目的 建立重组人内皮抑素（恩度）联合顺铂一线治疗肿瘤进展的小鼠模型，继续应用内皮抑素联合紫杉醇二线治疗，研究内皮抑素协同紫杉醇抗肿瘤的作用及其机制。 方法 建立小鼠Lewis 肺癌移植瘤动物模型，内皮抑素联合顺铂治疗后观察肿瘤生长情况，遴选出肿瘤进展小鼠16只，随机留取1只，余15只小鼠随机分成紫杉醇组和联合用药组治疗，观察疗效。另取上述肿瘤进展小鼠1只，剥离肿瘤组织，重新接种，将成瘤小鼠随机分成生理盐水组，紫杉醇组及联合用药组治疗，观察疗效。治疗结束后24 h处死所有小鼠，采用免疫组织化学CD31单克隆抗体标记检测微血管密度（MVD），采用原位末端转移酶（TUNEL）检测细胞凋亡。 结果 只肿瘤进展小鼠中，联合用药组相比紫杉醇组生存时间无明显延长，但肿瘤体积增长较慢；而在重新接种成瘤的小鼠中，联合用药组较其余各组微血管密度明显减低（P＜0.05），凋亡指数明显增加（P＜0.05），肿瘤体积抑制明显。 结论 在内皮抑素联合顺铂治疗肿瘤进展的小鼠模型中，继续应用内皮抑素治疗与紫杉醇有较明显的协同抗肿瘤作用。
ObjectiveTo summarize the biological function of extracellular matrix metalloproteinase inducer (EMMPRIN) in tumor progression, and its roles in clinical diagnosis and treatment in recent years. MethodsLiteratures about the recent studies on molecular structure of EMMPRIN and biological function in tumor progression were reviewed according to the results searched from PubMed database. ResultsEMMPRIN play important roles in the tumor progression, involved in inducing the degradation of extracellula matrix, promoting angiogenesis, inhibiting apoptosis, enhancing chemoresistance and so on. ConclusionEMMPRIN could be a potential therapeutic target in turmor.
ObjectiveCD44 and CD54 are two specific biomarkers of gastric cancer stem cells and were used as targets in this study. The number of CD45–CD44+CD54+ cell subsets in peripheral blood of gastric cancer patients was detected by flow cytometry. Further, we combined these results with the clinicopathological characteristics of gastric cancer patients to analyze the significance of CD45–CD44+CD54+ cell subsets.MethodsFrom December 2016 to September 2017, 38 patients with gastric cancer in gastrointestinal surgery of West China Hospital of Sichuan University were included as the study object. The content of CD45–CD44+CD54+ cell subsets in their peripheral blood was detected by flow cytometry and its clinical significance was analyzed.ResultsThe median number of CD45–CD44+CD54+ cells were 541.9/mL (71.7–8 057.0/mL) in 38 patients and 555.9/mL (71.7–8 057.0/mL) in the group of patients with R0 resection. Patients without lymph node metastasis were found to have more CD45–CD44+CD54+ cells than patients with lymph node metastasis [941.4/mL (183.5–8 057.0)/mL vs 379.3/mL (71.7–2 269.7/mL, P=0.002], and more CD45–CD44+CD54+ cells in patients with TNM stage Ⅰ–Ⅱ than in TNM stage Ⅲ–Ⅳ [858.6/mL (183.5–8 057.0/mL) vs 364.6/mL (71.7–2 269.7/mL, P=0.015]. The patients with T3–4 stages (P= 0.025), N+ stage (P=0.009) and TNM Ⅲ–Ⅳ stage (P=0.012) had low ratios of the subgroup with high number of CD45–CD44+CD54+ cells, respectively. We made a more accurate judgment of N stage and TNM stage when we combined tumor size and the number of CD45–CD44+CD54+ cells together. However, there was no significant correlation between the number of CD45–CD44+CD54+ cells and other clinicopathological features and prognosis.ConclusionsThe number of CD45–CD44+CD54+ cell subsets is correlated with tumor progression, which might be used to predict TNM stage and N stage. However, the number of patients included in this study is too small, and the clinical significance of CD45–CD44+CD54+ subsets in gastric cancer patients needs to be further demonstrated by expanding the sample size.
ObjectiveTo study the effect of tumor associated neutrophil (TAN) releasing a proliferation-inducing ligand (APRIL) on the proliferation of pancreatic cancer cells in microenvironment.Methods① The expressions of APRIL in neutrophils (differentiated by HL-60 cell) and TAN cells were detected by use ELISA. ② The expressions of APRIL receptors B cell maturation antigen (BCMA) and trans-membrane activator and CAML interactor (TACI) in pancreatic cancer cell line PANC-1 were confirmed by use Western blotting. ③ Pancreatic cancer PANC-1 cells were co-cultured with TAN, and divided into a PANC-1 control group (referred to as the control group), a PANC-1+TAN treatment group (referred to as the PANC-1+TAN group), PANC-1+TAN+APRIL antibody treatment group (referred to as PANC-1+TAN+APRIL group), and PANC-1+rtificial recombinant APRIL protein (rAPRIL) treatment group (referred to as PANC-1+rAPRIL group). The CCK8 method was used to determine TAN release of APRIL on PANC-1 effect of cell proliferation activity.Results① The APRIL content in the culture medium of TAN cell group was higher than that of neutrophil group [(556.20±84.38) pg/mL vs. (377.17±57.07) pg/mL, P=0.038]. ② PANC-1 cells express the receptors BCMA and TACI of APRIL. ③ PANC-1 cell activity of PANC-1+TAN group and PANC-1+rAPRIL group [(126.80±1.42)%, (168.95±12.54)%] were significantly higher than the control group [(100 ± 0.00)%, P<0.05, P<0.001], the activity of PANC-1 cells in the PANC-1+TAN group was significantly higher than that in the PANC-1+TAN+APRIL group [(86.29 ± 12.20)%, P=0.003] and significantly lower than that of PANC-1+rAPRIL group (P=0.002), the activity of PANC-1 cells in PANC-1+rAPRIL group was significantly higher than that in PANC-1+TAN+APRIL antibody group (P<0.001).ConclusionIn the microenvironment of pancreatic cancer, the release of APRIL from TAN increases, which promotes the proliferative activity of PANC-1 in pancreatic cancer cells, which provides a new idea for the mechanism research and treatment of pancreatic cancer progression.
Objective To summarize the research progress of alternative splicing in pancreatic cancer, and to provide reference for further research. MethodThe experimental and clinical studies of alternative splicing in pancreatic cancer were reviewed.Results Alternative splicing dysregulation resulted in changed gene expression or novel isoform formation, thereby influencing the carcinogenesis, progression or chemoresistance of pancreatic cancer. The differentially expressed alternative splicing isoforms may serve as diagnostic markers, indicators of aggressiveness or prognostic markers of pancreatic cancer. Conclusion Further investigation of the molecular mechanisms of alternative splicing in carcinogenesis and progression of pancreatic cancer is a new way to improve the early diagnosis and treatment of pancreatic cancer.
ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.