Cell proliferation, cell death and angiogenesis in early and advanced gastric cancer of intestinal type

1997 ◽  
Vol 74 (6) ◽  
pp. 637-641 ◽  
Author(s):  
Carla Vindigni ◽  
Clelia Miracco ◽  
Donatella Spina ◽  
Loretta Presenti ◽  
Marcella Gallorini ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Advanced Gastric Cancer ◽  
Intestinal Type

Single-chain Antibody Against Reg4 Suppresses Gastric Cancer Cell Growth and Enhances 5-FU-induced Cell Death in vitro

2019 ◽  
Vol 19 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Xue-Qing Zhang ◽  
Lu-Ting Yu ◽  
Pei Du ◽  
Tian-Qi Yin ◽  
Zhi-Yuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Ags Cells ◽  
Thiazolyl Blue Tetrazolium Bromide

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

scholarly journals Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer

2022 ◽  
Vol 27 ◽  
Author(s):  
Zhiheng Li ◽  
Zhenhua Zhao ◽  
Chuchu Wang ◽  
Dandan Wang ◽  
Haijia Mao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Advanced Gastric Cancer ◽  
Predictive Value ◽  
Intestinal Type ◽  
Imaging Biomarkers ◽  
Diffuse Type ◽  
Vegf Expression ◽  
Dce Mri ◽  
Sensitivity Specificity

Objective: To investigate the correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion histogram parameters and vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions in advanced gastric cancer (AGC).Methods: This retrospective study included 80 pathologically confirmed patients with AGC who underwent DCE-MRI before surgery from February 2017 to May 2021. The DCE-MRI perfusion histogram parameters were calculated by Omni Kinetics software in four quantitative parameter maps. Immunohistochemical methods were used to detect VEGF and EGFR expressions and calculate the immunohistochemical score.Results: VEGF expression was relatively lower in patients with intestinal-type AGC than those with diffuse-type AGC (p < 0.05). For VEGF, Receiver operating characteristics (ROC) curve analysis revealed that Quantile 90 of Ktrans, Meanvalue of Kep and Quantile 50 of Ve provided the perfect combination of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for distinguishing high and low VEGF expression, For EGFR, Skewness of Ktrans, Energy of Kep and Entropy of Vp provided the perfect combination of sensitivity, specificity, PPV and NPV for distinguishing high and low EGFR expression. Ktrans (Quantile 90, Entropy) showed the strongest correlation with VEGF and EGFR in patients with intestinal-type AGC (r = 0.854 and r = 0.627, respectively); Ktrans (Mean value, Entropy) had the strongest correlation with VEGF and EGFR in patients with diffuse-type AGC (r = 0.635 and 0.656, respectively).Conclusion: DCE-MRI perfusion histogram parameters can serve as imaging biomarkers to reflect VEGF and EGFR expressions and estimate their difference in different Lauren classifications of AGC.

Identification of novel 3-nitroacridines as autophagy inducers in gastric cancer cells

2017 ◽  
Vol 41 (10) ◽  
pp. 4087-4095
Author(s):  
Jia Yu ◽  
Xiaoqing Zhao ◽  
Nanmengzi Zhang ◽  
Chaoqun You ◽  
Gang Yao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Gastric Cancer Cells ◽  
Cell Death Pathway ◽  
Gastric Cancer Cell Proliferation

Nine novel 3-nitroacridines were synthesized, of which 3 compounds inhibited gastric cancer cell proliferation via an autophagy-associated cell death pathway.

scholarly journals Evaluation of the concentration and profile of serum proteins and immunoglobulins in Mexican patients with advanced gastric cancer

2019 ◽  
Author(s):  
María Alicia Díaz y Orea ◽  
Héctor Adrián Díaz Hernández ◽  
Rogelio Gonzalez Lopez ◽  
Eduardo Gómez Conde ◽  
Maria Elena Cárdenas Perea ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Serum Proteins ◽  
Demographic Data ◽  
Tnm Stage ◽  
Intestinal Type ◽  
Control Group ◽  
Diffuse Type ◽  
Tnm System ◽  
Mexican Patients

AbstractIntroductionGastric cancer remains an important health problem. It’s molecular mechanisms and interactions with the immune system are still not well elucidated. Therefore, we aimed to evaluate the concentration and profile of serum proteins and immunoglobulins in Mexican patients with advanced gastric cancer.Materials and methodsWe performed a descriptive study. Adult patients from both sexes were included. The problem group was formed of patients with advanced gastric cancer and the control group was formed of healthy subjects. Demographic data, gastric cancer histological type and stage of tumor node metastasis (TNM) system were recorded. The profile and concentration of serum proteins and immunoglobulins was determined and analyzed in different subgroups classified by sex, histologic type and stage of TNM system. To compare the concentrations of serum proteins and immunoglobulins the ANOVA test was performed. A p <0.05 was considered statistically significant.ResultsWe included 88 patients with advanced gastric cancer and 74 healthy controls. There were no differences in demographic data among the groups, and the most common gastric cancer type was the diffuse (67.04%). Women with gastric cancer from any type presented higher levels of immunoglobulin G (IgG) compared with the control group (p <0.001) and men with gastric cancer of intestinal type in TNM stage III presented higher levels of IgG compared with it’s counterpart of diffuse type (p <0.001). Also, patients with intestinal type gastric cancer presented higher concentrations of alpha-1 globulins compared with patients with the diffuse type (p <0.05). Finally, patients with diffuse gastric cancer TNM stage IV presented the lowest albumin/globulin ratios.ConclusionThere is a greater concentration of serum IgG in some subgroups of patients with advanced gastric cancer, the concentration of alpha-1 globulins is different between the intestinal and diffuse types and the albumin/globulin ratio is lower in the diffuse type.

Is there a role for histology based treatment choice in advanced gastric cancer (GC)?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 135-135
Author(s):  
Rosalba Barile ◽  
Michela Squadroni ◽  
Federica Brena ◽  
Eleonora Cerchiaro ◽  
Valeria Zurlo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Predictive Factors ◽  
Signet Ring Cell ◽  
Histological Diagnosis ◽  
Intestinal Type ◽  
Diffuse Type ◽  
First Line ◽  
Signet Ring ◽  
Ring Cell

135 Background: Medical management of advanced GC is mostly dependent on prognostic assessment based on tumor stage (TNM) and clinical patients (pts)’ characteristics, other than HER2 expression. Prognostic and predictive factors are clearly needed, and histotype could be proposed as a surrogate marker of disease biology. Methods: We retrospectively analyzed pts with advanced GC treated with first line chemotherapy (CT) at Oncology Unit of Humanitas Gavazzeni (Bergamo) and Policlinico Gemelli (Roma). Pts were divided in three subgroups according to histological diagnosis: diffuse type carcinoma, intestinal type carcinoma and signet ring cell carcinoma. HER2 positive tumors were excluded from the analysis. The aim of our analysis was to compare clinical outcomes of metastatic GC pts receiving first line CT according to histological classification (overall survival: OS and Progression Free Survival: PFS). Results: We analyzed 170 pts. Histological diagnosis was as follows: 24.1% (n=41) signet ring cell, 54.4% (n=92) diffuse type, 21.1%(n=37) intestinal type. Pts received a fluoropyrimidine-based doublet containing cisplatin, oxaliplatin or irinotecan; in three drugs regimen anthracycline was added. In diffuse type subgroup OS was: 11.3 months with oxaliplatin based CT, 7.3 months in cisplatin and 6.2 months in irinotecan (p=0.0054); PFS was 5.2, 3.5 and 4.4 months for oxaliplatin, cisplatin and irinotecan based CT respectively (p=0.0036). In signet ring cell carcinomas OS was 12.1 months with oxaliplatin 13.9 with irinotecan, and 5.6 months with cisplatin (p=0.04), and PFS was 6.5, 8.5 and 2.9 months in pts treated with oxaliplatin, cisplatin and irinotecan respectively (p=0.0008). Among pts with intestinal type we did not detect any significant difference in term of OS and PFS comparing first line schedules. Conclusions: Based on our results, histology may be used as a simple, costless and easy tool in advanced gastric cancer treatment management. Clinical use of biomarkers (with the exception for HER2) which are being evaluated as prognostic or predictive factors in GC, is still controversial. In this scenario, the prognostic / predictive value of histology could play a significant role in treatment decision making.

scholarly journals Current status of immunotherapy for advanced gastric cancer

2020 ◽  
Vol 51 (1) ◽  
pp. 20-27
Author(s):  
Akihito Kawazoe ◽  
Kohei Shitara ◽  
Narikazu Boku ◽  
Takaki Yoshikawa ◽  
Masanori Terashima
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Additional Treatment ◽  
Current Status ◽  
Number Of Patients

Abstract Recently, immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) monoclonal antibodies have improved the overall survival of various types of cancers including advanced gastric cancer (AGC). Until now, two ant-PD-1 inhibitors were approved for AGC in Japan: nivolumab as third- or later-line treatment for AGC and pembrolizumab for previously treated patients with microsatellite instability-high tumours. However, a limited number of patients achieved clinical benefit, highlighting the importance of the better selection of patients or additional treatment to overcome resistance to PD-1/PD-L1 blockade. This review focused on pivotal clinical trials, biomarkers and novel combination therapy of immune checkpoint inhibitors forAGC.

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