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BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.
Assuntos
Neoplasias de Cabeça e Pescoço , Células Matadoras Naturais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Modelos Animais de Doenças , Linhagem Celular Tumoral , Camundongos Endogâmicos NOD , Camundongos SCID , Células Matadoras Naturais/metabolismo , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/metabolismoRESUMO
This descriptive study aimed to identify the factors influencing obstructive sleep apnea (OSA) by age between middle-aged and elderly people. These groups have not been evaluated separately until now. This study is a secondary analysis of data from the Eighth Korea National Health and Nutrition Examination Survey 2021. Of the 3942 participants with OSA in this study, 2397 were middle-aged and 1545 were elderly, and 2509 had low risk and 1433 had moderate-high risk. Age-specific factors related to their OSA were identified using complex sample logistic regression. Factors associated with OSA in middle-aged individuals included the number of household members, smoking, subjective health, and subjective body image. Smoking and subjective health were significantly related to OSA in elderly people. Not smoking was 0.23 times less likely than smoking to be associated with OSA, and 0.3 times less likely when participants were healthy than when unhealthy. Hence, influencing factors differed depending on the age of individuals with OSA. Therefore, to develop public health measures, it may be more effective to establish intervention strategies to improve symptoms and prevent complications in middle-aged and elderly patients with OSA by distinguishing and applying influential age-specific factors.
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Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7-8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.
Assuntos
Doença de Alzheimer , Escopolamina , Ratos , Masculino , Animais , Escopolamina/efeitos adversos , Escopolamina/metabolismo , Acetilcolinesterase/metabolismo , Ratos Sprague-Dawley , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Plasticidade Neuronal , Hipocampo/metabolismo , Doença de Alzheimer/metabolismoRESUMO
Raw enoki mushroom is a high-risk vector for listeriosis, which led to foodborne outbreaks resulting in four deaths in the United States in 2020. This study aimed to investigate the washing method for the inactivation of L. monocytogenes in enoki mushrooms for household and food service establishments. Five methods of washing fresh agricultural products without using disinfectants were selected: (1) rinsing under running water (2 L/min, 10 min), (2-3) dipping in water (200 ml/20 g) at 22 or 40 °C for 10 min, and using (4) 10% NaCl or (5) 5% vinegar at 22 °C for 10 min. The antibacterial efficacy of each washing method along with the final rinse was tested with enoki mushrooms inoculated with a 3-strain cocktail of L. monocytogenes (ATCC 19111, 19115, 19117; ca. 6 log CFU/g). The 5% vinegar showed a significant difference in antibacterial effect compared to the other treatments except 10% NaCl (P < 0.05), with the maximum elimination of L. monocytogenes by 1.23 log CFU/g. Therefore, a disinfectant for enoki mushrooms that can complement the commonly used washing method was developed using antimicrobials (caprylic acid, CA: 0, 0.20, 0.40%; thymol, TM: 0, 0.075, 0.15%). By combined treatment of 0.40% CA and 0.15% TM at 22 °C for 10 min, L. monocytogenes was completely inactivated (>5.55 log reduction CFU/g) and did not recover after enrichment, although individual treatments of antimicrobials showed low bactericidal effects of <1.50 log reduction CFU/g. The bacterial membrane disintegration induced by the disinfectant was analyzed through flow cytometry. Additionally, the sensory scores (odor and appearance) and color parameters (L*, a*, and b*) of enoki mushrooms treated with the disinfectant were not significantly different from those of enoki mushrooms washed with water (P > 0.05). Our findings suggest a washing disinfectant consisting of low concentrations of CA and TM with synergistic antibacterial effects without quality deterioration that can ensure the safe consumption of raw enoki mushrooms in homes and food service establishments.
Assuntos
Agaricales , Desinfetantes , Flammulina , Serviços de Alimentação , Listeria monocytogenes , Timol/farmacologia , Ácido Acético/farmacologia , Manipulação de Alimentos/métodos , Cloreto de Sódio/farmacologia , Microbiologia de Alimentos , Contagem de Colônia Microbiana , Desinfetantes/farmacologia , Água , Antibacterianos/farmacologiaRESUMO
Background: Adolescence is a period of physical and psychological change that causes adolescents to experience anxiety, stress, and loss of control. These experiences can lead to thoughts about suicide. However, not all adolescents with suicidal thoughts attempt suicide. This study aimed to identify the factors that influence suicide attempts among adolescents with suicidal thoughts, and to prepare a theoretical basis for a method to prevent suicide among adolescents. Methods: In this descriptive cross-sectional study, the 15th Korean Youth Risk Behavior Web-Based Survey (2019) was used. The participants were 7,498 adolescents aged 12-18 yr with thoughts of suicide. Factors influencing suicide attempts among adolescents with suicidal thoughts were analyzed using a complex sample logistic analysis. Results: Gender, age, academic performance, and economic level were the general factors associated with suicide attempts of adolescents with suicidal thoughts. Physical and psychological factors included smoking, alcohol use, drug use, sex-related experience, experiencing violence, efforts to reduce weight, level of physical activity, and depression. Conclusion: Age and gender should be taken into consideration when designing suicide prevention activities. In addition, in order to lower the suicide rate of adolescents in Korea, an effective system of prevention and intervention strategies should be implemented, which attend to the issues of adolescents from low-income families, adolescent weight and body image concerns, and adolescent depression.
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Anaplastic thyroid cancer (ATC) is characterized by a rapid and aggressive course of progression. Despite significant advances in surgery, radiotherapy and chemotherapy, the diseasespecific mortality due to ATC is approximately 100%. New strategies, such as molecular targeted therapies, are imperative for improving survival. Livin, a member of the human inhibitor of apoptosis protein family, has been found to be associated with tumor progression and poor prognosis in various human cancers. The aim of the present study was to evaluate the role of Livin in cancer progression and chemoradioresistance of ATC and to investigate its potential as a therapeutic target. Endogenous Livin expression in the human BHT101 ATC cell line was silenced by Livinspecific small interfering RNA. To assess the impact of Livin on cancer cell behavior in human ATC cells, various methods such as cell invasion, cell viability and cell apoptosis assays were applied. To assess the expression of Livin and the change of apoptosisrelated proteins associated with Livin expression, reverse transcriptionquantitative PCR and western blotting were performed. Immunohistochemistry was performed to detect Livin protein expression in human ATC tissues. The association between Livin expression and apoptotic/proliferation index was analyzed in human ATC cells. Livinknockdown suppressed tumor cell invasion; and conversely, it enhanced cell apoptosis, with elevated expression levels of cleaved caspase3 and 7 and cleaved PARP. Livinknockdown enhanced radiationinduced apoptosis, while reducing cell viability following radiotherapy, as well as lenvatinib treatment. In addition, human ATC tissues with high Livinexpression exhibited a high Ki67 labeling index and low apoptotic index. In summary, these findings indicate the contribution of Livin to tumor progression and chemoradioresistance in ATC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Carcinoma Anaplásico da Tireoide/metabolismo , Carcinoma Anaplásico da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Resistencia a Medicamentos Antineoplásicos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Proteínas Inibidoras de Apoptose/biossíntese , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Invasividade Neoplásica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Compostos de Fenilureia/farmacologia , Quinolinas/farmacologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Tolerância a Radiação , Carcinoma Anaplásico da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismoRESUMO
The receptor tyrosine kinase, recepteur d'origine nantais (RON), is known to be associated with the progression, metastasis, and prognosis of various types of cancers. Nevertheless, the role of RON in human oral squamous cell carcinoma (OSCC) is unclear. This study evaluated whether RON affects oncogenic behavior, oncogenic signaling pathways, and clinical outcomes, including survival, in human OSCC. Reverse transcriptionPCR, quantitative PCR, western blotting and immunohistochemical staining were used to determine mRNA and protein expression levels of RON. Cell invasion, migration and apoptosis assays were used to assess the functional effects of small interfering RNAmediated knockdown of RON or snail family transcriptional repressor 2 (SLUG). RON knockdown suppressed tumor cell invasion and migration and enhanced apoptosis in human OSCC cells. RON knockdown also decreased the phosphorylation of MAPK signaling proteins, such as ERK1/2, JNK and p38. In addition, RON knockdown suppressed the expression of the epithelial mesenchymal transition (EMT)related transcription factor, SLUG. SLUG knockdown blocked the enhancement of cell invasion and migration induced by macrophagestimulation protein (MSP)mediated RON activation in OSCC cells. The cell morphology was changed to spindlelike shape under MSPmediated RON activation in OSCC cells. RON was overexpressed in both fresh and paraffinembedded human OSCC tissues. Taken together, these results indicate that RON contributed to tumor progression by regulating the EMTrelated factor, SLUG, and the MAPK pathway in OSCC. This study may provide a theoretical basis for the application of RONtargeting agents, currently being studied in various cancer fields, for the treatment of OSCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/secundário , Transição Epitelial-Mesenquimal , Sistema de Sinalização das MAP Quinases , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/patologia , Receptores Proteína Tirosina Quinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Movimento Celular , Proliferação de Células , Terapia Combinada , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/terapia , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Fosforilação , Prognóstico , Receptores Proteína Tirosina Quinases/genética , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
The present study was conducted to investigate the prognostic significance of p16 (also known as cyclin-dependent kinase inhibitor 2A) in the treatment of induction chemoradiotherapy for advanced hypopharyngeal squamous cell carcinoma (HPSCC). Patients who were treated with at least two cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced HPSCC were reviewed in the study. The staining results were analyzed to examine the association between the chemotherapy response and the survival outcome. A total of 45 patients were enrolled for the present study; the majority had received induction chemotherapy with docetaxel, cisplatin, and 5-FU. Following induction chemotherapy, 17 patients (37.8%) exhibited a complete response and 28 patients (62.2%) exhibited a partial response. There were 11 patients (24.4%) with p16-positive immunohistochemical stains and 30 patients (66.7%) with p53-positive immunohistochemical stains. There was no significant difference in chemotherapy response, overall survival, or progression-free survival time between groups with p16-positive and p16-negative stains. Low p53 expression and chemotherapy response were not associated with each other. High p16 expression did not correlate with low p53 expression. In this study, p16 was not determined to predict the chemotherapy response for HPSCC. High p16 expression did not correlate with survival incidence for patients with HPSCC.
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WNT1-inducible-signaling pathway protein-1 (WISP-1) belongs to the family of cysteine rich 61/connective tissue growth factor/nephroblastoma overexpressed matricellular proteins, which are involved in various biological processes, including cell adhesion, proliferation, differentiation, angiogenesis and carcinogenesis. In the present study, the expression of WISP-1 was investigated, and its association with clinicopathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC) was evaluated. Additionally, the role of WISP-1 in invasion and apoptosis of human OSCC cells was evaluated. Immunoreactivity of WISP-1 was increased in OSCC tissue compared with adjacent normal tissue samples. High expression of WISP-1 protein was observed in 24/84 (28.57%) OSCC specimens. Additionally, high WISP-1 expression was significantly associated with treatment failure (P=0.042). The 5-year overall survival rate was 33% in patients with high WISP1 expression, and 66% in patients with low WISP-1 expression. WISP-1 expression in the human OSCC SCC-1483 cell line was observed. Furthermore, WISP-1 knockdown using small interfering (si)RNA significantly reduced cell invasion and induced apoptosis compared with control siRNA-transfected cells. These findings suggested that WISP-1 is associated with tumor progression and poor prognosis by increasing tumor cell invasion and inhibiting cell apoptosis in human OSCC.
RESUMO
The responsiveness of head and neck squamous cell carcinoma (HNSCC) to chemotherapy widely affects prognosis. Overcoming chemoresistance is necessary to improve prognoses in patients with advanced HNSCC. Evasion of apoptosis by cancer cells is a major cause of chemoresistance. Livin, a member of the human inhibitors of apoptosis protein family, is highly expressed in various human cancer tissues and is associated with tumor progression and poor prognosis in human cancers. The aim of the present study was to evaluate the role of Livin in the susceptibility to popularly used chemotherapeutic drugs such as cisplatin, 5-fluorouracil (FU) and docetaxel in human HNSCC cell lines (SNU1041, PCI1 and PCI50 cells). Reverse transcription polymerase chain reaction and western blotting were performed to determine mRNA and protein expression levels. Cell viability and apoptosis assays were used to assess the functional effects of small-interfering RNA-mediated knockdown of Livin. Each HNSCC cell line had different sensitivity to chemotherapeutic drugs. Livin knockdown significantly enhanced cytotoxicity to cisplatin, 5-FU and docetaxel in human HNSCC cells. Livin knockdown induced apoptosis and enhanced chemotherapy-induced apoptosis to cisplatin, 5-FU and docetaxel. Consistent with this, Livin-knockdown cells showed greater expression of cleaved caspases-3 and -7 and poly(ADP-ribose)polymerase compared with that in control cells after cisplatin, 5-FU, or docetaxel treatment. In conclusion, our results suggest that siRNA-mediated Livin knockdown enhanced the chemosensitivity of the three HNSCC cell lines to cisplatin, 5-FU and docetaxel. Although further investigations are required to support these findings, our results demonstrated that novel therapeutic strategies with combined use of siRNA targeting Livin and chemotherapeutic agents may have applications in the treatment of advanced HNSCC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/administração & dosagem , Docetaxel , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxoides/administração & dosagemRESUMO
The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit VSMC proliferation and explored the underlying mechanisms. Both the phosphorylation and expression of LKB1 were increased by NDGA. In addition, NDGA significantly attenuated angiotensin II (Ang II)-induced VSMC proliferation. To elucidate the estrogenic effects, we confirmed that NDGA increased estrogen receptor α (ERα) expression, similar to treatment with E2 and estriol (E3). Furthermore, tamoxifen and ERα siRNA obstructed the effects of NDGA including ERα expression, AMPK phosphorylation and both LKB1 phosphorylation and expression. VSMC proliferation was restored by tamoxifen and ERα siRNA. LKB1 siRNA also reversed the NDGA-mediated inhibition of VSMC proliferation. The estrogenic activity of NDGA induced LKB1 translocation from nucleus to cytosol, and tamoxifen obstructed LKB1 translocation. The absence of LKB1 completely abolished the increase of ERα expression induced by NDGA. Taken together, the beneficial effects of estrogenic compound (E2 and NDGA) on inhibition of VSMC proliferation are mediated by interaction between LKB1 and ERα, suggesting a potential mechanism for females having less cardiovascular disease.
Assuntos
Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Masoprocol/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Proteínas Quinases Ativadas por AMP/metabolismo , Angiotensina II/farmacologia , Animais , Aorta Torácica/citologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Di-Hidrotestosterona/farmacologia , Estriol/farmacologia , Receptor alfa de Estrogênio/genética , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/genética , Ratos Sprague-DawleyRESUMO
Livin, a member of the human inhibitor of apoptosis protein (IAP) family, is expressed at high levels in various human cancer tissues and may have prognostic significance. The aim of the present study was to evaluate the effect of Livin on tumor cell behavior and oncogenic signaling pathways in human hypopharyngeal squamous cell carcinoma (HSCC). Reverse transcriptionquantitative polymerase chain reaction and western blot analyses were used to determine the mRNA and protein expression levels, respectively. A cell proliferation assay and cell cycle analysis were used to assess the functional effects of small interfering RNAmediated Livin knockdown. Livin was overexpressed in fresh HSCC tissues, compared with the adjacent normal mucosa. Livin knockdown led to significantly reduced cell proliferation and cell cycle arrest in the G1 phase of the human HSCC cells. The expression levels of cmyc, cyclin D1, cyclin D3, cyclindependent kinase (CDK)4 and CDK6 were decreased. The phosphorylation levels of extracellular signalregulated kinase 1/2, p38, cJun N-terminal kinase and Akt were also decreased by Livin knockdown in the HSCC cells. Taken together, the results of the present study suggested that Livin may enhance tumorigenesis by modulating the mitogenactivated/Akt signaling pathways in human HSCC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/metabolismo , Proteínas Inibidoras de Apoptose/genética , Sistema de Sinalização das MAP Quinases , Proteínas de Neoplasias/genética , Idoso , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNARESUMO
BACKGROUND: In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). METHODS: We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry. RESULTS: SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and -7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC. CONCLUSIONS: SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC.
Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Bucais/genética , Fatores de Transcrição SOXC/biossíntese , Adulto , Idoso , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Prognóstico , Tolerância a Radiação/genética , Fatores de Transcrição SOXC/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Falha de TratamentoRESUMO
The transcription factor, early growth response 1 (EGR1) belongs to the early growth response family. EGR1 regulates the transactivation of genes involved in growth inhibition and apoptosis by ionizing radiation. The aims of the present study were to evaluate the expression of EGR1, and its relationship to prognosis, in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) receiving chemoradiation therapy, and to observe the effect of EGR1 on the apoptosis of head and neck squamous cell carcinoma (HNSCC) cells treated with ionizing radiation. Expression of the EGR1 protein in tissue samples from patients with LHSCC was detected by immunohistochemistry. A high expression of the EGR1 protein was observed in 37 (67.3%) of the 55 LHSCC tissue samples examined. A high EGR1 protein expression in patients with LHSCC who were treated with chemoradiation was significantly associated with improved larynx-preservation survival (p=0.04). The 5-year disease-specific survival rate with larynx preservation was 59% in patients with a high EGR1 protein expression vs. 30% in those with a low EGR1 protein expression. In the human HNSCC cell line, PCI50, EGR1 mRNA expression was induced at 30-60 min, and EGR1 protein expression was induced at 60-120 min, after exposure to a 5 Gy dose of ionizing radiation. To evaluate the impact of EGR1 on radiation-induced apoptosis, we used smallinterfering RNA to knock down endogenous EGR1 gene expression. Cleaved caspase 3, cleaved caspase 7, and cleaved PARP were decreased, while XIAP was increased, in EGR1-knockdown PCI50 cells compared to negative control PCI50 cells, at all observed post-irradiation time points. These findings suggested that EGR1 knockdown inhibits radiation-induced apoptosis. In conclusion, EGR1 may be associated with larynx-preservation survival, through the regulation of radiation-induced apoptosis in patients with LHSCC treated with chemoradiation. Although further investigations are required to support the present study, EGR1 serves as a favorable biomarker of radiosensitivity in the treatment of LHSCC.
Assuntos
Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Proteína 1 de Resposta de Crescimento Precoce/fisiologia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/terapia , Proteínas de Neoplasias/fisiologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Docetaxel , Proteína 1 de Resposta de Crescimento Precoce/antagonistas & inibidores , Proteína 1 de Resposta de Crescimento Precoce/genética , Feminino , Fluoruracila/administração & dosagem , Regulação Neoplásica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Genes Precoces/efeitos da radiação , Humanos , Neoplasias Hipofaríngeas/mortalidade , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Laringe , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Tratamentos com Preservação do Órgão , Fótons , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , RNA Interferente Pequeno/genética , Tolerância a Radiação , Taxoides/administração & dosagem , TransfecçãoRESUMO
Livin is one of the most important members of the inhibitor protein (IAP) family. It is overexpressed in several types of tumors and may have prognostic significance. The purpose of this study was to investigate Livin expression in human oral squamous cell carcinomas (OSCCs) and to determine whether Livin affects tumor cell behavior in OSCC cell lines and thus evaluate its potential usefulness in serving as a possible target for molecular-targeted therapy in a preclinical model. The expression of Livin protein was investigated in human OSCC tissues through immunohistochemistry and western blot analysis. To evaluate the impact of Livin knockdown on the behavior of human OSCC cell lines, invasion, migration, proliferation and apoptosis assays using small-interfering RNA (siRNA) were performed. RT-PCR and western blot analysis were used to assess alteration of Livin expression at the mRNA and protein levels. The results revealed that expression of Livin was increased in the human OSCC tissues compared with the adjacent normal mucosa. In addition, immunoreactivity of Livin was expressed in 8 OSCC tissues (44.4%). Knockdown of Livin resulted in significantly reduced cell invasion, migration and proliferation in the human OSCC cells. Livin knockdown induced cell apoptosis in the human OSCC cells. Moreover, Livin inhibited apoptosis by suppressing the activity of caspases in the human OSCC cells. In conclusion, livin is associated with invasive and oncogenic phenotypes such as tumor cell invasion, tumor cell migration, tumor cell proliferation, and resistance to apoptosis in human OSCC cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Bucais/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Apoptose , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Invasividade NeoplásicaRESUMO
AIM: To evaluate the expression of Livin in human laryngohypopharyngeal squamous cell carcinoma (LHSCC) and investigate whether Livin-knockdown using small interfering-RNA (siRNA) affects tumor aggressiveness in LHSCC cells. MATERIALS AND METHODS: Immunohistochemistry, reverse transcription-polymerase chain reaction, western blotting, cell invasion assay, cell migration assay, and cell apoptosis assays were performed to assess the impact of Livin on cancer cell behavior in human LHSCC. RESULTS: High immunoreactivity of Livin was observed in 22 (36.7%) of the 60 LHSCC tissues relative to adjacent normal mucosa. In the positive-Livin expression group, distant metastasis tended to occur frequently, but the difference was not statistically significant (p=0.06). Livin-knockdown by siRNA induced cell apoptosis through activation of caspase 3, caspase 7, and poly ADP ribose polymerase in LHSCC cells. Livin-knockdown also resulted in significantly reduced cell invasion and migration in LHSCC cells. CONCLUSION: siRNA-mediated silencing of Livin may be associated with the reversal of invasive capacity in LHSCC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Inativação Gênica , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/patologia , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Quimiorradioterapia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/terapia , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , Resultado do TratamentoRESUMO
Bromhidrosis is a disease presenting as malodor caused by interaction between the discharge of apocrine glands and bacteria. The main therapeutic modalities are applying topical agents, liposuction surgery, and elective surgery. Among these, elective surgery is reported to be most effective. However, the efficiency largely depends on surgical technique. Additionally, other side effects, such as hematoma and scarring, are occasionally reported. Currently, CO2 laser and 1,064 nm Nd:YAG laser therapy are used, but as the wavelength is not specific to apocrine glands, these laser therapies have certain limitations. Recently, a 1,444 nm wavelength Accusculpt™ laser (LutronicCorp., Seoul, Korea) has been developed which is now commonly used for facial fat plasty and laser liposuction therapy. The use of this laser for bromhidrosis therapy targeting apocrine sweat glands is currently being discussed. Still, no studies on practical clinical use and side effects of this 1,444 nm wavelength laser have been published. In this report, we treated one bromhidrosis patient with 1,444 nm wavelength Accusculpt™ laser therapy on one side while conventional surgery was performed on the other side using a modified Inaba's method. We compared the efficacy of this laser therapy to the surgical modality by measuring malodor severity and overall satisfaction by questionnaire. We also checked for other complications and recurrence for 12 months after the treatment. This patient was largely satisfied as it has a much shorter down time with the same therapeutic outcome. As subdermal coagulation treatment by 1,444 nm Nd:YAG laser may be less invasive but effective therapy, we would like to recommend this modality as a possible treatment option.
RESUMO
OBJECTIVES: Several human tumor tissues show an aberrant expression and activation of recepteur d'origine nantais (RON). In this paper, we investigate the expression of RON in human laryngeal squamous cell carcinoma (SCC) and evaluate whether RON affects the tumor cell progression in human laryngeal SCC cell line. METHODS: Immunohistochemistry was used to assess RON expression in human laryngeal SCC. To evaluate the impact of RON knockdown, the cell invasion assay and cell migration assay using small-interfering RNA were performed. RESULTS: The expression of RON protein was dominantly observed in laryngeal SCC tissues relative to adjacent normal mucosa in all cases. Knockdown of RON resulted in significantly reduced cell invasion in human laryngeal SCC cells. Cell migration showed a marked decrease in RON knockdown laryngeal SCC cells compared to the negative control laryngeal SCC cells. Laryngeal SCC cell migration was enhanced by incubation with macrophage stimulating protein (MSP). CONCLUSION: RON is highly expressed in human laryngeal SCC. We suggest that RON plays an important role in invasion, and metastasis of laryngeal SCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Laríngeas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Idoso , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Ensaios de Migração Celular , Movimento Celular/genética , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , RNA Interferente Pequeno , Receptores Proteína Tirosina Quinases/genética , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of this study was to investigate expression of KITENIN in patients with oral cavity squamous cell carcinoma (SCC) and to determine whether KITENIN affects tumor cell behavior in oral cavity SCC cell line. METHODS: Western blotting and immunohistochemistry was used to assess alteration of KITENIN expression in human oral cavity SCC and normal oral cavity mucosa. To evaluate the impact of KITENIN knockdown, the cell invasion assay and cell migration assay using small-interfering RNA were performed. RESULTS: KITENIN protein expression was significantly increased in human oral cavity SCC tissues than in normal oral cavity mucosa by Western blotting. KITENIN immunoreactivity was strongly identified in human oral cavity SCC relative to adjacent normal tissue. Knockdown of KITENIN resulted in significantly reduced cell invasion in human oral cavity SCC cells (p=0.001). Cell migration showed a marked decrease in KITENIN knockdown oral cavity SCC cells compared to the negative control oral cavity SCC cells (p=0.01). CONCLUSION: KITENIN is associated with tumor invasiveness and metastasis in human oral cavity SCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Bucais/metabolismo , Proteínas de Neoplasias/metabolismo , Western Blotting , Carcinoma de Células Escamosas/secundário , Proteínas de Transporte/fisiologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Ensaios de Migração Celular , Técnicas Citológicas , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Proteínas de Membrana/fisiologia , Neoplasias Bucais/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/fisiologiaRESUMO
BACKGROUND: The purpose of this study was to investigate expression of recepteur d'origine nantais (RON) in human hypopharyngeal squamous cell carcinoma (SCC) and to determine whether RON affects tumor cell behavior in hypopharyngeal SCC cell line and if this would serve as a target for molecular therapy in a preclinical model. METHODS: Reverse transcriptase-polymerase chain reaction, immunohistochemistry, Western blotting, cell invasion, migration, proliferation, and apoptosis assays were used to assess alteration of RON expression and its impact to cancer progression in human hypopharyngeal SCC. RESULTS: Immunoreactivity of RON was observed in hypopharyngeal SCC tissues relative to adjacent normal mucosa in all cases. RON protein expression was significantly increased in metastatic lymph nodes than nonmetastatic lymph nodes by Western blotting. Knockdown of RON resulted in significantly reduced cell invasion, migration, and proliferation in human hypopharyngeal SCC cells. Knockdown of RON enhanced cell apoptosis through activation of caspase 3, caspase 7, and poly ADP-ribose polymerase (PARP). CONCLUSION: These results indicate that knockdown of RON expression may be associated with the reversal of invasive phenotype in hypopharyngeal SCC.