RESUMEN
Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The current case-control study aimed to examine the effects of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) single-nucleotide polymorphisms (SNPs) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP -2548 have a significant low risk for the development of clinical stage (A/G: adjusted odds ratio [AOR] = 0.670, 95% confidence interval [CI] = 0.454-0.988, P < 0.05; A/G + G/G: AOR = 0.676, 95% CI = 0.467-0.978, P < 0.05) compared to patients with ancestral homozygous A/A genotype. In addition, an interesting result was found that the impact of LEP -2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP -2548 G/A showed a poor clinicopathological development of oral cancer; population without tobacco consumption and with polymorphic LEP -2548 G/A gene may significantly increase the risk to have oral cancer.
Asunto(s)
Carcinogénesis/genética , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Leptina/genética , Neoplasias de la Boca/genética , Polimorfismo de Nucleótido Simple/genética , Fumar/genética , Carcinogénesis/patología , Estudios de Casos y Controles , Intervalos de Confianza , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Receptores de Leptina/genéticaRESUMEN
From several decades ago to now, cancer continues to be the leading cause of death worldwide, and metastasis is the major cause of cancer-related deaths. For health benefits, there is a great desire to use non-chemical therapy such as nutraceutical supplementation to prevent pathology development. Over 10,000 different natural bioactives or phytochemicals have been known that possessing potential preventive or supplementary effects for various diseases including cancer. Previously, the in vitro and in vivo anti-invasive and anti-metastatic activities of phenolic acids, monophenol, polyphenol and their derivatives and flavonoids and their derivatives have been reviewed. However, a vast number of natural dietary compounds other than phenolics have been demonstrated to potentially possess the ability to inhibit the invasion and metastasis of various cancers. In this review, we summarize the studies in recent decade on in vitro and in vivo effects and molecular mechanisms of natural bioactives, excluding the phenolics in food, in cancer invasion and metastasis. By combining this review of non-phenolics with the previous phenolics reviews, the puzzle for the contribution of natural dietary bioactives on cancer invasive or/and metastatic progress will be almost complete and more clear.
Asunto(s)
Suplementos Dietéticos/análisis , Neoplasias/tratamiento farmacológico , Fitoquímicos/administración & dosificación , Animales , Humanos , Metástasis de la Neoplasia , Neoplasias/patologíaRESUMEN
Single nucleotide polymorphism (SNP) in some genes is a candidate for having or developing a cancer. Cathepsin B (CTSB) is considered to be the biomarker of cancers. The study aimed to evaluate the impacts of three SNPs in CTSB gene on the risk and progress of hepatocellular carcinoma (HCC). The SNPs of CTSB C76G (rs12338), CTSB A4383C (rs13332), and CTSB A8422G (rs8898) from 135 patients with HCC and 520 control participants in Taiwan were determined by real-time PCR. Through analyzing by statistics, we found that the polymorphism of rs13332 was significantly associated to the risk of HCC cancer; a significantly high frequent tumor size development was observed in HCC patients carrying rs12338 polymorphic genotype than those carrying ancestral genotype. The SNPs of rs12338, rs13332, and rs8898 were irrelevant to the frequencies of HCC clinical status and the levels of HCC clinicopathological markers. In conclusions, CTSB A4383C SNP is observed modestly more often in patients who developed HCC than in healthy controls and might be associated with the risk of HCC. The association between CTSB C76G SNP and greater tumor size may warrant further study in regards to the biology of HCC.
Asunto(s)
Carcinoma Hepatocelular/etiología , Catepsina B/genética , Neoplasias Hepáticas/etiología , Polimorfismo de Nucleótido Simple/genética , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Uso de Tabaco/efectos adversosRESUMEN
Patients with lung adenocarcinoma are often diagnosed with metastasizing symptoms and die of early and distal metastasis. Metastasis is made up of a cascade of interrelated and sequential steps, including cell adhesion, extracellular matrix degradation, cell movement, and invasion. Hence, substances carrying the ability to stop one of the metastasis-associated steps could be a potential candidate for preventing tumor cells from metastasizing and prolonging the life of cancer patients. Cinnamic acid (CA) was demonstrated to be such a candidate for human lung adenocarcinoma cells. Nevertheless, the effectiveness of CA derivatives on invasion of lung cancer cells is still unclear. The aims of this study were to explore the mechanisms underlying several select CA derivatives against invasion of human lung adenocarcinoma A549 cells. The results revealed that caffeic acid (CAA), chlorogenic acid (CHA), and ferulic acid (FA) can inhibit phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of A549 cells at a concentration of ≥100 µM. The MMP-9 activity was suppressed by these compounds through regulating urokinase-type plasminogen activator (uPA), tissue inhibitor of metalloproteinase (TIMP)-1, plasminogen activator inhibitor (PAI)-1, and PAI-2; the cell-matrix adhesion was decreased by CAA only. The proposed molecular mechanism involved not only decreasing the signaling of MAPK and PI3K/Akt but also inactivating NF-κB, AP-1, and STAT3. In the present study, we selected CAA, CHA, and FA as potential inhibitors for invasive behaviors of human lung adenocarcinoma cells and disclosed the possible mechanisms. The association between structural features and anti-invasive activity of these compounds cannot be determined here and needs to be further verified.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Cinamatos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Antineoplásicos Fitogénicos/química , Ácidos Cafeicos/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Ácido Clorogénico/farmacología , Cinamatos/química , Ácidos Cumáricos/farmacología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica/patología , Invasividad Neoplásica/prevención & control , Transducción de Señal/efectos de los fármacosRESUMEN
Dietary polyphenols have been reported as an effective phytochemical for health protection and cinnamic acid (CA) is one of the polyphenols that has been demonstrated having chemopreventive potential. It was known that the early and distal metastasis might lead to the high mortality of patients with lung adenocarcinoma. We previously compared and verified the inhibitory effect of cis-CA and trans-CA on phorbol-12-myristate-13-acetate (PMA)-induced invasion of human lung adenocarcinoma A549 cells. The aim of this study was to explore the underlying molecular mechanism. By gelatin zymography and semi-quantitative RT-PCR, the activities and mRNA of MMP-9/MMP-2 exerted a significantly (p<.05) dose-dependent reduction by treating with cis-CA and trans-CA. Western blots further showed that the cis-CA- and trans-CA-inhibited MMPs might partly through modulating TIMP-1 and the PAI-2-regulated uPA activity. In molecular level, the AP-1 and NF-κB as well as the downstream of the MAPK pathway might be involved in cis-CA- and trans-CA-inhibited MMPs expression. This study disclosed the molecular mechanism underlying the anti-invasive activity of cis-CA and trans-CA and concluded the cis- and trans-form of CA should be a safe and potential agent to prevent lung tumor cells from metastasizing.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Cinamatos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Modelos Biológicos , Adenocarcinoma/inducido químicamente , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anticarcinógenos/efectos adversos , Anticarcinógenos/química , Anticarcinógenos/farmacología , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/química , Carcinógenos/antagonistas & inhibidores , Carcinógenos/toxicidad , Línea Celular Tumoral , Cinamatos/efectos adversos , Cinamatos/química , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/química , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/química , Metaloproteinasa 9 de la Matriz/genética , Invasividad Neoplásica , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Concentración Osmolar , Estereoisomerismo , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/antagonistas & inhibidores , Acetato de Tetradecanoilforbol/toxicidad , Inhibidor Tisular de Metaloproteinasa-1/agonistas , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/antagonistas & inhibidores , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismoRESUMEN
Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Cathepsin B (CTSB) is a lysosomal cysteine protease and may serve as a candidate biomarker of oral cancer. The current study aimed to explore the influences of three single nucleotide polymorphisms (SNPs) in CTSB gene, combined with environmental carcinogens on the risk and clinicopathological development of oral cancer. Three SNPs of CTSB, CTSB C76G (rs12338), CTSB A4383C (rs13332), and CTSB A8422G (rs8898), from 444 male patients with oral cancer and 426 control participants (males not diagnosed with cancer) in Taiwan were analyzed. These three CTSB SNPs all exhibited insignificant (P > 0.05) effects on the risk of oral cancer. However, the risk for developing the poor clinical stage of moderately or poorly differentiated cells was significantly (P < 0.001) increased to 3.325-fold in patients with oral cancer carrying the polymorphic genotype of rs8898 compared to patients with the ancestral genotype. Additionally, while considering the exposure of environmental carcinogens, the presence of these three CTSB SNPs, combined with betel quid chewing [adjusted odds ratio (AOR) was 36.570, 21.772, and 43.962 for rs12338, rs13332, and rs8898, respectively] and/or tobacco use (AOR was 3.794, and 8.972 for rs12338 and rs13332, respectively), robustly elevated the susceptibility to oral cancer. These results suggest that the genetic polymorphism of CTSB A8422G (rs8898) was associated with a high risk for the clinicopathological development of oral cancer and CTSB gene polymorphisms may increase the susceptibility to environmental carcinogens-mediated oral cancer.
Asunto(s)
Catepsina B/genética , Neoplasias de la Boca/etiología , Neoplasias de la Boca/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Carcinógenos Ambientales/toxicidad , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/genética , Estudios de Casos y Controles , Exposición a Riesgos Ambientales , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/enzimología , Factores de Riesgo , TaiwánRESUMEN
BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is seldom available because of the lack of reliable markers. Survivin is an anti-apoptotic protein that is implicated in the regulation of apoptosis and cell cycle, and it is undetectable in normal adult tissues but is overexpressed in various types of cancers. Survivin is thus commonly considered to be a marker of malignancy. The aim of this study was to explore the association between survivin gene polymorphisms and the risk and diagnostic progress of HCC. METHODS: A total of 135 patients with HCC and 496 healthy control subjects were recruited. Five single nucleotide polymorphisms (SNPs) of survivin genes were determined by real-time polymerase chain reaction (real-time PCR) and further analyzed statistically. RESULTS: We first found that the -241 C/T and -235 G/A genetic polymorphisms of survivin did not occur frequently enough or even lacked in Taiwanese population. The +9809 C/C polymorphism exhibited a significant (P < .05) low risk of 0.525-fold (95% confidence interval [95% CI] = 0.297-0.930) to have HCC compared with the wild-type homozygotes and a low ratio of 0.214-fold (95% CI = 0.051-0.890) for positive anti-HCV was shown in the individuals with survivin +9809 polymorphic CC allele compared with the TT/TC genotypic subgroup. CONCLUSIONS: Survivin +9809 polymorphic genotype is associated with the risk of HCC, and the HCC patients with survivin +9809 CC homozygotes might have a low risk of developing infected HCV-dependent HCC. The results suggest that the survivin T9809C SNP might contribute to the prediction of susceptibility and pathological development to HCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Predisposición Genética a la Enfermedad , Proteínas Inhibidoras de la Apoptosis/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Anciano , Alanina Transaminasa/sangre , Pueblo Asiatico/genética , Aspartato Aminotransferasas/sangre , Carcinoma Hepatocelular/sangre , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Intervalos de Confianza , Femenino , Humanos , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Estadísticas no Paramétricas , Survivin , Taiwán , Secuencias Repetidas Terminales/genética , alfa-Fetoproteínas/metabolismoRESUMEN
Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis. The long course of treatments on TB with a combination of antibiotics leads unfavorable side effects and poor patient compliance which contributes to sustaining multiple-drug resistant tuberculosis (MDR-TB). Therefore, the development of a new effective drug or synergist to reduce the prevalence of MDR-TB is urgent to date. Cinnamic acid (CA) is a natural occurring phenolic compound with anti-microbial activity. Both trans- and cis-isoforms of CA exist in planta, and cis-cinnamic acid (c-CA) can be transformed from trans-cinnamic acid (t-CA) under sunlight. Due to the unavailability of c-CA, the literature regarding the biological functions of c-CA is still limited. We had previously developed a practicable method for the transformation of c-CA from t-CA and the isolation of c-CA. Using the techniques, sufficient c-CA was obtained to evaluate its antituberculosis activity against a MDR M. tuberculosis strain. Moreover, the synergistic effects of c-CA and t-CA with two first-line anti-TB antibiotics, isoniazid (INH) and rifampicin (RIF), were also determined. Although both of c-CA and t-CA decreased the viability of MDR-TB bacilli in a dose-dependent manner, the antituberculosis activity of c-CA was approximately 120-fold of t-CA. Furthermore, the c-CA exhibited higher synergistic effect with INH or RIF against tuberculosis than t-CA. The micrographs of scanning electron microscope (SEM) display that c-CA caused an injury on the out-layer of MDR-TB bacilli. The c-CA might be a potential anti-mycobacterial or synergistic agent that can be developed to against tuberculosis.
Asunto(s)
Antibióticos Antituberculosos/farmacología , Cinamatos , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antibióticos Antituberculosos/uso terapéutico , Cinamatos/química , Cinamatos/farmacología , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Humanos , Isomerismo , Isoniazida/farmacología , Isoniazida/uso terapéutico , Microscopía Electrónica de Rastreo , Mycobacterium tuberculosis/ultraestructura , Rifampin/farmacología , Rifampin/uso terapéuticoRESUMEN
BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is seldom available because of the lack of reliable markers. Matrix metalloproteinase (MMP) 14 is a cell surface proteinase that displays a broad spectrum of activity against extracellular matrix components and promotes the invasion/metastasis of cells. MMP14 is overexpressed in HCC, and the level is correlated with poor overall survival. The purpose of this study was to examine whether the MMP14 gene polymorphisms are associated with the susceptibility and clinicopathological development of HCC. METHODS: A total of 135 patients with HCC and 496 healthy control subjects were recruited. Six single nucleotide polymorphisms (SNPs) of MMP14 genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping and haplotype-base analysis. RESULTS: A significant (p < 0.05) lower risk for HCC was shown in the individuals with MMP14 +6767 G/A and +7096 C/C genotypes compared with those with corresponding wild-type homozygotes; high frequency for anti-hepatitis C virus and cirrhosis positive were shown in the HCC patients with MMP14 +7096 TC/CC genotype after adjusting for other confounding factors. The distribution frequency of -165 T: +221 T: +6727 C: +6767 G: +7096 T: +8153 G haplotype and diplotype was significantly higher in the HCC patients than healthy control subjects. CONCLUSIONS: The +6767 and +7096 polymorphic genotypes and haplotype -165 T: +221 T: +6727 C: +6767 G: +7096 T: +8153 G of MMP14 gene might contribute to the prediction of susceptibility and pathological development to HCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Metaloproteinasa 14 de la Matriz/genética , Recurrencia Local de Neoplasia/genética , Polimorfismo de Nucleótido Simple/genética , Carcinoma Hepatocelular/secundario , Estudios de Casos y Controles , ADN de Neoplasias/genética , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The levels of urokinase plasminogen activator (uPA) system in tumor tissues are implicated as prognostic biomarkers in a wide range of malignancies. However, their possible impact on the risk and prognosis of oral cancer and the susceptibility of environmental carcinogens to oral cancer remains poorly investigated. METHODS: The genetic polymorphisms of uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 253 patients with oral cancer and 344 healthy controls. RESULTS: There was no significant effect of uPA system genes on the susceptibility of oral cancer; however, the impact of uPA system gene polymorphisms on the susceptibility of betel nut and tobacco consumptions to oral cancer was revealed, except for that of uPAR gene polymorphism on tobacco consumption. Patients with oral cancer with at least one 5G allele of PAI-1 gene have a low risk for the development of clinical stage III or IV (p ≤ 0.05) and lymph node metastasis (p ≤ 0.05) compared with those with 4G/4G homozygotes. CONCLUSIONS: Our results suggest that the combination of uPA system gene polymorphisms and environmental carcinogens was related to the risk of oral cancer, and the genetic polymorphism of PAI-1 was associated with a low risk to the clinicopathological development of oral cancer.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Inactivadores Plasminogénicos/genética , Polimorfismo de Nucleótido Simple/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , Carcinoma de Células Escamosas/secundario , Estudios de Casos y Controles , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , NicotianaRESUMEN
BACKGROUND: The urokinase plasminogen activator (uPA) system is a serine proteinase system involved in extracellular matrix (ECM) degradation. The levels of uPA system components in tumor tissues are implicated as prognostic biomarkers in a wide range of malignancies. Although the contributions of uPA system components to the formation of many types of cancer are well known, their possible association with the prediction of risk and prognosis of hepatocellular carcinoma (HCC) remains poorly investigated. METHODS: A total of 102 HCC patients and 344 controls were recruited. Genetic polymorphisms of uPA system genes, including uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1, were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. RESULTS: When individuals were classified into male and female subgroups to estimate adjusted odds ratios (AORs) with their 95% confidence intervals (CIs) of each uPA system gene, the HCC risks of males and females with PAI-1 5G/5G genotype were 6.06-fold (95% CI = 1.39-26.36) and 0.04-fold (95% CI = 0.003-0.69), respectively, as compared with those with PAI-1 4G/4G genotype. High risk for hepatitis B surface antigen (HBsAg)-positive clinical status and significantly higher serum aspartate aminotransferase (AST) concentration were exhibited in HCC patients with PAI-1 4G/5G and 5G/5G genotypes as compared with 4G/4G homozygotes. CONCLUSIONS: The results suggest that PAI-1 genotypes could be an important factor contributing to increased susceptibility and pathological development of HCC in Taiwanese population.
Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Hígado/patología , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo de Nucleótido Simple/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , Anciano , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , ADN de Neoplasias/genética , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Hígado/metabolismo , Neoplasias Hepáticas/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , PronósticoRESUMEN
Inflammation can be induced by cytokines, chemokines, and their receptors, and it is believed to be a risk factor on tumor initiation and progression. The contribution of CC chemokine ligand 5 (CCL5) and CC chemokine receptor 5 (CCR5) on the risk and prognosis of oral cancer is still poorly investigated. The aims of this study were to investigate the impacts of single nucleotide polymorphisms (SNPs) in CCL5 and CCR5 genes and the synergistic effects of these SNPs on the risk and clinicopathological characteristics of oral cancer. In this case-control study, a total of 253 oral cancer patients and 347 controls were recruited. The genetic polymorphisms of CCL5-28, -403 and CCR5-59029 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. The results of statistical analysis showed that the subjects with CCL5-28 CG, CCL5-28 CG or GG, and CCL5-403 TT polymorphic genotype as well as the subjects with the combinations of CCL5-28 CG/-403 CT and CCL5-28 CG/-403 TT genotypes having a significant higher risk to oral cancer than those with wild-type genotypes. Moreover, the oral cancer patients with the combination of CCL5-28 CG/-403 TT genotype presented a lower risk for developing a moderately or poorly differentiated status as compared to those with the combination of CCL5-28 CC/-403 CC genotype. These results suggest that the SNPs in CCL5-28 and -403 genes could increase the risk to have oral cancer, and the combinative effect of CCL5-28 CG and -403 TT genes might also increase the oral cancer risk but reduce the clinicopathological development of oral cancer patients.
Asunto(s)
Quimiocina CCL5/genética , Neoplasias de la Boca/genética , Polimorfismo de Nucleótido Simple/genética , Receptores CCR5/genética , Estudios de Casos y Controles , Quimiocina CCL5/metabolismo , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Polimorfismo de Longitud del Fragmento de Restricción/genética , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. The insulin-like growth factors (IGFs) system consists of a group of proteins which may induce cell proliferation and inhibit cell apoptosis through several signal pathways, leading to transformation of normal cells into cancer cells. However, the impact of genetic polymorphisms of the IGFs system on HCC has not been clarified. METHODS: In this case-control study, a total of 102 HCC patients and 306 age- and gender-matched controls were recruited. The genetic polymorphisms of the IGFs system genes, including IGF-1, IGF-2, IGF-1receptor (IGF-1R), IGF-2R, IGF binding protein (IGFBP-3), and insulin (INS) genes, were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and real-time PCR genotyping analysis. RESULTS: A significant difference (p = 0.02) between case and control group in the distribution frequency of IGF-2 +3580 polymorphism was observed. Multiple regression model analysis showed that the presence of AA or AG at IGF-2R may exhibit a potential protective effect against hepatitis C [odds ratio (OR) = 0.35, 95% confidence interval (CI) = 0.15-0.82]. The combination of IGF-2 +3580 AA genotype and IGF-2R GG genotype may present a significantly lower risk of HCC (OR = 0.20, 95% CI = 0.05-0.87). Additionally, no polymorphisms of any IGFs system genes were associated with liver-related clinicopathological markers in serum. CONCLUSIONS: Among IGFs system genes, IGF-2 and IGF-2R gene polymorphisms and combination could be considered as the most important factors contributing to increased susceptibility and pathological development of HCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Predisposición Genética a la Enfermedad , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Polimorfismo Genético/genética , Somatomedinas/genética , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Insulina/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 2/genética , Factores de RiesgoRESUMEN
The effects of n-acetyl cysteine (NAC), s-allyl cysteine (SAC), s-ethyl cysteine, s-methyl cysteine and s-propyl cysteine (SPC) activity on Balb/cA mice against diabetic complications were examined. These complications included hyperglycemia, hyperlipidemia, oxidation stress, blood coagulation, and cytokine imbalance. To induce diabetes, mice were treated with streptozotocin i.p. for 5 consecutive days. Five cysteine-containing compounds at 1 g/L were added to the drinking water. After intake of the 5 cysteine-containing agents for 4 wk, body weight loss, plasma concentrations of glucose and insulin, and fibronectin levels were improved (P < 0.05) in diabetic mice. The administration of these agents restored the glutathione level (P < 0.05), reduced the loss of catalase and glutathione peroxidase activities in kidney and liver (P < 0.05), and decreased glucose-induced lipid oxidation, as assessed by malondialdehyde formation (P < 0.05). In all diabetic mice, the intake of these agents reduced triglyceride levels in plasma and liver (P < 0.05); however, only NAC, SAC and SPC treatments reduced cholesterol level in liver (P < 0.05). These cysteine-containing agents elevated the activity of 2 fibrinolytic factors, protein C and antithrombin III (P < 0.05). The overexpression of interleukin-6 and tumor necrosis factor-alpha in diabetic mice was suppressed by the intake of the 5 cysteine-containing agents (P < 0.05). Via their antioxidant activities, the 5 compounds effectively improved glycemic control, delayed oxidation damage, downregulated inflammatory cytokines, and enhanced anticoagulant activity in diabetic mice. These data support the multiple roles of these agents as potential protective agents for delaying diabetic deterioration.