• Helicobacter pylori
• Histology
• Receptors, androgen
• Receptors, estrogen

• RS-2024-00337453 National Research Foundation of Korea

• Breast metastasis
• Case report
• Gastric cancer
• Metastatic breast cancer
• Treatment

• Estrogens
• MHT
• Postmenopause
• Premenopause

• Male
• Humans
• Female
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/etiology
• Risk Factors
• Premenopause
• Incidence

• ZIA CP010212 Intramural NIH HHS
• 21378 Associazione Italiana per la Ricerca sul Cancro

• Alcian blue
• Gastric
• Periodic acid-Schiff
• Prognosis
• Signet ring cell carcinoma

• aggressive histology
• gastric adenocarcinoma
• young gastric cancer

• Gender medicine
• Neoplasms/sex-specific outcome
• Neoplasms/sex-specific risk factors
• Precision medicine
• Treatment-associated toxicity

• Humans
• Male
• Female
• Sex Characteristics
• Neoplasms/epidemiology
• Medical Oncology

• Adolescent
• Cancer burden
• GLOBOCAN
• Gastric cancer
• Young adult

• Adolescent
• Databases, Factual
• Female
• Global Health
• Humans
• Incidence
• Male
• Social Class
• Stomach Neoplasms/epidemiology
• World Health Organization
• Young Adult

• Gastric cancer, Adenocarcinoma, Signet-ring cell carcinoma, Non-signet-ring cell carcinoma, Prognosis

• Adenocarcinoma/epidemiology
• Adenocarcinoma/therapy
• Carcinoma, Signet Ring Cell/secondary
• Cohort Studies
• Humans
• Peritoneal Neoplasms/epidemiology
• Peritoneal Neoplasms/secondary
• Peritoneal Neoplasms/therapy
• Prognosis
• Retrospective Studies
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/therapy

• Female reproductive factor
• Gastric carcinoma
• Menopause
• Signet-ring cell

• D1(+) lymphadenectomy
• Signet ring cell
• hospital mortality
• long-term survival
• peritoneal seeding

• Carcinoma, Signet Ring Cell/surgery
• Gastrectomy
• Humans
• Lymph Node Excision
• Retrospective Studies
• Stomach Neoplasms/surgery

• adenocarcinoma
• gastric cancer
• histopathology
• signet ring cell carcinoma

• sex steroid hormones
• shbg
• gastric cancer
• chinese men

• Adult
• Aged
• Androgens/blood
• Biomarkers, Tumor/blood
• Body Mass Index
• Case-Control Studies
• China/epidemiology
• Estrogens/blood
• Female
• Humans
• Male
• Middle Aged
• Risk Assessment/methods
• Risk Assessment/statistics & numerical data
• Risk Factors
• Sex Hormone-Binding Globulin/analysis
• Stomach Neoplasms/blood
• Stomach Neoplasms/epidemiology

• N01RC47701 CCR NIH HHS
• Z99 CA999999 Intramural NIH HHS

• Breast metastasis
• Chemotherapy
• Gastric carcinoma
• Signet ring cell

• clinicopathologic analysis
• estrogen receptor beta (ERß)
• mTOR
• pseudopodia
• signet ring cell gastric carcinoma

It has been widely accepted that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human diseases. Many association prediction models have been proposed for predicting lncRNA functions and identifying potential lncRNA-disease associations. Nevertheless, among them, little effort has been attempted to measure lncRNA functional similarity, which is an essential part of association prediction models.

In this study, we presented an lncRNA functional similarity calculation model, IDSSIM for short, based on an improved disease semantic similarity method, highlight of which is the introduction of information content contribution factor into the semantic value calculation to take into account both the hierarchical structures of disease directed acyclic graphs and the disease specificities. IDSSIM and three state-of-the-art models, i.e., LNCSIM1, LNCSIM2, and ILNCSIM, were evaluated by applying their disease semantic similarity matrices and the lncRNA functional similarity matrices, as well as corresponding matrices of human lncRNA-disease associations coming from either lncRNADisease database or MNDR database, into an association prediction method WKNKN for lncRNA-disease association prediction. In addition, case studies of breast cancer and adenocarcinoma were also performed to validate the effectiveness of IDSSIM.

Results demonstrated that in terms of ROC curves and AUC values, IDSSIM is superior to compared models, and can improve accuracy of disease semantic similarity effectively, leading to increase the association prediction ability of the IDSSIM-WKNKN model; in terms of case studies, most of potential disease-associated lncRNAs predicted by IDSSIM can be confirmed by databases and literatures, implying that IDSSIM can serve as a promising tool for predicting lncRNA functions, identifying potential lncRNA-disease associations, and pre-screening candidate lncRNAs to perform biological experiments. The IDSSIM code, all experimental data and prediction results are available online at https://github.com/CDMB-lab/IDSSIM.

• Disease semantic similarity
• LncRNA functional similarity
• lncRNA-disease associations

• Gastric cancer
• breast
• case report
• metastasis
• pregnancy

Gastric cancer is one of the most common cancers worldwide. In Turkey, stomach cancer is ranked 5th among men and 8th among women in all cancers and is located in the forefront in cancer-related deaths. Signet ring cell adenocarcinoma, which is the histopathological subtype of gastric cancer, has a poor prognosis. The incidence of signet ring cell adenocarcinoma is rising. In the present study, we aimed to describe the clinicopathologic features of signet ring cell adenocarcinoma.

A total of 79 patients with 30 being female (38%) and 49 male (62%) who were diagnosed with gastric signet ring cell adenocarcinoma in the Medical Oncology Department of Ankara Numune Training and Research Hospital between January 2004 and October 2015 were retrospectively evaluated.

The baseline demographic characteristics of the patients, such as tumor localization, tumor stage, preoperative serum tumor markers, and treatment type (surgery and chemotherapy regimen), and the effects of these variables on survival and mortality were evaluated. Total surgery, stage III disease, moderate to poor grade, preoperative serum CA 19-9 and CEA levels were found as independent predictors of progression risk (p < 0.05). Each 1 ng/mL increase in preoperative serum CEA level was found to increase the risk of progression by 1.20 folds. Again, each 1 U/mL in preoperative serum CA 19-9 level was found to increase the risk of progression and mortality by 1.06 folds.

The clinicopathologic features of signet ring cell stomach cancer were described. Tumor localization and disease, CA 19-9 and CEA levels, and treatment type (surgery and chemotherapy regimen) were effective on survival and mortality. However, further studies with larger patient groups are needed on this issue.

Altay SB, Akkurt G, Yılmaz N, et al. Clinicopathological Evaluation of Gastric Signet Ring Cell Carcinoma: Our Experience. Euroasian J Hepato-Gastroenterol 2020;10(2):76–84.

• Clinicopathologic features
• Early gastric cancer
• Signet ring cell adenocarcinoma

• G protein-coupled estrogen receptor 1
• colon cancer
• esophageal cancer
• estrogen
• estrogen receptor α
• estrogen receptor β
• estrogen receptors
• gastric cancer
• gastroesophageal reflux disease
• inflammatory bowel disease
• irritable bowel syndrome
• peptic ulcer disease

• estrogen receptor
• image analysis
• pancreas
• proliferative activity
• quantitative biomarker analysis

• UL1 TR000371 NCATS NIH HHS

• Autophagy
• TFs
• cancer
• cell homeostasis
• estrogen
• histone modifications
• miRNAs
• receptors of estrogen

• Breast metastasis; Gastric signet-ring cell carcinoma; Extra-mammary neoplasm

Despite the mounting studies exploring the role of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ) and androgen receptor (AR) in gastric cancer (GC), there remain controversies in those findings. The present study investigated the expression of ERα, ERβ and AR in Chinese gastric cancer by immunohistochemistry, analyzed their clinical relevance in gastric cancer, and examined the potential mechanisms by which ERα and AR modulated GC progression. The positive rate of ERα, ERβ and AR in GC tissues was 6% (9/150), 93.5% (143/153), and 42.4% (59/139), respectively. The expression of ERα was an independent unfavorable risk factor for overall survival (OS) (hazard ratio [HR] = 3.639, 95% confidence interval [CI] = 1.432-9.246, p = 0.007) for GC patients. Moreover, AR was borderline significantly associated with poor progress free survival (PFS) after adjustment with other variables (HR = 1.573, 95% CI = 0.955-2.592, p = 0.075). Knockdown of ERα inhibited the proliferation, migration and invasion of GC cells possibly via modulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. Downregulation of AR suppressed the migration and invasion of GC cells and inhibited the epithelial-mesenchymal transition (EMT) associated pathways.

• androgen receptor
• epithelial-mesenchymal transition
• estrogen receptor
• gastric cancer

• Estrogen receptor alpha
• Estrogen receptor beta
• Meta-Analysis
• Stomach neoplasms
• TCGA

Signet ring cell carcinoma (SRC) of the stomach is a histological type based on microscopic characteristics. SRC's clinicopathological characteristics and prognosis are still controversial. Our study is to describe the clinicopathological features and multidetector computed tomography (MDCT) findings of patients with SRC of the stomach in comparison with nonsignet ring cell adenocarcinoma (NSRC). We retrospectively analyzed data from 241 patients who had undergone curative gastrectomy, including 62 SRC and 179 NSRC. Clinicopathological outcomes and MDCT findings were evaluated, and we investigated whether these variables were correlated with histopathological type. In early gastric carcinoma, patients with SRC were younger (50.2 vs. 60.2 years; P = 0.000) and more likely to be observed in the middle and lower third stomach (P = 0.010). Early SRC had a tendency to be confined to the mucosa (82.1%). There were significant differences in degree of enhancement between early SRC and NSRC on MDCT imaging (P < 0.001). In advanced gastric carcinoma, SRC was more likely to be stage T3‐4 (100%). SRC patients had thicker tumors (P = 0.001) and a higher frequency of diffusely infiltrative gross appearance (P < 0.001). SRC was more likely to have high‐degree contrast enhancement than were NSRC (P = 0.001). The maximal diameter of SRC tumor on MDCT imaging correlated with lymph node metastasis (sensitivity 93.9%, specificity 74.1%) and serosal invasion (sensitivity 89.5%, specificity 78.0%) of SRC. In conclusion, SRC differs significantly from NSRC in clinicopathological features at presentation. MDCT could help differentiate advanced gastric SRC from NSRC based on the thickened stomach wall, high‐degree contrast enhancement, and a higher frequency of diffusely infiltrative gross appearance, particularly in combination.

• Comparative study
• gastric cancer
• multidetector computed tomography
• signet ring cell carcinoma

• gastric cancer
• steroid hormone receptor co-regulators
• steroid hormone receptors
• steroidogenesis
• steroidogenic enzymes

• Gastric carcinoma
• Mucinous adenocarcinoma
• SEER
• Signet ring cell carcinoma
• Survival

• Adenocarcinoma/epidemiology
• Aged
• Carcinoma, Squamous Cell/complications
• Carcinoma, Squamous Cell/metabolism
• Case-Control Studies
• Cohort Studies
• Esophageal Neoplasms/complications
• Esophageal Neoplasms/epidemiology
• Esophageal Neoplasms/metabolism
• Esophageal Squamous Cell Carcinoma
• Female
• Hormone Replacement Therapy/adverse effects
• Hormones/adverse effects
• Humans
• Menopause
• Middle Aged
• Odds Ratio
• Registries
• Regression Analysis
• Risk
• Stomach Neoplasms/epidemiology
• Sweden
• Treatment Outcome

• Colorectal Neoplasms
• Humans
• Reproductive History
• Risk Factors

• Adenocarcinoma/genetics
• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor/genetics
• Chi-Square Distribution
• Estrogen Receptor beta/genetics
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Japan
• Kaplan-Meier Estimate
• Los Angeles
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• Phenotype
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic
• Proportional Hazards Models
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Stomach Neoplasms/genetics
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/therapy
• Time Factors
• Treatment Outcome

• P30 CA014089 NCI NIH HHS

The present study aimed to investigate the effects of 17β-estradiol and tamoxifen, an agonist and inhibitor of the estrogen receptor (ER), respectively, on the proliferation and apoptosis of gastric cancer cells, as well as the messenger (m)RNA expression levels of ER-α36. Nested reverse transcription-polymerase chain reaction (RT-PCR) confirmed that ER-α36 was expressed in the BGC823, MKN45 and SGC7901 human gastric cancer cell lines. Subsequently, the BGC823 cell line was stimulated with various concentrations of 17β-estradiol or tamoxifen for 24 or 48 h, and the proliferation, apoptosis and mRNA expression levels of ER-α36 were determined by water-soluble tetrazolium (WST)-1 assay, flow cytometry and RT-quantitative PCR, respectively. The activity of BGC823 cells was significantly increased following treatment with 10⁻¹² mol/l 17β-estradiol for 24 h (P=0.013), as compared with the control, and reached a peak at 48 h (P=0.002). Notably, the activity of BGC823 cells was decreased with increasing concentrations of 17β-estradiol, although it remained higher compared with that of the control. In the tamoxifen-treated groups, the cell activity decreased as the drug concentration increased. The apoptosis rate was markedly reduced in the 17β-estradiol group after 24 h (10⁻¹² mol/l, P=0.013; 10⁻¹¹ mol/l, P=0.023; and 10⁻¹⁰ mol/l, P=0.017) and after 48 h (10⁻¹² mol/l, P=0.002; 10⁻¹¹ mol/l, P=0.011; and 10⁻¹⁰ mol/l, P=0.033), whereas the rate of apoptosis increased as the tamoxifen concentration increased (24 h: 5×10⁻⁶ mol/l, P=0.002; and 10⁻⁵ mol/l, P=0.001; and 48 h: 5×10⁻⁶ mol/l, P=0.014 and 10⁻⁵ mol/l, P=0.0021), as compared with the control group. The mRNA expression levels of ER-α36 were significantly increased after 24 h of treatment with 10⁻¹² mol/l (P=0.024), 10⁻¹¹ mol/l (P=0.0113) and 10⁻¹⁰ mol/l (P=0.0037) 17β-estradiol compared with the control group when the concentration of 17β-estradiol was low, and the same was observed after 48 h of treatment 10⁻¹² mol/l (P=0.0164), 10⁻¹¹ mol/l (P=0.0342) and 10⁻¹⁰ mol/l (P=0.0198) 17β-estradiol. The mRNA expression levels of ER-α36 were significantly decreased with increasing concentrations of tamoxifen after 24 h (5×10⁻⁶ mol/l, P=0.0233; and 10⁻⁵ mol/l, P=0.007) and after 48 h (5×10⁻⁶ mol/l, P=0.001; and 10⁻⁵ mol/l, P=0.0153). In addition, the ability of tamoxifen to inhibit the growth of gastric cancer cells was concentration-dependent. The results of the present study suggested that gastric cancer cells were sensitive to the effects of 17β-estradiol and tamoxifen, and that tamoxifen is able to induce gastric cancer cell apoptosis. The expression levels of ER-α36 were upregulated, and the growth of gastric cancer cells was increased, following treatment with 17β-estradiol, thus suggesting that gastric cancer tumors are stimulated by estrogen.

• 17β-estradiol
• estrogen receptor-α36
• gastric cancer cell growth
• tamoxifen

• E-cadherin
• Early-onset gastric cancer (EOGC)
• P53
• estrogen receptors (ERs)

• Estrogen
• Molecular
• Phase I clinical trials
• Progesterone
• Receptor
• Therapy

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.

• Gastric cancer
• Estrogen receptor
• Isoform
• Carcinogenesis
• Mechanism
• Genomic pathway
• Non-genomic pathway

• Animals
• Antineoplastic Agents, Hormonal/therapeutic use
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Estrogen Antagonists/therapeutic use
• Humans
• Receptors, Estrogen/antagonists & inhibitors
• Receptors, Estrogen/genetics
• Receptors, Estrogen/metabolism
• Signal Transduction
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

To investigate the clinicopathological features and prognosis of signet ring cell carcinoma of the stomach (SRC).

A total of 1464 gastric cancer patients who underwent curative gastrectomy from 2000 to 2008 at a single center were evaluated. Signet ring cell carcinoma (SRC) was defined as the presence of at least 50% signet ring cells in the pathologic specimen. The clinicopathological parameters and prognosis of SRC were analyzed by comparing with non-signet ring cell carcinoma (NSRC).

Of 1464 patients, 138 patients (9.4%) were classified as SRC. There were significant differences in gender, age, tumor location, TNM stage, p21 expression, and p53 expression between SRC and NSRC. The 5-year survival rates of SRC and NSRC were 36.2% and 49.5%, respectively. The prognosis of SRC was poorer than that of NSRC (P <0.001). Multivariate analysis showed that SRC histology was an independent factor for poor prognosis (P <0.001).

Patients with SRC tend to present with a more advanced stage and poorer prognosis than patients with other types of gastric carcinoma.

While the incidence of gastric cancer has decreased worldwide in recent decades, the incidence of signet-ring cell carcinoma (SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer, which can be resected endoscopically in some cases and which has a better outcome than non-SRCC, and advanced gastric cancer, which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However, the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified, as the benefit of perioperative chemotherapy and the value of taxane-based chemotherapy are unclear. In this review we analyze recent data on the epidemiology, oncogenesis, prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.

• Gastric cancer
• Signet ring cell carcinoma
• Diffuse gastric cancer
• Hereditary diffuse gastric cancer
• CDH1

• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoma, Signet Ring Cell/epidemiology
• Carcinoma, Signet Ring Cell/pathology
• Carcinoma, Signet Ring Cell/therapy
• Chemotherapy, Adjuvant
• Drug Resistance, Neoplasm
• Gastrectomy
• Humans
• Incidence
• Neoplasm Staging
• Predictive Value of Tests
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/therapy
• Treatment Outcome

• endocrine therapy
• gastric cancer
• lemur tyrosine kinase-3
• prognosis

• Diabetes mellitus
• Epidemiology
• Gastric cancer
• Literature review
• Meta-analysis

• Asian People
• Comorbidity
• Diabetes Complications/therapy
• Diabetes Mellitus/epidemiology
• Diabetes Mellitus/therapy
• Feeding Behavior
• Female
• Helicobacter Infections/complications
• Helicobacter pylori
• Humans
• Hyperglycemia/complications
• Insulin/metabolism
• Male
• Meta-Analysis as Topic
• Metformin/therapeutic use
• Risk Factors
• Sodium Chloride, Dietary
• Stomach Neoplasms/complications
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/therapy

• lmtk3
• estrogen
• estrogen receptor
• gastric cancer
• prognostic factor

• Adult
• Aged
• Biomarkers, Tumor
• Disease-Free Survival
• Estrogen Receptor alpha/genetics
• Estrogen Receptor alpha/metabolism
• Female
• Genetic Association Studies
• Humans
• Japan
• Male
• Membrane Proteins/genetics
• Middle Aged
• Prognosis
• Protein Serine-Threonine Kinases/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Stomach Neoplasms/therapy
• United States

• P30 CA014089-27S1 NCI NIH HHS
• 14549 Cancer Research UK
• MR/L000172/1 Medical Research Council
• P30 CA014089 NCI NIH HHS
• NIHR-RP-011-053 Department of Health

The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-α and -β mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of 17β-estradiol and estrogen receptor antagonists on the proliferation of the cell lines.

Detection of estrogen receptor-α and estrogen receptor-β mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of 17β-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with 17β-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test.

Estrogen receptor-α and estrogen receptor-β mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, 17β-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-α nor estrogen receptor-β antagonist blocked the anti-proliferative effect of 17β-estradiol.

Our results indicate that estrogen receptor-β mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-β positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

• Cell line
• Estrogens
• Receptors, estrogen
• Stomach neoplasms