Investigatory study of biomarkers for gastric cancer based on a cDNA bank.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4070-4070
Author(s):  
Takashi Oshima ◽  
Toshio Imada ◽  
Chikara Kunisaki ◽  
Takaki Yoshikawa ◽  
Yasushi Rino ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Anticancer Agents ◽  
Quantitative Polymerase Chain Reaction ◽  
Gastric Cancer Tissue ◽  
Stage Ii ◽  
High Expression ◽  
Disease Stage ◽  
Cancer Tissue ◽  
Expression Levels

4070 Background: We have constructed a cDNA bank using mRNA extracted from frozen specimens of gastric cancer tissue and adjacent normal gastric mucosa and studied biomarkers for the individualized therapy of gastric cancer and the identification of new treatment targets. We report currently available results. Methods: We studied 227 patients in whom at least 5 years had elapsed since surgery for gastric cancer. The disease stage was IB in 29 patients, II in 66, III in 103, and IV in 29. Among the 139 patients who postoperatively received fluoropyrimidine anticancer agents, 82 with stage II or III disease were given adjuvant chemotherapy with S-1. A total 116 genes were selected as candidate biomarkers on the basis of the results of comprehensive DNA microarray analysis, extraction from a serial analysis of gene expression (SAGE) database, and other studies. The relative expression levels of these 116 genes in gastric cancer tissue and adjacent normal mucosa were measured in each case by a quantitative polymerase chain reaction assay using the cDNA databank described above, and the relations between clinical histopathological factors and treatment outcomes were examined. Results: In patients who underwent gastrectomy, high expression levels of the secreted protein acidic and rich in cysteine (SPARC), sulfatase 1 (SULF1), and inhibin, beta A (INHBA) genes were significantly associated with poor outcomes. In patients with stage II or III disease who received adjuvant chemotherapy with S-1, high expression levels of the insulin-like growth factor receptor 1 (IGF-1R), KIAA1199, thymidylate synthase (TS), and regenerating IV (Reg IV) genes were significantly associated with poor survival. Conclusions: Investigatory studies using a cDNA bank of biomarkers for gastric cancer suggested that expression levels of the SPARC, SULFI, and INHBA genes are useful prognostic factors in patients who undergo gastrectomy for gastric cancer. Expression levels of the IGF-1R, KIAA1199, TS, Reg IV, and INHBA genes may be useful biomarkers in patients who receive adjuvant chemotherapy with S-1.

Five-Year Outcomes of a Randomized Phase III Trial Comparing Adjuvant Chemotherapy With S-1 Versus Surgery Alone in Stage II or III Gastric Cancer

2011 ◽  
Vol 29 (33) ◽  
pp. 4387-4393 ◽  
Author(s):  
Mitsuru Sasako ◽  
Shinichi Sakuramoto ◽  
Hitoshi Katai ◽  
Taira Kinoshita ◽  
Hiroshi Furukawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Disease Stage ◽  
Relapse Free Survival ◽  
Free Survival ◽  
End Point

Purpose The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients and Methods Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. Results The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. Conclusion On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.

Effect of upregulation of ANGPT2 by DARPP-32 on angioenesis in gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 34-34
Author(s):  
Zheng Chen ◽  
Shoumin Zhu ◽  
Jun Hong ◽  
Abbes Belkhiri ◽  
Wael El-Rifai
Keyword(s):  
Gastric Cancer ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Level ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Ags Cells ◽  
Tissue Samples ◽  
Over Expression ◽  
Tnf Α

34 Background: Gastric cancer is the second most frequent cause of cancer-related death worldwide. We have previously shown that Dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) and its truncated form (t-DARPP) are overexpressed in two-thirds of gastric adenocarcinomas. Angiopoietin 2 (ANGPT2) -TIE2 signaling is a secreted protein that acts as a key regulator of adult vascular homeostasis and blood vessel formation. Methods: The expression of DARPP-32 in the multi-step carcinogenesis cascade was examined using IHC analysis on 533 samples. ANGPT2 mRNA level was detected by real-time quantitative polymerase chain reaction (PCR) in 30 gastric cancer tissue samples and 30 normal gastric tissues. DARPP-32 and t-DARPP were over expressed using stable and transient expression in AGS and MKN-28 gastric cancer cell lines, lacking endogenous DARPP-32 to investigate the induction of ANGPT2 by DARPP-32 and t-DARPP. Results: We found that ANGPT2 was higher expressed in cancer samples than normal tissues from RT-PCR. We also found gastric cancer tissue samples expressed higher DARPP-32 and t-DARPP mRNA than normal gastric tissues. Over expression of DARPP-32 and t-DARPP led to a significant increase of the mRNA and protein levels of ANGPT2 as compared to empty vector control. Consistent with these findings, the condition media from DARPP-32 and t-DARRP expressing cells showed high levels of secreted ANGPT-2. TNF-α treatment induced the levels of ANGPT2 further in DARPP-32 and t-DARPP expressing cells as compared to control. Of note, this increase in NF-κB activity was significantly higher in DARPP-32 and t-DARPP expressing cells as compared to control. To confirm the angiogenic potential, we used condition media from DARPP-32 and t-DARPP expressing AGS cells and demonstrated its ability to stimulate tube formation on human umbilical vein endothelial cells (HUVEC) models than the condition medium from control cells. Conclusions: Our results suggest that DARPP-32 and t-DARPP over expression may participate in the angiogenesis of gastric cancer. The in vitro studies indicate that DARPP-32 and t-DARPP play a role in up regulation of ANGPT2 in gastric cancer cells by enhancing the TNF-α induced activation of NF-κB signaling pathway.

scholarly journals Current Situation of Adjuvant Chemotherapy for Stage II/III Gastric Cancer in our Hospital

2012 ◽  
Vol 23 ◽  
pp. xi151
Author(s):  
T. Miyamoto ◽  
M. Gotoh ◽  
H. Takiuchi ◽  
M. Yoshida ◽  
T. Kii ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Current Situation ◽  
Stage Ii

scholarly journals ELISA study of matrix metalloproteinases 2, 7, 9 and their type 2 tissue inhibitor in the tumors of gastric cancer patients: clinical and pathologic correlations

2018 ◽  
Vol 46 (4) ◽  
pp. 323-329
Author(s):  
E. S. Gershtein ◽  
A. A. Ivannikov ◽  
V. L. Chang ◽  
N. A. Ognerubov ◽  
М. M. Davydov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Patients

Background: Over the last 10 years the incidence of gastric cancer has declined significantly. Nevertheless, it remains one of the most prevalent malignancies both in Russia and worldwide. Therefore, the problems of early diagnostics, prognosis and individualized treatment choice are still on the agenda. Much attention is paid to the evaluation of molecular biological characteristics of the tumor, as well as to the development of multiparametric prognostic systems for gastric cancer based on its identified characteristics. An important place among potential tumor biological markers belongs to matrix metalloproteinases (MMPs) involved into all the stages of tumor progression, first of all, into the regulation of invasion and metastasizing.Aim: Comparative quantitative evaluation of some MMP family members (MMP-2, 7, and 9) and one of the tissue MMP inhibitors (TIMP-2) levels in the tumors and adjacent histologically unchanged mucosa in gastric cancer patients, the analysis of their associations with the main clinical and pathological features of the disease and its prognosis.Materials and methods: Sixty six (66) primary gastric cancer patients (32 male and 34 female) aged 24 to 82 years (median, 61 year) were recruited into the study. Twenty two (22) patients were with stage I of the disease, 11 with stage II, 28 with stage III, and 5 with stage IV. The concentrations of the proteins studied were measured in the tumor and unchanged mucosa extracts by standard direct ELISA kits (Quantikine®, R&D Systems, USA).Results: Tumor MMP-2, 7 and 9 levels were significantly increased, compared to those in the adjacent histologically unchanged mucosa, in 80, 70 and 72% of gastric cancer patients, respectively, while the increase of TIMP-2 level found in 61% of the tumors was not statistically significant. Tumor MMP-2 and TIMP-2 content was increasing significantly with higher T index – size and advancement of the primary tumor (p < 0.01 and p < 0.05 respectively). Tumor MMP-2 level was also increasing in parallel with the N index (regional lymph node involvement; p < 0.01); it was significantly higher in the patients with distant metastases than in those without them (p < 0.05). Tumor MMP-9 and MMP-7 concentrations were not significantly associated with the indices of the tumor progression. The patients were followed up for 1 to 85 months (median, 18.3 months). According to the univariate analysis, high (> 32.6 ng/mg protein) MMP-2 and low MMP-7 (< 1.1 ng/mg protein) levels in the gastric cancer tissue represent statistically significant unfavorable prognostic factors for overall survival. Increased TIMP-2 level is associated with a non-significant decrease in the overall survival (p > 0.05), whereas the MMP-9 level was unrelated to the gastric cancer prognosis. Only T index (p = 0.0034) and tumor MMP-7 content (p = 0.026) remained independent prognostic factors in the multivariate regression analysis.Conclusion: The majority of gastric cancer patients demonstrate a significant increase in the expression of three MMP family members, i.e. gelatinases (MMP-2 and 9), and matrilysin (MMP-7), in the tumors, as compared to adjacent histologically unchanged mucosa. Only MMP-2 levels were associated with the disease progression, increasing with higher TNM system indices. High MMP-2 and low MMP-7 content in the gastric cancer tissue are significant unfavorable prognostic factors for the overall survival in the univariate analysis, but only MMP-7 has retained its independent prognostic value in the multivariate assessment.

scholarly journals Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II And III Colorectal Cancer: Novel Tumor Prognostic Markers

2021 ◽  
Author(s):  
Mai Hashimoto ◽  
Noriyuki Uesugi ◽  
Mitsumasa Osaka ◽  
Naoki Yanagawa ◽  
Koki Otsuka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Prognostic Markers ◽  
Multivariate Analyses ◽  
Expression Patterns ◽  
Stage Ii ◽  
High Expression ◽  
Disease Stage ◽  
Neoplastic Progression ◽  
Tenascin C

Abstract Background. Biological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression. Patients and Methods. Immunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts. Results. Stage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses. Conclusions. We suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.

scholarly journals Adjuvant chemotherapy is an additional option for locally advanced gastric cancer after radical gastrectomy with D2 lymphadenectomy: a retrospective control study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei Chen ◽  
Chenghai Zhang ◽  
Zhendan Yao ◽  
Ming Cui ◽  
Jiadi Xing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Radical Gastrectomy ◽  
D2 Lymphadenectomy ◽  
D2 Gastrectomy ◽  
Group A ◽  
Group B

Abstract Background This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. Methods We retrospectively identified 428 patients with stage II–III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7–8 cycles every 3 weeks or 10–12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4–6 cycles every 3 weeks or 6–9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. Results The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4–6/6–9 and 7–8/10–12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). Conclusions To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4–6 cycles every 3 weeks or FOLFOX regimen for 6–9 cycles every 2 weeks might be a favorable option for patients with stage II–III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.

A glycopeptide from gastric cancer tissue

1978 ◽  
Vol 20 (3) ◽  
pp. 305-314
Author(s):  
Hiroshi Masuda ◽  
Shigeki Shichijo ◽  
Mutsuya Takeuchi
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue
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