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1.
Int Orthop ; 48(4): 1089-1096, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38332113

RESUMO

PURPOSE: Although rare, non-metastatic proximal femoral fracture (PFF) can develop in patients with active cancer. However, little data are available regarding the risks and benefits of surgical treatment in such patients. The purpose of his study was to investigate the risks and benefits of surgical treatment of PFF in patients with and without cancer. METHODS: We retrospectively examined the medical records of all patients treated for PFF, excluding those with pathological fracture, at our hospital from July 2013 to December 2020. The patients were divided into two groups; The active cancer group and the standard group. We investigated in both groups about surgical and medical complications during the perioperative period, walking ability two weeks postoperatively, and one-year postoperative mortality rate. RESULT: After the inclusion and exclusion criteria, 39 patients in the active cancer group and 331 patients in the standard group were finally investigated. There were no statistically significant differences between the two groups. The complication rate did not appear statistical significance between two groups (16.7% in active cancer group vs 10.7% in standard group: p = 0.272). Walking ability was also similar in two groups. Mortality rate at one year was significantly higher in the active cancer group. (41.2% in active cancer group vs 6.0% in standard group: p < 0.05). CONCLUSION: Although the active cancer group had a higher mortality rate at one year, which was influenced by the prognosis of the cancer, the benefits of surgical intervention, such as regaining walking ability, were the same in patients with and without active cancer.


Assuntos
Artroplastia de Quadril , Fraturas Espontâneas , Fraturas do Quadril , Neoplasias , Humanos , Estudos Retrospectivos , Fraturas Espontâneas/cirurgia , Neoplasias/cirurgia
2.
BMC Musculoskelet Disord ; 21(1): 279, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359366

RESUMO

BACKGROUND: Delirium is a well-known complication following surgery, especially with the increasing age of patients undergoing surgery. The increasing demands resulting from a prolonged healthy life expectancy has resulted in more arthroplasties despite their age and existing comorbidities. The purpose of this study is to explore the various risk factors that may contribute to delirium in unilateral and bilateral total knee arthroplasties in the elderly population. METHODS: 170 patients who underwent unilateral or bilateral total knee arthroplasties were analyzed retrospectively for delirium. Age, sex, comorbidities, use of sedative-hypnotics, peri-operative blood loss, pre- and post-operative laboratory blood test results were investigated and analyzed. RESULTS: The incidence of post-operative delirium was 6.5% (11 out of 170 patients) with a mean age of 79.5 (± 6.9) years, compared to 73.0 (± 9.0) years in the non-delirium group. Higher age, use of sedative-hypnotics, low pre-operative Hb and Ht, low post-operative Hb, Ht and BUN were observed in the delirium group. Multivariate logistic regression analysis identified that the use of sedative-hypnotics and pre-operative Hb level were independent risk factors for post-operative delirium after TKA. The odds ratios for the use of sedative-hypnotics and pre-operative Hb level were 4.6 and 0.53, respectively. Receiver operating characteristic curve analysis showed that pre-operative Hb of less than 11.1 g/dL was a predictor for the development of delirium, with a sensitivity of 54.6% and a specificity of 91.6%. CONCLUSION: Patients with a pre-operative Hb level of < 11.1 g/dL or those using sedative-hypnotics are associated with post-operative delirium. Peri-operative management and preventative measures are therefore needed to reduce the risks of post-operative delirium in such patients.


Assuntos
Artroplastia do Joelho/efeitos adversos , Delírio/etiologia , Hipnóticos e Sedativos/efeitos adversos , Complicações Pós-Operatórias/psicologia , Fatores Etários , Idoso , Perda Sanguínea Cirúrgica , Estudos de Casos e Controles , Comorbidade , Delírio/diagnóstico , Delírio/epidemiologia , Feminino , Hemoglobinas/análise , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
3.
Ann Hepatol ; 17(4): 655-660, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29893706

RESUMO

A 76-year-old woman was referred to our hospital due to massive gingival bleeding following teeth extraction. Laboratory findings suggested disseminated intravascular coagulopathy (DIC). Enhanced computed tomography and magnetic resonance imaging disclosed multiple hypervascular liver masses of 2-6 cm in diameter, the largest of which displaying an irregular enhancement pattern. We considered that her DIC was caused by the multiple liver masses and commenced repeated erythrocyte/fresh frozen plasma infusión and gabexate mesilate administration. However, the DIC proved uncontrollable and trans-arterial embolization could not be attempted. The patient eventually died 4 months after admission due to spontaneous hepatic tumor rupture and hepatic failure. Post-mortem hepatic tumor biopsy led to a final diagnosis of hepatic angiosarcoma with Kasabach-Merritt phenomenon (KMP). Among the 7 cases of hepatic angiosarcoma representing KMP found in the literature, mortality occurred within 4 months of the appearance of bleeding tendency primarily due to abdominal bleeding and hepatic failure. The possibility of hepatic angiosarcoma should be considered in patients with DIC and hypervascular liver tumors. Since treatment is uncertain and prognosis is poor, novel diagnostic and therapeutic advances are needed for angiosarcoma.


Assuntos
Hemangiossarcoma/diagnóstico , Síndrome de Kasabach-Merritt/diagnóstico , Neoplasias Hepáticas/diagnóstico , Idoso , Biópsia , Coagulação Intravascular Disseminada/etiologia , Evolução Fatal , Feminino , Hemangiossarcoma/complicações , Hemangiossarcoma/terapia , Hemorragia/etiologia , Humanos , Imuno-Histoquímica , Síndrome de Kasabach-Merritt/complicações , Síndrome de Kasabach-Merritt/terapia , Falência Hepática/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Ruptura Espontânea , Tomografia Computadorizada por Raios X , Ultrassonografia
4.
Biochim Biophys Acta Proteins Proteom ; 1865(9): 1160-1166, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28668639

RESUMO

Myxofibrosarcoma (MFS) is a mesenchymal malignancy characterized by frequent recurrence even after radical wide resection. To optimize therapy for MFS patients, we aimed to identify candidate tissue biomarkers of MFS invasion potential. Invasion characteristics of MFS were evaluated by magnetic resonance imaging and protein expression profiling of primary tumor tissues performed using two-dimensional difference gel electrophoresis (2D-DIGE). Protein expression profiles were compared between invasive and non-invasive tumors surgically resected from 11 patients. Among the 3453 protein spots observed, 59 demonstrated statistically significant difference in intensity (≥2-fold) between invasive and non-invasive tumors (p<0.01 by Wilkoxon test), and were identified by mass spectrometry as 47 individual proteins. Among them, we further focused on discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2), a receptor tyrosine kinase with aberrant expression in malignant tumors. Immunohistochemistry analysis of 21 additional MFS cases revealed that higher DCBLD2 expression was significantly associated with invasive properties of tumor cells. DCBLD2 sensitivity and specificity, and positive and negative predictive values for MFS invasion were 69.2%, 87.5%, 90%, and 63.6%, respectively. The expression level of DCBLD2 was consistent in different portions of tumor tissues. Thus, DCBLD2 expression can be a useful biomarker to evaluate invasive properties of MFS. Further validation studies based on multi-institutional collaboration and comprehensive analysis of DCBLD2 biological functions in MFS are required to confirm its prognostic utility for clinical application.


Assuntos
Biomarcadores Tumorais/análise , Fibrossarcoma/química , Perfilação da Expressão Gênica/métodos , Proteínas de Membrana/análise , Proteínas de Neoplasias/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Eletroforese em Gel Bidimensional , Feminino , Fibrossarcoma/diagnóstico , Fibrossarcoma/genética , Fibrossarcoma/patologia , Humanos , Masculino , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Espectrometria de Massas em Tandem
5.
BMC Musculoskelet Disord ; 18(1): 31, 2017 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-28114920

RESUMO

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of intermediate biologic potential. Because of its rarity and nonspecific radiological and diverse pathological findings, AFH is often clinically misdiagnosed. However, few clinical reports have described this tumor. As reported herein, we analyzed the clinical and radiological features and clinical outcomes of AFH. METHODS: We retrospectively reviewed the medical records of seven cases histopathologically diagnosed as AFH. We examined clinical features, MRI findings, histopathological diagnoses, treatments, and outcomes. RESULTS: These seven cases comprised five male and two female patients with ages ranging from 8 to 50 years old. The primary locations included upper extremities in 2, lower extremities in 4, and the inguinal region in one patient. Of the tumors, 4 occurred in subcutaneous tissues and 3 occurred in deep tissues. No cases were diagnosed as AFH from MRI and needle biopsy results. All cases were diagnosed histopathologically after excision. After treatment, 2 patients (29%) had tumor recurrence and metastasis, one of whom died from disease progression. These 2 aggressive cases involved both EWSR1 and CREB1 gene rearrangements as determined by FISH. The other patients were alive and well without recurrence or metastasis. CONCLUSION: AFH is a rare tumor that is difficult to diagnose. Therefore, it tends to be misdiagnosed and to be treated inadequately by referring physicians. Surgeons must therefore be mindful of the presence of AFH, learn about appropriate treatment necessary for this tumor, and conduct careful follow-up because AFH can engender poor outcomes.


Assuntos
Histiocitoma Fibroso Maligno/diagnóstico por imagem , Histiocitoma Fibroso Maligno/genética , Adulto , Criança , Evolução Fatal , Feminino , Seguimentos , Histiocitoma Fibroso Maligno/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Adulto Jovem
6.
Mod Pathol ; 29(11): 1424-1432, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27469332

RESUMO

Recently, several studies have reported that dysfunctions in protein phosphatase 2A (PP2A) caused by alterations in protein phosphatase 2 regulatory subunit A, alpha (PPP2R1A) are responsible for tumorigenesis and tumor progression in several types of cancers. The impact of PPP2R1A mutations remains unknown in gastrointestinal stromal tumors (GISTs), although mutations in KIT and PDGFRA, which result in constitutive activation of the receptor tyrosine kinase pathway, are important in GIST tumorigenesis. In this study, we performed mutation analysis of PPP2R1A to examine the frequency of PPP2R1A mutations and their clinicopathological correlation in 94 GIST cases. In addition, we performed an in vitro analysis to investigate the effects of PPP2R1A mutations on cell proliferation and kinase phosphorylation in GIST cells. Seventeen GIST cases (18%) harbored mutations in PPP2R1A. All but one of these 17 cases harbored a KIT, PDGFRA, HRAS, NRAS, or KRAS mutation as the oncogenic driver mutation, and the remaining case was immunohistochemically negative for succinate dehydrogenase B (SDHB). Multivariate analysis showed that larger tumor size, higher mitotic rate, and PPP2R1A mutation are independent prognostic factors for overall survival; however, PPP2R1A mutation was not an independent prognostic factor for disease-free survival. The transduction of GIST cells with mutant PPP2R1A induced an accelerated growth rate via increased phosphorylation of Akt1/2, ERK1/2, and WNK1, a kinase associated with angiogenesis. In addition, the transduction of GIST cells with mutant PPP2R1A caused increased c-kit phosphorylation, suggesting that c-kit is also a target of PP2A, reinforcing the tumorigenic capabilities of c-kit. Furthermore, the transducing GIST cells with wild-type PP2A dephosphorylated mutant c-kit. This study provides a new insight into the biology of GISTs and their phosphatase activity, and activated PP2A could be a therapeutic target in GISTs.


Assuntos
Tumores do Estroma Gastrointestinal/genética , Proteína Fosfatase 2/genética , Idoso , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico
7.
BMC Cancer ; 16: 206, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26965049

RESUMO

BACKGROUND: A previous proteomics study demonstrated the overexpression of F-actin capping protein subunit beta (CAPZB) in tissue specimens of epithelioid sarcoma (EpiS). The aim of the present study was to elucidate the function of CAPZB in EpiS. METHODS: Cellular functional assays were performed in two EpiS cell lines using CAPZB siRNAs. In addition, comparative protein expression analyses using Isobaric Tags for Relative and Absolute Quantitation (i-TRAQ) method were performed to identify the specific proteins whose expression was dysregulated by CAPZB, and analysed the data with the Ingenuity Pathways Analysis (IPA) system using the obtained protein profiles to clarify the functional pathway networks associated with the oncogenic function of CAPZB in EpiS. Additionally, we performed functional assays of the INI1 protein using INI1-overexpressing EpiS cells. RESULTS: All 15 EpiS cases showed an immunohistochemical expression of CAPZB, and two EpiS cell lines exhibited a strong CAPZB expression. Silencing of CAPZB inhibited the growth, invasion and migration of the EpiS cells. Analysis of protein profiles using the IPA system suggested that SWI/SNF chromatin-remodeling complexes including INI1 may function as a possible upstream regulator of CAPZB. Furthermore, silencing of CAPZB resulted in a decreased expression of INI1 proteins in the INI1-positive EpiS cells, whereas the induction of INI1 in the INI1-deficient EpiS cells resulted in an increased CAPZB mRNA expression. CONCLUSIONS: CAPZB is involved in tumor progression in cases of EpiS, irrespective of the INI1 expression, and may be a potential therapeutic target. The paradoxical relationship between the tumor suppressor INI1 and the oncoprotein CAPZB in the pathogenesis of EpiS remains to be clarified.


Assuntos
Proteína de Capeamento de Actina CapZ/genética , Movimento Celular/genética , Proliferação de Células/genética , Proteína SMARCB1/genética , Sarcoma/genética , Citoesqueleto de Actina/genética , Proteína de Capeamento de Actina CapZ/biossíntese , Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , RNA Interferente Pequeno/genética , Proteína SMARCB1/biossíntese , Sarcoma/patologia , Transdução de Sinais
8.
Stem Cells ; 32(4): 959-73, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24715690

RESUMO

Novel strategies against treatment-resistant tumor cells remain a challenging but promising therapeutic approach. Despite accumulated evidence suggesting the presence of highly malignant cell populations within tumors, the unsolved issues such as in vivo targeting and clinical relevance remain. Here, we report a preclinical trial based on the identified molecular mechanisms underlying osteosarcoma-initiating cells and their clinical relevance. We identified key microRNAs (miRNAs) that were deregulated in a highly malignant CD133(high) population and found that miR-133a regulated the cell invasion that characterizes a lethal tumor phenotype. Silencing of miR-133a with locked nucleic acid (LNA) reduced cell invasion of this cell population, and systemic administration of LNA along with chemotherapy suppressed lung metastasis and prolonged the survival of osteosarcoma-bearing mice. Furthermore, in a clinical study, high expression levels of CD133 and miR-133a were significantly correlated with poor prognosis, whereas high expression levels of the four miR-133a target genes were correlated with good prognosis. Overall, silencing of miR-133a with concurrent chemotherapy would represent a novel strategy that targets multiple regulatory pathways associated with metastasis of the malignant cell population within osteosarcoma.


Assuntos
Neoplasias Ósseas , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs/biossíntese , Osteossarcoma , RNA Neoplásico/biossíntese , Antígeno AC133 , Adulto , Animais , Antígenos CD/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Masculino , Camundongos , Camundongos Nus , Camundongos SCID , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Osteossarcoma/terapia , Peptídeos/metabolismo , Taxa de Sobrevida
9.
Skeletal Radiol ; 44(1): 55-62, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25172220

RESUMO

OBJECTIVE: Myxofibrosarcoma (MFS) is characterized by a high frequency of local recurrence after surgery because of infiltrative growth of the tumor cells. This infiltrative growth creates a characteristic 'tail-like' pattern on magnetic resonance imaging (MRI), and it has been reported that this pattern is especially obvious on gadolinium-enhanced MRI (Gd MRI). However, the relationship between the tail-like pattern seen on Gd MRI and clinicopathological features of MFS is still not clear. In this study, we performed a retrospective analysis to identify clinicopathological factors related to the tail-like pattern of the MRI findings in patients with MFS. MATERIALS AND METHODS: We retrospectively analyzed 50 patients with MFS to identify factors related to the tail-like pattern. RESULTS: On Gd MRI, 32 of the 50 patients presented the tail-like pattern, whereas 18 presented a solid pattern. The clincopathological factors related to the tail-like pattern were evaluated by chi-squared test. A superficial origin (p = 0.0009) was most significantly related to the tail-like pattern. The 5-year recurrence-free survival (RFS) rate was 75.6 % for patients showing the tail-like pattern and 90.9 % for those showing the solid pattern. The corresponding 5-year disease-free survival (DFS) rates were 64.7 and 79.3 %, respectively. Thus in terms of both 5-year RFS and DFS, patients with the tail-like pattern tended to have a poorer outcome. CONCLUSION: A superficial origin of MFS is significantly related to a tail-like pattern on Gd MRI. The tail-like pattern is associated with poorer prognosis. Further studies of tumor depth and the tail-like pattern on Gd MRI are needed.


Assuntos
Fibroma/diagnóstico , Fibrossarcoma/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias de Tecidos Moles/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Diagnóstico Diferencial , Feminino , Gadolínio , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
10.
Pediatr Int ; 57(5): 996-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26508182

RESUMO

Myositis ossificans (MO) is a rare benign cause of heterotopic bone formation in soft tissue that most commonly affects young adults, typically following trauma. We report the case of an 11-year-old girl who developed MO mimicking osteosarcoma in her right shoulder. Plain radiography and computed tomography showed poorly defined flocculated densities in the soft tissue and a periosteal reaction along the proximal humerus. On magnetic resonance imaging, the mass displayed an ill-defined margin and inhomogeneous signal change. Histologically, the mass had a pseudosarcomatous appearance. Based on these findings, the patient was initially misdiagnosed with osteosarcoma at another hospital. The diagnosis was difficult because the patient was 11 years old and had no trauma history, with atypical radiographic changes and a predilection for the site of origin for osteosarcomas. We finally made the correct diagnosis of MO by carefully reviewing and reflecting on the pathological differences between stages.


Assuntos
Neoplasias Ósseas/diagnóstico , Erros de Diagnóstico , Miosite Ossificante/diagnóstico , Osteossarcoma/diagnóstico , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
11.
Nihon Shokakibyo Gakkai Zasshi ; 112(3): 500-7, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-25759224

RESUMO

A 58-year-old woman completely edentulous man was transported to our hospital by ambulance with complaints of abdominal pain and vomiting. Abdominal computed tomography revealed multiple objects in the dilated ileum. An emergency laparotomy was performed and a diagnosis of ileus caused by ingestion of lotus root was established. We advised the patient to obtain and wear dentures. However, she did not comply and continued to swallow food without chewing. After 11 months, she was readmitted with the same symptoms. A second emergency laparotomy also revealed food-induced ileus. No recurrence of food-induced ileus has occurred after the patient agreed to wearing dentures. When encountering patients presenting with ileus, the patient's diet and eating habits should be verified, and the condition of the teeth at the time of diagnosis should be evaluated. Encouragement of patients to improve eating habits, along with adequate dental care, sufficiently prevents food-induced ileus.


Assuntos
Alimentos/efeitos adversos , Íleus/cirurgia , Feminino , Humanos , Íleus/diagnóstico por imagem , Íleus/etiologia , Laparotomia , Lotus/efeitos adversos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
12.
J Proteome Res ; 13(5): 2250-61, 2014 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-24621013

RESUMO

Alveolar soft part sarcoma (ASPS) is an exceedingly rare sarcoma refractory to standard chemotherapy. Although several molecular targeting drugs have been applied for ASPS, their clinical significance has not yet been established, and novel therapeutic strategies have long been required. The aim of this study was to identify proteins aberrantly regulated in ASPS and to clarify their clinical significance. Protein expression profiling of tumor and nontumor tissues from 12 ASPS patients was performed by 2-D difference gel electrophoresis and mass spectrometry. We found that the expression of 145 proteins differed significantly. Among them, further investigation was focused on the SET protein, which has multifunctional roles in cancers. Immunohistochemistry confirmed overexpression of SET in all 15 ASPS cases examined. Gene silencing of SET significantly decreased cell proliferation, invasion, and migration against a background of induced apoptosis. SET is known to be an inhibitor of phosphatase 2A (PP2A), which functions as a tumor suppressor by inhibiting the signal transduction pathway and inducing apoptosis. We found that a PP2A activator, FTY720, decreased cell proliferation through apoptosis. Together, our findings may suggest the possible contribution of SET to the tumor progression and the utility of FTY720 for treatment of ASPS.


Assuntos
Chaperonas de Histonas/metabolismo , Proteína Fosfatase 2/metabolismo , Proteômica/métodos , Sarcoma Alveolar de Partes Moles/metabolismo , Fatores de Transcrição/metabolismo , Adolescente , Adulto , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA , Eletroforese em Gel Bidimensional , Ativadores de Enzimas/farmacologia , Feminino , Cloridrato de Fingolimode , Chaperonas de Histonas/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Propilenoglicóis/farmacologia , Proteoma/metabolismo , Interferência de RNA , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Fatores de Transcrição/genética , Adulto Jovem
13.
J Proteome Res ; 13(11): 4847-58, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-24967658

RESUMO

This study used global protein expression profiling to search for biomarkers to predict early recurrent hepatocellular carcinoma (HCC). HCC tissues surgically resected from patients with or without recurrence within 2 years (early recurrent) after surgery were compared with adjacent nontumor tissue and with normal liver tissue. We used the PROTOMAP strategy for comparative profiling, which integrates denaturing polyacrylamide gel electrophoresis migratory rates and high-resolution, semiquantitative mass-spectrometry-based identification of in-gel-digested tryptic peptides. PROTOMAP allows examination of global changes in the size, topography, and abundance of proteins in complex tissue samples. This approach identified 8438 unique proteins from 45 708 nonredundant peptides and generated a proteome-wide map of changes in expression and proteolytic events potentially induced by intrinsic apoptotic/necrotic pathways. In the early recurrent HCC tissue, 87 proteins were differentially expressed (≥20-fold) relative to the other tissues, 46 of which were up-regulated or specifically proteolyzed and 41 of which were down-regulated. This data set consisted of proteins that fell into various functional categories, including signal transduction and cell organization and, notably, the major catalytic pathways responsible for liver function, such as the urea cycle and detoxification metabolism. We found that aberrant proteolysis appeared to occur frequently during recurrence of HCC in several key signal transducers, including STAT1 and δ-catenin. Further investigation of these proteins will facilitate the development of novel clinical applications.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/diagnóstico , Proteínas/análise , Proteômica/métodos , Biomarcadores Tumorais/metabolismo , Eletroforese em Gel de Gradiente Desnaturante , Eletroforese em Gel de Poliacrilamida , Humanos , Neoplasias Hepáticas/genética , Espectrometria de Massas/métodos , Redes e Vias Metabólicas/genética , Transdução de Sinais/genética
14.
J Hand Microsurg ; 16(2): 100026, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38855517

RESUMO

The transposition of an adjacent finger following the loss of a finger due to a malignant tumor resection improves hand function. However, patients may not accept the resulting appearance of a three-finger hand. A 28-year-old male with a malignant fibroblastic tumor at the base of the ring finger underwent resection of the tumor, excising the phalanx and a portion of the metacarpal. He refused a ray amputation and subsequent fifth-finger transposition. Therefore, we reconstructed the defect with a long-vascularized subtotal second toe from the metacarpal neck to the middle phalanx base of the fourth finger. There was no tumor recurrence, and the patient was highly satisfied with hand function and cosmetic appearance at 3 years of follow-up.

15.
Sci Rep ; 14(1): 768, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191907

RESUMO

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.


Assuntos
Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/genética , Prognóstico , Receptores Proteína Tirosina Quinases , Proto-Oncogenes , Proteínas Proto-Oncogênicas c-kit
16.
Proteomics ; 13(15): 2351-60, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23712969

RESUMO

Chemoresistance is one of the most critical prognostic factors in osteosarcoma, and elucidation of the molecular backgrounds of chemoresistance may lead to better clinical outcomes. Spheroid cells resemble in vivo cells and are considered an in vitro model for the drug discovery. We found that spheroid cells displayed more chemoresistance than conventional monolayer cells across 11 osteosarcoma cell lines. To investigate the molecular mechanisms underlying the resistance to chemotherapy, we examined the proteomic differences between the monolayer and spheroid cells by 2D-DIGE. Of the 4762 protein species observed, we further investigated 435 species with annotated mass spectra in the public proteome database, Genome Medicine Database of Japan Proteomics. Among the 435 protein species, we found that 17 species exhibited expression level differences when the cells formed spheroids in more than five cell lines and four species out of these 17 were associated with spheroid-formation associated resistance to doxorubicin. We confirmed the upregulation of cathepsin D in spheroid cells by western blotting. Cathepsin D has been implicated in chemoresistance of various malignancies but has not previously been implemented in osteosarcoma. Our study suggested that the spheroid system may be a useful tool to reveal the molecular backgrounds of chemoresistance in osteosarcoma.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Proteoma/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Eletroforese em Gel Bidimensional , Humanos , Osteossarcoma/patologia , Proteoma/análise , Proteômica , Esferoides Celulares
17.
Electrophoresis ; 34(11): 1670-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23483572

RESUMO

Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/metabolismo , Proteínas Nucleares , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Prognóstico , Ligação Proteica , Mapas de Interação de Proteínas , Interferência de RNA , RNA Interferente Pequeno/genética , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia
18.
Jpn J Clin Oncol ; 43(11): 1093-104, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23969617

RESUMO

OBJECTIVE: Myxofibrosarcoma is clinically characterized by a high frequency of local recurrence after surgery. To improve the clinical outcome of patients with myxofibrosarcoma, it is imperative to control any postsurgical local recurrence. METHODS: In this study, we performed a retrospective clinicopathologic analysis of 100 consecutive patients with myxofibrosarcoma to identify factors related to poor prognosis. All of the patients had been diagnosed, and had undergone surgery at the National Cancer Center Hospital between 1999 and 2008. RESULTS: At the initial visit to our hospital, 64 patients had primary myxofibrosarcoma, whereas 36 had undergone primary unplanned resection at other facilities. Of the 36 patients, 11 consulted our hospital before recurrence and 25 did so after recurrence. A histologically positive margin after surgery was evident in 28% of the cases overall. The estimated 5-year recurrence-free survival rate was 74.8%. Univariate analysis showed that primary unplanned resection at another facility (P = 0.0001) and a histologically positive margin (P = 0.0224) were significant predictors of local recurrence. When these two factors were subjected to multivariate analysis, only primary unplanned resection at another facility was significantly correlated with the estimated recurrence-free survival rate (P = 0.0011). Primary unplanned resection was also significantly related to the 5-year disease-free survival rate (P = 0.0401). CONCLUSIONS: Our findings indicate that primary unplanned resection at a non-referral hospital is the most important risk factor related to poor prognosis of myxofibrosarcoma. Accurate diagnosis and adequate initial surgery are most important factors for improving the clinical outcomes of myxofibrosarcoma.


Assuntos
Fibroma/prevenção & controle , Fibroma/cirurgia , Fibrossarcoma/prevenção & controle , Fibrossarcoma/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Prevenção Secundária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Intervalo Livre de Doença , Análise Fatorial , Feminino , Fibroma/patologia , Fibrossarcoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/normas
19.
Jpn J Clin Oncol ; 43(6): 669-75, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23619989

RESUMO

OBJECTIVE: Adjuvant treatment with imatinib mesylate is an effective treatment for gastrointestinal stromal tumor. However, 50% of patients with gastrointestinal stromal tumor can be cured by surgery alone; hence, risk stratification for therapy with imatinib mesylate is the next challenge. Previously, using a proteomic approach, we discovered a potential prognostic biomarker for gastrointestinal stromal tumor, pfetin, and immunohistochemically validated its clinical utility using our original monoclonal antibody. In the present study, we examine the usefulness of a commercially available polyclonal antibody against pfetin. METHODS: Western blotting and immunohistochemistry were performed using surgical specimens of primary tissues from gastrointestinal stromal tumor patients using a polyclonal antibody against pfetin and our original monoclonal antibody. Formalin-fixed and paraffin-embedded primary tissue sections from 112 gastrointestinal stromal tumor patients were subjected to immunohistochemistry. The immunohistochemistry results were integrated with the clinico-pathological observations. RESULTS: Western blotting revealed that both antibodies recognized multiple post-translationally modified pfetin isoforms. The immunohistochemical study with the commercial antibody demonstrated that the disease-free survival rate was 88 and 56% for pfetin-positive and pfetin-negative patients, respectively. Univariate and multivariate analyses showed that pfetin expression as measured by the commercial antibody was a significant and independent prognostic factor among the clinico-pathological parameters examined. Of the 112 gastrointestinal stromal tumor cases examined, 13 yielded discordant results between the commercial antibody and our original antibody, and there were no significantly different clinical or pathological factors to account for this discrepancy. CONCLUSIONS: Our observations suggest that the pfetin expression level assessed by the commercial antibody could be a prognostic biomarker in gastrointestinal stromal tumors.


Assuntos
Anticorpos , Biomarcadores Tumorais/análise , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/mortalidade , Proteínas/análise , Proteínas/imunologia , Idoso , Western Blotting , Eletroforese em Gel de Poliacrilamida , Feminino , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida
20.
Radiol Case Rep ; 18(2): 499-502, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36439922

RESUMO

Case: We report a case of quadratus lumborum muscle strain that occurred in a 16-year-old soccer player during a game. According to a video recording of the game, the injury occurred when the leg landed just after kicking the ball with the same leg while dribbling. The mechanism was suspected to be right lateral flexion of the trunk while the pelvis was simultaneously forced to tilt backward. The injury healed and he was able to return to competition 3 weeks later.Conclusion: This is the first report of a sports-related quadratus lumborum muscle strain.

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