Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases.

BACKGROUNDS: The present study aimed to evaluate benefit of hepatic arterial infusion chemotherapy (HAI) combined with systemic chemotherapy (SCT) for patients with colorectal liver metastases (CLMs) in a palliative setting. METHODS: This was a retrospective single-center study including 43 consecutive patients with CLM after failure of standard SCT. Among them, 20 (47 %) patients underwent HAI combined with SCT (Group A) and 23 historical control patients who had received SCT with or without targeted agent treatment (Group B). RESULTS: The two groups had similar characteristics. Compared with SCT alone, HAI combined with SCT prolonged survival (median 19.8 vs. 9.0 months; P = 0.045). Median hepatic progression-free survival was significantly longer for HAI combined with SCT vs. SCT alone (median 8.1 vs. 4.7 months; P = 0.027), as were response rates (25 and 0 %; P = 0.038) and progression-free survival (median 5.7 vs. 3.0 months; P = 0.02). Three patients (15 %) achieved conversion to potentially curative surgery. Grade 3/4 toxicities for Group A and Group B were neutropenia (5 and 8.7 %, respectively), anemia (5 and 0 %, respectively), and hyperbilirubinemia (0 and 4.3 %, respectively). Other complications were mostly grade 1 or 2. CONCLUSIONS: HAI combined with SCT treatment can improve overall survival compared with SCT alone in highly advanced CLM refractory to intravenous chemotherapy.

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase

Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 μM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H2O2)-mediated decreases in cell viability, and decreased the extent of H2O2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H2O2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H2O2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.

Caffeic acid improves cell viability and protects against DNA damage: involvement of reactive oxygen species and extracellular signal-regulated kinase.

Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 µM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H2O2)-mediated decreases in cell viability, and decreased the extent of H2O2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H2O2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H2O2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A.

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-ß) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-ß production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-ß production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.

X-cephalometric study of different parts of the upper airway space and changes in hyoid position following mandibular fractures / Estudio cefalométrico con rayos X de diferentes partes del espacio de las vías respiratorias superiores y cambios en la posición hioidea tras fracturas mandibulares

OBJECTIVE: This study analyses the different parts of the upper airway space and the changes in hyoid position. The results provide a clinical reference for developing timely and effective treatment programmes for patients with mandibular fractures caused by maxillofacial trauma. METHODS: Standard X-cephalometric measurements of the lateral skull of 210 subjects were taken. The subjects were divided into four fracture groups: condylar, mandibular angle, mandibular body, and parasymphyseal. RESULTS: The radiographs of the mandibular fracture groups were compared with the normal occlusion group to analyse the upper airway space and the changes in hyoid position. Different types of fractures have different effects on the upper airway space. Bilateral mandibular body fracture and the parasymphyseal fracture have a significant influence on the lower oropharyngeal and laryngopharyngeal airway spaces, with serious obstructions severely restricting the ventilatory function ofpatients. CONCLUSIONS: Fractures at different parts of the mandibular structure are closely related to the upper airway and hyoid position.

OBJETIVO: Este estudio analiza las diferentes partes del espacio de las vías respiratorias superiores y los cambios de posición hioidea. Los resultados proporcionan una referencia clínica para desarrollar programas de tratamiento oportuno y eficaz para los pacientes con fracturas de la mandíbula, causadas por trauma maxilofacial. MÉTODOS: Se hicieron mediciones X-cefalométricas estándares del cráneo lateral a 210 sujetos. Los sujetos fueron divididos en cuatro grupos de fractura: ángulo mandibular, condilar, cuerpo mandibular y parasinfisaria. RESULTADOS: Las radiografías de los grupos de fractura mandibular fueron comparadas con el grupo de oclusión normal para analizar el espacio de las vías respiratorias superiores y los cambios de posición hioidea. Diferentes tipos de fracturas tienen diferentes efectos sobre el espacio de las vías respiratorias superiores. La fractura de cuerpo mandibular bilateral y la fractura de parasinfisaria tienen una influencia significativa en los espacios de las vías respiratorias orofaríngea y laringofaríngea inferiores, con serios obstáculos restringiendo severamente la función respiratoria de los pacientes. CONCLUSIONES: Las fracturas en diferentes partes de la estructura mandibular se hallan estrechamente vinculadas a las vías respiratorias superiores y a la posición hioidea.

X-cephalometric study of different parts of the upper airway space and changes in hyoid position following mandibular fractures.

OBJECTIVE: This study analyses the different parts of the upper airway space and the changes in hyoid position. The results provide a clinical reference for developing timely and effective treatment programmes for patients with mandibular fractures caused by maxillofacial trauma. METHODS: Standard X-cephalometric measurements of the lateral skull of 210 subjects were taken. The subjects were divided into four fracture groups: condylar, mandibular angle, mandibular body, and parasymphyseal. RESULTS: The radiographs of the mandibular fracture groups were compared with the normal occlusion group to analyse the upper airway space and the changes in hyoid position. Different types of fractures have different effects on the upper airway space. Bilateral mandibular body fracture and the parasymphyseal fracture have a significant influence on the lower oropharyngeal and laryngopharyngeal airway spaces, with serious obstructions severely restricting the ventilatory function of patients. CONCLUSIONS: Fractures at different parts of the mandibular structure are closely related to the upper airway and hyoid position.