Search for biomarkers of stage II/III gastric cancer and development of individualized therapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4068-4068
Author(s):  
Takashi Oshima ◽  
Naoya Sakamoto ◽  
Takaki Yoshikawa ◽  
Yasushi Rino ◽  
Chikara Kunisaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Treatment Outcomes ◽  
Gastric Cancer Cell ◽  
Stage Ii ◽  
Individualized Therapy ◽  
Gastric Cancer Cell Lines ◽  
Resected Stage ◽  
New Biomarkers

4068 Background: Standard therapy for stage II/III gastric cancer is curative resection followed by adjuvant chemotherapy. Treatment outcomes are expected to be further improved by the development of individualized therapy based on new biomarkers. We have extracted mRNA from frozen specimens of gastric cancer to construct a cDNA bank and searched for new biomarkers of stage II/III gastric cancer. We report currently available results. Methods: The study group comprised 256 patients with stage II/III gastric cancer in whom at least 5 years had passed since surgery (among whom 149 received S-1 as adjuvant chemotherapy). A total of 130 genes were selected on the basis of the results of comprehensive DNA microarray analyses and extraction from serial analysis of gene expression (SAGE) libraries, and other studies. Relative expression levels of each gene in gastric cancer tissue and adjacent normal mucosa were measured by quantitative PCR, and the relations between clinicopathological factors and treatment outcomes were studied. In addition, using 9 types of gastric cancer cell lines, we knocked down the new cancer biomarkers obtained in this study with small interfering RNA (siRNA) and performed functional analysis. Results: In patients with resected stage II/III gastric cancer, INHBA, IGF-1R, CLDN7, and DPD genes were independent prognostic factors. In the subgroup of patients who received S-1-based adjuvant chemotherapy, IGF-1R, INHBA, SULF1, REG4, MMP11, and KIAA1199 genes were independent prognostic factors. Knockdown of the KIAA1199 gene with siRNA markedly inhibited the proliferative and invasive activities of the gastric cancer cell lines and lowered resistance to 5-fluorouracil. Conclusions: Investigatory studies of new biomarkers of gastric cancer identified prognostic factors for patients with resected stage II/III gastric cancer and those who received adjuvant chemotherapy with S-1. At present, the development of small molecule drugs that target KIAA1199 and the joint development of risk stratification tools with the goal of individualized therapy for stage II/III gastric cancer are ongoing.

scholarly journals Survival analysis of stage II gastric cancer patients after D2 gastrectomy: a Chinese people-based research

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zi-Jian Deng ◽  
Run-Cong Nie ◽  
Jun Lu ◽  
Xi-Jie Chen ◽  
Jun Xiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Linitis Plastica ◽  
Stage Ii ◽  
Gastric Cancer Patients

Abstract Objective The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. Methods We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan–Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Results In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. Conclusion Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.

scholarly journals Survival Analysis of Stage II Gastric Cancer Patients after D2 Gastrectomy: A Chinese People-based Research Running Head: Survival of Stage II Gastric Cancer

2021 ◽  
Author(s):  
Zi-Jian Deng ◽  
Run-Cong Nie ◽  
Jun Lu ◽  
Xi-Jie Chen ◽  
Jun Xiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Individual Therapy ◽  
Stage Ii ◽  
Gastric Cancer Patients

Abstract Objective: The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients.Methods: We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007-2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching (PSM) was used to ensure that the baseline data were balanced between the adjuvant chemotherapy (AC) group and surgery-only group. Kaplan-Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Results: In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. Conclusion: Adjuvant chemotherapy is helpful for stage II gastric cancer patients. These prognostic factors can help guide individual therapy.

Macroscopic tumor size as an independent prognostic factor for patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 56-56
Author(s):  
Toru Aoyama ◽  
Takaki Yoshikawa ◽  
Tsutomu Hayashi ◽  
Hiroshi Kuwabara ◽  
Yo Mikayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Stage Ii ◽  
Tumor Diameter ◽  
D2 Gastrectomy ◽  
Significant Difference ◽  
Macroscopic Tumor

56 Background: In patients with stage II/III gastric cancer, tumors often recur even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the prognostic factors in these patients that might be useful for future patients. Methods: Overall survival was examined in 82 gastric cancer patients who underwent curative D2 surgery, were diagnosed with stage IIA, II B, IIIA, IIIB, or IIIC pathologically, and received adjuvant S-1 after surgery between June of 2002 and March of 2010. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter and the depth of tumor invasion. A macroscopic tumor diameter greater than 70mm was regarded as a critical point of classification considering the survival. Uni- and muliti-variate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 64.9% in patients with a macroscopic tumor diameter <70mm, and 33.1% in patients with a macroscopic tumor diameter ≥70mm (P=0.022). Conclusions: The macroscopic tumor diameter was the most important prognostic factor for survival in patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant S-1 chemotherapy. Prognostic factors can be affected by adjuvant chemotherapy.

The effect of delay of adjuvant chemotherapy on survival in patients with resected stage II and III gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15144-e15144
Author(s):  
Minkyu Jung ◽  
Hyoung Soon Park ◽  
Han Na Park ◽  
Seungtaek Lim ◽  
Ji Soo Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Hazards Model ◽  
Resected Stage

e15144 Background: Adjuvant chemotherapy improved survival in patients with gastric cancer. However, the association between the timing of adjuvant chemotherapy and survival has not been investigated. Methods: Patients with stage II and III gastric cancer who received adjuvant chemotherapy at Yonsei University Health System were included in this study. Time to adjuvant chemotherapy, relapse free survival (RFS), and overall survival (OS) were calculated from the day of surgery. RFS and OS were compared using log-rank test and multivariate analysis by the Cox proportional hazards model. Results: Among 675 patients, 226 patients (33.5%) began adjuvant chemotherapy within 1 month, 421 patients (60.1%) began adjuvant chemotherapy in 1 to 2 months, and 28 patients (4.1%) began adjuvant chemotherapy > 2 months after surgery. Intervals > 2 months between chemotherapy and surgery was associated with worse RFS and OS in both univariate analysis (RFS, p=0.039; OS, p=0.022, respectively) and a Cox proportional hazards model (RFS, hazard ratio [HR] =1.81, 95% confidential interval [CI] =1.05-3.12; OS, HR=1.96, 95% CI=1.11-3.47, respectively). Conclusions: Only 4.1% of patients initiated adjuvant chemotherapy >2 months after the date of curative surgery. Adjuvant chemotherapy delay > 2 months after surgical resection is associated with worse survival among patients with resected stage II and III gastric cancer.

scholarly journals LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
An Yang ◽  
Xin Liu ◽  
Ping Liu ◽  
Yunzhang Feng ◽  
Hongbo Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Development Of Gastric Cancer

Abstract Background Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. Methods The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. Results UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. Conclusions UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

scholarly journals Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines

2021 ◽  
Vol 14 (3) ◽  
pp. 230
Author(s):  
Waseem El-Huneidi ◽  
Khuloud Bajbouj ◽  
Jibran Sualeh Muhammad ◽  
Arya Vinod ◽  
Jasmin Shafarin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Carnosic Acid ◽  
Human Gastric Cancer ◽  
Cancer Cell Proliferation ◽  
Human Gastric Cancer Cell ◽  
Gastric Cancer Cell Lines ◽  
Gastric Cancer Cell Proliferation

Gastric cancer is among the most common malignancies worldwide. Due to limited availability of therapeutic options, there is a constant need to find new therapies that could target advanced, recurrent, and metastatic gastric cancer. Carnosic acid is a naturally occurring polyphenolic abietane diterpene derived from Rosmarinus officinalis and reported to have numerous pharmacological effects. In this study, the cytotoxicity assay, Annexin V-FITC/PI, caspases 3, 8, and 9, cell cycle analysis, and Western blotting were used to assess the effect of carnosic acid on the growth and survival of human gastric cancer cell lines (AGS and MKN-45). Our findings showed that carnosic acid inhibited human gastric cancer cell proliferation and survival in a dose-dependent manner. Additionally, carnosic acid is found to inhibit the phosphorylation/activation of Akt and mTOR. Moreover, carnosic acid enhanced the cleavage of PARP and downregulated survivin expression, both being known markers of apoptosis. In conclusion, carnosic acid exhibits antitumor activity against human gastric cancer cells via modulating the Akt-mTOR signaling pathway that plays a crucial role in gastric cancer cell proliferation and survival.

Pharmacological Synergism Between Cannabinoids and Paclitaxel in Gastric Cancer Cell Lines

2009 ◽  
Vol 155 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Hideyo Miyato ◽  
Joji Kitayama ◽  
Hiroharu Yamashita ◽  
Daisuke Souma ◽  
Masahiro Asakage ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Gastric Cancer Cell Lines
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