RESUMO
The protein phosphatase 2A (PP2A), a serine/threonine phosphatase, is recognized as a tumor suppressor involved in diverse cellular processes and essential for maintaining cell viability in vivo. However, endogenous inhibitors of PP2A such as cancerous inhibitor of PP2A (CIP2A) and endogenous nuclear protein inhibitor 2 of PP2A (SET) counteract the anticancer function of PP2A, promoting tumorigenesis, development, and drug resistance in tumors. Surprisingly though, contrary to conventional understanding, inhibition of the tumor suppressor gene PP2A with exogenous small molecule compounds can enhance the efficacy of cancer treatment and achieve superior tumor inhibition. Moreover, exogenous PP2A inhibitors resensitize cancers to treatment and provide novel therapeutic strategies for drug-resistant tumors, which warrant further investigation.
RESUMO
BACKGROUND: Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs). RESULTS: We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4-/- mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice. CONCLUSIONS: Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.
RESUMO
Recently, cytokine-induced killer (CIK) cells have a broad application prospect in the comprehensive diagnosis and treatment of tumors owing to their unique characteristics of killing and targeting malignant tumors. Herein, we report a facile strategy for synthesis of monodisperse gold nanostars (GNSs) based on PEGylation and co-loaded with the photosensitizer chlorin e6 (Ce6) to form GNSs-PEG@Ce6 NPs. Then employing CIK cells loading the as-prepared GNSs-PEG@Ce6 NPs to fabricate a CIK cells-based drug delivery system (GNSs-PEG@Ce6-CIK) for lung cancer. Among them, GNSs was functioned as transport media, Ce6 acted as the near-infrared (NIR) fluorescence imaging agent and photodynamic therapy (PDT), and CIK cells served as targeting vectors for immunotherapy, which can increase the efficiency of tumor enrichment and treatment effect. The results of cellular experiments demonstrated that GNSs-PEG@Ce6 NPs had good dispersibility, water solubility and low toxicity under physiological conditions, and the cultured CIK cells had strong anti-tumor properties. Subsequently, GNSs-PEG@Ce6-CIK could effectively inhibit the growth of A549 cells under the exposure of 633 nm laser, which showed stronger killing effect than that of GNSs-PEG@Ce6 NPs or CIK cells. In addition, they showed good tumor targeting and tumor synergistic killing activityin vivo. Therefore, GNSs-PEG@Ce6-CIK was constructed for targeted NIR fluorescence imaging, enhanced PDT and immunotherapy of lung cancer.
Assuntos
Clorofilídeos , Células Matadoras Induzidas por Citocinas , Ouro , Neoplasias Pulmonares , Nanopartículas Metálicas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Ouro/química , Fotoquimioterapia/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Humanos , Animais , Porfirinas/química , Porfirinas/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas Metálicas/química , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Células A549 , Imagem Óptica/métodos , Camundongos NusRESUMO
OBJECTIVE: Synovial Sarcoma (SS), a highly malignant mesenchymal neoplasm, typically carries a grim prognosis for patients presenting with high-grade or metastatic disease. Although Anlotinib, a new agent for treating soft tissue sarcomas, holds promise, its underlying mechanism remains incompletely understood. This investigation aims to delineate Anlotinib's anticancer effectiveness and potential mechanistic underpinnings in patients suffering from advanced, refractory SS. MATERIALS AND METHODS: Employing microarray assay, we examined the potential downstream targets of Anlotinib in SS therapy. A shRNA-based high-content screening was performed to identify candidate genes with the greatest influence on SW982 cell proliferation. The knockdown efficacy of selected genes within SW982 cells was confirmed using RT-qPCR as well as western blot analysis. To assess the effect of putative downstream elimination of genes with synovial sarcoma cells, cell proliferation, and apoptotic assays were carried out. Gene chip microarray as well as bioinformatics techniques were utilized to scrutinize potential signaling networks associated with the candidate downstream gene. RESULTS: QPCR verified high expression of FAM83D in SW982 cells, shRNA was designed to silence FAM83D by lentivirus transfection, apoptosis assay, and cell cycle arrest showing that FAM83D downregulation augments apoptosis in SW982 cells and arrests cell cycle progression in the S stage. Inhibition of FAM83D expression upregulated STAT1 while downregulated BIRC5, MCM2, and CDK1 genes in vitro. CONCLUSIONS: This experimental study identified FAM83D as a critical regulator that contributes to the proliferation and progression of SS, suggesting that FAM83D-regulated signaling pathway may serve as a prospective target in SS management.
RESUMO
BACKGROUND: High serum CA19-9 is usually caused by pancreaticobiliary malignancies, but it has also been found in a tiny minority of calculous cholecystitis patients. AIMS: To clarify the relationship between calculous cholecystitis and serum CA19-9. METHODS: Clinical data of calculous cholecystitis patients with high serum CA19-9 (high group, n = 20) and normal serum CA19-9 (normal group, n = 40) who underwent cholecystectomy were analyzed. Serum CA19-9 of high group were followed-up and gallbladder specimens were analyzed by immunohistochemistry. RESULTS: Serum CA19-9 in the high group ranged from 105 to 1635 U/ml, of which 30% exceeded 1000 U/ml. Follow-up results showed that 20 patient's serum CA19-9 returned to normal after cholecystectomy, including 4 closely followed-up patients whose serum CA19-9 recovered within one month. Immunohistochemical results revealed that CA19-9 was mildly positive only in mucosal epithelial cells in the normal group, but positive in mucosal epithelial cells, vascular endothelial cells, and intercellular substances in the high group, accounting for high serum CA19-9. CONCLUSION: Serum CA19-9 is proved to be associated with calculous cholecystitis for the first time, so that clinicians should consider calculous cholecystitis associated CA19-9 elevation in the clinic practice besides other CA19-9 related diseases.
Assuntos
Antígeno CA-19-9 , Colecistectomia , Colecistite , Humanos , Colecistite/cirurgia , Antígeno CA-19-9/sangue , Biomarcadores Tumorais , Resultado do Tratamento , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Vesícula Biliar/patologiaRESUMO
The long noncoding RNA growth-arrest specific 5 (GAS5) is a suppressor of many cancers. However, the role and mechanism of action of GAS5 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. Here, the expression of hepatitis B virus x gene (HBx) mRNA and GAS5 was assessed by qRT-PCR, and western blot analysis was performed to determine the protein expression levels. In addition, the cell viability and invasion of cells were confirmed using MTT assay and Transwell assay, respectively. The DNA methylation level of GAS5 was measured by methylation-specific PCR. Moreover, RIP assay and RNA pull down assay were carried out to examine the combination of Y-box-binding protein 1 (YBX1) and GAS5. First, our data proved that HBx is increased, while GAS5 is decreased in HCC cell lines. Subsequently, we found that HBx facilitates HCC cell viability and invasion by inhibiting GAS5 expression. Then, we further clarified that HBx induces the DNA methylation of GAS5 by promoting methyltransferase expression, thereby suppressing GAS5 expression. Furthermore, GAS5 binds YBX1 and promotes YBX1 and p21 expression. Finally, the functional analysis revealed that the upregulation of GAS5 could attenuate cell viability and invasion by boosting p21 expression via binding YBX1. Overall, our results demonstrated that HBx promotes HCC progression by inducing GAS5 methylation to reduce its expression. The upregulation of GAS5 suppressed HBV-related HCC by activating YBX1/p21 signaling. Our data provide novel evidence supporting the potential of GAS5 as a treatment target in HBV-related HCC.
RESUMO
Escalator-related incidents (EIs) have recently resulted in serious injuries and even deaths. Given the frequency and severity of EIs, a systematic exploration of factors influencing EIs is critical in order to identify preventive measures. Twenty-two factors influencing EIs were identified by analyzing 213 EI cases in China and related literatures. A combination of the Interpretive Structural Modeling (ISM) and Decision Making Trial and Evaluation Laboratory (DEMATEL) methods were utilized to establish a hierarchical structure of the influencing factors and to distinguish cause factors and effect factors. The results show: (i) behavior, emergency plan, safety rules, safety supervision, information exchange, safety culture, and safety education are the most important factors influencing EIs; (ii) safety education is the cause factor imposing the greatest influence on other factors while behavior is the effect factor that is the most influenced; and (iii) the structure of influencing factors has five hierarchies, and factors in the root cause layer are settings and components, safety rules, safety supervision, safety culture, and safety education. Management priority should be given according to the hierarchy level, and the interaction of factors should be considered when taking preventive measures. The corresponding five-layer countermeasures are proposed to reduce escalator-related injuries.
Assuntos
Acidentes/estatística & dados numéricos , Elevadores e Escadas Rolantes , Segurança/estatística & dados numéricos , China , Tomada de Decisões , Humanos , Fatores de RiscoRESUMO
Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young people with poor prognosis. At present, the mechanisms underlying tumorigenesis in OS are not well understood. The methionine adnosyltransferase 2B (MAT2B) gene encodes the regulatory subunit of methionine adenosyltransferase (MAT). Recent studies demonstrated that it is highly expressed in a number of human malignancies; however, is undefined in OS. In the present study, MAT2B expression was investigated in tumor samples and cell lines. In vivo and in vitro, lentivirusmediated small hairpin RNA was constructed to target the MAT2B gene and examine the role of MAT2B in OS proliferation. Microarray analysis was performed to examine the possible downstream molecular target of MAT2B in OS. MAT2B was markedly increased in OS specimens compared with the normal bone tissues, and it was additionally abundantly expressed in OS cell lines. Inhibition of MAT2B expression caused a marked decrease in proliferation and significant increase in apoptosis. In vivo, MAT2B silencing significantly inhibited OS cell growth. Microarray analysis suggested that epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) may function as downstream targets of MAT2B in OS, as confirmed by reverse transcriptionquantitative polymerase chain reaction assays and western blotting. Collectively, these results suggested that MAT2B serves a critical role in the proliferation of OS by regulating EGFR and PCNA and that it may be a potential therapeutic target and prognostic factor of OS.
Assuntos
Neoplasias Ósseas/patologia , Metionina Adenosiltransferase/metabolismo , Osteossarcoma/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Animais , Apoptose/genética , Osso e Ossos/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Receptores ErbB/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Metionina Adenosiltransferase/genética , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Osteossarcoma/genética , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Osteosarcoma pulmonary metastases are typically treated with resection and/or chemotherapy. We hypothesize that stereotactic radiosurgery (SRS) can be an alternative to surgery that can achieve high rates of local control with limited toxicity. From January 2005 to December 2013, 73 patients who developed pulmonary metastasis during period of adjuvant chemotherapy or follow-up were analyzed. 33 patients were treated by stereotactic radiosurgery using the body gamma-knife system. A total dose of 50 Gy was delivered at 5 Gy/fraction to the 50% isodose line covering the planning target volume, whereas a total dose of 70 Gy was delivered at 7 Gy/fraction to the gross target volume. The other 40 patients were treated by surgical resection. Four-year progression-free survival rate, four-year survival rate, median time of PRPFS (post-relapse progress-free survival) and PROS (post-relapse overall survival) in SRS group were parallel to that in surgical group. Patients tolerated gamma knife radiosurgery well. Our study demonstrates that SRS is well-tolerated with excellent local control and less complications. SRS should be considered as a potential option in patients with pulmonary metastases from osteosarcoma, especially in those who are medically inoperable, refuse surgery.
Assuntos
Neoplasias Ósseas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Osteossarcoma/radioterapia , Radiocirurgia , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Dosagem Radioterapêutica , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The purpose of this study was to investigate the relationship between platelet indices [mean platelet volume (MPV), platelet count (PLT), platelet distribution width (PDW) and plateletcrit (PCT)] at diagnosis in osteosarcoma. METHODS: The information of 233 patients with osteosarcoma at diagnosis between 2007 and 2015 was retrospectively reviewed. Clinical parameters such as gender, age, size and site of tumor, and tumor necrosis rate after neoadjuvant chemotherapy were analyzed. RESULTS: No significant difference was noted in the mean values of MPV, PLT, PDW and PCT among stage I, II and III patients. In localized patients, the median disease-free survival (DFS) values were 42 and 22 months in the PLT<300×109/L and ≥300×109/L groups, respectively, but the difference was not statistically significant (P = 0.2611). No difference in the DFS among the three different levels of MPV was observed. CONCLUSION: No significantly different platelet indices were noted among the different stages. Although a shorter median DFS was found in localized patients with PLT≥300×109/L, there was still a lack of strong evidence to demonstrate the association between platelet indices and osteosarcoma.
Assuntos
Neoplasias Ósseas/sangue , Volume Plaquetário Médio , Osteossarcoma/sangue , Contagem de Plaquetas , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Osteossarcoma/diagnóstico , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Adulto JovemRESUMO
The aim of the present study was to assess the efficacy and safety of topical timolol maleate combined with oral propranolol for parotid infantile hemangiomas. Between October 2012 and April 2014, propranolol was administered orally at a dose of 1.0-1.5 mg/kg/day to 22 infants with proliferating hemangiomas in the Department of Oral and Maxillofacial Surgery (Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China). A small amount of 0.5% timolol maleate eye drop solution was topically applied with medical cotton swabs to the area of the lesion twice a day, every 12 h. The study group consisted of 9 males and 13 females, aged 2-9 months, with a median age of 4.7 months. The lesions were all located in the parotid region, and measured between 3.5×4×0.5 and 7×8×3 cm in volume. The planned duration of therapy was 6-8 months, or the two drugs were stopped when complete regression of the lesions was obtained. The therapeutic outcomes and safety were assessed by the change in the size and color of the tumor, and the presence of adverse effects throughout the course of treatment. The mean duration of therapy was 21.1 weeks and ranged from 3 to 8 months. Of the 22 patients, 16 demonstrated an excellent response, 6 showed a good response and 2 displayed a moderate response. No major collateral effects were observed. Overall, oral propranolol combined with topical timolol maleate may be used as the first-line therapeutic choice in the treatment of infantile parotid mixed hemangioma.
RESUMO
The role of transforming growth factor-ß1 (TGF-ß1) in normal human fracture healing has been previously demonstrated. The objective of the present study was to examine the biocompatibility of TGF-ß1-silk fibroin-chitosan (TGF-ß1-SF-CS) three-dimensional (3D) scaffolds in order to construct an ideal scaffold for bone tissue engineering. We added TGF-ß1 directly to the SF-CS scaffold to construct a 3D scaffold for the first time, to the best of our knowledge, and performed evaluations to determine whether it may have potential applications as a growth factor delivery device. Bone marrow-derived mesenchymal stem cells (BMSCs) were seeded on the TGF-ß1-SF-CS scaffolds and the silk fibroin-chitosan (SF-CS) scaffolds. On the TGF-ß1SF-CS and the SF-CS scaffolds, the cell adhesion rate increased in a timedependent manner. Using a Cell Counting Kit-8 (CCK-8) assay and analyzing the alkaline phosphatase (ALP) expression proved that TGF-ß1 significantly enhanced the growth and proliferation of BMSCs on the SF-CS scaffolds in a time-dependent manner. To examine the in vivo biocompatibility and osteogenesis of the TGF-ß1SF-CS scaffolds, the TGF-ß1-SF-CS scaffolds and the SF-CS scaffolds were implanted in rabbit mandibles and studied histologically and microradiographically. The 3D computed tomography (CT) scan and histological examinations of the samples showed that the TGF-ß1-SF-CS scaffolds exhibited good biocompatibility and extensive osteoconductivity with the host bone after 8 weeks. Moreover, the introduction of TGF-ß1 to the SF-CS scaffolds markedly enhanced the efficiency of new bone formation, and this was confirmed using bone mineral density (BMD) and biomechanical evaluation, particularly at 8 weeks after implantation. We demonstrated that the TGF-ß1SF-CS scaffolds possessed as good biocompatibility and osteogenesis as the hybrid ones. Taken together, these findings indicate that the TGF-ß1-SF-CS scaffolds fulfilled the basic requirements of bone tissue engineering, and have the potential to be applied in orthopedic, reconstructive and maxillofacial surgery. Thus, TGF-ß1-SF-CS composite scaffolds represent a promising, novel type of scaffold for use in bone tissue engineering.
Assuntos
Quitosana/farmacologia , Fibroínas/farmacologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Fator de Crescimento Transformador beta1/farmacologia , Absorção Fisico-Química , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Imageamento Tridimensional , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Mandíbula/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Tamanho do Órgão/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Periorbital infantile hemangiomas (IHs) require early intervention because they have the potential risk of causing visual disturbances. In recent years, propranolol has shown promise in the effective management of periocular and periorbital IHs. The objective of our study was to assess the clinical outcomes, efficacy, and safety of propranolol in the management of infants with high-risk periorbital IHs. PATIENTS AND METHODS: This retrospective study was conducted at the Stomatological Hospital affiliated with China Medical University. The medical records of infants with periorbital hemangiomas who were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg per day between January 2014 and June 2015 were reviewed. We excluded infants who did not qualify for propranolol treatment and infants who received previous therapy or other treatments. The records were reviewed for treatment response, adverse events during treatment, length of treatment, and recurrences. Treatment response was classified using a 4-point scale system based on reduction in volume as poor (<25%), moderate (25 to 50%), good (50 to 75%), or excellent (>75 to 100%) and change in color, as well as surface texture, by a panel of 3 plastic surgeons using 2-dimensional photographs, clinical examination, and Doppler ultrasonography measurements taken before and after treatment. RESULTS: Of 38 infants with periorbital hemangiomas, 26 were treated with systemic propranolol at a dose of 1.0 to 1.5 mg/kg administered once daily. A total of 11 male and 15 female infants with a mean age of 5.2 months (range, 2 to 12 months) were treated. The mean length of treatment was 22 weeks (range, 4 to 41 weeks). Adverse events of diarrhea (n = 3) and sleep changes (n = 1) were encountered during treatment in 4 patients. The overall treatment response was scored as excellent in 17 patients, good in 7, moderate in 2, and poor in 0. No patients required discontinuation of treatment because of adverse events, and there were no cases of recurrence or tumor regrowth noted during the mean follow-up period of 6.5 months (range, 3 to 10 months). CONCLUSIONS: Oral propranolol at a dose of 1.0 to 1.5 mg/kg per day (age ≤3 months, 1.0 mg/kg; age >3 months, 1.5 mg/kg) was effective and well tolerated for the management of 26 Chinese infants with high-risk periorbital IHs. Early intervention should be considered to reduce risk of visual impairment and improve esthetic outcomes.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Hemangioma/tratamento farmacológico , Propranolol/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Esquema de Medicação , Olho , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Infantile hemangiomas (IHs) are the most common benign tumors affecting infants, and most IHs are self-limiting. However, there are cases that require specific treatment. Propranolol is now widely used to treat severe IHs. Several studies have shown the efficacy and limited side effects associated with propranolol as the first-line treatment for IHs. There are a limited number of publications describing the role of propranolol in treating IHs beyond the proliferative phase (>12 months). The purpose of this study was to evaluate the effects and safety of oral high-dose (2.0 mg/kg per day) propranolol for IHs beyond the proliferative phase (>12 months). PATIENTS AND METHODS: This study enrolled patients with IHs who accepted systemic propranolol treatment from the Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated China Medical University. This is a single-center retrospective study conducted from April 2011 to July 2015. All children who were older than 12 months were eligible for the study. Digital photographs taken before and after treatment were analyzed by a panel of 3 plastic surgeons. The esthetic results were evaluated using a 4-point scale and ranked as poor, moderate, good, or excellent. The patient follow-up visits were scheduled monthly, and changes in the size, texture, and color of the lesions were recorded. The adverse effects after medication were evaluated and managed accordingly. RESULTS: We collected data on 31 eligible patients. The 31 patients had 32 hemangiomas (1 female patient had 2 lesions) and were treated with systemic propranolol at a high dose of 2 mg/kg per day. The mean age at the initiation of propranolol therapy was 18.4 months (range, 12 to 48 months), and the mean treatment duration was 10.1 months (range, 8 to 16 months). The treatment responses for the 32 hemangiomas included 17 excellent responses (53.1%), 8 good responses (25%), and 7 moderate responses (21.9%). There were no severe side effects encountered and recurrence was observed in 3 patients during the treatment and follow-up course. CONCLUSIONS: Oral propranolol, 2 mg/kg per day, is a safe and effective treatment for IHs beyond the proliferative phase (>12 months of age) in the Chinese population.
Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Hemangioma/tratamento farmacológico , Propranolol/uso terapêutico , Vasodilatadores/uso terapêutico , Administração Oral , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Propranolol/administração & dosagem , Estudos Retrospectivos , Vasodilatadores/administração & dosagemRESUMO
The objective of the study was to discuss the biocompatibility of the vascular endothelial growth factor-silk fibroin-chitosan (VEGF-SF-CS) scaffolds. To offer an ideal scaffold for bone tissue engineering, the author added vascular endothelial growth factor (VEGF) into silk fibroin-chitosan (SF-CS) scaffold directly to reconstruct a three-dimensional scaffold for the first time, SF-CS scaffold was loaded with VEGF and evaluated as a growth factor-delivery device. Human fetal osteoblast cell was seeded on the VEGF-SF-CS scaffolds and SF-CS scaffolds. On VEGF-SF-CS and SF-CS scaffolds, the cell adhesion rate was increased as time went on. Scanning electron microscopy: the cells grew actively and had normal multiple fissions, granular and filamentous substrates could be seen around the cells, and cell microfilaments were closely connected with the scaffolds. The cells could not only show the attached growth on surfaces of the scaffolds, but also extend into the scaffolds. Cell Counting Kit-8 and alkaline phosphatase analysis proved that the VEGF could significantly promote human fetal osteoblast1.19 cells growth and proliferation in the SF-CS scaffolds, but the enhancement of osteoblasts cell proliferation and activity by VEGF was dependent on time.
Assuntos
Quitosana/química , Fibroínas/química , Osteogênese/fisiologia , Seda/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/química , Citoesqueleto de Actina/fisiologia , Citoesqueleto de Actina/ultraestrutura , Fosfatase Alcalina/análise , Materiais Biocompatíveis/química , Adesão Celular/fisiologia , Contagem de Células , Técnicas de Cultura de Células , Proliferação de Células , Forma Celular/fisiologia , Células Cultivadas , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Osteoblastos/fisiologia , Osteoblastos/ultraestrutura , Propriedades de SuperfícieRESUMO
The aim of the present study was to examine the biocompatibility of transforming growth factor-ß1-silk fibroin-chitosan (TGF-ß1-SF-CS) scaffolds. In order to provide an ideal scaffold for use in bone tissue engineering, TGF-ß1 was introduced into the SFCS scaffold in order to reconstruct a three dimensional scaffold, following which hFOB1.19 osteoblast cells were seeded onto TGFß1SFCS and SFCS scaffolds. On the TGFß1SFCS and SFCS scaffolds, the cell adhesion rate increased in a timedependent manner. Scanning electron microscopy revealed that the cells grew actively and exhibited normal morphological features with multiple fissions, and granular and filamentous substrates were observed surrounding the cells. In addition, the cell microfilaments were closely connected with the scaffolds. The cells exhibited attached growth on the surfaces of the scaffolds, however, the growth also extended into the scaffolds. Cell Counting Kit8 and ALP analyses revealed that TGFß1 significantly promoted the growth and proliferation of the hFOB1.19 osteoblast cells in the SFCS scaffolds, and the enhancement of osteoblast cell proliferation and activity by TGFß1 occurred in a timedependent manner. The TGF-ß1-SF-CS composite material may offer potential as an ideal scaffold material for bone tissue engineering.
Assuntos
Técnicas de Cultura de Células/métodos , Quitosana/farmacologia , Feto/citologia , Fibroínas/farmacologia , Osteoblastos/citologia , Alicerces Teciduais/química , Fator de Crescimento Transformador beta1/farmacologia , Fosfatase Alcalina/metabolismo , Adesão Celular/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Humanos , Osteoblastos/efeitos dos fármacosRESUMO
The objective of this study was to discuss the construction method, characterization, and biocompatibility of three-dimensional silk fibroin-chitosan (SF-CS) scaffolds which met the requirements of bone tissue engineering scaffolds. Silk fibroin (SF) and chitosan (CS) were mixed at different ratios -3 to 7, 5 to 5, and 7 to 3- to fabricate the composite materials. To find out the optimum mixing ratio of SF and CS, parameters such as pore size, porosity, water absorption, and the mechanical properties were evaluated. Osteoblast cells hFOB1.19 were seeded on SF-CS scaffolds and pure CS scaffolds for the first time. Cell adhesion rate, cell proliferation, and cell activity were evaluated, and cell growth and formation of mineralized nodules were observed. Results showed that SF-CS scaffolds are a suitable candidate for bone tissue engineering.
Assuntos
Quitosana/química , Fibroínas/química , Osteoblastos/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Materiais Biocompatíveis , Adesão Celular , Linhagem Celular , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Propriedades de Superfície , ÁguaRESUMO
The aim of our study was to assess the efficacy and safety of oral propranolol for the treatment of parotid infantile hemangiomas. Between October 2009 and January 2013, propranolol was given orally to 30 infants with proliferating hemangiomas at a dose of 1.0 to 1.5 mg/kg per day in our department. The patients included 12 male infants and 18 female infants, aged between 2 and 13 months, with a median of 5.9 months. The lesions were located in the parotid region and measured from 1.5 cm × 2 cm × 0.5 cm to 6 cm × 8 cm × 3 cm in volume. Oral propranolol was administered once daily for a mean duration of 22.7 weeks (range, 14-32 wk). Follow-up times were from 1 to 10 months (median, 6.4 mo). Changes in the color and size of the tumor were recorded using hemisphere measurements and digital photographs. The treatment results were scored according to a 4-point scale. Overall response was graded scale 4 (excellent) in 18 patients, scale 3 (good) in 11 patients, scale 2 (moderate) in 1 patient, and scale 1 (poor) in none. No major collateral effects and rebounds were observed in any of the patients. Oral propranolol was a well-tolerated and effective treatment with mild adverse effects for parotid infantile hemangiomas.