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1.
Mol Cell Proteomics ; 22(3): 100504, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36708875

RESUMO

MYCN amplification is an independent risk factor for poor prognosis in neuroblastoma (NB), but its protein product cannot be directly targeted because of protein structure. Thus, this study aimed to explore novel ways to indirectly target N-Myc by regulating its post-translational modifications (PTMs) and therefore protein stability. N-Myc coimmunoprecipitation combined with HPLC-MS/MS identified 16 PTM residues and 114 potential N-Myc-interacting proteins. Notably, both acetylation and ubiquitination were identified on lysine 199 of N-Myc. We then discovered that p300, which can interact with N-Myc, modulated the protein stability of N-Myc in MYCN-amplified NB cell lines and simultaneously regulated the acetylation level and ubiquitination level on lysine-199 of N-Myc protein in vitro. Furthermore, p300 correlated with poor prognosis in NB patients. Taken together, p300 can be considered as a potential therapeutic target to treat MYCN-amplified NB patients, and other identified PTMs and interacting proteins also provide potential targets for further study.


Assuntos
Lisina , Neuroblastoma , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteína Proto-Oncogênica N-Myc/uso terapêutico , Lisina/metabolismo , Espectrometria de Massas em Tandem , Processamento de Proteína Pós-Traducional , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Neuroblastoma/metabolismo , Estabilidade Proteica , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
2.
Br J Cancer ; 130(11): 1841-1854, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38553589

RESUMO

BACKGROUND: Despite the extensive study of MYCN-amplified neuroblastomas, there is a significant unmet clinical need in MYCN non-amplified cases. In particular, the extent of heterogeneity within the MYCN non-amplified population is unknown. METHODS: A total of 1566 samples from 16 datasets were identified in Gene Expression Omnibus (GEO) and ArrayExpress. Characterisation of the subtypes was analysed by ConsensusClusterPlus. Independent predictors for subgrouping were constructed from the single sample predictor based on the multiclassPairs package. Findings were verified using immunohistochemistry and CIBERSORTx analysis. RESULTS: We demonstrate that MYCN non-amplified neuroblastomas are heterogeneous and can be classified into 3 subgroups based on their transcriptional signatures. Within these groups, subgroup_2 has the worst prognosis and this group shows a 'MYCN' signature that is potentially induced by the overexpression of Aurora Kinase A (AURKA); whilst subgroup_3 is characterised by an 'inflamed' gene signature. The clinical implications of this subtype classification are significant, as each subtype demonstrates a unique prognosis and vulnerability to investigational therapies. A total of 420 genes were identified as independent subgroup predictors with average balanced accuracy of 0.93 and 0.84 for train and test datasets, respectively. CONCLUSION: We propose that transcriptional subtyping may enhance precision prognosis and therapy stratification for patients with MYCN non-amplified neuroblastomas.


Assuntos
Proteína Proto-Oncogênica N-Myc , Neuroblastoma , Humanos , Neuroblastoma/genética , Neuroblastoma/classificação , Neuroblastoma/patologia , Neuroblastoma/mortalidade , Proteína Proto-Oncogênica N-Myc/genética , Prognóstico , Aurora Quinase A/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Amplificação de Genes
3.
J Surg Res ; 290: 116-125, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37257402

RESUMO

INTRODUCTION: Intraoperative leveling biopsy by identifying ganglion cells is crucial to determine surgical margin during surgery for Hirschsprung disease (HSCR). The anastomosis should be performed at least 5 cm proximal to the ganglionic segment to prevent transition zone pull-through. However, the length of the transition zone could be much longer than expected and the histological evaluation of the entire circumference of the proximal margin is recommended, which is time-consuming and not applicable for leveling biopsy. We found that the histopathologic features of ganglion cells varied in the examined bowel specimens and demonstrated a pattern similar to immature and degenerated neuron cells. We assumed that the histopathologic features of ganglion cells in the proximal resected bowel were associated with the clinical outcome and might guide the leveling biopsy. In this study, we described a histopathologic grade of ganglion cells based on the degree of maturity and degeneration. We assessed the correlation between the histopathological grade of ganglion cells in the proximal surgical margin and clinical outcome. METHODS: Three hundred fifty seven patients with HSCR treated between 2013 and 2020 were included. The ganglion cells were divided into six grades based on the histopathologic features in frozen sections. Medical records and detailed histopathologic results of intraoperative frozen sections were reviewed. Follow-up data were collected to evaluate clinical outcomes. The pediatric incontinence and constipation scoring system was used to predict bowel function. RESULTS: The histopathologic results of proximal resected bowel from 357 HSCR patients were presented as follows: Grade I in 52 patients (14.6%), Grade II in 186 patients (52.1%), Grade III in 107 patients (30.0%), and Grade IV in 12 patients (3.4%). The median follow-up time was 46.8 mo (13.0-97.6 mo). The histopathologic grade of ganglion cells from the proximal resected margin was significantly related to postoperative constipation problems and the incidence of Hirschsprung-associated enterocolitis. The results from the pediatric incontinence and constipation scoring system indicated a positive correlation between better postoperative bowel function and lower histopathologic grade of ganglion cells. CONCLUSIONS: This pilot study showed an association between the histopathologic features of ganglion cells in the proximal surgical margin and the clinical outcome. It may provide additional information for intraoperative pathologic consultation in leveling biopsy to prevent insufficient resection of the affected colon. A prospective study is warranted to validate these findings before clinical application.


Assuntos
Doença de Hirschsprung , Criança , Humanos , Lactente , Doença de Hirschsprung/cirurgia , Doença de Hirschsprung/complicações , Projetos Piloto , Margens de Excisão , Estudos Prospectivos , Constipação Intestinal/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neurônios/patologia
4.
BMC Cancer ; 21(1): 784, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233647

RESUMO

BACKGROUND: Minichromosome maintenance complex component 6 (MCM6), as an important replication permission factor, is involved in the pathogenesis of various tumors. Here we studied the expression of MCM6 in neuroblastoma and its influence on tumor characteristics and prognosis. METHODS: Publicly available datasets were used to explore the influence of the differential expression of MCM6 on neuroblastoma tumor stage, risk and prognosis. In cell experiments, human neuroblastoma cell lines SK-N-SH and SK-N-BE [ (2)] were utilized to verify the ability of MCM6 to promote cell proliferation, migration and invasion. We further explored the possible molecular mechanism of MCM6 affecting the phenotype of neuroblastoma cells by mutual verification of RNA-seq and western blotting, and flow cytometry to inquire about its potential specific roles in the cell cycle. RESULTS: Through multiple datasets mining, we found that high expression of MCM6 was positively correlated with elevated tumor stage, high risk and poor prognosis in neuroblastoma. At the cellular level, neuroblastoma cell proliferation, migration and invasion were significantly inhibited after MCM6 was interfered by siRNA. Mutual verification of RNA-seq and western blotting suggested that the downstream cell cycle-related genes were differentially expressed after MCM6 interference. Flow cytometric analysis revealed that neuroblastoma cells were blocked in G1/S phase after MCM6 interference. CONCLUSION: MCM6 is considered to be the driving force of G1/S cell cycle progression, and it is also a prognostic marker and a potential novel therapeutic target in neuroblastoma.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Componente 6 do Complexo de Manutenção de Minicromossomo/efeitos adversos , Neuroblastoma/genética , Animais , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Camundongos Nus , Neuroblastoma/patologia , Prognóstico , Transfecção , Resultado do Tratamento
5.
Int J Med Sci ; 18(14): 3214-3223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34400891

RESUMO

Infantile hemangioma (IH), which threatens the physical and mental health of patients, is the most common benign tumor in infants. Previously, we found that 15,16-dihydrotanshinone I (DHTS) was significantly more effective at inhibiting hemangioma proliferation in vitro and in vivo than the first-line treatment propranolol. To investigate the underlying mechanism of DHTS, we used EOMA cells as a model to study the effect of DHTS. We compared the transcriptomes of control and DHTS-treated EOMA cells. In total, 2462 differentially expressed genes were detected between the groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed downregulated activity of the hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway in EOMA cells following treatment with DHTS. Thus, we investigated HIF-1α expression at protein and mRNA levels. Our results revealed that DHTS downregulated HIF-1α expression by interfering in its posttranscriptional processing, and the RNA-binding protein HuR participated in this mechanism. Our findings provide a basis for clinical transformation of DHTS and insight into pathogenic mechanisms involved in IH.


Assuntos
Furanos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hemangioma/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Fenantrenos/farmacologia , Quinonas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismo , Furanos/uso terapêutico , Técnicas de Silenciamento de Genes , Hemangioma/genética , Hemangioma/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fenantrenos/uso terapêutico , Quinonas/uso terapêutico , Processamento Pós-Transcricional do RNA/efeitos dos fármacos , RNA-Seq , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
6.
Pediatr Blood Cancer ; 65(9): e27229, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29797641

RESUMO

BACKGROUND: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. PROCEDURE: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. RESULTS: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. CONCLUSIONS: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy.


Assuntos
Biomarcadores Tumorais/análise , Galectina 1/análise , Proteínas de Neoplasias/análise , Neuroblastoma/química , Neoplasias Retroperitoneais/química , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Medula Óssea/secundário , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Galectina 1/biossíntese , Galectina 1/sangue , Humanos , Técnicas Imunoenzimáticas , Lactente , Estimativa de Kaplan-Meier , Masculino , Neoplasias do Mediastino/sangue , Neoplasias do Mediastino/química , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/patologia , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/sangue , Estadiamento de Neoplasias , Neuroblastoma/sangue , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Prognóstico , Intervalo Livre de Progressão , Neoplasias Retroperitoneais/sangue , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Análise Serial de Tecidos , Carga Tumoral
7.
BMC Pediatr ; 18(1): 162, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29751786

RESUMO

BACKGROUND: Meconium peritonitis is an infrequent congenital disease usually caused by perforation of the fetal digestive tract. Meconium peritonitis resulting from intrauterine appendiceal perforation has been rarely reported and is often overlooked during pregnancy. We herein report two cases of fetal appendiceal perforation. CASE PRESENTATION: Two neonates were found to have intestinal distension and gradually increasing ascites antenatally. After birth, diagnostic abdominal punctures revealed meconium peritonitis. Urgent surgery showed both neonates had developed gangrenous appendicitis in utero. Pathological examination supported the diagnosis of fetal appendiceal perforation in both neonates, and one also had deformity of cecal duplication. In the present report, we also review the presentation, diagnosis, pathology, management, and recent literature of fetal appendiceal perforation. CONCLUSION: Meconium peritonitis due to fetal appendiceal perforation is extremely rare, and preoperative diagnosis is almost impossible. However, clinicians should be aware of abnormal gastrointestinal manifestations in the fetus during the antenatal examination. For neonates with severe meconium peritonitis, an early operation with careful intraoperative exploration is necessary.


Assuntos
Apendicite/complicações , Mecônio , Peritonite/etiologia , Apendicite/diagnóstico , Apendicite/patologia , Apendicite/cirurgia , Ceco/anormalidades , Humanos , Recém-Nascido , Masculino , Peritonite/diagnóstico , Peritonite/patologia , Peritonite/cirurgia
8.
Med Sci Monit ; 23: 17-23, 2017 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-28042962

RESUMO

BACKGROUND Sacrococcygeal teratoma (SCT) is a relatively uncommon tumor. Recurrence with poor survival and anorectal dysfunction are the 2 leading problems for patients. Here, we would review the clinic features of patients with SCTs in our hospital to identify risk factors of recurrent SCTs and to analyze anorectal functional sequelae. MATERIAL AND METHODS A retrospective review of all patients with SCTs in our center between 2007 and 2013 was performed. We analyzed the recorded data on each patient and performed follow-up through phone calls. RESULTS Our study included 105 inpatients (78 girls and 27 boys); 104 cases underwent surgical resection, and 62.5% cases had a mature histopathology. The proportion of malignant teratomas rose with increasing age. Fifteen children developed recurrent SCTs with a median of 11.5 months, and most of them had an elevation of AFP levels. Four recurrent children experienced a second tumor relapse. We observed a statistically significant difference in survival rate through Kaplan-Meier method between relapsed (66.7%) and non-relapsed (94.4%) patients. In univariate analysis, incomplete primary resection and malignant histology were proven to increase recurrence risks. Nearly half of patients had at least 1 of the parameters reflecting abnormal bowel function (e.g., involuntary bowel movements, fecal incontinence, and constipation). For those recurrent SCTs patients, difficulty defecating was a major problem. CONCLUSIONS Tumor recurrence affected the prognosis of children with SCT. In our research, incomplete resection and malignant histology were considered risk factors. Constipation was the main problem in anorectal functional sequelae for children who had recurrence.


Assuntos
Canal Anal/fisiopatologia , Reto/fisiopatologia , Região Sacrococcígea/patologia , Região Sacrococcígea/fisiopatologia , Teratoma/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva , Fatores de Risco , Região Sacrococcígea/cirurgia , Taxa de Sobrevida , Teratoma/mortalidade , Teratoma/cirurgia , Resultado do Tratamento
9.
Pediatr Surg Int ; 33(5): 627-629, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28213679

RESUMO

We report a case of gastroschisis in male twins. Both twins were preterm and low birth weight, with intestinal malrotation; they were diagnosed by antenatal ultrasound at 20 weeks of gestation. Immediately after delivery, they underwent evaluation and early surgical one-stage repair under anesthesia. One of the twins was found to have duodenal perforation at laparotomy, at the horizontal part near Treitz ligament. Both twins stayed in hospital for 30 days and were in good health at discharge.


Assuntos
Gastrosquise/diagnóstico por imagem , Gastrosquise/cirurgia , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/cirurgia , Adulto , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Gêmeos Monozigóticos , Ultrassonografia Pré-Natal
10.
Pharm Biol ; 55(1): 1592-1600, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28399694

RESUMO

CONTEXT: Essential oils (EOs) have shown the potential to reversibly overcome the stratum corneum (SC) barrier to enhance the skin permeation of drugs. OBJECTIVE: The effectiveness of turpentine, Angelica, chuanxiong, Cyperus, cinnamon, and clove oils were investigated for the capacity and mechanism to promote skin penetration of ibuprofen. MATERIALS AND METHODS: Skin permeation studies of ibuprofen across rat abdominal skin with the presence of 3% w/v EOs were carried out; samples were withdrawn from the receptor compartment at 8, 10, 22, 24, 26, 28, 32, 36, and 48 h and analyzed for ibuprofen content by the HPLC method. The mechanisms of penetration enhancement of EOs were further evaluated by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis and determination of the properties of EOs. Moreover, the toxicities of EOs on skin cells were also measured. RESULTS: The enhancement ratio (ER) values of turpentine, Angelica, chuanxiong, Cyperus, cinnamon, clove oils and azone were determined to be 2.23, 1.83, 2.60, 2.49, 2.63 and 1.97, respectively. Revealed by ATR-FTIR analysis, a linear relationship (r = 0.9045) was found between the ER values and the total of the shift of peak position of SC lipids. Furthermore, the results of HaCaT skin cell toxicity evaluation revealed that the natural EOs possessed relatively lower skin irritation potential. CONCLUSION: Compared with azone, the investigated EOs possess significantly higher penetration enhancement effect and lower skin toxicity. EOs can promote the skin permeation of ibuprofen mainly by disturbing rather than extracting the SC lipids.


Assuntos
Excipientes/química , Ibuprofeno/farmacocinética , Óleos Voláteis/química , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Sistemas de Liberação de Medicamentos , Excipientes/isolamento & purificação , Excipientes/toxicidade , Humanos , Ibuprofeno/administração & dosagem , Lipídeos/química , Masculino , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/toxicidade , Permeabilidade , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo
12.
Zhongguo Zhong Yao Za Zhi ; 41(23): 4362-4367, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-28933113

RESUMO

The study was carried out to investigate the pharmacokinetics and in vitro/in vivo correlation of ibuprofen with essential oils as penetration enhancers (PE) following transdermal administration. With Azone as the positive control, ibuprofen hydrogels containing Chuanxiong oil, Angelica oil or Cinnamon oil as PE were prepared and administered to the rat abdominal skin. Then the pharmacokinetics of ibuprofen following transdermal administration were investigated and compared. In comparison with negative control (no PE was added), the relative bioavailability values with the addition of Chuanxiong oil, Angelica oil, Cinnamon oil and Azone as PE were determined to be 161.87%, 171.05%, 151.37% and 148.66%, respectively. In vitro/in vivo correlation analysis was performed by deconvolution method and the results demonstrated a good correlation between in vitro and in vivo percutaneous absorption studies. The correlation coefficients were measured to be 0.999 7, 0.995 2 and 0.999 4 for Chuanxiong oil, Angelica oil and Cinnamon oil respectively. In summary, Chuanxiong oil, Angelica oil and Cinnamon oil as PE could significantly enhance the bioavailability of ibuprofen following transdermal administration. A satisfactory in vitro/in vivo correlation could be obtained by using hydrogel as the dosage form.


Assuntos
Ibuprofeno/farmacocinética , Óleos Voláteis/química , Absorção Cutânea , Administração Cutânea , Animais , Hidrogéis , Ratos , Pele
13.
Molecules ; 20(10): 18219-36, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26457698

RESUMO

The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil >> Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05). The contents of calcium ion and nitric oxide (NO) were also significantly changed after the addition of Chuanxiong oil (p < 0.05). In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea.


Assuntos
Analgésicos não Narcóticos/administração & dosagem , Dismenorreia/tratamento farmacológico , Ibuprofeno/administração & dosagem , Queratinócitos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Administração Cutânea , Analgésicos não Narcóticos/farmacocinética , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Ibuprofeno/farmacocinética , Queratinócitos/citologia , Camundongos , Absorção Cutânea
14.
J Proteome Res ; 13(10): 4211-9, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25160476

RESUMO

Emerging evidence suggests that suberoylanilide hydroxamic acid (SAHA), a clinically approved HDAC inhibitor for cutaneous T-cell lymphoma, shows promising clinical benefits in neuroblastoma, the most common extra cranial solid neoplasm with limited choice of therapeutic intervention. However, the molecular mechanism under which the compound exerts its antitumor effect remains elusive. Here we report a quantitative proteomics study that determines changes of protein expression, histone lysine acetylation, and butyrylation in response to SAHA treatment. We detected and quantified 28 histone lysine acetylation and 18 histone lysine butyrylation marks, most of which are dramatically induced by SAHA. Importantly, we identified 11 histone Kbu sites as novel histone marks in human cells. Furthermore, quantitative proteomic analysis identified 5426 proteins, among which 510 proteins were up-regulated and 508 proteins were down-regulated (significant p value <0.05). The subsequent bioinformatics analysis identified distinct SAHA-response gene ontology (GO) categories and signaling pathways, including cellular metabolism and DNA-dependent pathways. Our study therefore reveals new histone epigenetic marks and offers key insights into the molecular mechanism by which SAHA regulates proteomic changes in neuroblastoma cells and identifies biomarker candidates for SAHA.


Assuntos
Antineoplásicos/farmacologia , Ácido Butírico/metabolismo , Histonas/metabolismo , Ácidos Hidroxâmicos/farmacologia , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Acetilação , Sequência de Aminoácidos , Western Blotting , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Dados de Sequência Molecular , Proteínas de Neoplasias/química , Neuroblastoma/patologia , Espectrometria de Massas em Tandem , Vorinostat
15.
Eur J Pediatr ; 173(12): 1569-72, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23942746

RESUMO

The majority of patients with symptomatic cryptococcosis have an underlying immunocompromising condition. In the absence of coexisting immunocompromising condition, Cryptococcus neoformans is rarely considered in the differential diagnosis of obstructive jaundice that occurs in children with hilar masslike lesion. Here, we report a 5-year-old boy without immunoglobulin or lymphocyte abnormalities who developed a hepatobiliary infection with C. neoformans. Ultrasonography and computed tomography showed dilatation of the bilateral intrahepatic bile ducts and a low-attenuated mass in the hepatic hilum. Microscopic examination of tissue samples revealed abundant numbers of encapsulated yeast cell suggestive of C. neoformans. After 4 months of antifungal therapy (liposomal amphotericin B for 2 weeks and oral fluconazole for 3 months), the disease was effectively controlled. Unnecessary operation could be avoided by an early and accurate diagnosis. By sharing our experience, we suggest hepatobiliary surgeons and gastroenterologists should have a suspicion of this unusual entity to make earlier diagnosis and treatment.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos/microbiologia , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Imunocompetência , Icterícia Obstrutiva/microbiologia , Hepatopatias/diagnóstico , Doenças dos Ductos Biliares/complicações , Doenças dos Ductos Biliares/imunologia , Doenças dos Ductos Biliares/microbiologia , Pré-Escolar , Criptococose/complicações , Criptococose/imunologia , Humanos , Hepatopatias/complicações , Hepatopatias/imunologia , Hepatopatias/microbiologia , Masculino
16.
Mol Cell Proteomics ; 11(5): 100-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22389435

RESUMO

Histone protein post-translational modifications (PTMs) are significant for gene expression and DNA repair. Here we report the identification and validation of a new type of PTM in histones, lysine succinylation. The identified lysine succinylated histone peptides were verified by MS/MS of synthetic peptides, HPLC co-elution, and isotopic labeling. We identified 13, 7, 10, and 7 histone lysine succinylation sites in HeLa, mouse embryonic fibroblast, Drosophila S2, and Saccharomyces cerevisiae cells, respectively. We demonstrated that this histone PTM is present in all eukaryotic cells we examined. Mutagenesis of succinylation sites followed by functional assays implied that histone lysine succinylation can cause unique functional consequences. We also identified one and two histone lysine malonylation sites in HeLa and S. cerevisiae cells, respectively. Our results therefore increase potential combinatorial diversity of histone PTMs and suggest possible new connections between histone biology and metabolism.


Assuntos
Histonas/metabolismo , Lisina/metabolismo , Malonatos/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Saccharomyces cerevisiae/metabolismo , Succinatos/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Linhagem Celular , Sequência Conservada , Drosophila , Histonas/química , Histonas/genética , Humanos , Camundongos , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fenótipo , Estrutura Terciária de Proteína , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Espectrometria de Massas em Tandem
17.
Pediatr Surg Int ; 30(1): 19-24, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24100524

RESUMO

PURPOSE: Diaphragmatic plication by minimally invasive surgery is thought to allow for a quick recovery and has been performed on small children. Here, we report our experience with different plication procedures to discuss how to choose among these different plication procedures in endoscopic surgery for pediatric patients with diaphragmatic eventration. PATIENTS AND METHODS: We retrospectively analyzed clinical data of 27 pediatric patients (21 boys, 6 girls; median age: 12.7 months, range 2 months-3 years) admitted to our hospital between November 2008 and July 2013. Three different plication procedures were used: the "reefing the mainsail" technique (8 patients), "invaginating the diaphragmatic dome" technique (10 patients), and "pleating" technique (9 patients). Indications included ventilator dependency (7.41 %), respiratory distress (22.22 %), chronic lung lobe collapse (11.11 %), persistent atelectasis with recurrent pneumonias (18.52 %), and asymptomatic severe eventration (40.74 %). RESULTS: Descending distance of diaphragm after surgery ranged from 1 to 4.5 intercostal spaces (mean distance: 2.65 intercostal spaces). All patients recovered well postoperatively, except for one patient with a pneumothorax. Two patients who required respiratory support before the operation no longer required it within 7 d after surgery. Follow-up ranged from 1 to 35 months. Clinical results were satisfactory with obvious improvement in symptoms and a slight re-elevation within a distance of one intercostal space. CONCLUSION: For pediatric patients with diaphragmatic eventration, different endoscopic surgeries and plication procedures all yielded satisfactory results. We believe that the choice of one procedure over the other depends only on the surgeon's experience.


Assuntos
Diafragma/cirurgia , Eventração Diafragmática/cirurgia , Laparoscopia/métodos , Toracoscopia/métodos , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
18.
Transl Pediatr ; 13(1): 137-145, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38323180

RESUMO

Background: Infantile hemangiomas (IHs) on skin are conventionally treated with beta blockers, pulsed dye laser (PDL), or surgery, either invasive or limited to clinical conditions. Our preclinical studies suggested that Tanshinone, extracted from Salvia miltiorrhiza (Tanshin), had a beneficial effect on IHs. Thus, we conducted a pilot clinical study to evaluate the safety and efficacy of topical Tanshinone compounds on superficial IHs. Methods: The single-armed pilot study included a total of 29 infants diagnosed with IHs. Thrice daily (at an interval of 6-8 hours) topical applications of Tanshinone were used for each patient. The primary response was the skin erythema index assessed by investigators using SkinColorCatch colorimeter instrument (Delfin). The Achauer score and the satisfaction of parents were also evaluated. Results: A total of 29 infants, 22 females (76%) and 7 males (24%), with a median age of 60 days (interquartile range, 45 to 99 days) were included. The position of IHs was distributed in the trunk (44.8%), head (34.5%), and limbs (20.7%). After 6 months of IHs treatment, the decrease in skin erythema index (baseline: 566.79±854.67 vs. after treatment: 467.97±1,118.39, P<0.001) was indicated. A total of 79.31% [23/29] of parents of the participants reported satisfaction on the responses after treatment. No serious side effects were documented. Conclusions: The topical use of Tanshinone compounds might be a potentially effective and noninvasive therapy in treating IHs.

19.
Cell Physiol Biochem ; 31(6): 854-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23816987

RESUMO

AIMS: Retinoic acid (RA) is used pharmacologically to treat neuroblastoma (NB), but its mechanism of action is unclear and it has limited use against refractory disease. This study investigated the expression of LSD1 (also known as KDM1A) in tumors, and assessed the efficacy of combining RA treatment with the inhibition of LSD1 expression. METHODS: LSD1 protein expression levels were assessed semi-quantitatively in specimens of NB and ganglioneuroblastoma (GNB), along with the apoptosis markers, Bcl-2 and Bax. The combined effect of RA and LSD1 siRNA inhibition on cell death was then assessed in the human neuroblastoma cell line, SH-SY5Y. RESULTS: LSD1 expression was higher in NB compared to GNB, and LSD1 overexpression directly correlated with Bcl-2 expression and inversely correlated with Bax expression. RA treatment or LSD1 siRNA inhibition alone inhibited the growth of SH-SY5Y cells, but did not cause significant apoptosis or cell death. Combined treatment led to higher rates of SH-SY5Y cell death, as reflected by an increased Bax/Bcl-2 ratio. CONCLUSIONS: The combined effect of RA and LSD1 siRNA inhibition had a synergistic effect on promoting the apoptosis of NB cells. This novel approach may improve the clinical treatment of NB.


Assuntos
Apoptose/efeitos dos fármacos , Histona Desmetilases/metabolismo , Neuroblastoma/patologia , RNA Interferente Pequeno/metabolismo , Tretinoína/farmacologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/genética , Humanos , Lactente , Masculino , Neuroblastoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , Proteína X Associada a bcl-2/metabolismo
20.
J Urol ; 189(4): 1498-502, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23201375

RESUMO

PURPOSE: We evaluated the safety and efficacy of extracorporeal shock wave lithotripsy in the treatment of single melamine induced urolithiasis in infants and young children. MATERIALS AND METHODS: A total of 189 infants and young children with single melamine induced urolithiasis were referred to our center for treatment with extracorporeal shock wave lithotripsy between March 2009 and July 2010. Location of the calculus was proximal ureteral in 17 patients, mid ureteral in 5, distal ureteral in 26 and kidney in 141. Stone size ranged from 3.8 to 25 mm (mean ± SD 9.79 ± 3.83). RESULTS: All patients underwent extracorporeal shock wave lithotripsy using the same device with an energy ranging from 8 to 12 kV. Stone-free rate was 97.88%, clinically insignificant residual fragment rate was 1.59% and repeat treatment rate was 2.65%. A total of 180 patients (95.24%) required only 1 lithotripsy session and 5 (2.65%) required 2 sessions. Mean ± SD number of shock waves delivered per session was 580.36 ± 190.69 (range 65 to 950). Extracorporeal shock wave lithotripsy failed to fragment stones in only 1 infant, who had a proximal ureteral stone. A total of 181 specimens were collected and analyzed by infrared spectrum, with results demonstrating that the main composition was uric acid and melamine. All patients were followed for a mean of 28 months (range 20 to 36). No severe complication, such as renal subcapsular hemorrhage, hypertension, kidney rupture or lung injury, was observed. CONCLUSIONS: Extracorporeal shock wave lithotripsy with low energy can effectively disintegrate melamine induced calculi. This approach has become our preferred method for treating single melamine induced urolithiasis in infants and young children.


Assuntos
Litotripsia/métodos , Resinas Sintéticas/efeitos adversos , Triazinas/efeitos adversos , Urolitíase/terapia , Pré-Escolar , China , Feminino , Contaminação de Alimentos , Humanos , Lactente , Fórmulas Infantis/química , Litotripsia/efeitos adversos , Litotripsia/instrumentação , Masculino , Triazinas/análise , Ácido Úrico/análise , Urolitíase/induzido quimicamente , Urolitíase/complicações
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