RESUMO
Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.
Assuntos
Proteína da Leucemia Promielocítica , Fator de Crescimento Transformador beta1 , Proteína Supressora de Tumor p53 , Humanos , Fibroblastos/metabolismo , Fibrose , Coração , Fator de Crescimento Transformador beta1/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína da Leucemia Promielocítica/metabolismoRESUMO
This study aimed to investigate the inhibitory effect of EM-2, a natural active monomer purified from Elephantopusmollis H.B.K., on the proliferation of human hepatocellular carcinoma cells and the molecular mechanism involved. The results from the MTT assay revealed that EM-2 significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) cells in a dose-dependent manner but exhibited less cytotoxicity to the normal liver epithelial cell line LO2. EdU staining and colony formation assays further confirmed the inhibitory effect of EM-2 on the proliferation of Huh-7 hepatocellular carcinoma cells. According to the RNA sequencing and KEGG enrichment analysis results, EM-2 markedly activated the MAPK pathway in Huh-7 cells, and the results of Western blotting further indicated that EM-2 could activate the ERK and JNK pathways. Meanwhile, EM-2 induced apoptosis in a dose-dependent manner and G2/M phase arrest in Huh-7 cells, which could be partially reversed when treated with SP600125, a JNK inhibitor. Further study indicated that EM-2 induced endoplasmic reticulum stress and blocked autophagic flux in Huh-7 cells by inhibiting autophagy-induced lysosome maturation. Inhibition of autophagy by bafilomycin A1 could reduce cell viability and increase the sensitivity of Huh-7 cells to EM-2. In conclusion, our findings revealed that EM-2 not only promoted G2/M phase arrest and activated ER stress but also induced apoptosis by activating the JNK pathway and blocked autophagic flux by inhibiting autolysosome maturation in Huh-7 hepatocellular carcinoma cells. Therefore, EM-2 is a potential therapeutic drug with promising antitumor effects against hepatocellular carcinoma and fewer side effects.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Lactonas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Lisossomos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacosRESUMO
AIM: Norcantharidin (NCTD) has been used as a clinical antineoplastic drug in China for several years, and diamminedichloroplatinum is a valuable clinical cancer chemotherapy agent. Here, we tried to investigate the effects of NCTD plus diamminedichloroplatinum on hepatic carcinoma in murine. MATERIALS AND METHODS: In vivo and in vitro investigations on anticancer effects of the two drugs were individually made. RESULT: In vitro, the combination of the two drugs resulted in apparent apoptosis and cell proliferation inhibitions of H22 cancer cells. Meanwhile, their coadministration in vivo produced significant suppressions of tumor growth and cancerometastasis. Further, CD31 immunohistochemistry and matrigel tube formation assay demonstrated that angiogenesis was inhibited by NCTD plus diamminedichloroplatinum in vivo and in vitro, respectively. CONCLUSION: Based on the findings, we concluded that NCTD plus diamminedichloroplatinum may have an additive anticancer efficacy because the two drugs work in different ways, and thus, their combination had inhibited cancer cell proliferations and tumor angiogenesis more effectively than either of the compounds alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Carcinoma Hepatocelular/secundário , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Cisplatino/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Resultado do TratamentoRESUMO
Cancer vaccines mostly aim to induce cytotoxic T lymphocytes (CTLs) against tumors. An appropriate adjuvant is of fundamental importance for inducing cellular immune response. Since the antigen in particulate form is substantially more immunogenic than soluble form antigen, it is beneficial to interact with antigen-presenting cells membrane to induce robust CD8+ T cell activation following vaccination. Based on previous research, we designed an adjuvant formulation by combining Astragalus saponins, cholesterol, and liposome to incorporate antigen into a particulate delivery system, so as to enhance cellular immune response. Meanwhile, angiogenesis contributes to tumor growth and metastasis, and basic fibroblast growth factor (bFGF) is involved in tumor angiogenesis. Therefore, using lipo-saponins adjuvant formulation and a human recombinant bFGF antigen protein, we tried to induce bFGF-specific CTL response to inhibit tumor angiogenesis to achieve antitumor activity. After five immunizations, the lipo-saponins/bFGF complex elicited robust antibody response and markedly higher amount of interferon-γ in BALB/c mice, resulting in superior antitumor activities. Decreased microvessel density in CD31 immunohistochemistry and the lysis of vascular endothelial cells by the T lymphocytes from the immunized mice indicated that the immunity inhibited the angiogenesis of tumors and further led to the inhibition of tumors. Our data suggest that the approach to construct adjuvant formulation between liposome and Astragalus saponins appeared highly desirable, and that Astragalus saponins may be utilized as a valuable additive for enhancing the effectiveness of vaccines and stimulating an appropriate immune response that can benefit tumor therapy.
Assuntos
Adjuvantes Imunológicos/química , Vacinas Anticâncer/química , Lipossomos/química , Saponinas/química , Saponinas/imunologia , Sequência de Aminoácidos , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Tumor growth and metastasis are closely related to angiogenesis. Basic fibroblast growth factor(bFGF) is an angiogenic factor, and up-regulated expression of bFGF plays a crucial role in the development and metastasis of melanoma. Therefore, in this study, we sought to achieve antitumor activity by immunity targeting bFGF which would inhibit tumor angiogenesis and simultaneously induce bFGF specific cytotoxic T lymphocytes to kill melanoma cells. A human bFGF protein was used as exogenous antigen, coupled with a saponin-liposome adjuvant formulation to enhance CTL response. The results showed that the immunity induced strong immune response and produced prominent anti-cancer activities. CD31 immunohistochemistry and alginate-encapsulated tumor cell assay displayed that tumor angiogenesis was effectively inhibited. Further, the higher production of IFN-γ and cytotoxic T lymphocyte killing assay suggested that the anti-cancer activities may mainly depend on cellular immune response, which could cause the inhibition of tumor angiogenesis and specific killing of tumor cells by bFGF-specific cytotoxic T lymphocytes. We concluded that immunotherapy targeting bFGF may be a prominent strategy for melanoma, and that the adjuvant formulation of saponin-liposome is very desirable in enhancing cytotoxic T lymphocytes response.
Assuntos
Vacinas Anticâncer/uso terapêutico , Fator 2 de Crescimento de Fibroblastos/imunologia , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Animais , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Melanoma/patologia , CamundongosRESUMO
Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.
Assuntos
Cistite Intersticial/metabolismo , Transição Epitelial-Mesenquimal , GTP Fosfo-Hidrolases/metabolismo , MicroRNAs/fisiologia , Proteínas Mitocondriais/metabolismo , Pós-Menopausa/metabolismo , Bexiga Urinária/patologia , Tecido Adiposo/citologia , Animais , Biomarcadores/análise , Cistite Intersticial/patologia , Modelos Animais de Doenças , Exossomos/metabolismo , Feminino , Fibrose , GTP Fosfo-Hidrolases/genética , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/antagonistas & inibidores , Proteínas Mitocondriais/genética , Inibidores da Síntese de Ácido Nucleico/farmacologia , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
PURPOSE: This prospective study analyzes clinical characteristics and outcomes of sacral extradural spinal meningeal cysts (SESMC) without spinal nerve root fibers (SNRF) undergoing neck transfixion. METHODS: Using the relationship between the cysts and SNRF, SESMCs were divided into two types: cysts with SNRF known as Tarlov cysts and cysts without. If the SESMCs were identified as those without SNRFs, the neck of the cyst was transfixed, ligated and the remaining cyst wall removed distal to the clip. The improved Japanese Orthopedic Association (IJOA) scoring system was used to evaluate preoperative and postoperative neurological functions of the patients. RESULTS: Twenty-seven patients were included in this study. The average age was 42.7 ± 11.93 years. The mean preoperative IJOA score was 17.5 ± 2.47, and postoperative IJOA score was 19.1 ± 1.41. The difference between preoperative and postoperative IJOA scores was statistically significant (t = -3.75, P = 0.001), with a significant improvement in neurological function after surgery. Among the improvements in neurological function, the most significant was bowel/bladder function (z = -2.33, P = 0.02). CONCLUSION: Most patients experienced significant improvement in their neurological function after surgery. The most significant area of neurological improvement was bowel/bladder dysfunction, however, preoperative stool or urine incontinence did not recover completely.
Assuntos
Procedimentos Neurocirúrgicos , Cistos de Tarlov/cirurgia , Adolescente , Adulto , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Feminino , Humanos , Hipestesia/etiologia , Hipestesia/cirurgia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/cirurgia , Dor/etiologia , Dor/cirurgia , Prognóstico , Estudos Prospectivos , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/cirurgia , Cistos de Tarlov/complicações , Transtornos Urinários/etiologia , Transtornos Urinários/cirurgia , Adulto JovemRESUMO
OBJECTIVE: The pharyngocutaneous fistula (PCF) is the troublesome complication after total laryngectomy. Despite a large number of investigations having been performed, there is still controversy about which factors are most significant for PCF. The objective of the present meta-analysis was to analyze the potential risk factors for PCF after total laryngectomy. DATA SOURCES: Published English-language literature. REVIEW METHODS: PubMed, Ovid, Cochrane, and Web of Science databases were systematically searched using multiple search terms. Twenty-one studies with 3832 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. RESULTS: Sixteen studies involving 2598 patients were included for the meta-analysis. The results showed that, tumor subsite (RR=0.64, 95% CI 0.47-0.88, P<0.01), T stage (RR=0.70, 95% CI 0.51-0.96, P=0.03), previous radiotherapy (RR=0.62, 95% CI 0.46-0.84, P<0.01), postoperative hemoglobin <12.5g/L (RR=0.46, 95% CI 0.27-0.76, P<0.01), and surgical margin (RR=0.41, 95% CI 0.22-0.74, P<0.01) were the risk factors associated with the development of PCF. CONCLUSIONS: From the results of our study, several significant risk factors for PCF are identified. Methodologically high-quality comparative studies are needed for further evaluation.
Assuntos
Fístula Cutânea/epidemiologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Doenças Faríngeas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Hemoglobinas/metabolismo , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Laringe/patologia , Fatores de RiscoRESUMO
Mouse embryonic fibroblasts (MEFs) are commonly used as feeder cells for the generation of human induced pluripotent stem cells (hiPSCs). However, medical applications of cell derivatives of hiPSCs generated with a MEF feeder system run the risk of having xeno-factor contamination due to long-term cell culturing under an animal factor-containing environment. We developed a new method for the derivation of human fibroblast-like cells (FLCs) from a previously established hiPSC line in an FLC differentiation medium. The method was based on direct differentiation of hiPSCs seeded on Matrigel followed by expansion of differentiating cells on gelatin. Using inactivated FLCs as feeder layers, primary human foreskin fibroblasts were successfully reprogrammed into a state of pluripotency by Oct4, Sox2 Klf4, and c-Myc (OSKM) transcription factor genes, with a reprogramming efficiency under an optimized condition superior to that obtained on MEF feeder layers. Furthermore, the FLCs were more effective in supporting the growth of human pluripotent stem cells. The pluripotency and differentiation capability of the cells cultured on FLC feeder layers were well retained. Our results suggest that FLCs are a safe alternative to MEFs for hiPSC generation and expansion, especially in the clinical settings wherein hiPSC derivatives will be used for medical treatment.
Assuntos
Técnicas de Cultura de Células/métodos , Diferenciação Celular , Células Alimentadoras/citologia , Fibroblastos/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Animais , Proliferação de Células , Separação Celular , Células Cultivadas , Reprogramação Celular , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Fator 3 de Transcrição de Octâmero/genética , Células-Tronco Pluripotentes/citologia , Proteínas Proto-Oncogênicas c-myc/genética , Fatores de Transcrição SOXB1/genéticaRESUMO
BACKGROUND: The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. METHODS: Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. RESULTS: On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. CONCLUSION: ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.
Assuntos
Biomarcadores/sangue , Proteína Ligante Fas/sangue , Rejeição de Enxerto/diagnóstico , Molécula 1 de Adesão Intercelular/sangue , Receptor fas/sangue , Aloenxertos , Animais , Duodeno/transplante , Glucagon/sangue , Rejeição de Enxerto/patologia , Insulina/sangue , Leucócitos/química , Pâncreas/patologia , Transplante de Pâncreas , SuínosRESUMO
A series of amphiphilic 4- and 6-armed star triblock co-polymers poly(ε-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (4/6AS-PCL-b-PDEAEMA-b-PPEGMA) were developed by a combination of ring opening polymerization and continuous activators regenerated by electron transfer atom transfer radical polymerization. The critical micelle concentration values of the star co-polymers in aqueous solution were extremely low (2.2-4.0mgl(-1)), depending on the architecture of the co-polymers. The self-assembled blank and doxorubicin (DOX)-loaded three layer micelles were spherical in shape with an average size of 60-220nm determined by scanning electron microscopy and dynamic light scattering. The in vitro release behavior of DOX from the three layer micelles exhibited pH-dependent properties. The DOX release rate was significantly accelerated by decreasing the pH from 7.4 to 5.0, due to swelling of the micelles at lower pH values caused by the protonation of tertiary amine groups in DEAEMA in the middle layer of the micelles. The in vitro cytotoxicity of DOX-loaded micelles to HepG2 cells suggested that the 4/6AS-PCL-b-PDEAEMA-b-PPEGMA micelles could provide equivalent or even enhanced anticancer activity and bioavailability of DOX and thus a lower dosage is sufficient for the same therapeutic efficacy. The results demonstrate that the pH-sensitive multilayer micelles could have great potential application in delivering hydrophobic anticancer drugs for improved cancer therapy.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Metacrilatos/química , Nanocápsulas/administração & dosagem , Nylons/química , Polietilenoglicóis/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Cristalização/métodos , Difusão , Doxorrubicina/química , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Teste de Materiais , Micelas , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Tamanho da Partícula , Poliésteres , Ácidos PolimetacrílicosRESUMO
The aim of this study was to explore the association between the single-nucleotide polymorphisms of interleukin-1 receptor-associated kinase-M (IRAK-M) gene and the susceptibility of sepsis. The allele frequency and genotype distribution of IRAK-M gene polymorphisms were assessed in 118 controls and 82 sepsis patients by semiquantitative polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis. The plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were detected by enzyme-linked immunosorbent assay. Associations between IRAK-M polymorphisms and the susceptibility of sepsis were analyzed by Cox regression. Data were analyzed by the χ(2) test and the Student's t test, whenever appropriate. Statistical calculations were performed by using statistical package SPSS version 18.0. The genotype distribution of IRAK-M+22148 polymorphism significantly differed between the sepsis and control groups (P < 0.0001). The frequency of the G allele was remarkably more common in the sepsis group than that of the control group (P < 0.0001). However, the frequency of the A allele was significantly less common in the sepsis group than that of control group (P < 0.0001). Moreover, the plasma levels (in picograms per milliliter) of TNF-α and IL-6 in patients with G/G genotype were greatly higher than those with A/A genotype after lipopolysaccharide stimulation (P < 0.05). The genetic polymorphism of IRAK-M+22148 G>A is associated with the susceptibility of sepsis. The G/G genotype of IRAK-M increases the risk of developing sepsis, and the A/A genotype may play a protective role in the process of developing sepsis.
Assuntos
Quinases Associadas a Receptores de Interleucina-1/genética , Interleucina-6/sangue , Sepse/genética , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Mediadores da Inflamação/sangue , Lipopolissacarídeos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sepse/microbiologiaRESUMO
This prospective study compares different clinical characteristics and outcomes of patients with two types of sacral extradural spinal meningeal cysts (SESMC) undergoing different means of surgical excision. Using the relationship between the cysts and spinal nerve roots fibers (SNRF) as seen under microscope, SESMCs were divided into two types: cysts with SNRF known as Tarlov cysts and cysts without. The surgical methods were tailored to the different types of SESMCs. The improved Japanese Orthopedic Association (IJOA) scoring system was used to evaluate preoperative and postoperative neurological function of the patients. Preoperative IJOA scores were 18.5 ± 1.73, and postoperative IJOA scores were 19.6 ± 0.78. The difference between preoperative and postoperative IJOA scores was statistically significant (t = -4.52, p = 0.0001), with a significant improvement in neurological function after surgery. Among the improvements in neurological functions, the most significant was sensation (z=-2.74, p=0.006), followed by bowel/bladder function (z=-2.50, p=0.01). There was a statistically significant association between the types of SESMC and the number (F=12.57, p=0.001) and maximum diameter (F=8.08, p=0.006) of the cysts. SESMC with SNRF are often multiple and small, while cysts without SNRF tend to be solitary and large. We advocate early surgical intervention for symptomatic SESMCs in view of significant clinical improvement postoperatively.
Assuntos
Sacro , Cistos de Tarlov/cirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recuperação de Função Fisiológica , Nervos Espinhais/fisiopatologia , Cistos de Tarlov/diagnóstico , Cistos de Tarlov/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Cicatrização , Adulto JovemRESUMO
OBJECTIVE: To prospectively analyze the clinical features and characteristics of multi-segments intramedullary spinal cord tumors in adolescent patients. METHODS: In our study, 25 consecutive adolescent patients with multi-segments intramedullary spinal cord tumors were recruited, who underwent microsurgery for the tumor using a posterior approach and were hospitalized in Peking University Third Hospital within a period of 8 years. The tumor was exposed through dorsal myelotomy. Preoperative and postoperative neurological functions were scored using the improved Japanese orthopaedic association score system (IJOA) grading system. The functional outcome was defined as postoperative IJOA score minus preoperative IJOA score. All the patients were followed-up until Oct. 30, 2011. RESULTS: There were 15 male and 10 female adolescent patients younger than 25 years. Their mean age was (15.3±6.83) years. The most common initial symptom was sensory disturbance (including pain and/or numbness, 52%, 13/25), followed by motor disturbance (including limbs weakness and gait deterioration, 24%, 6/25), pain and motor disturbance (12%, 3/25), as well as fever, limbs deformities, and sphincter dysfunction, respectively. The preoperative IJOA scores of the patients were (14.4±3.38). The postoperative IJOA scores of the patients were (15.5±3.31). The most commonly involved location was the cervicothoracic segments (36%, 9/25), followed by the conus terminalis (24%, 6/25), the cervical region(16%, 4/25), the thoracic region (16%, 4/25), and the lumbus region (8%, 2/25). The average involved segments were (4.4±1.38). The most frequent tumors were neurodevelopmental tumors (including lipoma, epidermoid cyst and teratoma) (32%, 8/25), followed by astrocytomas (28%, 7/25), ependymomas (20%, 5/25), hemangioblastomas (12%, 3/25), and glioblastomas and schwannomas, respectively. CONCLUSION: In adolescent patients with multi-segments intramedullary spinal cord tumors, the most commonly involved locations are the cervicothoracic segments and the conus terminalis, while the most frequent tumors are neurodevelopmental tumors and astrocytomas. Good prognosis in adolescent patients is observed in a long-term follow-up.
Assuntos
Astrocitoma/cirurgia , Lipoma/cirurgia , Neoplasias da Medula Espinal/cirurgia , Adolescente , Vértebras Cervicais , Ependimoma/cirurgia , Feminino , Humanos , Vértebras Lombares , Masculino , Neoplasias da Medula Espinal/patologia , Vértebras Torácicas , Adulto JovemRESUMO
Multisegment intramedullary spinal cord tumors (MSICT) are a special type of spinal cord tumor. Up to now, no comparative clinical study of MSICT has been performed according to different age groups. Seventy-seven patients underwent microsurgery for MSICT. As grouped with two different methods, the parametric and nonparametric data of MSICT and patients were comparatively analyzed using statistically correlative methods. Forty-eight patients were males and 29 were females, ranging in age from 4 to 64 years (mean, 32.9 years). Among the six groups, being divided with intervals of 10 years, the whole difference in the initial symptoms of patients (Z = 17.4, P = 0.004) and in the histological classification of tumors (Z = 12.5, P = 0.03) was statistically significant, respectively. Neurodevelopmental tumor and benign glioma predominated in adolescents and decreased in frequency into adulthood where ependymoma became more predominant. In the 25 years old grouping method, there were 27 adolescent and 50 adult patients. The difference in initial symptoms of patients (Z = -2.08, P = 0.04) was statistically significant between the two groups. Pain with motor weakness and gait deterioration predominated in adolescents and decreased in frequency into adulthood where sensory disturbances became more predominant.
Assuntos
Astrocitoma/patologia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Fatores Etários , Astrocitoma/classificação , Criança , Feminino , Seguimentos , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Neoplasias da Medula Espinal/classificação , Adulto JovemRESUMO
OBJECTIVE: To evaluate the results of reconstruction by free anterolateral thigh flaps (ALT) after operation of head and neck tumors. METHODS: Forty-three cases underwent the reconstruction of postoperative defects with free anterolateral thigh flaps after head and neck cancer surgeries between November 2007 and June 2010 were reviewed. Ages of the patients ranged from 40 to 81 years, with a median of 56 years; 32 males and 11 females; 23 cases of oral carcinoma, 7 cases of tonsil carcinoma, 11 cases of hypopharyngeal carcinoma, and 2 cases of head skin cancer. TNM classified as follows: no case of distant metastasis; T1 9 cases; T2 17 cases; T3 11 cases; T4 6 cases. All patients were applied with ALT to restore swallowing and respiratory functions. The mean length of blood vessel pedicles of the ALT free flaps was 12.5 (8 - 18) cm. The flaps were 4 - 15 cm in width, 5 - 25 cm in length. RESULTS: In the 43 cases applied with ALT free flaps, 40 cases were successful and 3 cases unsuccessful. Two of the failed cases were reconstructed with pectoralis major flap. In 11 cases of hypopharyngeal carcinoma, except 3 cases with total laryngectomy, 8 cases (72.7%) had their laryngeal function been preserved. CONCLUSIONS: The successful rate of ALT free flaps is perfect. There were no serious complication in offered areas. The flap could be shaped into various forms. ALT free flap is an ideal flap to reconstruct the defect after surgery in some head and neck tumors.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cabeça/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: To comparatively analyze the different and common points between multi-segments intramedullary spinal cord congenital tumors and benign ependymomas, such as the patient's age, gender, nervous functions and tumor location, longitudinal extension, and removed extent. METHODS: Data were studied from 12 patients with multi-segments intramedullary spinal cord congenital tumors and 19 patients with multi-segments intramedullary spinal cord benign ependymomas who underwent microsurgery for the tumor using a posterior approach. The tumor was exposed through dorsal myelotomy. Preoperative and postoperative nervous functions were scored using the Improved JOA (improved Japanese orthopaedic association, IJOA) score system. Independent sample t-test was performed for ages, preoperative IJOA scores, postoperative IJOA scores and IJOA difference values of the patients, and longitudinal extension of tumors in the two groups with congenital tumors and benign ependymomas. Two independent sample Mann-Whitney tests was performed for the patient's gender, stool and urine functions, limbs weakness, and tumor removed extent in the two groups. All patients were followed-up until June 30, 2009. RESULTS: The average age of patients in congenital tumors group was 23.5+/-14.3, and in benign ependymomas group was 37.8+/-12.9, the age difference between the two groups was statistically significant (t=-2.89, P=0.007). The difference for location (Z=-3.59, P=0.001) and removed extent (Z=-2.89, P=0.004) of tumors between the two groups was statistically significant. Those located at the conus accounted for almost 83.3% (10/12) multi-segments intramedullary spinal cord congenital tumors. Because of the stiff adhesion with adjacent neural structures or penetrative growth in surrounding spinal marrow, some congenital tumors could not totally removed by force. The main purpose of surgery for these tumors was not total removal but decompression on the adjacent neural structures. Total or nearly total resection was achieved in 66.7% (8/12) patients diagnosed with congenital tumors. 78.9 (15/19) percent of multi-segments intramedullary spinal cord benign ependymomas were located at the cervical and cervicothoracic segments. Total or nearly total resection was achieved in 94.7% (18/19) patients with benign ependymomas. CONCLUSION: It is known from the clinical files that most multi-segments intramedullary spinal cord congenital tumors are found in young patients and most benign ependymomas in the middle-aged. Most congenital tumors are located at the conus, and they are difficult to totally remove. Most benign ependymomas are located at the cervical and cervicothoracic segments, and they are easy to totally remove.
Assuntos
Ependimoma/cirurgia , Neoplasias da Medula Espinal/congênito , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Criança , Ependimoma/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Neoplasias da Medula Espinal/diagnóstico , Teratoma/congênito , Teratoma/diagnóstico , Teratoma/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To explore the protection methods of parathyroid glands (PTGs) and their functions during total thyroidectomy. METHODS: The locations and the blood supplies of parathyroid glands in 292 cases underwent total thyroidectomy between February 1990 and December 2009 were studied. The protective measures for PTGs and their blood supplies during total thyroidectomy were analyzed. RESULTS: Total of 542 superior PTGs and 467 inferior PTGs were found in 296 cases of total thyroidectomy. Of the superior PTGs, 444 (81.9%) consistently located in the back sides of the thyroid glands and at the level of inferior edge of thyroid cartilage. The locations of the inferior PTGs were variable, 231 (49.5%) of them located in the inferior 1/3 part of the back sides of the thyroids and 116 (24.8%) at the inferior thyroid, in where inferior thyroid artery (ITA) branches enter thyroid. The fine dissections showed that the blood supplies to superior PTGs were mainly from the upper branch of ITA, accounting for 71 (68.3%) of 104 superior PTGs and the blood supplies to inferior PTGs were from the inferior branches of ITA system, accounting for 114 (80.3%) of 142 inferior PTGs. There was 13 cases with short-term hypocalcemia postoperatively, but no case with permanent hypoparathyroidism. CONCLUSIONS: The blood supplies of PTGs are associated with their locations. During total or subtotal thyroidectomy, parathyroid glands and their artery blood-supply should be exposed and preserved to prevent hypoparathyroidism after surgery.