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1.
Onco Targets Ther ; 12: 8379-8386, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31632085

RESUMEN

OBJECTIVE: To evaluate the impact of systematic nutrition management (SNM) on nutritional status, treatment-related toxicity, quality of life (QoL), response rates, and survival in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) treated by radiotherapy (RT). METHODS: In this retrospective study, 56 patients with LA-NPC were selected as nutrition management group (NG) for SNM during RT till 1 month later. Another 56 patients with LA-NPC receiving RT without SNM as control group (CG) were identified from the hospital database and matched pairs with NG patients according to age, gender, stage, and body mass index (BMI) prior to RT. RESULTS: At 1 month after RT, the percentage of malnourished patients with BMI <18.5 kg/m2 was statistically significant reduced in NG as compared to the CG group (35.7% vs 58.9%, P=0.014). Nutritional indexes of body weight, hemoglobin, prealbumin, and lymphocyte in the NG were statistically significant higher than those in the CG group (P<0.05). NG patients had statistically significant less grade 3-4 oral mucositis during RT compared with the CG group (32.1% vs 51.8%, P=0.035). Furthermore, at 1 month after RT, an improved QoL was observed in NG patients with respect to physical, role and social functions, symptom scales of fatigue and pain, and the global health status as compared to the CG group (P<0.05). With a median follow-up of 24.8 months, there were no statistical differences between NG and CG (P>0.05) for the 2-year progression-free survival and overall survival (84.2% versus 79.5% and 94.7% versus 92.3%, respectively.). CONCLUSION: SNM for LA-NPC patients treated by RT resulted in better nutritional status, reduced treatment-related toxicity and improved QoL.

2.
Oncotarget ; 8(2): 2457-2465, 2017 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-27974693

RESUMEN

Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Carcinoma/terapia , Quimioradioterapia/métodos , Quimioterapia de Inducción/métodos , Neoplasias Nasofaríngeas/terapia , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma/patología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
3.
Med Phys ; 43(7): 4349, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27370150

RESUMEN

PURPOSE: Lower radiation tolerance of the whole liver hinders dose escalations of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) treatment. This study was conducted to define the exact doses that result in radiation-induced liver disease (RILD) as well as to determine dose constraints for the critical organs at risk (OARs) in mice; these parameters are still undefined in HCC SBRT. METHODS: This study consisted of two phases. In the primary phase, mice treated with helical tomotherapy-based SBRT were stratified according to escalating radiation doses to the livers. The pathological differences, signs [such as mouse performance status (MPS)], and serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/albumin levels were observed. Radiation-induced disease severities of the OARs were scored using systematic evaluation standards. In the validation phase in humans, 13 patients with HCC who had undergone radiotherapy before hepatectomy were enrolled to validate RILD pathological changes in a mouse study. RESULTS: The evaluation criteria of the mouse liver radiotherapy-related signs were as follows: MPS ≥ 2.0 ± 0.52, AST/ALT ≥ 589.2 ± 118.5/137.4 ± 15.3 U/L, serum albumin ≤ 16.8 ± 2.29 g/L. The preliminary dose constraints of the OARs were also obtained, such as those for the liver (average dose ≤ 26.36 ± 1.71 Gy) and gastrointestinal tract (maximum dose ≤ 22.63 Gy). Mouse RILD models were able to be developed when the livers were irradiated with average doses of ≥31.76 ± 1.94 Gy (single fraction). RILD pathological changes in mice have also been validated in HCC patients. CONCLUSIONS: Mouse RILD models could be developed with SBRT based on the dose constraints for the OARs and evaluation criteria of mouse liver radiotherapy-related signs, and the authors' results favor the study of further approaches to treat HCC with SBRT.


Asunto(s)
Hepatopatías/etiología , Hígado/efectos de la radiación , Traumatismos Experimentales por Radiación , Radiocirugia/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Adulto , Anciano , Alanina Transaminasa/sangre , Albúminas/metabolismo , Animales , Aspartato Aminotransferasas/sangre , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirugía , Relación Dosis-Respuesta en la Radiación , Femenino , Tracto Gastrointestinal/efectos de la radiación , Humanos , Hígado/patología , Hígado/cirugía , Hepatopatías/sangre , Hepatopatías/patología , Hepatopatías/terapia , Masculino , Ratones Endogámicos ICR , Persona de Mediana Edad , Órganos en Riesgo , Traumatismos Experimentales por Radiación/sangre , Radiocirugia/métodos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada/métodos , Distribución Aleatoria
4.
World J Gastroenterol ; 22(27): 6235-45, 2016 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-27468213

RESUMEN

AIM: To investigate the role of activating transcription factor 4 (ATF4) in glucose deprivation (GD) induced colorectal cancer (CRC) drug resistance and the mechanism involved. METHODS: Chemosensitivity and apoptosis were measured under the GD condition. Inhibition of ATF4 using short hairpin RNA in CRC cells under the GD condition and in ATF4-overexpressing CRC cells was performed to identify the role of ATF4 in the GD induced chemoresistance. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA and protein expression of drug resistance gene 1 (MDR1), respectively. RESULTS: GD protected CRC cells from drug-induced apoptosis (oxaliplatin and 5-fluorouracil) and induced the expression of ATF4, a key gene of the unfolded protein response. Depletion of ATF4 in CRC cells under the GD condition can induce apoptosis and drug re-sensitization. Similarly, inhibition of ATF4 in the ATF4-overexpressing CRC cells reintroduced therapeutic sensitivity and apoptosis. In addition, increased MDR1 expression was observed in GD-treated CRC cells. CONCLUSION: These data indicate that GD promotes chemoresistance in CRC cells through up-regulating ATF4 expression.


Asunto(s)
Factor de Transcripción Activador 4/genética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/genética , Glucosa/deficiencia , Microambiente Tumoral , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Factor de Transcripción Activador 4/metabolismo , Apoptosis/genética , Western Blotting , Línea Celular Tumoral , Chaperón BiP del Retículo Endoplásmico , Fluorouracilo/administración & dosificación , Técnicas de Silenciamiento del Gen , Glucosa/metabolismo , Células HCT116 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismo
5.
Environ Toxicol Pharmacol ; 40(1): 156-63, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26122083

RESUMEN

Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. This study aimed to investigate the radioprotective effects of CAPE on X-ray irradiation induced intestinal injury in rats. Rats were intragastrically administered with 10 µmol/kg/d CAPE for 7 consecutive days before exposing them to a single dose of X-ray irradiation (9Gy) to abdomen. Rats were sacrificed 72 h after exposure to radiation. We found that pretreatment with CAPE effectively attenuated intestinal pathology changes, apoptosis, oxidative stress, bacterial translocation, the content of nitric oxide and myeloperoxidase as well as the concentration of plasma tumor necrosis factor-α. Pretreatment with CAPE also reversed the activation of p38MAPK and the increased expression of intercellular cell adhesion molecule-1 induced by radiation in intestinal mucosa. Taken together, these results suggest that pretreatment with CAPE could be a promising candidate for treating radiation-induced intestinal injury.


Asunto(s)
Apoptosis/efectos de los fármacos , Ácidos Cafeicos/farmacología , Intestinos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Radiación Ionizante , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Apoptosis/efectos de la radiación , Mucosa Intestinal/metabolismo , Intestinos/efectos de la radiación , Masculino , Alcohol Feniletílico/farmacología , Ratas , Ratas Sprague-Dawley
6.
BMC Cancer ; 14: 878, 2014 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-25421498

RESUMEN

BACKGROUND: The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. METHODS: We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. RESULTS: The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high γ-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. CONCLUSIONS: Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/radioterapia , Neoplasias de las Glándulas Suprarrenales/secundario , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
7.
Mol Med Rep ; 10(4): 1725-33, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25109274

RESUMEN

The aim of the present study was to examine the effects of activated hepatic stellate cells (HSCs) and their paracrine secretions, on hepatocellular cancer cell growth and gene expression in vitro and in vivo. Differentially expressed genes in McA-RH7777 hepatocellular carcinoma (HCC) cells following non-contact co-culture with activated stellate cells, were identified by a cDNA microarray. The effect of the co-injection of HCC cells and activated HSCs on tumor size in rats was also investigated. Non-contact co-culture altered the expression of 573 HCC genes by >2-fold of the control levels. Among the six selected genes, ELISA revealed increased protein levels of hepatic growth factor, matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9). Incubation of HCC cells with medium conditioned by activated HSCs significantly increased the proliferation rate (P<0.001), migration rate and the number of invasive HCC cells (P=0.001). Co-injection of HCC cells and activated HSCs into rats significantly increased the weight of the resulting HCC tumors (P<0.01). The paracrine activity of activated HSCs markedly altered the gene expression profile of HCC cells and affected their growth, migration and invasiveness. The results from the present study indicate that the interaction between the activated HSCs and HCC has an important role in the development of HCC.


Asunto(s)
Células Estrelladas Hepáticas/metabolismo , Transcriptoma , Animales , Pruebas de Carcinogenicidad , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular , Movimiento Celular , Proliferación Celular , Técnicas de Cocultivo , Femenino , Células Estrelladas Hepáticas/citología , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Endogámicas BUF , Trasplante Homólogo
8.
Cancer Immunol Immunother ; 63(3): 235-45, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24337704

RESUMEN

Toll-like receptor 4 (TLR4) is an important trigger of the immune response against hepatitis B virus (HBV) infection and liver injuries. The roles of HBV reactivation versus TLR4-dependant immune response may be critical factors in preventing radiation-induced liver diseases (RILDs) after liver cancer radiotherapy. This study consists of three phases. In the primary phase, livers of mutant TLR4 (TLR4(-)) mice were irradiated with 30 Gy in either the absence or presence of HBV infection. The latter was done by introduction of plasmid pAAV/HBV 1.2. In the advanced phase, RILDs were compared in normal TLR4 (TLR4(+)) versus TLR4(-) mice. In the validation phase, 28 liver cancer patients who had undergone radiotherapy before hepatectomy were enrolled. Liver biopsies near tumors, irradiated with 35-48 Gy, were used to construct tissue microarrays. HBV reactivation, TLR4 expression, and severity of RILDs were studied in both mouse and human. More HBV reactivation, without significant RILD, was observed in irradiated versus unirradiated TLR4(-) mice. RILD scores of TLR4(+) mice were higher than TLR4(-) mice. In humans, serious RILDs tended to develop in patients with high TLR4 expression, but not in patients with low TLR4 or high HBV surface antigen expression. High TLR4 expression was seen in only 2 of 12 HBV-reactive patients, but in HBV-nonreactive patients, it was seen in 6 of 9 (P < 0.03). In summary, RILDs correlated with high TLR4 expression, but not with HBV reactivation, which is inhibited in liver with high TLR4 expression after liver cancer radiotherapy.


Asunto(s)
Virus de la Hepatitis B/efectos de la radiación , Hepatitis B Crónica/etiología , Hepatitis B Crónica/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/radioterapia , Traumatismos por Radiación/etiología , Receptor Toll-Like 4/metabolismo , Adulto , Anciano , Animales , ADN Viral/análisis , Femenino , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/virología , Humanos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Noqueados , Análisis por Micromatrices , Persona de Mediana Edad , Mutación/genética , Traumatismos por Radiación/inmunología , Radioterapia/efectos adversos , Estudios Retrospectivos , Receptor Toll-Like 4/genética , Carga Viral , Activación Viral/efectos de la radiación
9.
J Cancer Res Clin Oncol ; 139(4): 669-79, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23307318

RESUMEN

PURPOSE: The biology underlying bone-specific metastasis (BM) of hepatocellular carcinoma (HCC) is poorly understood. The goal of the present study is to further elucidate the molecular and cellular mechanisms underlying HCC with BM. METHODS: The expression of connective tissue growth factor (CTGF) and interleukin-11 (IL-11) in RNA extracted from 127 formalin-fixed, paraffin-embedded HCC specimens was examined by quantitative real-time polymerase chain reaction. A cellular hypoxic model was established in vitro to investigate CTGF and osteoprotegerin (OPG) expression and roles in hypoxia-induced tumor aggressiveness. RESULTS: The mean CTGF expression in BM versus non-metastatic samples was 3.63-times higher, and IL-11 expression was detected in 62.5 % (10/16) of BM samples versus only in 18.9 % (21/111) of the non-metastatic ones. Highly metastatic HCC cell lines tended to show strong expression of CTGF and IL-11, but low expression of OPG. Hypoxic stimulation of HCC 97L cells increased the level of CTGF mRNA by 2.80-fold within 1.5 h, and hypoxia-inducible factor-1α mRNA levels in these cells could be increased by stimulation with recombinant CTGF protein. Furthermore, OPG and matrix metalloproteinase-2 and -9 levels were also induced under hypoxic conditions. CONCLUSIONS: Expression levels of intratumoral CTGF or IL-11 were independent prognostic factors for the development of BM in HCC patients. Tumor hypoxia enhanced the expression of CTGF, which initiates the invasive angiogenesis cascade and enhances expression of many hypoxia-associated genes. Cellular release of OPG may play a role in tumor cell survival. The hypoxia-induced cascade in HCC cells may contribute to invasion and metastasis in vivo.


Asunto(s)
Neoplasias Óseas/secundario , Carcinoma Hepatocelular/patología , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Hipoxia , Interleucina-11/metabolismo , Neoplasias Hepáticas/patología , Apoptosis , Western Blotting , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Adhesión Celular , Movimiento Celular , Proliferación Celular , Factor de Crecimiento del Tejido Conjuntivo/antagonistas & inhibidores , Factor de Crecimiento del Tejido Conjuntivo/genética , Medios de Cultivo Condicionados/farmacología , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Técnicas para Inmunoenzimas , Interleucina-11/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
10.
Int J Radiat Oncol Biol Phys ; 84(3): 822-8, 2012 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-22420973

RESUMEN

PURPOSE: To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. METHODS AND MATERIALS: Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). RESULTS: In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 ± 4.74) than in RH10Gy-SnonR (30.6 ± 3.85) cells, and lowest in McA-RH7777 (11.4 ± 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 ± 5.38), RH10Gy-SnonR (22.17 ± 4.26), and McA-RH7777 (8.3 ± 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-α and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. CONCLUSIONS: Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of metastasis-related cytokines and factors from NPCs after irradiation may be a possible mechanism for the radiation-induced invasiveness and metastatic potential of HCC.


Asunto(s)
Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/secundario , Citocinas/metabolismo , Hepatocitos/efectos de la radiación , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Animales , Técnicas de Cultivo de Célula , Colágeno , Combinación de Medicamentos , Factor de Crecimiento Epidérmico/metabolismo , Hepatocitos/metabolismo , Interleucina-6/metabolismo , Laminina , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Proteoglicanos , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
11.
Mol Biol Rep ; 38(7): 4359-67, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21116849

RESUMEN

The aim of this study was to determine whether caffeine enhanced radiosensitivity of normal liver tissue in a rat radiation-induced liver disease model. Buffalo rat McA-RH7777 hepatocellular cancer cells and BRL3A normal liver cells were irradiated, and cell cycle distribution and apoptosis rates were analyzed. A rat model of radiation-induced liver disease was established, rats were randomized into four groups: control; caffeine alone; irradiation (IR) alone; and caffeine plus IR (Caff + IR) group. Apoptosis rates in normal rat liver tissue after IR were evaluated by TUNEL staining and caspase-3 Western blot. Transaminase activity was measured and histopathological examination was done after IR. Caffeine abrogated IR-induced G2 phase arrest (Caff + IR vs. IR: 40.9 ± 4.0 vs. 60.7 ± 5.5%, at 12 h after IR) and increased apoptosis rates (Caff + IR vs. IR: 56.1 ± 6.8 vs. 35.5 ± 4.0%, at 72 h after IR) in McA-RH7777 cells, but did not affect IR-induced G2 phase arrest and apoptosis rates at any time point after IR in BRL3A cells. Caffeine did not enhance apoptosis, transaminase activity, or histopathological injury of normal rat liver tissue at any time points after IR. This study suggests that caffeine might not enhance radiosensitivity of normal liver tissue in vivo. In an earlier study, we reported that caffeine enhanced radiosensitivity of human hepatocellular cancer in a nude mice model. Together, these results offer feasibility of clinical application.


Asunto(s)
Cafeína/farmacología , Hígado/efectos de los fármacos , Hígado/efectos de la radiación , Tolerancia a Radiación/efectos de los fármacos , Tolerancia a Radiación/efectos de la radiación , Alanina Transaminasa/sangre , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Aspartato Aminotransferasas/sangre , Línea Celular , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de la radiación , Humanos , Hígado/enzimología , Hígado/patología , Masculino , Ratones , Radiación Ionizante , Ratas , Proteína p53 Supresora de Tumor/metabolismo
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