scholarly journals Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model

2021 ◽  
Vol 27 ◽  
Author(s):  
Sunyi Lee ◽  
Kyoung Mee Kim ◽  
Seung Yeon Lee ◽  
Joohee Jung
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Rna Sequencing ◽  
Xenograft Model ◽  
Diffuse Gastric Cancer ◽  
Diffuse Type ◽  
Female Mice ◽  
Exogenous Estrogen ◽  
Endogenous Estrogen ◽  
Diffuse Type Gastric Cancer

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.

scholarly journals Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

2018 ◽  
Vol 19 (8) ◽  
pp. 2424 ◽  
Author(s):  
Shamshul Ansari ◽  
Boldbaatar Gantuya ◽  
Vo Tuan ◽  
Yoshio Yamaoka
Keyword(s):  
Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Cell Integrity ◽  
Diffuse Type ◽  
Asian Countries ◽  
Contributing Factors ◽  
Incidence And Mortality ◽  
Genetic Abnormalities ◽  
H Pylori ◽  
Diffuse Type Gastric Cancer

Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and Helicobacter pylori infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa’s cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years, H. pylori infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer.

scholarly journals Doxorubicin Embedded into Nanofibrillated Bacterial Cellulose (NFBC) Produces a Promising Therapeutic Outcome for Peritoneally Metastatic Gastric Cancer in Mice Models via Intraperitoneal Direct Injection

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1697
Author(s):  
Hidenori Ando ◽  
Takashi Mochizuki ◽  
Amr S. Abu Lila ◽  
Shunsuke Akagi ◽  
Kenji Tajima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Delivery ◽  
Tumor Growth ◽  
Bacterial Cellulose ◽  
Anticancer Agents ◽  
Intraperitoneal Administration ◽  
In Vitro Release ◽  
Xenograft Model ◽  
Tumor Growth Inhibition

Natural materials such as bacterial cellulose are gaining interest for their use as drug-delivery vehicles. Herein, the utility of nanofibrillated bacterial cellulose (NFBC), which is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) in a medium supplemented with carboxymethylcellulose (CMC) that is referred to as CM-NFBC, is described. Recently, we demonstrated that intraperitoneal administration of paclitaxel (PTX)-containing CM-NFBC efficiently suppressed tumor growth in a peritoneally disseminated cancer xenograft model. In this study, to confirm the applicability of NFBC in cancer therapy, a chemotherapeutic agent, doxorubicin (DXR), embedded into CM-NFBC, was examined for its efficiency to treat a peritoneally disseminated gastric cancer via intraperitoneal administration. DXR was efficiently embedded into CM-NFBC (DXR/CM-NFBC). In an in vitro release experiment, 79.5% of DXR was released linearly into the peritoneal wash fluid over a period of 24 h. In the peritoneally disseminated gastric cancer xenograft model, intraperitoneal administration of DXR/CM-NFBC induced superior tumor growth inhibition (TGI = 85.5%) by day 35 post-tumor inoculation, compared to free DXR (TGI = 62.4%). In addition, compared with free DXR, the severe side effects that cause body weight loss were lessened via treatment with DXR/CM-NFBC. These results support the feasibility of CM-NFBC as a drug-delivery vehicle for various anticancer agents. This approach may lead to improved therapeutic outcomes for the treatment of intraperitoneally disseminated cancers.

scholarly journals Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3833
Author(s):  
Shihori Tanabe ◽  
Sabina Quader ◽  
Ryuichi Ono ◽  
Horacio Cabral ◽  
Kazuhiko Aoyagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Pathway Analysis ◽  
Rna Binding ◽  
Binding Protein ◽  
Diffuse Type ◽  
Mesenchymal Transition ◽  
Diffuse Type Gastric Cancer

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

scholarly journals Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

2019 ◽  
Vol 23 (3) ◽  
pp. 473-482 ◽  
Author(s):  
Seon-Kyu Kim ◽  
Hee-Jin Kim ◽  
Jong-Lyul Park ◽  
Haejeong Heo ◽  
Seon-Young Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tissue Microarray ◽  
Microarray Analysis ◽  
Cox Regression ◽  
Molecular Signature ◽  
Diffuse Type ◽  
Rna Seq ◽  
Tissue Samples ◽  
Diffuse Type Gastric Cancer ◽  
Tissue Microarray Analysis

Abstract Background Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for diffuse-type GC have been identified. Here, we aim to identify a prognostic and predictive signature of diffuse-type GC heterogeneity. Methods We analyzed RNA-seq-based transcriptome data to identify a molecular signature in 150 gastric tissue samples including 107 diffuse-type GCs. The predictive value of the signature was verified using other diffuse-type GC samples in three independent cohorts (n = 466). Log-rank and Cox regression analyses were used to estimate the association between the signature and prognosis. The signature was also characterized by somatic variant analyses and tissue microarray analysis between diffuse-type GC subtypes. Results Transcriptomic profiling of RNA-seq data identified a signature which revealed distinct subtypes of diffuse-type GC: the intestinal-like (INT) and core diffuse-type (COD) subtypes. The signature showed high predictability and independent clinical utility in diffuse-type GC prognosis in other patient cohorts (HR 2.058, 95% CI 1.53–2.77, P = 1.76 × 10–6). Integrative mutational and gene expression analyses demonstrated that the COD subtype was responsive to chemotherapy, whereas the INT subtype was responsive to immunotherapy with an immune checkpoint inhibitor (ICI). Tissue microarray analysis showed the practical utility of IGF1 and NXPE2 for predicting diffuse-type GC heterogeneity. Conclusions We present a molecular signature that can identify diffuse-type GC patients who display different clinical behaviors as well as responses to chemotherapy or ICI treatment.

scholarly journals Inactivation of the E-Cadherin Gene in Sporadic Diffuse-Type Gastric Cancer

2001 ◽  
Vol 14 (10) ◽  
pp. 942-949 ◽  
Author(s):  
Jennifer J Ascaño ◽  
Henry Frierson ◽  
Christopher A Moskaluk ◽  
Jeffrey C Harper ◽  
Franco Roviello ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Diffuse Type ◽  
Diffuse Type Gastric Cancer ◽  
E Cadherin
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