative analyses of clinical and immuno-genomic data to characterize molecular features associated with radiosensitivity. RESULTS: Radiosensitivity was significantly associated with activation of antitumor immunity. In contrast, radioresistance was associated with a reactive stromal microenvironment. The immuno-genomic analysis revealed that estrogen receptor (ER) pathway activity was correlated with suppression of antitumor immunity. In ER-negative disease, the best prognosis was shown in the immune-high and radiosensitive group patients, and the lowest was in the immune-low and radioresistant group patients. In ER-positive disease, immune signature and radiosensitivity had no prognostic significance. CONCLUSION: Taken together, these results suggest that tumor radiosensitivity is associated with activation of antitumor immunity and a better prognosis, particularly in patients with ER-negative breast cancer.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Neoplasias de la Mama Triple Negativas/patología , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Pronóstico , Transducción de Señal , Tolerancia a Radiación/genética , Microambiente Tumoral/genética
2.
World J Surg ; 47(10): 2347-2355, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37423908

RESUMEN

BACKGROUND: Traumatic inferior vena cava (IVC) injuries are uncommon, but the mortality rate remains high at 38-70%. To date, most studies on traumatic IVC injuries have evaluated blunt rather than penetrating injuries. We aimed to identify the clinical features and risk factors that affect the prognosis of patients with blunt IVC injuries to improve treatment strategies for these patients. METHODS: We retrospectively analyzed patients diagnosed with blunt IVC injury over 8 years at a single trauma center. Clinical and biochemical parameters; transfusion, surgical, and resuscitation methods; associated injuries; intensive care unit stay; and complications data were compared between survival and death groups to identify clinical features and risk factors of blunt IVC injury-related mortality. RESULTS: Twenty-eight patients with blunt IVC injury were included during the study periods. Twenty-five (89%) patients underwent surgical treatment, and the mortality was 54%. The mortality rate according to the IVC injury location was the lowest for supra-hepatic IVC injury (25%, n = 2/8), whereas it was the highest for retrohepatic IVC injury (80%, n = 4/5). In the logistic regression analysis, Glasgow Coma Scale (GCS) (odds ratio [OR] = 0.566, 95% confidence interval [CI] [0.322-0.993], p = 0.047) and red blood cell (RBC) transfusion for 24 h (OR = 1.132, 95% CI [0.996-1.287], p = 0.058) were independent predictors for mortality. CONCLUSIONS: Low GCS score and high-volume packed RBC transfusion requirements for 24 h were significant predictors of mortality in patients with blunt IVC injuries. Unlike IVC injuries caused by penetrating trauma, supra-hepatic IVC injuries caused by blunt trauma have a good prognosis.


Asunto(s)
Traumatismos Abdominales , Heridas no Penetrantes , Heridas Penetrantes , Humanos , Estudios Retrospectivos , Vena Cava Inferior/cirugía , Pronóstico , Factores de Riesgo , Heridas Penetrantes/complicaciones , Heridas Penetrantes/diagnóstico , Heridas Penetrantes/cirugía , Traumatismos Abdominales/cirugía , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/terapia
3.
BMC Emerg Med ; 23(1): 57, 2023 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-37248552

RESUMEN

BACKGROUND: Ketamine and etomidate are commonly used as sedatives in rapid sequence intubation (RSI). However, there is no consensus on which agent should be favored when treating patients with trauma. This study aimed to compare the effects of ketamine and etomidate on first-pass success and outcomes of patients with trauma after RSI-facilitated emergency intubation. METHODS: We retrospectively reviewed 944 patients who underwent endotracheal intubation in a trauma bay at a Korean level 1 trauma center between January 2019 and December 2021. Outcomes were compared between the ketamine and etomidate groups after propensity score matching to balance the overall distribution between the two groups. RESULTS: In total, 620 patients were included in the analysis, of which 118 (19.9%) were administered ketamine and the remaining 502 (80.1%) were treated with etomidate. Patients in the ketamine group showed a significantly faster initial heart rate (105.0 ± 25.7 vs. 97.7 ± 23.6, p = 0.003), were more hypotensive (114.2 ± 32.8 mmHg vs. 139.3 ± 34.4 mmHg, p < 0.001), and had higher Glasgow Coma Scale (9.1 ± 4.0 vs. 8.2 ± 4.0, p = 0.031) and Injury Severity Score (32.5 ± 16.3 vs. 27.0 ± 13.3, p < 0.001) than those in the etomidate group. There were no significant differences in the first-pass success rate (90.7% vs. 90.1%, p > 0.999), final mortality (16.1% vs. 20.6, p = 0.348), length of stay in the intensive care unit (days) (8 [4, 15] (Interquartile range)), vs. 10 [4, 21], p = 0.998), ventilator days (4 [2, 10] vs. 5 [2, 13], p = 0.735), and hospital stay (days) (24.5 [10.25, 38.5] vs. 22 [8, 40], p = 0.322) in the 1:3 propensity score matching analysis. CONCLUSION: In this retrospective study of trauma resuscitation, those receiving intubation with ketamine had greater hemodynamic instability than those receiving etomidate. However, there was no significant difference in clinical outcomes between patients sedated with ketamine and those treated with etomidate.


Asunto(s)
Etomidato , Ketamina , Humanos , Etomidato/uso terapéutico , Ketamina/uso terapéutico , Estudios Retrospectivos , Anestésicos Intravenosos/efectos adversos , Intubación e Inducción de Secuencia Rápida , Centros Traumatológicos , Intubación Intratraqueal , República de Corea
4.
BMC Emerg Med ; 22(1): 101, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35672707

RESUMEN

BACKGROUND: We evaluated the accuracy of the prehospital Field Triage Decision Scheme, which has recently been applied in the Korean trauma system, and the factors associated with severe injury and prognosis at a regional trauma center in Korea. METHODS: From 2016 to 2018, prehospital data of injured patients were obtained from the emergency medical services of the national fire agency and matched with trauma outcomes at our institution. Severe injury (Injury Severity Score > 15), overtriage/undertriage rate, positive predictive value, negative predictive value, and accuracy were reviewed according to the triage protocol steps. A multivariate logistic regression analysis was performed to identify influencing factors in the field triage. RESULTS: Of the 2438 patients reviewed, 853 (35.0%) were severely injured. The protocol accuracy was as follows: step 1, 72.3%; step 2, 65.0%; step 3, 66.2%; step 1 or 2, 70.2%; and step 1, 2, or 3, 66.4%. Odds ratios (OR) (95% confidence interval [CIfor systolic blood pressure < 90 mmHg (3.535 [1.920-6.509]; p < 0.001), altered mental status (17.924 [8.980-35.777]; p < 0.001), and pedestrian injuries (2.473 [1.339-4.570], p = 0.04) were significantly associated with 24-h mortality. Penetrating torso injuries (7.108 [4.108-12.300]; p < 0.001); two or more proximal long bone fractures (4.134 [2.316-7.377]); p < 0.001); crushed, degloved, and mangled extremities (8.477 [4.068-17.663]; p < 0.001); amputation proximal to the wrist or ankle (42.964 [5.764-320.278]; p < 0.001); and fall from height (2.141 [1.497-3.062]; p < 0.001) were associated with 24-h surgical intervention. CONCLUSION: The Korean field triage protocol is not yet accurate, with only some factors reflecting injury severity, making reevaluation necessary.


Asunto(s)
Servicios Médicos de Urgencia , Heridas y Lesiones , Heridas Penetrantes , Adulto , Humanos , Puntaje de Gravedad del Traumatismo , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Centros Traumatológicos , Triaje/métodos , Heridas y Lesiones/epidemiología , Heridas y Lesiones/terapia
5.
J Korean Med Sci ; 36(22): e149, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34100561

RESUMEN

BACKGROUND: This study examined the impact of the performance improvement and patient safety (PIPS) program implemented in 2015 on outcomes for trauma patients in a regional trauma center established by a government-led project for a national trauma system in Korea. METHODS: The PIPS program was based on guidelines by the World Health Organization and American College of Surgeons. The corrective strategies were proceeded according to the loop closure principle: data-gathering and monitoring, identification of preventable trauma deaths (PTDs), evaluation of preventable factors, analysis of findings, and corrective action plans. We established guidelines and protocols for trauma care, conducted targeted education and peer review presentations for problematic cases, and enhanced resources for improvement accordingly. A comparative analysis was performed on trauma outcomes over a four-year period (2015-2018) since implementing the PIPS program, including the number of trauma team activation and admissions, time factors related to resuscitation, ventilator duration, and the rate of PTDs. RESULTS: Human resources in the center significantly increased during the period; attending surgeons responsible for trauma resuscitation from 6 to 11 and trauma nurses from 85 to 218. Trauma admissions (from 2,166 to 2,786), trauma team activations (from 373 to 1,688), and severe cases (from 22.6 to 33.8%) significantly increased (all P < 0.001). Time to initial resuscitation and transfusion significantly decreased from 120 to 36 minutes (P < 0.001) and from 39 to 16 minutes (P < 0.001). Time to surgery for hemorrhage control and decompressive craniotomy improved from 99 to 54 minutes (P < 0.001) and 181 to 135 minutes (P = 0.042). Ventilator duration and rate of PTDs significantly decreased from 6 to 4 days (P = 0.001) and 22.2% to 8.4% (P = 0.008). CONCLUSION: Implementation of the PIPS program resulted in improvements in outcomes at a regional trauma center that has just been opened in Korea. Further establishment of the PIPS program is required for optimal care of trauma patients.


Asunto(s)
Hospitalización/estadística & datos numéricos , Seguridad del Paciente , Mejoramiento de la Calidad , Centros Traumatológicos/organización & administración , Heridas y Lesiones/terapia , Humanos , Mortalidad , Evaluación de Programas y Proyectos de Salud , Resucitación , Factores de Tiempo , Resultado del Tratamiento
6.
Surg Today ; 51(6): 891-896, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33170365

RESUMEN

PURPOSE: The likelihood of re-bleeding after damage-control surgery (DCS) and perihepatic packing for high-grade liver injuries is a major concern. Thus, although early re-laparotomy tends to be recommended, we conducted this study to evaluate the feasibility of performing definite laparotomy within ≤ 48 h in this clinical population. METHODS: The subjects of this retrospective study were 65 patients (n = 24, ≤ 48-h group; n = 41, > 48-h group) who underwent DCS and perihepatic packing. The primary outcome was the rate of repacking for bleeding during re-laparotomy and the secondary outcomes were mortality and length of stay in the intensive care unit (ICU). RESULTS: The ≤ 48-h group had a higher rate of angioembolization and transfusion of red blood cells (RBCs), fresh frozen plasma, and platelets, but the rates of repacking and mortality were not significantly different between the groups. However, the incidence of pneumonia and ventilation support requirement were significantly lower in the ≤ 48-h group than in the > 48-h group. CONCLUSION: The re-laparotomy performed within ≤ 48 h after DCS and perihepatic packing is feasible for patients with high grade liver injury, using angioembolization and aggressive transfusion, as required. Early re-laparotomy reduces the need for prolonged ventilator support and the incidence of ventilator-associated pneumonia.


Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Embolización Terapéutica/métodos , Técnicas Hemostáticas , Laparotomía , Hígado/lesiones , Hígado/cirugía , Adulto , Estudios de Factibilidad , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neumonía/prevención & control , Reoperación , Respiración Artificial/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
7.
Nucleic Acids Res ; 46(13): 6592-6607, 2018 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-29846698

RESUMEN

Transcription factors and chromatin remodeling proteins control the transcriptional variability for ESC lineage commitment. During ESC differentiation, chromatin modifiers are recruited to the regulatory regions by transcription factors, thereby activating the lineage-specific genes or silencing the transcription of active ESC genes. However, the underlying mechanisms that link transcription factors to exit from pluripotency are yet to be identified. In this study, we show that the Ctbp2-interacting zinc finger proteins, Zfp217 and Zfp516, function as linkers for the chromatin regulators during ESC differentiation. CRISPR-Cas9-mediated knock-outs of both Zfp217 and Zfp516 in ESCs prevent the exit from pluripotency. Both zinc finger proteins regulate the Ctbp2-mediated recruitment of the NuRD complex and polycomb repressive complex 2 (PRC2) to active ESC genes, subsequently switching the H3K27ac to H3K27me3 during ESC differentiation for active gene silencing. We therefore suggest that some zinc finger proteins orchestrate to control the concise epigenetic states on active ESC genes during differentiation, resulting in natural lineage commitment.


Asunto(s)
Diferenciación Celular/genética , Células Madre Embrionarias/metabolismo , Silenciador del Gen , Transactivadores/fisiología , Oxidorreductasas de Alcohol/metabolismo , Animales , Células Cultivadas , Proteínas Co-Represoras , Células Madre Embrionarias/citología , Humanos , Ratones , Proteínas del Tejido Nervioso/metabolismo , Transcripción Genética
8.
World J Surg ; 43(6): 1519-1524, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30737554

RESUMEN

BACKGROUND: Resuscitative thoracotomy (RT) can be a lifesaving treatment, but it has not yet been performed in Korea. In this study, we review our experience of RT after a regional trauma center was constructed. METHODS: This is a retrospective study of RT conducted at a single Korean trauma center from May 2014 to March 2018. The primary outcome was survival, and the secondary outcome was return of spontaneous circulation (ROSC). The clinical characteristics of the patients were compared between the ROSC and non-ROSC groups. Survivors were also reviewed. RESULTS: A total of 62 patients were reviewed, and 60 patients had experienced blunt injury. Thirty-nine patients had ROSC. The ROSC group had short cardiopulmonary resuscitation (CPR) time (6 [2-10] min vs 11 [8-12] min, p < 0.001), the presence of sign of life at the trauma bay [32 (86.5%) vs 7 (28.0%), p < 0.001], and a low Injury Severity Score [26 (25-39) vs 37 (30-75), p = 0.038] compared to the non-ROSC group. On multivariate analysis, only the presence of sign of life was significantly associated with ROSC [11.297 (1.496-85.309) OR (95% CI), p = 0.019]. The 24-h survival rate was 8.1%, and the successful discharge rate was 4.8%. CONCLUSION: The outcome of RT in a Korean trauma center was favorable. ROSC after RT was strongly associated with the presence of sign of life, and RT may be performed in the presence of sign of life regardless of prehospital CPR time.


Asunto(s)
Circulación Sanguínea , Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario/terapia , Toracotomía , Adulto , Anciano , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/mortalidad , Reflejo Pupilar , República de Corea/epidemiología , Respiración , Estudios Retrospectivos , Centros Traumatológicos , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapia
9.
World J Surg ; 42(6): 1742-1747, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29344689

RESUMEN

BACKGROUND: Although there have been many studies dealing with tracheostomy timing in trauma patients, the optimal timing is still being debated. This study aimed to compare outcomes between early tracheostomy (ET) and late tracheostomy (LT) in trauma populations to estimate the optimal timing of tracheostomy after intubation. METHODS: We retrospectively reviewed the 5 years' data of trauma patients who underwent tracheostomy during their acute intensive care unit (ICU) stay. The cases were divided into two groups: ET was defined as tracheostomy performed within 7 days after intubation, and LT, after the seventh day. Propensity score matching was utilized using a 1-to-1 matching technique, and outcomes between two groups were compared. RESULTS: Among 236 enrolled patients, 76 met the criteria for ET and 160 were included for LT. Using propensity matching, 70 patients who met the criteria for ET were matched to 70 patients in the LT. Based on the comparison of outcomes after matching, ET showed significantly shorter values than LT in overall ventilator duration, length of stay at the ICU, and post-tracheostomy ventilation duration. Furthermore, the incidence of pneumonia was significantly lower with ET than with LT, although the rate of postoperative complications showed no significant differences. CONCLUSIONS: We suggest that ET should be considered in trauma patients needing prolonged mechanical ventilation. Also, we recommend that surgeons perform tracheostomy as early as within 7 days after intubation to not only reduce the ventilation and ICU days but also prevent pneumonia without worrying about an increase in postoperative complications.


Asunto(s)
Traqueostomía/métodos , Heridas y Lesiones/cirugía , Adulto , Anciano , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Neumonía/etiología , Complicaciones Posoperatorias/etiología , Puntaje de Propensión , Estudios Retrospectivos , Traqueostomía/efectos adversos
11.
Nucleic Acids Res ; 43(9): 4505-16, 2015 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-25813038

RESUMEN

Post-translational modifications of core histones affect various cellular processes, primarily through transcription. However, their relationship with the termination of transcription has remained largely unknown. In this study, we show that DNA damage-activated AKT phosphorylates threonine 45 of core histone H3 (H3-T45). By genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis, H3-T45 phosphorylation was distributed throughout DNA damage-responsive gene loci, particularly immediately after the transcription termination site. H3-T45 phosphorylation pattern showed close-resemblance to that of RNA polymerase II C-terminal domain (CTD) serine 2 phosphorylation, which establishes the transcription termination signal. AKT1 was more effective than AKT2 in phosphorylating H3-T45. Blocking H3-T45 phosphorylation by inhibiting AKT or through amino acid substitution limited RNA decay downstream of mRNA cleavage sites and decreased RNA polymerase II release from chromatin. Our findings suggest that AKT-mediated phosphorylation of H3-T45 regulates the processing of the 3' end of DNA damage-activated genes to facilitate transcriptional termination.


Asunto(s)
Daño del ADN , Histonas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Terminación de la Transcripción Genética , Línea Celular , Células HeLa , Histonas/química , Humanos , Células MCF-7 , Fosforilación , Treonina/metabolismo , Sitio de Iniciación de la Transcripción
12.
J Korean Med Sci ; 32(12): 2058-2063, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29115091

RESUMEN

A new blood bank system was established in our trauma bay, which allowed immediate utilization of uncross-matched type O packed red blood cells (UORBCs). We investigated the efficacy of UORBC compared to that of the ABO type-specific packed red blood cells (ABO RBCs) from before the bank was installed. From March 2016 to February 2017, data from trauma patients who received UORBCs in the trauma bay were compared with those of trauma patients who received ABO RBCs from January 2013 to December 2015. Propensity matching was used to overcome retrospective bias. The primary outcome was 24-hour mortality, while the secondary outcomes were in-hospital mortality and intensive care unit (ICU) length of stay (LOS). Data from 252 patients were reviewed and UORBCs were administered to 64 patients. The time to transfusion from emergency room admission was shorter in the UORBC group (11 [7-16] minutes vs. 44 [29-72] minutes, P < 0.001). After propensity matching, 47 patients were included in each group. The 24-hour mortality (4 [8.5%] vs. 9 [13.8%], P = 0.135), in-hospital mortality (14 [29.8%] vs. 18 [38.3%], P = 0.384), and ICU LOS (9 [4-19] days vs. 5 [0-19] days, P = 0.155) did not differ significantly between groups. The utilization of UORBCs resulted in a faster transfusion but did not significantly improve the clinical outcomes in traumatic shock patients in this study. However, the tendency for lower mortality in the UORBC group suggested the need for a large study.


Asunto(s)
Transfusión de Eritrocitos , Choque Traumático/terapia , Sistema del Grupo Sanguíneo ABO , Adulto , Femenino , Escala de Coma de Glasgow , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Choque Traumático/mortalidad , Choque Traumático/patología , Resultado del Tratamiento
13.
Stem Cells ; 33(9): 2699-711, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26059508

RESUMEN

Pluripotent stem cells (PSCs) have distinct metabolic properties that support their metabolic and energetic needs and affect their stemness. In particular, high glycolysis is critical for the generation and maintenance of PSCs. However, it is unknown how PSCs maintain and acquire this metabolic signature. In this study, we found that core pluripotency factors regulate glycolysis directly by controlling the expression of glycolytic enzymes. Specifically, Oct4 directly governs Hk2 and Pkm2, which are important glycolytic enzymes that determine the rate of glycolytic flux. The overexpression of Hk2 and Pkm2 sustains high levels of glycolysis during embryonic stem cell (ESC) differentiation. Moreover, the maintenance of high glycolysis levels by Hk2 and Pkm2 overexpression hampers differentiation and preserves the pluripotency of ESCs in the absence of leukemia inhibitory factor. Overall, our study identifies a direct molecular connection between core pluripotency factors and ESC metabolic signatures and demonstrates the significance of metabolism in cell fate determination.


Asunto(s)
Proteínas Portadoras/biosíntesis , Células Madre Embrionarias/metabolismo , Glucólisis/fisiología , Hexoquinasa/biosíntesis , Proteínas de la Membrana/biosíntesis , Factor 3 de Transcripción de Unión a Octámeros/biosíntesis , Células Madre Pluripotentes/metabolismo , Hormonas Tiroideas/biosíntesis , Animales , Diferenciación Celular/fisiología , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas de Unión a Hormona Tiroide
14.
Stem Cells ; 33(8): 2442-55, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25944056

RESUMEN

For cells to exit from pluripotency and commit to a lineage, the circuitry of a core transcription factor (CTF) network must be extinguished in an orderly manner through epigenetic modifications. However, how this choreographed epigenetic remodeling at active embryonic stem cell (ESC) genes occurs during differentiation is poorly understood. In this study, we demonstrate that C-terminal binding protein 2 (Ctbp2) regulates nucleosome remodeling and deacetylation (NuRD)-mediated deacetylation of H3K27 and facilitates recruitment of polycomb repressive complex 2 (PRC2)-mediated H3K27me3 in active ESC genes for exit from pluripotency during differentiation. By genomewide analysis, we found that Ctbp2 resides in active ESC genes and co-occupies regions with ESC CTFs in undifferentiated ESCs. Furthermore, ablation of Ctbp2 effects inappropriate gene silencing in ESCs by sustaining high levels of H3K27ac and impeding H3K27me3 in active ESC genes, thereby sustaining ESC maintenance during differentiation. Thus, Ctbp2 preoccupies regions in active genes with the NuRD complex in undifferentiated ESCs that are directed toward H3K27me3 by PRC2 to induce stable silencing, which is pivotal for natural lineage commitment.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Epigénesis Genética/fisiología , Histonas/metabolismo , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/metabolismo , Células Madre Embrionarias de Ratones/metabolismo , Fosfoproteínas/metabolismo , Proteínas Represoras/metabolismo , Oxidorreductasas de Alcohol , Animales , Línea Celular , Ensamble y Desensamble de Cromatina/fisiología , Proteínas Co-Represoras , Proteínas de Unión al ADN/genética , Histonas/genética , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , Ratones , Células Madre Embrionarias de Ratones/citología , Nucleosomas/genética , Nucleosomas/metabolismo , Fosfoproteínas/genética , Proteínas Represoras/genética
15.
JCO Precis Oncol ; 8: e2300263, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38452311

RESUMEN

PURPOSE: The estrogen receptor-positive (ER+) breast cancer (BC), which constitutes the majority of BC cases, exhibits highly heterogeneous clinical behavior. To aid precision treatments, we aimed to find molecular subtypes of ER+ BC representing the tumor microenvironment and prognosis. METHODS: We analyzed RNA-seq data of 113 patients with BC and classified them according to the PAM50 intrinsic subtypes using gene expression profiles. Among them, we further focused on 44 patients with luminal-type (ER+) BC for subclassification. The Cancer Genome Atlas (TCGA) data of patients with BC were used as a validation data set to verify the new classification. We estimated the immune cell composition using CIBERSORT and further analyzed its association with clinical or molecular parameters. RESULTS: Principal component analysis clearly divided the patients into two subgroups separately from the luminal A and B classification. The top differentially expressed genes between the subgroups were distinctly characterized by immunoglobulin and B-cell-related genes. We could also cluster a separate cohort of patients with luminal-type BC from TCGA into two subgroups on the basis of the expression of a B-cell-specific gene set, and patients who were predicted to have high B-cell immune activity had better prognoses than other patients. CONCLUSION: Our transcriptomic approach emphasize a molecular phenotype of B-cell immunity in ER+ BC that may help to predict disease prognosis. Although further researches are required, B-cell immunity for patients with ER+ BC may be helpful for identifying patients who are good responders to chemotherapy or immunotherapy.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Inmunidad Celular , Microambiente Tumoral/genética
16.
Sci Rep ; 14(1): 9164, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38644449

RESUMEN

Recently, resuscitative endovascular balloon occlusion of the aorta (REBOA) had been introduced as an innovative procedure for severe hemorrhage in the abdomen or pelvis. We aimed to investigate risk factors associated with mortality after REBOA and construct a model for predicting mortality. This multicenter retrospective study collected data from 251 patients admitted at five regional trauma centers across South Korea from 2015 to 2022. The indications for REBOA included patients experiencing hypovolemic shock due to hemorrhage in the abdomen, pelvis, or lower extremities, and those who were non-responders (systolic blood pressure (SBP) < 90 mmHg) to initial fluid treatment. The primary and secondary outcomes were mortality due to exsanguination and overall mortality, respectively. After feature selection using the least absolute shrinkage and selection operator (LASSO) logistic regression model to minimize overfitting, a multivariate logistic regression (MLR) model and nomogram were constructed. In the MLR model using risk factors selected in the LASSO, five risk factors, including initial heart rate (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.98-1.00; p = 0.030), initial Glasgow coma scale (aOR, 0.86; 95% CI 0.80-0.93; p < 0.001), RBC transfusion within 4 h (unit, aOR, 1.12; 95% CI 1.07-1.17; p < 0.001), balloon occlusion type (reference: partial occlusion; total occlusion, aOR, 2.53; 95% CI 1.27-5.02; p = 0.008; partial + total occlusion, aOR, 2.04; 95% CI 0.71-5.86; p = 0.187), and post-REBOA systolic blood pressure (SBP) (aOR, 0.98; 95% CI 0.97-0.99; p < 0.001) were significantly associated with mortality due to exsanguination. The prediction model showed an area under curve, sensitivity, and specificity of 0.855, 73.2%, and 83.6%, respectively. Decision curve analysis showed that the predictive model had increased net benefits across a wide range of threshold probabilities. This study developed a novel intuitive nomogram for predicting mortality in patients undergoing REBOA. Our proposed model exhibited excellent performance and revealed that total occlusion was associated with poor outcomes, with post-REBOA SBP potentially being an effective surrogate measure.


Asunto(s)
Aorta , Oclusión con Balón , Mortalidad Hospitalaria , Nomogramas , Resucitación , Humanos , Oclusión con Balón/métodos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Resucitación/métodos , Adulto , Procedimientos Endovasculares/métodos , Factores de Riesgo , Heridas y Lesiones/mortalidad , Heridas y Lesiones/complicaciones , Heridas y Lesiones/terapia , Anciano , República de Corea/epidemiología , Hemorragia/mortalidad , Hemorragia/terapia , Hemorragia/etiología , Modelos Logísticos
17.
Biochem Biophys Res Commun ; 431(1): 8-13, 2013 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-23291169

RESUMEN

CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Proteína X Asociada a bcl-2/genética , Proteínas Quinasas Activadas por AMP/biosíntesis , Oxidorreductasas de Alcohol/genética , Proteínas de Unión al ADN/genética , Activación Enzimática , Células HEK293 , Humanos , Fosforilación , Serina/genética , Serina/metabolismo , Transcripción Genética , Ubiquitinación
18.
Eur J Trauma Emerg Surg ; 49(6): 2495-2503, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37277572

RESUMEN

PURPOSE: Recently, trauma centers in the Republic of Korea introduced resuscitative endovascular balloon occlusion of the aorta (REBOA) for application in severe pelvic fracture cases. This study aimed to determine the efficacy of REBOA and its associated factors in enhancing survival. METHODS: Data from patients with severe pelvic injuries at two regional trauma centers from 2016 to 2020 were retrospectively reviewed. Patients were dichotomized into REBOA and no-REBOA groups, and patient characteristics and clinical outcomes were compared using 1:1 propensity score matching. Additional survival-based analysis was performed in the REBOA group. RESULTS: REBOA was performed in 42 of the 174 patients with pelvic fractures. As patients in the REBOA group had more severe injuries than did patients in the no-REBOA group, 1:1 propensity score matching was performed to adjust for severity. After matching, 24 patients were included in each group and mortality was not significantly different (REBOA 62.5% vs. no-REBOA 41.7%, P = 0.149). Kaplan-Meier analysis revealed no significant differences in mortality between the two matched groups (log-rank test, P = 0.408). Among the 42 patients treated with REBOA, 14 survived. Shorter REBOA duration (63 [40-93] vs. 166 [67-193] min, P = 0.015) and higher systolic blood pressure before REBOA (65 [58-76] vs. 54 [49-69] mmHg, P = 0.035) were associated with better survival. CONCLUSIONS: The effectiveness of REBOA has not been definitively established; however, it was not associated with increased mortality in this study. Additional studies are required to better understand how REBOA can be effectively used for treatment.


Asunto(s)
Oclusión con Balón , Procedimientos Endovasculares , Fracturas Óseas , Choque Hemorrágico , Humanos , Estudios Retrospectivos , Puntaje de Gravedad del Traumatismo , Aorta , Fracturas Óseas/terapia , Resucitación , Choque Hemorrágico/terapia
19.
Cancer Res Treat ; 55(3): 865-874, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36701844

RESUMEN

PURPOSE: We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non-small cell lung cancer (LA-NSCLC). Materials and Methods: Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS). RESULTS: PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001). CONCLUSION: PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/terapia , Estudios Retrospectivos , Pulmón , Quimioradioterapia/efectos adversos
20.
Injury ; 54(4): 1156-1162, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36849305

RESUMEN

INTRODUCTION: Open pelvic fractures are commonly associated with life-threatening, uncontrollable haemorrhages. Although management methods for pelvic injury-associated haemorrhage have been established, the early mortality rate associated with open pelvic fractures remains high. This study aimed to identify predictors of mortality and effective treatment methods for open pelvic fractures. METHODS: We defined open pelvic fractures as pelvic fractures with an open wound directly connected to the adjacent soft tissue, genitals, perineum, or anorectal structures, resulting in soft tissue injuries. This study was performed on trauma patients (age ≥15 years) injured by a blunt mechanism between 2011 and 2021 at a single trauma centre. We collected and analysed the data on the Injury Severity Score (ISS), the Revised Trauma Score (RTS), the Trauma and Injury Severity Score (TRISS), length of hospital stay, length of intensive care unit stay, transfusion, preperitoneal pelvic packing (PPP), resuscitative endovascular balloon occlusion of the aorta (REBOA), therapeutic angio-embolisation, laparotomy, faecal diversion, and mortality. RESULTS: Forty-seven patients with blunt open pelvic fractures were included. The median age was 45 years (interquartile range, 27-57 years) and median ISS was 34 (24-43). The most frequently performed treatment methods were laparotomy (53%) and pelvic binder (53%), followed by faecal diversion (40%) and PPP (38%). PPP was the only method performed at a higher rate in the survival group for haemorrhagic control (41% vs. 30%). Haemorrhagic mortality was present in one case that received PPP. The overall mortality was 21%. In the univariate logistic regression analysis, initial systolic blood pressure (SBP), TRISS, RTS, packed red blood cell transfusion for the first 24 h, and base excess showed statistical significance (p<0.05). In the multivariate logistic regression model, initial SBP was identified as an independent risk factor for mortality (odds ratio, 0.943; 95% confidence interval, 0.907-0.980; p = 0.003). CONCLUSION: A low initial SPB may be an independent predictor of mortality in patients with open pelvic fractures. Our findings suggest that PPP might be a feasible method to decrease haemorrhagic mortality from open pelvic fractures, especially for haemodynamically unstable patients with low initial SBP. Further studies are required to validate these clinical findings.


Asunto(s)
Fracturas Óseas , Fracturas Abiertas , Huesos Pélvicos , Humanos , Persona de Mediana Edad , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones , Fracturas Abiertas/complicaciones , Hemorragia/terapia , Hemorragia/complicaciones , Puntaje de Gravedad del Traumatismo , Huesos Pélvicos/lesiones , Pelvis , Estudios Retrospectivos , Adulto
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