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1.
Sci Rep ; 13(1): 11769, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474710

RESUMO

Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin-Eosin, Masson's trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-ß1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-ß pathway was found to play an important role in its development.


Assuntos
Neoplasias Esofágicas , Estenose Esofágica , Humanos , Ratos , Animais , Qualidade de Vida , Mucosa/patologia , Mucosa Esofágica/patologia , Neoplasias Esofágicas/patologia
3.
Int J Ophthalmol ; 12(12): 1908-1916, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850177

RESUMO

AIM: To ensure the diagnostic value of computer aided techniques in diabetic retinopathy (DR) detection based on ophthalmic photography (OP). METHODS: PubMed, EMBASE, Ei village, IEEE Xplore and Cochrane Library database were searched systematically for literatures about computer aided detection (CAD) in DR detection. The methodological quality of included studies was appraised by the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-DiSc was utilized and a random effects model was plotted to summarize data from those included studies. Summary receiver operating characteristic curves were selected to estimate the overall test performance. Subgroup analysis was used to identify the efficiency of CAD in detecting DR, exudates (EXs), microaneurysms (MAs) as well as hemorrhages (HMs), and neovascularizations (NVs). Publication bias was analyzed using STATA. RESULTS: Fourteen articles were finally included in this Meta-analysis after literature review. Pooled sensitivity and specificity were 90% (95%CI, 85%-94%) and 90% (95%CI, 80%-96%) respectively for CAD in DR detection. With regard to CAD in EXs detecting, pooled sensitivity, specificity were 89% (95%CI, 88%-90%) and 99% (95%CI, 99%-99%) respectively. In aspect of MAs and HMs detection, pooled sensitivity and specificity of CAD were 42% (95%CI, 41%-44%) and 93% (95%CI, 93%-93%) respectively. Besides, pooled sensitivity and specificity were 94% (95%CI, 89%-97%) and 87% (95%CI, 83%-90%) respectively for CAD in NVs detection. No potential publication bias was observed. CONCLUSION: CAD demonstrates overall high diagnostic accuracy for detecting DR and pathological lesions based on OP. Further prospective clinical trials are needed to prove such effect.

5.
J Zhejiang Univ Sci B ; 20(3): 205-218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829009

RESUMO

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.


Assuntos
Tratos Piramidais/patologia , Medicina Regenerativa/métodos , Traumatismos da Medula Espinal/terapia , Animais , Astrócitos/citologia , Axônios/fisiologia , Transplante de Células , Modelos Animais de Doenças , Estimulação Elétrica , Humanos , Microglia/citologia , Neurônios Motores/citologia , Regeneração Nervosa , Neuroglia/citologia , Plasticidade Neuronal , Neurônios/citologia , Oligodendroglia/citologia , Recuperação de Função Fisiológica
6.
J Foot Ankle Surg ; 55(3): 529-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26874831

RESUMO

The present study investigated the clinical outcomes of the posterior midline approach in the treatment of 34 patients with significantly calcified insertional Achilles tendinopathy. The posterior midline approach was applied for the surgical treatment of 34 patients with chronic significantly calcified insertional Achilles tendinopathy after failed conservative treatment. Gastrocnemius recession was performed simultaneously for patients with gastrocnemius contracture. The Fowler-Philip angle and parallel pitch lines were measured before surgery, and the visual analog scale, Tegner score, and Victorian Institute of Sport tendon study group score were recorded before and after surgery. The mean follow-up period was 45.2 ± 17.7 (range 24 to 84) months. After surgery, the visual analog scale score had decreased notably, and the Tegner score and Victorian Institute of Sport tendon study group score had increased significantly. The posterior midline approach can achieve satisfactory outcomes in the treatment of significantly calcified insertional Achilles tendinopathy, and gastrocnemius recession (Strayer procedure) should be performed for patients with gastrocnemius contracture to improve the surgical outcome.


Assuntos
Tendão do Calcâneo/cirurgia , Calcinose/cirurgia , Músculo Esquelético/cirurgia , Procedimentos Ortopédicos/métodos , Tendinopatia/cirurgia , Tendão do Calcâneo/diagnóstico por imagem , Adulto , Contratura/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor
7.
Mol Med Rep ; 9(1): 345-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24173687

RESUMO

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Benzilisoquinolinas/farmacologia , Caspases/metabolismo , Antineoplásicos Fitogênicos/química , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Benzilisoquinolinas/química , Linhagem Celular Tumoral , Citocromos c/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
8.
Cancer Biother Radiopharm ; 27(10): 701-10, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22849560

RESUMO

To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Ácido Gálico/farmacologia , Sistema de Sinalização das MAP Quinases/genética , Proteína Quinase 8 Ativada por Mitógeno/genética , Osteossarcoma/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Neoplasias Ósseas/enzimologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Osteossarcoma/enzimologia , Osteossarcoma/genética , Osteossarcoma/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Asian Pac J Cancer Prev ; 13(4): 1171-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22799300

RESUMO

OBJECTIVE: The current study aimedto screen for possible factors which affect prognosis of chondrosarcoma. METHODS: Thirty seven cases were selected and analyzed statistically. The patients received surgical treatment at our hospital between December 2005 and March 2008. All of them had complete follow-up data. The survival rates were calculated by univariate analysis using the Kaplan-Meier method and tested by Log-rank. χ2 or Fisher exact tests were carried out for the numeration data. The significant indexes after univariate analysis were then analyzed by multivariate analysis using COX regression model. Based on the literature, factors of gender, age, disease course, tumor location, Enneking grades, surgical approaches, distant metastasis and local recurrence were examined. RESULTS: Univariate analysis showed that there were significant differences in Enneking grades, surgical approaches and distant metastasis related to the patients' 3-year survival rate after surgery (P<0.001). No significant difference was not found in gender, age, disease course, tumor location or local recurrence (P>0.05). Multivariate analysis showed that Enneking grade (P=0.007) and surgical approaches (P=0.010) were independent factors affecting the prognosis of chondrosarcoma, but distant metastasis was not (P=0.942). CONCLUSION: Enneking grades, surgical approaches and distant metastasis are risk factors for prognosis of chondrosarcoma, among which the former two are independent factors.


Assuntos
Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Condrossarcoma/patologia , Condrossarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Criança , Condrossarcoma/secundário , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Anticancer Agents Med Chem ; 12(5): 554-63, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22263786

RESUMO

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together, these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Regulação para Baixo/efeitos dos fármacos , Genisteína/uso terapêutico , Osteossarcoma/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , Osteossarcoma/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Gencitabina
11.
Cancer Chemother Pharmacol ; 69(2): 317-31, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21717192

RESUMO

PURPOSE: Matrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has potent anti-tumor activity in various cancer cell lines. However, the activity of matrine against osteosarcoma remains unclear. In the present study, we examined the effects of matrine on human osteosarcoma cells and explored the underlying mechanism. METHODS: Four human osteosarcoma cell lines: MG-63, U-2OS, Saos-2, and MNNG/HOS were treated by matrine and subjected to MTT assay, annexin V-FITC/PI double staining, and TUNEL assay. The activation of caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined by qRT-PCR and Western blot. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered to evaluate the anti-cancer capacity of matrine in vivo. RESULTS: We found that matrine inhibited the proliferation and induced apoptosis of the four osteosarcoma cell lines in vitro and induced the activation of caspase-3, -8, and -9 in a dose-dependent manner. Furthermore, the pro-apoptotic factors Bax and Fas/FasL were upregulated, and the anti-apoptotic Bcl-2 was downregulated. More importantly our in vivo, studies showed that administration of matrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of Bcl-2 and upregulation of Bax and Fas/FasL in MNNG/HOS tumor tissues following matrine treatment, consistent with the in vitro results. CONCLUSION: Our results demonstrate that matrine inhibits the proliferation and induces apoptosis of human osteosarcoma cells in vitro and in vivo. The induction of apoptosis appears to occur through the upregulation of Fas/FasL and Bax, downregulation of Bcl-2, and activation of caspase-3, -8, and -9, which then trigger major apoptotic cascades.


Assuntos
Alcaloides/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Quinolizinas/farmacologia , Alcaloides/química , Animais , Proteínas Reguladoras de Apoptose/genética , Western Blotting , Caspases/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quinolizinas/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Receptor fas/genética , Receptor fas/metabolismo , Matrinas
12.
Orthopedics ; 34(12): e960-4, 2011 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-22146219

RESUMO

Cerebrotendinous xanthomatosis is a rare, autosomal-recessive, lipid-storage disease with accumulation of cholestanol in most tissues, particularly within the Achilles tendons. It has been characterized both clinically and biochemically, and recently from the molecular biological aspect as well. Juvenile cataract, childhood diarrhea, mental retardation, cerebellar ataxia, and tendon xanthomas are the most prominent features of this disease. Bilateral symmetrical firm masses of Achilles tendons may be the first symptom the patient recognizes because it can jeopardize his or her ability to walk. However, the treatment strategies for tendon tumors vary. In a recent case, we diagnosed the disease properly, according to the clinical manifestations and the radiological and laboratory examinations. The genetic mutation was characterized by analyzing sterol 27-hydroxylase from the patient's family (located on nucleotide 599) and led to a nonsense mutation. It is a unique type of mutation that has never been reported to our knowledge. Tendon lesions are characterized by the loss of muscle fibers and accumulation of lipid products. To help the patient regain the strength of the Achilles tendon and walking abilities, a large area of tendon tumor was excised, followed by reconstruction with a tibialis posterior allograft, which is the second strongest tendon in the foot and ankle. Although the use of this type of graft is uncommon, the final result was satisfactory. At the 10-month follow-up examination, the patient could walk easily without pain. This case report suggests that the surgical procedure will provide an alternative for the repair of large-area degenerative Achilles tendons.


Assuntos
Tendão do Calcâneo/patologia , Xantomatose Cerebrotendinosa/diagnóstico , Tendão do Calcâneo/fisiopatologia , Tendão do Calcâneo/cirurgia , Adulto , Tornozelo/patologia , Colestanotriol 26-Mono-Oxigenase/genética , Códon sem Sentido , Diagnóstico Diferencial , Saúde da Família , Feminino , Humanos , Hipertrofia , Imageamento por Ressonância Magnética , Masculino , Mutação , Resultado do Tratamento , Xantomatose Cerebrotendinosa/genética , Xantomatose Cerebrotendinosa/cirurgia
13.
Zhonghua Wai Ke Za Zhi ; 49(1): 79-82, 2011 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-21418845

RESUMO

OBJECTIVE: To discuss the resection pseudoarthrosis for pelvic malignant tumors around acetabular. METHODS: From May 1997 to June 2005, 25 patients with malignant tumors around acetabular were treated surgically with resection pseudoarthrosis. The series comprised 15 males and 10 females with an average age of 42 years old (range from 16 to 75 years old). There were 4 osteosarcomas, 12 chondrosarcomas, 1 Ewing's sarcoma, 1 neuroectodermal tumor, 1 myeloma, 1 malignant fibrohistiocytoma, 2 synovial sarcomas, and 3 metastases. Pseudoarthrosis was performed after resection of pelvic malignant tumors around acetabular. The affected side was protected postoperatively by skin traction with 2 - 3 kg weight for 6 to 8 weeks. After then, the patients walked gradually with a cane. RESULTS: Among 25 patients, 6 had complications (24%). At a follow-up ranging from 3 to 10 years, 11 patients died of lung metastases, 2 relapsed, 12 remained alive free of disease. There was an average crispation of 5 cm (range from 2.5 to 7.5 cm). The patients were functionally evaluated according to Enneking's MSTS criteria in 1993. The average MSTS functional score was 17 points (12 to 19 points). After 3 months postoperative, the patients could sit normally, walk with a cane, and even walk limpingly without cane. CONCLUSIONS: Resection pseudoarthrosis for pelvic malignant tumors around acetabular results in good clinical results at the time of mid-term and long-term follow-up. And pseudoarthrosis is advisable especially for patients with malignant highly tumors around acetabular, poor soft tissue reconstruction condition, high risk for infection, poor economy.


Assuntos
Acetábulo , Cabeça do Fêmur/cirurgia , Neoplasias Pélvicas/cirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Anticancer Drugs ; 21(3): 288-96, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20038829

RESUMO

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cell lines. This study was designed to investigate whether combination therapy with gemcitabine and genistein enhances antitumor efficacy in osteosarcoma cell lines (MG-63 and U2OS). Our results show that significant reduction in cell viability and corresponding induction of apoptosis were observed with combination treatment in both cell lines. On the molecular level, we found that gemcitabine alone can activate nuclear factor kappaB (NF-kappaB) in osteosarcoma, suggesting the potential mechanism of acquired chemoresistance. In contrast, genistein reversed the cancer's resistance to gemcitabine through the downregulation of NF-kappaB activity and the suppression of Akt. These findings suggest that the combination of gemcitabine and genistein enhanced the antitumor efficacy by abrogating the Akt/NF-kappaB pathway. The marked ability to induce apoptosis with a combination of gemcitabine and genistein suggests that this could be a rational and novel approach for osteosarcoma preclinical and clinical trials.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos Antineoplásicos , Neoplasias Ósseas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Genisteína/uso terapêutico , NF-kappa B/antagonistas & inibidores , Osteossarcoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/uso terapêutico , Sinergismo Farmacológico , Humanos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Gencitabina
15.
Chemotherapy ; 55(6): 433-40, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19996588

RESUMO

AIMS: Studies on cancer biology have shown that overexpression of oncogenes (with or without functional loss of tumor suppressor genes), which is responsible for the progression of human malignancies via a multistep process, may be reduced by antisense technology. Caffeine enhances the effect of cisplatin (CDDP) chemotherapy on osteosarcoma cells. We constructed the recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment and investigated the synergic effect of caffeine and Myc-AS on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin. METHODS: The recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment was constructed by cloning c-myc cDNA of about 750 bp in a reverse direction into adenovirus vector, then undergoing recombination, amplification and complementation in vivo. Myc-AS and caffeine were used either alone or in combination with CDDP to treat osteosarcoma MG-63 cells in vitro. Western blot, MTT, flow cytometry (FCM) and electron microscopy were used to evaluate the expression of c-myc protein, tumor cell proliferation in vitro and apoptosis and to perform cell cycle analysis. RESULTS: Myc-AS encoding antisense c-myc fragment was obtained with a titer of 2 x 10(9) pfu/ml. Myc-AS downregulated the expression of c-myc protein after transfecting MG-63 cells for 48 h, induced tumor cell apoptosis and inhibited tumor cell proliferation in vitro. Myc-AS or caffeine can enhance the cytotoxic effects of 2.0 and 5.0 microg/ml CDDP on MG-63 cells. Moreover, the significantly enhancing effect of the Myc-AS-caffeine combination on CDDP chemotherapy of MG-63 cells was not restricted to apoptosis but also decreased tumor cell proliferation in vitro. Expression of the apoptosis-associated bcl-2 gene was downregulated and bax was upregulated, with no changes in E2F-1 expression. FCM analysis showed that CDDP treatment induced a block in S phase, and caffeine reversed this block and accelerated cell progression through the S phase. CONCLUSIONS: Myc-AS can induce obvious G2/M phase arrest in transfected cells. Myc-AS combined with caffeine can enhance apoptosis induction and chemotherapeutic effects of CDDP on osteosarcoma MG-63 cells.


Assuntos
Antineoplásicos/farmacologia , Cafeína/farmacologia , Cisplatino/farmacologia , Proteínas Proto-Oncogênicas c-myc/administração & dosagem , Adenoviridae/genética , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA Antissenso/administração & dosagem , Sinergismo Farmacológico , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos , Humanos , Microscopia Eletrônica , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo
16.
Zhonghua Wai Ke Za Zhi ; 47(14): 1079-82, 2009 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-19781274

RESUMO

OBJECTIVE: To observe the long-term result of fibula grafting for reconstruction of the distal radius after giant cell tumor excision. METHODS: From March 1994 to November 2004, 31 cases of fibula grafting for reconstruction of the distal radius for giant cell tumors performed were analysed. There were 12 males and 19 females. The patients were from 19 to 48 years old, and the mean age was 31 years. Twenty-four patients had Campanacci grade 3 lesions, and 7 patients had Campanacci grade 2 lesions. There were 6 cases of vascularized fibular grafting and 25 cases of non-vascularized fibular grafting. All cases were evaluated by clinical and radiologic examinations; the movement of the wrist and the grip strength was measured; the MSTS score and Mayo Wrist scores were calculated. RESULTS: Clinical follow-up time after reconstruction averaged 86.3 months, range from 41 to 169 months. The mean time for bone union at the host-graft junctions was 5.1 months range from 3 to 9 months in vascularized group and 10.3 months range from 7 to 15 months in non-vascularized group. One patient who had non-vascularized fibula grafting developed non-union at the host-graft junction, and one patient had local recurrence (3.2%). Five patients developed an wrist dislocation after surgery. The average movements of the wrist were: 67.3 +/- 9.4 degrees of extension, 31.2 +/- 5.1 degrees of flexion, 14.1 +/- 4.7 degrees of radial deviation, 19.4 +/- 3.9 degrees of ulnar deviation, 33.8 +/- 6.6 degrees of pronation, 15.3 +/- 4.0 degrees of supination. Average grip strength was 33.1 kg range from 15.5 to 52.1 kg. Compared with the contralateral side, there were accounted for 73%. MSTS score averaged 25.5 from 23 to 29, Mayo wrist score averaged 56 from 40 to 65. CONCLUSIONS: En bloc resection of giant cell tumor of the distal radius followed by reconstruction with a fibula graft is proved to be an effective method and results in a good functional outcome at long term follow-up evaluation. The stability of wrist is achieved by reconstruction of the capsule.


Assuntos
Neoplasias Ósseas/cirurgia , Fíbula/transplante , Tumor de Células Gigantes do Osso/cirurgia , Rádio (Anatomia) , Adulto , Transplante Ósseo/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
18.
Zhonghua Wai Ke Za Zhi ; 46(12): 900-3, 2008 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-19035147

RESUMO

OBJECTIVE: To study the limb salvage methods and treatment outcomes in malignant periacetabular bone tumors. METHODS: The data of 31 patients of periacetabular malignant tumors who had limb salvage surgery between January 1999 and December 2006 was retrospectively reviewed. There were 14 females and 17 males with a mean age of 53 years (range, 42-75 years). Twenty-four patients had chondrosarcomas, 4 patients had Ewing sarcomas, 1 patient had osteosarcoma, and the remaining 2 patients had metastatic disease. Sixteen patients had Types II pelvic resections, 5 patients had Types I and II pelvic resections, another 5 had Type I and III pelvic resections, and Type I , II and III pelvic resections in the remaining patients. Seventeen patients had reconstructions after tumor resection. RESULTS: The mean follow-up time for all patients was 52 months (range, 12-84 months). Fourteen patients were alive with no evidence of disease, 4 patients were alive with disease at the most recent follow-up, and 13 patients died of disease. The local recurrence rate and mortality rate in 24 patients with chondrosarcomas was 20.8% and 33.3% respectively. Two patients with metastatic disease died at 11 and 34 months postoperatively. One patient with osteosarcoma and 2 patients with Ewing sarcoma died of lung metastases. Enneking scoring system was used to evaluate the functional outcome in 18 alive patients. In 13 patients who had reconstructions, 6 were in excellent, 6 were in good, and 1 was in poor. While in 6 patients who had no reconstructions, 3 were in excellent, 2 were in good, and 1 was in poor. Minor complications occurred in 6 patients. CONCLUSIONS: Clear margin tumor resection with decreased local recurrence rate is critical for limb salvage surgery in periacetabular sarcomas. The ranges of tumor invasion and resection, the principle of individual treatment should be considered in functional reconstruction.


Assuntos
Acetábulo , Neoplasias Ósseas/cirurgia , Adulto , Idoso , Artroplastia de Quadril , Feminino , Seguimentos , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
Cell Biol Int ; 32(5): 494-501, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18078766

RESUMO

Cyclooxygenase-2 (COX-2), involved in the inhibition of apoptosis and, the potentiation of cell growth, is frequently overexpressed in human malignancies including osteosarcoma (OS). We have attempted to identify the anti-proliferation of celecoxib, a selective COX-2 inhibitor, and the combination of celecoxib and cisplatin in MG-63 cells, and to explore the potential molecular mechanisms involved. MG-63 cells were treated with the combination of celecoxib and cisplatin or either agent alone for 48h in serum-supplemented medium. Celecoxib caused G1 phase arrest and significantly inhibited cell growth, as well as potentiating cisplatin-induced apoptosis. The effect was dose-dependent, and apoptotic changes such as DNA fragments and apoptotic bodies were observed. However, downregulation of COX-2 did not occur in cells treated with celecoxib. Phosphoinositide-3-kinase (PI3K)/Akt, survivin, bcl-2 were significantly downregulated in cells treated with the combination of celecoxib and cisplatin, and decreased survivin and bcl-2 levels were found in cells with wortmannin, a specific PI3K inhibitor. Moreover, the decreased expressions of procaspase-9, procaspase-3 and cleaved PARP-1 were detected by Western blot analysis. Therefore, celecoxib exerts its anti-tumor activities through COX-2-independent mechanisms, which may be PI3K/Akt-dependent, and survivin and bcl-2-related. PI3K may be at the center of the celecoxib effects, which play an essential role in the regulation of survivin and Bcl-2.


Assuntos
Apoptose/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Regulação para Baixo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Androstadienos/farmacologia , Antineoplásicos/farmacologia , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Ciclo-Oxigenase 2/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Osteossarcoma , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Survivina , Wortmanina
20.
Zhonghua Wai Ke Za Zhi ; 45(10): 665-8, 2007 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-17688816

RESUMO

OBJECTIVE: To evaluate the effect and complication of the endoprosthetic reconstruction after wide resection of primary bone tumor around the knee. METHODS: The retrospective analysis was performed on 83 patients undergoing the prosthetic reconstruction after the resection of the primary tumor around the knee between December 1995 and December 2005. All the diagnoses were pathologically confirmed (58 patients with osteosarcoma, 2 with osteosarcomatosis, 1 with parosteal osteosarcoma, 4 with malignant fibrous histiocytoma, 13 with giant cell tumor of bone, 1 with leiomyosarcoma, 2 with Ewing's sarcoma, 2 with chondrosarcoma). The distal femur group was involved in 44 patients, proximal tibia group in 34 (including 33 deficit in proximal tibia, 1 deficit both in proximal tibia and distal femur), total femur replacement group in 5. After operation, the Musculoskeletal Tumor Society (MSTS) score was used to evaluate the recovery of their corresponding functions. RESULTS: The follow-up for 12 - 130 months (with a median of 41 months) revealed that the 3-year survival rate of the prosthesis was 88.2%, and the 5-year survival rate was 82.1%. As for the complications, local recurrence developed in 6 patients, peri-prosthesis infection in 2 patients, aseptic loosening in 2 patients. The mean MSTS core was 25.0 (19.0 - 29.0) in the distal femur group, 24.4 (17.0 - 28.0) in the proximal tibia group, and 19.0 (16.0 - 21.0) in the total femur replacement group. As to the statistical analysis, the function of the former two groups were greater than the latter one (F = 11.666, P < 0.001), however, there was no significant difference between the former 2 groups (F = 0.813, P = 0.370). CONCLUSIONS: Taken together, the tumor prosthesis gives a satisfactory functional outcome after the tumor around the knee is removed with a lower incidence of complication.


Assuntos
Artroplastia do Joelho/métodos , Neoplasias Ósseas/cirurgia , Joelho , Adolescente , Adulto , Artroplastia do Joelho/efeitos adversos , Neoplasias Ósseas/patologia , Criança , Feminino , Seguimentos , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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