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INTRODUCTION: Crystallization test is based on the principle that, when a salt crystallizes out of an aqueous solution, the crystal growth is influenced by the presence of other substances in the solution, such as blood or plant extracts. If a mixture of copper chloride solution with a small amount of whole blood is allowed to crystallize under controlled experimental conditions, an aggregate of crystals forms. Crystallization method can be used as a diagnostic aid to provide information about the systemic conditions and general health of the patient. AIM: This study aims to study the patterns of crystallization and to further determine the efficacy of crystallization test as a screening modality in premalignant lesions and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Fifty patients of OSCC, 50 patients of premalignant lesions, and 50 healthy individuals were selected. One drop of blood was collected from the study groups to perform crystallization using cupric chloride. STATISTICAL ANALYSIS USED: Statistical analysis was performed using Chi-square test, Student's t-test (two-tailed), and analysis of variance. RESULTS: The different patterns of crystals formed were studied and statistically analyzed. CONCLUSION: Based on the study, it was concluded that Crystallization test can be used as an effective screening modality for detection of premalignant lesions and OSCC.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Cobre/química , Cristalización/métodos , Leucoplasia/sangre , Neoplasias de la Boca/diagnóstico , Lesiones Precancerosas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/química , Estudios de Casos y Controles , Femenino , Humanos , Leucoplasia/patología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Neoplasias de la Boca/sangre , Neoplasias de la Boca/química , Estadificación de Neoplasias , Lesiones Precancerosas/sangre , Adulto JovenRESUMEN
PURPOSE: Glycerol usage is increasing in food industry for human and animal nutrition. This study analyzed the impact of glycerol metabolism when orally supplemented during the early stage of rat liver carcinogenesis. METHODS: Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group). IP animals also received glycerol by gavage (200 mg/kg body weight, IPGly group). RESULTS: Glycerol treatment reduced the volume of preneoplastic lesions by decreasing the proliferative status of liver foci, increasing the expression of p53 and p21 proteins and reducing the expression of cyclin D1 and cyclin-dependent kinase 1. Besides, apoptosis was enhanced in IPGly animals, given by an increment of Bax/Bcl-2 ratio, Bad and PUMA mitochondrial expression, a concomitant increase in cytochrome c release and caspase-3 activation. Furthermore, hepatic levels of glycerol phosphate and markers of oxidative stress were increased in IPGly rats. Oxidative stress intermediates act as intracellular messengers, inducing p53 activation and changes in JNK and Erk signaling pathways, with JNK activation and Erk inhibition. CONCLUSION: The present work provides novel data concerning the preventive actions of glycerol during the development of liver cancer and represents an economically feasible intervention to treat high-risk individuals.
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Anticarcinógenos/uso terapéutico , Apoptosis , Suplementos Dietéticos , Glicerol/uso terapéutico , Neoplasias Hepáticas Experimentales/prevención & control , Estrés Oxidativo , Lesiones Precancerosas/prevención & control , Animales , Anticarcinógenos/sangre , Anticarcinógenos/metabolismo , Biomarcadores/sangre , Carcinogénesis , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glicerol/sangre , Glicerol/metabolismo , Peroxidación de Lípido , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas Experimentales/sangre , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Sistema de Señalización de MAP Quinasas , Masculino , Mitocondrias Hepáticas/enzimología , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/patología , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosforilación , Lesiones Precancerosas/sangre , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Ratas Wistar , Carga TumoralRESUMEN
Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.
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Quimioprevención , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/prevención & control , Metabolómica , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/prevención & control , Té/química , Animales , Azoximetano , Peso Corporal/efectos de los fármacos , Colon/efectos de los fármacos , Colon/patología , Neoplasias Colorrectales/sangre , Citocinas/sangre , Análisis Discriminante , Factores Inmunológicos/farmacología , Análisis de los Mínimos Cuadrados , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Lesiones Precancerosas/sangre , Lesiones Precancerosas/patología , Ratas WistarRESUMEN
OBJECTIVE: To investigate the effect of direct moxibustion at Ganshu (BL18) on the serum concentrations of tumor specific growth factor (TSGF) and tumor necrosis factor α (TNF-α) in a rat model with precancerous lesion of primary hepatocellular carcinoma (HCC), so as to explore the mechanism of moxibustion underlying improvement of HCC. METHODS: Sixty male Wistar rats were randomly divided into control group (n=10), model group (n=20), prevention group 1 (n=15) and prevention group 2 (n=15). The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibustion with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 (1 treatment course, 20 days) and prevention group 2 (2 treatment courses, 40 days), 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point (before model establishment, the end of 1st course prevention, the end of 2nd course prevention and the end of model establishment), serum levels of TSGF and TNF-α were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, there was a remarkably increase of serum TSGF and TNF-α contents in the model group at the end of the experiment (P<0.05). At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF-α of rats in the prevention group 1 were significantly increased compared with that of the model group (P<0.05). At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-α levels of rats in the model group were higher than the normal group with significantly difference (P<0.05), and the levels of TSGF and TNF-α in the prevention group 2 were significantly reduced in comparison with the model group (P<0.05). CONCLUSION: It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the therapeutic effect of two courses were better than one course.
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Puntos de Acupuntura , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Moxibustión , Proteínas de Neoplasias/sangre , Lesiones Precancerosas/sangre , Factor de Necrosis Tumoral alfa/sangre , Animales , Masculino , Ratas WistarRESUMEN
Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of glutathione S-transferase placental form (GST-P)-positive (GST-P(+)) foci, a hepatic preneoplastic lesion, in SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of GST-P(+) foci and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. In conclusion, obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed GST-P(+) foci hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis.
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Anticarcinógenos/uso terapéutico , Catequina/análogos & derivados , Hígado Graso/tratamiento farmacológico , Hipertensión/complicaciones , Neoplasias Hepáticas/prevención & control , Obesidad/complicaciones , Lesiones Precancerosas/tratamiento farmacológico , Angiotensina II/sangre , Animales , Anticarcinógenos/farmacología , Catequina/farmacología , Catequina/uso terapéutico , Hígado Graso/sangre , Hígado Graso/etiología , Expresión Génica , Interleucina-6/sangre , Interleucina-6/genética , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Masculino , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Lesiones Precancerosas/sangre , Lesiones Precancerosas/etiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
OBJECTIVE: To observe clinical efficacy of Huazhuo Jiedu Recipe (HJR) on chronic atrophic gastritic precancerosis (CAGP), and its effect on contents of lactic acid, total acid, free acid, and nitrite in the gastric juice, as well as tumor markers in gastric juice and blood. METHODS: Two hundred and twenty-nine patients with CAGP were randomly assigned to two groups, the 119 patients in the treated group orally took HJR and the 110 patients in the control group orally took Weifuchun Tablet. The therapeutic course for all was three months, two courses in total. The therapeutic efficacy, changes of gastric acid contents before and after treatment were observed, and the tumor markers in the gastric juice and blood were detected using electrochemical luminescence immunoassay. RESULTS: The pathological effective rate was 83.2% (99/119) in the treated group and 60.9% (67/110) in the control group, showing significant difference between the two groups (P <0.05). The total acids and free acids in the gastric juice were significantly improved, contents of lactic acid and nitrite were significantly lowered in the two groups. Both contents of carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen72-4 (CA72-4), and carbohydrate antigen125 (CA125) in the gastric juice and serum were significantly lowered after treatment in the treated group (P<0.05). Compared with the normal control group, the therapeutic effect was more obvious in the treated group (P<0.05). CONCLUSIONS: HJR could stimulate the gastric membranous secretion, enhance contents of total acids and free acids. It could prevent the further progress of CAGP by decreasing contents of lactic acid and nitrite in the gastric juice, and lowering contents of CEA, CA19-9, CA72-4, and CA125 in the gastric juice and serum.
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Medicamentos Herbarios Chinos/farmacología , Jugo Gástrico/química , Gastritis Atrófica/metabolismo , Lesiones Precancerosas/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/sangre , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Gastritis Atrófica/sangre , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Lesiones Precancerosas/sangre , Neoplasias Gástricas/sangreRESUMEN
In cancer cell lines and rodent models, calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis in colonic epithelia. These effects may be modulated by local expression of the calcium receptor (CaR), the vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however, they have yet to be investigated in humans. To address this gap, we conducted a randomized, double-blinded, placebo-controlled 2×2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months (n=92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution in biopsies of normal appearing rectal mucosa were detected by standardized, automated immunohistochemistry and quantified by image analysis. In the calcium-supplemented group, CaR expression increased 27% (P=0.03) and CYP24A1 expression decreased 21% (P=0.79). In the vitamin D3-supplemented group, CaR expression increased 39% (P=0.01) and CYP27B1 expression increased 159% (P=0.06). In patients supplemented with both calcium and vitamin D3, VDR expression increased 19% (P=0.13) and CaR expression increased 24% (P=0.05). These results provide mechanistic support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal neoplasms.
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Adenoma/tratamiento farmacológico , Biomarcadores de Tumor/metabolismo , Calcio/administración & dosificación , Colecalciferol/administración & dosificación , Neoplasias Colorrectales/prevención & control , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/biosíntesis , Adenoma/sangre , Adenoma/metabolismo , Calcio/metabolismo , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Método Doble Ciego , Femenino , Humanos , Inmunohistoquímica , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Lesiones Precancerosas/sangre , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/metabolismo , Receptores de Calcitriol/biosíntesis , Receptores Sensibles al Calcio/biosíntesis , Esteroide Hidroxilasas/biosíntesis , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitamina D3 24-HidroxilasaRESUMEN
This study represents a multiplex cytokine analysis of serum from a 10-month randomized, controlled trial of 238 subjects that investigated the effects of selenomethionine and/or celecoxib in subjects with mild or moderate esophageal squamous dysplasia. The original chemoprevention study found that, among those with mild dysplasia, selenomethionine treatment favorably altered dysplasia grade. The current analysis found that selenomethionine downregulated interleukin (IL)-2 by 9% (P = 0.04), whereas celecoxib downregulated IL-7 by 11% (P = 0.006) and upregulated IL-13 by 17% (P = 0.008). In addition, an increase in IL-7 tertile from baseline to t10 was significantly associated with an increase in dysplasia grade, both overall [odds ratio (OR), 1.47; P = 0.03] and among those with mild dysplasia at t0 (OR, 2.53; P = 0.001). An increase in IL-2 tertile from baseline to t10 was also nonsignificantly associated with worsening dysplasia for all participants (OR, 1.32; P = 0.098) and significantly associated with worsening dysplasia among those with mild dysplasia at baseline (OR, 2.0; P = 0.01). The association of increased IL-2 with worsening dysplasia remained significant in those on selenomethionine treatment who began the trial with mild dysplasia (OR, 2.52; P = 0.03). The current study shows that selenomethionine supplementation decreased serum IL-2 levels, whereas celecoxib treatment decreased IL-7 levels and increased IL-13 levels during a 10-month randomized chemoprevention trial. An increase in IL-2 or IL-7 was associated with increased severity of dysplasia over the course of the trial, especially in those who began the trial with mild dysplasia. The favorable effect of selenomethionine on esophageal dysplasia in the original trial may have been mediated in part by its effect in reducing the levels of IL-2.
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Anticarcinógenos/uso terapéutico , Citocinas/sangre , Neoplasias Esofágicas/sangre , Interleucina-2/sangre , Neoplasias de Células Escamosas/sangre , Lesiones Precancerosas/sangre , Selenometionina/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Celecoxib , Neoplasias Esofágicas/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Escamosas/prevención & control , Oportunidad Relativa , Lesiones Precancerosas/tratamiento farmacológico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéuticoRESUMEN
Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage.
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Antioxidantes/uso terapéutico , Curcumina/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Neoplasias de la Boca/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Lesiones Precancerosas/tratamiento farmacológico , Saliva/química , 8-Hidroxi-2'-Desoxicoguanosina , Adolescente , Adulto , Antioxidantes/análisis , Ácido Ascórbico/análisis , Ácido Ascórbico/sangre , Biomarcadores/análisis , Biomarcadores/sangre , ADN/efectos de los fármacos , Daño del ADN , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Desoxiguanosina/sangre , Femenino , Estudios de Seguimiento , Humanos , Leucoplasia Bucal/sangre , Leucoplasia Bucal/tratamiento farmacológico , Leucoplasia Bucal/metabolismo , Liquen Plano Oral/sangre , Liquen Plano Oral/tratamiento farmacológico , Liquen Plano Oral/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/análisis , Malondialdehído/sangre , Persona de Mediana Edad , Neoplasias de la Boca/sangre , Neoplasias de la Boca/metabolismo , Fibrosis de la Submucosa Bucal/sangre , Fibrosis de la Submucosa Bucal/tratamiento farmacológico , Fibrosis de la Submucosa Bucal/metabolismo , Dimensión del Dolor , Lesiones Precancerosas/sangre , Lesiones Precancerosas/metabolismo , Sustancias Protectoras/uso terapéutico , Vitamina E/análisis , Vitamina E/sangre , Adulto JovenRESUMEN
The current study was conducted to evaluate the chemoprevention effects of ginseng extract (GE) against pre-cancerous lesions in female Sprague-Dawley rats treated with aflatoxin B1 (AFB1) and fumonisin (FB). Six experimental groups treated for 12 weeks and included: the control group; the GE alone-treated group (150 mg/kg b.w); the group treated orally with AFB1 (17 microg/kg b.w) during the first 2 weeks and fed FB-contaminated diet (250 mg/kg diet) during the 6th to 8th weeks; the group treated with GE during the mycotoxin protocol and continued till week 10; the group treated with GE 2 weeks before AFB1 administration and continued till the end of FB treatment and the group treated with GE for 4 weeks after the toxin protocol stopped. The sequential mycotoxins treatment induced significant changes in serum biochemical parameters accompanied by severe histological and histochemical changes of the liver tissue. Treatment with GE during, before or after the treatment with the mycotoxins improved all biochemical parameters and histological picture of the liver. Moreover, treatment with GE after the administration of the mycotoxins was found to be more effective. It could be concluded that GE has a protective effects as pre-cancerous lesions and therapeutic effects as well.
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Anticarcinógenos/farmacología , Neoplasias Hepáticas/prevención & control , Panax/química , Extractos Vegetales/farmacología , Lesiones Precancerosas/prevención & control , Aflatoxina B1/toxicidad , Animales , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Quimioprevención , Femenino , Fumonisinas/toxicidad , Ginsenósidos/análisis , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/patología , Extractos Vegetales/química , Lesiones Precancerosas/sangre , Lesiones Precancerosas/inducido químicamente , Lesiones Precancerosas/patología , Ratas , Ratas Sprague-DawleyRESUMEN
UNLABELLED: Rudolf Steiner, the founder of anthroposophy, suggested the development of visualisation methods for "etheric formative forces". The essential methods, their "spiritual scientific" basis and indications are described and their claims critically tested. SUMMARY: The methods are not validated, the key criteria for diagnostic tests (reproducibility, sensitivity, specifity) are not given.
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Medicina Antroposófica , Sangre , Terapias Complementarias , Neoplasias Intestinales/diagnóstico , Lesiones Precancerosas/diagnóstico , Charlatanería , Espiritualidad , Adulto , Cristalización , Síndrome de Fatiga Crónica/sangre , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/psicología , Femenino , Humanos , Neoplasias Intestinales/sangre , Neoplasias Intestinales/terapia , Neurastenia/sangre , Neurastenia/diagnóstico , Neurastenia/psicología , Lesiones Precancerosas/sangre , Lesiones Precancerosas/terapia , Trastornos Somatomorfos/sangre , Trastornos Somatomorfos/diagnóstico , Trastornos Somatomorfos/psicologíaRESUMEN
Several human and animal studies have shown that n-3 polyunsaturated fatty acids (PUFA) might be associated with a decreased risk, whereas other studies showed that n-6 PUFA may be associated with an increased risk of colorectal cancer. However, results from these studies are not consistent. We evaluated the associations between serum n-3 and n-6 PUFA levels and colorectal adenoma risk in an endoscopy-based case-control study, conducted in The Netherlands between 1997 and 2002. We included 363 cases of colorectal adenomas and 498 adenoma-free controls. Serum fatty acids were measured in cholesteryl esters. Logistic regression models were used to calculate odds ratios (OR), which were adjusted for age, gender and alcohol intake. Total serum n-3 PUFA levels were inversely associated with colorectal adenoma risk, the OR comparing the third tertile with the first tertile was 0.67 [95% confidence interval (CI) 0.46-0.96, p for trend = 0.03]. Serum eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) and the n-3/n-6 ratio were inversely associated with colorectal adenoma risk, but these were not statistically significant. In contrast, the risk of colorectal adenomas was increased by total n-6 PUFA with an OR of 1.68 (95% CI, 1.17-2.42, p for trend = 0.006) and by linoleic acid (LA; C18:2n-6) with an OR of 1.65 (95% CI, 1.15-2.38, p for trend = 0.007). This is the first observational study that simultaneously finds an inverse association of serum n-3 PUFA and a positive association of n-6 PUFA with colorectal adenoma risk.
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Adenoma/sangre , Neoplasias Colorrectales/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Adenoma/patología , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Endoscopía Gastrointestinal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/sangre , Lesiones Precancerosas/patología , Factores de RiesgoRESUMEN
Obesity and diabetes mellitus are risk factors for colon cancer. The activation of the insulin-like growth factor (IGF)/IGF-IR axis plays a critical role in this carcinogenesis. (-)-Epigallocatechin gallate (EGCG), the major constituent of green tea, seems to have both antiobesity and antidiabetic effects. This study examined the effects of EGCG on the development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) mice, which are obese and develop diabetes mellitus. Male db/db mice were given four weekly s.c. injections of azoxymethane (15 mg/kg body weight) and then they received drinking water containing 0.01% or 0.1% EGCG for 7 weeks. At sacrifice, drinking water with EGCG caused a significant decrease in the number of total aberrant crypt foci, large aberrant crypt foci, and beta-catenin accumulated crypts in these mice, all of which are premalignant lesions of the colon. The colonic mucosa of db/db mice expressed high levels of the IGF-IR, phosphorylated form of IGF-IR (p-IGF-IR), p-GSK-3beta, beta-catenin, cyclooxygenase-2, and cyclin D1 proteins, and EGCG in drinking water caused a marked decrease in the expression of these proteins. Treating these mice with EGCG also caused an increase in the serum level of IGFBP-3 while conversely decreasing the serum levels of IGF-I, insulin, triglyceride, cholesterol, and leptin. EGCG overcomes the activation of the IGF/IGF-IR axis, thereby inhibiting the development of colonic premalignant lesions in an obesity-related colon cancer model, which was also associated with hyperlipidemia, hyperinsulinemia, and hyperleptinemia. EGCG may be, therefore, useful in the chemoprevention or treatment of obesity-related colorectal cancer.
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Azoximetano/toxicidad , Carcinoma/prevención & control , Catequina/análogos & derivados , Neoplasias del Colon/prevención & control , Lesiones Precancerosas/inducido químicamente , Animales , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , Carcinoma/inducido químicamente , Carcinoma/metabolismo , Catequina/farmacología , Catequina/uso terapéutico , Colesterol/sangre , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Evaluación Preclínica de Medicamentos , Insulina/sangre , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Leptina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Lesiones Precancerosas/sangre , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Receptor IGF Tipo 1/metabolismo , Triglicéridos/sangreRESUMEN
Tobacco is the major etiological factor for oral cancer development through the generation of oxidative stress. Therefore, markers of oxidative stress such as total antioxidant status, lipid peroxidation, and total thiol levels might be useful to monitor oxidative stress and predict overall survival in oral cancer patients. The study included 140 oral cancer patients and 50 healthy controls, who were classified as with the habit of tobacco and no habit of tobacco. Adjacent normal and malignant tissue samples were collected from oral cancer patients. Plasma and tissue levels of lipid peroxidation, thiol, and total antioxidant status were assayed by spectrophotometric methods. Thiol levels were significantly lower in controls with the habit of tobacco (P= .033), oral cancer patients (P= .0001), and malignant tissues (P= .015) as compared to controls with no habit of tobacco, controls with the habit of tobacco, and adjacent normal tissues, respectively. Tobacco exposure was higher in oral cancer patients than controls with the habit of tobacco. Controls with the habit of tobacco who had lower thiol (odds ratio [OR]=10.58, P= .008) and high tobacco exposure (OR=0.251, P= .05) showed an elevated risk of oral cancer development. Patients showing a lipid peroxidation level above the cutoff level as compared to patients below the cutoff level showed poor overall survival, whereas those with thiol and total antioxidant status levels below the cutoff level as compared to their respective counterparts showed poor overall survival. In conclusion, lipid peroxidation and thiol could be useful for predicting the risk of oral carcinogenesis in healthy tobacco consumers and predicting overall survival of oral cancer patients.
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Antioxidantes/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Peróxidos Lipídicos/sangre , Neoplasias de la Boca/diagnóstico , Compuestos de Sulfhidrilo/sangre , Adulto , Anciano , Carcinoma de Células Escamosas/sangre , Femenino , Humanos , India , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/sangre , Análisis Multivariante , Oportunidad Relativa , Lesiones Precancerosas/sangre , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/etiología , Pronóstico , Factores de Riesgo , Fumar/efectos adversos , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Tabaco sin Humo/efectos adversosRESUMEN
BACKGROUND: Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins. METHODS: A randomized, double-blind chemoprevention trial was conducted among 1980 subjects in Tachira State, Venezuela (whose population is at high risk for gastric cancer), to determine the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of precancerous gastric lesions. Subjects were randomly assigned to receive either a combination of vitamin C (750 mg/day), vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years. Changes in the gastric mucosa were determined by histologic diagnosis based on five biopsies taken from prespecified areas of the stomach at baseline and annually for 3 years. All biopsies were reviewed by a single expert pathologist. Progression rates (and regression rates) were calculated by comparing the first and last available gastroscopies for each subject and dividing the number of subjects whose diagnoses increased (decreased) in severity by the total follow-up time. Overall rate ratios were calculated by Poisson regression, controlling for baseline diagnosis. All statistical tests were two-sided. RESULTS: Median plasma vitamin levels were increased in the treatment group between baseline and 1 year after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69) to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from 47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for vitamin C. Overall progression rates per 100 person-years were 74.3 in the placebo group and 67.8 in the group randomly assigned to vitamins. Overall regression rates were 109.4 in the placebo group and 116.5 in the group randomly assigned to vitamins. There was no statistically significant difference in progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15) or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and placebo groups. CONCLUSION: Supplementation with antioxidant micronutrients is not an effective tool for gastric cancer control in this high-risk population. The results of this trial are consistent with previous findings on the lack of effect of nutritional supplementation on precancerous gastric lesions.
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Antioxidantes/administración & dosificación , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Lesiones Precancerosas/prevención & control , Neoplasias Gástricas/prevención & control , Vitaminas/administración & dosificación , Adulto , Anciano , Antioxidantes/metabolismo , Ácido Ascórbico/administración & dosificación , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/patología , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Gastroscopía , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Selección de Paciente , Lesiones Precancerosas/sangre , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/microbiología , Medición de Riesgo , Tamaño de la Muestra , Fumar/efectos adversos , Neoplasias Gástricas/sangre , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Insuficiencia del Tratamiento , Venezuela , Vitamina E/administración & dosificación , Vitaminas/sangre , beta Caroteno/administración & dosificaciónRESUMEN
AIM: To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. METHODS: Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment.
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Complejo Antígeno-Anticuerpo/sangre , Cobre/sangre , Hierro/sangre , Neoplasias de la Boca/sangre , Lesiones Precancerosas/sangre , Selenio/sangre , Adulto , Anciano , Biomarcadores de Tumor/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Oligoelementos/sangreRESUMEN
The present study was performed to investigate the influence of fish oil on the genotoxic effects of azaserine, using the formation of micronucleated erythrocytes as a measure for the degree of initiating potency and the number and size of putative preneoplastic pancreatic atypical acinar cell foci (AACF) as a measure for the actual number of initiated cells. Male Wistar rats were treated twice i.p. with 30 mg azaserine per kg body weight to induce AACF. During the initiation/early promotion phase the rats were maintained on diets containing 5 wt% vegetable oil (safflower and high-oleic sunflower oil), 25 wt% vegetable oil, 25 wt% fat (15% vegetable oil + 10 wt% fish oil), or 25 wt% fat (5% vegetable oil + 20 wt% fish oil), respectively. One day after carcinogen treatment, the numbers of micronucleated polychromatic erythrocytes were determined in blood smears obtained from 10 animals per group. Each high-fat diet resulted in higher percentages of micronucleated polychromatic erythrocytes than the low-fat diet. Dietary fish oil did not significantly influence the number of micronucleated cells. Two weeks after carcinogen treatment, the diets containing fish oil were replaced by the diet containing 25% vegetable oil, and the animals were further maintained for about 14 wk. Pancreatic tissue slides were microscopically evaluated for the number and size of AACF. Dietary fish oil caused an increase in the number and size of AACF, although a clear dose-effect relationship was absent. It was concluded that a high level of dietary fish oil, when given during the induction/early promotion phase, enhances azaserine-induced pancreatic carcinogenesis in rats.
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Azaserina/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Eritrocitos/ultraestructura , Aceites de Pescado/administración & dosificación , Micronúcleos con Defecto Cromosómico/patología , Neoplasias Pancreáticas/sangre , Animales , Grasas Insaturadas en la Dieta/administración & dosificación , Combinación de Medicamentos , Femenino , Masculino , Neoplasias Pancreáticas/inducido químicamente , Aceites de Plantas/administración & dosificación , Lesiones Precancerosas/sangre , Lesiones Precancerosas/inducido químicamente , Ratas , Ratas WistarAsunto(s)
Anticarcinógenos/uso terapéutico , Lesiones Precancerosas/prevención & control , Neoplasia Intraepitelial Prostática/prevención & control , Neoplasias de la Próstata/prevención & control , Transferasas Alquil y Aril/antagonistas & inhibidores , Antagonistas de Andrógenos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/uso terapéutico , Biomarcadores de Tumor/sangre , Quimioterapia Combinada , Inhibidores Enzimáticos/uso terapéutico , Antagonistas de Estrógenos/uso terapéutico , Humanos , Masculino , Micronutrientes/uso terapéutico , Persona de Mediana Edad , Lesiones Precancerosas/sangre , Lesiones Precancerosas/tratamiento farmacológico , Neoplasia Intraepitelial Prostática/sangre , Neoplasia Intraepitelial Prostática/tratamiento farmacológico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas de Soja/uso terapéutico , Esteroides , Vitamina D/análogos & derivados , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Nariño, Colombia, in the Andes Mountains. METHODS: A randomized, controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia, two precancerous lesions. Individuals were assigned to receive anti-Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Gastric biopsy specimens taken at baseline were compared with those taken at 72 months. Relative risks of progression, no change, and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects. All statistical tests were two-sided. RESULTS: All three basic interventions resulted in statistically significant increases in the rates of regression: Relative risks were 4.8 (95% confidence interval [CI] = 1.6-14.2) for anti-H. pylori treatment, 5. 1 (95% CI = 1.7-15.0) for beta-carotene treatment, and 5.0 (95% CI = 1.7-14.4) for ascorbic acid treatment in subjects with atrophy. Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 (95% CI = 1.0-9.3), 3.4 (95% CI = 1.1-9.8), and 3.3 (95% CI = 1.1-9.5). Combinations of treatments did not statistically significantly increase the regression rates. Curing the H. pylori infection (which occurred in 74% of the treated subjects) produced a marked and statistically significant increase in the rate of regression of the precursor lesions (relative risks = 8.7 [95% CI = 2.7-28.2] for subjects with atrophy and 5.4 [95% CI = 1.7-17.6] for subjects with intestinal metaplasia). CONCLUSIONS: In the very high-risk population studied, effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma.
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Antibacterianos/uso terapéutico , Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Gastritis Atrófica/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Lesiones Precancerosas/tratamiento farmacológico , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/prevención & control , Estómago/patología , beta Caroteno/uso terapéutico , Adulto , Anciano , Biopsia , Transformación Celular Neoplásica , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Gastritis Atrófica/sangre , Gastritis Atrófica/microbiología , Gastritis Atrófica/patología , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/sangre , Lesiones Precancerosas/patología , Remisión Espontánea , Riesgo , Estómago/microbiología , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
The protective effect of garlic (Allium sativum Linn.) on circulatory lipid peroxidation and antioxidants was investigated during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis in male Syrian hamsters. Enhanced lipid peroxidation in the circulation of tumour-bearing animals was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. Administration of garlic extract significantly decreased lipid peroxidation with simultaneous depletion of antioxidants. We speculate that garlic exerts its protective effects by decreasing circulatory lipid peroxides and enhancing antioxidants.