RESUMO
This study examined the correlation of titin (TTN) polymorphisms with the sensitivity of oral squamous cell cancer (OSCC) and clinical characteristics. Six TTN SNPs, including rs10497520, rs12463674, rs12465459, rs2042996, rs2244492, and rs2303838, were evaluated in 322 control groups and 606 patients with oral cancer. We then investigated whether the SNP genotypes rs10497520 had associations with clinical pathological categories. Our data showed that the TC + CC genotype of rs10497520 was associated with moderate/poor tumor cell differentiation. The carriers of TTN rs10497520 polymorphic variant "TC + CC" in OSCC patients with cigarette smoking were linked with poor tumor differentiation (p = 0.008). Our results suggest that the TTN SNP rs10497520 is a possible genetic marker for oral cancer patients in the cigarette-smoking population. The TTN rs10497520 polymorphisms may be essential biomarkers to predict the onset and prognosis of oral cancer disease.
Assuntos
Carcinoma de Células Escamosas , Conectina , Predisposição Genética para Doença , Neoplasias Bucais , Polimorfismo de Nucleotídeo Único , Humanos , Conectina/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Idoso , Adulto , Progressão da Doença , Genótipo , Estudos de Casos e ControlesRESUMO
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is one of the most common types. There is strong evidence that ryanodine receptor 2 (RYR2) plays an important role in different types of cancer according to previous studies. Its expression is associated with survival in patients with HNSCC, but it is unknown whether altered RYR2 expression contributes to tumorigenesis. Therefore, we examined how RYR2 polymorphisms affect OSCC susceptibility and clinicopathological characteristics. Five single nucleotide polymorphisms (SNPs) of RYR2, rs12594, rs16835904, rs2779359, rs3765097, and rs3820216, were analyzed in 562 cases of OSCC and 332 healthy controls using real-time PCR. We demonstrated that RYR2 SNP rs12594 was significantly different between the case and control groups, but this difference was not significant after adjusting for personal habits. In contrast, we found that different genotypes of SNP rs2779359 were significantly associated with the characteristics of clinical stage and tumor size in OSCC patients, according to the odds ratios and the adjusted odds ratios; specifically, patients with the T genotype had 1.477-fold (95% CI, 1.043 to 2.091; p = 0.028) and 1.533-fold (95% CI, 1.087-2.162; p = 0.015) increases in clinical stage and tumor size, respectively, compared with patients with the C allele. The results of our study, in which RYR2 SNPs associated with OSCC progression and development were examined for the first time, suggest that clinicopathological characteristics may alter OSCC susceptibility. Finally, RYR2 SNP rs2779359 not only plays a role in both the prognosis and diagnosis of oral cancer but is also likely an important predictive factor for recurrence, response to treatment, and medication toxicity.
Assuntos
Carcinoma de Células Escamosas , Predisposição Genética para Doença , Neoplasias Bucais , Polimorfismo de Nucleotídeo Único , Canal de Liberação de Cálcio do Receptor de Rianodina , Humanos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Idoso , Adulto , Genótipo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estadiamento de NeoplasiasRESUMO
Background and objectives: The objective of this study is to elucidate peripheral occlusion artery disease (PAOD) as a risk factor for cellulitis. Materials and Methods: This is a retrospective population-based cohort study. The database is the Longitudinal Health Insurance Database, which covers two million beneficiaries from the entire population of the 2010 registry for beneficiaries in Taiwan. The PAOD group is composed of patients who were newly diagnosed with PAOD from 2001 to 2014. The non-PAOD group is composed of patients who were never diagnosed with PAOD from 2001 to 2015. All patients were followed until the onset of cellulitis, death, or until the end of 2015. Results: Finally, 29,830 patients who were newly diagnosed with PAOD were included in the PAOD group, and 29,830 patients who were never diagnosed with PAOD were included in the non-PAOD group. The incidence densities (ID) of cellulitis were 26.05 (95% CI = 25.31-26.80) patients per 1000 person-years in the PAOD group and 49.10 (95% CI = 48.04-50.19) in the non-PAOD group. The PAOD group had an increased risk of cellulitis (adjusted HR = 1.94, 95% CI = 1.87-2.01) compared to the non-PAOD group. Conclusions: Patients with PAOD were associated with a higher risk of subsequent cellulitis compared to patients without PAOD.
Assuntos
Arteriopatias Oclusivas , Doença Arterial Periférica , Humanos , Estudos Retrospectivos , Estudos de Coortes , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/complicações , Doença Arterial Periférica/complicações , Doença Arterial Periférica/epidemiologia , Fatores de Risco , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/epidemiologiaRESUMO
Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops (Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 µM, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis-related pathways. Xn upregulated the expression of apoptosis-related proteins, namely DR5, cleaved RIP, caspase-3, caspase-8, caspase-9, PARP, Bim, and Bak, and it downregulated the expression of Bcl-2. Xn upregulated the c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn-activated cleaved caspase-3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.
Assuntos
Neoplasias Nasofaríngeas , Inibidores de Poli(ADP-Ribose) Polimerases , Apoptose , Proteínas Reguladoras de Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Flavonoides/farmacologia , Humanos , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Carcinoma Nasofaríngeo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Propiofenonas , Transdução de SinaisRESUMO
Background and objectives: We aimed to evaluate the correlation between periodontal disease (PD) and following ocular diseases via the National Health Insurance Research Database in Taiwan. Materials and Methods: A retrospective cohort study was conducted. Subjects were regarded as having PD according to the diagnostic codes. For comparison, each subject with PD was matched to one non-PD individual from the database after exclusion. The main outcome was defined as the development of infectious keratitis, endophthalmitis, orbital cellulitis, lacrimal duct infection, uveitis and infectious scleritis. Cox proportional hazard regression was used to yield the adjusted hazard ratios (aHR) of ocular diseases between the study and control groups. Results: A total of 426,594 subjects were enrolled in both the study and control groups. In the multivariable analysis, significantly higher rates of infectious keratitis (aHR: 1.094, 95% CI: 1.030-1.161), uveitis (aHR: 1.144, 95% CI: 1.074-1.218) and infectious scleritis (aHR: 1.270, 95% CI: 1.114-1.449) were found in the study group. Concerning the PD interval, infectious keratitis (aHR: 1.159, 95% CI: 1.041-1.291) and infectious scleritis (aHR: 1.345, 95% CI: 1.055-1.714) would significantly occur in PD patients with an interval shorter than two years, individuals with a PD interval that ranged from two to five years were under a higher risk of developing uveitis (aHR: 1.184, 95% CI: 1.065-1.315) and infectious scleritis (aHR: 1.386, 95% CI: 1.125-1.708), and the rate of uveitis (aHR: 1.149, 95% CI: 1.038-1.272) was significantly higher if PD persisted more than five years. Conclusions: The presence of PD was moderately associated with the risk of developing infectious keratitis, uveitis and infectious scleritis.
Assuntos
Doenças Periodontais , Estudos de Coortes , Humanos , Incidência , Doenças Periodontais/complicações , Doenças Periodontais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Background and objectives: Breast cancer is a common cancer in women and has been the fourth leading cause of death in Taiwanese women. Risk factors for breast cancer include family history of breast cancer, genetic factors, and not breastfeeding. Several studies have reported an association between repeated inflammation at a young age, especially among lactating women, and cancer; however, the number of studies about the association of mastitis and breast cancer in nonlactating women is still limited. Therefore, the aim of this study was to determine the relationship between mastitis in women aged ≥40 years and breast cancer. Materials and Methods: This was a retrospective cohort study design. The data source was the Longitudinal Health Insurance Database 2010 (LHID 2010), comprising data collected by Taiwan's National Health Insurance program. Cases of newly diagnosed mastitis in women aged ≥40 years (ICD-9-CM code = 611.0) were selected from the years 2010 to 2012. Women not diagnosed with mastitis were selected as the control group, and their data for the years 2009 to 2013 were obtained through the database. In addition, the non-mastitis group was matched 1:10 by age. Results: A total of 8634 participants were selected from the LHID 2010, which included 734 cases with mastitis and 7900 cases without mastitis. After adjustment for age, hypertension, hyperlipidemia, diabetes, hypothyroidism, and autoimmune diseases, the Cox proportional hazard model showed that patients with mastitis had a higher risk of breast cancer (aHR = 3.71, 95% CI = 1.9-7.02) compared with the non-mastitis group. The Kaplan-Meier curve also showed that women with mastitis had a higher risk of developing breast cancer. Conclusions: This study confirmed that women with mastitis have a higher risk of developing breast cancer. Therefore, women aged ≥40 years could reduce breast cancer risk by taking precautions to prevent mammary gland infection and mastitis.
Assuntos
Neoplasias da Mama/diagnóstico , Mastite/complicações , Medição de Risco/métodos , Adulto , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Correlação de Dados , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertireoidismo/complicações , Hipertireoidismo/epidemiologia , Mastite/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30-70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (ß = -5.705; p = 0.001) followed by lacto-ovo vegetarians (ß = -3.900; p < 0.001) and former vegetarians (ß = -0.329; p = 0.475). The test for trend was significant (p < 0.001). After categorization by exercise modalities, the ß-value was -13.984 for strict vegetarians, -4.419 for lacto-ovo vegetarians, and -1.864 for former vegetarians, respectively (p < 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.
Assuntos
HDL-Colesterol/análise , Dieta Vegetariana/normas , Exercício Físico/fisiologia , Adulto , Idoso , Índice de Massa Corporal , HDL-Colesterol/sangue , Dieta Vegetariana/métodos , Dieta Vegetariana/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIMS: Praeruptorins, a seselin-type coumarin, possess anti-inflammatory and antitumor promoting properties. However, molecular mechanisms through which Praeruptorin-B (Pra-B) exerts an antimetastatic effect on cervical cancer cells remain unclear. METHODS: Cell viability was examined using the MTT assay, whereas cell migration and invasion were examined using the Boyden chamber assay. Western blotting and RT-PCR were performed to investigate the inhibitory effect of Pra-B on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-2/-9 (MMP-2/-9) expression in HeLa cells. The findings of the luciferase assay confirmed the inhibitory effect of Pra-B on TPA-induced transcriptional activity of MMP2/-9 in HeLa cells. RESULTS: Pra-B inhibited TPA-induced metastatic ability of human cervical cancer cells without any significant toxicity. Pra-B suppressed TPA-induced mRNA and protein expression and transcriptional activity of MMP-2/-9 in HeLa cells. Furthermore, Pra-B inhibited AKT phosphorylation but did not affect the MAPK pathway. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 (a PI3K inhibitor) reduced cell invasion and MMP-2/-9 expression and transcriptional activity. In addition, Pra-B attenuated TPA-induced nuclear translocation of NF-κB-p65/-p50, which reduced Ikk-α phosphorylation in HeLa cells. Cotreatment of HeLa cells with TPA plus Pra-B or LY294002 reduced NF-κB nuclear translocation. CONCLUSION: These results suggested that Pra-B-mediated inhibition of TPA-induced cell metastasis involved the suppression of p-AKT/NF-κB via MMP-2/-9 expression in HeLa cells. Pra-B can be a potential antimetastatic agent against cervical cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Células HeLa , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , NF-kappa B/metabolismo , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Acetato de Tetradecanoilforbol , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismoRESUMO
The incidence of oral cancer is increasing all over the world, with rates particularly high in Southeast Asian countries, such as Taiwan. Coronarin D (CD) has been confirmed to have anti-inflammatory, anti-bacterial effects, and anti-apoptotic effects in human hepatocellular carcinoma and nasopharyngeal carcinoma. The purpose of this study is to explore whether CD has a suppression effect on oral cancer cells and the mechanisms involved. The results of our study revealed the significantly decreased cancer cell viability and increased activation of apoptosis via increased loss of mitochondrial membrane potential, increased death receptors, leading to the activation of caspase-8, -9, -3. Moreover, the rate of apoptosis of cells treated with CD plus JNK inhibitors was decreased compared to CD-treated cells. This is the first study to demonstrate that CD induces apoptosis in human oral cancer cells and can be expected to be a promising anticancer agent for oral cancer treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diterpenos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Bucais/patologia , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Bucais/enzimologia , Zingiberaceae/químicaRESUMO
Gallic acid (GA) possesses potential antitumoral activity on different types of malignancies. In this study, we aimed to explore the antitumoral effects of GA on triple-negative breast cancer (TNBC) cells, the breast cancer cells showing resistance to hormonal therapy or HER2 receptor targeting therapy. We observed that GA treatment significantly decreased the cell viability of human TNBC cell line MDA-MB-231 and HS578T in a dose-dependent manner. In addition, GA exerted a relative lower cytotoxicity on noncancer breast fibroblast MCF-10F. Next, we analyzed the changes of cell-cycle distribution in response to GA treatment and found that GA led to an increase of G0/G1 and sub-G1 phase ratio in MDA-MB-231 cells. We further explored the crucial mediators controlling cell cycle and inducing apoptotic signaling, and the findings showed that GA downregulated cyclin D1/CDK4 and cyclin E/CDK2, upregulated p21and p27, and induced activation of caspase-9 and caspase-3. In addition, we demonstrated that p38 mitogen-activated protein kinase was involved in the GA-mediated cell-cycle arrest and apoptosis. Collectively, our findings indicate that GA inhibits the cell viability of TNBC cells, which may attribute to the G1 phase arrest and cellular apoptosis via p38 mitogen-activated protein kinase/p21/p27 axis. Thus, we suggest that GA could be beneficial to TNBC treatment.
Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Ácido Gálico/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/enzimologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Reduced nuclear p27 expression is associated with a poor outcome in various cancers, including non-small cell lung cancer (NSCLC). Cytoplasmic p27 expression was shown to be associated with an unfavorable response to chemotherapy and poor outcomes in some carcinomas, but it has not been well studied in NSCLC. Herein, p27 expression in 219 tumors surgically resected from NSCLC patients was evaluated by immunohistochemistry (IHC). The most common of p27 immunostaining in lung tumors was observed in the cytoplasm (N-/C+, 32 %), followed by negative (N-/C-, 29 %), nucleus (N+/C-, 24 %), and nucleus plus cytoplasm (N+/C+, 15 %). Kaplan-Meier and Cox regression models showed that p27 N-/C+ tumors exhibited the worst overall survival (OS) and relapse-free survival (RFS) among the four categories of tumors. Among 135 of 219 patients who received cisplatin-based chemotherapy, p27 N-/C+ tumors most commonly showed an unfavorable response to cisplatin-based chemotherapy, followed by p27 N-/C- tumors when p27 N+/C- tumors were used as a reference. IHC analysis for phosphorylated extracellular signal-regulated kinase (p-ERK) and Bcl-2 expression in the lung tumors was performed to test whether ERK activation could enhance p27 nuclear export and the expression of Bcl-2 to test whether ERK activation could enhance p27 nuclear export and Bcl-2 expression. The data showed that p-ERK expression was positively correlated with cytoplasmic p27 (N-/C+) and Bcl-2 expression in the lung tumors. Patients with high Bcl-2-expressing tumors treated with cisplatin-based chemotherapy showed unfavorable predictive values in a subset of this study population. Therefore, we suggest that cytoplasmic p27 (N-/C+) via ERK-activated Bcl-2 expression may predict an unfavorable response to cisplatin-based chemotherapy and poor outcomes in NSCLC.
Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cisplatino/farmacologia , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Neoplasias Pulmonares/metabolismo , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/uso terapêutico , Citoplasma/metabolismo , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Intercellular adhesion molecule-1 (ICAM-1) is a human protein encoded by the ICAM-1 gene and is typically expressed on endothelial cells and immune cells. ICAM-1 is associated with episode, growth, invasion, and metastasis of hepatocellular carcinoma (HCC). However, the association between ICAM-1 genetic variants and the risk of HCC is undetermined. In this study, we investigated the potential associations of ICAM-1 single nucleotide polymorphisms (SNPs) with susceptibility to HCC and its clinicopathological characteristics. A total of 918 participants, including 613 controls participants and 305 patients with HCC, were selected for the analysis of ICAM-1 SNPs (rs3093030, rs5491, rs281432, and rs5498) by using real-time PCR genotyping. After adjusting for covariants of age, sex, and alcohol consumption, 125 smoker patients with HCC carrying at least one G genotype (AG and GG) in rs5498 were observed to have a higher HCC risk compared with 231 smoker control participants carrying the wild-type allele AA (adjusted odds ratio (AOR), 1.713; 95 % confidence interval (CI), 1.091-2.690; P = 0.019). However, patients who possess at least one polymorphic allele of rs5498 are less prone to develop vascular invasive (AOR, 0.309; 95 % CI, 0.103-0.926; P = 0.036). The results suggest that the genetic polymorphism in ICAM-1 rs5498 SNPs with genotype AG and GG is associated with HCC risk among smokers. Moreover, gene and environment interactions of ICAM-1 rs5498 polymorphisms might alter susceptibility to liver cancer. Therefore, ICAM-1 rs5498 may serve as a marker to predict the vascular invasion risk in smoker patients with HCC.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Neoplasias Hepáticas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Molécula 1 de Adesão Intercelular , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Fumar/efeitos adversosRESUMO
Oral cancer is a common cancer with poor prognosis. We evaluated the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its prognostic significance in oral cancer. PBK/TOPK expression was measured by immunohistochemical staining of samples from 287 patients with oral cancer. The association between PBK/TOPK expression and clinicopathological features was analyzed. The prognostic value of PBK/TOPK for overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. A high PBK/TOPK expression level was correlated with long overall survival. The prognostic role of PBK/TOPK expression was significant in young patients (p < 0.05), patients with smoking habits (p < 0.05), and late stage disease (p < 0.05). Our results suggest that PBK/TOPK expression is enhanced in oral cancer. High PBK/TOPK expression, either alone or in subgroups according to clinicopathological features, may serve as a favorable prognostic marker for patients with oral cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neoplasias Bucais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Neoplasias Bucais/patologiaRESUMO
BACKGROUND: MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear. METHODS: Wild-type or mutant CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan-Meier and Cox regression analysis. RESULTS: MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors. CONCLUSIONS: MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fosfatases cdc25/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas , Fosfatases cdc25/genéticaRESUMO
MiR-21 has been associated with poor prognosis in colon adenocarcinomas. However, in our preliminary data, the prognostic value of miR-21 levels was observed only in adenomatous polyposis coli (APC)-mutated tumours, not in APC-wild-type tumours. We explored whether ß-catenin nuclear translocation was synergistically promoted by miR-21 in APC-mutated cells but not in APC-wild-type cells. We enrolled 165 colorectal tumour to determine APC mutation, miR-21 levels and nuclear ß-catenin expression by direct sequencing, real-time PCR and immunohistochemistry. Overall survival and relapse-free survival were analysed by Kaplan-Meier and Cox regression models. The mechanistic action of ß-catenin nuclear translocation modulated by miR-21 and its effect on cell invasion were evaluated in a cell model. Positive nuclear ß-catenin expression was more commonly occurred in APC-mutated tumours than in APC-wild-type tumours. High miR-21 levels were relatively more common in tumours with positive nuclear ß-catenin expression than in those with negative nuclear ß-catenin expression. APC-mutated tumours with high miR-21 levels had shorter overall survival and relapse-free survival periods compared with others. However, the prognostic value of miR-21 levels was not observed in APC-wild-type tumours. Phosphorylation of ß-catenin at Ser552 via the miR-21-mediated PTEN/AKT axis plays a critical role in ß-catenin nuclear translocation in APC-mutated cells but not in APC-wild-type cells. Moreover, nuclear ß-catenin expression increased by miR-21 is responsible for the capability of invasiveness. In summary, nuclear translocation of ß-catenin increased by miR-21 promotes tumour malignancy and a poor outcome in APC-mutated patients but not in APC-wild-type colorectal cancer.
Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , MicroRNAs/genética , Mutação , beta Catenina/metabolismo , Idoso , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Transporte Proteico , Serina/metabolismo , beta Catenina/genéticaAssuntos
Artrite Reumatoide/etiologia , Infecções por Papillomavirus/complicações , Vigilância da População/métodos , Adulto , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Autoimunidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/imunologia , Taiwan/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Liver kinase B1 (LKB1) loss by gene mutation, loss of heterozygosity, and promoter methylation rarely occurs in colorectal cancer. We wondered whether LKB1 loss could be deregulated at the transcriptional level to promote tumor progression and poor outcome in colorectal cancer. METHODS: Mechanistic studies were performed in two each of p53 wild-type (HCT116, LoVo) and p53-mutated (SW480, HT29) colon cancer cells to explore whether LKB1 loss could be deregulated by NKX2-1-mediated p53 pathway. LKB1 and NK2 homeobox 1 (NKX2-1) expressions in colorectal tumors were determined by immunohistochemistry, and the prognostic value of both molecules was assessed by Kaplan-Meier test and Cox regression model. RESULTS: Mechanistically, LKB1 loss at the transcriptional level due to alteration of the NKX2-1-mediated p53 pathway promotes invasiveness in colon cancer cells. The cell invasiveness induced by LKB1 loss was nearly suppressed by mammalian target of rapamycin (mTOR) inhibitor (rapamycin and everolimus) and mTOR/AKT dual inhibitor Palomid 529 (P529). Among patients, low LKB1 tumors exhibited shorter overall survival (OS) and relapse-free survival periods than high LKB1 tumors. The highest hazard ratio value for OS and relapse-free survival was observed in wild-type p53 with low LKB1/low NKX2-1 tumors and in mutated p53 with low LKB1/high NKX2-1 tumors when wild-type p53 with high LKB1/high NKX2-1 and mutated p53 with high LKB1/low NKX2-1 tumors were used as references. CONCLUSIONS: LKB1 loss at the transcriptional level via alteration of the NKX2-1/p53 axis promotes cell invasion, consequently resulting in poor outcome in colorectal cancer patients.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Proteína Supressora de Tumor p53/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Idoso , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Neoplasias Colorretais/química , Progressão da Doença , Intervalo Livre de Doença , Everolimo , Técnicas de Silenciamento de Genes , Células HCT116 , Células HT29 , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Nucleares/análise , Proteínas Nucleares/genética , Modelos de Riscos Proporcionais , Proteínas Serina-Treonina Quinases/análise , Transdução de Sinais , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Taxa de Sobrevida , Fator Nuclear 1 de Tireoide , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Transcrição Gênica/efeitos dos fármacos , Proteína Supressora de Tumor p53/genéticaRESUMO
CONTEXT: Mitochondrial DNA (mtDNA) copy number correlates with tumor pathology in some cancers. OBJECTIVE: To investigate mtDNA copy number in head and neck cancer (HNC). MATERIALS AND METHODS: mtDNA copy number was determined and compared between HNC patients and malignancy-free controls. RESULTS: The mtDNA copy number was significantly higher in HNC patients, increased with cancer progression and correlated negatively with patient survival. DISCUSSION: mtDNA copy number appears to be associated with HNC stage and survival, but confirmation requires similar studies in larger cohorts. CONCLUSION: Studies to establish the nature of the relationship between mtDNA copy number and HNC are warranted.