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1.
Mater Sci Eng C Mater Biol Appl ; 97: 431-437, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678929

RESUMO

We investigate the mechanical properties and structure of silk resins as potential alternatives to tortoiseshell for producing eyeglass frames and various ornaments. Silk powders are obtained from Bombyx mori and Eri silk waste fibers before the degumming process. The powders are fabricated into resins via simple hot pressing under a pressure of 31.2 MPa at temperatures in the range 150-180 °C. The results indicate that the B. mori resins have higher micro-Vickers hardness, three-point bending strength, and elastic modulus (66 Hv, 122 MPa, and 8.7 GPa, respectively) compared to the Eri silk resins (58 Hv, 95 MPa, and 8.2 GPa, respectively). The better mechanical properties of the fibroin resins are related directly to longer drying times. The optimum drying conditions are found to be at a temperature of 100 °C under a-vacuum of -0.1 MPa for a time of 7 d. ATR-FTIR and XRD results show how the fibroin structure changes after resinification and drying. The morphology and the distribution size of particle of the silk powders and the fractured surfaces of the resins are analyzed from SEM micrographs. The present findings demonstrate that silk resins are suitable materials for developing useful applications because of their favorable mechanical properties.


Assuntos
Bombyx/metabolismo , Lepidópteros/metabolismo , Seda/química , Aminoácidos/análise , Animais , Módulo de Elasticidade , Temperatura Alta , Pressão , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Difração de Raios X
2.
Transplant Proc ; 49(1): 175-177, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28104130

RESUMO

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) co-infections progress rapidly and lead to cirrhosis. In Japan, the prevalence of HBV and HDV co-infected patients is low. Therefore, there are few reports of patients with HBV and HDV co-infection having undergone liver transplantation. Herein, we report a rare case of recurrence of HBV and HDV in a 41-year-old man who underwent living donor liver transplantation 4 years prior.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/prevenção & controle , Hepatite D Crônica , Imunoglobulinas/uso terapêutico , Transplante de Fígado , Complicações Pós-Operatórias/prevenção & controle , Adulto , Coinfecção , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B , Vírus Delta da Hepatite , Humanos , Japão , Cirrose Hepática/cirurgia , Masculino , Prevalência , RNA Viral/sangue , Recidiva , Ativação Viral
3.
J Oral Rehabil ; 43(11): 847-854, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27611827

RESUMO

Wearing dentures and dysphagia are common in older individuals; however, it is still unknown how dentures affect oral and pharyngeal swallowing. The purpose of this study was to reveal the effects of wearing and removing dentures on oropharyngeal movements during pharyngeal swallowing in the feeding sequence of solid food. Participants were 25 edentulous volunteers (nine men, 16 women; mean age 76·2 years) who wore complete dentures. The test food was minced agar jelly containing barium sulphate. Subjects were instructed to feed and swallow the test food with or without dentures during observation using videofluorography. We quantitatively evaluated the range, distance and duration of oropharyngeal movements during pharyngeal swallowing. When dentures were absent, the range of mandible and hyoid movements were significantly expanded in the anterosuperior direction, and the range of laryngeal movement was significantly expanded in the anterior direction. Additionally, the posterior pharyngeal wall contraction and upper oesophageal sphincter opening significantly increased. In addition, the distances of the mandible, hyoid and laryngeal movements and the mandibular duration were significantly extended when dentures were absent. No significant differences were observed in the duration of movements of other organs between wearing and removing dentures. The hyoid bone, larynx, posterior pharyngeal wall and upper oesophageal sphincter do not change their duration of movements when dentures were removed but, rather, expand their range of movement. This might be a spatial change of oropharyngeal movement to avoid temporal changes in pharyngeal swallowing when dentures were absent in edentulous older individuals.


Assuntos
Transtornos de Deglutição/fisiopatologia , Deglutição/fisiologia , Prótese Total/efeitos adversos , Mastigação/fisiologia , Boca Edêntula/fisiopatologia , Orofaringe/fisiopatologia , Idoso , Feminino , Humanos , Osso Hioide , Masculino , Qualidade de Vida , Reprodutibilidade dos Testes
4.
Cell Death Dis ; 7: e2207, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27124581

RESUMO

In this study, we identify signaling network of necrotic cell death induced by transcriptional repression (TRIAD) by α-amanitin (AMA), the selective RNA polymerase II inhibitor, as a model of neurodegenerative cell death. We performed genetic screen of a knockdown (KD) fly library by measuring the ratio of transformation from pupa to larva (PL ratio) under TRIAD, and selected the cell death-promoting genes. Systems biology analysis of the positive genes mapped on protein-protein interaction databases predicted the signaling network of TRIAD and the core pathway including heterogeneous nuclear ribonucleoproteins (hnRNPs) and huntingtin (Htt). RNA sequencing revealed that AMA impaired transcription and RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing molecule. The impairment in RNA splicing and PL ratio was rescued by overexpresion of hnRNP that had been also affected by transcriptional repression. Fly genetics with suppressor or expresser of Htt and hnRNP worsened or ameliorated the decreased PL ratio by AMA, respectively. Collectively, these results suggested involvement of RNA splicing and a regulatory role of the hnRNP-Htt axis in the process of the transcriptional repression-induced necrosis.


Assuntos
Apoptose , Proteínas de Drosophila/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteína Huntingtina/metabolismo , Amanitinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Drosophila/genética , Embrião de Mamíferos/citologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Proteína Huntingtina/antagonistas & inibidores , Proteína Huntingtina/genética , Larva/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Pupa/metabolismo , Splicing de RNA/efeitos dos fármacos , Ratos , Ratos Wistar , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Proteínas Contendo Repetições de beta-Transducina/genética , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Quinase 1 Polo-Like
7.
J Oral Rehabil ; 40(12): 923-31, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24237359

RESUMO

Prosthetic treatment with dentures is often required for the elderly who have reduced swallowing function. Therefore, it is important to understand the relationship between denture-wearing and feeding function from the perspective of swallowing. To clarify changes in bolus transport during feeding in elderly edentulous patients with or without complete dentures. Subjects were 15 elderly edentulous volunteers who were treated with maxillary and mandibular complete dentures. The test food was 10 g of minced agar jelly containing barium sulphate with a particle diameter of 4·0-5·6 mm. Lateral videofluoroscopy was performed to assess the position of the leading edge of the bolus, the bolus volume in each area at swallow onset, bolus transit time and the mandibular position during pharyngeal swallowing. There were significant changes between the bolus transport with and without dentures. Without dentures, the leading edge of the bolus at swallow onset fell from the valleculae area to the hypopharynx, and the bolus volume in the hypopharynx increased. Bolus transit time increased in the oral cavity, valleculae and hypopharynx. The mandibular position shifted anterosuperior direction. The results arose owing to anatomical changes in the oral and pharyngeal structure and the following functional changes: poor food manipulation, poor bolus formation and delayed swallowing reflex. Removing dentures in elderly edentulous individuals influences bolus transport during feeding, resulting in the exacerbation of the reduced swallowing reserve capacity that accompanies ageing, and may increase the risk of dysphagia.


Assuntos
Sulfato de Bário/administração & dosagem , Meios de Contraste/administração & dosagem , Transtornos de Deglutição/fisiopatologia , Deglutição , Mastigação , Boca Edêntula/fisiopatologia , Administração Oral , Idoso , Transtornos de Deglutição/diagnóstico por imagem , Prótese Total , Feminino , Fluoroscopia/métodos , Humanos , Masculino , Orofaringe/diagnóstico por imagem , Qualidade de Vida
8.
J Oral Rehabil ; 40(10): 751-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23927717

RESUMO

Palatal coverage is often required for elderly edentulous patients with complete dentures. The purpose of this study was to clarify impacts of palatal coverage on bolus formation and subsequent adaptive changes. Subjects were 18 healthy young dentulous adults who wore 1·5-mm-thick palatal plates. Subjects were asked to feed 12 g of bicoloured rice as usual, and the bolus formation by mastication and swallowing in the pharynx was observed using a nasal videoendoscopy. The bolus formation index (BFI), number of mastication strokes until swallowing, visual analogue scale about swallowing easiness and masticatory performance using colour-changeable gum were measured under three conditions: before placement of the palatal plate (day 0), immediately after placement (day 1) and after 7 days of wearing the plate (day 7). BFI and visual analogue scale on day 1 were significantly lower than those on day 0, but those on day 7 significantly recovered to the level of day 0. The number of mastication strokes did not change from day 0 to day 1, however, that on day 7 was significantly higher. Masticatory performance on days 1 and 7 was significantly lower than that on day 0. Although palatal coverage inhibits bolus formation during feeding, subjects increased the number of mastication strokes until swallowing threshold as they adapted to palatal coverage over time. This adaptive change was due to compensate for the lowered masticatory performance to achieve bolus formation for comfortable swallowing.


Assuntos
Deglutição/fisiologia , Prótese Dentária/efeitos adversos , Mastigação/fisiologia , Palato , Adulto , Cor , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Oryza , Faringe/fisiologia , Gravação em Vídeo
9.
Dent Mater ; 29(5): 530-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23477950

RESUMO

OBJECTIVE: A theoretical model, based on fluid dynamics, was developed to measure impression pressure. The purpose of this study was to evaluate the validity of this theoretical model by comparing its theoretical analysis against actual pressure measurements conducted using an impression tray and edentulous oral mucosa analog embedded with pressure sensors. METHODS: In the theoretical model, a hollow tube was mounted onto an impression tray by penetrating through the tray. When force was applied to the tray, pressure was produced which then caused the impression material to flow into the hollow tube. Length of impression material which flowed into tube was denoted as l. In the calculation formula for theoretical model, pressure impulse I was expressed as a function of impression flow length l. For actual pressure measurements, four electric pressure sensors were embedded in an experimental edentulous arch. To visually observe and measure length of impression material flow, four transparent silicon tubes were mounted vertically at different positions on tray. During tray seating, impression material flowed into tubes and pressure which caused material flow movement was measured by the embedded sensor at each tube's position. RESULTS: Based on actual pressure measurements under one experimental condition, regression analysis of pressure data acquired from electric sensors yielded the formula, Y=0.056X²+0.124X. Based on theoretical analysis using a particular viscosity value, the numerical formula yielded was Y=0.057X², which resembled that of the regression formula. SIGNIFICANCE: Theoretical model presented in this paper augured well for clinical application as an easy and economical means to examine magnitude and distribution of impression pressure by measuring lengths of impression material flow in tubes fixed to impression tray.


Assuntos
Materiais para Moldagem Odontológica/química , Técnica de Moldagem Odontológica/instrumentação , Prótese Total , Modelos Dentários , Modelos Teóricos , Pressão , Análise de Regressão , Viscosidade
11.
J Oral Rehabil ; 39(4): 277-84, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21999810

RESUMO

Dysphagia rehabilitation in the elderly includes direct therapy to alter the three-dimensional shape of the oropharynx so that food boluses can pass safely through the poorly functioning pharynx. Alteration of the mandibular position is thought to affect oropharyngeal shape, but this relationship remains poorly understood. We therefore studied the relationship between mandibular position and three-dimensional shape of the oropharynx in the seated posture normal for feeding. Ten healthy, dentate subjects participated (average age, 28·1 years). Experimental mandibular positions were the intercuspal position, bite-raised position and mandible-advanced position. The oropharynx was scanned in a 90° seated posture using dental cone-beam computed tomography, and the effects of changes in mandibular position were analysed after obtaining oropharyngeal volume, height, sectional area, average sectional area of oropharynx and the position of the epiglottis. Oropharyngeal volume and average sectional area increased significantly in the mandible-advanced position compared with other mandibular positions. Notably, the volume and average sectional area of the inferior part of the oropharynx increased significantly. Oropharyngeal height and sectional area at the base of the epiglottis showed no significant difference in bite-raised position and mandible-advanced position compared with intercuspal position. The position of the epiglottis moved significantly forward in the mandible-advanced position. The results of this study show that in a seated posture, volume of the oropharynx increases as a result of changes in the mandible-advanced position. The increase in oropharyngeal volume demands greater muscular constriction to generate swallowing pressure and could lead to a decrease in reserve capacity of swallowing.


Assuntos
Deglutição/fisiologia , Epiglote/fisiologia , Mandíbula/fisiologia , Orofaringe/anatomia & histologia , Adulto , Tomografia Computadorizada de Feixe Cônico , Epiglote/diagnóstico por imagem , Feminino , Humanos , Imageamento Tridimensional , Masculino , Mandíbula/diagnóstico por imagem , Orofaringe/diagnóstico por imagem , Postura
12.
J Eur Acad Dermatol Venereol ; 25(4): 475-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20569287

RESUMO

BACKGROUND: Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is widely used for treating Bowen's disease (BD), but recurrence and tumour cell persistence after ALA-PDT is sometimes problematic. Radiation therapy (RT) is also effective for BD, but is limited by its side-effects, such as refractory ulcers. OBJECTIVE: The objective of the study was to observe a synergic effect of combination therapy with ALA-PDT and RT for BD cases that did not respond effectively to prior ALA-PDT. METHODS: Subjects were BD patients whose lesion did not show complete remission or showed recurrence after prior ALA-PDT. A total of four cases involving four lesions were studied (three male and one female, mean age 69.5). ALA ointment (20%) was applied to the lesions. After 4 to 6h, subjects received combination therapy consisting of excimer-pumped dye laser radiation at 630nm (50J/cm(2) ) followed by electron-beam radiation (3Gy). The combination therapy was repeated every 2 to 3days for a total of four treatments. The lesions were evaluated clinically or histologically after the final combination therapy session. RESULTS: Following combination therapy, all of the lesions disappeared. Recurrence was not detected during the observations periods, which averaged 14.0months in duration. CONCLUSION: Our results indicate that the cure rate of BD could be improved by combination therapy with ALA-PDT and RT. Compared with conventional RT, the synergetic effect of this therapy might reduce the dose of radiation required, thereby also reducing skin side-effects such as refractory ulcers.


Assuntos
Doença de Bowen/terapia , Fotoquimioterapia , Idoso , Idoso de 80 Anos ou mais , Doença de Bowen/tratamento farmacológico , Doença de Bowen/radioterapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Int J STD AIDS ; 21(3): 213-4, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20215631

RESUMO

Disseminated mucocutaneous herpes simplex virus (HSV) infection in an immunocompetent person is quite rare. A 19-year-old healthy Japanese woman presented with painful, umbilicated vesicles and pustules on her genital region, both nipples and on the forearm 10 days after the last sexual contact with her partner who had cold sore at that time. Tzanck test and biopsy confirmed the diagnosis of disseminated mucocutaneous HSV infection. She did not have any visceral HSV disease. Skin lesions improved after treatment with acyclovir and erythromycin for seven days. We propose that like herpes gladiatorum, HSV dissemination in this case was acquired by close body contact.


Assuntos
Herpes Genital/diagnóstico , Herpes Simples/diagnóstico , Herpesvirus Humano 1/isolamento & purificação , Imunocompetência , Feminino , Antebraço/patologia , Antebraço/virologia , Herpes Genital/patologia , Herpes Simples/patologia , Humanos , Imuno-Histoquímica , Pele/patologia , Pele/virologia , Adulto Jovem
14.
Int J STD AIDS ; 21(1): 66-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19884358

RESUMO

A 28-year-old Japanese man presented with grouped erosions and vesicles on an erythematous base affecting the right areola and the surrounding skin. A Tzanck smear from the vesicle revealed giant cells. An initial clinical diagnosis of mammary herpes simplex was considered but to explore the differential diagnosis, viral DNA was amplified by the loop-mediated isothermal amplification (LAMP) method. DNA replication was observed only in varicella zoster virus LAMP mixture, and this confirmed a diagnosis of herpes zoster. The patient was treated with 3000 mg of daily oral valacyclovir for seven days. After antiviral treatment, the lesion had healed and the pain had resolved completely.


Assuntos
Herpes Zoster/diagnóstico , Herpesvirus Humano 3/isolamento & purificação , Mamilos/virologia , Adulto , DNA Viral/análise , Diagnóstico Diferencial , Herpesvirus Humano 3/genética , Humanos , Masculino , Mamilos/patologia , Técnicas de Amplificação de Ácido Nucleico
15.
Photodermatol Photoimmunol Photomed ; 25(1): 37-40, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19152514

RESUMO

BACKGROUND/PURPOSE: Topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) is effective for actinic keratosis (AK); few studies have examined Oriental patients. The aim of this study is to assess the efficacy of PDT for the treatment of Japanese AK patients classified by lesion size and histological severity. METHODS: Thirty patients with solitary AK lesions were divided into two groups according to diameter: a small lesion group (SL), diameter < or =10 mm and a larger lesion group (LL), diameter >10 mm, and histological severity: Group I (mild and moderate) and Group II (severe). After application of 20% ALA for 4 h, exposure to an excimer-dye laser at 630 nm was performed at a dose of 50 J/cm(2) three times at an interval of 7 days. Therapeutic effects were assessed and followed for 12 months. RESULTS: In all 10 SL patients, atypical cells disappeared after PDT and did not recur for 12 months. However, for the 20 LL patients, recurrence was seen in 2 of the 14 Group I patients, while 4 of 6 Group II patients showed residual tumor cells after the first PDT session. CONCLUSION: The present study demonstrated that ALA-PDT might be useful for treatment of Japanese AK. The therapeutic outcome might depend on the lesion size and the histopathological severity.


Assuntos
Ceratose Actínica/tratamento farmacológico , Ceratose Actínica/patologia , Fotoquimioterapia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Feminino , Humanos , Ceratose Actínica/classificação , Masculino , Pessoa de Meia-Idade , Projetos Piloto
17.
Clin Exp Dermatol ; 34(3): 385-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19077103

RESUMO

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (5-ALA) is a noninvasive and effective treatment for superficial skin cancers. Etretinate, a derivate of vitamin A, with the chemical formula ethyl(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona-tetraenoate, has been reported to have antitumour effects and to regulate the proliferation and differentiation of skin cancers. OBJECTIVE: In order to develop more efficient PDT, we investigated whether etretinate enhanced the cytotoxic action of ALA-based PDT against human squamous cell carcinoma cell line, HSC-5. METHOD: The in vitro cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected by double-staining with fluorescent annexin V and propidium iodide. Intracellular protoporphyrin IX (PpIX) converted from exogenous ALA was measured by a fluorescence meter. RESULTS: HSC-5 cells pretreated with a nontoxic concentration of etretinate became more susceptible to the cytotoxic action of ALA-based PDT. Etretinate-pretreated cells underwent apoptosis in response to ALA-based PDT. Etretinate pretreatment resulted in enhanced accumulation of ALA-dependent intracellular PpIX. CONCLUSIONS: The results suggest that etretinate enhances the susceptibility of HSC-5 cells to ALA-based PDT via the intracellular increase of ALA-dependent PpIX. Etretinate might be useful for improvement of ALA-based PDT.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Etretinato/farmacologia , Ceratolíticos/farmacologia , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Sinergismo Farmacológico , Humanos , Fármacos Fotossensibilizantes/farmacologia , Protoporfirinas/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas
18.
Anim Genet ; 39(3): 301-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18410475

RESUMO

A large number of significant QTL for economically important traits including average daily gain have been located on SSC1q, which, as shown by chromosome painting, corresponds to four human chromosomes (HSA9, 14, 15 and 18). To provide a comprehensive comparative map for efficient selection of candidate genes, 81 and 34 genes localized on HSA9 and HSA14 respectively were mapped to SSC1q using a porcine 7000-rad radiation hybrid panel (IMpRH). This study, together with the cytogenetic map (http://www2.toulouse.inra.fr/lgc/pig/cyto/genmar/htm/1GM.HTM), demonstrates that SSC1q2.1-q2.13 corresponds to the region ranging from 44.6 to 63.2 Mb on HSA14q21.1-q23.1, the region from 86.5 to 86.8 Mb on HSA15q24-q25, the region from 0.9 to 27.2 Mb on HSA9p24.3-p21, the region from 35.1 to 38.0 Mb on HSA9p13, the region from 70.3 to 79.3 Mb on HSA9q13-q21 and the region from 96.4 to 140.0 Mb on HSA9q22.3-q34. The conserved synteny between HSA9 and SSC1q is interrupted by at least six sites, and the synteny between HSA14 and SSC1q is interrupted by at least one site.


Assuntos
Cromossomos de Mamíferos , Mapeamento de Híbridos Radioativos/veterinária , Sus scrofa/genética , Animais , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 9 , Humanos , Locos de Características Quantitativas , Sintenia
19.
Int J Gynecol Cancer ; 18(5): 996-1006, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18028379

RESUMO

In recent years, antibody therapy employing monoclonal antibodies has become a new approach for treating cancer. This study was performed to establish a human monoclonal antibody recognizing an epitope related to CA125 using KM mice and to assess its reactivity with ovarian cancer cells. A human ovarian clear cell adenocarcinoma cell line (RMG-I) was used to immunize KM mice, and hybridoma supernatant was obtained by a standard method employing enzyme-linked immunosorbent assay screening. Next, selection of hybridomas was performed with two antibodies (MA602-1 and MA602-6) and a sandwich immunoassay for CA125-like antigen, and then the limiting dilution was used to obtain a human monoclonal antibody. Immunohistochemical reactivity of this antibody (human monoclonal antibody for ovarian clear cell carcinoma-2 [HMOCC-2]) with ovarian cancer was assessed, while its specificity was analyzed by Western blotting. Various antibodies were used to identify the epitope targeted by HMOCC-2. Finally, the antitumor effect of HMOCC-2 was assessed by intraperitoneal administration to SCID (severe combined immunodeficiency) mice with heterografts of RMG-I tumors. HMOCC-2 showed a positive reaction with 60% (63/105) of ovarian cancer specimens. Western blotting of the membrane fraction of RMG-I revealed several bands at 120-250 kd. HMOCC-2 recognized the CA125-like antigens identified by several antibodies. HMOCC-2 also exhibited significant antitumor activity (P < 0.01) against ovarian cancer heterografts. HMOCC-2 reacts specifically with ovarian cancer cells via a target epitope analogous to that of CA125 and also exhibits activity against ovarian tumors. These findings suggest that it may have the potential to be employed clinically for molecular-targeting therapy.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Antígeno Ca-125/imunologia , Imunoterapia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
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