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1.
Oper Dent ; 48(5): 483-489, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37503684

RESUMO

Direct composite restorations are accepted as a treatment option for microdontia, which is a relatively prevalent condition that poses esthetic concerns. While free-hand composite placement is technique-sensitive and time-consuming, the resin composite injection technique is more straightforward and predictable. A fully digital workflow has been recently introduced, but the 3D-printed resin index is rigid and challenged by undercuts, as opposed to the silicone index. This case report presents a flexible 3D-printed resin index, which can accurately transfer the digitally simulated functional and esthetic form to the final restoration. In addition, a rigid stabilization holder was designed to stabilize the flexible index.


Assuntos
Resinas Compostas , Estética Dentária , Humanos , Fluxo de Trabalho , Resinas Compostas/uso terapêutico , Silicones , Impressão Tridimensional
2.
Leukemia ; 29(1): 207-17, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24787487

RESUMO

Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-α, transforming growth factor-ß (TGF-ß) and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF-ß signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Osteoporose/tratamento farmacológico , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Sequência de Bases , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Primers do DNA , Progressão da Doença , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Osteoblastos/citologia , Osteoporose/complicações , Osteoporose/patologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
3.
Leukemia ; 26(9): 2124-34, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22430632

RESUMO

Cancer stem cells have been proposed to be responsible for tumorigenesis and recurrence in various neoplastic diseases, including multiple myeloma (MM). We have previously reported that MM cells specifically express HLA class I at high levels and that single-chain Fv diabody against this molecule markedly induces MM cell death. Here we investigated the effect of a new diabody (C3B3) on cancer stem cell-like side population (SP) cells. SP fraction of MM cells highly expressed ABCG2 and exhibited resistance to chemotherapeutic agents; however, C3B3 induced cytotoxicity in both SP cells and main population (MP) cells to a similar extent. Moreover, C3B3 suppressed colony formation and tumorigenesis of SP cells in vitro and in vivo. Crosslinking of HLA class I by C3B3 mediated disruption of lipid rafts and actin aggregation, which led to inhibition of gene expression of ß-catenin and pluripotency-associated transcription factors such as Sox2, Oct3/4 and Nanog. Conversely, knockdown of Sox2 and Oct3/4 mRNA reduced the proportion of SP cells, suggesting that these factors are essential in maintenance of SP fraction in MM cells. Thus, our findings reveal that immunotherapeutic approach by engineered antibodies can overcome drug resistance, and provide a new basis for development of cancer stem cell-targeted therapy.


Assuntos
Antígenos HLA/imunologia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células da Side Population/metabolismo , Anticorpos de Cadeia Única/uso terapêutico , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos/uso terapêutico , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Camundongos , Camundongos SCID , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/imunologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células da Side Population/imunologia , Células da Side Population/patologia , Anticorpos de Cadeia Única/imunologia , beta Catenina/metabolismo
4.
Leukemia ; 25(7): 1182-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21475253

RESUMO

Bone marrow stromal cells (BMSCs) and osteoclasts (OCs) confer multiple myeloma (MM) cell survival through elaborating factors. We demonstrate herein that IL-6 and TNF family cytokines, TNFα, BAFF and APRIL, but not IGF-1 cooperatively enhance the expression of the serine/threonine kinase Pim-2 in MM cells. BMSCs and OCs upregulate Pim-2 expression in MM cells largely via the IL-6/STAT3 and NF-κB pathway, respectively. Pim-2 short interfering RNA reduces MM cell viability in cocultures with BMSCs or OCs. Thus, upregulation of Pim-2 appears to be a novel anti-apoptotic mechanism for MM cell survival. Interestingly, the mammalian target of rapamycin inhibitor rapamycin further suppresses the MM cell viability in combination with the Pim-2 silencing. The Pim inhibitor (Z)-5-(4-propoxybenzylidene) thiazolidine-2, 4-dione and the PI3K inhibitor LY294002 cooperatively enhance MM cell death. The Pim inhibitor suppresses 4E-BP1 phosphorylation along with the reduction of Mcl-1 and c-Myc. Pim-2 may therefore become a new target for MM treatment.


Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Apoptose/fisiologia , Mieloma Múltiplo/enzimologia , Proteínas de Neoplasias/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ciclo Celular , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Cromonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Morfolinas/farmacologia , Mieloma Múltiplo/patologia , Proteína de Sequência 1 de Leucemia de Células Mieloides , NF-kappa B/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Osteoclastos/efeitos dos fármacos , Osteoclastos/enzimologia , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sirolimo/farmacologia , Células Estromais/efeitos dos fármacos , Células Estromais/enzimologia , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo
5.
Xenobiotica ; 38(7-8): 1107-18, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18668441

RESUMO

1. Multidrug and toxic compound extrusion (MATE)-type transporters, which were first identified as a bacterial drug transporter family, are present in almost all prokaryotes and eukaryotes, and are thus one of the mostly conserved transporter families in nature. 2. Recently, a mammalian MATE transporter was shown to be a long hypothesized electroneutral H(+)/organic cation exporter that is responsible for the excretion of metabolic waste products and xenobiotics at renal brush border membranes and bile canaliculi. Plant MATE-type transporters are involved in the detoxification of metals and secondary metabolites such as phenols through their vesicular storage or extrusion at the plasma membrane. 3. Thus, MATE transporters are involved in one of the basic mechanisms that maintain homeostasis through the excretion of metabolic waste products and xenobiotics in nature.


Assuntos
Antiporters/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Xenobióticos/metabolismo , Animais , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Canalículos Biliares/metabolismo , Transporte Biológico/fisiologia , Resistência a Múltiplos Medicamentos/fisiologia , Humanos , Metais/metabolismo , Microvilosidades/metabolismo , Fenóis/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo
7.
Biochem Pharmacol ; 62(3): 363-7, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11434910

RESUMO

The inhibitory effects of quinolone antimicrobial agents and nonsteroidal anti-inflammatory drugs on purified mouse liver mitochondrial medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation were examined, using hexanoic acid as a substrate. Enoxacin, ofloxacin, nalidixic acid, diflunisal, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid, which do not act as substrates, were potent inhibitors. Diflunisal, nalidixic acid, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid inhibited competitively this medium chain acyl-CoA synthetase with K(i) values of 0.6, 12.4, 19.6, 13.4, and 15.0 microM, respectively. Enoxacin and ofloxacin inhibited this medium chain acyl-CoA synthetase in a mixed-type manner with K(i) values of 23.7 and 38.2 microM, respectively. Felbinac, which is a substrate, inhibited the activity of this medium chain acyl-CoA synthetase for hexanoic acid (IC50 = 25 microM). The concomitant presence of enoxacin and felbinac strongly inhibited this medium chain acyl-CoA synthetase. These findings indicate that medium chain acyl-CoA synthetases may be influenced by quinolone antimicrobial and nonsteroidal anti-inflammatory drugs.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Coenzima A Ligases/antagonistas & inibidores , 4-Quinolonas , Animais , Coenzima A Ligases/metabolismo , Técnicas In Vitro , Cinética , Camundongos , Mitocôndrias Hepáticas/enzimologia
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