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1.
Cancer Prev Res (Phila) ; 8(11): 1076-83, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26323483

RESUMEN

We have shown that dietary fish oil is protective against experimentally induced colon cancer, and the protective effect is enhanced by coadministration of pectin. However, the underlying mechanisms have not been fully elucidated. We hypothesized that fish oil with butyrate, a pectin fermentation product, protects against colon cancer initiation by decreasing cell proliferation and increasing differentiation and apoptosis through a p27(Kip1)-mediated mechanism. Rats were provided diets of corn or fish oil, with/without butyrate, and terminated 12, 24, or 48 hours after azoxymethane (AOM) injection. Proliferation (Ki-67), differentiation (Dolichos Biflorus Agglutinin), apoptosis (TUNEL), and p27(Kip1) (cell-cycle mediator) were measured in the same cell within crypts in order to examine the coordination of cell cycle as a function of diet. DNA damage (N(7)-methylguanine) was determined by quantitative IHC analysis. Dietary fish oil decreased DNA damage by 19% (P = 0.001) and proliferation by 50% (P = 0.003) and increased differentiation by 56% (P = 0.039) compared with corn oil. When combined with butyrate, fish oil enhanced apoptosis 24 hours after AOM injection compared with a corn oil/butyrate diet (P = 0.039). There was an inverse relationship between crypt height and apoptosis in the fish oil/butyrate group (r = -0.53, P = 0.040). The corn oil/butyrate group showed a positive correlation between p27(Kip1) expression and proliferation (r = 0.61, P = 0.035). These results indicate the in vivo effect of butyrate on apoptosis and proliferation is dependent on dietary lipid source. These results demonstrate the presence of an early coordinated colonocyte response by which fish oil and butyrate protects against colon tumorigenesis.


Asunto(s)
Apoptosis , Butiratos/administración & dosificación , Colon/patología , Neoplasias del Colon/prevención & control , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Aceites de Pescado/administración & dosificación , Animales , Azoximetano/química , Diferenciación Celular , Proliferación Celular , Neoplasias del Colon/patología , Aceite de Maíz/administración & dosificación , Daño del ADN , Grasas Insaturadas en la Dieta/administración & dosificación , Fermentación , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Masculino , Pectinas/química , Ratas , Ratas Sprague-Dawley
2.
Exp Biol Med (Maywood) ; 235(6): 710-7, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20511675

RESUMEN

Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture or a control diet (0% flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57% (P < 0.05), while naringenin lowered both the number of HMACF by 51% (P < 0.05) and the proliferative index by 32% (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78% and 97%, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer.


Asunto(s)
Antineoplásicos/administración & dosificación , Apigenina/administración & dosificación , Azoximetano/toxicidad , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/prevención & control , Flavanonas/administración & dosificación , Animales , Antineoplásicos/farmacología , Apigenina/farmacología , Apoptosis , Western Blotting , Proliferación Celular , Citrus/química , Colon/patología , Ciclooxigenasa 2/biosíntesis , Dieta/métodos , Flavanonas/farmacología , Histocitoquímica , Masculino , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Ratas , Ratas Sprague-Dawley
3.
CNS Spectr ; 13(5): 393-403, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18496477

RESUMEN

Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic delta9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic delta9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the "high" on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.


Asunto(s)
Cannabis , Dronabinol/uso terapéutico , Alucinógenos/uso terapéutico , Abuso de Marihuana/tratamiento farmacológico , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/terapia , Distonía Paroxística Nocturna/etiología , Distonía Paroxística Nocturna/terapia , Fitoterapia/métodos , Tics/etiología , Tics/terapia , Adulto , Femenino , Humanos , Masculino
4.
Carcinogenesis ; 27(6): 1257-65, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16387741

RESUMEN

This study evaluated the hypothesis that untreated and irradiated grapefruit as well as the isolated citrus compounds naringin and limonin would protect against azoxymethane (AOM)-induced aberrant crypt foci (ACF) by suppressing proliferation and elevating apoptosis through anti-inflammatory activities. Male Sprague-Dawley rats (n = 100) were provided one of five diets: control (without added grapefruit components), untreated or irradiated (300 Gy, 137Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg). Rats were injected with saline or AOM (15 mg/kg) during the third and fourth week and colons were resected (6 weeks post second injection) for evaluation of ACF, proliferation, apoptosis, and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein levels. Experimental diets had no effect on the variables measured in saline-injected rats. However, in AOM-injected rats, the experimental diets suppressed (P < or = 0.02) aberrant crypt and high multiplicity ACF (HMACF; P < or = 0.01) formation and the proliferative index (P < or = 0.02) compared with the control diet. Only untreated grapefruit and limonin suppressed (P < or = 0.04) HMACF/cm and expansion (P < or = 0.008) of the proliferative zone that occurred in the AOM-injected rats consuming the control diet. All diets elevated (P < or = 0.05) the apoptotic index in AOM-injected rats, compared with the control diet; however, the greatest enhancement was seen with untreated grapefruit and limonin. Untreated grapefruit and limonin diets suppressed elevation of both iNOS (P < or = 0.003) and COX-2 (P < or = 0.032) levels observed in AOM-injected rats consuming the control diet. Although irradiated grapefruit and naringin suppressed iNOS levels in AOM-injected rats, no effect was observed with respect to COX-2 levels. Thus, lower levels of iNOS and COX-2 are associated with suppression of proliferation and upregulation of apoptosis, which may have contributed to a decrease in the number of HMACF in rats provided with untreated grapefruit and limonin. These results suggest that consumption of grapefruit or limonin may help to suppress colon cancer development.


Asunto(s)
Neoplasias del Colon/prevención & control , Animales , Carcinógenos , Proliferación Celular , Citrus paradisi , Neoplasias del Colon/tratamiento farmacológico , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Flavanonas/farmacología , Limoninas/metabolismo , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/metabolismo , Ratas , Ratas Sprague-Dawley
5.
Nutr Cancer ; 52(2): 166-75, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16201848

RESUMEN

To determine if dietary fish oil protects against colon cancer by decreasing oxidative DNA damage at the initiation stage of colon tumorigenesis, oxidative DNA damage, proliferation, and apoptosis were assessed by colonic crypt cell position using quantitative immunohistochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG), Ki-67, and TUNEL assay, respectively. Sixty rats were provided one of two diets (corn oil or fish oil) and dextran sodium sulfate (DSS, an inducer of oxidative DNA damage) treatments (no DSS, 3% DSS, or DSS withdrawal). Fish oil feeding resulted in lower 8-OHdG levels (P = 0.038), higher levels of apoptosis (P = 0.035), and a lower cell proliferative index (P = 0.05) compared with corn oil feeding. In the top third of the crypt, fish oil caused an incremental stimulation of apoptosis with increased DNA damage (P = 0.043), whereas there was no such relationship with corn oil. Because polyps and tumors develop from DNA damage that leads to loss of growth and death control, the significant difference in fish oil vs. corn oil on these variables may account, in part, for the observed protective effect of fish oil against oxidatively induced colon cancer.


Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias del Colon/prevención & control , Daño del ADN/efectos de los fármacos , Aceites de Pescado/farmacología , Animales , Colon/citología , Colon/efectos de los fármacos , Neoplasias del Colon/metabolismo , Aceites de Pescado/administración & dosificación , Inmunohistoquímica , Masculino , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley
6.
Clin J Oncol Nurs ; 8(4): 368-76, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15354923

RESUMEN

Malignant gliomas are among the most devastating tumors, with survival only one to three years after diagnosis even with the best of treatments. For this reason, long-term follow-up has not been established. Patients who do survive have significant disabilities, which compromise patient and family quality of life (QOL). Side effects from a brain tumor are dependent on the location of the tumor in the brain and can cause significant cognitive, emotional, and social effects on patients and families. Surgical treatment options also are dependent on the location of the tumor in the brain, and some sites remain inoperable (e.g., brain stem, motor strip). Radiation therapy continues to remain the mainstay of treatment for this patient population. The advent of newer technologies in radiation and chemotherapy and the development of novel treatments have increased survival. As survival increases, QOL issues become more important to patients and families. Impairment, disability, and handicap are measurements of QOL used by healthcare professionals. A multitude of studies has produced evidence regarding the impact of tumor location and size on QOL, whereas other studies have demonstrated the effects that various treatment modalities have on QOL. Few studies actually have provided insight into the everyday consequences that tumors pose on patients. Understanding the significance and causes of these impairments, disabilities, and handicaps will assist oncology nurses in caring for this special population.


Asunto(s)
Astrocitoma/complicaciones , Neoplasias Encefálicas/complicaciones , Glioblastoma/complicaciones , Astrocitoma/patología , Astrocitoma/terapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Trastornos del Conocimiento/etiología , Progresión de la Enfermedad , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Necrosis , Calidad de Vida , Traumatismos por Radiación/patología , Radioterapia/efectos adversos
7.
Free Radic Biol Med ; 35(2): 149-59, 2003 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-12853071

RESUMEN

Prolonged generation of reactive oxygen species by inflammatory mediators can induce oxidative DNA damage (8-oxodG formation), potentially resulting in intestinal tumorigenesis. Fish oil (FO), compared to corn oil (CO), has been shown to downregulate inflammation and upregulate apoptosis targeted at damaged cells. We hypothesized FO could protect the intestine against 8-oxodG formation during dextran sodium sulfate- (DSS-) induced inflammation. We provided 60 rats with FO- or CO-supplemented diets for 2 weeks with or without 3% DSS in drinking water for 48 h. Half the treated rats received 48 additional h of untreated water before termination. Due to DSS treatment, the intestinal epithelium had higher levels of 8-oxodG (p =.04), induction of repair enzyme OGG1 mRNA (p =.02), and higher levels of apoptosis at the top of colonic crypts (p =.01) and in surface cells (p <.0001). FO-fed rats, compared to CO, had lower levels of 8-oxodG (p =.05) and increased apoptosis (p =.04) in the upper crypt region; however, FO had no significant effect on OGG1 mRNA. We conclude that FO protects intestinal cells against oxidative DNA damage in part via deletion mechanisms.


Asunto(s)
Colon/citología , Colon/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Grasas Insaturadas en la Dieta/farmacología , Aceites de Pescado/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Colon/metabolismo , Colon/patología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/prevención & control , Aductos de ADN/análisis , Aductos de ADN/efectos de los fármacos , ADN Glicosilasas/genética , Dieta , Grasas Insaturadas en la Dieta/administración & dosificación , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Aceites de Pescado/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Aumento de Peso/efectos de los fármacos
8.
Carcinogenesis ; 23(11): 1919-25, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12419841

RESUMEN

We have shown that a combination of fish oil (high in n-3 fatty acids) with the butyrate-producing fiber pectin, upregulates apoptosis in colon cells exposed to the carcinogen azoxymethane, protecting against colon tumor development. We now hypothesize that n-3 fatty acids prime the colonocytes such that butyrate can initiate apoptosis. To test this, 30 Sprague-Dawley rats were provided with diets differing in the fatty acid composition (corn oil, fish oil or a purified fatty acid ethyl ester diet). Intact colon crypts were exposed ex vivo to butyrate, and analyzed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP), translocation of cytochrome C to the cytosol, and caspase-3 activity (early events in apoptosis). The fatty acid composition of the three major mitochondrial phospholipids was also determined, and an unsaturation index calculated. The unsaturation index in cardiolipin was correlated with ROS levels (R = 0.99; P = 0.02). When colon crypts from fish oil and FAEE-fed rats were exposed to butyrate, MMP decreased (P = 0.041); and translocation of cytochrome C to the cytosol (P = 0.037) and caspase-3 activation increased (P = 0.032). The data suggest that fish oil may prime the colonocytes for butyrate-induced apoptosis by enhancing the unsaturation of mitochondrial phospholipids, especially cardiolipin, resulting in an increase in ROS and initiating apoptotic cascade.


Asunto(s)
Apoptosis/efectos de los fármacos , Colon/citología , Aceites de Pescado/farmacología , Mucosa Intestinal/citología , Membranas Intracelulares/efectos de los fármacos , Lípidos de la Membrana/metabolismo , Mitocondrias/efectos de los fármacos , Fosfolípidos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Butiratos/farmacología , Cardiolipinas/química , Cardiolipinas/metabolismo , Caspasa 3 , Caspasas/metabolismo , Colon/metabolismo , Aceite de Maíz/farmacología , Grupo Citocromo c/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Activación Enzimática , Ésteres/farmacología , Ácidos Grasos/farmacología , Mucosa Intestinal/metabolismo , Membranas Intracelulares/metabolismo , Peroxidación de Lípido , Masculino , Lípidos de la Membrana/química , Mitocondrias/metabolismo , Estrés Oxidativo , Fosfolípidos/química , Ratas , Ratas Sprague-Dawley
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