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Apert's syndrome (AS) is a rare congenital malformation characterized by distinctive clinical manifestations such as syndactyly of the extremities and midface retrusion, which set it apart from other syndromes. This condition often presents with craniosynostosis and, less commonly, central nervous system abnormalities like encephalocele. In this report, we present a typical case of Apert syndrome with an occipital encephalocele. The infant had plagio-brachycephaly due to craniosynostosis and required urgent repair of the occipital encephalocele. At 1 month of age, we performed both the encephalocele repair and early cranioplasty for autologous bone grafting. This case underscores the importance of early diagnosis and surgical interventions in Apert's syndrome cases with encephalocele.
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Because of essential role in homeostasis of the body fluid and excretion of wastes, kidney damage can lead to severe impacts on health and survival of humans. For most chemicals, nephrotoxic potentials and associated mechanisms are unclear. Hence, fast and sensitive screening measures for nephrotoxic chemicals are required. In this study, the utility of zebrafish (Danio rerio) was evaluated for the investigation of chemical-induced kidney toxicity and associated modes of toxicity, based on the literature review. Zebrafish has a well-understood biology, and many overlapping physiological characteristics with mammals. One such characteristic is its kidneys, of which histology and functions are similar to those of mammals, although unique differences of zebrafish kidneys, such as kidney marrow, should be noted. Moreover, the zebrafish kidney is simpler in structure and easy to observe. For these advantages, zebrafish has been increasingly used as an experimental model for screening nephrotoxicity of chemicals and for understanding related mechanisms. Multiple endpoints of zebrafish model, from functional level, i.e., glomerular filtration, to transcriptional changes of key genes, have been assessed to identify chemical-induced kidney toxicities, and to elucidate underlying mechanisms. The most frequently studied mechanisms of chemical-induced nephrotoxicity in zebrafish include oxidative stress, inflammation, DNA damage, apoptosis, fibrosis, and cell death. To date, several pharmaceuticals, oxidizing agents, natural products, biocides, alcohols, and consumer chemicals have been demonstrated to exert different types of kidney toxicities in zebrafish. The present review shows that zebrafish model can be efficiently employed for quick and reliable assessment of kidney damage potentials of chemicals, and related toxic mechanisms. The toxicological information obtained from this model can be utilized for identification of nephrotoxic chemicals and hence for protection of public health.
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Poluentes Químicos da Água , Peixe-Zebra , Animais , Embrião não Mamífero/metabolismo , Humanos , Mamíferos/metabolismo , Estresse Oxidativo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismoRESUMO
PURPOSE: Correcting facial contour deformities is a challenge, as it demands thoughtful planning on design, composition of flap, and secondary procedures. The thoracodorsal artery perforator (TDAP) flap has become a workhorse flap for various reconstructions. In this report, we present our experience of reconstructing facial contour deformities using the free TDAP adipofascial flap, focusing on its customized design. PATIENTS AND METHOD: Sixteen patients underwent correction of a facial contour deformity with free TDAP adipofascial flaps from 2002 to 2012. The causes of defects were Romberg disease (n = 7), oncological defects (n = 5), craniofacial microsomia (n = 3), and trauma (n = 1). The flaps were three-dimensionally designed in a contour map fashion to have different thickness according to the defects by adjusting the height of adipose tissue and varying tissue composition. Customized dimension of flaps having reliable perfusion were harvested with minimized sacrifice of overlying skin. RESULTS: Flap size ranged from 6 × 3 cm to 25 × 25 cm. Six flaps were based on two perforators and the other 10 on one. Five flaps were harvested in a chimeric fashion. All flaps survived completely. No donor morbidity developed in any case. Seven patients underwent secondary corrections including fat injection or liposuction. Improved contour and symmetry were achieved in all patients and was confirmed by a photographic evaluation. Mean follow-up period was 37.8months. CONCLUSIONS: Our results suggest that the stereoscopic TDAP adipofascial flaps with diligent secondary approaches may be a reliable alternative for aesthetic reconstruction of facial contour deformities. © 2015 Wiley Periodicals, Inc. Microsurgery 37:300-306, 2017.
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Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/transplante , Procedimentos de Cirurgia Plástica/métodos , Artérias Torácicas/transplante , Cicatrização/fisiologia , Tecido Adiposo/cirurgia , Tecido Adiposo/transplante , Adolescente , Adulto , Criança , Estudos de Coortes , Anormalidades Craniofaciais/cirurgia , Estética , Traumatismos Faciais/cirurgia , Neoplasias Faciais/cirurgia , Fáscia/transplante , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Artérias Torácicas/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Currently, few prognostic factors are available to predict the emergence of castration-resistant prostate cancer and no curative options are available. Epigenetic gene regulation has been shown to trigger prostate cancer metastasis and androgen independence. Histone lysine demethylases (KDMs) are epigenetic enzymes that can remove both repressive and activating histone marks. KDM5 family members are capable of removing the histone H3 lysine 4 dimethylation-activating mark, rendering them potential players in the down-regulation of tumor suppressors and suggesting that their activity could repress oncogenes. Here, we systematically investigated KDM5C expression patterns in two independent radical prostatectomy cohorts (822 prostate tumors in total) by immunohistochemistry. Positive nuclear KDM5C staining was significantly associated with a reduced prostate-specific antigen relapse-free survival. Our study confirmed that nuclear KDM5C expression is an independent prognostic parameter. Most strikingly, the prognostic value of nuclear KDM5C expression for progression-free survival was exclusively pronounced for the Gleason group 7. In addition, KDM5C knockdown resulted in growth retardation of prostate cancer cells in vitro and induced regulation of several proliferation-associated genes. Our data indicate that KDM5C is functionally involved in proliferation control of prostate cancer cells and might represent a novel attractive therapy target. Moreover, overexpression of KDM5C is an independent new predictive marker for therapy failure as determined by biochemical recurrence in patients after prostatectomy.
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Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia/patologia , Oxirredutases N-Desmetilantes/biossíntese , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Intervalo Livre de Doença , Histona Desmetilases , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , TransfecçãoRESUMO
BACKGROUND: Despite the decrease in donor-site morbidity with the advent of deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, abdominal complications still occur. There have been few studies on donor morbidity considering the ethnic differences in the Asian population, as represented by a lower BMI with less redundant tissue and a tendency for poor scarring. In the present study, the authors investigated the incidence of abdominal complications and their risk factors following DIEP flap breast reconstruction in an Asian population. PATIENTS AND METHODS: The authors conducted a retrospective review of DIEP flap based breast reconstructions performed in the past 5 years. Data regarding patient demographics, surgical details, and abdominal complications were collected from our prospectively maintained database and analyzed. RESULTS: A total of 217 patients who underwent DIEP flap breast reconstruction were included. There were 51 abdominal complications (23.5%), including 18 delayed wound healing, 17 hypertrophic scarring, 12 seroma formation, and 8 abdominal bulges with no hernias. Secondary procedures were performed for the donor-site complications in 36 cases. Flap height was a significant risk factor for overall donor-site morbidity. Harvesting a bipedicle flap was significantly associated with abdominal fat necrosis and hypertrophic scarring. Harvesting a flap based on perforators from both rows was significantly associated with abdominal delayed wound healing and hypertrophic scarring. CONCLUSIONS: DIEP flap breast reconstruction performed in Asian patients showed acceptable donor-site morbidity without significant complications. This study suggests that donor-site morbidity from harvesting a DIEP flap is comparable to that described in Western literatures.
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Abdome/cirurgia , Povo Asiático , Artérias Epigástricas/cirurgia , Mamoplastia/métodos , Retalho Perfurante , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Modelos Logísticos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , República da Coreia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Preoperative breast magnetic resonance imaging (MRI) is a routine test for oncologic evaluation. However, determining breast volume using a preoperative MRI obtained as a part of oncologic evaluation has not yet been attempted for immediate breast reconstruction. The study introduces the benefit of MRI-based volumetry, not only in autologous breast reconstruction but also in implant-based breast reconstruction. METHODS: Forty patients preparing for autologous breast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap and 30 patients for implant-based breast reconstruction from June 2011 to June 2012 were included in this study. In every DIEP case, we collected data about actual resected breast tissue weight during mastectomy and final flap weight inserted intraoperatively. Computed tomography (CT) was for preoperative CT angiography for microsurgical breast reconstruction, whereas MRI was performed for oncologic evaluation. In every implant-based reconstruction case, MRI-based breast volume was measured in the same way for DIEP patients and resected breast tissue weight was measured intraoperatively. In addition, we also added or subtracted the breast volume by any modification, such as reduction and augmentation on the ipsilateral or contralateral side. To determine the accuracy of MRI-based volumetry, Pearson correlation coefficients were calculated to quantify the correlation between CT and MRI-based volumetry data and intraoperative volume measurements. RESULTS: For DIEP patients, the mean resected breast tissue weight during mastectomy was more closely related to the mean estimated breast volume using MRI than to the mean estimated breast volume using CT (Pearson coefficient 0.928 and 0.782; p = 0.001). MRI gave a closer correlation to final flap weight than CT (Pearson correlation coefficient 0.959 and 0.873; p = 0.001). For implant-based reconstruction patients, the breast volume measured by MRI correlated closely with the actual mean weight of resected breast specimens (0.937; p = 0.001). Mean net implanted volume was more closely related to mean estimated breast volume using MRI than to mean resected breast tissue weight during mastectomy (0.893 and 0.880; p = 0.001). CONCLUSIONS: Reliable volumetric information can be obtained using MRI for breast implant volume and autologous tissue needed in optimizing symmetry in breast reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Artérias Epigástricas/transplante , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Mamoplastia/métodos , Retalho Perfurante/irrigação sanguínea , Adulto , Distribuição de Qui-Quadrado , Estudos de Coortes , Tomografia Computadorizada de Feixe Cônico/métodos , Estética , Feminino , Sobrevivência de Enxerto , Humanos , Mamoplastia/efeitos adversos , Mastectomia/métodos , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Tamanho do Órgão , Retalho Perfurante/transplante , Cuidados Pós-Operatórios/métodos , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
BACKGROUND: There are several methods that may be used to confirm the status of rib cartilage, such as physical examinations or chest radiography, for subjects with microtia. However, these methods are limited because of clinicians' inability to gain accurate information about the rib cartilage. We performed 3-dimensional chest computed tomography to preoperatively evaluate the accuracy of rib cartilage imaging. METHODS: A total of 37 patients preparing for auricular reconstruction using a rib cartilage graft underwent preoperative 3-dimensional rib cage computed tomography (3-D rib CT). The 3-D rib CT was performed in cases of secondary revisional reconstruction, those with a history of surgery using rib cartilage, in those with a history of trauma related to the rib cage, older patients with question of calcification of rib cartilage, or those with a suspected rib cartilage anomaly on physical examination. Preoperatively, the appropriateness of using the rib cartilage were evaluated. RESULTS: With the aid of the 3-D rib CT, successful autogenous auricular reconstruction was achieved in 36 patients. Framework fabrication in combination with a porous polyethylene implant and autogenous rib cartilage was performed in the remaining patient as planned preoperatively. By analyzing the 3-D rib CT image preoperatively, auricular reconstruction using a recycled rib cartilage graft with newly harvested rib cartilage was performed successfully in 13 of 14 secondary revisional cases. Based on preoperative CT images, modified surgical planning in terms of cartilage harvest and framework fabrication was needed in 8 of 11 patients who had a history of operation using rib cartilage and in 3 of 5 subjects with suspected rib cage anomalies on physical examination. Successful reconstruction was achieved using the modified surgical plan. CONCLUSIONS: A preoperative 3-D rib CT helps in surgical planning for autogenous auricular reconstruction for microtia, especially in patients with suspicious rib cartilage status.
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Cartilagem/transplante , Microtia Congênita/cirurgia , Imageamento Tridimensional , Tomografia Computadorizada Multidetectores/métodos , Procedimentos de Cirurgia Plástica/métodos , Cuidados Pré-Operatórios/métodos , Costelas/diagnóstico por imagem , Adolescente , Adulto , Cartilagem/diagnóstico por imagem , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Endoscopic excision is a growing treatment option for benign facial tumors; however, its outcome has not been reported in a large series with long-term follow-up. The purpose of this study was to present the outcome of our decade-long experience with endoscopic excision, compared with direct excision.We retrospectively reviewed patients who underwent surgical treatment using either the endoscopic or direct approach for benign facial tumors from January 2001 to January 2012. Patient demographics, complications, recurrence, and pathological results were collected. Patient satisfaction was assessed using survey questionnaires. The results of endoscopic excision and direct excision were compared.Endoscopic excision was performed for 152 patients consisting of 77 lipomas (50.7%), 45 osteomas (29.6%), 24 dermoid cysts (15.8%), and 6 others (3.9%). The masses were located on the forehead in 138 patients (90.8%) and on the cheeks in 14 patients (9.2%). Direct excision was performed for 123 patients composed of 62 lipomas (50.4%), 46 dermoid cysts (37.4%), 11 osteomas (8.9%), and 4 others (3.3%). The mean follow-up period was 4.6 years. In the endoscopic excision group, hematomas developed in 2 and wound dehiscence in 1 patient. In the direct excision group, 1 hematoma and 1 wound dehiscence occurred. There were 4 recurrent cases in the endoscopic excision group and 1 recurrent case in the direct excision group, but there was no statistically significant difference in the recurrence rate between the 2 groups (2.6% vs 0.8%, P=0.258). Patient satisfaction was higher in the endoscopic excision group than in the direct excision group (satisfaction for aesthetics, 92.98 vs 71.71%, P<0.001; satisfaction for procedure, 89.9 vs 76.15%, P=0.001).Compared with direct excision, endoscopic excision provided a comparable recurrence rate and higher patient satisfaction in this decade-long study. Endoscopic excision is a safe and valuable treatment option for selected benign tumors on the forehead and cheek.
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Cisto Dermoide/cirurgia , Endoscopia/métodos , Neoplasias Faciais/cirurgia , Lipoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Osteoma/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Endoscopia/efeitos adversos , Feminino , Seguimentos , Hematoma , Humanos , Incidência , Masculino , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/cirurgia , Satisfação do Paciente , Reoperação , Estudos Retrospectivos , Deiscência da Ferida Operatória/etiologia , Resultado do TratamentoRESUMO
Several researches have shown that negative-pressure wound dressings can secure split-thickness skin grafts and improve graft survival. However, in anatomically difficult body regions such as the perineum it is questionable whether these dressings have similar beneficial effects. In this study, we evaluated the effects of negative-pressure wound dressings on split-thickness skin grafts in the perineum by comparing wound healing rate and complication rate with that of tie-over dressings. A retrospective chart review was performed for the patients who underwent a split-thickness skin graft to reconstruct perineal skin defects between January 2007 and December 2011. After grafting, the surgeon selected patients to receive either a negative-pressure dressing or a tie-over dressing. In both groups, the initial dressing was left unchanged for 5 days, then changed to conventional wet gauze dressing. Graft success was assessed 2 weeks after surgery by a single clinician. A total of 26 patients were included in this study. The mean age was 56·6 years and the mean wound size was 273·1 cm(2). Among them 14 received negative-pressure dressings and 12 received tie-over dressings. Negative-pressure dressing group had higher graft taken rate (P = 0·036) and took shorter time to complete healing (P = 0·01) than tie-over dressing group. The patients with negative-pressure dressings had a higher rate of graft success and shorter time to complete healing, which has statistical significance. Negative-pressure wound dressing can be a good option for effective management of skin grafts in the perineum.
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Períneo/cirurgia , Neoplasias Cutâneas/cirurgia , Transplante de Pele , Sítio Doador de Transplante/cirurgia , Adulto , Idoso , Fasciite Necrosante/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento de Ferimentos com Pressão Negativa , Estudos Retrospectivos , Transplante de Pele/métodos , Estresse Mecânico , CicatrizaçãoRESUMO
Purpose: The purpose of this study is to build a prediction model for estimating graft weight about different graft volumetry methods combined with other variables. Methods: Donors who underwent living-donor right hepatectomy from March 2021 to March 2023 were included. Estimated graft volume measured by conventional method and 3-dimensional (3D) software were collected as well as the actual graft weight. Linear regression was used to build a prediction model. Donor groups were divided according to the 3D volumetry of <700 cm3, 700-899 cm3, and ≥900 cm3 to compare the performance of different models. Results: A total of 119 donors were included. Conventional volumetry showed R2 of 0.656 (P < 0.001) while 3D software showed R2 of 0.776 (P < 0.001). The R2 of the multivariable model was 0.842 (P < 0.001) including for 3D volume (ß = 0.623, P < 0.001), body mass index (ß = 7.648, P < 0.001), and amount of weight loss (ß = -7.252, P < 0.001). The median errors between different models and actual graft weight did not differ in donor groups (<700 and 700-899 cm3), while the median error of univariable linear model using 3D software (122.5; interquartile range [IQR], 61.5-179.8) was significantly higher than multivariable-adjusted linear model (41.5; IQR, 24.8-69.8; P = 0.003) in donors with estimated graft weight ≥900 cm3. Conclusion: The univariable 3D volumetry model showed an acceptable outcome for donors with an estimated graft volume <900 cm3. For donors with an estimated graft volume ≥900 cm3, the multivariable-adjusted linear model showed higher accuracy.
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PURPOSE: Hepatocellular carcinoma (HCC) is a significant health concern, and the complexity of liver anatomy poses challenges in conveying radiologic findings and surgical plans to patients. This study aimed to evaluate the impact of a virtual reality (VR) education program on anxiety and knowledge in HCC patients undergoing hepatic resection. METHOD: From 1 January 2022 to 28 February 2023, 88 patients were enrolled in a randomized controlled trial, divided into the VR group ( n =44) and the control group ( n =44). The VR group received patient-specific 3D liver model education through a VR platform, while the control group underwent conventional explanation processes. Both groups completed preintervention and postintervention questionnaires assessing anxiety (using STAI-X-1, STAI-X-2, and VAS) and knowledge about liver resection. Comparison of the questionnaires were performed between the two groups. Multivariable logistic regression was performed to analyze factor related to decrease in anxiety. RESULT: While there was no significant difference in preintervention anxiety and knowledge scores between the two groups, the VR group exhibited significant reduction in STAI-X-1 scores (-4.14±7.5) compared to the control group (-0.84±5.7, P =0.023), as well as knowledge scores (17.20±2.6) compared to the control group (13.42±3.3, P <0.001). In the multivariable logistic regression model, VR education showed significant impact on decrease in STAI-X-1 score, postintervention. (OR=2.902, CI=1.097-7.674, P =0.032). CONCLUSION: The VR education program significantly improved knowledge and reduced anxiety among HCC patients compared to conventional methods. This study suggests that VR can be a valuable tool in patient education, enhancing comprehension and alleviating presurgical anxiety.
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Ansiedade , Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Educação de Pacientes como Assunto , Realidade Virtual , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Feminino , Ansiedade/prevenção & controle , Ansiedade/etiologia , Pessoa de Meia-Idade , Hepatectomia/educação , Hepatectomia/métodos , Educação de Pacientes como Assunto/métodos , Inquéritos e Questionários , Adulto , Idoso , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
The aim of the present study was to evaluate the effect of ETS homologous factor (EHF) in malignant breast cancer cells. The overexpression and knockdown of the EHF gene in human and mouse breast cancer cells were performed, and the TCGA dataset and Q-omics were analyzed. We found that the tumor suppressor NDRG2 is correlated with EHF gene expression in triple-negative breast cancer cells, that EHF overexpression results in reduced cell proliferation and that apoptosis is promoted by the chemotherapeutic reagent treatment of EHF-overexpressing cells. By EHF overexpression, senescence-associated ß-galactosidase activity and p21WAF1/CIP1 expression were increased, suggesting that EHF may induce cellular senescence. In addition, the overexpression of EHF reduced the migratory ability and inhibited epithelial-mesenchymal transition (EMT). Furthermore, EHF inhibited the phosphorylation of STAT3. The overexpression of EHF also reduced the tumor size, and lung metastasis in vivo. At the tumor site, ß-galactosidase activity was increased by EHF. Finally, the Kaplan-Meier-plotter analysis showed that TNBC patients with a high expression of EHF had a longer relapse-free survival rate. Our findings demonstrated that EHF inhibits breast tumor progression by inducing senescence and regulating EMT in TNBC cells.
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BACKGROUND: Microphthalmia-associated transcription factor (MITF) is a master regulator of melanogenesis and is mainly expressed in melanoma cells. MITF has also been reported to be expressed in non-pigmented cells, such as osteoclasts, mast cells, and B cells. However, the roles of MITF in immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSCs), remain unclear. Here, we investigated the role of MITF in the differentiation process of MDSCs during tumor development. METHODS: In vitro-generated murine MDSCs and primary MDSCs from breast cancer-bearing mice or lung carcinoma-bearing mice were used to determine the expression level of MITF and the activity of MDSCs. Additionally, we investigated whether in vivo tumor growth can be differentially regulated by coinjection of MDSCs in which MITF expression is modulated by small molecules. Furthermore, the number of MITF+ monocytic (MO)-MDSCs was examined in human tumor tissues or tumor-free lymph nodes by immunohistochemistry (IHC). RESULTS: The expression of MITF was strongly increased in MO-MDSCs from tumors of breast cancer-bearing mice compared with polymorphonuclear MDSCs. We found that MITF expression in MDSCs was markedly induced in the tumor microenvironment (TME) and related to the functional activity of MDSCs. MITF overexpression in myeloid cells increased the expression of MDSC activity markers and effectively inhibited T-cell proliferation compared with those of control MDSCs, whereas shRNA-mediated knockdown of MITF in myeloid cells altered the immunosuppressive function of MDSCs. Modulation of MITF expression by small molecules affected the differentiation and immunosuppressive function of MDSCs. While increased MITF expression in MDSCs promoted breast cancer progression and CD4+ or CD8+ T-cell dysfunction, decreased MITF expression in MDSCs suppressed tumor progression and enhanced T-cell activation. Furthermore, IHC staining of human tumor tissues revealed that MITF+ MO-MDSCs are more frequently observed in tumor tissues than in tumor-free draining lymph nodes obtained from patients with cancer. CONCLUSIONS: Our results indicate that MITF regulates the differentiation and function of MDSCs and can be a novel therapeutic target for modulating MDSC activity in immunosuppressive s.
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Neoplasias da Mama , Fator de Transcrição Associado à Microftalmia , Células Supressoras Mieloides , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Diferenciação Celular , Fator de Transcrição Associado à Microftalmia/genética , Células Mieloides/metabolismo , Células Supressoras Mieloides/metabolismo , Microambiente TumoralRESUMO
Postoperative nausea and vomiting (PONV) are common complications after surgery. This study aimed to present the utilization of machine learning for predicting PONV and provide insights based on a large amount of data. This retrospective study included data on perioperative features of patients, such as patient characteristics and perioperative factors, from two hospitals. Logistic regression algorithms, random forest, light-gradient boosting machines, and multilayer perceptrons were used as machine learning algorithms to develop the models. The dataset of this study included 106,860 adult patients, with an overall incidence rate of 14.4% for PONV. The area under the receiver operating characteristic curve (AUROC) of the models was 0.60-0.67. In the prediction models that included only the known risk and mitigating factors of PONV, the AUROC of the models was 0.54-0.69. Some features were found to be associated with patient-controlled analgesia, with opioids being the most important feature in almost all models. In conclusion, machine learning provides valuable insights into PONV prediction, the selection of significant features for prediction, and feature engineering.
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Postoperative pulmonary complications (PPCs) are significant causes of postoperative morbidity and mortality. This study presents the utilization of machine learning for predicting PPCs and aims to identify the important features of the prediction models. This study used a retrospective cohort design and collected data from two hospitals. The dataset included perioperative variables such as patient characteristics, preexisting diseases, and intraoperative factors. Various algorithms, including logistic regression, random forest, light-gradient boosting machines, extreme-gradient boosting machines, and multilayer perceptrons, have been employed for model development and evaluation. This study enrolled 111,212 adult patients, with an overall incidence rate of 8.6% for developing PPCs. The area under the receiver-operating characteristic curve (AUROC) of the models was 0.699-0.767, and the f1 score was 0.446-0.526. In the prediction models, except for multilayer perceptron, the 10 most important features were obtained. In feature-reduced models, including 10 important features, the AUROC was 0.627-0.749, and the f1 score was 0.365-0.485. The number of packed red cells, urine, and rocuronium doses were similar in the three models. In conclusion, machine learning provides valuable insights into PPC prediction, significant features for prediction, and the feasibility of models that reduce the number of features.
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Post-translational modifications of histones by chromatin modifying enzymes regulate chromatin structure and gene expression. As deregulation of histone modifications contributes to cancer progression, inhibition of chromatin modifying enzymes such as histone demethylases is an attractive therapeutic strategy to impair cancer growth. Lysine-specific demethylase 1 (LSD1) removes mono- and dimethyl marks from lysine 4 or 9 of histone H3. LSD1 in association with the androgen receptor (AR) controls androgen-dependent gene expression and prostate tumor cell proliferation, thus highlighting LSD1 as a drug target. By combining protein structure similarity clustering and in vitro screening, we identified Namoline, a γ-pyrone, as a novel, selective and reversible LSD1 inhibitor. Namoline blocks LSD1 demethylase activity in vitro and in vivo. Inhibition of LSD1 by Namoline leads to silencing of AR-regulated gene expression and severely impairs androgen-dependent proliferation in vitro and in vivo. Thus, Namoline is a novel promising starting compound for the development of therapeutics to treat androgen-dependent prostate cancer.
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Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Pironas/farmacologia , Androgênios/metabolismo , Animais , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatina/genética , Cromatina/metabolismo , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Nus , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Histone modifying enzymes confer epigenetic marks, directing the changes in gene expression required for diverse cellular processes. Lysine-specific demethylase 1 (LSD1) functions as a transcriptional coregulator by demethylating histone H3 on lysine 4 and lysine 9. Analyzing transcriptomes on microarrays, we identified genes which represent inflammatory-related targets of LSD1. We demonstrate a repressive role of LSD1 in proinflammatory cytokine expression such as IL1α, IL1ß, IL6 and IL8 and classical complement components. Consistently, LSD1 occupies and regulates the promoter of these genes. In addition, we demonstrate that HDAC1 and LSD1 synergistically regulate these inflammatory-related genes. Our data reveal a novel role for LSD1 in suppressing immune responses.
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Via Clássica do Complemento/genética , Citocinas/genética , Epigênese Genética , Histona Desacetilase 1/metabolismo , Histona Desmetilases/metabolismo , Imunidade/genética , Inflamação/genética , Linhagem Celular Tumoral , Citocinas/antagonistas & inibidores , Regulação para Baixo , Técnicas de Silenciamento de Genes , Células Hep G2 , Histona Desacetilase 1/genética , Histona Desmetilases/genética , HumanosRESUMO
BACKGROUND: The objective of this study was to estimate the outcomes of surgical treatment for patients with venous malformations (VMs). METHODS: We retrospectively reviewed the data of 48 patients who underwent surgical management for VMs from 1994 to 2009 at our institute. The 1-year responses to surgeries were classified into three groups based on the results: "remission," "improvement," and "no change." RESULTS: The indications of surgeries were mass or swelling in 48 patients (100%), intractable pain in 11 (23%), limb length discrepancy in seven (15%), bleeding in three (6%), and limitation of the range of motion in one (2%). The locations of the VMs were head and neck in 17 patients (35%), abdomen and pelvis in one (2%), perineum and genitalia in three (6%), upper extremities in 12 (25%), and lower extremities or buttocks in 15 (31%). Of the 48 surgeries for radical excision and debulking, 25 (52%) resulted in remission, 11 (23%) in improvement, and 12 (25%) in no change. During follow-up (mean: 44.8 ± 36.6 months, range: 0-111 months), recurrence after radical excision occurred in 10% (3 of 31) of the patients, and size increase after debulking surgery in 24% (4 of 17) of the patients. CONCLUSIONS: Surgical treatment can be an option in patients with VMs, especially with symptoms that cannot be managed with conservative therapy or sclerotherapy. After excisional or debulking surgery in patient with VMs, remission or improvement can be observed in 75%.
Assuntos
Malformações Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares , Veias/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Embolização Terapêutica , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , República da Coreia , Estudos Retrospectivos , Escleroterapia , Fatores de Tempo , Resultado do Tratamento , Malformações Vasculares/complicações , Malformações Vasculares/diagnóstico , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Veias/anormalidades , Adulto JovemRESUMO
The extended latissimus dorsi flap has been widely used for breast reconstruction. However, seroma at the donor site is a common complication and makes it difficult for reconstructive surgeons to choose it as a primary option. We analyzed the association between seroma and reconstructions with extended latissimus dorsi flaps. A series of 120 consecutive cases were included in this study. The average body mass index (BMI) was 22.1 kg/m, and the mean ratio of the flap weight to the extirpated breast weight was equivalent to 101.6%. The mean age of patients was 40.3 years. Donor-site seroma was reported in 69.2% (83 cases) of the total patients. With respect to BMI, flap weight, and age, the incidence and duration of donor-site seroma showed statistically significant differences (P<0.05). Both the incidence and duration of seroma were significantly higher and longer in patients who had high BMI (>23 kg/m), large flap (>450 g) for reconstructions, or advanced age (>45 y). In these cases, greater attention and additional adjunctive procedures would be needed to prevent seroma.
Assuntos
Mamoplastia/métodos , Complicações Pós-Operatórias , Seroma/etiologia , Retalhos Cirúrgicos , Adulto , Neoplasias da Mama/cirurgia , Feminino , Humanos , Incidência , Mastectomia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Seroma/epidemiologiaRESUMO
Three-dimensional (3D) modeling of the liver can be especially useful for both the surgeon and patient to understand the actual location of the tumor and planning the resection plane. Virtual reality (VR) can enhance the understanding of 3D structures and create an environment where the user can focus on contents provided. In the present study, a VR platform was developed using Unreal Engine 4 software (Epic Games, Potomac, MD, USA). Patient's liver based on magnetic resonance image was imported as a 3D model that could distinguish liver parenchyma, vascular structure, and cancer. Preoperative education videos for patients were developed. They could be viewed inside the VR platform. To evaluate the usefulness of VR education program for patients undergoing liver resection for hepatocellular carcinoma, a randomized clinical trial evaluating the knowledge and anxiety of the patient was designed. The case presented in this report was the first experience of performing the VR education program and examining the knowledge and anxiety using questionnaires. When the knowledge score increased, the anxiety score also increased after the education program. Based on findings of this pilot case study, the timing and place where the questionnaire will be answered can be modified for formal initiation of the randomized controlled study to examine the usefulness of VR in patient education.