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1.
Life Sci ; 241: 117143, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31811855

RESUMO

AIM: To investigate the effect of propofol on the migration and invasion of oral squamous cell carcinoma (OSCC) cells and explore the underlying mechanism. MAIN METHODS: Cal-27 and SCC-25 cells treated with or without propofol, then the cells metastasis were determined. The levels of SNAI1 mRNA and protein were detected by real-time PCR and western blot. Cell migration ability was evaluated by wound healing assay, and the invasion of cells was measured using transwell assay. KEY FINDINGS: Propofol treatment significantly promoted cell migration and invasion of OSCC. Further mechanistic studies of the stimulating effects of propofol on OSCC cell metastasis revealed that propofol treatment dose-dependently upregulated the expression of SNAI1, a member of the Snail superfamily of zinc-finger transcription factors. Additionally, the inhibition of endogenous SNAI1 expression reversed the effect of propofol on cell migration and invasion in Cal-27 and SCC-25 cells. SIGNIFICANCE: Our results demonstrate that propofol at clinically relevant concentrations facilitates cell migration and invasion through up-regulation of SNAI1 in OSCC cells, and suggest propofol may not be suitable for anesthesia management in OSCC patients.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Neoplasias Bucais/patologia , Propofol/farmacologia , Fatores de Transcrição da Família Snail/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Invasividade Neoplásica , Fatores de Transcrição da Família Snail/genética , Células Tumorais Cultivadas
2.
J Oncol Pharm Pract ; 26(1): 240-243, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042137

RESUMO

Recurrent or metastatic disease occurs in two-thirds of head and neck squamous cell carcinomas and it is associated with poor prognosis. Systemic treatment with platinum-based chemotherapy in combination with the epidermal growth factor receptor-targeting monoclonal antibody cetuximab represents a preferred option for these patients. Upon the achievement of tumor response by combined treatment, maintenance with single-agent cetuximab is usually administered with the aim of prolonging disease control at the price of reasonable toxicity. Although rarely, however, cetuximab needs to be discontinued in the absence of disease progression because of intolerable side effects. Here we describe the case of a 66-year-old man with a metastatic cancer of oral cavity, who had to discontinue maintenance cetuximab and who achieved prolonged disease control with metronomic capecitabine. We suggest that capecitabine could be an effective and safe maintenance option in case of cetuximab intolerance.


Assuntos
Capecitabina/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cetuximab/efeitos adversos , Cetuximab/uso terapêutico , Humanos , Masculino , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
Anticancer Res ; 39(12): 6479-6488, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810912

RESUMO

BACKGROUND/AIM: 4H-1-Benzopyran-4-one (chromone), present in various flavonoids as a backbone structure, has been used for the synthesis of anticancer drugs. The study aimed at investigating the cytotoxicity of eight 2-arylazolylchromones and twelve 2-triazolylchromones against four human oral squamous cell carcinoma (OSCC) cell lines and three human normal mesenchymal oral cells, and then performed a quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The distribution of cells to various phases of cell cycle was determined by cell cycle analysis. A total of 3,218 physicochemical, structural and quantum chemical features were calculated for QSAR analysis from the most stabilized structure optimized using CORINA. RESULTS: 2-[4-(4-fluorophenyl)-1H-imidazol-1-yl]-4H-1-benzopyran-4-one [6] had the highest tumor-specificity (TS), comparable with that of 5-flurouracil (5-FU) and doxorubicin, inducing cytostatic growth inhibition, accumulation of G2+M phase cells with no cells in the G1 phase. All eight 2-triazolylchromones showed much lower tumor-specificity, confirming our previous finding. Tumor-specificity was also correlated with 3D shape, topological shape, size, ionization potential, and the presence of more than two aromatic rings in the molecule and imidazole ring in the nitrogen-containing heterocyclic ring. CONCLUSION: [6] can be a lead compound for designing anticancer drugs.


Assuntos
Antineoplásicos/síntese química , Carcinoma de Células Escamosas/tratamento farmacológico , Cromonas/síntese química , Neoplasias Bucais/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/química , Cromonas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Quantitativa Estrutura-Atividade , Teoria Quântica
4.
Anticancer Res ; 39(12): 6489-6498, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810913

RESUMO

BACKGROUND/AIM: Studies of biological activity of 2-styrylchromone derivatives focusing on antioxidant, anti-inflammatory, antiviral and antitumor activity are limited. In this study, eighteen synthetic 2-styrylchromone derivatives were investigated for their cytotoxicity against human malignant and non-malignant cells, and then subjected to quantitative structure-activity relationship (QSAR) analysis. MATERIALS AND METHODS: Tumor-specificity was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against four normal oral cells to that against oral squamous cell carcinoma cell lines. Induction of apoptosis and growth arrest were evaluated by cell-cycle analysis. For QSAR analysis, 3,117 types of physicochemical, structural, and quantum chemical features were calculated from the most stabilized structure of 2-styrylchromone derivatives. RESULTS: Two 2-styrylchromone derivatives in which a methoxy group was introduced at the 4-position of the benzene ring showed tumor-specificity equivalent to or higher than doxorubicin in TS value. These compounds accumulated the subG1 and G2/M phase cells, suggesting the induction of apoptosis. Their tumor-specificity can be explained mainly by molecular shape and electronic state. CONCLUSION: These findings suggest the applicability of 2-styrylchromone to develop safe and effective anticancer agents as seed compounds.


Assuntos
Antineoplásicos/síntese química , Carcinoma de Células Escamosas/tratamento farmacológico , Cromonas/síntese química , Neoplasias Bucais/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/química , Cromonas/farmacologia , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Quantitativa Estrutura-Atividade
5.
Anticancer Res ; 39(12): 6673-6684, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810932

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the antitumor potential and combination effects of chemotherapeutic drugs. MATERIALS AND METHODS: The cytotoxicity of 20 drip-type classical and molecular-targeted anticancer drugs was examined against 4 human oral squamous cell carcinoma cell lines and 5 human oral normal mesenchymal and epithelial cells. Cell cycle progression was monitored by a cell sorter. Combination effect was evaluated by combination index. RESULTS: Most of the classical anticancer drugs showed much higher antitumor activity than molecular-targeted drugs, except bortezomib. Among 12 classical anticancer drugs, taxanes and gemsitabine showed the highest tumor-specificity (TS) and potency-selectivity expression (PSE) values, whereas platinum analogs showed the least TS value. Combination of two classical or a classical and a molecular-targeted drug showed mostly additive or antagonistic effect. 5-FU and cisplatin did not produce a subG1 population, but induced G2/M or G1/S arrest, regardless of the addition of cetuximab. Cetuximab, nibolumab and bortezomib showed potent keratinocyte toxicity. CONCLUSION: The present TS monitoring system may provide useful information for building up the treatment regimens of anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias Bucais/tratamento farmacológico , Bortezomib/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cetuximab/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Fluoruracila/farmacologia , Hormese , Humanos , Técnicas In Vitro , Queratinócitos/efeitos dos fármacos , Mucosa Bucal/citologia , Nivolumabe/farmacologia , Compostos de Platina/farmacologia , Taxoides/farmacologia
6.
Medicine (Baltimore) ; 98(51): e18210, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860968

RESUMO

BACKGROUND: Cisplatin is often used for the treatment of oral cancer (OC). However, there are inconsistent results. Thus, this study plans to systematically assess the clinical efficacy and safety of cisplatin for adult patients with OC. METHODS: We will search for PUBMED, EMBASE, Cochrane Library, AMED, Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All of them will be searched from the construction of each database up to the present with no restrictions of language and publication status. The data analysis will be conducted using RevMan 5.3 software to assess the efficacy and safety of cisplatin for adult patients with OC. RESULTS: This study will summarize the most recent high-quality evidence and will provide helpful information about the efficacy and safety of cisplatin for adult patients with OC. CONCLUSION: The findings of this study will provide convinced evidence of cisplatin for adult patients with OC, and provide recommendations for clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019156558.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Humanos , Resultado do Tratamento
7.
Anticancer Res ; 39(11): 5933-5942, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704818

RESUMO

BACKGROUND/AIM: Perineural invasion (PNI) is a significant pathological feature in head and neck cancer. The molecular mechanisms of PNI are poorly understood. Contrary to the previous belief that cancer cells invade nerves, recent studies have shown that Schwann cells (SC) can dedifferentiate, intercalate between cancer cells, and promote cancer dispersion. Communication between cells through brain-derived neurotrophic factor (BDNF) activation of its receptor tropomyosin receptor kinase B (TRKB) may contribute to these cellular events. We aimed to determine the effect of TRKB inhibitor ANA-12 on the direction of cell migration and degree of SC-induced oral cancer cell dispersion. MATERIALS AND METHODS: Cell migration and dispersion assays were performed in vitro using murine SC and oral carcinoma cell lines. Assays were performed with and without ANA-12. RESULTS: Although SCs preferentially migrated towards cancer cells in control medium, there was minimal SC-associated cancer cell dispersion. In contrast, treatment with ANA-12 reduced migration of SCs and cancer cells towards each other and initiated more SC-associated cancer cell dispersion. CONCLUSION: This pilot study shows that BDNF-TRKB signaling may have a role in regulating interactions between SC and oral cancer cells that affect cell migration, intercalation, and cancer cell dispersion. Further research into these interactions may provide important clues about the molecular and cellular mechanisms of PNI.


Assuntos
Azepinas/farmacologia , Benzamidas/farmacologia , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Carcinoma de Células Escamosas/patologia , Glicoproteínas de Membrana/antagonistas & inibidores , Neoplasias Bucais/patologia , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Receptor trkB/antagonistas & inibidores , Células de Schwann/patologia , Animais , Apoptose , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Movimento Celular , Proliferação de Células , Técnicas de Cocultura , Humanos , Técnicas In Vitro , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Projetos Piloto , Receptor trkB/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Células Tumorais Cultivadas
8.
Anticancer Res ; 39(11): 6057-6062, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704832

RESUMO

BACKGROUND/AIM: The prognosis of patients with osteosarcoma is poor; therefore, new treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of the 11 families (PDE1-PDE11) of the phosphodiesterase superfamily that regulates the intracellular concentrations and effects of cAMP and cGMP. This in vitro study was performed to investigate the role of PDE2 in human oral osteosarcoma HOSM-1 cells. MATERIALS AND METHODS: PDE2 expression was measured by a cAMP-PDE assay and real-time-PCR. The effects of the PDE2-specific inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 8-bromo-cAMP, and 8-bromo-cGMP on cell proliferation and migration were assessed. RESULTS: PDE2 activity and PDE2A mRNA expression were detected in HOSM-1 cells. Cell proliferation was inhibited by EHNA and 8-bromo-cAMP but not by 8-bromo-cGMP. Cell migration was stimulated by EHNA and 8-bromo-cGMP, but it was inhibited by 8-bromo-cAMP. CONCLUSION: Cell proliferation is regulated by PDE2-cAMP signaling and cell migration is regulated by PDE2-cGMP signaling in HOSM-1 cells.


Assuntos
Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Neoplasias Bucais/patologia , Osteossarcoma/patologia , Adenina/análogos & derivados , Adenina/farmacologia , Apoptose , Compostos de Benzil/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/enzimologia , Ciclo Celular , AMP Cíclico/farmacologia , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/enzimologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/enzimologia , Transdução de Sinais , Células Tumorais Cultivadas
9.
Int J Oncol ; 55(4): 949-959, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485602

RESUMO

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. Despite advances in surgery, radiotherapy and chemotherapy, the overall 5­year survival rate of patients with OSCC has not significantly improved. In addition, the prognosis of patients with advanced­stage OSCC remains poor. Therefore, it is necessary to develop novel therapeutic modalities. Vincristine (VCR), a naturally occurring vinca alkaloid, is a classical microtubule­destabilizing agent and is widely used in the treatment of a number of cancers. Despite the proven antitumor benefits of VCR treatment, one of the major reasons for the failure of treatment is drug resistance. Changes in the tumor microenvironment are responsible for cross­talk between cells, which may facilitate drug resistance in cancers; secreted proteins may promote communication between cancer cells to induce the development of resistance. To identify the secreted proteins involved in VCR resistance, conditioned media was obtained, and an antibody array was conducted to screen a comprehensive secretion profile between VCR­resistant (SAS­VCR) and parental (SAS) OSCC cell lines. The results showed that amphiregulin (AREG) was highly expressed and secreted in SAS­VCR cells. Pretreatment with exogenous recombinant AREG markedly increased drug resistance against VCR in OSCC cells, as assessed by an MTT assay. Colony formation, MTT and western blot assays were performed to investigate the effects of AREG knockdown on VCR sensitivity. The results indicated that AREG expression can regulate VCR resistance in OSCC cells; overexpression of AREG increased VCR resistance in parental cells, whereas AREG knockdown decreased the VCR resistance of resistant cells. In addition, it was also demonstrated that the glycogen synthase kinase­3ß pathway may be involved in AREG­induced VCR resistance. These findings may provide rationale to combine VCR with blockade of AREG­related pathways for the effective treatment of OSCC.


Assuntos
Anfirregulina/metabolismo , Carcinoma de Células Escamosas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Bucais/metabolismo , Anfirregulina/genética , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Prognóstico , Transdução de Sinais , Regulação para Cima , Vincristina/farmacologia
10.
Shanghai Kou Qiang Yi Xue ; 28(3): 225-230, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489406

RESUMO

PURPOSE: To investigate the mechanism of ANXA1 in TPF chemotherapy of oral squamous cell carcinoma (OSCC). METHODS: ANXA1 overexpression and low-expression cell lines were constructed. The role of ANXA1 in TPF chemotherapy was analyzed by cell proliferation, cytotoxicity test, real-time PCR and Western blot, and the mechanism of ANXA1 in TPF chemotherapy through EMT (epithelial-mesenchymal transition) pathway was discussed. The data were analyzed with SPSS 18.0 software package. RESULTS: After overexpression of ANXA1, cell growth rate decreased, cell cycle slowed down, sensitivity to TPF-induced drugs decreased, and EMT occurred in OSCC. After underexpression of ANXA1, cell growth rate increased, cell cycle accelerated, sensitivity to TPF chemotherapeutic drugs increased, and reverse EMT occurred in OSCC. CONCLUSIONS: In TPF chemotherapy of OSCC, overexpression of ANXA1 results in EMT of cells, which leads to decreased chemosensitivity.


Assuntos
Anexina A1 , Antineoplásicos , Carcinoma de Células Escamosas , Transição Epitelial-Mesenquimal , Neoplasias Bucais , Anexina A1/metabolismo , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética
11.
Med Hypotheses ; 129: 109241, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31371076

RESUMO

Oral Squamous Cell Carcinoma (OSCC) is one of the major causes of cancer related deaths worldwide. Presence of chemoresistant cancer stem cells is the major reason behind metastasis, tumor relapse and treatment resistance in OSCC. STAT 3 signalling plays a key role in survival of cancer stem cells (CSC's), Epithelial Mesenchymal Transition (EMT) mediated metastasis in OSCC. CD 133 is the surface marker for identification of cancer stem cells. In the present study we hypothesise the selective targeting of CSC's using CD 133 mediated delivery of STAT 3 inhibitor, Niclosamide to specifically target CSC's and Non CSC's.


Assuntos
Antígeno AC133/química , Carcinoma de Células Escamosas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Neoplasias Bucais/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Niclosamida/administração & dosagem , Fator de Transcrição STAT3/antagonistas & inibidores , Apoptose , Portadores de Fármacos , Transição Epitelial-Mesenquimal , Humanos , Modelos Teóricos , Recidiva Local de Neoplasia , Transdução de Sinais
12.
Biomed Pharmacother ; 117: 109160, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387166

RESUMO

BACKGROUND: Pinosylvin possesses several biological properties, including anti-inflammatory, antitumor, and antioxidant characteristics. However, the effects of pinosylvin on the migration and invasion of human oral cancer cells and the underlying mechanisms remain unclear. HYPOTHESIS/PURPOSE: In this research, we investigated the outcome of different concentrations of pinosylvin (0-80 µM) on the metastatic and invasive abilities of SAS, SCC-9, and HSC-3 cells. METHODS AND RESULTS: Western blotting assay and Gelatin zymography assay indicated that pinosylvin inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and reduced its protein level but increased the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). Additionally, the wound healing assay and Transwell method showed that pinosylvin reduced the migration of SAS, SCC-9 and HSC-3 oral cancer cells. Besides, pinosylvin decreased the phosphorylation of ERK1/2 protein experssion in both SAS and SCC-9 cells. CONCLUSION: These results indicate that pinosylvin is a potential anticancer agent for preventing oral cancer metastasis.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Bucais/tratamento farmacológico , Invasividade Neoplásica/patologia , Estilbenos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/farmacologia , Neoplasias Bucais/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-2/metabolismo
13.
Comput Methods Programs Biomed ; 178: 105-112, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31416538

RESUMO

BACKGROUND AND OBJECTIVES: The computational prediction of drug responses based on the analysis of multiple clinical features of the tumor will be a novel strategy for accomplishing the long-term goal of precision medicine in oncology. The cancer patients will be benefitted if we computationally account all the tumor characteristics (data) for the selection of most effective and precise therapeutic drug. In this study, we developed and validated few computational models to predict anticancer drug efficacy based on molecular, cellular and clinical features of 31 oral squamous cell carcinoma (OSCC) cohort using computational methods. METHODS: We developed drug efficacy prediction models using multiple tumor features by employing the statistical methods like multi linear regression (MLR), modified MLR-weighted least square (MLR-WLS) and enhanced MLR-WLS. All the three developed drug efficacy prediction models were then validated using the data of actual OSCC samples (train-test ratio 31: 31) and actual Vs hypothetical samples (train-test ratio 31: 30). The selected best statistical model i.e. enhanced MLR-WLS has then been cross-validated (CV) using 341 theoretical tumor data. Finally, the performances of the models were assessed by the level of learning confidence, significance, accuracy and error terms. RESULTS: The train-test process for the real tumor samples of MLR-WLS method revealed the drug efficacy prediction enhancement and we observed that there was very less priming difference between actual and predicted. Furthermore, we found there was a less difference between actual apoptotic priming and predicted apoptotic priming for the tumors 6, 8, 21 and 30 whereas, for the remaining tumors there were no differences between predicted and actual priming data. The error terms (Actual Vs Predicted) also revealed the reliability of enhanced MLR-WLS model for drug efficacy prediction. CONCLUSION: We developed effective computational prediction models using MLR analysis for anticancer drug efficacy which will be useful in the field of precision medicine to choose the choice of drug in a personalized manner. We observed that the enhanced MLR-WLS model was the best fit to predict anticancer drug efficacy which may have translational applications.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Simulação por Computador , Neoplasias Bucais/tratamento farmacológico , Adulto , Idoso , Algoritmos , Apoptose , Feminino , Humanos , Análise dos Mínimos Quadrados , Modelos Lineares , Masculino , Oncologia , Pessoa de Meia-Idade , Análise Multivariada , Medicina de Precisão , Reprodutibilidade dos Testes
14.
BMJ Case Rep ; 12(8)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31451454

RESUMO

A 52-year-old male patient with hyaluronic acid-based dermal fillers injected in his cheeks was diagnosed with glossotonsillary malignancy, and managed with concurrent cetuximab (epidermal growth factor receptor inhibitor) and radiation therapy. He developed significant inflammation around the dermal filler sites after first cycle of cetuximab which improved with dissolution of the dermal fillers with hyaluronidase. This suggests that cetuximab can lead to inflammation around the dermal filler sites, which can be treated with dissolution of the filler.


Assuntos
Cetuximab , Preenchedores Dérmicos/efeitos adversos , Dermatite , Ácido Hialurônico , Hialuronoglucosaminidase/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Técnicas Cosméticas , Dermatite/tratamento farmacológico , Dermatite/etiologia , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Resultado do Tratamento
15.
Gan To Kagaku Ryoho ; 46(6): 1027-1031, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273169

RESUMO

BACKGROUND: In our department, patients with oral squamous cell carcinoma(OSCC)received preoperative chemotherapy containing S-1 to prevent the growth and dissemination of tumors during the waiting time before definitive surgery. We retrospectively evaluated the usefulness of this treatment. PATIENTS AND METHODS: One hundred and five patients comprising stages T1(26), T2(64), T3(7), and T4(8 cases)were enrolled in this study from July 2001 to June 2013. In principle, patients were administered S-1(80mg/m / 2/day, days 1-14)and followed by a drug holiday(days 15-21), continuing until 1 week before surgery. RESULTS: The median administration period was 14 days(256 days). Ninety-eight patients underwent definitive surgery, but 7 patients who revealed clinical CR underwent only biopsy and showed histological CR. The histological responses of all patients were CR(24), PR(22), and NC(59), and the response rate was 43.8%. Almost all adverse effects were Grade 1 or 2, except 1 case of neutropenia(Grade 3)and 1 case of urticaria(Grade 3). The 5-year overall survival rates were 86.7% in all cases, 95.3% in CR/PR cases, and 79.7% in NC cases. CONCLUSION: Preoperative S-1 administration during the waiting time was a safe and very effective method and was considered beneficial for patients with OSCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas , Neoplasias Bucais , Carcinoma de Células Escamosas/tratamento farmacológico , Combinação de Medicamentos , Humanos , Neoplasias Bucais/tratamento farmacológico , Ácido Oxônico , Estudos Retrospectivos , Tegafur , Listas de Espera
16.
J Exp Clin Cancer Res ; 38(1): 299, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291983

RESUMO

BACKGROUND: Programmed death 1 (PD-1) blockade has great effect in the prevention of oral precancerous lesions, but the drug resistance has also been observed. The determinants of immune resistance during the malignant transformation are poorly understood. METHODS: Anti-PD-1 antibody was administered in the 4NQO-induced carcinogenesis mouse models. The mice were then subdivided into PD-1 resistance(PD-1R) group and PD-1 sensitive(PD-1S) group according to the efficacy. The expression of PD-1 and PD-L1, and the abundance of CD3+ T cells in tumor microenvironment between the two groups was tested by immunohistochemistry. In addition, the activation and effector functions, as well as the accumulation of immunosuppressive cells and expression of immune checkpoints of T cells in the draining lymph nodes and spleen between PD-1R and PD-1S group were analyzed by flow cytometry. RESULTS: Our results showed that T cell infiltration in tumor microenvironment, effector T cell cytokine secretion and central memory T cell accumulation in peripheral lymphoid organs were all inhibited in the anti-PD-1 resistance group. Furthermore, we found that an increase of regulatory T cell (Treg) population contributed to the resistance of the anti-PD-1 therapy. Notably, TIM-3 was found to be the only immunosuppressive molecule that mediated the resistance to anti-PD-1 therapy in the oral malignant transformation model. CONCLUSIONS: Our findings identified a novel mechanism that T cell dysfunction contributes to the immune resistance during the malignant transformation of the oral mucosa. This study provides new targets for improving the efficacy of immunotherapy for early stage of tumorigenesis.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Memória Imunológica , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas , Linfócitos T/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Oral Pathol Med ; 48(10): 897-905, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31318467

RESUMO

BACKGROUND: Casticin expresses multiple anti-cancer activities, whereas the effect of casticin on oral squamous cell carcinoma (OSCC) is still unclear. ß-catenin signaling plays a crucial role in the epithelial-mesenchymal transition which is closely related to tumorigenesis. Herein, we aimed to study the functions of casticin on invasion and migration of OSCC, and clarify whether the effect of casticin on OSCC has a relationship with ß-catenin signaling. METHODS: Human OSCC cell lines UM1 and HSC-3 were treated with different concentrations of casticin. The cell viability was evaluated by MTT and soft agar colony formation. Transwell assay and wound-healing assay were performed to measure the ability of cell invasion and migration. The protein expression was assessed by Western blotting. RESULTS: Casticin displayed inhibitory activities of cell viability, invasion, and migration on OSCC cell lines. Meanwhile, casticin could reverse EMT process and inhibit the expression of ß-catenin in OSCC. Knock-down or overexpression of ß-catenin could alter the effect of casticin on OSCC. CONCLUSIONS: Casticin impaired invasion and migration of OSCC by inhibition of ß-catenin and reversal of EMT and could be a potential anti-cancer bioactive agent.


Assuntos
Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal , Flavonoides/farmacologia , Neoplasias Bucais/patologia , beta Catenina/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo , Humanos , Neoplasias Bucais/tratamento farmacológico , Invasividade Neoplásica , Transdução de Sinais
18.
Toxicol Lett ; 314: 142-152, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31319114

RESUMO

Cadmium (Cd), an established carcinogen, is a risk factor for oral squamous cell carcinoma (OSCC). Macroautophagy/autophagy is proposed to play a pivotal role in Cd-mediated carcinogenic activity. However, the mechanisms underlying Cd-induced autophagy are poorly understood. In the present study, a CAL27 OSCC cell line exposed to 10-6 M Cd for 8 weeks was used as a model system. Repeated Cd exposure induced significant migration and invasion of CAL27 cells. Furthermore, we showed that Cd increased the autophagic flux in CAL27 cells, as evidenced by the upregulation of LC3-II and the downregulation of P62/SQSTM1. The genetic blocking of autophagy inhibited Cd-induced migration and invasion, indicating a carcinogenic role of autophagy in Cd-treated CAL27 cells. Cd-induced NUPR1 expression, which contributes to lysosomal biogenesis and expression of autophagy-related gene, was found to mechanistically initiate autophagy in CAL27 cells. Of note, NUPR1 shRNA abolished Cd-induced autophagy both in vitro and in vivo. We also found that Cd triggered the generation of MDA in a xenograft tumour model and that N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger, abrogated the effects of Cd on NUPR1-dependent autophagy in vivo. Taken together, these results demonstrate that ROS-dependent NUPR1-mediated autophagy plays an important role in repeated Cd exposure -induced cell growth, migration and invasion in OSCC cells.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cloreto de Cádmio/toxicidade , Movimento Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Animais , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Anticancer Res ; 39(7): 3507-3518, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262875

RESUMO

BACKGROUND/AIM: Very few studies of anticancer activity of azulene amides led us to investigate the cytotoxicity of 21 N-alkylazulene-1-carboxamides introduced either with 3-methyl [1-7], 7-isopropyl-3-methyl [8-14] or 2-methoxy group [15-21] Materials and Methods: Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC50) against three normal human oral mesenchymal cells to that against four human oral squamous cell carcinoma (OSCC) cell lines. Potency-selectivity expression (PSE) was calculated by dividing TS value by CC50 value against OSCC cell lines. Apoptosis-inducing activity was evaluated by caspase-3 activation and appearance of subG1 cell population. RESULTS: [8-14] showed higher TS and PSE values, than [1-7] and [15-21] The most active compound [8-14] induced apoptosis in C9-22 OSCC cells at 4-times higher CC50 Quantitative structure-activity relationship analysis of [1-14] demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the molecular shape and hydrophobicity. CONCLUSION: 7-Isopropyl-3-methyl-N-propylazulene-1-carboxamide [8] can be a potential candidate of lead compound for manufacturing new anticancer drug.


Assuntos
Amidas/farmacologia , Antineoplásicos/farmacologia , Azulenos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Amidas/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Azulenos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Relação Quantitativa Estrutura-Atividade
20.
Anticancer Res ; 39(7): 3519-3529, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262876

RESUMO

BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Catalase/farmacologia , Células Cultivadas , Criança , Clonidina/farmacologia , Fragmentação do DNA , Dexmedetomidina/farmacologia , Epinefrina/farmacologia , Humanos , Isoproterenol/farmacologia , Fenilefrina/farmacologia , Superóxido Dismutase/farmacologia
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