Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated wi...Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.展开更多
Advanced gastric cancer(a GC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve s...Advanced gastric cancer(a GC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve survival and tumor related symptoms in the frontline setting, second-line therapy(SLT) is subject to much debate in the scientific community, mainly because of the debilitating effects of GC, which would impede the administration of cytotoxic therapy. Recent data has provided sufficient evidence for the safe use of SLT in patients with an adequate performance status. Taxanes, Irinotecan and even some Fluoropyrimidine analogs were found to provide a survival advantage in this subset of patients. Most importantly, quality of life measures were also improved through the use of adequate therapy. Even more pertinent were the findings involving antiangiogenic agents, which would add measurable improvements without significantly jeopardizing the patients' well-being. Further lines of therapy are cause for much more debate nowadays, but specific targeted agents have shown considerable promise in this context. We herein review noteworthy published data involving the use of additional lines of the therapy after failure of standard frontline therapies in patients with a GC.展开更多
AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 tre...AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.展开更多
AIM: To explore the synergistic effect of docosahexaenoic acid(DHA)/5-fluorouracil(5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with...AIM: To explore the synergistic effect of docosahexaenoic acid(DHA)/5-fluorouracil(5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes(METCs)?Ⅰ, Ⅱ and Ⅴ in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU(G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase(G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells.CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.展开更多
AIM： To study the antitumor effect of Chinese compound Jinlongshe （JLS） granules on sarcoma 180 and MKN-45 human gastric cancer cell lines in vivo and its mechanism. METHODS： After establishment of S180 sarcoma （...AIM： To study the antitumor effect of Chinese compound Jinlongshe （JLS） granules on sarcoma 180 and MKN-45 human gastric cancer cell lines in vivo and its mechanism. METHODS： After establishment of S180 sarcoma （S180） and MKN-45 gastric cancer model of nude mice, the tumor-bearing mice were divided into 5 groups at random. Three experimental groups were respectively given the aqueous extract of JLS granules at doses of 120 g, 60 g and 20 g/（kg per 6/wk,i.g） for 3 wk in S180 and 6 wk in nude mice model. Positive control was given cyclophosphamide （Cy） at a dose of 50 mg/（kg per 3/wk, i.g） for 3 wk in S180 models and 5-Fluorouracil （5-FU） 20 mg/（kg per 3/wk, i.g） for 3 wk in nude mice model. Negative control was given normal saline （NS） at a dose of 0.18 g/（kg per 6/wk, i.g） respectively. After 3 wk in mice bearing S180 tumor and 6 wk in nude mice model, the experimental animals were sacrificed and the masses of tumor were weighed, and the rates of tumor inhibition of each treated group were calculated respectively. To determine the antitumor mechanisms, the morphological changes, cell cycle and apoptosis were observed in MKN-45 nude mice model. Annexin V-FITC/PI double staining FCM assay was used to further determine the live cells, apoptotic cells, necrotic cells and debris. RESULTS： The inhibitory rates of JLS granules at the doses of 20 g/kg, 60 g/kg and 120 g/kg were 50.31%, 55.94% and 68.13% （P 〈 0.01） in nude mice models and 40.90%, 50.32% and 58.46% （P 〈 0.01） in S180 model. The inhibitory rate of Cy was 85.22% in S180 models and the inhibitory rate of 5-FU was 53.43% in nude mice model （P 〈 0.01）. Nuclear chromatin and margination were observed under a transmission electron microscope （TEM）. The G0/G1 phase was arrested, typical apoptotic peak appeared, the apoptotic rate was 22.81%-38.54% in three JLS granule-treated groups. Annexin V-FITC/PI double staining FCM assay showed that the apoptotic cells were 4.36%, 3.08% and 7.08% in three dosages, most cells were localized in the low right quadrant. CONCLUSION：Jinlongshe granules possess anti-tumor effects on experimental tumor models in vivo, and apoptosis induction is one of its anti-tumor mechanisms.展开更多
[目的]评价消癌平注射液联合一线化疗治疗晚期胃癌的疗效及安全性。[方法]检索发表于中国知网(CNKI)、万方数据库(WanFang)、维普数据库(VIP)、Pubmed以及Web of science共5个中英文数据库中有关消癌平注射液联合一线化疗方案治疗晚期...[目的]评价消癌平注射液联合一线化疗治疗晚期胃癌的疗效及安全性。[方法]检索发表于中国知网(CNKI)、万方数据库(WanFang)、维普数据库(VIP)、Pubmed以及Web of science共5个中英文数据库中有关消癌平注射液联合一线化疗方案治疗晚期胃癌的随机对照试验(RCT),检索时间范围设定为各数据库自建库以来至2023年10月27日,对符合纳入排除标准的研究进行偏倚风险评价及Meta分析。[结果]共纳入10项RCT,共包含814例晚期胃癌患者;在近期疗效方面消癌平注射液联合一线化疗方案能够有效提升客观缓解率(ORR)[RR:1.35,95%CI(1.15,1.58),P=0.0002]以及卡氏评分(KPS)[RR:1.62,95%CI(1.16,2.26),P=0.005];且3-4级不良反应事件(SAE)发生数量少于单纯化疗[RR:0.32,95%CI(0.06,0.90),P=0.04];在远期生存获益方面,消癌平注射液联合一线化疗方案在无进展生存期(PFS)[HR:0.32,95%CI(0.17,0.62),P=0.0007]以及总生存期(OS)[HR:0.33,95%CI(0.16,0.65),P=0.002]方面均优于单纯化疗;GRADE分级结果显示,ORR、KPS、PFS、OS为低等级质量证据,SAE为极低等级质量证据。[结论]消癌平注射液联合一线化疗具有良好的临床疗效及安全性,但纳入文献的方法学质量较低,尚需要更加全面的大样本、多中心、随机双盲对照实验进行验证。展开更多
文摘Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.
文摘Advanced gastric cancer(a GC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve survival and tumor related symptoms in the frontline setting, second-line therapy(SLT) is subject to much debate in the scientific community, mainly because of the debilitating effects of GC, which would impede the administration of cytotoxic therapy. Recent data has provided sufficient evidence for the safe use of SLT in patients with an adequate performance status. Taxanes, Irinotecan and even some Fluoropyrimidine analogs were found to provide a survival advantage in this subset of patients. Most importantly, quality of life measures were also improved through the use of adequate therapy. Even more pertinent were the findings involving antiangiogenic agents, which would add measurable improvements without significantly jeopardizing the patients' well-being. Further lines of therapy are cause for much more debate nowadays, but specific targeted agents have shown considerable promise in this context. We herein review noteworthy published data involving the use of additional lines of the therapy after failure of standard frontline therapies in patients with a GC.
文摘AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.
文摘AIM: To explore the synergistic effect of docosahexaenoic acid(DHA)/5-fluorouracil(5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes(METCs)?Ⅰ, Ⅱ and Ⅴ in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU(G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase(G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells.CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.
基金Supported by the Modernization Programs of Chinese Materia Medica of Science and Technology Commission Foundation of Shanghai, No. 04DZ19811
文摘AIM： To study the antitumor effect of Chinese compound Jinlongshe （JLS） granules on sarcoma 180 and MKN-45 human gastric cancer cell lines in vivo and its mechanism. METHODS： After establishment of S180 sarcoma （S180） and MKN-45 gastric cancer model of nude mice, the tumor-bearing mice were divided into 5 groups at random. Three experimental groups were respectively given the aqueous extract of JLS granules at doses of 120 g, 60 g and 20 g/（kg per 6/wk,i.g） for 3 wk in S180 and 6 wk in nude mice model. Positive control was given cyclophosphamide （Cy） at a dose of 50 mg/（kg per 3/wk, i.g） for 3 wk in S180 models and 5-Fluorouracil （5-FU） 20 mg/（kg per 3/wk, i.g） for 3 wk in nude mice model. Negative control was given normal saline （NS） at a dose of 0.18 g/（kg per 6/wk, i.g） respectively. After 3 wk in mice bearing S180 tumor and 6 wk in nude mice model, the experimental animals were sacrificed and the masses of tumor were weighed, and the rates of tumor inhibition of each treated group were calculated respectively. To determine the antitumor mechanisms, the morphological changes, cell cycle and apoptosis were observed in MKN-45 nude mice model. Annexin V-FITC/PI double staining FCM assay was used to further determine the live cells, apoptotic cells, necrotic cells and debris. RESULTS： The inhibitory rates of JLS granules at the doses of 20 g/kg, 60 g/kg and 120 g/kg were 50.31%, 55.94% and 68.13% （P 〈 0.01） in nude mice models and 40.90%, 50.32% and 58.46% （P 〈 0.01） in S180 model. The inhibitory rate of Cy was 85.22% in S180 models and the inhibitory rate of 5-FU was 53.43% in nude mice model （P 〈 0.01）. Nuclear chromatin and margination were observed under a transmission electron microscope （TEM）. The G0/G1 phase was arrested, typical apoptotic peak appeared, the apoptotic rate was 22.81%-38.54% in three JLS granule-treated groups. Annexin V-FITC/PI double staining FCM assay showed that the apoptotic cells were 4.36%, 3.08% and 7.08% in three dosages, most cells were localized in the low right quadrant. CONCLUSION：Jinlongshe granules possess anti-tumor effects on experimental tumor models in vivo, and apoptosis induction is one of its anti-tumor mechanisms.
文摘[目的]评价消癌平注射液联合一线化疗治疗晚期胃癌的疗效及安全性。[方法]检索发表于中国知网(CNKI)、万方数据库(WanFang)、维普数据库(VIP)、Pubmed以及Web of science共5个中英文数据库中有关消癌平注射液联合一线化疗方案治疗晚期胃癌的随机对照试验(RCT),检索时间范围设定为各数据库自建库以来至2023年10月27日,对符合纳入排除标准的研究进行偏倚风险评价及Meta分析。[结果]共纳入10项RCT,共包含814例晚期胃癌患者;在近期疗效方面消癌平注射液联合一线化疗方案能够有效提升客观缓解率(ORR)[RR:1.35,95%CI(1.15,1.58),P=0.0002]以及卡氏评分(KPS)[RR:1.62,95%CI(1.16,2.26),P=0.005];且3-4级不良反应事件(SAE)发生数量少于单纯化疗[RR:0.32,95%CI(0.06,0.90),P=0.04];在远期生存获益方面,消癌平注射液联合一线化疗方案在无进展生存期(PFS)[HR:0.32,95%CI(0.17,0.62),P=0.0007]以及总生存期(OS)[HR:0.33,95%CI(0.16,0.65),P=0.002]方面均优于单纯化疗;GRADE分级结果显示,ORR、KPS、PFS、OS为低等级质量证据,SAE为极低等级质量证据。[结论]消癌平注射液联合一线化疗具有良好的临床疗效及安全性,但纳入文献的方法学质量较低,尚需要更加全面的大样本、多中心、随机双盲对照实验进行验证。
