RESUMO
Survival for patients with advanced gastric cancer (GC) remains poor. Systemic chemotherapy which has reached a plateau stays the standard first-line (1L) treatment for advanced human epidermal growth-factor receptor 2 (HER2)-negative GC. To maximize the benefit of 1L treatment, the concept of maintenance treatment is constantly being explored. In advanced HER2-negative GC, current clinical guidelines do not recommend a standard maintenance therapy strategy. In addition to the monotherapy maintenance with fluorouracil after 4-6 cycles of 1L chemotherapy, some agents that are active against novel targets have been evaluated in clinical trials for maintenance treatment. Whereas most of these trials do not reach their primary endpoints, they open new horizons for the 1L treatment of advanced HER2-negative GC. Therefore, we reviewed the clinical trials in the field of maintenance treatment in advanced HER2-negative GC and discussed some of the problems in clinical trials.
Assuntos
Quimioterapia de Manutenção , Receptor ErbB-2 , Neoplasias Gástricas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase III como Assunto , Fluoruracila/uso terapêutico , Humanos , Oxaliplatina/uso terapêutico , Pirimidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , RamucirumabRESUMO
The accuracy of quantitative trait loci (QTLs) identified using different sample sizes and marker densities was evaluated in different genetic models. Model I assumed one additive QTL; Model II assumed three additive QTLs plus one pair of epistatic QTLs; and Model III assumed two additive QTLs with opposite genetic effects plus two pairs of epistatic QTLs. Recombinant inbred lines (RILs) (50-1500 samples) were simulated according to the Models to study the influence of different sample sizes under different genetic models on QTL mapping accuracy. RILs with 10-100 target chromosome markers were simulated according to Models I and II to evaluate the influence of marker density on QTL mapping accuracy. Different marker densities did not significantly influence accurate estimation of genetic effects with simple additive models, but influenced QTL mapping accuracy in the additive and epistatic models. The optimum marker density was approximately 20 markers when the recombination fraction between two adjacent markers was 0.056 in the additive and epistatic models. A sample size of 150 was sufficient for detecting simple additive QTLs. Thus, a sample size of approximately 450 is needed to detect QTLs with additive and epistatic models. Sample size must be approximately 750 to detect QTLs with additive, epistatic, and combined effects between QTLs. The sample size should be increased to >750 if the genetic models of the data set become more complicated than Model III. Our results provide a theoretical basis for marker-assisted selection breeding and molecular design breeding.
Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Plantas/genética , Locos de Características Quantitativas , Simulação por Computador , Epistasia Genética , Endogamia , Modelos Genéticos , Melhoramento Vegetal , Tamanho da Amostra , Seleção GenéticaRESUMO
In this study, we examined changes in meat quality and content of muscle types during porcine growth. The influence of the longissimus dorsi muscle fiber composition on meat quality and the correlation between 2 fiber-typing methods (histochemistry and real-time quantitative polymerase chain reaction) were examined. Type IIx and type IIb fibers accounted for most of the total number of fibers; the proportion of these fibers increased during porcine growth (75.42, 80.09, and 79.88%, respectively, at 3 different stages of growth). There was a strong positive correlation between the 2 fiber-typing methods; the correlation coefficients of type I, IIa, and IIx+IIb fiber contents were 0.65, 0.88, and 0.92, respectively. The a* value of meat color was significantly lower at 98 days and negatively correlated with white fiber content (r = -0.69, P < 0.01). Water-holding capacity decreased during porcine growth. The drip loss parameter was positively correlated with type IIx+IIb fiber content (r = 0.55, P < 0.05). Decreased pH was strongly positively correlated with type IIx+IIb fiber content (r = 0.61, P < 0.01) and negatively correlated with type IIa fiber content (r = -0.44, P < 0.05). Therefore, we found that the composition of muscle fibers influenced the establishment of meat quality and its alteration during the early postmortem period.
Assuntos
Carne/normas , Fibras Musculares Esqueléticas/metabolismo , Sus scrofa/crescimento & desenvolvimento , Animais , Cor , Regulação da Expressão Gênica no Desenvolvimento , Concentração de Íons de Hidrogênio , Masculino , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Sus scrofa/genéticaRESUMO
This study compared the abnormal corneal epithelium after laser-assisted subepithelial keratectomy (LASEK) with dystrophic cornea using in vivo using confocal microscopy (IVCM) and examined the effects of the abnormal epithelium on postoperative recovery of uncorrected distance visual acuity (UDVA) and sub-basal nerve plexus regeneration. The UDVA and wound healing were examined in 50 eyes of 25 patients undergoing LASEK at 1 week, 1 month, and 1 year postoperatively, including the visual acuity, slit lamp microscopy, and IVCM. After 1 week, the corneal epithelium was healed in all patients, but abnormal epithelial cells were detected in 33/50 patients using IVCM. Abnormal cells were limited to the surgical margin, and highly reflective granules were observed underneath. At 1 month and 1 year postoperatively, the abnormal epithelium was unchanged in size. At 1 year postoperatively, there were clear differences between the sub-basal nerve plexus in the normal and abnormal epithelium. At 1 month postoperatively, the UDVA was >1.0 in 88% of patients, which increased to 94% at 1 year, and there was no clear difference in the UDVA between abnormal (N = 33) and normal (N = 17) epithelium. After LASEK, abnormal epithelial cells may arise at the margin of the epithelial flap and persist 1 year postoperatively accompanied by poor regeneration of the sub-basal nerve plexus. However, this does not affect the UDVA postoperatively. The abnormal epithelium may be caused by residual necrotic basal cell debris on the epithelial basement membrane and abnormal neurotrophic metabolism between the corneal epithelium and nerve plexus.
Assuntos
Ceratectomia Subepitelial Assistida por Laser/métodos , Adulto , Feminino , Humanos , Masculino , Microscopia Confocal , Miopia/fisiopatologia , Miopia/cirurgia , Acuidade Visual , Adulto JovemRESUMO
OBJECTIVES: A variety of inflammatory cytokines have been demonstrated to participate in tumorigenesis and progression. Secretory leukocyte protease inhibitor (SLPI) has been demonstrated to show a broad-spectrum of anti-inflammatory effects. This study investigates the expression of SLPI in human pancreatic cancer tissues and cells as well as its biological effects in human pancreatic cancer cells. METHODS: Reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot were used to detect SLPI mRNA and protein levels in human pancreatic cancer tissues, adjacent tissues, and pancreatic cancer Bxpc-3 and Panc-1 cells. Knockout of SLPI expression was established by recombinant viral vector expressing short hairpin RNA (shRNA) targeting SLPI. Cell viability was analyzed by MTT assay. Cell apoptosis was detected by Hochest33258 staining and flow cytometry assay. RESULTS: Higher SLPI expression was observed in pancreatic tissues, Bxpc-3 cells, and Panc-1 cells compared to the peritumoral tissues (p < 0.01). SLPI expression in Bxpc-3 and Panc-1 cells was effectively silenced by shRNA (p < 0.001). Silencing of SLPI expression significantly reduced cell viability, inhibited cell proliferation, and induced cell apoptosis (p < 0.001). CONCLUSIONS: Abnormal over-expression of SLPI in pancreatic cancer cells may be associated with the development of disease through its roles in promoting cancer cell survival and proliferation as well as anti-apoptosis. SLPI can be used as a target for developing targeted therapy of pancreatic cancer.
Assuntos
Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Inibidor Secretado de Peptidases Leucocitárias/genética , Adulto , Idoso , Apoptose , Western Blotting/métodos , Proliferação de Células , Sobrevivência Celular , Feminino , Citometria de Fluxo , Inativação Gênica , Vetores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transfecção , Células Tumorais Cultivadas , Adulto JovemRESUMO
This experiment was conducted to evaluate the combination effect of low dietary non-phytate phosphorus (NPP) concentrations, phytase (PHY) levels, and 25-hydroxycholecalciferol (25-OH-D3) levels on the growth performance and meat quality of broilers. Two levels of NPP, two levels of PHY, and two levels of 25-OH-D3 resulted in a 222 factorial arrangements, with eight treatments (TRT). The birds on TRT 1-4 were fed diet 1 (NRC NPP was reduced by 0.1) and the birds on TRT 5-8 were fed with diet 2 (NRC NPP was reduced by 0.2). Each diet was mixed with different levels PHY and 25-OH-D3. Performance and meat quality parameters were measured. Results showed that during entire experiment the most advantageous effects were obtained with TRT 3 (NRC NPP reduced by 0.1 + 600 U/kg phytase + 34.5g/kg 25-OH-D3) and TRT 4 (NRC NPP reduced by 0.1 + 600 U/kg phytase + 69g/kg 25-OH-D3). The lowest body weight gain (BWG) and feed intake(FI) were observed with TRT 5 (NRC NPP reduced by 0.2 + 300 U/kg phytase + 34.5g/kg 25-OH-D3). Lowering NRC NPP by 0.1 to 0.2 significantly reduced weight gain (WG) (p 0.05) and FI (p 0.05) during the starter phase (ST), while during grower phase (GF) lowering NRC NPP by 0.1 to 0.2 did not affect WG (p>0.05) and produced small decrease in FI. BWG, FI and feed conversion ratio were not influenced (p>0.05) by different PHY or 25-OH-D3 levels. In addition, the meat color, pH, and shear force were not affected by the different NPP, PHY or 25-OH-D3levels.
Assuntos
Animais , Calcitriol/administração & dosagem , Calcitriol/análogos & derivados , Carne/análise , Fósforo/administração & dosagem , Aumento de Peso , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismoRESUMO
This experiment was conducted to evaluate the combination effect of low dietary non-phytate phosphorus (NPP) concentrations, phytase (PHY) levels, and 25-hydroxycholecalciferol (25-OH-D3) levels on the growth performance and meat quality of broilers. Two levels of NPP, two levels of PHY, and two levels of 25-OH-D3 resulted in a 222 factorial arrangements, with eight treatments (TRT). The birds on TRT 1-4 were fed diet 1 (NRC NPP was reduced by 0.1) and the birds on TRT 5-8 were fed with diet 2 (NRC NPP was reduced by 0.2). Each diet was mixed with different levels PHY and 25-OH-D3. Performance and meat quality parameters were measured. Results showed that during entire experiment the most advantageous effects were obtained with TRT 3 (NRC NPP reduced by 0.1 + 600 U/kg phytase + 34.5g/kg 25-OH-D3) and TRT 4 (NRC NPP reduced by 0.1 + 600 U/kg phytase + 69g/kg 25-OH-D3). The lowest body weight gain (BWG) and feed intake(FI) were observed with TRT 5 (NRC NPP reduced by 0.2 + 300 U/kg phytase + 34.5g/kg 25-OH-D3). Lowering NRC NPP by 0.1 to 0.2 significantly reduced weight gain (WG) (p 0.05) and FI (p 0.05) during the starter phase (ST), while during grower phase (GF) lowering NRC NPP by 0.1 to 0.2 did not affect WG (p>0.05) and produced small decrease in FI. BWG, FI and feed conversion ratio were not influenced (p>0.05) by different PHY or 25-OH-D3 levels. In addition, the meat color, pH, and shear force were not affected by the different NPP, PHY or 25-OH-D3levels.(AU)
Assuntos
Animais , Carne/análise , Fósforo/administração & dosagem , Calcitriol/análogos & derivados , Calcitriol/administração & dosagem , Galinhas/metabolismo , Galinhas/crescimento & desenvolvimento , Aumento de PesoRESUMO
Ziyuglycoside II is an active compound of Sanguisorba officinalis L. that has anti-inflammation, antioxidation, antibiosis, and homeostasis properties. We report here on the anticancer effect of ziyuglycoside II on human gastric carcinoma BGC-823 cells. We investigated the effects of ziyuglycoside II on cell growth, cell cycle, and cell apoptosis of this cell line. Our results revealed that ziyuglycoside II could inhibit the proliferation of BGC-823 cells by inducing apoptosis but not cell cycle arrest, which was associated with regulation of Bax/Bcl-2 expression, and activation of the caspase-3 pathway. Our study is the first to report the antitumor potential of ziyuglycoside II in BGC-823 gastric cancer cells. Ziyuglycoside II may become a potential therapeutic agent against gastric cancer in the future.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Caspase 3/efeitos dos fármacos , Inibidores de Caspase/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fluorometria , Fluoruracila/farmacologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Sanguisorba/química , Neoplasias Gástricas/tratamento farmacológico , Proteína X Associada a bcl-2/efeitos dos fármacosRESUMO
Ziyuglycoside II is an active compound of Sanguisorba officinalis L. that has anti-inflammation, antioxidation, antibiosis, and homeostasis properties. We report here on the anticancer effect of ziyuglycoside II on human gastric carcinoma BGC-823 cells. We investigated the effects of ziyuglycoside II on cell growth, cell cycle, and cell apoptosis of this cell line. Our results revealed that ziyuglycoside II could inhibit the proliferation of BGC-823 cells by inducing apoptosis but not cell cycle arrest, which was associated with regulation of Bax/Bcl-2 expression, and activation of the caspase-3 pathway. Our study is the first to report the antitumor potential of ziyuglycoside II in BGC-823 gastric cancer cells. Ziyuglycoside II may become a potential therapeutic agent against gastric cancer in the future.