scholarly journals Epithelial-mesenchymal transition in main types of gastric carcinoma

2021 ◽  
Vol 10 (2) ◽  
pp. 13-20
Author(s):  
I.V. Vasilenko ◽  
◽  
R.B. Kondratyk ◽  
I.S. Grekov ◽  
A.M. Yarkov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Mixed Type ◽  
Epithelial Mesenchymal Transition ◽  
Rapid Development ◽  
Tumor Formation ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology

scholarly journals Pleckstrin-2 as a Prognostic Factor and Mediator of Gastric Cancer Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jun Wang ◽  
Zhigang He ◽  
Bo Sun ◽  
Wenhai Huang ◽  
Jianbin Xiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
In Vivo Studies ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Gastric Cancer Patients

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.

scholarly journals The clinicopathological characteristics and genetic alterations of gastric cancer patients according to the Lauren classification

2020 ◽  
Author(s):  
Han-Fang Cheng ◽  
Kuo-Hung Huang ◽  
Ming-Huang Chen ◽  
Wen-Liang Fang ◽  
Chien-Hsing Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mixed Type ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Clinicopathological Features ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Lauren Classification ◽  
Borrmann Type ◽  
Laurén Classification

ObjectiveThe Lauren classification is an important histological classification of gastric cancer (GC) with different biological behaviors between histological types.BackgroundTo date, there are few reports on the genetic alterations and survival differences between different histological types according to the Lauren classification.MethodsIn total, 433 GC patients undergoing surgery were enrolled. The clinicopathological features, prognoses, and genetic alterations of the different Lauren types were compared.ResultsDiffuse-type GC was associated with a younger age, female predominance, more Borrmann type 3 and 4 tumors, more advanced pathological tumor (T) and node (N) categories, more tumor recurrences (especially peritoneal recurrence), and worse 5-year overall survival and disease-free survival rates than intestinal-type GC and mixed-type GC. Regarding genetic alterations, mixed-type GC was associated with more TP53 mutations than intestinal-type GC and diffuse-type GC. Multivariate analysis demonstrated the following independent prognostic factors: age, Lauren classification, and pathological T and N categories. Regarding mixed-type GC, diffuse-type major tumors were associated with more lymphovascular invasion, a more advanced N category and TNM stage, and fewer PI3K/AKT pathway mutations than intestinal-type major tumors.ConclusionsDiffuse-type GC had unfavorable clinicopathological features and a worse prognosis than intestinal-type GC. For mixed-type GC, the clinicopathological features and genetic alterations were different between intestinal-type major tumors and diffuse-type major tumors.

scholarly journals Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial–mesenchymal transition of gastric cancer cells

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chen Zeng ◽  
Ran Yan ◽  
Guanghua Yang ◽  
Sen Xiang ◽  
Fuli Zhao
Keyword(s):  
Gastric Cancer ◽  
Hedgehog Signaling ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Signaling Activation

Abstract Gastric cancer (GC) is the fifth most common cancer worldwide and one of the most aggressive cancers in China. Glypican 6 is highly expressed in gastric adenocarcinoma and may act as a diagnostic and prognostic marker; however, the functional importance and molecular mechanism of glypican 6 in GC remains unclear. In the current study, we aimed to reveal the function and mechanism of glypican 6 in two GC cell lines: MKN-45 and SGC-7901. We found higher expression of glypican 6 in MKN-45 and SGC-7901 cells than in cells from the normal gastric mucosa epithelial cell line GES-1. Glypican 6 knockdown suppressed MKN-45 and SGC-7901 cell proliferation. A Transwell assay confirmed that glypican 6 silencing inhibited the migration and invasiveness of MKN-45 and SGC-7901 cells. Epithelial-to-mesenchymal transition (EMT) markers were determined by western blotting, and the results showed reduced Vimentin expression and elevated E-cadherin expression in glypican 6 short interfering RNA (siRNA) transfected MKN-45 and SGC-7901 cells. However, glypican 6 overexpression in GES-1 cells showed no significant promotion on GES-1 cells proliferation and migration. Further studies confirmed that glypican 6 siRNA regulated Hedgehog and Gli1 signaling and participated in the function of glypican 6 on MKN-45 and SGC-7901 cell migration and invasion. Our findings suggest that decreased glypican 6 expression inhibits the migration and invasion ability of GC cells.

scholarly journals Computed tomographic pneumogastrography in determining the types of gastric cancer according to the Lauren classification

2021 ◽  
Vol 11 (2) ◽  
pp. 13-26
Author(s):  
A. D. Amelina ◽  
D. V. Nesterov ◽  
L. N. Shevkunov ◽  
A. M. Karachun ◽  
A. S. Artemyeva ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mixed Type ◽  
Intestinal Type ◽  
Clinical Staging ◽  
Tumor Type ◽  
Diffuse Type ◽  
Computed Tomographic ◽  
Contrast Pattern ◽  
Definition Of ◽  
Stomach Tumor

Objective. To assess the capabilities of computed tomographic pneumogastrography in determining the types of gastric cancer according to the Lauren classification at the stage of clinical staging.Materials and methods. This study is a single-center retrospective study with 202 patients with gastric cancer included who was treated at the National Medical Research Center of Oncology named after N. N. Petrov from 2015 to 2018. All patients underwent subtotal gastric resection or gastrectomy and computed tomographic pneumogastrography at the stage of clinical staging. For patients undergoing neoadjuvant chemotherapy, CT was performed twice: before chemotherapy and after, immediately before surgery. We studied quantitative and qualitative imaging biomarkers, measured densitometric indices of stomach tumor density in the arterial, portal and delayed phases of scanning at five different points. For patients receiving NACT, all density indices were recorded twice — both before the start of therapeutic treatment, and after, immediately before the surgery.Results. The distribution of gastric cancer types according to Lauren»s classification was as follows: in 59 (29,2 %) intestinal type, 69 (34,2 %) — diffuse, 16 (7,9 %) — mixed, 58 (28,7 %) — indeterminate type. Based on visual characteristics, taking into account the characteristics of tumor growth, 3 main CT-PGG of the gastric cancer type were identified: 1 — tuberous (n = 68, 34,0 %), 2 — intramural (n = 57,3 %) and 3 — mixed (n = 77,4 %). CT-PGG tumor type is associated with Lauren type (χ2 = 185,19, p <0,001). With a tuberous CT-PGG type, it is possible to assume that the tumor is of an intestinal or indeterminate Lauren type; sensitivity 0,58 (95% CI: 0,49-0,67), specificity 0,1 (95% CI: 0,96-0,1). With an intramural CT-PGG type, the diffuse type of tumor according to Lauren is most likely; sensitivity 0,75 (95% CI: 0,64-0,85), specificity 0,96 (95% CI: 0,91-0,99). With a mixed CT-PGG type, the definition of the type according to Lauren is difficult. In the definition of mixed tumor type according to Lauren, the sensitivity and specificity of mixed CT-PGG tumor type are 0,94 (95% CI: 0,70% -0,1) and 0,67 (95% CI: 0,59-0,73) respectively.Conclusion. The shape of the stomach tumor, determined by CT-PGG, has a high diagnostic efficiency in determining the types of gastric cancer according to Lauren. The tuberous CT-PGG type is typical for tumors of the intestinal type according to Lauren, and the intramural CT-PGG type is typical for tumors of the diffuse type according to Lauren. Tumors of indeterminate Lauren type have any CT-PGG type and contrast pattern. For tumors of a mixed type according to Lauren, a mixed type according to CT-PGG is characteristic, but differential diagnosis with tumors of a tuberous and diffuse type according to Lauren of an atypical form for them is impossible. Tumors of the intestinal and diffuse Lauren type of the CT-PGG type, which is not typical for them, have an atypical contrast pattern.

scholarly journals Pathobiological Characteristics of Intestinal and Diffuse-Type of Gastric Carcinoma-Retrospective Study of Gastric Cancers

2017 ◽  
Vol 6 (2) ◽  
pp. 1462
Author(s):  
M. Priyadharshini ◽  
R. Narmadha ◽  
S. Dhanalakshmi ◽  
Rajesh Natarajan ◽  
S. Subitha ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Study ◽  
Gastric Carcinoma ◽  
Nodal Metastasis ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Cell Type ◽  
Gastric Cancers ◽  
Microscopic Features ◽  
Glandular Structures

<p><strong>Background:</strong> Gastric carcinomas have various pathological features. Based on patterns of growth and invasiveness, however, they fall into two types: diffuse type and intestinal type. These two types of carcinoma appear to be different in their histogenetic origins.</p><p><strong>Objectives:</strong> To analyse various types of gastric cancer reported in last five years. To compare the features of intestinal and diffuse type gastric carcinoma including gross appearance, staging, grading of tumor.</p><p><strong>Materials and Methods:</strong> This was a retrospective study of 324 gastric cancer which were surgically resected and received over 5 years. The tumors were divided into groups according to their gross and microscopic patterns. Gross appearance was classified based on Borrmann classification. Microscopic features evaluated include tumor cell type, extent of invasion, degree of maturation, formation of glandular structures, nodal metastasis.</p><p><strong>Results:</strong> Totally 320 cases of gastric cancer were received of which 218(68%) were male, 102(32%) were female. Gastric cancers are rare below the age of 30 years. Comparing the type of gastric cancer intestinal type were 269(84%), diffuse type were 24(7.5%) and other type of gastric cancer including GIST, lymphoma, mucinous adenocarcinoma were 27(8.5%). Younger patients have higher stage of lymph node metastasis in diffuse type, but not for the intestinal type.</p><p><strong>Conclusion:</strong> Gastric cancer more common in male (M:F= 2:1) and most frequently seen in 5th decade. Intestinal type constitutes the most common type of gastric tumor. Gross appearance of diffuse type was predominantly infiltrative (79%).</p>

Differential Trends in the Intestinal and Diffuse Types of Gastric Carcinoma in the United States, 1973–2000: Increase in the Signet Ring Cell Type

2004 ◽  
Vol 128 (7) ◽  
pp. 765-770 ◽  
Author(s):  
Donald Earl Henson ◽  
Christopher Dittus ◽  
Mamoun Younes ◽  
Hong Nguyen ◽  
Jorge Albores-Saavedra
Keyword(s):  
Gastric Cancer ◽  
African Americans ◽  
Gastric Carcinoma ◽  
Signet Ring Cell ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Cell Type ◽  
Gastric Carcinomas ◽  
Signet Ring ◽  
Ring Cell

Abstract Context.—During the last 50 years, the incidence and mortality of gastric cancer has declined in many countries. This decline has primarily included the intestinal type (Lauren classification). However, there is an impression among pathologists that the diffuse type, especially the signet ring cell subtype, has become more prevalent. Objectives.—Using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, we analyzed the trends of the 2 primary types (intestinal and diffuse) of gastric carcinomas from 1973 through 2000. Design.—Trends in age-adjusted rates were determined for gastric carcinomas through the SEER statistical program (SEER*Stat), which is available on the Internet to the public. Results.—During the period studied, the intestinal type continued to decline in males, females, African Americans, and whites. The intestinal type was more common in males than in females and more common in African Americans than in whites. In contrast, a consistent increase in the rate of the diffuse type of gastric carcinoma was seen during this period. The rate increased from 0.3 cases per 100 000 persons in 1973 to 1.8 cases per 100 000 persons in 2000. This increase was seen in males, females, African Americans, and whites. The predominant increase occurred in the signet ring type. Conclusions.—The results indicate a progressive decrease in the incidence of the intestinal type of gastric cancer and an increase in the diffuse type of gastric carcinoma, especially the signet ring cell type. The clinical implications of the increase are considered.

scholarly journals BAP-1 Inhibits Gastric Cancer Progression via PI3K/AKT Pathway by Suppressing FOXK1 Expression

2021 ◽  
Author(s):  
Chen Mi ◽  
Yan Zhao ◽  
Li Ren ◽  
Dan Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Ags Cells ◽  
Mesenchymal Transition

Abstract BRCA1-Associated Protein-1 (BAP-1) gene functions as a vital mediator in tumor formation, progression, and metastasis. The involvement of BAP-1 in colon cancer has been widely reported, but the role of BAP-1 in gastric cancer (GC) is still unclear. In this study, we sought to investigate the contribution of BAP-1 in the pathogenesis of GC. qPCR and Western blot assay were used to detect the mRNA and protein expression of BAP-1 in GC cell lines. MTT and transwell assay were employed to determine the cell viability, migration, and invasion. Annexin V-PI double staining was used to evaluate cell apoptosis. We reported that BAP-1 was expressed at a low level in GC cell lines. Overexpression of BAP-1 inhibited cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) and promoted apoptosis in HGC-27 and AGS cells. BAP-1 inactivated the PI3K/AKT pathway by suppressing Forkhead-box K1 (FOXK1) expression. Moreover, overexpression of FOXK1 reversed the effect of BAP-1 on cell viability, apoptosis, migration, invasion, and EMT. Our data revealed that BAP-1 inhibits cell viability, migration, invasion, and EMT process and promoted apoptosis in HGC-27 and AGS cells through PI3K/AKT pathway via suppressing FOXK1 expression. Thus, BAP-1 can serve as a potential therapeutic target in GC treatment.

Sign in / Sign up

Export Citation Format

Share Document