ObjectiveTo observe the effects of different concentrations of trastuzumab alone or in combination with oxaliplatin on proliferation, apoptosis, and cell cycle of SW-620 human colon cancer cell, and to explore its mechanism. MethodsSW-620 human colon cancer cells were cultured in vitro. ① Cell proliferation experiment: the cells were divided into two large groups: trastuzumab group and trastuzumab combined with oxaliplatin group. There were eight concentration groups in each large group (five holes for each group). The concentration of the trastuzumab group was 0, 0.001, 0.01, 0.1, 1, 10, 100, and 1 000 μg/mL, corresponding to the trastuzumab combined with oxaliplatin group. The concentration of the antibiotic was the same as before, except that oxaliplatin (10 μmol/L) was added. The absorbance (A) value of each group was measured by CCK-8 method. ② Apoptosis experiment: the same proliferation experiment was performed in the group, except that the concentrations of trastuzumab only included 0, 0.1, 1 and 10 μg/mL. Flow cytometry was used to detect the proportion of apoptotic cells and cell cycle distribution in each group. ③ Determination of human epidermalgrowth factor receptor-2 (her-2). The SW-620 cells were divided into two large groups, the concentration of trastuzumab group concluded 0, 100, and 1 000 μg/mL, as well as the concentration of trastuzumab in the trastuzumab combined with oxaliplatin group concluded 0, 1, and 10 μg/mL. Expressions of her-2 protein in SW-620 cells were detected by Western blot method. Results① Cell proliferation assay: the A values at100 μg/mL and 1 000 μg/mL were significantly lower than that at 0 μg/mL (P<0.05). At the same concentration, the A value of the trastuzumab combined with oxaliplatin group was lower than that of the trastuzumab group (P<0.05 ), and the A value gradually decreased with the increase of the concentration of trastuzumab. ② Apoptosis experiment: the proportion of apoptotic cells in the trastuzumab combined with oxaliplatin group was higher than that in the trastuzumab group (P<0.05) at the same concentration of trastuzumab. Flow cytometry: after treatment with different concentrations of trastuzumab combined with oxaliplatin, cells in G1 phase showed a downward trend, and cells in S phase showed an upward trend in a dose-dependent manner. At 1 and 10 μg/mL concentration of trastuzumab, the trastuzumab combined with oxaliplatin group significantly reduced the proportion of cells in the G1 phase of SW-620 cell cycle compared with the trastuzumab group, but S phase ratio was higher (P<0.05). The proportion of G2 phase cells was significantly higher in the trastuzumab combined with oxaliplatin group than the trastuzumab group at 0.1, 1 and 10 μg/mL concentrations of trastuzumab (P<0.01). ③ Expressions of her-2 protein: the expression level of her-2 protein gradually decreased at 1, 100, and 1 000 μg/mL trastuzumab group (P<0.05). The expression levels of her-2 protein in 0, 1 and 10 μg/mL trastuzumab combined with oxaliplatin group also gradually decreased (P<0.01). ConclusionsHigh concentration of trastuzumab can inhibit the proliferation of SW-620 human colon cancer cells and induce apoptosis. Trastuzumab combined with oxaliplatin has synergistic effect on inhibiting cell proliferation and promoting apoptosis.
目的 观察替吉奥胶囊联合奥沙利铂治疗晚期结直肠癌的近期疗效和毒性反应。 方法 2011年5月－12月，将30例晚期结直肠癌患者根据体表面积来确定初始剂量，体表面积＜1.25 m2者，替吉奥胶囊40 mg/次，2次/d；体表面积1.25～1.50 m2者，替吉奥胶囊50 mg/次，2次/d；体表面积＞1.50 m2者，替吉奥胶囊60 mg/次，2次/d。早饭后和晚饭后分别口服1次，第1～4天服用奥沙利铂注射液 130 mg/ m2，静脉滴注，第1、21天重复，此为1个月周期。连用2周期后，按美国国立癌症研究所拟定的药物不良反应的分级评价标准3.0版本评价不良反应，按实体瘤治疗疗效评价标准评价疗效。 结果 30例患者中，完全缓解1例（3.3%），部分缓解7例（23.3%），稳定12例（40%），进展10例（33.3%），疾病控制率为66.6%。不良反应主要是血液学毒性、胃肠道反应、皮肤色素沉着及外周神经毒性；1例Ⅳ度骨髓抑制，3例3度贫血，2例3度腹泻，2例3度皮肤色素沉着，2例3度恶心、呕吐，其余且均在Ⅰ～Ⅱ度骨髓抑制。 结论 替吉奥胶囊联合奥沙利铂方案治疗晚期结直肠癌可获得较高的疾病控制率，不良反应可控。
Objective To investigate the efficacy of Docetaxel injection and Capecitabine tablets combined with Oxaliplatin injection in chemotherapy for patients after esophageal cancer surgery. Methods We retrospectively analyzed the clinical data of 101 patients with esophageal cancer who underwent radical surgery from June 2010 to December 2012, including 58 males and 43 females. According to the different treatment methods they were divided into a study group (58 patients, 32 males and 26 females, postoperatively receiving Docetaxel injection, Capecitabine tablets, Oxaliplatin injection and chemotherapy) and a control group (43 patients, 26 males and 17 females, taking Docetaxel injection and Capecitabine tablets for 4 consecutive courses). We compared the difference in the outcomes between the two groups. Results There was no significant difference in the level of serum anticancer antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and squamous cell carcinoma antigen (SCC) before chemotherapy between two groups (P>0.05). After chemotherapy, the level of serum CEA, CA125, CA199, SCC in the study group was significantly lower than that in the control group (P<0.05). The 1-year survival rate of the study group was 92.59% and the 2-year survival rate was 70.37%, which were not significantly different from those of the control group (P>0.05). The 3-year survival rate of the study group was significantly higher than that of the control group (57.41 %vs. 32.43%, P<0.05). The mean survival time of the study group was longer than that of the control group (31 monthsvs. 22 months, P=0.001). Conclusion Docetaxel injection and Capecitabine tablets combined with Oxaliplatin injection for the treatment of esophageal cancer surgery can significantly reduce levels of tumor markers in serum after esophageal cancer surgery, and is favorable for the long-term survival of patients, but adverse reactions should be noted.
ObjectiveTo evaluate the efficacy and safety of docetaxel (DOC) combined with oxaliplatin (OXA) regimen in the treatment of advanced gastric cancer. MethodsSixty patients with advanced gastric cancer treated in our hospital from January 2008 to January 2011 were randomly divided into two groups. The treatment group (n=30) was given DOC combined with OXA regimen. Patients in this group were treated with DOC 75 mg/m2, ivgtt, d1; OXA 130 mg/m2, ivgtt, d4; with 21 days as a cycle. The control group (n=30) was given DCF regimen. Patients in the control group were treated with DOC 75 mg/m2, ivgtt, d1; cisplatin 75 mg/m2, ivgtt, d1; calcium folinate 200/m2, ivgtt, 2 h, d1-2; fluorouracil 400 mg/m2, bolus 10 minutes, fluorouracil 600 mg/m2 civ 22 h d1-2; also with 21 days as a cycle. All patients received two cycles of chemotherapy at least. The effective rate (complete remission+partial remission), adverse reactions, median survival time and quality of life were analyzed and compared between the two groups. ResultsThe effective rates in the treatment group and the control group were 60.0% and 46.7% respectively, showing a non-significant difference (P>0.05). The appetite increasing rate (70.0% vs 43.3%), the weight gain rate (60.0% vs 33.3%), and the Karnofsky score improvement rate (63.3% vs 30.0%) of the treatment group were significantly higher than those of the control group (P<0.05). The adverse reactions were fewer in the treatment group, and most of them were between grade Ⅰ and Ⅱ. The median time of disease progression (5.8 months vs 5.6 months) and the median survival period (11.8 months vs 9.2 months) of the treatment group were longer than those in the control group. ConclusionDOC combined with OXA regimen is effective in treating advanced gastric cancer. It can significantly improve the quality of life of the patients, and it has fewer adverse reactions. Meanwhile, the median survival period is prolonged. DOC combined with OXA regimen is worth to be applied in clinic.
ObjectiveTo systematically review the efficacy and safety of capecitabine combined with irinotecan (CAPIRI) versus capecitabine combined with oxaliplatin (CAPOX) for patients with advanced/metastatic colorectal cancer.MethodsPubMed, EMbase, The Cochrane Library, VIP, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) on CAPIRI versus CAPOX for patients with advanced/metastatic colorectal cancer from inception to August 2018. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 12 RCTs involving 1 049 patients were included. The results of meta-analysis showed that: there were no significant differences in complete response (CR), partial response (PR), stable disease (SD), progression disease (PD), overall respond rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) between two groups (P>0.05). However, CARIRI group was lower on the disease control rate (RR=0.93, 95%CI 0.86 to 1.00, P=0.04) than CAPOX group. Incidence of diarrhea was higher in CAPIRI group (RR=1.83, 95%CI 1.37 to 2.45, P<0.000 1). However, the incidence rate of peripheral neurotoxicity in CAPOX group was higher (RR=0.13, 95%CI 0.05 to 0.35, P<0.000 1). There were no significant differences between two groups in the incidence rates of nausea and vomiting, hand-foot syndrome, anemia, thrombocytopenia, leukocytopenia and alopecia (P>0.05).ConclusionsCurrent evidence shows that two groups are equivalent in terms of curative effects. CAPIRI has a higher incidence rate of diarrhea, while CAPOX has a higher risk of peripheral neurotoxicity. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
Objective To assess clinical efficacy and safety of Oxaliplatin plus Vinorelbine in the treatment of advanced non-small cell lung cancer (NSCLC). Methods We used the methods of Cochrane reviews, electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2008), MEDLINE (1966 to April 2008), EMbase (1984 to Dec. 2006), Cancerlit (1996 to Dec. 2005), CBM (1978 to April 2008), CNKI (1994 to April 2008), VIP (1989 to April 2008), and handsearched 15 Chinese medical core journals, to collect randomized controlled trials (RCTs) of Oxaliplatin combined with Vinorelbine in the treatment of advanced NSCLC. RCTs were included according to the inclusion and exclusion criteria, the quality of included trials was evaluated and RevMan 4.2.8 software was used for metaanalyses after the extraction of the data. Results Seventeen RCTs involving 1 399 patients with advanced NSCLC were included. All of them reported the use of a random method, but with no detailed reports of allocation concealment and whether the blind method was used. The results of meta-analyses showed that NO program (vinorelbine + oxaliplatin) and NP program (vinorelbine + cisplatin) were similar in efficient rate (RR=0.97, 95%CI 0.85 to 1.10) and 1-year survival rate (RR=0.82, 95%CI 0.66 to 1.03). Compared with NP program, NO program induced lower III-IV degree of nausea and vomiting response (RR=0.20, 95%CI 0.14 to 0.28), III-IV degree of leukopenia reaction (RR=0.64, 95%CI 0.52 to 0.79), and I-II degree of renal damage RR=0.27, 95%CI 0.11 to 0.60) after chemotherapy. No study reported treatmentrelated death. Conclusion Oxaliplatin and Cisplatin plus Vinorelbine are similar in efficacy in the treatment of advanced NSCLC. Oxaliplatin plus Vinorelbine could be used as a chemotherapy of advanced NSCLC because of its better tolerance and more liability to be accepted by patients. However, highly-potential selection bias and measurement bias would affect the demonstration level of the outcome, so more high-quality double-blind RCTs are needed.
Objective To investigate whether miRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colon cancer cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway. Methods miR-34a expression levels were detected in colon cancer tissues and colon cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Computational search, functional luciferase assay, and Western blotting method were used to demonstrate the downstream target of miR-34a in colon cancer cells. Cell viability was measured with cell counting kit-8. Apoptosis and macroautophagy of colon cancer cells were analyzed by flow cytometry and transmission electron microscopy, and expressions of Beclin1 and LC3Ⅱ protein were detected by Western blotting method. Results Expression of miR-34a was significantly reduced while expressions of TGF-β and Smad4 mRNA were increased in colon cancer patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a expression levels and increased TGF-β and Smad4 expression levels in both parental cells and the OXA-resistant colon cancer cells. Activation of macroautophagy contributed to OXA resistance in colon cancer cells. Expression levels of Smad4 and miR-34a in colon cancer patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in colon cancer cells. Conclusion miR-34a mediates OXA resistance of colon cancer by inhibiting autophagy via the TGF-β/Smad4 pathway.