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OBJECTIVE: This study aimed to investigate the effect of occlusal thickness design on fracture resistance of endocrowns restored with lithium disilicate ceramic and zirconia. METHODS: A total of 24 artificial first mandibular molars were randomly divided into four groups with six teeth in each group as follows: group lithium disilicate ceramic-2 mm (lithium disilicate ceramic, with an occlusal thickness of 2 mm and a retainer length of 4 mm); group lithium disilicate ceramic-4 mm (lithium disilicate ceramic, with an occlusal thickness of 4 mm and a retainer length of 2 mm); group zirconia-2 mm (zirconia, with an occlusal thickness of 2 mm and a retainer length of 4 mm); and group zirconia-4 mm (zirconia, with an occlusal thickness of 4 mm and a retainer length of 2 mm). After adhesive cementation (RelyX Ultimate Clicker), all specimens were subjected to thermocycling (10 000 cycles). The specimens were subjected to fracture resistance testing at a 135° angle to the teeth at a crosshead speed of 0.5 mm·min⻹ in a universal testing machine. Data were analyzed with ANOVA and Tukey's HSD test by SPSS 15.0. The failure modes were classified. RESULTS: The fracture resistances of groups lithium disilicate ceramic-2 mm, lithium disilicate ceramic-4 mm, zirconia-2 mm, and zirconia-4 mm were (890.54±83.41), (2 320.87±728.57), (2 258.05±557.66), and (3 847.70±495.99) N respectively. Group zirconia-4 mm had the highest fracture resistance, whereas group lithium disilicate ceramic-2 mm had the lowest. CONCLUSIONS: The fracture resistance of molar endocrown with zirconia is higher than that with lithium disilicate ceramic. Increasing the occlusal thickness can improve the fracture resistance but increase the risk of fracture of abutment.
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Coronas , Fracaso de la Restauración Dental , Cerámica , Porcelana Dental , Análisis del Estrés Dental , Ensayo de Materiales , CirconioRESUMEN
OBJECTIVE: To study the effects of universal adhesives and resin cement on the shear bond strength and durability of zirconia ceramics. METHODS: Zirconia ceramics were sintered into 20 mm×10 mm×10 mm and 10 mm×10 mm×10 mm specimens. The experiment was divided into 12 groups. The two types of specimens were bonded using two variants of resin cement (RelyX Ultimate and Clearfil SAC self-adhesive resin cement), universal adhesives (non-adhesive, Scotchbond uni-versal adhesive, and Clearfil SE One adhesive), and storage conditions (water bath and water bath-thermal cycling). The shear bond strengths were tested, and the fracture morphologies were analyzed. RESULTS: The cement (F=8.41, P<0.01) and adhesive (F=30.34, P<0.01) exerted a significant effect on the shear bond strength of zirconia, whereas storage condition showed no significant effect on this property (F=1.83, P=0.18). The lowest shear bond strength (14.02 MPa±6.86 MPa) was exhibited by the group treated with RelyX Ultimate resin cement, non-adhesive, and water bath-thermal cycling, whereas the highest shear bond strength (54.12 MPa±8.37 MPa) was displayed by the group treated with RelyX Ultimate resin cement, Scotchbond universal adhesive, and water bath-thermal cycling. CONCLUSIONS: Universal adhesives can improve the durability of the bonding of resin cement to zirconia. If non-self-adhesive resin cement is used without a universal adhe-sive, the durability of the bond will be greatly reduced.
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Recubrimiento Dental Adhesivo , Cementos de Resina , Cerámica , Cementos Dentales , Análisis del Estrés Dental , Ensayo de Materiales , Resistencia al Corte , Propiedades de Superficie , CirconioRESUMEN
Gastric cancer is the most common type of gastrointestinal cancer, causing mortality worldwide. However, the underlying molecular mechanism in gastric cancer progression remains unclear. The autophagic flux was determined in gastric cancer cells overexpressing or inhibiting Sp1 transcription factor (SP1) using western blotting, reverse transcriptionpolymerase chain reaction and immunofluorescence staining. Luciferase and ChIP assays were performed to detect the potential underlying mechanism of SP1 in gastric cancer cells. Lastly, immunohistochemistry was also performed on SP1 and p62 expression levels in human gastric cancer specimens. It was demonstrated that SP1 diminished autophagic flux via activating p62 in gastric cancer. Moreover, SP1 deficiency increased the rate of autophagy of gastric cancer cells. Notably, it was observed that SP1 enhanced the expression levels of p62 by directly binding to the promoter of p62. Analysis of gastric cancer specimen staining established that p62 expression levels were increased in SP1positve gastric tissues. The present study provided evidence for a novel mechanism regulating autophagy in gastric cancer cells.
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Proteínas de Unión al ARN/metabolismo , Factor de Transcripción Sp1/metabolismo , Autofagia , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Humanos , Microscopía Fluorescente , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Proteínas de Unión al ARN/genética , Factor de Transcripción Sp1/antagonistas & inhibidores , Factor de Transcripción Sp1/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
INTRODUCTION: Laparoscopy-assisted gastrectomy (LAG) is a minimally invasive procedure for the treatment of gastric cancer. It is generally thought that a minimally invasive technique results in less visible blood loss during the surgery. Nevertheless, a meaningful perioperative hidden blood loss (HBL) is often ignored. In this study, we investigated the amount of HBL and the influential factors after LAG for gastric cancer. METHODS: A retrospectively analyzed clinical data of 62 consecutive patients who underwent laparoscopy-assisted total or distal gastrectomy at our center from May 2016 to May 2017. The HBL was calculated according to Gross's and Nadler's formula. The data of patient gender, age, height, weight, body mass index, preoperative and postoperative hematocrit, postoperative drainage, albumin loss, diabetes mellitus, and hypertension were analyzed by multivariate linear regression analysis. The type of surgical reconstruction was analyzed by one-way analysis of variance. The difference between the preoperative blood pressure and postoperative blood pressure was measured by paired sample t-test and boxplot. RESULTS: The HBL was 322.2 ± 195.9 mL (64.3% ± 14.1% in total blood loss [TBL]), the TBL was 475.6 ± 222.8 mL, and the hemoglobin (HB) loss was 15.0 ± 8.7 (11.5% ± 6.1% of HB level loss). Multivariate linear regression analysis revealed that gender, hypertension, and albumin loss between preoperation and postoperation are influential factors of HBL in patients after LAG for gastric cancer. Compared to male patients, female patients are positively associated with HBL. CONCLUSION: In our study, we found HBL is a significant segment of TBL and is much larger than what we considered previously in LAG for gastric cancer. Gender, hypertension, and albumin loss are significantly correlated with HBL. Therefore, paying attention to HBL is significant for promoting clinical treatment and ensuring patients' safety.
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Pérdida de Sangre Quirúrgica , Gastrectomía/métodos , Hemoglobinas/metabolismo , Laparoscopía , Hemorragia Posoperatoria/etiología , Neoplasias Gástricas/cirugía , Anciano , Volumen Sanguíneo , Femenino , Gastrectomía/efectos adversos , Humanos , Hipertensión/complicaciones , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Albúmina Sérica/metabolismo , Factores Sexuales , Neoplasias Gástricas/sangreRESUMEN
BACKGROUND AND OBJECTIVES: Oligosaccharide or oligopeptide supplementation may have a significant impact on endurance performance. This study evaluated the effects of adding maltooligosaccharides (MO) or soy oligopeptides (SO) to compressed food (CF) on the physical response of soldiers to daily military training. METHODS AND STUDY DESIGN: Twelve soldiers were randomized to four diet groups: regular meals, CF, CFMO, and CFSO (crossover design). They participated in exercise tests including 90 minutes running at 55-65% VO2max and exhaustive running. Heart rates, rating of perceived exertion (RPE), and blood and urine samples were collected during exercise and recovery. RESULTS: The recovery heart rates were significantly lower with the CFMO diet compared with the other diets. Compared with all other diets, blood glucose levels were higher, post-exercise blood lactate levels were lower, and lactate clearance during recovery was higher with the CFMO diet, followed by the CFSO diet. Post-exercise levels of erythrocytes and hematocrit were significantly higher with the CFSO diet. Post-exercise urine specific gravity was lower with the CFMO diet and urine pH was decreased with the CFSO diet. Blood urea nitrogen (BUN) and uric acid (UA) were significantly higher with the CFSO diet than with the other diets. There was no significant difference in skeletal and cardiac muscle injury indices and RPE among diets. CONCLUSIONS: CFMO led to better heart rate recovery, improved and maintained blood glucose and increased removal of blood lactate. CFSO accelerated removal of blood lactate during recovery, maintained oxygen supply, and increased fluid retention.
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Análisis de los Alimentos , Manipulación de Alimentos , Personal Militar , Oligopéptidos/administración & dosificación , Resistencia Física , Glucemia , Estudios Cruzados , Frecuencia Cardíaca , Humanos , Lactatos/sangre , Oligopéptidos/químicaRESUMEN
Gossypol is a polyphenolic, yellowish compound derived from cottonseed extract. The present study examined the effects of gossypol on the apoptosis and autophagy of HT29 cells. A Cell Counting Kit8 assay, Annexin VFITC, JC1 staining and western blotting were used to identify the viability of cells, stages of apoptosis and the expression levels of the signaling proteins. Gossypol promoted apoptosis and induced the loss of mitochondrial membrane potential. Further investigation of the apoptotic mechanism revealed that gossypol increased the ratio of Bcell lymphoma 2 (Bcl-2)-associated X protein/Bcl2 protein levels and upregulated the expression of caspase3. Gossypol also enhanced the activity of microtubuleassociated protein light chain 3 LC3II and Beclin1 and downregulated LC3I, in a dosedependent manner. Together, these finding suggested that gossypol may be a novel and potential antitumor agent.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Gosipol/farmacología , Beclina-1/metabolismo , Caspasa 3/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células HT29 , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The aim of the study is to demonstrate the effect of Romidepsin in hepatocellular carcinoma (HCC) by inducing G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis through JNK/c-Jun/caspase3 pathway in vitro and in vivo. Human HCC cell lines were cultured with Romidepsin and DMSO (negative control) and 5-fluorouracil (positive control). Then the cells' viability and apoptosis were determined by cell proliferation assay and flow cytometry. Protein concentrations and expression changes were measured by Western blot. Subsequently, Huh7 cells were subcutaneously inoculated into the nude mice, which were employed to further probe the tumor-suppressive effect of Romidepsin in vivo. Romidepsin treatment led to a time- and dose-dependent induction of cell cycle arrest in the G2/M phase and apoptosis. G2/M phase arrest inhibited the proliferation of HCC cells by alterations in p21/cdc25C/cdc2/cyclinB proteins. Increased concentrations of Erk and JNK phosphorylations were observed in a dose-dependent manner in the Romidepsin group, but p38 phosphorylation was not affected. G2/M phase arrest and the apoptosis of HCC cells induced by Romidepsin were mediated by the activation of Erk/MAPK pathways and JNK/MAPK pathways. The tumor size was significantly larger in the negative control group compared to Romidepsin group and no significant loss in body weight was observed in the Romidepsin group. Our findings offer proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC.
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Antineoplásicos/farmacología , Apoptosis , Carcinoma Hepatocelular/metabolismo , Depsipéptidos/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Neoplasias Hepáticas Experimentales/metabolismo , Animales , Antineoplásicos/uso terapéutico , Proteína Quinasa CDC2 , Carcinoma Hepatocelular/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ciclina B/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Depsipéptidos/uso terapéutico , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Xenoinjertos , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Neoplasias Hepáticas Experimentales/patología , Ratones Desnudos , Trasplante de Neoplasias , Transducción de Señal , Fosfatasas cdc25/metabolismoRESUMEN
@#An id eal balance between the post length within root and the coronal extension should exist. Some theories advocated the use of the longest post as possible as the apical seal is not disturbed. Others advocated that the post should be longer than the crown or that the post should be a certain fraction of the length of the root. The conventional post length has been equal to 2/3-3/4 of the root length from half a century ago. Most of these theories have emphasized the post length in order to achieve sufficient retention and rigidity for coronal restoration. However, dental materials are evolving.With the use of fiber post and resin cement, stress distribution and post retention are improved over conventional metal post and zinc phosphate or glass-ionomer cement. Therefore, with improved bonding strength of fiber post, the post length within root should be minimized to maintain sufficient coronal rigidity. Factors affecting fracture resistance balance of a post-and-core system include the amount of Ferrule height (FH), Post length in root (PLIR), Post length in bone (PLIB), Abutment height (AH), Core length (CL) and Post length out of bone (PLOB). In view of the factors mentioned above, this paper investigated the mechanical factorsin a post-and-core system with literature review.
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RATIONALE AND OBJECTIVE: Recently, interest in the role of aquaporin 1 (AQP1) in human gastrointestinal carcinogenesis has developed. However, to date no studies have examined relationships between AQP1 expression and specific characteristics of gastric adenocarcinoma. METHODS: We investigated 109 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine AQP1 expression. We then evaluated disease free survival (DFS) and overall survival (OS) in these patients in association with AQP1 expression. RESULTS: Both immunohistochemical and RT-PCR analyses identified increased AQP1 expression in tumors from patients with gastric adenocarcinoma (p < 0.001). The 3-year DFS and OS rates were higher in the AQP1-negative group than in the positive group (DFS: 77.2 vs. 52.8%, p < 0.001; OS: 85.1 vs. 70.7%, p < 0.001). The 5-year DFS and OS rates exhibited a similar trend (p < 0.001). Subgroup analysis of patients with early gastric adenocarcinoma (stages I and II) revealed a total 5-year OS of 90.0%, with 5-year OS being higher in the AQP1-negative group than in the positive group (95.2 vs. 84.2%). Furthermore, incidence of tumor recurrence following surgical treatment was significantly higher in the AQP1-positive group (4/19, 21.1%) compared with the negative group (0/21, 0%). CONCLUSIONS: Our study demonstrates that AQP1 plays an important role in gastric adenocarcinoma and may therefore represent a novel therapeutic target and prognostic marker in this disease.
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Adenocarcinoma/genética , Acuaporina 1/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Gástricas/genética , Adenocarcinoma/química , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Acuaporina 1/análisis , Supervivencia sin Enfermedad , Femenino , Mucosa Gástrica/química , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/química , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Cancers have dysfunctional redox regulation resulting in production of reactive oxygen species (ROS), damaging DNA, RNA and free NTPs, and causing the accumulation of oxidative nucleic acids in cytoplasm. The major types are 8-oxo-7,8-dihydroguanine(8-oxoGsn) in RNA and 8-oxo-7,8-dihydro-2' deoxyguanosine(8-oxodGsn) in Mt-DNA. The MTH1 protein sanitizes oxidized nucleotide pools from NTPs to monophosphates, preventing the occurrence of transversion mutations. This study concerned cytoplasmic 8-oxodGsn/Gsn and MTH1 expression in gastric cancer and para-cancer tissues and elucidated roles of nucleic-acid oxidation and anti-oxidation. MATERIALS AND METHODS: A polymer HRP detection system was used to detect 8-oxo-Gsn/dGsn and MTH1 expression in 51 gastric cancer and para-cancer tissue samples. Analyses of patient clinical and pathological data were also performed. RESULTS: The expression of MTH1 and the 8-oxo-dGsn/Gsn ratio were significantly higher in cancer tissues than para-cancer tissues (P<0.05). Cytoplasmic 8-oxo-Gsn and MTH1 were both found to positively correlate (P<0.05) with tumor differentiation, while no significant associations were found with gender, age, invasion depth, lymph node metastasis and clinical stage (P>0.05). CONCLUSIONS: We found 8-oxo-dGsn/Gsn and MTH1 are both highly expressed in gastric cancer tissues, especially in well differentiated lesions. In addition, oxidated mtDNA is prevalently expressed in gastric cancers, while 8-oxo-Gsn expression in cytoplasmic RNA is a bit lower, but more selectively.
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Adenocarcinoma/química , Adenocarcinoma/patología , Enzimas Reparadoras del ADN/análisis , Desoxiguanosina/análogos & derivados , Guanina/análogos & derivados , Monoéster Fosfórico Hidrolasas/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Anciano , Anciano de 80 o más Años , Citoplasma/química , Desoxiguanosina/análisis , Femenino , Guanina/análisis , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/química , Clasificación del Tumor , Estómago/químicaRESUMEN
OBJECTIVE: This study was conducted to investigate the effects of orally administered apigenin on the pharmacokinetics of venlafaxine (VEN) in rats and on the metabolism of VEN in human and rat liver microsomes in vitro. METHODS: Ten healthy male SD rats were randomly divided into 2 groups: A group (control group), B group (a single dose of 250 mg/kg apigenin). A single dose of 20 mg/kg VEN was administered orally 30 min after administration of apigenin (250 mg/kg). VEN plasma levels were measured by HPLC with fluorescence detection, and pharmacokinetic parameters were calculated by DAS 3.0 software. RESULTS: The single dose of 250 mg/kg apigenin significantly increased the AUC0-t of VEN by 40.9% (p < 0.05) and obviously increased the peak plasma concentration (Cmax) of VEN (p < 0.05). Furthermore, apigenin showed inhibitory effect on human and rat microsomes and the IC50 of apigenin was 58.37 and 25.73 µmol/l, respectively. CONCLUSIONS: Our results indicated that an intake of apigenin could increase VEN plasma levels and some of its pharmacokinetic parameters (AUC, Tmax). Thus, more attention should be paid when VEN was administrated combined with apigenin.
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Antidepresivos de Segunda Generación/farmacocinética , Apigenina/farmacología , Clorhidrato de Venlafaxina/farmacocinética , Animales , Área Bajo la Curva , Interacciones Farmacológicas , Semivida , Humanos , Técnicas In Vitro , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-Dawley , Clorhidrato de Venlafaxina/antagonistas & inhibidoresRESUMEN
BACKGROUND: Previous studies regarding the association between cruciferous vegetable intake and pancreatic cancer risk have reported inconsistent results. We conducted a meta-analysis to demonstrate the potential association between them. METHODS: A systematic literature search of papers was conducted in March 2014 using PubMed, EMBASE, and Web of Science, and the references of the retrieved articles were screened. The summary odds ratios (ORs) with 95% confidence interval (CI) for the highest versus the lowest intake of cruciferous vegetables were calculated. RESULTS: Four cohort and five case-control studies were eligible for inclusion. We found a significantly decreased risk of pancreatic cancer associated with the high intake of cruciferous vegetables (OR 0.78, 95% CI 0.64-0.91). Moderate heterogeneity was detected across studies (P = 0.065). There was no evidence of significant publication bias based on Begg's funnel plot (P = 0.917) or Egger's test (P = 0.669). CONCLUSIONS: Cruciferous vegetable intake might be inversely associated with pancreatic cancer risk. Because of the limited number of studies included in this meta-analysis, further well-designed prospective studies are warranted to confirm the inverse association between cruciferous vegetable intake and risk of pancreatic cancer.
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Dieta , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/prevención & control , Verduras , Estudios de Casos y Controles , Humanos , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Treatment for gastric cancer with portal hypertension must consider the eradication of the tumor and the change of hemodynamics in portal hypertension (PHT). Few reports have described the surgical procedures and postoperative complications of surgery for gastric cancer associated with PHT. METHODS: The clinical data of 22 patients with PHT undergoing curative surgery for gastric cancer during 5 years were retrospectively analyzed. For 12 patients classified in Child's class A, D2 lymph node (LN) dissection was performed, and 10 patients classified into Child's class B were treated with D1 LN dissection. Surgical treatment included total gastrectomy combined with pericardial devascularization, distal subtotal gastrectomy, distal subtotal gastrectomy combined with splenectomy, and distal subtotal gastrectomy combined with pericardial devascularization with posterior gastric artery and left inferior phrenic artery preserved. A liver biopsy was analyzed in all patients. RESULTS: Postoperative complications developed in 50 % (11/22 patients) and the mortality rate was 9 % (2/22). The rate of postoperative ascites in patients with Child's class A was much lower than in those with Child's class B (P < 0.05). "Operation time," "volume of hemorrhage," "platelet count," and "treatment of PHT" are all risk factors of liver function deterioration. However, there was no significant difference in liver function deterioration rate between patients with Child's class A and Child's class B (P > 0.05). The occurrence rate of complications in patients with PHT was much higher compared to those without with PHT (P < 0.05). CONCLUSIONS: Individualized selection of surgical approaches is crucial for treatment of gastric carcinoma accompanied by PHT. Surgical treatment should be based on preoperative TNM stage, liver function, and degree of PHT.
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Gastrectomía , Hipertensión Portal/cirugía , Complicaciones Posoperatorias , Neoplasias Gástricas/cirugía , Anciano , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/mortalidad , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/mortalidad , Tasa de SupervivenciaRESUMEN
AIM: To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stage III/IV gastric cancer. METHODS: A total of 53 stage III/IV gastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy. Two of the cases were excluded. The program was as follows: 75 mg/m(2) docetaxel and 85 mg/m(2) oxaliplatin on day 1 and 1500 mg/m(2) fluorouracil on days 1 to 3 for three weeks. RESULTS: The tumour changes, postoperative remission rate, changes in the symptoms and adverse reactions were observed. The overall clinical efficacy (complete remission + partial remission) of the neoadjuvant chemotherapy was 62.7%. R0 radical resection was performed on 60.8% of the patients, with a remission rate (pathological complete response + pathological subtotal response + pathological partial response) of 74.2%. The Karnofksy score improved in 42 cases. The toxicity reactions mostly included myelosuppression, followed by gastrointestinal mucosal lesions, nausea, vomiting and diarrhoea. CONCLUSION: Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stage III/IV gastric cancer. However, the treatment is associated with a high incidence of bone marrow suppression, which should be managed clinically.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gastrectomía , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Diagnóstico por Imagen/métodos , Docetaxel , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Inducción de Remisión , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Taxoides/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: An increasing number of evidence suggests that pancreatic cancer contains cancer stem cells (CSCs), which may be relevant to the resistance of chemotherapy. Latexin (Lxn) is a negative regulator of stem cell proliferation and we investigate the effects of Lxn on CD133+ pancreatic cancer stem-like cells. METHODS: CD133+ miapaca-2 cells, a human pancreatic carcinoma cell line, were isolated and sorted by magnetic activated cell sorting and flow cytometry. The capacity for self-renewal, proliferation, and tumorigenicity of CD133+ miapaca-2 cells was determined by the floating spheres test and tumor xenograft assays. Protein and mRNA expression of Lxn in CD133+ and CD133- miapaca-2 cells were detected by Western blotting and qRT-PCR, respectively. After CD133+ miapaca-2 cells were treated with Lxn in serum-free medium (SFM), cell proliferation was assayed with a Cell Counting Kit 8 (CCK-8) and apoptosis was analyzed by flow cytometry. The protein and mRNA expression levels of Bcl-2, bax, and c-myc were also analyzed. RESULTS: We successfully isolated CD133+ miapaca-2 cells that exhibited the capacity for self-renewal in SFM, a proliferation potential in DMEM supplemented with FBS, and high tumorigenicity in nude mice. Lxn protein and mRNA expression levels in CD133+ miapaca-2 cells were significantly lower than those in CD133- cells. Lxn-treated CD133+ miapaca-2 cells exhibited increased apoptosis and low proliferation activity, down-regulation of Bcl-2 and c-myc expression, and up-regulation of Bax expression in a dose-dependent manner. CONCLUSIONS: Lxn induces apoptosis and inhibits the proliferation of CD133+ miapaca-2 cells. These changes are associated with down-regulation of Bcl-2 and c-myc and up-regulation of Bax.
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Antígenos CD/genética , Antígenos/genética , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/genética , Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/genética , Péptidos/genética , ARN Neoplásico/genética , Antígeno AC133 , Animales , Antígenos/biosíntesis , Antígenos CD/metabolismo , Apoptosis , Western Blotting , Línea Celular Tumoral , Proliferación Celular , Citometría de Flujo , Glicoproteínas/metabolismo , Humanos , Masculino , Ratones , Ratones Desnudos , Neoplasias Experimentales , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Péptidos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study aims to investigate the significance and mechanism of artesunate involved in suppressing the proliferation of gastric cancer in vitro and in vivo. In the in-vitro experiments, artesunate inhibited the growth of gastric cancer cell lines (SGC-7901, BGC-823, and AGS) with concentration-dependent activity, with no significant effect on GES-1 cells. BGC-823 cells treated with artesunate showed the typical morphologic features of oncosis rather than apoptosis. Meanwhile, we observed calcium overload, downregulation of vascular endothelial growth factor expression, and upregulation of calpain-2 expression in the artesunate-treated BGC-823 cells. In addition, the in-vivo study showed that artesunate produced a dose-dependent tumor regression in nude mice. The antitumor activity of 240 mg/kg artesunate was similar to that of 10 mg/kg docetaxel. Furthermore, compared with the control group, no significant difference was observed in the body weight of artesunate-treated nude mice other than docetaxel-treated nude mice. These observations show that artesunate has concentration-dependent inhibitory activities against gastric cancer in vitro and in vivo by promoting cell oncosis through an impact of calcium, vascular endothelial growth factor, and calpain-2 expression.
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Antineoplásicos Fitogénicos/uso terapéutico , Artemisininas/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacología , Artemisininas/efectos adversos , Artemisininas/farmacología , Artesunato , Señalización del Calcio/efectos de los fármacos , Calpaína/química , Calpaína/metabolismo , Muerte Celular/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Concentración 50 Inhibidora , Masculino , Ratones , Ratones Desnudos , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Distribución Aleatoria , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Carga Tumoral/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To observe the effect of curcumin combined folinic acid fluorouracil oxaliplatin (FOLFOX) on the gastric adenocarcinoma cell line BGC-823 and to explore its possible mechanisms. METHODS: Cells were divided into five groups, i.e. the blank control group, the curcumin group, the FOLFOX group (0.1 mmol/L 5-FU +5 micromol/L oxaliplatin), and the curcumin combined FOLFOX group. CCK-8 was used to detect cell activity. The cell apoptosis was observed using Hoechst dyeing. Caspase-3 test kit was applied to test Caspase-3 vitality. The mRNA expressions of Bcl-2 and Bax were detected by real time fluorescent quantitative PCR. The expressions of Bcl-2 and Bax protein were determined by Western blot. RESULTS: The BGC-823 cells' proliferation could be inhibited, apoptosis induced, the Caspase-3 activity increased, expressions of Bcl-2 mRNA and Bcl-2 protein lowered, while Bax mRNA and Bax protein expressions increased in each medicated group. Besides, the efficacy of the curcumin combined FOLFOX group was superior to that of the curcumin group and the FOLFOX group, showing statistical difference (P < 0.01). CONCLUSION: Curcumin combined FOLFOX could significantly inhibit the proliferation of BGC-823 cells possibly via promoting Bax expression and Caspase-3 activity, inhibiting Bcl-2 expression, thus inducing apoptosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Curcumina/farmacología , Neoplasias Gástricas/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fluorouracilo/farmacología , Humanos , Leucovorina/farmacología , Compuestos Organoplatinos/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
In this study, the unilateral and bilateral syrinx nerve (NXIIts) were resected in the red-billed Leiothrix (Leiothrix lutea) to assess the roles of NXIIts in vocalization. Wavesurfer and Sound Analysis Pro were used to analyze pre- and postsurgical acoustic changes. After resecting of unilateral NXIIts, red-billed Leiothrix produced the common calls with lengthened syllable interval, shortened duration and a declined FM index. The effects of left NXIIts resction on temporal and spectral characteristics of syllables were more significant than that of right NXIIts. These results indicated that the neural control of NXIIts was unilateral and left-side dominated. Moreover, the left NXIIts could produce high frequency components and harmonic waves. After resecting of bilateral NXIIts, the calls were characterized by monotone, reduced loudness and increased syllable pulse numbers.
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Passeriformes/fisiología , Passeriformes/cirugía , Pliegues Vocales/inervación , Vocalización Animal , Animales , Desnervación , Masculino , Pliegues Vocales/fisiopatología , Pliegues Vocales/cirugíaRESUMEN
Lysine acetylation refers to transfer of the acetyl moiety from acetyl-CoA to the ε-amino group of a lysine residue on a protein. This has recently emerged as a major covalent modification and interplays with other modifications, such as phosphorylation, methylation, ubiquitination (addition of a small protein called ubiquitin) and SUMOylation [addition of a ubiquitin-like protein known as SUMO (small ubiquitin-related modifier)], to form multisite modification programmes for cellular regulation in diverse organisms. This modification is post-translational (i.e. after synthesis of a protein) and reversible, with its level being dynamically balanced by two groups of enzymes known as lysine acetyltransferases and deacetylases. The acetyltransferases belong to three major families, whereas deacetylases have been divided into the classical and sirtuin [Sir-tu-in, for Sir2 (silent information regulator 2)-like protein; named after the yeast protein Sir2] families. In addition to these enzymes, proteins containing the bromodomain, a protein module named after the fly protein Brahma (God of creation in Hindu), are relevant to lysine acetylation biology due to their ability to recognize acetyl-lysine-containing peptides. Importantly, recent studies have made intimate links between these three different groups of proteins to different pathological conditions. In this chapter, we provide a brief overview of these proteins and emphasize their direct links to related human diseases.
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Acetiltransferasas/metabolismo , Lisina/metabolismo , Sirtuinas/metabolismo , Acetilación , Acetiltransferasas/genética , Animales , Humanos , Modelos Biológicos , Sirtuinas/genéticaRESUMEN
Histone acetyltransferases and deacetylases are two groups of enzymes whose opposing activities govern the dynamic levels of reversible acetylation on specific lysine residues of histones and many other proteins. Gastrointestinal (GI) carcinogenesis is a major cause of morbidity and mortality worldwide. In addition to genetic and environmental factors, the role of epigenetic abnormalities such as aberrant histone acetylation has been recognized to be pivotal in regulating benign tumorigenesis and eventual malignant transformation. Here we provide an overview of histone acetylation, list the major groups of histone acetyltransferases and deacetylases, and cover in relatively more details the recent studies that suggest the links of these enzymes to GI carcinogenesis. As potential novel therapeutics for GI and other cancers, histone deacetylase inhibitors are also discussed.