Objective: To explore the correlation among the serum concentrations of HIF-1α, VEGF-A, CEA, CA19-9, the patients' clinicopathological features, recurrence or metastasis in gastric cancer patients after curative resection. Methods: Using retrospective method, a total of 76 cases of gastric cancer patients after radical surgery from January 2010 to September 2012 in our department were extracted. The serum concentrations of HIF-1α, VEGF-A, CEA and CA19-9 were analyzed before and after adjuvant chemotherapy, at the last visit before follow-up deadline/the occurrence of recurrence or metastasis. Results: There were no signiifcant differences in the concentrations of HIF-1α, VEGF-A, CEA and CA19-9 before and after adjuvant chemotherapy in 76 patients (P>0.05). The concentrations of HIF-1αand CEA of 35 gastric cancer patients increased signiifcantly after recurrence or metastasis compared with those before adjuvant chemotherapy (P<0.05). The concentrations of HIF-1αand CEA of 35 gastric cancer patients with recurrence or metastasis was signiifcantly higer than those of 41 patients without recurrence or metastasis at the last visit before follow-up deadline (P<0.05). The subgroup analysis showed that among 31 patients with normal CEA level, serum HIF-1αlevels of with 12 patients recurrence or metastasis was signiifcantly higher than those of 19 patients without recurrence or metastasis (P=0.022). Conclusion: The serum levels of HIF-1αand CEA of gastric cancer patients increased after recurrence or metastasis. For the patients with normal CEA level, the serum level of HIF-1α increased after recurrence or metastasis, which indicated that the increase of HIF-1αwould predict the patients' recurrence or metastasis in gastric cancer.
抗血管生成的贝伐珠单抗已被广泛应用于多种恶性肿瘤的治疗.但因其受益人群有限及逐渐出现的获得性耐药,也限制了其对患者总生存的改善.迫切需要寻找有效的预测贝伐珠单抗疗效的预测因子指导临床应用.人们在生物标记物、影像学方面进行了大量探索,但目前尚没有一个公认的普遍适用的临床预测指标,仍需要从多角度出发,进行进一步的基础研究及临床研究去发现和验证有效的疗效预测指标.
Background: Overall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1 alpha overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1 alpha in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1 alpha, TGF-beta, VEGF and pERK1/2 in gastric cancer patients following gastrectomy.Methods: This study included 446 patients with confirmed gastric cancer who underwent gastrectomy in a single Chinese Cancer Center between 2005 and 2006. Clinicopathologic features, as well as immunohistochemical analysis of TGF-beta, HIF-1 alpha, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.Results: HIF-1 alpha overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, chi(2) = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, chi(2) = 13.691). In univariate analysis, patients with HIF-1 alpha overexpression had a shorter disease-free survival (DFS) and overall survival (OS) than patients with weak-expression (DFS: NA VS. 16.8 m, P = 0.000, chi(2) = 74.937; OS: NA VS. 25.5 m, P = 0.000, chi(2) = 90.594). Importantly, HIF-1 alpha overexpression was a promising prognostic marker for poor survival by multivariate analysis (DFS: HR 2.766, 95% CI 2.136-2.583, P = 0.000; OS: HR 3.529, 95% CI 2.663-4.667, P = 0.000).Conclusions: HIF-1 alpha overexpression could be considered a useful independent prognostic biomarker in gastric cancer after gastrectomy, and is correlated to both a poor overall survival and disease-free survival in these patients. HIF-1 alpha expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients.
The purpose of this study was to determine the disease-free and overall survival (DFS and OS, respectively) in 991 postgastrectomy gastric cancer patients untreated (n = 372) or treated with either oxaliplatin-based (n = 376) or docetaxel-based (n = 243) chemotherapy and to identify prognostic factors that could help establish subgroups of patients who would benefit from such treatment. The median follow-up duration was 55.3 months (range 31.2–90.8 months). Subgroup analyses revealed that gastric adenocarcinoma (DFS 56.9 vs 53.2 months, P = 0.180, χ2 = 1.802; OS not reached vs 70.7 months, P = 0.521, χ2 = 0.412), but not absolute signet ring cell (SRC) carcinoma (DFS 15.1/18.0 vs 10.1 months, P = 0.171/0.259, χ2 = 1.874/1.275; OS 21.0/26.1 vs 20.5 months, P = 0.551/0.196, χ2 = 0.355/1.674), patients undergoing either docetaxel- or oxaliplatin-based chemotherapy had a lower risk of recurrence and increased survival in comparison to those without chemotherapy. In the mixed SRC carcinoma patients, DFS and OS of patients treated with docetaxel-based regimen had a longer survival (DFS 50.1 vs 29.9 months, P = 0.046, χ2 = 3.987; OS not reached vs 48.6 months, P = 0.016, χ2 = 5.854) and lower risk of recurrence and death (DFS HR 0.540, 95 % CI 0.355–0.874, P = 0.012; OS HR 0.452, 95 % CI 0.259–0.790, P = 0.005) than oxaliplatin-based chemotherapy. Cumulatively, our results indicate that adjuvant chemotherapy is beneficial and that docetaxel-based regimen should be considered for patients with mixed SRC carcinoma.
Objective To investigate the efficacy and side effects of cetuximab plus chemotherapy in treatment of advanced gastric cancer.Methods Thirteen patients with advanced gastric cancer were treated with cetuximab plus traditional chemotherapy.Cetuximab 400mg/m2 was taken at the first dose and a maintenance dose was 250mg/m2 every week.The curative effects were evaluated after 2-3 cycles.Results Out of the total 13 patients,6 cases received first-line treatment,2 with PR,4 with SD;seven cases received multi-chemotherapy treatment,1 with PR,2 with SD,3 with PD,and 1 case could not be evaluated.The main toxic reactions were myelosuppression,digestive tract reaction and skin and mucosa reactions.Until the deadline date(December 30,2012),two of the 13 patients survived,and 11 patients died.The survival time ranged from 3.9 to 40.8 months,and the median survival time was 16.4 months(95% CI:8.4-20.4).Conclusion Cetuximab plus chemotherapy in the treatment of advanced gastric cancer may have good efficacy and toxicity can be tolerated.
Objective To investigate the efficacy and toxicity of bevacizumab combined with FOLFOX regimen or FOLFIRI regimen for patients with metastatic colorectal cancer(mCRC) as firstor second-line treatment. Methods Fifty-seven patients with mCRC treated by bevacizumab combined with FOLFOX or FOLFIRI in the PLA General Hospital from December 2005 to August 2012 were analyzed retrospectively with their overall response rate(RR), disease control rate(DCR), progression-free survival(PFS), and overall survival(OS). The tumor responses were assessed by response evaluation criteria in solid tumors guidelines(RECIST) version 1.1. The adverse reation was evaluated by common terminology criteria for adverse events version 3.0. The survival analysis was used by Kaplan-Meier method. Results Of 57 patients with mCRC, 19(33.3%) patients achieved partial response(PR) and 28 patients(49.2%) had stable disease(SD), exhibited an RR of 33.3%, and a DCR of 82.5%. Stratification analysis by firstand second-line treatment or different chemotherapy of bevacizumab combined FOLFOX regimen or FOLFIRI regimen,there were no statistical significance in RR and DCR(P>0.05). The median PFS and OS of 57 patients were 8.83 months and 14.80 months, respectively. Stratification analysis by firstand second-line treatment or different chemotherapy of bevacizumab combined FOLFOX regimen or FOLFIRI regimen,there were no statistical significance in median PFS and OS(P>0.05).The main side effects were leukocytopenia, leukocytopenia and nausea and vomiting. The adverse events related to bevacizumab included hypertension,proteinuria and epistaxis,which were mostly in grade1-2 and alleviated by drug treatment. Conclusion Bevacizumab combined with FOLFOX regimen or FOLFIRI regimen is effective and well tolerated in patients with metastatic colorectal cancer.
Objective To analyze the TTF-1 expression in patients with advanced non-small cell lung cancer and its prognostic significance.Methods Clinicopathological data were collected from patients with advanced non-small cell lung cancer who underwent TTF-1 in our hospital from June 2008 to June 2011.Relation of TTF-1 expression with clinicopathological features and prognosis of patients with advanced non-small cell lung cancer was studied.Results The TTF-1 expression level and histological classification were significantly higher in 67 patients with squamous cell carcinoma and adenocarcinoma(P0.05).However,no significant difference was observed in gender,age,smoking,TNM staging and histological classification,as well as in overall survival time of patients with positive or negative TTF-1 expression(median survival time 27.5 months vs 29.2 months,P0.05).Conclusion TTF-1 can be used in differential diagnosis of squamous cell carcinoma from adenocarcinoma,but TTF-1 expression may not be related with the prognosis of patients with advanced non-small cell lung cancer.