Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer

AIM: To evaluate the expression of galectin-1 and vascular endothelial growth factor (VEGF) in gastric cancer and investigate their relationships with clinicopathologic factors and prognostic significance. METHODS: Galectin-1 and VEGF were immunohistochemically investigated in tumor samples obtained from 214 gastric cancer patients with all tumor stages. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on formalin-fixed, paraffin-embedded sections of surgical specimens. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathologic variables, and patient survival were analyzed. All patients underwent follow-up until cancer-related death or more than five years after tumor resection. P values < 0.05 were considered statistically significant.RESULTS: Immunohistochemical staining demonstrated that 138 of 214 gastric cancer samples (64.5%) were positive for galectin-1, and 116 out of 214 gastric cancer samples (54.2%) were positive for VEGF. There was a significant association between galectin-1 and VEGF expression; VEGF was detected in 60.1% of galectin-1-positive samples and 43.4% of galectin-1-negative samples (P < 0.05). Galectin-1 expression was associated with tumor size, tumor location, stage, lymph node metastases, and VEGF expression (all P < 0.05). VEGF expression was related to tumor size, stage, and lymph node metastases (all P < 0.05). The 5-year survival rate was 56.6% for galectin-1-positive patients and 69.2% for galectin-1-negative patients, and the prognosis for galectin-1-positive patients was significantly poorer compared with galectin-1-negative patients (χ 2 = 13.880, P = 0.000). The 5-year survival rates for VEGF-positive and VEGF-negative patients were 53.4% and 70.5%, respectively (χ2 = 4.619, P = 0.032). The overall survival rate of patients with both galectin-1 and VEGF overexpression in gastric cancer tissue samples was significantly poorer than other groups (both P < 0.05).CONCLUSION: Galectin-1 expression was positively associated with VEGF expression. Both galectin-1 and VEGF can serve as independent prognostic indicators of poor survival for gastric cancer after gastrectomy.

(-)-Epigallocatechin-3-gallate inhibits growth of gastric cancer by reducing VEGF production and angiogenesis

AIM： To investigate the effect of （-）-epigallocatechin-3-gallate （EGCG） on growth of gastric cancer and its possible mechanism. METHODS： Heterotopic tumors were induced by subcutaneously injection of SGC-7901 cells in nude mice. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density （MVD） by immunohistology. Vascular endothelial growth factor （VEGF） protein level and activation of signal transducer and activator of transcription 3 （Star3） were examined by Western blotting. VEGF mRNA expression was determined by RT-PCR and VEGF release in tumor culture medium by ELISA. VEGF-induced cell proliferation was studied by MTT assay, cell migration by gelatin modified Boyden chamber （Transwell） and in vitro angiogenesis by endothelial tube formation in Matrigel. RESULTS： Intraperitoneal injection of EGCG inhibited the growth of gastric cancer by 60.4%. MVD in tumor tissues treated with EGCG was markedly reduced. EGCG treatment reduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Star3, but EGCG treatment did not change the total Star3 expression. EGCG also inhibited VEGF-induced endothelial cell proliferation, migration and tube formation. CONCLUSION： EGCG inhibits the growth of gastric cancer by reducing VEGF production and angiogenesis, and is a promising candidate for anti-angiogenic treatment of gastric cancer.

Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density(MVD)(endocan-MVD), VEGF and vascular endothelial growth factor receptor 2(VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student's t-test or an analysis of variance test. Spearman's rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues(108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type(P > 0.05), while endocan-MVD was associated with tumour size,Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage(P < 0.05). According to the Spearman's rank correlation analysis, endocan-MVD had a positive correlation with VEGF(r = 0.167, P = 0.047) and VEGFR2(r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD(17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.

Spectral computed tomography in advanced gastric cancer: Can iodine concentration non-invasively assess angiogenesis?

AIM To investigate the correlation of iodine concentration(IC) generated by spectral computed tomography(CT) with micro-vessel density(MVD) and vascular endothelial growth factor(VEGF) expression in patients with advanced gastric carcinoma(GC).METHODS Thirty-four advanced GC patients underwent abdominal enhanced CT in the gemstone spectral imaging mode. The IC of the primary lesion in the arterial phase(AP) and venous phase(VP) were measured, and were then normalized against that in the aorta to provide the normalized IC(nI C). MVD and VEGF were detected by immunohistochemical assays, using CD34 and VEGF-A antibodies, respectively. Correlations of nI C with MVD, VEGF, and clinical-pathological features were analyzed.RESULTS Both nI Cs correlated linearly with MVD and were higher in the primary lesion site than in the normal control site, but were not correlated with VEGF expression. After stratification by clinical-pathological subtypes, nI C-AP showed a statistically significant correlation with MVD, particularly in the group with tumors at stage T4, without nodular involvement, of a mixed Lauren type, where the tumor was located at the antrum site, and occurred in female individuals. nI C-VP showed a positive correlation with MVD in the group with the tumor at stage T4 and above, had nodular involvement, was poorly differentiated, was located at the pylorus site, of a mixed and diffused Lauren subtype, and occurred in male individuals. nI C-AP and nI C-VP showed significant differences in terms of histological differentiation and Lauren subtype.CONCLUSION The IC detected by spectral CT correlated with the MVD. n IC-AP and n IC-VP can reflect angiogenesis in different pathological subgroups of advanced GC.

Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- els and clinicopathological parameters in gastric cancer.METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

Current and emerging therapies in unresectable and recurrent gastric cancer

Gastric cancer is one of the most lethal cancers worldwide despite many advances and options in therapy. As it is often diagnosed at an advanced stage, prognosis is poor with a median overall survival of less than twelve months. Chemotherapy remains the mainstay of treatment for these patients but it confersonly a moderate survival advantage. There remains a need for new targeted treatment options and a way to better define patient populations who will benefit from these agents. In the past few years, there has been a better understanding of the biology, molecular profiling, and heterogeneity of gastric cancer. Our increased knowledge has led to the identification of gastric cancer subtypes and to the development of new targeted therapeutic agents. There are now two new targeted agents, trastuzumab and ramucirumab, that have recently been approved for the treatment of advanced and metastatic gastric cancer. There are also many other actively investigated targets, including epidermal growth factor receptor, the phosphatadylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, c-Met, poly ADP-ribose polymerase, and immune checkpoint inhibition. In this review, we discuss the current management of advanced gastric cancer as well as emerging targeted therapies and immunotherapy.

(-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer. METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditionedmedium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR). Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay. RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490, VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited Stat3 nucleus translocation, and Stat3-DNA binding activity was also markedly decreased by EGCG. Furthermore, EGCG inhibited IL-6 induced vascular endothelial cell proliferation and tube formation in vitro and angiogenesis in vitro . CONCLUSION: EGCG inhibits IL-6-induced VEGF expression and angiogenesis via suppressing Stat3 activity in gastric cancer, which has provided a novel mechanistic insight into the anti-angiogenic activity of EGCG.

Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs).

Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer

AIM: To clarify the significance of vascular endothelial growth factor(VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45 P. METHODS: The supernatant of culture medium of MKN-45 cells or MKN-45 P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse modelof peritoneal metastasis. RESULTS: The concentrations of interleukin-6(IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer. CONCLUSION: Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.

Molecular targeting to treat gastric cancer

Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.

Effect of Jianpi Jiedu Recipe on angiogenesis and the PTEN/PI3K/AKT signaling pathway in the course of Helicobacter pylori-induced gastric cancer in C57BL/6 mice

Objective： To reveal the effect of Jianpi Jiedu recipe （JPJDR） on angiogenesis and the PTEN （Phosphatase and tensinhomolog deleted on chromosome ten）/PI3K/AKT signaling pathway in the course of H. pylori infection-inducedcarcinogenesis of gastric mucosa in C57BL/6 mice. Methods： Two-hundred C57BL/6 mice were randomly divided intofive groups （control group, model group, JPJDR low-dose group, JPJDR medium-dose group, and JPJDR high-dosegroup）, 40 in each group. A mouse model of gastric cancer, induced by H. pylori standard strain infection, wasestablished. The mice of JPJDR low-dose, middle-dose, and high-dose groups were intragastrically administered 250,500, and 1000 mg/kg JPJDR per day, respectively. After 72 weeks, the H. pylori infection in gastric mucosa of the micewas analyzed by rapid urease test; the pathological changes in the gastric mucosa of mice were assessed byhistopathological examination, and micro-vessel density （MVD）, vascular endothelial growth factor （VEGF）, andPTEN/PI3K/AKT levels were determined. Results： The incidence of gastric cancer in each group （control group, modelgroup, JPJDR low-dose, medium-dose, high-dose group） was 0%, 26.3%, 13.2%, 10%, and 7.5% respectively. Theincidence of gastric cancer in the Chinese medicine group was significantly lower than that of the model group （P =0.020, P = 0.023, P = 0.007）. The expression of MVD and VEGF in the model group was significantly higher than thatin the control group （P = 0.002, P 〈 0.001）, while the expression of MVD and VEGF decreased in the Chinese medicinegroup. The expression of p-PTEN and p-AKT in the model group was significantly higher than that in the control group（All P 〈 0.001）, while Chinese medicine could reduce the expression of p-PTEN and p-AKT to varying extents.Conclusion： Long-term infection of C57BL/6 mice with H. pylori induces gastric carcinogenesis, by increasing gastricmucosal MVD, promoting the expression of VEGF, inhibiting the activity of PTEN, and activating the PI3K/AKTsignaling pathway. JPJDR can reduce the infection rate of H. pylori in mouse gastric mucosa, inhibit the expression ofMVD and VEGF, and reduce the inactivation of PTEN.

Relationship between VEGF,EGF and Invasion,Metastasis of Gastric Cancer Cells

Objective： To investigate the relationship between expression of vascular endothelial growth factor （VEGF）, epidermal growth factor （EGF） and the biological properties of gastric cancer cells such as invasion and metastasis. Methods： RT-PCR was performed to semi-quantitatively detect the mRNA expressions of EGF, EGFR, VEGF and VEGFR in four kinds of gastric cancer cell lines BGC823, MGCS03, HGC27 and SGC7901, which were classified by their differentiation degree in our experiment. We obtained cell line growth curves from MTT assays. The migration of gastric cancer cells was observed under inverted phase contrast microscope. The changes of invasion and adhesion were detected by a Transwell assay. Results： The growth rates slowed down sequentially in MGC803, HGC27, BGC823 and SGC7901（P〈 0.05）. The ability of migration, invasion and adhesion were reduced sequentially, and the difference was significant. The expressions of EGF, EGFR, VEGF and VEGFR were significantly stronger in MGCS03 and HGC27 than in BGC823 and SGC7901 cells, and the difference was statistically significant（P〈0.05）. Conclusion： The expressions of VEGF and EGF had close relationship with the properties of migration, adhesion and invasion of gastric cancer cells in vitro. Thus, targeting VEGF and EGF may be a potential therapeutic strategy for inhibiting peritoneal metastasis of gastric cancer.

Issues of origin,morphology and clinical significance of tumor microvessels in gastric cancer

Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC,including the identification and characterization of diagnostic,prognostic,predictive,and therapeutic biomarkers.It is known that the main cause of death from malignant neoplasms and GC,in particular,is tumor metastasis.Given that angiogenesis is a critical process for tumor growth and metastasis,it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy.In the presented review,modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered;data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized;and various approaches to the classification of tumor vessels,as well as the methods for assessing angiogenesis activity in a tumor,are highlighted.Here,results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed,and a new classification of tumor microvessels in GC,based on their morphology and clinical significance,is proposed for consideration.

Effects of shRNA Targeting VEGF on VEGF mRNA Expression in Gastric Cancer Cells

In order to investigate the inhibitory effect of plasmid-mediated short hairpin RNA targeting vascular endothelial growth factor （VEGF） on the expression of VEGF mRNA in human gastric cancer cells, a plasmid vector for transcribing specific short hairpin RNA targeting VEGF （ pU6-VEGF ） was constructed, and then transfected into human gastric cancer cells using Lipofectamine2000. The VEGF mRNA expression level was detected by RT-PCR. RPMI1640 was used for blank control, and pSilencer 1.0-U6 empty plasmid for the negative control. Results showed the clone and sequence analysis revealed that the recombinant plasmid vector of pU6-VEGF was successfully constructed. The VEGF mRNA expression levels in blank control group, experimental group （pU6-VEGF） and negative control group （pSilencerl,0-U6） were 100%, 49% and 94%, respectively, indicating VEGF mRNA expression in the cells transfected with pU-VEGF vector was inhibited significantly as compared with blank control group and negative control group. It was concluded that the short hairpin RNA could significantly inhibit the expression of VEGF mRNA, which provided an experimental basis for treating human cancer with anti-angiogenesis.

血管内皮生长因子、程序性死亡受体-1联合胃功能三项对早期胃癌的诊断及预后评估价值

目的:探讨血管内皮生长因子(VEGF)、程序性死亡受体-1(PD-1)联合胃功能三项对早期胃癌(EGC)的诊断及预后评估价值。方法:选取EGC患者167例为EGC组,对术中的胃癌及癌旁组织进行收集,免疫组织化学染色后比较VEGF、PD-1阳性表达情况。另选取本院同期体检健康者74例为对照组,比较EGC组与对照组胃功能三项[胃蛋白原Ⅰ(PGⅠ)、胃蛋白原Ⅱ(PGⅡ)和胃泌素17(G17)]水平。所有患者均进行为期3年随访,根据是否病死分为预后良好组和预后不良组,比较两组临床病理资料。Logistic回归分析EGC患者预后不良的影响因素,Pearson法分析各指标的相关性,受试者工作特征(ROC)曲线分析VEGF、PD-1联合胃功能三项检测在EGC患者诊断及预后评估中的应用价值。结果:EGC组患者癌旁组织VEGF、PD-1阳性表达率低于胃癌组织(均P<0.05)。与对照组比较,EGC组PGⅠ水平降低,PGⅡ、G17水平升高(均P<0.05)。根据随访结果,预后不良组59例,预后良好组108例。预后不良组患者VEGF和PD-1阳性表达率以及PGⅡ、G17水平高于预后良好组,中高分化占比和PGⅠ水平低于预后良好组(均P<0.05)。低PGⅠ水平、高VEGF和PD-1阳性表达率、低分化、高PGⅡ和G17水平是EGC患者预后不良的危险因素(均P<0.05)。VEGF、PD-1、PGⅡ、G17水平与分化程度呈负相关,PGⅠ水平与分化程度呈正相关(均P<0.05)。VEGF、PD-1联合胃功能三项检测对EGC患者均有一定的诊断和预后评估价值,联合检测的价值更高(均P<0.05)。结论:VEGF、PD-1在胃癌组织中高表达,两者联合胃功能三项对EGC的诊断和预后评估均有较高价值。

血管内皮生长因子、PD-1联合胃泌素三项检测在早期胃癌中的应用及预后价值

目的探讨血管内皮生长因子(VEGF)、程序性死亡受体1(PD-1)联合胃泌素三项检测在早期胃癌中的应用及预后价值。方法选取2020年3月至2022年8月沧州市中心医院收治的早期胃癌患者120例为研究对象,纳入早期胃癌组;另取同期胃部良性疾病与体检证实健康者各50例,分别纳入胃部良性疾病组和对照组。检测早期胃癌组、胃部良性疾病组治疗前及对照组体检当天的外周血PD-1含量,同时检测VEGF、血清胃功能三项[胃泌素17(G-17)、胃蛋白酶原-Ⅰ(PG-Ⅰ)、胃蛋白酶原-Ⅱ(PG-Ⅱ)]含量,评估各指标联合对早期胃癌的诊断价值。早期胃癌患者均行内镜下黏膜剥离术(ESD)治疗,术后随访12个月,以复发为随访终点事件,复发患者纳入复发组,未复发患者纳入未复发组,比较2组资料,重点分析VEGF、PD-1、胃泌素三项与预后的关系。结果3组VEGF、PD-1、G-17比较,早期胃癌组>胃良性疾病组>对照组,3组PG-Ⅰ水平比较,早期胃癌组<胃良性疾病组<对照组(P<0.05),3组PG-Ⅱ比较,对照组低于其他2组,但其他2组组间比较差异无统计学意义(P>0.05)。血清VEGF、PD-1、G-17、PG-Ⅰ单独诊断胃癌的AUC均>0.70,均有一定诊断价值,PG-Ⅱ诊断胃癌的AUC<0.7,诊断价值较差,联合诊断的AUC为0.968,诊断价值最高。早期胃癌患者ESD术后随访12个月,复发15例,复发率为12.50%。复发组入院时血清VEGF、PD-1、G-17、PG-Ⅰ水平高于未复发组,PG-Ⅱ水平低于未复发组,术后各时点VEGF、PD-1、G-17、PG-Ⅰ水平均较术前逐渐降低,PG-Ⅱ逐渐升高(P<0.05);经Logistic回归分析,结果显示,入院时血清VEGF、PD-1、G-17、PG-Ⅰ、PG-Ⅱ异常表达均与早期胃癌患者术后复发有关,其中VEGF、PD-1、G-17、PG-Ⅱ为危险因素,PG-Ⅰ为保护因素(P<0.05)。结论血清VEGF、PD-1及胃泌素三项均在早期胃癌患者中呈异常表达,可用于早期胃癌的诊断,其异常表达也可能是术后复发的影响因素。

表皮生长因子蛛毒素受体7次跨膜结构域1通过血管内皮生长因子信号通路调控胃癌迁移的机制研究

目的探究表皮生长因子蛛毒素受体7次跨膜结构域1(ADGRL4)通过血管内皮生长因子(VEGF)信号通路调控胃癌迁移的机制。方法将正常胃黏膜上皮细胞GES⁃1、胃癌细胞SGC⁃7901、HGC⁃27、Hs⁃746T传代培养后,检测ADGRL4表达量。将胃癌SGC⁃7901细胞分为对照组、过表达组、沉默组。对照组转染空载体,过表达组转染ADGRL4上调质粒,沉默组转染ADGRL4沉默质粒。分析并比较3组胃癌细胞侵袭、迁移数及VEGF信号通路蛋白表达量。结果与正常胃黏膜上皮细胞GES⁃1比较,胃癌细胞SGC⁃7901、HGC⁃27、Hs⁃746T中ADGRL4表达量均上升(P<0.05);与胃癌细胞HGC⁃27、Hs⁃746T比较,胃癌细胞SGC⁃7901中ADGRL4表达量较高(P<0.05),故选择SGC⁃7901进行后续实验。与对照组比较,过表达组ADGRL4表达量上升,沉默组ADGRL4表达量下降(P<0.05);与过表达组比较,沉默组ADGRL4表达量下降(P<0.05),说明ADGRL4转染成功。与对照组比较,过表达组细胞侵袭数、迁移数、基质金属蛋白酶(MMP)⁃2、MMP⁃9、VEGF、血管内皮生长因子受体⁃2(VEGFR⁃2)表达量上升,E⁃钙黏蛋白(E⁃cadherin)表达量下降,沉默组细胞侵袭数、迁移数、MMP⁃2、MMP⁃9、VEGF、VEGFR⁃2表达量下降,E⁃cadherin表达量上升(P<0.05);与过表达组比较,沉默组细胞侵袭数、迁移数、MMP⁃2、MMP⁃9、VEGF、VEGFR⁃2表达量下降,E⁃cadherin表达量上升(P<0.05)。结论胃癌细胞经下调ADGRL4干预后,侵袭、迁移数减少,迁移、侵袭相关蛋白表达量得到调节,其机制可能与VEGF通路受到抑制有关。

阿帕替尼联合mFOLFOX6化疗对ⅢB期、Ⅳ期胃癌患者疗效及血清肿瘤标志物水平的影响

目的:探讨阿帕替尼联合mFOLFOX6化疗(亚叶酸钙、氟尿嘧啶联合奥沙利铂)对ⅢB期、Ⅳ期胃癌患者疗效及血清肿瘤标志物水平的影响。方法:选取2017年12月—2019年10月靖江市人民医院收治的102例ⅢB期、Ⅳ期胃癌患者作为研究对象,采用随机数表法将患者分为联合组(阿帕替尼联合mFOLFOX6化疗)与参照组(mFOLFOX6化疗治疗),各51例。比较两组治疗效果、血管内皮生长因子(VEGF)、胰岛样素生长因子1(IGF-1)、生存时间、不良反应。结果:联合组总有效率高于参照组,差异有统计学意义(P<0.05);治疗后,两组血清IGF-1、VEGF水平较治疗前降低,且联合组低于参照组,差异有统计学意义(P<0.05);联合组总平均生存时间长于参照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:阿帕替尼联合mFOLFOX6化疗对ⅢB期、Ⅳ期胃癌患者疗效显著,可明显降低血清IGF-1、VEGF水平,延长总平均生存时间,且安全可靠。

贝伐珠单抗对晚期胃癌患者化疗的增效效果及作用机制研究

目的基于缺氧诱导因子/血管内皮生长因子(HIF-1α/VEGF)信号通路探究贝伐珠单抗对晚期胃癌患者化疗的增效效果及其作用机制。方法前瞻性选取2022年6月至2023年8月南阳市中心医院收治的136例晚期胃癌患者,按照随机数表法分为观察组和对照组各68例。对照组患者予以SOX方案治疗,观察组患者予以贝伐珠单抗+SOX方案治疗,21d为一个周期,共治疗两个周期。治疗后比较两组患者的临床疗效、治疗期间毒副反应以及治疗前后的HIF-1α/VEGF信号通路、血清肿瘤标志物[糖类抗原(CA)19-9、CA72-4、癌胚抗原(CEA)、组织多肽特异抗原(TPS)]和免疫功能,同时采用卡氏功能状态评分评价两组患者的生活质量。结果观察组患者的客观缓解率(ORR)、疾病控制率(DCR)分别为60.29%、77.94%,明显高于对照组的45.59%、61.76%,差异均有统计学意义(P<0.05);两组患者毒副反应发生率比较差异无统计学意义(P>0.05);治疗1个周期、2个周期后,观察组患者的HIF-1α、VEGF水平明显低于对照组,差异均有统计学意义(P<0.05);治疗1个周期、2个周期后,观察组患者的血清CA19-9、CA72-4、CEA、TPS明显低于对照组,差异均有统计学意义(P<0.05);治疗1个周期、2个周期后,观察组患者的血清CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)明显高于对照组,但血清CD8^(+)明显低于对照组,差异均有统计学意义(P<0.05);治疗后观察组患者的生存质量总有效率为79.41%,明显高于对照组的55.88%,差异有统计学意义(P<0.05)。结论贝伐珠单抗治疗晚期胃癌可改善患者的免疫功能、血清肿瘤标志物、生存质量,其治疗效果确切且相对安全,其作用机理可能与调节HIF-1α/VEGF信号通路有关。

甲磺酸阿帕替尼联合多西他赛二线治疗晚期胃癌的效果及对外周血肿瘤异常蛋白、血管内皮生长因子与基质金属蛋白酶-9的影响

目的探讨甲磺酸阿帕替尼联合多西他赛二线治疗晚期胃癌的效果及对外周血肿瘤异常蛋白、血管内皮生长因子(VEGF)与基质金属蛋白酶-9(MMP-9)的影响。方法选取2020年3月至2022年3月收治的90例晚期胃癌患者为研究对象,随机将其分为对照组与观察组,各45例。对照组采用多西他赛化疗方案,观察组在对照组基础上加甲磺酸阿帕替尼治疗。比较两组的治疗效果。结果观察组的疾病控制率高于对照组(P<0.05)。治疗后,观察组的糖类抗原19-9(CA19-9)、肿瘤特异性生长因子(TSGF)及癌胚抗原(CEA)水平均低于对照组(P<0.05)。治疗后,观察组的VEGF、MMP-9、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平均低于对照组(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论甲磺酸阿帕替尼联合多西他赛二线治疗晚期胃癌的效果较好,可对外周血肿瘤异常蛋白有良好的抑制作用,同时还能调节VEGF、MMP-9水平,且不会增加不良反应发生风险,值得应用与推广。